JP2021531247A - A cosmetic composition for removing or adsorbing fine dust containing a peptide complex as an active ingredient. - Google Patents

Abstract

The present invention relates to a cosmetic composition for removing or adsorbing fine dust containing a fatty acid-amino acid complex or a fatty acid-oligopeptide complex as an active ingredient, and the complex of the present invention removes fine dust without skin toxicity. Since the effect is excellent, it can be usefully utilized as a composition for preventing or treating various diseases induced by fine dust.

Description

The present invention relates to a cosmetic composition for removing or adsorbing fine dust containing a peptide complex as an active ingredient.

Fine dust (particulate matter, PM) is nitrate (NO ₃ ^-), ammonium (NH ₄ ^+), was in air pollutants, including ionic components, carbon compound or a metal compound, such as sulfate (SO ₄ ^2-) It means a particulate matter with a diameter of 10 μm or less that floats in the atmosphere for a long period of time. If the particle size is 10 μm or less, the fine dust is referred to as PM10, and if the particle size is less than 2.5 μm, it is referred to as PM2.5, and is referred to as ultrafine dust or ultrafine dust. Most of the ultra-fine dust is generated by human factors such as automobile exhaust gas, industrial processes, and dust flying on roads.

When exposed to fine dust for a long period of time, the immune system is rapidly weakened and can be exposed not only to respiratory diseases such as colds, asthma and bronchitis, but also to various diseases such as cardiovascular diseases, skin diseases and eyeball diseases. .. Fine dust has been reported to exacerbate respiratory illnesses such as asthma and cause pulmonary dysfunction, in particular ultrafine dust has very fine particles that are not filtered through the nasal mucosa. Immediately penetrates into the alveoli, increasing the prevalence and premature mortality of waste disease. In addition, fine dust invades the body not only through the nose and mouth but also through the skin. Fine dust is up to 20 times smaller than the size of the pores, so it is difficult to easily invade and remove the fine dust, and the increased inflammatory cytokines and active oxygen in the body due to the absorbed fine dust reduce skin immunity. It further accelerates skin aging phenomena such as acne induction, wrinkle formation, skin dryness and pigmentation. Specifically, fine dust causes an inflammatory reaction that damages the skin barrier, exacerbates atopic dermatitis, produces reactive oxygen species in mitochondria, reduces collagen synthesis, and degrades collagen. Can induce skin aging. Also, polynuclear aromatic hydrocarbons (PAHs) attached to fine dust proliferate melanocytes and increase pigment spots on the face, especially for Asians, because their skin color is darker than white. There is a high possibility that pigmented spots due to fine dust will increase, and for people with sensitive skin, dermatitis, burning sensation, and itching sensation may be increased. With long-term exposure to fine dust, irreparable skin damage not only causes the skin to lose its ability to protect the body from environmental stressors, but can also cause serious illnesses such as skin cancer.

Recently, as the danger and damage of fine dust have become more serious, interest in developing products for blocking fine dust has increased, and as a result, cosmetics, health functional foods, air purifiers, masks, and other products related to fine dust have become more serious. The sales volume is increasing rapidly, and in particular, there is a continuous demand for the development of cosmetic compositions that can remove fine dust or significantly prevent the adsorption of fine dust. A typical example of a highly functional biomaterial that conforms to such a trend is a peptide material. It has physiological activity in vivo or in the skin depending on the sequence and structure of the amino acid sequence in the peptide, and is widely applied to the development of biological materials for wrinkle improvement, whitening, troublesome skin, and improvement of various skin diseases. It is also applicable to the development of semi-therapeutic products for the purpose, and is expected to have high industrial utility value as a cosmetic and pharmaceutical material.

On the other hand, Korean Registered Patent No. 1723941 discloses "a cosmetic composition for adsorbing and removing fine dust containing a coral tree and Bengal rubber wood resin extract as an active ingredient", and is disclosed in Korean Registered Patent No. 1850313. Discloses "a cosmetic composition for removing heavy metal or fine dust containing chrysanthemum extract as an active ingredient", but a cosmetic for removing fine dust or adsorbing containing the peptide complex of the present invention as an active ingredient. The composition is not disclosed.

Korean Registered Patent No. 1723941

The present invention has been derived by the above-mentioned requirements, and the present inventors have attached a saturated fatty acid or an unsaturated fatty acid to an amino acid; or an N-terminal, C-terminal or side chain of an oligopeptide; By developing a fatty acid-amino acid complex and a fatty acid-oligopeptide complex, and confirming that the complex can reduce cytotoxicity due to fine dust and can be aggregated with fine dust to remove fine dust. The present invention has been completed.

In order to solve the above-mentioned problems, the present invention presents a cosmetic composition for removing or adsorbing fine dust containing a complex in which a fatty acid is bound to an amino acid; or the N-terminal, C-terminal or side chain of an oligopeptide; as an active ingredient. Provide things.

The peptide complex according to the present invention is excellent not only in the cell protective effect against fine dust but also in the effect of agglutinating or binding to the fine dust to remove the fine dust. Therefore, the composition containing the peptide complex of the present invention has a fine dust. It is expected that it can be usefully used as a cosmetic or pharmaceutical composition for the prevention and treatment of various diseases caused by exposure.

It is a conceptual diagram which shows the method of binding a fatty acid to the N-terminal (A), C-terminal (B), or the side chain (C) of an oligopeptide (pentapeptide). It is the result of analysis of the peptide complex (Table 5-Category 9) purified through High Performance Liquid Chromatography (HPLC). It is the result of analysis of the peptide complex (Table 5-Category 9) purified through High Performance Liquid Chromatography (HPLC). It is the result of analysis of the peptide complex (Table 5-Category 9) purified through High Performance Liquid Chromatography (HPLC). This is the result of confirming the cell viability after simultaneously treating HaCaT cells with ultrafine dust (diesel exhaust particles; fine dust having a diameter of 2.5 μm or less, PM2.5) and the peptide complex of the present invention. N.C. (negative control group): 0.2% DMSO (dimethyl sulfoxide) / DMEM (Dulbecco's Modified Eagle Medium) treatment, P.C. (positive control group): 10% DMSO / DMEM treatment. This is the result of confirming the cell viability after simultaneously treating HaCaT cells with ultrafine dust (diesel exhaust particles; fine dust having a diameter of 2.5 μm or less, PM2.5) and the peptide complex of the present invention. N.C. (negative control group): 0.2% DMSO (dimethyl sulfoxide) / DMEM (Dulbecco's Modified Eagle Medium) treatment, P.C. (positive control group): 10% DMSO / DMEM treatment. This is the result of confirming the cell viability after simultaneously treating HaCaT cells with ultrafine dust (diesel exhaust particles; fine dust having a diameter of 2.5 μm or less, PM2.5) and the peptide complex of the present invention. N.C. (negative control group): 0.2% DMSO (dimethyl sulfoxide) / DMEM (Dulbecco's Modified Eagle Medium) treatment, P.C. (positive control group): 10% DMSO / DMEM treatment. This is the result of confirming the cell viability after simultaneously treating HaCaT cells with ultrafine dust (diesel exhaust particles; fine dust having a diameter of 2.5 μm or less, PM2.5) and the peptide complex of the present invention. N.C. (negative control group): 0.2% DMSO (dimethyl sulfoxide) / DMEM (Dulbecco's Modified Eagle Medium) treatment, P.C. (positive control group): 10% DMSO / DMEM treatment. This is the result of confirming the cell viability after simultaneously treating HaCaT cells with ultrafine dust (diesel exhaust particles; fine dust having a diameter of 2.5 μm or less, PM2.5) and the peptide complex of the present invention. N.C. (negative control group): 0.2% DMSO (dimethyl sulfoxide) / DMEM (Dulbecco's Modified Eagle Medium) treatment, P.C. (positive control group): 10% DMSO / DMEM treatment. This is the result of confirming the cell viability after simultaneously treating HaCaT cells with ultrafine dust (diesel exhaust particles; fine dust having a diameter of 2.5 μm or less, PM2.5) and the peptide complex of the present invention. N.C. (negative control group): 0.2% DMSO (dimethyl sulfoxide) / DMEM (Dulbecco's Modified Eagle Medium) treatment, P.C. (positive control group): 10% DMSO / DMEM treatment. This is the result of confirming the cell viability after simultaneously treating HaCaT cells with ultrafine dust (diesel exhaust particles; fine dust having a diameter of 2.5 μm or less, PM2.5) and the peptide complex of the present invention. N.C. (negative control group): 0.2% DMSO (dimethyl sulfoxide) / DMEM (Dulbecco's Modified Eagle Medium) treatment, P.C. (positive control group): 10% DMSO / DMEM treatment. This is the result of confirming the cell viability after simultaneously treating HaCaT cells with ultrafine dust (diesel exhaust particles; fine dust having a diameter of 2.5 μm or less, PM2.5) and the peptide complex of the present invention. N.C. (negative control group): 0.2% DMSO (dimethyl sulfoxide) / DMEM (Dulbecco's Modified Eagle Medium) treatment, P.C. (positive control group): 10% DMSO / DMEM treatment. This is the result of confirming the cell viability after simultaneously treating HaCaT cells with ultrafine dust (diesel exhaust particles; fine dust having a diameter of 2.5 μm or less, PM2.5) and the peptide complex of the present invention. N.C. (negative control group): 0.2% DMSO (dimethyl sulfoxide) / DMEM (Dulbecco's Modified Eagle Medium) treatment, P.C. (positive control group): 10% DMSO / DMEM treatment. This is the result of confirming the cell viability after simultaneously treating HaCaT cells with ultrafine dust (diesel exhaust particles; fine dust having a diameter of 2.5 μm or less, PM2.5) and the peptide complex of the present invention. N.C. (negative control group): 0.2% DMSO (dimethyl sulfoxide) / DMEM (Dulbecco's Modified Eagle Medium) treatment, P.C. (positive control group): 10% DMSO / DMEM treatment. This is the result of confirming the cell viability after simultaneously treating HaCaT cells with ultrafine dust (diesel exhaust particles; fine dust having a diameter of 2.5 μm or less, PM2.5) and the peptide complex of the present invention. N.C. (negative control group): 0.2% DMSO (dimethyl sulfoxide) / DMEM (Dulbecco's Modified Eagle Medium) treatment, P.C. (positive control group): 10% DMSO / DMEM treatment. It is a graph which shows cytotoxicity by treating the solution which contained the ultrafine dust in the human lung cancer epithelial cell line (A549) according to the concentration. This is the result of confirming the cell viability after simultaneously treating A549 cells with a complex of ultrafine dust and oligopeptides bound with saturated fatty acids. The information of the graph X-axis sample is the same as Table 10 below. Peptide complex (P11, a complex in which capric acid (C10) is bound to the 9th K-side chain of oligopeptide (llwialrkk) of SEQ ID NO: 30) using silver staining method and ultrafine dust aggregation effect. It is an SDS-PAGE gel photograph analyzed. It is a graph which shows the particle removal efficiency of the general mask (HIP's) and the fine dust mask (KF84) which are commercially available using the dust collection (particle removal) efficiency evaluation system. A general mask in which nothing was sprayed using the dust collection (particle removal) efficiency evaluation system, a general mask in which purified water was sprayed, and a general mask in which a 250 ppm solution of fatty acid-oligopeptide complex (diluted distilled water) was sprayed. It is a graph which shows the ultrafine dust particle removal efficiency of a mask. A general mask in which nothing was sprayed using the dust collection (particle removal) efficiency evaluation system, a general mask in which purified water was sprayed, and a general mask in which a 250 ppm solution of fatty acid-oligopeptide complex (diluted distilled water) was sprayed. It is a graph which shows the ultrafine dust particle removal efficiency of a mask.

In order to achieve the object of the present invention, the present invention is for fine dust removal or adsorption containing a complex in which an amino acid is bound to an amino acid; or an N-terminal, C-terminal, or side chain of an oligopeptide; as an active ingredient. Provide cosmetic compositions.

In the present invention, the term "fine dust" is a concept including ultra-fine dust, the term "fine dust" means dust having a diameter of 10 μm or less, and the term “ultra-fine dust” means dust having a diameter of 2.5 μm or less. It includes, but is not limited to, air pollutants such as yellow sand, automobile exhaust gas, factory soot, combustible gas around daily life, and heavy metals.

In the present invention, the term "fine dust adsorption" means to adsorb and remove fine substances remaining in pores in the skin and the like. Treatment of a cosmetic composition based on a fatty acid-amino acid complex or a fatty acid-oligopeptide complex enhances the adsorption power for fine dust in the skin and is hypoallergenic to the skin, but can occur when the fine dust remains. It can eliminate inflammation or skin troubles.

In the present invention, the terms "N-terminal and C-terminal" _{mean one end having an amino group (-NH 2} ) and the other end having a carboxyl group (-COOH) in the amino acid sequence of a peptide, and the term "side chain" is used. It means an aliphatic carbon chain attached to a ring in a carbon chain or a cyclic compound branched from a linear carbon atom in which carbon atoms are regularly connected.

In the fine dust removing or adsorbing cosmetic composition of the present invention, the amino acids are alanine (A), cysteine (Cysteine, C), aspartic acid (D), glutamic acid (E), and the like. Phenylalanine, F, Glycine, G, Histidine, H, Isoleucine, I, Lysine, K, Leucine, L, Methionine, M, Asparagine (Asparagine, N), Pyrrolysine, O, Proline, P, Glutamine, Q, Arginine, R, Serine, S, Threonine, T, Serenocysteine It is also one or more selected from the group consisting of (Selenocysteine, U), Valin (Valine, V), Tryptophan, W, and Tyrosine, Y, preferably glycine (G), glutamic acid (Glysine (G), glutamate (Y). E) or lysine (K), but not limited to them. The amino acids include, but are not limited to, both D-type amino acids and L-type amino acids.

Further, in the cosmetic composition for removing fine dust or adsorbing the fine dust of the present invention, the oligopeptide is a peptide consisting of two or more amino acids, preferably AAPV (SEQ ID NO: 1) and AAP (SEQ ID NO: 2). , AA (SEQ ID NO: 3), GHK (SEQ ID NO: 4), GH (SEQ ID NO: 5), KTTKS (SEQ ID NO: 6), KTTK (SEQ ID NO: 7), KTT (SEQ ID NO: 8), KT (SEQ ID NO: 9), EEMQRR (SEQ ID NO: 10), EEMQR (SEQ ID NO: 11), EEMQ (SEQ ID NO: 12), EEM (SEQ ID NO: 13), EE (SEQ ID NO: 14), KKKKKKKKK (SEQ ID NO: 15), KKKKK (SEQ ID NO: 16), KKK (SEQ ID NO: 17), KK (SEQ ID NO: 18), GPO (SEQ ID NO: 19), GP (SEQ ID NO: 20), GQPR (SEQ ID NO: 21), GQP (SEQ ID NO: 22), GQ (SEQ ID NO: 23), TTKS ( Group consisting of SEQ ID NO: 24), TKS (SEQ ID NO: 25), TK (SEQ ID NO: 26), RRRRRRRRR (SEQ ID NO: 27), RRRRR (SEQ ID NO: 28), RRR (SEQ ID NO: 29), and LLWIAL RKK (SEQ ID NO: 30). One or more selected from, but not limited to them. The amino acid of the oligopeptide is composed of a D-type amino acid or an L-type amino acid, and the amino acid PO of SEQ ID NO: 19 is also O-hydroxyproline, but this is not the case.

In the fine dust removing or adsorbing cosmetic composition of the present invention, the fatty acid is also a saturated or unsaturated fatty acid, but is not limited to this.

The saturated fatty acids according to the present invention include capric acid (C6: 0), caprylic acid (C8: 0), pelargonic acid (C9: 0), and capric acid (C10: 0). ), Undecylic acid (C11: 0), Lauric acid (C12: 0), Myristic acid (C14: 0), Pentadecylic acid (C15: 0), Palmitic acid (Palmitic) acid, C16: 0), Margaric acid (C17: 0), Stealic acid (C18: 0), Nonadecylic acid (C19: 0), Arachidic acid (C20: 0) , Heneicosylic acid (C21: 0), Behenic acid (C22: 0), Tricosylic acid.C23: 0, Lignoceric acid (C24: 0), Pentacosylic acid, C25: 0), Cerotic acid (C26: 0), Heptacosylic acid (C27: 0), Montanic acid (C28: 0), Nonacosylic acid (C29: 0), Melicin Acid (Melissic acid, C30: 0), Henatria contylic acid (C31: 0), Lacceroic acid (C32: 0), Psyllic acid (C33: 0), Geddic One or more selected from the group consisting of acid, C34: 0), Ceroplastic acid (C35: 0) and Hexatria contylic acid (C36: 0), preferably capric acid, It is also, but is not limited to, capric acid, lauric acid, myristic acid, palmitic acid, margaric acid, stearic acid, behenic acid or lignoseric acid.

The unsaturated fatty acids include palmitoleic acid (C16: 1), oleic acid (C18: 1), Elaidic acid (C18: 1), and petroselinic acid (C18: 1). ), Vaccenic acid (C18: 1), Gondoic acid (C20: 1), Erucic acid (C22: 1), Nervonic acid (C24: 1), Linoleic acid, C18: 2), cis-Linolenic acid (C18: 3), Punicic acid (C18: 3), Eleostearic acid (C18: 3), stearidonic acid, C18: 4), Arachidonic acid (C20: 4), Eicosapentaenoic acid (C20: 5), Docosapentaenoic acid (C22: 5), Adrenic acid (C22) It is also one or more selected from the group consisting of: 4), Docosahexaenoic acid (C22: 6), and Ricinoleic acid (C18: 1), preferably oleic acid, linoleic acid, palmitoleic acid. , Elysinic acid, petroseric acid, baxenoic acid, gondoic acid, erucic acid, nervonic acid, cis-linolenic acid, punicic acid, eleostearic acid, docosapentaenoic acid, or ricinoleic acid, but not limited to them.

The cosmetic composition for removing or adsorbing fine dust of the present invention is a fatty acid-amino acid complex or a fatty acid-oligopeptide complex in which a fatty acid is bound to an amino acid; or the N-terminal, C-terminal or side chain of an oligopeptide. The complex of the fatty acid and the amino acid is also a complex of glycine (G), glutamic acid (E) or lysine (K) bound to oleic acid, which is an unsaturated fatty acid, but is not limited thereto. The fatty acid-oligopeptide complex is an oligopeptide consisting of the amino acid sequences of SEQ ID NOs: 1, 4, 6, 7, 8, 10, 11, 15, 16, 17, 19, 21, 27, 28, 29 and 30. One selected from the group consisting of capric acid, capric acid, lauric acid, myristic acid, palmitic acid, margaric acid, stearic acid, behenic acid and lignoseric acid at any one of the N-terminal, C-terminal or side chains. Saturated fatty acids above; or oleic acid, linoleic acid, palmitoleic acid, ellagic acid, petroseric acid, bacsenic acid, gondoic acid, erucic acid, nervonic acid, cis-linolenic acid, punicic acid, eleostaic acid, docosapentaenoic acid And one or more unsaturated fatty acids selected from the group consisting of lysinolic acid; but not limited thereto.

In the fine dust removing or adsorbing cosmetic composition of the present invention, the complex in which the fatty acid is bound to the side chain of the oligopeptide is preferably the oligopeptide of SEQ ID NO: 30 (LLWIALRKK, L-type amino acid; llwialrkk, D. Type amino acid) 9th lysine (K) in the amino acid sequence; 4th lysine in the oligopeptide amino acid sequence of SEQ ID NO: 6 (KTTKS) and SEQ ID NO: 7 (KTTK); oligopeptide amino acid of SEQ ID NO: 16 (KKKKK) It is also the amino acid bound to the fifth lysine in the sequence; but is not limited to it.

The peptide complex of the present invention is also in the form of an amino group (-NH ₂ ) or a carboxyl group (-COOH) bonded to _{the N-terminal or C-terminal, specifically, NH 2} -amino acid-fatty acid-. COOH; NH _2- Oligoxy-Carboxylic Acid-COOH; COOH-Amino Acid-Carboxylic Acid-NH ₂ ; COOH-Oligopeptide-Carboxylic Acid-NH ₂ ; NH _2- Amino Acid-Amino Acid-COOH; NH _2- Carboxylic Acid-Oligopeptide-COOH; It is also in the form of COOH-fatty acid-amino acid-NH ₂ ; and COOH-fatty acid-oligopeptide-NH _{2, but is not limited thereto.}

The complex in which saturated or unsaturated fatty acids are bound to the N-terminal, C-terminal, or side chain of the amino acid; or oligopeptide of the present invention is not toxic to normal skin cells and is toxic to cell toxicity due to fine dust. It can be reduced and has the effect of removing ultrafine dust particles (dust collection).
Specifically, a complex in which the capric acid of the present invention is bound to the oligopeptide of SEQ ID NO: 6, 7, 15, 16, 27, 28 or 29; palmitic acid and SEQ ID NO: 4, 6, 7, 15, 16 , 27, 28, 29 or 30 oligopeptides bound; oleic acid and SEQ ID NOs: 1, 4, 6, 7, 8, 11, 15, 16, 21, 27, 28 or 30 oligopeptides Bound complex; a complex of linoleic acid bound to the oligopeptide of SEQ ID NO: 10, 16, 27, 28 or 30; a complex of capric acid bound to the oligopeptide of SEQ ID NO: 15, 16, 27 or 28. Body; complex in which lauric acid is bound to the oligopeptide of SEQ ID NO: 4, 15, 16, 17, 27 or 28; complex in which myristic acid is bound to the oligopeptide of SEQ ID NO: 10, 15, 16, 27 or 28. Body; complex with margaric acid bound with the oligopeptide of SEQ ID NO: 15, 16, 27, 28 or 30; complex with stearic acid bound with the oligopeptide of SEQ ID NO: 15, 16, 27, 28 or 30; A complex in which behenic acid and an oligopeptide of SEQ ID NO: 15, 16, 19, 27, 28 or 30 are bound; a complex in which lignoseric acid and an oligopeptide of SEQ ID NO: 15, 16, 27, 28 or 30 are bound; A complex of palmitoleic acid bound to an oligopeptide of SEQ ID NO: 1, 15, 21 or 27; a complex of ellagic acid bound to an oligopeptide of SEQ ID NO: 6, 15, 16, 19 or 27; a complex of petroseric acid and a sequence. A complex to which the oligopeptide of No. 6, 15, 16, 27 or 30 is bound; a complex to which the oligopeptide of SEQ ID NO: 15, 27 or 28 is bound to vacenoic acid; Gondoic acid and SEQ ID NO: 6, 15, 27 , 28 or 30 oligopeptides bound; erucic acid plus SEQ ID NO: 15, 27, 28 or 30 oligopeptides bound; nervonic acid plus SEQ ID NOs: 4, 6, 15, 16, 27 , 28 or 30 oligopeptides bound; cis-linolenic acid and SEQ ID NOs: 15, 16, 27, 28 or 30 oligopeptides bound; punicic acid and SEQ ID NOs: 6, 15, 16 Or a complex in which 27 oligopeptides are bound; a complex in which eleostearic acid and an oligopeptide of SEQ ID NO: 6, 15, 27 or 30 are bound; docosapentaenoic acid and SEQ ID NO: 1, 15, 16 or 29 Oligopeptides are bound Complex; or complex in which ricinoleic acid and oligopeptide of SEQ ID NO: 15, 27 or 30 are bound; reduces the cytotoxicity increased by ultrafine dust and increases the rate of ultrafine dust particle removal (dust collection). Excellent in increasing effect.

The fine dust removing or adsorbing cosmetic composition of the present invention comprises solutions, suspensions, emulsions, pastes, gels, creams, lotions, powders, soaps, cleansing agents containing surfactants, oils, powder foundations, foundations, etc. It is desirable that it is one of the selected dosage forms of wax foundation and spray, and more preferably, skin lotion, cream, soft lotion, nutritional lotion, pack, essence, hair tonic, shampoo, and rinse. , Hair Conditioner, Hair Treatment, Gel, Skin Lotion, Skin Softener, Skin Toner, Astringent, Lotion, Milk Lotion, Moisture Lotion, Nutrition Lotion, Massage Cream, Nutrition Cream, Eye Cream, Moisture Cream, Hand Cream, Foundation, Nutrition Essence , Sunscreen, soap, cleansing foam, cleansing lotion, cleansing cream, body lotion and body cleanser may have any one dosage form selected from, but not limited to. The composition of each of these dosage forms is necessary for the formulation of the dosage form and can contain various suitable bases and additives, and the types and amounts of these components are easily selected by those skilled in the art. Can be done.

When the dosage form of the present invention is a paste, cream or gel, the carrier components include animal fiber, plant fiber, wax, paraffin, starch, tracant, cellulose derivative, polyethylene glycol, silicon, bentonite, silica, talc or zinc acid. Etc. are used.

When the dosage form of the present invention is a powder or spray, lactouse, talc, silica, aluminum hydroxide, calcium silicate or polyamide powder is used as a carrier component, and in particular, when it is a spray, chlorofluorocarbonation is used. It may contain propellants such as hydrogen, propane / butane or dimethyl ether.

When the dosage form of the present invention is a solution or an emulsion, a solvent, a solvent agent or an emulsion agent is used as a carrier component, for example, water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol. , Benzylbenzoate, propylene glycol, 1,3-butylglycol oil, glycerol aliphatic esters, polyethylene glycols or fatty acid esters of sorbitan.

When the dosage form of the present invention is a suspension, the carrier component may be water, a liquid diluent such as ethanol or propylene glycol, an ethoxylated isostearyl alcohol, a polyoxyethylene sorbitol ester and a polyoxyethylene sorbitan ester. Suspension agents such as, microcrystalline cellulose, aluminum metahydroxydo, bentonite, aga or tracant, etc. are used.

When the dosage form of the present invention is a surfactant-containing cleansing, fatty alcohol sulfate, fatty alcohol ether sulfate, sulfosuccinic acid monoester, acetylonic acid, imidazolinium derivative, methyl taurine, sarcosinate, etc. Fatty acid amide ether sulfate, alkylamide betaine, fatty alcohol, fatty acid glyceride, fatty acid diethanolamide, vegetable oil, lanolin derivative, ethoxylated glycerol fatty acid ester and the like are used.

Hereinafter, the present invention will be described in detail by way of examples. However, the following examples are merely examples of the present invention, and the content of the present invention is not limited to the following examples.

Example 1. Production of peptide complex The amino acid raw material used for complex synthesis was purchased from GLS (GL Biochem, Shanghai), and the fatty acid was purchased from TCI (TCI chemicals, India) and Sigma (Sigma Aldrich, US). Purchased (Table 1), dimethylformamide (DMF), diisopropylethylamine (N, N-diisopropylethylamine, DIEA), dichloromethane (dichloromethane, DCM) and piperidin (piperidine) are available from Daejungchem, Korea. ) And used it.

1-1. Resin swelling
Using a solid-phase synthesis reactor equipped with a filter membrane, peptide synthesis with a carboxy group (-COOH) at the end of the complex is performed by 2-Chlorotrityl chloride resin (Bead Tech, Bead Tech, (Korea) was used, and Rinkamide resin (GLS, China) was used for peptide synthesis terminated by a peptide _{bond (-CONH 2) at the end of the complex.} The resin was swollen for 20 minutes with dichloromethane and dimethylformamide to prepare for synthesis.

1-2. Amino acid loading
Synthesis with chlorotrityl chloride resin involves loading the first amino acid into the resin. The resin was removed under reduced pressure through a filtration membrane. After completely dissolving 3 to 5 equivalents of amino acid in DMF, the resin was added to chlorotrityl chloride resin, and diisopropylethylamine in consideration of density was added in an amount corresponding to 3 to 5 equivalents of chlorotrityl chloride resin. .. After that, the reaction was carried out at 24 ° C to 32 ° C for 5 hours or more using a reactor.

1-3. Resin Fmoc deprotection The synthetic process using the chlorotrityl chloride resin or link amide resin included a process of deprotecting Fmoc (Fluorenylmethyloxycarbonyl chloride). In the resin Fmoc deprotection process, the solvent was removed through the filtration membrane under reduced pressure, washed with DMF containing 20% (v / v) piperidine for 5 minutes, and then washed again for 10 minutes. The reaction solution was removed by filtration under reduced pressure, and the cells were washed 6 times or more for 5 minutes each using DCM or DMF.

1-4. Synthesis of fatty acid-amino acid complex and fatty acid-oligopeptide complex After completely dissolving 3 to 5 equivalents of amino acid in the above-mentioned link amide resin in DMF, it was injected into the link amide resin from which the solvent had been removed. 2 M HOBt / DIC (hydroxybenzotriazole / diisopropylcarbodiimide) was injected with a coupling reagent according to the amino acid equivalent and the linkamide resin amount. After that, the synthesis was carried out at 24-32 ° C for 5 hours or more using a reactor. When the reaction was completed, the solvent was removed under reduced pressure through a filtration membrane, and then washed with clean DMF 6 times for 5 minutes each. After the washing was completed, each amino acid was sequentially coupled by a method such as the above-mentioned amino acid binding method. Then, 3 equivalents of fatty acid and 2 M HOBt / DIC were injected into the resin in which the peptide was synthesized according to the amino acid equivalents and the resin amount. Then, the reaction was carried out at 24-32 ° C. for 5 hours or more using a reactor.

1-5. Cleavage
After completion of the reaction, the solvent was removed through the filtration membrane under reduced pressure, washed twice with clean DMF for 2 minutes each and twice with DCM for 2 minutes each, and then the solvent was removed under reduced pressure via the filtration membrane. Almost removed. The dried peptide complex resin was separated for 4 hours using a 70% (v / v) TFA / 29% (v / v) DCM / 1% (v / v) H _{2 O solution.}

1-6. Recrystallization (Crystallize)
The separated solvent was extracted by recrystallization of the crude product with ethyl ether. The specific synthesis process is shown in Table 2 below.

1-7. Synthetic products Through Solid Phase Peptide Synthesis (SPPS), fatty acids with 6 to 24 carbon atoms (Table 3) and amino acids glycine (G), glutamic acid (E), and lysine. (K), or a novel complex to which the oligopeptides of SEQ ID NOs: 1 to 30 are bound has been developed. _{Specifically, amino acids; or amino acids by binding the amino group (NH 2} ) present at the N-terminal of the oligopeptide to the carboxyl group (COOH) of the fatty acid (Fig. 1A) and using ethylene glycol as a linker. Alternatively, the carboxyl group of the amino acid can be bound to the carboxyl group present at the C-terminal of the oligopeptide (Fig. 1B), and the carboxyl group of the amino acid can be bound to the side chain present at the lysine (K) of the oligopeptide (Fig. 1C).

The finally synthesized amino acid or oligopeptide-fatty acid complex is shown in Tables 4 and 10 below, where uppercase letters mean L-type amino acids and lowercase letters mean D-type amino acids. Amino acid; or a complex in which a fatty acid is bound to the N-terminal of an oligopeptide is described in the order of fatty acid-peptide, and a complex in which a fatty acid is bound to the C-terminal of an amino acid or oligopeptide is described in the order of peptide-fatty acid. The complex in which the fatty acid is bound to the side chain of the peptide is indicated by underlining (_) the amino acid having the side chain to which the fatty acid is bound, and then in parentheses on the fatty acid.

Example 2. Complex Purification The crude complex product synthesized in Example 1 was dissolved in distilled water supplemented with 10% (v / v) acetonitrile (acetonitrile), and then high under gradient conditions. Performance Purified by liquid chromatography (HPLC) (Figs. 2 to 4) and lyophilized to obtain the desired complex. The HPLC conditions and the gradient conditions for separation are shown in Tables 11 and 12 below. The molecular weight of the purified crude composite product was measured using MALDI-TOF-MASS, the molecular weight measurement method is shown in Table 13, and the molecular weight measurement results are shown in Tables 14 to 23.

^{Example 3. Cytotoxicity analysis of ultrafine dust in HaCaT cells The number of cells is 2 × 10 4} to confirm the cytotoxicity of the fatty acid-amino acid complex and fatty acid-oligopeptide (SEQ ID NOs: 1 to 30) complex. The cells were diluted in DMEM (10% FBS) medium to a concentration of / ml, 100 ul each was dispensed into a 96-well culture vessel, and then cultured for 16 to 20 hours until the cells adhered to the plate surface. The medium was removed, each complex substance was diluted with DMEM medium to a concentration of 10 μM, treated with 100 μl cells _{, cultured in a 5% CO 2} incubator at 37 ° C for 24 hours, and then the medium was removed again. A 10-fold diluted solution of MTT (5 mg / ml in PBS) reagent in DMEM medium is dispensed in 100 μl increments, reacted for 3 to 4 hours, then the MTT reagent is removed, and DMSO (dimethyl sulfoxide) is dispensed in 100 μl increments. Then, after reacting in the incubator for 30 minutes, the DMEM medium-treated group, 0.2% DMSO / DMEM-treated group (negative control group), 10% DMSO / DMEM-treated group (positive control group) and the above table are measured through absorbance (540 nm) measurement. The cell viability of the group treated with the amino acids or oligopeptides disclosed in Table 10 and the complex in which the fatty acids were bound was analyzed.

As a result, it was confirmed that the cell viability of the complex-treated group was 100 ± 4%, which was similar to that of the negative control group, when compared with the negative control group having a cell viability of 100%. , The positive control group for cytotoxicity confirmed that the cell viability was 8 to 25% (holding result not presented). From these points, it was found that the complex in which the fatty acid is bound to the amino acid of the present invention; or the N-terminal, C-terminal or side chain of the oligopeptide; is not toxic to skin cells.

Example 4. Cell protective effect of amino acid or oligopeptide and fatty acid complex against ultrafine dust (HaCaT cells)
To see if the fatty acid-amino acid complex and the fatty acid-oligopeptide (SEQ ID NOs: 1-30) complex can reduce the cytotoxicity increased by ultrafine dust, human skin-derived keratinocytes ( HaCaT cells) were treated with ultrafine dust (Diesel exhaust particles, DEP) and complexes and analyzed for cytotoxicity through the MTT assay. The DEP (fine dust with a diameter of 2.5 μm or less, PM2.5) was purchased from the National Institute for Environmental studies, Japan, and is a 4JB1 type 2740cc 4-cylinder direct injection diesel engine (Isuzu). Automobile Co., Japan) was operated under 1500 rpm load conditions and 10 torque (10 kg / ml) conditions and collected by a glass fiber filter.

Dilute in DMEM (10% FBS) medium so that the number of cells is 2 × 10 ⁴ cells / ml, dispense 100 μl each into a 96-well culture vessel, and incubate for 16 to 20 hours until the cells adhere to the plate surface. bottom. After culturing, remove the medium, dispense 100 μl each of the solution containing 10 μM complex and 50 μg / ml concentration of ultrafine dust into each well, and use a 5% CO ₂ incubator at 37 ° C for 24 hours. After culturing, the medium was removed again. Then, the cell viability was confirmed by the MTT analysis method in the same manner as in Example 3.

As a result, it was confirmed that the cell viability was significantly increased in the group treated simultaneously with the ultrafine dust and the complex in which the amino acid or oligopeptide and the fatty acid were bound, as compared with the group treated with only the ultrafine dust (). Figures 5 to 15),
From these points, it was found that the complex in which a fatty acid is bound to the amino acid or oligopeptide of the present invention can aggregate ultrafine dust and efficiently protect skin cells.

Example 5. Cytotoxicity analysis of ultrafine dust in A549 cells After treating ultrafine dust in human lung cancer epithelial cell line (A549), cytotoxicity was analyzed by MTT analysis method. The MTT assay was performed in the same manner as in Example 3 above, and cultured A549 cells were treated with 50, 60, 70, 80, 90, 100, 110, 120 and 200 μg / ml concentrations of ultrafine dust. ..
As a result, it was confirmed that the cell viability decreased as the treatment concentration of ultrafine dust increased, and that only about 20% of the cells survived in the 200 μg / ml fine dust treatment group, which was the highest concentration (Fig. 16). ).

Example 6. Analysis of cytoprotective effect of peptide-fatty acid complex against ultrafine dust (A549 cells)
Analyzing cytotoxicity through MTT analysis to determine if the fatty acid-oligopeptide (saturated fatty acid binding to the side chain of the amino acid sequence of SEQ ID NO: 30) complex can reduce cytotoxicity from ultrafine dust. bottom. The MTT analysis method was carried out in the same manner as in Example 3 above.
As a result, the cell viability increased in the group treated with the fatty acid-oligopeptide complex compared to the group treated with only ultrafine dust (about 40%), and the remaining C8 to 16 excluding the saturated fatty acid of C6 in particular. Cell viability is significantly increased in the peptide complex bound with saturated fatty acids of, among which 70% is the complex bound with capric acid (C10) (P4, P11, P18, P25). It was confirmed that the above cell viability was shown and that the cell toxicity to ultrafine dust was reduced (Fig. 17).

Example 7. Analysis of aggregation effect of fatty acid-oligopeptide complex and ultrafine dust using silver staining method
20% SDS-PAGE gel is simultaneously treated with ultrafine dust and fatty acid-oligopeptide complex P11 (capric acid bond to the side chain of the amino acid sequence of SEQ ID NO: 30) and is not aggregated with ultrafine dust through silver staining. The amount of complex was confirmed.

In DMEM medium, 100 μg / ml concentration of ultrafine dust alone or ultrafine dust and 10, 50, 100 μM concentration of P11 complex are treated simultaneously, and then cultured for _{24 hours at 37 ° C. in a 5% CO 2 incubator.} A supernatant sample was prepared by centrifugation at a centrifugal force of 10,000 xg for 1 hour. After that, 15 μl of the supernatant was loaded on a 20% SDS-PAGE gel, and electropermanence was performed. The silver staining process was ^{carried out using Elpis Biotech kits (PeptiGel TM} , ELPISBIOTECH, EBA-1053) as follows. The gel after electrical eversion was reacted with a solution of 30% ethanol and 10% acetic acid for 1 hour to immobilize, and washed twice with distilled water. After that, the gel was immersed in solution A for 1 minute, washed twice with distilled water, and the gel was immersed in solution B containing formaldehyde again for 20 to 30 minutes. Finally, the gel was washed twice with distilled water for 1 minute, then dipped in solution C and waited for a band to appear before terminating the reaction using fixative.

As a result, the band strength was slightly reduced in the group treated with the ultrafine dust and the complex P11 at the same time as compared with the group treated with the complex P11 alone, which was due to the aggregation of the ultrafine dust and the fatty acid-oligopeptide complex. It was confirmed that the amount of peptide remaining in the supernatant was reduced (Fig. 18). From these points, it was found that the complex in which the fatty acid is bound to the oligopeptide of the present invention can remove the ultrafine dust by agglutinating with the ultrafine dust.

Example 8. Dust collection (particle removal) efficiency analysis of fatty acid-oligopeptide complex using comparison of fine dust particle permeation amount of mask Adsorbs ultrafine dust to which the fatty acid-oligopeptide complex moves and filters the mask In order to confirm whether or not to increase the efficiency, the dust collection (particle removal) efficiency is analyzed, and the evaluation method and calculation formula of the dust collection efficiency are as shown in Table 24 below.

As a result of measuring the mask particle removal efficiency (%) by quantifying the permeation amount of 50-300 nm size fine dust particles in the air before and after using a general mask (HIP's) and a fine dust mask (KF84), the fine dust mask is Approximately 89 to 100% particle removal (dust collection) efficiency is achieved for fine dust particles of 50 to 300 nm size, while general masks are approximately 39 to 57 for fine dust particles of 50 to 300 nm size. It was confirmed that there is a particle removal efficiency of% (Fig. 19).
In addition, after spraying distilled water or a fatty acid-oligopeptide complex 250 ppm solution (distilled water diluted) once on a general mask, the amount of fine dust particles of 50 to 300 nm in the air permeated before and after is quantified before and after the mask. As a result of measuring the particle removal (dust collection) efficiency (%), the bungib collection efficiency is similar between the general mask in which nothing is sprayed and the general mask in which distilled water is sprayed, and nothing is sprayed. Compared to general masks, masks treated with fatty acid-peptide complex (Palmitic acid-KTTKS, Palmitic acid-RRRRR, Palmitic acid-KKKKK, Capric acid-RRRRR, Capric acid-RRRRRRRRR) solution have increased dust collection efficiency. In particular, it was confirmed that the smaller the fine dust particle size, the more excellent the particle removal efficiency of the fatty acid-peptide complex (FIGS. 20 and 21).

Claims (5)

A cosmetic composition for removing or adsorbing fine dust, which comprises a complex in which a fatty acid is bound to an amino acid; or the N-terminal, C-terminal or side chain of an oligopeptide; as an active ingredient. The cosmetic composition for removing or adsorbing fine dust according to claim 1, wherein the oligopeptide is one or more selected from the group consisting of the amino acid sequences of SEQ ID NOs: 1 to 30. The cosmetic composition for removing or adsorbing fine dust according to claim 1, wherein the fatty acid is a saturated fatty acid or an unsaturated fatty acid. The saturated fatty acids include caproic acid (C6: 0), caprylic acid (C8: 0), pelargonic acid (C9: 0), capric acid (C10: 0), and undecyl. Acid (Undecylic acid, C11: 0), Lauric acid (C12: 0), Myristic acid (C14: 0), Pentadecylic acid (C15: 0), Palmitic acid (C16) 0), Margaric acid (C17: 0), Stealic acid (C18: 0), Nonadecylic acid (C19: 0), Arachidic acid (C20: 0), Henecosilic acid (Heneicosylic acid, C21: 0), Behenic acid (C22: 0), Tricosylic acid.C23: 0, Lignoceric acid (C24: 0), Pentacosylic acid, C25: 0), Cerotic acid (C26: 0), Heptacosylic acid (C27: 0), Montanic acid (C28: 0), Nonacosylic acid (C29: 0), Melicic acid (Nonacosylic acid, C29: 0) Melissic acid, C30: 0), Henatria contylic acid (C31: 0), Lacceroic acid (C32: 0), Psyllic acid (C33: 0), Geddic acid, Claim 3 is characterized in that it is one or more selected from the group consisting of C34: 0), Ceroplastic acid (C35: 0) and Hexatria contylic acid (C36: 0). The above-mentioned cosmetic composition for removing or adsorbing fine dust. The unsaturated fatty acids include Palmitoleic acid (C16: 1), Oleic acid (C18: 1), Elaidic acid (C18: 1), Petroselinic acid (C18: 1), Vaccenic acid (C18: 1), Gondoic acid (C20: 1), Erucic acid (C22: 1), Nervonic acid (C24: 1), Linoleic acid, C18: 2), cis-Linolenic acid (C18: 3), Punicic acid (C18: 3), Eleostearic acid (C18: 3), stearidonic acid, C18: 4), Arachidonic acid (C20: 4), Eicosapentaenoic acid (C20: 5), Docosapentaenoic acid (C22: 5), Adrenic acid (C22: 4) ), Docosahexaenoic acid (C22: 6) and Ricinoleic acid (C18: 1), according to claim 3, wherein the fine dust removal or is characterized by being one or more selected from the group. Cosmetic composition for adsorption.

Images