KR102634821B1 - Composition for reinforcing skin barrier - Google Patents

Abstract

The present invention relates to a composition for strengthening the skin barrier, wherein the composition for strengthening the skin barrier contains 5-methyl-2-(methylethyl)phenyl (2E)-3-(3,4,5-trimethoxyphenyl) as an active ingredient. ) Prop-2-enoethite compound is included in an appropriate content range, and the skin barrier function can be strengthened by forming a normal keratin layer by expressing skin barrier markers.

Description

Composition for strengthening the skin barrier {COMPOSITION FOR REINFORCING SKIN BARRIER}

The present invention relates to a composition for strengthening the skin barrier that exhibits skin moisturizing effect by strengthening the skin barrier.

The main function of the stratum corneum is to protect the skin by preventing evaporation of moisture from the skin or the penetration of harmful substances from the outside. In particular, the stratum corneum contains 30% of water relative to its dry weight, of which 20% exists in corneocytes and 10% exists in intercellular lipids. The water in keratinocytes exists in combination with natural moisturizing factors (NMFs), which are decomposed filaggrin.

Filaggrin is expressed in relation to final differentiation during the differentiation process of the epidermis, and in addition to filaggrin, involucrin and loricrin are also important markers related to moisturization. Loricrin is a protein expressed during terminal differentiation. It is necessary for keratinocytes to differentiate and form stable keratin. It is a substance that accounts for 7085% of the keratin mass. It participates in cross-linking between peptides catalyzed by transglutaminase. It has domains rich in glutamine and lysine, and plays an important role in keratin formation by helping cross-linking between keratin forming proteins. Since loricrin binds to the cell membrane in the upper granular layer and becomes a protein, it is used as a marker in tracking the final differentiation process of keratinocytes.

The increase in markers such as filaggrin, involucrin, and loricrin indicates that filaggrin, a precursor of NMF, and intercellular lipids in keratinocytes have been normalized through the formation of a normal stratum corneum. Therefore, to prevent skin aging and maintain skin health due to changes in the external environment such as atmospheric drying, ultraviolet rays, and various pollutants, it promotes moisture retention in skin tissue and strengthens the skin barrier to prevent loss of moisture in skin tissue. In order to form the stratum corneum, the development of skin moisturizing substances that promote the expression of markers such as filaggrin, involucrin, loricrin, etc. is required.

Korean Patent No. 457949

The present inventors conducted research from various angles to solve the above problems, and as a result, 5-methyl-2-(methylethyl)phenyl (2E)-3-(3,4,5-trime, which was previously recognized only as a whitening functional material. The aim is to provide a composition for strengthening the skin barrier that exhibits a moisturizing effect by strengthening the skin barrier using a toxyphenyl) prop-2-enoethite compound.

Therefore, the object of the present invention is to include 5-methyl-2-(methylethyl)phenyl (2E)-3-(3,4,5-trimethoxyphenyl)prop-2-enoethite compound as an active ingredient. To provide a composition for strengthening the skin barrier.

In order to achieve the above object, the present invention provides 5-methyl-2-(methylethyl)phenyl (2E)-3-(3,4,5-trimethoxyphenyl)prop-2 represented by the following formula (I) -Provides a composition for strengthening the skin barrier, comprising an enoethite compound as an active ingredient:

<Formula I>

R ₁ , R ₂ and R ₃ are each independently H, methyl, ethyl, propyl or butyl, and X is CO or CH ₂ =CH ₂ CO.

According to the present invention, 5-methyl-2-(methylethyl)phenyl (2E)-3-(3,4,5-trimethoxyphenyl)prop-2-enoethyte compound, which was previously recognized only as a whitening functional material. The composition for strengthening the skin barrier containing an appropriate amount of as an active ingredient promotes the production of filaggrin in keratinocytes and increases the expression of loricrin and involucrin to promote normal stratum corneum formation. This can strengthen the skin barrier function.

In addition, a composition containing an appropriate amount of the 5-methyl-2-(methylethyl)phenyl (2E)-3-(3,4,5-trimethoxyphenyl)prop-2-enoethite compound as an active ingredient When applied to the skin as an external skin composition, the effect of strengthening the skin barrier function, improving skin moisturization, or skin antioxidant function can be further improved.

1A to 1C show 5-methyl-2-(methylethyl)phenyl (2E)-3-(3,4,5-trimethoxyphenyl)prop-2-enoethyl according to an embodiment of the present invention. This is the result of measuring the amount of skin barrier marker expression according to the presence or absence of compound treatment and treatment amount.

Hereinafter, the present invention will be described in more detail to facilitate understanding of the present invention.

In this specification, “skin” refers to an organ that covers the outside of a living thing, and is composed of the epidermis, dermis, and subcutaneous fat layer, and is the broadest concept to include the scalp and hair as well as tissues covering the outside of the face or the entire body. am.\

As used herein, “5-methyl-2-(methylethyl)phenyl (2E)-3-(3,4,5-trimethoxyphenyl)prop-2-enoethite compound” generally refers to Melasolv It is also called by the brand name (melasolve).

Composition for strengthening skin barrier

The present invention uses 5-methyl-2-(methylethyl)phenyl (2E)-3-(3,4,5-trimethoxyphenyl)prop-2-enoethyl compound represented by the following formula (I) as an active ingredient: It relates to a composition for strengthening the skin barrier, comprising:

<Formula I>

R ₁ , R ₂ and R ₃ are each independently H, methyl, ethyl, propyl or butyl, and X is CO or CH ₂ =CH ₂ CO.

The 5-methyl-2-(methylethyl)phenyl (2E)-3-(3,4,5-trimethoxyphenyl)prop-2-enoethite compound represented by the formula (I) is a substance that exhibits whitening function. However, in the present invention, 5-methyl-2-(methylethyl)phenyl (2E)-3-(3,4,5-trimethoxyphenyl)prop-2-enoethyl represented by the formula (I) A composition for strengthening the skin barrier can be provided by using the property of the compound to increase the expression of one or more skin barrier markers selected from filaggrin, loricrin, and involucrin, which are skin barrier markers contained in keratinocytes.

The “5-methyl-2-(methylethyl)phenyl (2E)-3-(3,4,5-trimethoxyphenyl)prop-2-enoethyte compound” is commonly referred to as melasolve. It is also called a brand name.

In the present invention, the 5-methyl-2-(methylethyl)phenyl (2E)-3-(3,4,5-trimethoxyphenyl)prop-2-enoethite compound represented by the formula (I) The content may be 0.01 to 10% by weight, preferably 0.01 to 5% by weight, and more preferably 0.01 to 3% by weight, based on the total weight of the composition.

The content of 5-methyl-2-(methylethyl)phenyl (2E)-3-(3,4,5-trimethoxyphenyl)prop-2-enoethyte compound represented by the formula (I) is 0.01% by weight. If it is less than 10% by weight, the increase in the expression level of skin barrier markers filacrine, loricrin or involucrin is minimal, and if it is more than 10% by weight, the stability and formulation safety of the composition may be reduced and manufacturing costs may increase.

In the present invention, the composition for strengthening the skin barrier can increase the expression of one or more skin barrier markers selected from the group consisting of filaggrin, loricrin, and involucrin in keratinocytes.

The stratum corneum, which forms the outermost layer of the skin barrier, is composed of natural moisturizing factors and lipids. Filaggrin is a protein related to attachment to keratin fibers present in epidermal cells and promotes the final differentiation of the epidermis. It is decomposed into various types of hydrophilic amino acids through a posttranscriptional modification process, and the amino acid pool constitutes natural moisturizing factor (NMF), which is known to help maintain moisture in the stratum corneum. . In addition, filaggrin gene mutation reduces skin moisturizing factors, impairs skin barrier function, reduces skin defense ability against allergens and microbes, and activates T cell population, resulting in chronic inflammation caused by an autoimmune mechanism. It is also known to be an important genetic risk factor that causes chronic inflammation and induces atopic eczema. Involucrin is one of the crosslink elements of keratinocytes and is found in the cytoplasm, and is connected to membrane proteins by transglutaminase. Loricrin is one of the major proteins found in the cornified envelope and is mainly expressed in terminally differentiated epidermal cells.

5-methyl-2-(methylethyl)phenyl (2E)-3-(3,4,5-trimethoxyphenyl)prop-2-enoethyl compound represented by the formula (I) and skin barrier strengthening function and The relationship was not yet known.

However, through research, the inventors of the present invention found that 5-methyl-2-(methylethyl)phenyl (2E)-3-(3,4,5-trimethoxyphenyl)prop-2- represented by the formula (I) It was found that the enoethite compound promotes the differentiation of skin keratinocytes and increases the expression of one or more types selected from the group consisting of filaggrin, loricrin, and involucrin, thereby exhibiting a skin barrier strengthening function.

In the present invention, the composition for strengthening the skin barrier may be a composition for external skin application.

5-methyl-2-(methylethyl)phenyl (2E)-3-(3,4,5-trimethoxyphenyl)prop-2-enoethyte compound included as an active ingredient in the composition for strengthening the skin barrier When applied to the skin, it can be more advantageous in promoting differentiation of skin keratinocytes by increasing the expression level of skin barrier markers such as filaggrin, loricrin, and involucrin.

In the present invention, the composition for strengthening the skin barrier may be a cosmetic composition.

The cosmetic composition can be provided in any formulation suitable for topical application. For example, it may be provided in the form of a liquid, an emulsion obtained by dispersing an oil phase in an aqueous phase, an emulsion obtained by dispersing an aqueous phase in an oil phase, a suspension, solid, gel, powder, paste, foam, or aerosol composition. Compositions of this dosage form can be prepared according to conventional methods in the art.

In addition to the above-mentioned substances, the cosmetic composition may contain other ingredients that can have a synergistic effect on the skin barrier strengthening effect within the range that does not impair the skin barrier strengthening effect. The cosmetic composition according to the present invention may contain a substance selected from the group consisting of vitamins, high molecular weight peptides, molecular polysaccharides, and sphingolipids. In addition, the cosmetic composition according to the present invention may include moisturizers, emollients, surfactants, ultraviolet absorbers, preservatives, disinfectants, antioxidants, pH adjusters, organic and inorganic pigments, fragrances, cooling agents, or antiperspirants. . The mixing amount of the above components can be easily selected by a person skilled in the art within a range that does not impair the purpose and effect of the present invention.

In the present invention, the composition for strengthening the skin barrier may be a pharmaceutical composition. The pharmaceutical composition may be a pharmaceutical composition for preventing or treating diseases caused by weakened skin barrier function, for example, for preventing or treating dry skin, atopy, etc.

The pharmaceutical composition can be formulated into an oral or parenteral dosage form in solid, semi-solid or liquid form by using the composition as an active ingredient and adding a commonly used inorganic or organic carrier.

Examples of the preparations for oral administration include tablets, pills, granules, tablets, hard capsules, powders, fine granules, powders, emulsions, syrups, pellets, etc. In addition, preparations for parenteral administration include injections, drops, ointments, lotions, sprays, suspensions, emulsions, suppositories, etc. In order to formulate the active ingredient of the present invention, it can be easily formulated by carrying out conventional methods, and surfactants, excipients, colorants, spices, preservatives, stabilizers, buffers, suspending agents, and other commonly used auxiliaries can be appropriately used.

The pharmaceutical composition according to the present invention has an excellent effect in strengthening the skin barrier and can be usefully used in the treatment and prevention of skin diseases caused by damage to the skin barrier. Skin diseases caused by damage to the skin barrier include, but are not limited to, atopic dermatitis, xeroderma, psoriasis, ichthyosis, and acne.

The pharmaceutical composition may be administered orally, parenterally, rectally, topically, transdermally, intravenously, intramuscularly, intraperitoneally, subcutaneously, etc.

In addition, the dosage of the active ingredient will vary depending on the age, gender, and weight of the subject to be treated, the specific disease or pathological state to be treated, the severity of the disease or pathological state, the route of administration, and the judgment of the prescriber. Dosage determinations based on these factors are within the level of one skilled in the art. A typical dosage is 0.001 mg/kg/day to 2000 mg/kg/day, specifically 0.5 mg/kg/day to 1500 mg/kg/day.

Preferred examples are presented below to aid understanding of the present invention. However, the following examples are merely illustrative of the present invention, and it is clear to those skilled in the art that various changes and modifications can be made within the scope and spirit of the present invention. It is natural that changes and modifications fall within the scope of the attached patent claims.

Example 1

The compound 5-methyl-2-(methylethyl)phenyl (2E)-3-(3,4,5-trimethoxyphenyl)prop-2-enoethite was used.

Experimental Example 1

Depending on the application of 5-methyl-2-(methylethyl)phenyl (2E)-3-(3,4,5-trimethoxyphenyl)prop-2-enoethite compound and the amount of keratinocytes, In order to confirm the difference in the expression level of skin barrier markers, the following experiment was conducted.

First, human primary keratinocytes were purchased from Lonza, Inc. Walkersville, MD, USA, distributed in 60 pi dishes, and then incubated in keratinocyte growth medium (KGM-GoldTM, It was cultured at http://www.lonza.com/products-services/bio-research/primary-cHMGA1s/humancHMGA1s-and-media/keratinocytes-and-media/kgm-gold-keratinocyte-growthmedium.aspx).

Thereafter, 5-methyl-2-(methylethyl)phenyl (2E)-3-(3,4,5-trimethoxyphenyl)prop- of Example 1 was added to the cultured human primary keratinocytes. The human primary keratinocytes were differentiated by treating them with 5 ppm and 10 ppm of 2-enoethite compound, respectively. Primary human tissue not treated with the 5-methyl-2-(methylethyl)phenyl (2E)-3-(3,4,5-trimethoxyphenyl)prop-2-enoethite compound of Example 1 Keratinocytes were used as control.

On the 3rd day after differentiation began, RNA was extracted from the human primary keratinocytes. After dissolving the cells using 1 ml of Trizol (Invitrogen, Carlsbad, CA, USA), the supernatant was separated using a centrifuge, and 0.35 ml of isopropanol was added to form a nucleic acid pellet. After washing with % EtOH, the pellet was dissolved in water to isolate RNA. Approximately 1 μg of RNA was made into cDNA using oligo dT and reverse transcripase, and then a primer specific for filaggrin (FLG) mRNA (Genebank Accession No.: NM_002016) (taqman probe from Life technology) was used. ID: Hs00856927_g1), primer specific for involucrin (IVL) mRNA (Genebank Accession No.: NM_005547), a skin barrier function marker gene (taqman probe ID: Hs00846307_s1 from Life technology), loricrin (LOR) mRNA (Genebank Accession No.: NM_000427) using a specific primer (taqman probe ID: Hs01894962_s1 from Life technology) to perform quantitative analysis by RT-qPCR using the taqman method from Applied biosystems, and the results are shown in Figures 1A to 1C. Figures 1a, 1b, and 1c show the expression levels of filaggrin (FLG), involucrin (IVL), and lorigrin (LOR), respectively. At this time, the expression levels of filaggrin (FLG), involucrin (IVL), and loligrin (LOR) are relative values based on the expression level of control (1) (1a: Relative FLG/RPLP0 mRNA; 1b : Relative IVL/RPLP0 mRNA; 1c: Relative LOR/RPLP0 mRNA).

The PCR was carried out for a total of 45 cycles according to the temperature cycle below.

- Pre-denaturation: 95℃, 10min,

- Denaturation: 95℃, 10sec,

- Annealing and Extension: 60℃, 1min

As a result, referring to FIGS. 1A to 1C, 5-methyl-2-(methylethyl)phenyl (2E)-3-(3,4,5-trimethoxyphenyl)prop-2- of Example 1 Compared to the untreated group (control), the treatment group (5 ppm, 10 ppm) to which enoethite compound was applied showed increased expression of skin barrier markers filaggrin (FLG), involucrine (IVL), and lorigrin (LOR). Able to know.

In addition, the treatment group (5 ppm, 10 ppm), the expression levels of filaggrin (FLG), involucrin (IVL), and lorigrin (LOR) were found to be more increased in the 10 ppm treatment group compared to the 5 ppm treatment group.

A formulation example of a composition according to an embodiment of the present invention will be described below, but it can be applied to various other formulations, and this is not intended to limit the present invention, but is only intended to provide a detailed explanation.

Formulation example 1. Nourishing lotion

Nutritional lotion was prepared in a conventional manner according to the composition shown in Table 1 below.

Raw material name Content (% by weight) glycerin 3 Butylene glycol 3 propylene glycol 3 Carboxy vinyl polymer 0.1 5-Methyl-2-(methylethyl)phenyl (2E)-3-(3,4,5-trimethoxyphenyl)prop-2-enoethite compound of Example 1 One beeswax 4 Polysorbate 60 1.5 Caprylic/Capric Liglyceride 5 squalane 5 Sorvitasequiolate 1.5 cetearyl alcohol One Triethanolamine 0.2 Preservatives, flavorings Appropriate amount Purified water remaining amount total 100

Formulation example 2. Nourishing lotion

A nutritional lotion was prepared by a conventional method according to the composition shown in Table 2 below.

Raw material name Content (% by weight) Purified water remaining amount glycerin 3 Butylene glycol 3 liquid paraffin 5 beta glucan 7 5-Methyl-2-(methylethyl)phenyl (2E)-3-(3,4,5-trimethoxyphenyl)prop-2-enoethite compound of Example 1 One carbomer 0.1 Caprylic/Capric Triglyceride 3 squalane 5 Cetearyl Glucoside 1.5 Sorbitan Stearate 0.4 Polysorbate 60 1.5 antiseptic Appropriate amount incense Appropriate amount pigment Appropriate amount Triethanolamine 0.1 total 100

Formulation example 3. Nourishing cream

A nutritional cream was prepared by a conventional method according to the composition shown in Table 3 below.

Raw material name Content (% by weight) glycerin 3.5 liquid paraffin 3 beta glucan 7 carbomer 7 5-Methyl-2-(methylethyl)phenyl (2E)-3-(3,4,5-trimethoxyphenyl)prop-2-enoethite compound of Example 1 One Caprylic/Capric Triglyceride One squalane 3 Cetaryl Glucoside 5 Sorbitan Stearate 1.5 Polysorbate 60 0.4 Triethanolamine 1.2 Preservatives, flavorings Appropriate amount Purified water remaining amount total 100

Formulation example 4. Drugs for topical administration ( patch )Manufacture of

A medication (patch) for topical administration was prepared by a conventional method according to the composition shown in Table 4 below.

Raw material name Content (% by weight) 5-Methyl-2-(methylethyl)phenyl (2E)-3-(3,4,5-trimethoxyphenyl)prop-2-enoethite compound of Example 1 One Beta-1,3-glucan 3 Diethylamine 0.7 sodium sulfite 0.1 Polyoxyethylene lauryl ether (E.O=9) One Polyhydroxyethylenecetylstearyl ether (Cetomacrogol 1000) One viscous paraffin oil 2.5 Caprylic acid ester/Capric acid ester (Cetiol LC) 2.5 Polyethylene glycol 400 3 Polyacrylic acid (Carbopol 934P) One Purified water remaining amount total 100

Although the present invention has been described above with limited examples and drawings, the present invention is not limited thereto, and the technical idea of the present invention and the following description will be provided by those skilled in the art in the technical field to which the present invention pertains. Of course, various modifications and variations are possible within the scope of equivalence of the patent claims.

Claims (6)

5-methyl-2-(methylethyl)phenyl (2E)-3-(3,4,5-trimethoxyphenyl)prop-2-enoethyl (5-methyl-2-) represented by the following formula (I) A composition for strengthening the skin barrier comprising (methylethyl)phenyl (2E)-3-(3,4,5-trimethoxyphenyl)prop-2-enoate) compound as an active ingredient:
<Formula I>

R ₁ , R ₂ and R ₃ are each independently H, methyl, ethyl, propyl or butyl, and X is CO or CH ₂ =CH ₂ CO. According to paragraph 1,
The content of the 5-methyl-2-(methylethyl)phenyl (2E)-3-(3,4,5-trimethoxyphenyl)prop-2-enoethite compound represented by the formula (I) is the total amount of the composition. 0.1 to 10% by weight of a composition for strengthening the skin barrier. According to paragraph 1,
The composition is a composition for strengthening the skin barrier, which increases the expression of one or more skin barrier markers selected from the group consisting of filaggrin, loricrin, and involucrin in keratinocytes. According to paragraph 1,
The composition is a composition for strengthening the skin barrier, which is a composition for external application to the skin. According to paragraph 1,
The composition is a cosmetic composition, a composition for strengthening the skin barrier. According to paragraph 1,
The composition is a pharmaceutical composition, a composition for strengthening the skin barrier.