KR20240019216A - Cosmetic composition for preventing skin aging or improving skin wrinkles comprising an improved cell-permeable nuclear transport inhibitor - Google Patents

Abstract

The present invention relates to a composition comprising an improved cell-permeable nuclear import inhibitor (iCP-NI) peptide, and more specifically, SEQ ID NO: 1, which has the effect of preventing skin aging and improving skin wrinkles. It relates to a cosmetic composition or external skin preparation containing it as an active ingredient.

Description

Cosmetic composition for preventing skin aging or improving skin wrinkles comprising an improved cell-permeable nuclear transport inhibitor

Cross-reference to related applications

This application claims the benefit and priority of U.S. Provisional Patent Application Serial No. 63/232,766, filed August 13, 2021, which is incorporated herein by reference in its entirety.

The present invention relates to a composition comprising an improved cell-permeable nuclear import inhibitor (iCP-NI) peptide, and more specifically, SEQ ID NO: 1, which has the effect of preventing skin aging and improving skin wrinkles. It relates to a cosmetic composition or external skin preparation containing it as an active ingredient.

Skin is a membrane that covers the outside of the body. Its most important role is to act as a defense barrier that protects the skin from external bacterial invasion and damage, while also preventing heat and moisture loss from the inside. will be. Human skin constantly undergoes changes, the most representative of which are the decline in skin function and visual beauty due to aging. Skin aging is largely divided into internal aging caused by genetic factors and external aging caused by external environmental factors such as sunlight. This external aging causes wrinkles in the skin, and representative wrinkle formation factors include active oxygen, ultraviolet rays, and decreased collagen biosynthesis (Danielle, H.W., Ann Intern Med., 75(6), 873-880, 1971; Grove, G. L. et al., J Am Acad Dermatol., 21(3 Pt 2), 631-637, 1989). Collagen is a major matrix protein produced by skin fibroblasts. When collagen metabolism becomes active by promoting the synthesis of collagen in the skin, the components of the dermal matrix increase, which has been shown to have effects such as wrinkle improvement, elasticity improvement, and skin strengthening. . Substances conventionally used to promote collagen synthesis include retinoids, TGF-βgrowth factor, betulic acid, and chlorella extract. However, retinoic acid is unstable and has stability due to irritation when applied to the skin. The problem is that there is a limit to the amount of use, and the effect of chlorella extract, etc. is so minimal that it cannot be expected to actually improve skin function by promoting collagen synthesis in the skin. New wrinkle treatment methods that have emerged recently include ultrasound treatment, skin scaling, laser peeling, botulinum toxin injection, and Restylane injection, but they are not showing much effectiveness in terms of treatment cost and sustainability. Therefore, there is a need for the development of an accelerator that has an excellent effect in promoting collagen synthesis in vivo.

Under the above background, the present inventors made diligent efforts to develop a cosmetic composition for preventing skin aging and improving skin wrinkles, and as a result, based on TSDT (therapeutic molecule systemic delivery technology) on a cell-permeable nuclear import inhibitor (CP-NI, cSN50.1 peptide). An improved cell-permeable nuclear import inhibitor (iCP-NI) peptide was prepared by introducing an advanced macromolecule transduction domain (aMTD), and the iCP-NI peptide not only has excellent biocompatibility but also has excellent biocompatibility. , it was confirmed that it had the effect of increasing collagen production, suppressing ROS production, improving wrinkles, improving skin moisture content, improving epidermal elasticity, and improving skin density, and the present invention was completed.

The present invention provides a cosmetic composition for preventing skin aging and improving skin wrinkles, comprising an improved cell-permeable nuclear import inhibitor (iCP-NI) peptide consisting of the amino acid sequence shown in SEQ ID NO: 1 as an active ingredient. The purpose is to provide.

In the cosmetic composition according to the present invention, the skin aging may be photoaging due to UV exposure.

In the cosmetic composition according to the present invention, the iCP-NI peptide may be contained at a concentration of 0.001 to 20 mM in the cosmetic composition.

In the cosmetic composition according to the present invention, the formulation of the cosmetic composition includes lotion (skin lotion), skin softener, skin toner, astringent, lotion, milk lotion, moisture lotion, nutritional lotion, massage cream, nutritional cream, eye cream, and moisture. One or more may be selected from the group consisting of cream, hand cream, foundation, essence, nutritional essence, pack, soap, cleansing foam, cleansing lotion, cleansing cream, body lotion, and body cleanser.

The present invention also provides a skin treatment for preventing skin aging and improving skin for main use, comprising an improved cell-permeable nuclear import inhibitor (iCP-NI) peptide consisting of the amino acid sequence shown in SEQ ID NO: 1 as an active ingredient. The purpose is to provide topical medication.

In the skin external preparation according to the present invention, the formulation of the external preparation may be one or more selected from the group consisting of creams, gels, patches, sprays, ointments, warning agents, lotions, liniment agents, pasta agents, and cataplasma agents. there is.

In the skin external preparation according to the present invention, the skin aging may be photoaging due to UV exposure.

The present invention also provides a method for preventing skin aging and reducing skin wrinkles, comprising the step of applying an improved cell-permeable nuclear import inhibitor (iCP-NI) peptide consisting of the amino acid sequence shown in SEQ ID NO: 1 to a subject. The purpose is to provide methods for improvement.

The improved cell-permeable nuclear import inhibitor (iCP-NI) peptide according to the present invention exhibits excellent effects in skin care, such as preventing skin aging and improving skin wrinkles, and can therefore be used as a cosmetic composition or external skin agent. It is expected that it can be used effectively.

Meanwhile, the scope of the present invention is not limited by the effects described above.

Figure 1 shows the results of in-vitro efficacy evaluation of the biocompatibility of the iCP-NI peptide according to the present invention.
Figure 2 shows the results of in-vitro efficacy evaluation of the iCP-NI peptide according to the present invention on collagen production.
Figure 3 shows the results of in-vitro efficacy evaluation of the iCP-NI peptide according to the present invention on collagen production after UVB stimulation.
Figure 4 shows the results of quantitative analysis of intracellular reactive oxygen species (ROS) inhibition of the iCP-NI peptide according to the present invention.
Figure 5 shows the image measurement results of intracellular reactive oxygen species (ROS) inhibition of the iCP-NI peptide according to the present invention.

Best mode for carrying out the invention

Hereinafter, a cosmetic composition containing an improved cell-permeable nuclear import inhibitor (iCP-NI) peptide according to a specific embodiment of the present invention will be described in detail. However, this is only an illustrative example, the scope of the present invention is not limited thereto, and it is obvious to those skilled in the art that various modifications to the embodiments are possible within the scope of the present invention.

As used herein, the term “include” or “comprise” means including a specific component (or element) without specific limitation, unless otherwise stated throughout the specification, and other components It cannot be interpreted as excluding the addition of (or elements).

As used herein, the term “amino acid” in its broadest sense includes naturally occurring L α-amino acids or residues thereof as well as D-amino acids and chemically modified amino acids. For example, amino acids may include mimetics and analogs of the amino acids described above. In the present disclosure, mimetics and analogs may include functional equivalents.

The term “skin” used herein refers to the tissue that covers the body surface of an animal, and is the broadest concept that includes not only the tissue that covers the body surface of the face or body, but also the scalp and hair.

The term “skin aging” used herein refers to symptoms such as decreased skin elasticity, decreased luster, wrinkles, weakened regenerative capacity, or severe dryness, and may be caused by the passage of time or external environment. The skin aging may be photoaging. The photoaging refers to a phenomenon in which skin damage occurs, such as a decrease in skin elasticity and moisture and the formation of wrinkles, upon repeated or long-term exposure to ultraviolet rays of the sun.

The term "skin wrinkles" used herein refers to skin wrinkles formed on the skin without limitation, which includes skin wrinkles caused by intrinsic and external factors, for example, skin wrinkles accompanying skin photoaging due to UV stimulation, etc. Includes.

As used herein, the term “improvement” or “treatment” means (a) inhibiting the development of, (b) alleviating, and (c) eliminating a dermatitis disease in an individual.

As used herein, the term “prevention” refers to suppressing the occurrence of a disease or disease in an individual who has not been diagnosed as having the disease or disease but is prone to such disease or disease.

The term “application” used herein refers to any method of contacting the composition according to the present invention to the skin of an individual by any appropriate method, and the purpose is to allow the composition to be absorbed into the skin.

According to the first implementation example,

The present invention provides a cosmetic composition for preventing skin aging and improving skin wrinkles, comprising an improved cell-permeable nuclear import inhibitor (iCP-NI) peptide consisting of the amino acid of SEQ ID NO: 1 as an active ingredient. .

Prevention of skin aging according to the present invention refers to the action of suppressing skin aging due to photoaging or natural aging, but it is preferable that the skin aging is particularly photoaging due to UV exposure. In addition, according to another embodiment of the present invention, the skin wrinkles may be caused by photoaging or natural aging, more preferably photoaging, and more preferably photoaging due to UV exposure, but are not limited thereto.

The iCP-NI peptide according to the present invention is preferably contained in a cosmetic composition at a concentration of 0.01 to 10000 ppm, and more preferably contained at a concentration of 0.01 to 1000 ppm, but is not limited thereto. If the concentration of the peptide is less than 0.01 ppm, it is difficult to obtain the desired effect of preventing skin aging and improving skin wrinkles, and if it exceeds 10000 ppm, there is no clear increase in effect as the content increases, resulting in low production economics.

The iCP-NI peptide according to the present invention can be produced by general chemical synthesis, for example, solid-phase peptide synthesis, and can be produced by a microorganism transformed with a recombinant vector containing a nucleic acid encoding the peptide. The peptide may be expressed by culturing and then purified and manufactured by a conventional method, but the peptide is not limited to this.

In addition to the above-mentioned peptide, the cosmetic composition according to the present invention may further contain other ingredients that can preferably have a synergistic effect on the effect of the above-mentioned peptide within a range that does not impair the effect aimed at by the present invention. For example, the cosmetic composition of the present invention may contain conventional auxiliaries such as antioxidants, stabilizers, solubilizers, vitamins, pigments and fragrances, as well as any other substances known to have anti-skin aging and skin wrinkle-improving effects. It may contain a carrier.

The cosmetic composition according to the present invention is not particularly limited in its formulation and can be prepared in any formulation commonly manufactured in the art, for example, solution, suspension, emulsion, paste, gel, cream, It can be formulated as lotion, powder, soap, surfactant-containing cleansing, oil, powder foundation, emulsion foundation, wax foundation and spray. On the other hand, scalp treatments, soaps, hair tonics, shampoos, rinses, hair packs, hair gels, lotions, conditioners, hair oils, mousses, creams, solids, solutions, emulsions, dispersants, micelles, liposomes, ointments, It may also be manufactured in the form of lotion, essence, patch, or spray.

When the formulation of the cosmetic composition is paste, cream or gel, animal oil, vegetable oil, wax, paraffin, starch, tracant, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc or zinc oxide are used as carrier ingredients. In the case of powder or spray, lactose, talc, silica, aluminum hydroxide, calcium silicate, or polyamide powder may be used as carrier ingredients, and especially in the case of spray, chlorofluorohydrocarbon, propane/ It may contain a propellant such as butane or dimethyl ether.

When the formulation of the cosmetic composition is a solution or emulsion, a solvent, solubilizing agent, or emulsifying agent may be used as a carrier component, for example, water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, and benzyl benzoate. , propylene glycol, 1,3-butyl glycol oil, glycerol fatty esters, polyethylene glycol, or fatty acid esters of sorbitan.

When the formulation of the cosmetic composition is a suspension, the carrier ingredients include water, a liquid diluent such as ethanol or propylene glycol, a suspending agent such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester, and polyoxyethylene sorbitan ester, and miso. Crystalline cellulose, aluminum metahydroxide, bentonite, agar, or tracant can be used, and in the case of cleansing containing surfactants, aliphatic alcohol sulfate, aliphatic alcohol ether sulfate, sulfosuccinic acid monoester, and isethionate are used as carrier ingredients. , imidazolinium derivatives, methyl taurate, sarcosinate, fatty acid amide ether sulfate, alkylamidobetaine, fatty alcohol, fatty acid glyceride, fatty acid diethanolamide, vegetable oil, lanolin derivative or ethoxylated glycerol fatty acid ester, etc. It can be used.

According to a specific embodiment of the present invention, the iCP-NI peptide of the present invention has excellent biocompatibility, can reduce ROS production and wrinkles, and increase collagen production, skin moisture content, epidermal elasticity, and skin density. Therefore, the iCP-NI peptide of the present invention can be usefully used as an active ingredient in a cosmetic composition for preventing skin aging and improving skin wrinkles.

According to the second implementation,

The present invention provides a pharmaceutical composition for preventing skin aging and improving skin wrinkles, comprising an improved cell-permeable nuclear import inhibitor (iCP-NI) peptide consisting of the amino acid of SEQ ID NO: 1 as an active ingredient. do.

The pharmaceutical composition according to the present invention includes dermal, oral, intravenous, intramuscular, intraarterial, transdermal, subcutaneous, intraperitoneal, intranasal, enteral, topical, sublingual or rectal administration, and oral or parenteral administration is preferred. However, it is not limited to this. The parenteral administration includes subcutaneous, intradermal, intravenous, intramuscular, and intralesional injection or infusion techniques.

The pharmaceutical composition according to the present invention may contain one or more active ingredients that exhibit the same or similar functions in addition to the iCP-NI peptide according to the present invention. The composition can be formulated and used in the form of oral dosage forms such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, external preparations, suppositories, and sterile injection solutions according to conventional methods.

Solid preparations for oral administration of the pharmaceutical composition include powders, granules, tablets, capsules, soft capsules, pills, etc. Liquid preparations for oral use include suspensions, oral solutions, emulsions, syrups, etc. In addition to the commonly used simple diluents such as water and liquid paraffin, various excipients such as wetting agents, sweeteners, fragrances, and preservatives may be included. . Preparations for parenteral administration include external preparations such as powders, granules, tablets, capsules, sterilized aqueous solutions, solutions, non-aqueous solvents, suspensions, emulsions, syrups, suppositories, aerosols, etc. and sterilized injection preparations according to conventional methods. It can be formulated and used in the form of a cream, gel, patch, spray, ointment, warning agent, lotion, liniment agent, pasta agent, or cataplasma agent. It can be prepared and used as a pharmaceutical composition for external use on the skin. , but is not limited to this. Non-aqueous solvents and suspensions may include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, and injectable ester such as ethyl oleate. As a base for suppositories, witepsol, macrogol, tween 61, cacao, laurin, glycerogeratin, etc. can be used.

The pharmaceutical composition according to the present invention may further contain preservatives, stabilizers, hydrating agents or emulsification accelerators, auxiliaries such as salts and/or buffering agents for adjusting osmotic pressure, and other therapeutically useful substances, and may be prepared by conventional methods. It can be formulated according to mixing, granulating or coating methods.

The pharmaceutical composition according to the present invention may vary depending on various factors, including the subject's age, weight, general health, gender, administration time, administration route, excretion rate, drug combination, and severity of a specific disease.

When the pharmaceutical composition according to the present invention is formulated in a unit dose form containing the iCP-NI peptide as an active ingredient, the iCP-NI peptide as an active ingredient is administered in a unit dose of about 0.01 to 1,500 mg. It is preferable to contain it, and the dosage required for adult treatment is usually in the range of about 1 to 500 mg per day depending on the frequency and intensity of administration, but is not limited thereto. When administered intramuscularly or intravenously to adults, a single dose of approximately 5 to 300 mg per day will usually be sufficient, although higher daily doses may be desirable in some patients. The composition of the present invention can be used alone or in combination with surgery, radiation therapy, hormone therapy, chemotherapy, and methods using biological response modifiers.

According to the third implementation example,

The present invention includes the step of treating or administering a cosmetically or pharmaceutically effective amount of an improved cell-permeable nuclear import inhibitor (iCP-NI) peptide consisting of the amino acid of SEQ ID NO: 1 to an individual. Provides methods to prevent skin aging and improve skin wrinkles.

In the method according to the present invention, the cosmetically or pharmaceutically effective amount is 0.000001 to 100 mg/kg, preferably 0.001 to 10 mg/kg, but is not limited thereto. Treatment or dosage can be adjusted depending on the specific patient's weight, age, gender, health condition, diet, administration period, administration method, clearance rate, disease severity, etc. Treatment or administration may be administered once a day or may be divided into several times.

In the method according to the present invention, the subject is a vertebrate, preferably a mammal, more preferably a human or laboratory animal such as a rat, rabbit, guinea pig, hamster, dog, or cat, and most preferably a human. It may be, but is not limited to this.

In the method according to the present invention, the treatment or administration method can be applied, orally or parenterally, and when administered parenterally, intraperitoneal injection, intrarectal injection, subcutaneous injection, intravenous injection, intramuscular injection, intrauterine dura. It may be administered by injection, intracerebrovascular injection, or intrathoracic injection.

Forms for practicing the invention

Hereinafter, the present invention will be described in more detail through examples and experimental examples. However, the following examples and experimental examples are for illustrating the present invention, and the content of the present invention is not limited to the following examples and experimental examples.

<Example>

1. Preparation of improved cell-permeable nuclear transport inhibitor (iCP-NI)

The iCP-NI peptide consisting of the amino acid sequence of SEQ ID NO: 1 according to the present invention uses an advanced macromolecule transduction domain (aMTD) consisting of the amino acid of SEQ ID NO: 2 and the NF-κ nuclear site sequence (NLS) consisting of the amino acid of SEQ ID NO: 3. It was prepared (Table 1).

designation order SEQ No. iCP-NI IAAVLAAPALVPCVQRKRQKLMPC SEQ ID NO: 1 aMTD IAAVLAAPALVP SEQ ID NO: 2 NLS CVQRKRQKLMPC SEQ ID NO: 3

2. In-vitro efficacy evaluation of biocompatibility of iCP-NI peptide

NHDF cells were inoculated into a ²⁴ -well plate at a concentration of 2.0 ) and cultured for 24 hours. After incubation, 50 μl of EZ-Cytox was added per well and cultured for another hour. The cultured medium was transferred to a 96-well plate and the absorbance was measured at 450 nm using a VERSA max microplate reader (Molecular devices, LCC., USA). The average absorbance value for each sample group was obtained, and cell survival rate was investigated by comparing it with the absorbance value of the control group. As a result, it was confirmed that the iCP-NI peptide according to the present invention had no cytotoxicity compared to the control group in the concentration range of 1 to 50 μM (Figure 1).

3. Evaluation of in-vitro efficacy of iCP-NI peptide on collagen production

(1) Evaluation of collagen production

NHDF cells were inoculated into a ²⁴ -well plate at a concentration of 2.0 After culturing for 24 hours, the supernatant was taken, and the amount of free procollagen in the medium was measured by absorbance at 450 nm using the Procollagen Type I C-peptide (PIP) EIA Kit. The positive control group was compared using L-ascorbic acid (0.001 %). As a result, the iCP-NI peptide according to the present invention was confirmed to significantly increase intracellular collagen (PIP) production by about 130 to 150% compared to the control group in a concentration range of 1 to 50 μM (Figure 2).

(2) Quantification of collagen production after UVB stimulation

NHDF cells were inoculated into a ²⁴ -well plate at a concentration of 3.0 After adding 40mJ of ultraviolet rays (UVB), the phosphate buffered saline solution is removed. Afterwards, the samples were exchanged for serum-free FBM containing diluted samples at each concentration and cultured for 24 hours. After culturing for 24 hours, the supernatant was taken, and the amount of free procollagen in the medium was measured by absorbance at 450 nm using the Procollagen Type I C-peptide (PIP) EIA Kit. The positive control group was compared using L-ascorbic acid (0.001 %). As a result, the iCP-NI peptide according to the present invention was confirmed to significantly increase the amount of intracellular collagen (PIP) production reduced by UVB by about 110 to 175% in a concentration-dependent manner (Figure 3)

4. Evaluation of in-vitro efficacy of iCP-NI peptide in inhibiting ROS generation

(1) iCP-NI intracellular reactive oxygen species (ROS) quantitative analysis

DCF-DA assay was used to measure changes in intracellular reactive oxygen species (ROS). HaCaT cells were inoculated into a ²⁴ _- well _plate at 1.0 The concentration was treated for 30 minutes and further cultured. After adding 20uM of DCF-DA (dichlorofluorescein diacetate), a dye for measuring intracellular ROS, and incubating for 30 minutes, the amount of inhibition of intracellular ROS generation was measured using Oxiselect ^TM Intracellular ROS assay Kit (CELL BIOLABS, INC.) using Spectra Max. Measured using i3X (480nm/530nm). As a result, the iCP-NI peptide according to the present invention was confirmed to significantly inhibit ROS added by H ₂ O ₂ by about 10 to 20% (FIG. 4).

(2) Intracellular reactive oxygen species (ROS) image measurement

DCF-DA assay was used to measure changes in intracellular reactive oxygen species (ROS). HaCaT cells were inoculated into a ²⁴ _- well _plate at 1.0 The concentration was treated for 30 minutes and further cultured. 50uM of DCF-DA (dichlorofluorescein diacetate), a dye for measuring intracellular ROS, was added and incubated for 30 minutes. After washing with PBS, the level of fluorescence expression was measured and images were displayed using the EVOS™FL Imaging System. As a result, it was confirmed that the iCP-NI peptide according to the present invention inhibits the production of ROS in a concentration-dependent manner (FIG. 6).

<Manufacturing example>

1. Preparation of cosmetic composition containing iCP-NI peptide

A cream containing the iCP-NI peptide of the present invention as an active ingredient was prepared as shown in Table 2 below (content: parts by weight).

division Ingredient name Formulation example Comparative example Awards WATER To. 100 To. 100 GLYCERIN 5 5 1,3-BUTYLENE GLYCOL 8 8 1,2-Hexanediol 2 2 EDTA-2Na 0.02 0.02 AMMONIUM ACRYLOYLDIMETHYLTAURATE/VP COPOLYMER 0.5 0.5 paid CETEARYL ALCOHOL 2.0 2.0 PEG-100 STEARATE 1.5 1.5 GLYCERYL STEARATE 0.7 0.7 BEESWAX One One CETYLETHYLHEXANOATE 5 5 SQUALANE 3 3 C14-22 ALCOHOL 2.0 2.0 POLYSORBATE 20 0.5 0.5 SOLBITAN ISOSTEARATE 1.2 1.2 C12-20 ALKYLGLUCOSIDE 0.5 0.5 CYCLOMETHICONE 2 2 DIMETHICONE One One DIMETHICONOL 0.5 0.5 iCP-NI Award WATER One - iCP-NI 0.01 - additive FRAGRANCE Appropriate amount Appropriate amount

2. Evaluation of anti-aging efficacy of iCP-NI according to the present invention

A human application test was conducted on 20 test subjects. After washing the cheek area of the face, the patient waited at least 30 minutes under constant temperature and humidity (22 ± 2°C, 50 ± 5%) conditions to sufficiently stabilize the skin before participating in the test. The wrinkle improvement effect, skin moisture content improvement effect, epidermal elasticity improvement effect, and skin density improvement effect before and after using the test product were evaluated according to the following methods.

(1) Evaluation of wrinkle improvement effect using Antera 3D

Before the test, 2 weeks after the test, and 4 weeks after the test, the wrinkle index (Indentation index, Wrinkles: small, A.U.) around the eyes was measured using Antera 3D. As a result, it was confirmed that the cosmetic composition containing the iCP-NI peptide according to the present invention reduced the wrinkle index around the eyes at a statistically significant level (p<0.05) compared to before the test.

division Mean ± standard deviation improvement rate p-value test site Before exam 12.12 ± 1.61 ^a - <0.001 ¹⁾ 2 weeks after exam 11.69 ± 2.04 ^a 3.80% 4 weeks after exam 11.11 ± 1.89 ^b 8.65%

ab: Means that do not share a letter within the group have statistically significant (p<0.05) differences. by LSD test1) by Repeated measures ANOVA. Analysis of measurement time as a factor

(2) Evaluation of the effect of improving skin moisture content using Corneometer®

Skin moisture content (Corneometer value, A.U.) was measured using Corneometre® before the test, 2 weeks after the test, and 4 weeks after the test. As a result, it was confirmed that the cosmetic composition containing the iCP-NI peptide according to the present invention increased skin moisture content at a statistically significant level (p<0.05) compared to before the test.

division Mean ± standard deviation improvement rate p-value test site Before exam 39.81 ± 9.24 ^a - <0.001 ¹⁾ 2 weeks after exam 44.12 ± 10.17 ^a 11.08% 4 weeks after exam 47.31 ± 10.79 ^b 19.55%

(3) Evaluation of the effect of improving epidermal elasticity using Cutometer®

Epidermal elasticity (R7: Ur/Uf in cutometer, 2mm) was measured using the Cutometer®MPA 580 2mm Probe before the test, 2 weeks after the test, and 4 weeks after the test. As a result, it was confirmed that the cosmetic composition containing the iCP-NI peptide according to the present invention increased skin elasticity at a statistically significant level (p<0.05) compared to before the test.

division Mean ± standard deviation improvement rate p-value test site Before exam 0.2968 ± 0.0571 ^a - <0.001 ¹⁾ 2 weeks after exam 0.3316 ± 0.0449 ^a 13.52% 4 weeks after exam 0.3744 ± 0.0540 ^b 27.76%

(4) Evaluation of the effect of improving skin density using Ultrasound

Dermal density (%) was measured using Ultrasound before the test, 2 weeks after the test, and 4 weeks after the test. As a result, it was confirmed that the cosmetic composition containing the iCP-NI peptide according to the present invention increased skin density at a statistically significant level (p<0.05) compared to before the test.

division Mean ± standard deviation improvement rate p-value test site Before exam 35.00 ± 9.49 ^a - <0.001 ¹⁾ 2 weeks after exam 39.03 ± 10.95 ^a 11.67% 4 weeks after exam 41.85 ± 11.79 ^b 19.18%

The improved cell-permeable nuclear transport inhibitor (iCP-NI) peptide according to the present invention has excellent biocompatibility, can reduce ROS production and wrinkles, and increase collagen production, skin moisture content, epidermal elasticity, and skin density. Therefore, the iCP-NI peptide of the present invention can be usefully used as an active ingredient in a cosmetic composition for preventing skin aging and improving skin wrinkles.

Claims (7)

A cosmetic composition for preventing skin aging and improving skin wrinkles, comprising an improved cell-permeable nuclear import inhibitor (iCP-NI) peptide consisting of the amino acid sequence shown in SEQ ID NO: 1 as an active ingredient. According to paragraph 1,
A cosmetic composition, wherein the skin aging is photoaging due to UV exposure. According to paragraph 1,
A cosmetic composition, wherein the iCP-NI peptide is contained in a concentration of 0.01 to 10000 ppm in the cosmetic composition. According to paragraph 1,
The formulation of the cosmetic composition includes lotion (skin lotion), skin softener, skin toner, astringent, lotion, milk lotion, moisture lotion, nutritional lotion, massage cream, nutritional cream, eye cream, moisture cream, hand cream, foundation, essence, A cosmetic composition characterized by one or more selected from the group consisting of nutritional essence, pack, soap, cleansing foam, cleansing lotion, cleansing cream, body lotion and body cleanser. An external skin preparation for preventing skin aging and improving skin wrinkles, comprising an improved cell-permeable nuclear import inhibitor (iCP-NI) peptide consisting of the amino acid sequence shown in SEQ ID NO: 1 as an active ingredient. According to clause 5,
The formulation of the external preparation is one or more selected from the group consisting of creams, gels, patches, sprays, ointments, warning agents, lotions, liniment agents, pasta agents, and cataplasma agents. A method for preventing skin aging and improving skin wrinkles, comprising applying to a subject an improved cell-permeable nuclear import inhibitor (iCP-NI) peptide consisting of the amino acid sequence shown in SEQ ID NO: 1.

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