KR20190031682A - Cosmetic composition for improving atopic dermatitis containing micro rna-630 and its mimics - Google Patents

Abstract

The present invention provides a cosmetic composition for ameliorating atopic dermatitis comprising a miRNA containing a nucleotide sequence of sequence number one and having sequence homology of 85% or more with a nucleotide sequence of sequence number two or a mimic thereof as an active ingredient. The composition of the present invention can be used in treating atopic dermatitis by regulating the expression of inflammatory cytokines, and thus by regulating skin inflammation, moisturizing and barrier functions.

Description

TECHNICAL FIELD [0001] The present invention relates to a cosmetic composition for improving atopic skin containing miRNA-630 and a mimetic thereof. < Desc / Clms Page number 1 >

The present invention relates to a cosmetic composition containing microRNA miRNA-630 and a mimetic thereof, and more particularly to a cosmetic composition for improving atopic skin containing miRNA-630 and a mimetic thereof.

In general, the skin is an organ that is always in contact with the external environment, and acts as a protective barrier to prevent moisture loss. The horny layer of the epidermis also exists in the outermost part of the skin and inhibits the loss of moisture and electrolytes outside the skin, thereby preventing the skin from drying and providing an environment in which the skin can perform a normal metabolic process. It also plays an important role in protecting the body from external physical damage, chemical substances, and preventing invasion of bacteria, viruses, etc. into the skin.

Atopic dermatitis is a disease caused by environmental and genetic problems in these skin. Atopic dermatitis is the only disease associated with complex interactions between skin barrier dysfunction and environmental factors such as allergens and microorganisms (Incovaria et al., Clin. Exp. Immunol., 153: 27-29, 2003). All skin cells, including melanocytes and keratinocytes, produce reactive oxygen species (ROS) and reactive nitrogen species (RNS) (Pelle et al., J. Mol. Invest. Dermatol., 124: 793-797, 2005; Kornina and Pastore, Front. Biosci., 1: 123-141, 2005). In addition, ROS produced from skin cells also react with lipid radicals, peroxides, and lipid radicals by reaction with lipid molecules or redox-sensitive lipid metabolism enzymes such as lipoxigenase and cyclooxygenase. , Reactive lipid species such as hydroperoxide, or aldehydes. Atopic dermatitis, a chronic inflammatory disease, disrupts such redox balance leading to overproduction of ROS and RNS and high levels of lipid peroxides, which eventually worsens the disease state and biases towards the Th2-biased immune response (Briganti and Picardo , J. Eur. Acad. Dermatol., 17: 663-669, 2003; Wu et al., Clin. Exp. Immunol., 135: 194-199, 2004).

The inflammatory reactions that appear on the skin appear as redness, tingling, burning, swelling, and changes in tissue, which are physiological and physiologic factors that protect the body from harmful environmental conditions such as intrusion of external substances such as bacteria and mechanical damage Reaction. Typical skin troubles associated with inflammation include atopy and acne. Especially, if you talk about atopy, atopy is characterized by severe itching. When you stimulate the skin, the itching becomes worse, and when you scratch more, it gets hurt. This causes bacterial infections (Staphylococcus aureus, Streptococcus, etc.) and inflammation occurs. One of the important factors in the problem of atopy is the secondary infections and superantigen toxins that occur at this time. Staphylococcus aureus and Stereptococcus pyogenes infect skin with at least 80-90% of atopic patients, which produce anti- Staphylococcus , IgE, which is responsible for the T-cell response-stimulating superantigen Lt; / RTI > More specifically, the superantigen toxin of Staphylococcus aureus selectively stimulates T lymphocytes through antigen presenting cells in Langerhans cells to produce interleukin-1 and TNF-alpha, and stimulates T-cells It secretes various toxins called intracellular cytokines and causes inflammation. In other words, the superantigen toxin promotes the secretion of interleukin-4 and interleukin-5, thereby inhibiting the secretion of IFN-gamma and increasing the number of CLA, thereby promoting the production of IgE. Such IgE causes secretion of histamine from the basophil, and atopic dermatitis is exacerbated.

In general, it is known that atopic dermatitis patients are more susceptible to bacterial, viral, and fungal skin infections than normal people. In particular, 90% of atopic patients are multiplying and accumulating Staphylococcus aureus in their skin, and many studies have shown that the staphylococcal infections of atopic patients are infected with Staphylococcus aureus. However, the pathogenesis of staphylococcal infection and proliferation of epithelial cells in these atopic patients is unclear. It is known that the genetic predisposition is high due to the high incidence of atopic dermatitis in parents of children with atopic diseases. It is known that the incidence of atopic dermatitis increases with the feeding period from the mother with atopic dermatitis

These staphylococcal skin infections are mainly caused by reducing the content of ceramides in the stratum corneum. Atopic dermatitis is caused by dryness of the skin due to the loss of the water retention function of the stratum corneum, resulting in a large amount of keratin. As the skin barrier function is lowered, the stimulating substance enters the stratum corneum and induces stimulation. , Skin allergies and the like are easily occurred, resulting in severe pruritus. Therefore, more than 90% of atopic patients are infected with Staphylococcus aureus, which is caused by scraping because the patient can not tolerate the itching, but the bacterial exotoxin stimulates the body's immune system, causing chemicals that cause allergy, .

In order to solve this problem, currently available methods of treating atopic skin include, but are not limited to, the use of moisturizing agents, the use of tar preparations, the use of a proper or steroid preparation, ultraviolet light treatment, antibiotics such as clindamycin, dicloxacilline, Antioxidants, antioxidants, antioxidants, antioxidants, antioxidants, antioxidants, antioxidants, antioxidants, antioxidants, antioxidants, antioxidants, antioxidants, antimicrobial agents, antimicrobial agents, antibiotics such as povidone iodine and triclosan, immunotherapeutic agents, food, fragrance and herbal medicine.

However, Tar formulation has a disadvantage of irritating dry skin because it has an alcohol component. Steroid preparations have severe side effects such as rash, change of skin color, hypertension and cataract, and ultraviolet rays are a cause of sunburn, itching, During pigmentation and prolonged treatment, the risk of skin premature aging and cancer is high, and antibiotics are mainly used as an oral medicine.

MicroRNA is located in the intron region and is 17 to 25 nucleotides. It is a very small genetic material that selectively regulates cell gene expression and plays a role in cell growth, differentiation, aging, and activity. It is estimated that there are 1000 microRNAs in humans, and intracellular mechanism for each microRNA is actively under investigation.

To date, miRNAs have been associated with diseases such as cancer and developmental processes. For example, miR-17 and miR-92 have been reported to directly regulate the expression of E2F1, a transcription factor, to promote cell proliferation and overexpress in breast, lung, colon, stomach, and pancreatic cancer. In addition, miR-29a is located in the mitochondrial outer membrane and directly controls the expression of Mcl-1 gene, which inhibits apoptosis, to induce apoptosis. MiR-21 directly regulates the expression of PTEN, And it is reported that it is overexpressed in various carcinomas, inhibiting apoptosis and transforming normal cells into tumor cells.

On the other hand, studies on the role of miRNAs in the skin are at an early stage. As a representative example of miRNAs, miR-125b can control psoriasis by directly controlling gene expression of FGFR2 in keratinocytes in 2011 . In addition, there are reports that miR-152 and mir-630 control the aging of skin dermal cells by regulating extracellular matrix and that miR-434-5p is involved in skin cell whitening. Thus, miRNA plays an important role in the skin aging phenomenon, and the role of miRNA in skin aging in future will be of great academic or industrial value.

Korean Patent No. 10-1776000 relates to a cosmetic composition comprising miR-181a and a mimetic thereof.

Accordingly, the present inventors have conducted a search for a novel substance having an inflammatory cytokine expression inhibitory effect, an NF-κB activity inhibitory effect, a moisturizing effect, and an effect of improving skin barrier function. As a result, miR-630 or its mimic And found that the efficacy is very good.

It is an object of the present invention to provide a cosmetic composition for improving atopic skin containing miR-630 or a mimic thereof.

The present invention relates to a cosmetic composition for improving atopic skin comprising a nucleotide sequence of SEQ ID NO: 1 and comprising, as an active ingredient, a microRNA having a sequence homology of 85% or more with the nucleotide sequence of SEQ ID NO: 2 or a mimetic thereof.

Preferably, the cosmetic composition controls the activity of NF-kB.

Also preferably, the cosmetic composition has an effect of suppressing the expression of an inflammatory cytokine.

Also preferably, the cosmetic composition has a moisturizing effect.

Also preferably, the cosmetic composition has an effect of improving the skin barrier function.

The present invention relates to a composition comprising miR-630 and its mimetics as an active ingredient, which is effective for inhibiting NF-κB activity (Experimental Example 1), inhibiting the expression of inflammatory cytokines (Experimental Example 2), moisturizing effect (Experimental Example 3) , And skin barrier function improving effect (Experimental Example 4).

1 is a graph showing the expression levels of IkB protein according to SEQ ID NOS: 2 to 14;

Unless defined otherwise, all technical terms used in the present invention have the following definitions and are consistent with the meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. Also, preferred methods or samples are described in this specification, but similar or equivalent ones are also included in the scope of the present invention. The contents of all publications referred to herein are incorporated herein by reference. The term " drug " is used herein to refer to a reference quantity, level, value, number, frequency, percentage, dimension, size, quantity, Level, value, number, frequency, percentage, dimension, size, quantity, weight or length of a sample,

Throughout this specification, the words " comprising " and " comprising ", unless the context clearly requires otherwise, include the steps or components, or groups of steps or elements, And that they are not excluded.

As used herein, the term " seed sequence " refers to a nucleotide sequence that perfectly matches a target mRNA in a microRNA base sequence, and refers to a target protein, a sequence involved in gene expression, and the like.

As used herein, the term " sequence homology " refers to the degree to which the nucleotide sequence conforms to the reference sequence in percent.

The present invention relates to a composition for controlling the differentiation and skin moisturization of dermal keratinocytes, which comprises a microRNA consisting of a total of 15 to 22 oligonucleotides, preferably 22 oligonucleotides containing the nucleotide sequence of SEQ ID NO: 1 or a mimic thereof ) As an active ingredient to a cosmetic composition for improving atopic skin.

5 '- GUAUUC-3' (SEQ ID NO: 1)

The present invention also relates to a cosmetic composition for improving atopic skin comprising the nucleotide sequence of SEQ ID NO: 2. The nucleotide sequence of SEQ ID NO: 2 is an oligonucleotide comprising the oligonucleotide of SEQ ID NO: 1 and having the same sequence as miR-630.

5 '- AGUAUUCUGUACCAGGGAAGGU-3' (SEQ ID NO: 2)

The present invention relates to a cosmetic composition for improving atopic skin comprising an oligonucleotide having the nucleotide sequence of SEQ ID NO: 1 and having a sequence homology of 85% or more with the nucleotide sequence of SEQ ID NO: 2. Preferably, the present invention can include an oligonucleotide having 90% or more, more preferably 95% or more of the sequence homology with the nucleotide sequence of SEQ ID NO: 2. In the case of having a sequence homology lower than the above range, a desired effect can not be obtained because the binding with other base sequences is weak or limited.

In the present invention, the nucleotide sequence having 85% or more homology in the present invention means that 3 nucleotides are modified based on the oligonucleotide of the reference sequence (SEQ ID NO: 2) including the seed sequence (SEQ ID NO: 1) , 90% or more sequence homology means that two nucleotides are modified, and having 95% or more sequence homology means that one nucleotide has been modified. The length of the oligonucleotide of the reference sequence may be varied from 15 to 22, but in the present invention, the 5% sequence homology will be reduced when one nucleotide is modified.

One of the major causes of intractable skin diseases such as atopy and psoriasis is skin disease caused by inflammation. The common feature is that the lesions are increased by aggravation of inflammation. Common causes of inflammation are NF-κB and activation The symptoms are worse. Accordingly, the composition comprising the oligonucleotide according to the present invention can suppress the expression of inflammatory cytokines by modulating the activity of the NF-κB. Reduced expression of inflammatory cytokines can be used as a composition for improving atopic skin by reducing the inflammatory response.

In the present invention, miR-630 may be derived from human or mouse, but is not limited thereto.

The miRNA having the nucleotide sequence of SEQ ID NO: 1 of the present invention can be used to prepare oligonucleotide molecules having the same / similar sequence as miR-630 and its mimic as miR-630. In addition, the mimic of hsa-miR-630 is a sequence similar to the hsa-miR-630 nucleotide sequence and includes those that inhibit the activity of NF-kB and regulate the expression of an inflammatory cytokine gene can do.

The oligonucleotide of the present invention may also be composed of modified nucleotide molecules. Partially or wholly comprise a nucleotide molecule comprising a 2'-substituted ribose such as, for example, 2'-O-alkyl (e.g. methyl, ethyl), 2'-O-allyl, 2'- . In addition, the nucleotide molecule having a substituted base may be partially or entirely contained.

The present invention can provide a cosmetic composition having an effect of inhibiting NF-κB activity, inhibiting the expression of inflammatory cytokine, moisturizing effect, and skin barrier function, comprising the microRNA or the mimetic thereof according to the present invention as an active ingredient .

According to the present invention, the microRNA or the mimetic thereof according to the present invention is contained in an amount of 0.00001-30.0 wt% based on the total weight of the composition, more preferably 0.001-10.0 wt% of the oligonucleotide, By weight. When the content of the oligonucleotide is less than 0.00001% by weight, the effect of improving the skin is not exhibited. When the content of the oligonucleotide is more than 30.0% by weight, the degree of increase of the skin improving effect with respect to the increase of the content is insignificant, It is not economical.

Accordingly, the cosmetic composition for improving atopic skin comprising the oligonucleotide is characterized by having an inflammatory cytokine expression inhibiting effect, an NF-κB activity inhibiting effect, a moisturizing effect, and a skin barrier function improving effect.

The cosmetic composition of the present invention may further comprise a component that inhibits the activity of the ribonucleic acid decomposing enzyme. For example, it may contain Magnolia sieboldii extract and Clove extract as described in Korean Patent No. 10-1675916 and Korean Patent Application No. 10-2016-0055465. But is not limited thereto and may include all components capable of inhibiting the activity of ribonucleolytic enzymes.

The ingredients contained in the cosmetic composition of the present invention may contain, as an active ingredient, the ingredients commonly used in cosmetic compositions in addition to the above-mentioned effective ingredients, and may contain conventional ingredients such as antioxidants, stabilizers, solubilizers, vitamins, Supplements, and carriers. The cosmetic composition of the present invention can be prepared into any of the formulations conventionally produced in the art and can be used in the form of solutions, suspensions, emulsions, pastes, gels, creams, lotions, powders, soaps, , Oil, powdered foundation, emulsion foundation, wax foundation, pack, massage cream and spray, but is not limited thereto. More specifically, it can be manufactured in the form of a soft lotion, a nutritional lotion, a nutritional cream, a massage cream, an essence, an eye cream, a cleansing cream, a cleansing foam, a cleansing water, a pack, a spray or a powder.

When the formulation of the present invention is a paste, a cream or a gel, an animal oil, vegetable oil, wax, paraffin, starch, tracant, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc or zinc oxide . When the formulation of the present invention is a solution or an emulsion, a solvent, a dissolving agent or an emulsifying agent is used as a carrier component, and examples thereof include water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, , 3-butyl glycol oil, glycerol aliphatic ester, polyethylene glycol or sorbitan fatty acid esters. In the case where the formulation of the present invention is a suspension, a carrier such as 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, Cellulose, aluminum metahydroxide, bentonite, agar or tracant, etc. may be used. When the formulation of the present invention is a powder or a spray, lactose, talc, silica, aluminum hydroxide, calcium silicate or polyamide powder may be used as a carrier component. In the case of a spray, in particular, / Propane or dimethyl ether. When the formulation of the present invention is a surfactant-containing cleansing, the carrier component may include aliphatic alcohol sulfate, aliphatic alcohol ether sulfate, sulfosuccinic acid monoester, isethionate, imidazolinium derivative, methyltaurate, sarcosinate, fatty acid amide ether Alkylamido betaine, aliphatic alcohol, fatty acid glyceride, fatty acid diethanolamide, vegetable oil, lanolin derivative, or ethoxylated glycerol fatty acid ester.

When the cosmetic composition of the present invention is a soap, a surfactant-containing cleansing formulation or a surfactant-free cleansing formulation, it may be applied to the skin and then wiped off, washed or rinsed with water. The surfactant-containing cleansing formulation may be a cleansing foam, a cleansing water, a cleansing towel and a cleansing pack. The surfactant-free cleansing formulation may be a cleansing cream, , Cleansing lotion, cleansing water and cleansing gel, but is not limited thereto.

Hereinafter, the present invention will be described in more detail through experimental examples. It will be apparent to those skilled in the art that these experimental examples are merely intended to explain the present invention more specifically and that the scope of the present invention is not limited by these examples according to the gist of the present invention .

Example  Produce: miR -630 and its object Imitative  Produce

The liposomes were used to transfect human skin fibroblasts so that the concentration of miRNA-630 and its mimic was 100 nM. Transfection was performed using the TransITsiQUEST transfection reagent (Mirus, PanVera, Madison, Wis.) According to the manufacturer's instructions. The oligonucleotide having the same base sequence as miR-630 is SEQ ID NO: 2, the oligonucleotides having one base in the nucleotide sequence other than the seed sequence in miR-630 are SEQ ID NOS: 3, 4, 5 and 6, 630, oligonucleotides having two bases other than the seed sequence are SEQ ID NOS: 7, 8, 9, and 10, and oligonucleotides having three bases other than the seed sequence in miR-630 are SEQ ID NOS: 11 and 12 , 13 and 14, respectively. They can be injected into cells to induce overexpression of miR-630. As a control group, a sample in which an oligonucleotide (- control) which is not overlapped with any known miRNA was transfected was used. The nucleotide sequences of miR-630 and its mimic used in the experiment are shown in Table 1.

Name of sample   Base sequence SEQ ID NO: 2 5'-A GUAUUC UGUACCAGGGAAGGU-3 ' SEQ ID NO: 3 5'- A GUAUUC UGUAC G AGGGAAGGU-3 ' SEQ ID NO: 4 5'- A GUAUUC UGUACCAGG A AAGGU - 3 ' SEQ ID NO: 5 5'- A GUAUUC UGUACCAGGGAA U GU - 3 ' SEQ ID NO: 6 5'- A GUAUUC UGUACCA U GGAAGGU - 3 ' SEQ ID NO: 7 5'-A GUAUUC UGUACC G GG C AAGGU - 3 ' SEQ ID NO: 8 5'-A GUAUUC UGUACCAGGGA CC GU-3 ' SEQ ID NO: 9 5'- A GUAUUC UGUACCA A GGAAG C U - 3 ' SEQ ID NO: 10 5'- A GUAUUC UGUACCAGG CU AGGU - 3 ' SEQ ID NO: 11 5'- A GUAUUC UGU GGA AGGGAAGGU - 3 ' SEQ ID NO: 12 5'- A GUAUUC UG A ACCAG C GAAG C U - 3 ' SEQ ID NO: 13 5'- A GUAUUC UGUACCA C GGAA C G G - 3 ' SEQ ID NO: 14 5'- A GUAUUC UGUAC G AGGG CG GGU-3 '

Experimental Example  One: miR -630 and its object Imitative NF - κB  Activity modulating effect

In order to confirm the effect of miR-630 and its mimic on the activity of NF-κB, an important transcription factor for inflammatory reactions, the following experiment was conducted. When NF-κB binds to a protein called IkB in the cytoplasm, it is inhibited by IkB. However, when IkB is phosphorylated and degraded by a specific signal, it moves away from IkB to the nucleus and the expression of the gene related to the inflammation reaction .

To determine whether miR-630 and its mimetics regulate the activity of NF-κB, keratinocytes (HaCaT) transfected with SEQ ID NOs: 2 to 14 were treated with 20 ng / ml of TNF-α to induce an inflammatory response . Specifically, the cells transfected with TNF-α and SEQ ID NOS: 2 to 14 were treated with phosphate-buffered saline (PBS) containing 1% NP-40 and complete proteinase inhibitor (Roche) The same amount (20 μg) of SDS-PAGE was carried out to separate the proteins and transferred to nitrocellulose membranes. Then, the transferred membrane was blocked with 5% skim milk for 30 minutes and then incubated with anti-Ikb (abcam. USA) and anti-β-actin antibody (monoclonal antibody, abcam, USA) And incubated with anti-rabbit HRP (horseradish peroxidase) -fused secondary antibody (abcam, USA). Then, each membrane was treated with a chemiluminescence solution (Thermo Fisher cientific., USA), and protein expression was confirmed. The degree of protein expression was normalized with β-actin and quantitated using the Image J program. The results are shown in Fig.

As can be seen from FIG. 1, it was found that the amount of IkB protein reduced by TNF-α was significantly increased in keratinocytes transfected with SEQ ID NOS: 2 to 14 according to the present invention, 2 to 14 decreased the activity of NF-kB.

Experimental Example  2: miR -630 and its object Imitative  Inhibitory Effect on Inflammatory Cytokine Expression by UV Irradiation

Experimental Example 2 was conducted to evaluate the inhibitory effect of miR-630 and its mimetics of the preparation examples 2 to 14 on the expression of inflammatory cytokines expressed by ultraviolet irradiation, wherein 5x10 ⁴ cells were put into a 24-well test plate, (HaCaT) cells were transfected with SEQ ID NOS: 2 to 14, each well was washed once with PBS, and 500 占 퐇 of PBS was added to each well. This keratinocyte was irradiated with 10 mJ / cm ² of ultraviolet light using an ultraviolet B (UVB) lamp (Model: F15TB, UV B 15W, Sankyo Dennki Japan) and 150 μl of the culture supernatant was added to obtain IL- The inhibitory effects of inflammatory cytokines of SEQ ID NOS: 2 to 14 were determined by quantification. The amount of IL-1 alpha was quantitated using an enzyme-linked immunosorbent assay, and the inhibition rate (%) of inflammatory cytokine (IL-1 alpha) was calculated according to the following equation.

Bo: IL-1? Production in wells without UV irradiation

Bt: IL-1? Production in wells irradiated with ultraviolet light and not treated with sample

St: IL-1? Production in well irradiated and treated with UV

 Name of sample Inhibitory rate of inflammatory cytokine expression (%) SEQ ID NO: 2 72.74 ± 1.56 SEQ ID NO: 3 70.18 ± 2.11 SEQ ID NO: 4 69.84 + 1.89 SEQ ID NO: 5 70.21 + - 0.86 SEQ ID NO: 6 69.44 + - 1.01 SEQ ID NO: 7 66.84 + - 1.18 SEQ ID NO: 8 67.22 ± 1.21 SEQ ID NO: 9 67.10 + - 0.72 SEQ ID NO: 10 67.52 + 0.83 SEQ ID NO: 11 66.70 + - 0.72 SEQ ID NO: 12 65.10 + - 0.93 SEQ ID NO: 13 66.52 + - 0.84 SEQ ID NO: 14 65.17 ± 1.12 Indomethacin 100 ppm 61.23 + - 0.81 No treatment 8.24 0.35

According to Table 2, it was found that the cells transfected with SEQ ID NOS: 2 to 14 inhibited the production of IL-1 alpha, an inflammatory cytokine caused by ultraviolet light. The inventors of the present invention found that the inhibition rate of inflammatory cytokine expression is superior to that of indomethacin, which is an inhibitor of inflammatory cytokine expression. Thus, it can be seen that SEQ ID NOS: 2 to 14 of the present invention effectively prevent inflammation caused by ultraviolet irradiation.

Formulation Examples 1 to 7. Preparation of Cosmetic Composition Containing Mimics of miR-630 and miR-630

(Formulations 1 to 7) comprising miRNA-630 and its mimics SEQ ID NOS: 2 to 4, 7, 8, 11 and 12 were prepared and compared to the miRNA-630 and its mimics for comparison of effectiveness, (Comparative Formulation Example 1) containing glycerin and 1,3-butylene glycol, miR-630 and a cosmetic composition (Comparative Formulation Example 2) containing neither imipramine nor a moisturizer were prepared as shown in Table 3 below Respectively.

division ingredient Formulation Example 1 Formulation Example 2 Formulation Example 3 Formulation Example 4 Formulation Example 5 Formulation Example 6 Formulation Example 7 Comparative Formulation Example 1 Comparative Formulation Example 2 A SEQ ID NO: 2 0.01 - - - - - - - - SEQ ID NO: 3 - 0.01 - - - - - - - SEQ ID NO: 4 - - 0.01 - - - - - - SEQ ID NO: 7 - - - 0.01 - - - - SEQ ID NO: 8 - - - - 0.01 - - - - SEQ ID NO: 11 - - - - - 0.01 - - - SEQ ID NO: 12 - - - - - - 0.01 - - 1,3-butylene glycol - - - - - - - 5 - glycerin - - - - - - - 5 - Clove extract One One One One One One One One One Magnolia extract One One One One One One One One One EDTA-2Na 0.02 0.02 0.02 0.02 0.02 0.02 0.02 0.02 0.02 Purified water to 100 to 100 to 100 to 100 to 100 to 100 to 100 to 100 to 100 B PIGGY-60 Hydrogenated Castor Oil 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 Polyethylene glycol 400 3 3 3 3 3 3 3 3 3 Microcrystalline 0.3 0.3 0.3 0.3 0.3 0.3 0.3 0.3 0.3 Sorbitan stearate 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 Tocopheryl acetate 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 Cyclomethicone 0.3 0.3 0.3 0.3 0.3 0.3 0.3 0.3 0.3 BHT 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 C Incense, preservative Suitable amount Suitable amount Suitable amount Suitable amount Suitable amount Suitable amount Suitable amount Suitable amount Suitable amount

Experimental Example 3: Moisturizing effect of miR-630 and its mimetic

The clinical moisturizing effect of the cosmetic composition of the above formulation example was measured as follows. A, B, C, D, E, F, and G groups were divided into nine groups (A to I) of 135 healthy volunteers who feel skin dry through a questionnaire, The cosmetic composition of Comparative Formulation Example 1 was applied to the H group, and the cosmetic composition of Comparative Formulation Example 2 was applied to the face group for 2 weeks twice a day for 4 weeks. The moisturizing effect was evaluated by Corneomater CM820 (Corage + Khazaka, Germany) after every two weeks and after the start of the test. The results are shown in Table 4 below.

division Before use After 2 weeks of use After 4 weeks of use Formulation Example 1 30.15 45.48 55.89 Formulation Example 2 29.15 44.15 53.52 Formulation Example 3 28.98 44.19 53.29 Formulation Example 4 30.81 43.98 54.01 Formulation Example 5 30.11 42.15 51.45 Formulation Example 6 30.43 42.17 52.32 Formulation Example 7 31.21 41.88 52.19 Comparative Formulation Example 1 30.3 42.1 50.9 Comparative Formulation Example 2 28.5 29.4 28.9

As shown in Table 4, it was confirmed that the moisturizing effect of miR-630 of the present invention and Formulations 1 to 7 containing the mimetic thereof was excellent, as compared with Comparative Formulation Example 1 containing other humectants .

Experimental Example  4 : miR -630 and its object Imitative Skin barrier function  Improvement effect

The skin barrier function improving effects of Formulation Examples 1 to 7 and Comparative Formulation Examples 1 and 2 were evaluated. Ninety male adults over 20 years of age were randomly divided into 9 groups (groups 1 to 9) by 10 individuals. Twenty microliters of 1.0% SLS aqueous solution was applied to the whole buns for 16 hours, Damaged. Thereafter, the cosmetic composition of Formulation Examples 1 to 7 was added to Groups 1 to 7, the cosmetic composition containing glycerin and 1,3-butylene glycol as moisturizing agents in miR-630 and its mimic acid in Group 8 (Comparative Formulation Example 1 ), And a cosmetic composition (Comparative Formulation Example 2) containing no extract or moisturizing agent was applied to group 9 twice a day for one week. The effect of improving the skin barrier function was measured by Transepidermal Water Loss (TEWL) for 7 days after SLS application, coaptation, and application of the formulation. The results are shown in Table 5.

Before the test SLS Collaboration Day1 Day2 Day3 Day4 Day5 Day6 Day7 Formulation Example 1 6.7 21.7 17.3 9.2 7.0 6.5 6.3 6.0 6.2 Formulation Example 2 6.4 21.5 18.7 9.7 7.6 6.8 6.7 6.4 6.5 Formulation Example 3 6.7 21.8 18.8 9.8 7.5 6.8 6.7 6.6 6.7 Formulation Example 4 6.6 22.0 18.3 10.1 7.6 6.7 6.6 6.6 6.5 Formulation Example 5 6.7 21.2 19.4 11.3 8.1 6.8 6.4 6.7 6.8 Formulation Example 6 6.7 21.9 19.3 11.8 8.0 6.6 6.6 6.7 6.7 Formulation Example 7 6.6 21.6 18.8 10.9 7.8 6.8 6.5 6.8 6.7 Comparative Formulation Example 1 6.4 21.4 17.5 13.3 8.2 6.8 6.5 6.5 6.6 Comparative Formulation Example 2 6.3 22.2 20.4 19.5 18.7 17.8 15.7 13.6 10.7

As can be seen from Table 5, it was confirmed that the portions coated with Formulation Examples 1 to 7 recovered the barrier function more rapidly than Comparative Formulation Examples 1 and 2.

<110> COREANA COSMETICS CO., LTD. <120> COSMETIC COMPOSITION FOR IMPROVING ATOPIC DERMATITIS CONTAINING          MICRO RNA-630 AND ITS MIMICS <130> DP-2017-0184 <160> 14 <170> KoPatentin 3.0 <210> 1 <211> 6 <212> RNA <213> Artificial Sequence <220> <223> miRNA-630 seed sequence <400> 1 guauuc 6 <210> 2 <211> 22 <212> RNA <213> Artificial Sequence <220> <223> miRNA-630 <400> 2 aguauucugu accagggaag gu 22 <210> 3 <211> 22 <212> RNA <213> Artificial Sequence <220> <223> oligonucleotide <400> 3 aguauucugu acgagggaag gu 22 <210> 4 <211> 22 <212> RNA <213> Artificial Sequence <220> <223> oligonucleotide <400> 4 aguauucugu accaggaaag gu 22 <210> 5 <211> 22 <212> RNA <213> Artificial Sequence <220> <223> oligonucleotide <400> 5 aguauucugu accagggaau gu 22 <210> 6 <211> 22 <212> RNA <213> Artificial Sequence <220> <223> oligonucleotide <400> 6 aguauucugu accauggaag gu 22 <210> 7 <211> 22 <212> RNA <213> Artificial Sequence <220> <223> oligonucleotide <400> 7 aguauucugu accgggcaag gu 22 <210> 8 <211> 22 <212> RNA <213> Artificial Sequence <220> <223> oligonucleotide <400> 8 aguauucugu accagggacc gu 22 <210> 9 <211> 22 <212> RNA <213> Artificial Sequence <220> <223> oligonucleotide <400> 9 aguauucugu accaaggaag cu 22 <210> 10 <211> 22 <212> RNA <213> Artificial Sequence <220> <223> oligonucleotide <400> 10 aguauucugu accaggcuag gu 22 <210> 11 <211> 22 <212> RNA <213> Artificial Sequence <220> <223> oligonucleotide <400> 11 aguauucugu ggaagggaag gu 22 <210> 12 <211> 22 <212> RNA <213> Artificial Sequence <220> <223> oligonucleotide <400> 12 aguauucuga accagcgaag cu 22 <210> 13 <211> 22 <212> RNA <213> Artificial Sequence <220> <223> oligonucleotide <400> 13 aguauucugu accacggaac gg 22 <210> 14 <211> 22 <212> RNA <213> Artificial Sequence <220> <223> oligonucleotide <400> 14 aguauucugu acgagggcgg gu 22

Claims (5)

1. A cosmetic composition for improving atopic skin, comprising the microarray having a nucleotide sequence of SEQ ID NO: 1 and having a nucleotide sequence homology of 85% or more with the nucleotide sequence of SEQ ID NO: 2, or a mimetic thereof. The method according to claim 1,
Wherein the cosmetic composition has an effect of inhibiting the activity of NF-κB. The method according to claim 1,
Wherein the cosmetic composition has an inflammatory cytokine expression inhibiting effect. The method according to claim 1,
The cosmetic composition has a moisturizing effect. The method according to claim 1,
The cosmetic composition has an effect of improving skin barrier function.

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