KR101834790B1 - Composition for improving skin conditions comprising chlorogenic acid, myrcene, or these mixture as active ingredient - Google Patents

Abstract

The present invention relates to a composition for improving the skin condition of acne skin.
The composition of the present invention has antimicrobial activity against causative microorganisms of acne, inhibits inflammatory reaction generated in skin tissue, promotes regeneration of damaged skin, and effectively improves damaged skin condition due to acne.

Description

[0001] The present invention relates to a composition for improving skin condition containing chlorogenic acid, myrcene, or a mixture thereof as an active ingredient.

The present invention relates to a composition for improving skin condition, and more particularly to a composition for improving the skin condition of acne skin containing chlorogenic acid, myrcene or a mixture thereof as an active ingredient.

Acne, one of the most common skin inflammatory diseases, refers to inflammatory diseases of follicles, hair follicles and surrounding tissues due to hormonal action, excessive sebum secretion, bacterial infection, and the like.

Acne is caused by a variety of causes, but the increase in sebum secretion, hormones that stimulate the sebaceous glands (eg, androgens) and Propionibacterium acnes ), Inflammation of the hair follicle, abnormal keratinization of the hair follicle, and genetic predisposition. In addition, aerobic dermatophytes are not the primary cause of inflammation, but they have been found to exacerbate the inflammatory site and thereby exacerbate acne.

The treatment of acne is topical drug application and oral medication, and surgical treatment such as laser treatment, lapping, etc. Topical topical application is the use of antibacterial agents such as azelaic acid and salicylic acid for the purpose of antibacterial action against propionibacterium acnes, which is known as a cause of acne, and benzoyl peroxide ) Or the like is used as an external ointment type. However, this method has difficulties in formulating it, and it has been difficult to commercialize it due to regulations on related laws and the like. Oral medication is a method of using retinoids, corticosteroids, etc. for the purpose of inhibiting the function of the sebaceous gland and inhibiting the destruction of the hair follicle wall. However, excessive use of these oral preparations may cause side effects such as skin eruption, skin irritation, .

On the other hand, chlorogenic acid, an ester of caffeic acid and quinic acid, is a typical phenol resin complex extracted from coffee beans and coffee beans [Olthof MR. et al. J. Nutr., 131 (2001) 66-71] and is known as a powerful antioxidant [Iwai K. et al. Food Chem., 52 (2004) 4893-4898] anti-inflammatory, analgesic and antipyretic agents [dos Santos MD. et al. Biol. Pharm. Bull., 29 (2006) 2236-2240].

In addition, the aromatic hydrocarbon compound myrcene (or? -Myrcene) is a colorless or light yellow liquid monoterpenes compound. This olefinic organic compound is an important component found in abundance in essential oils in a large number of plants, including hops, lemon grass, cannabis, moxa, mangoes, myrsia, thyme, verbena, and bay leaves. Myrsene was first known as a precursor of pheromones in the Western pine beetle. However, afterwards its directional properties became widely known and it is widely used in household and fragrance industries as a flavoring active ingredient added to foods and beverages or medicines.

Although the medical properties related to the antiallergic, antioxidant, antiinflammatory, antitumor, and antimutagenic activity of the chlorogenic acid and the myrcene have already been known, despite the known various pharmacological activities, the skin condition in acne- Has not been known yet.

Accordingly, the present inventors have made intensive researches to develop effective substances for improving the condition of acne skin damaged by acne causing bacteria and skin-damaging bacteria while effectively inhibiting causative bacteria of acne skin. As a result, it has been found that chlorogenic acid, When applied to skin damaged by acne, it has an antimicrobial activity against causative microorganisms of acne, inhibits inflammatory reaction generated in skin tissue, promotes regeneration of damaged skin, and has an excellent effect of improving skin condition , Thereby completing the present invention.

Accordingly, it is a main object of the present invention to provide an antimicrobial effect on skin-damaging bacteria that affects the acne-causing worsening of acne causing bacteria and acne, and also to suppress the inflammatory reaction in the damaged skin tissue caused by acne causing bacteria and skin- The present invention provides a composition for improving the skin condition of acne skin, which has an effect of accelerating the regeneration of the skin.

According to one aspect of the present invention, there is provided a composition for improving the skin condition of acne skin comprising, as an active ingredient, at least one compound selected from chlorogenic acid and a myrcene compound.

The inventors of the present invention found that, in order to search for a substance effective for improving the skin condition of acne skin, among the various natural substances having antimicrobial activity, to regulate the skin damaged by acne and to search for a substance effective for suppressing the inflammatory reaction, As a result of research efforts, it was found that chlorogenic acid, myrcene, and mixed compounds thereof were effective for improving the skin condition of acne skin, and it was confirmed that there was no problem in safety when applied to skin.

The term "acne " as used in the present invention means an inflammatory disease that is infected by the causative bacteria of acne or fungi of the skin such as furgery lines, hair follicles and surrounding tissues, and the term" acne skin " Means acne-causing skin or acne-prone skin.

In addition, "improvement of the skin condition of acne skin" means that acne causal bacteria or skin ulcers are killed in inflammatory diseases infected by acne causal bacteria or skin ulcers, and the inflammatory reaction caused by the infection is relieved, Or promoting the regeneration of skin cells.

In the composition for improving skin condition of the present invention, the above-mentioned "chlorogenic acid" is a substance having a chemical formula of C ₁₆ H ₁₈ O ₉ and having a molecular weight of about 354.31, preferably represented by the following formula .

[Chemical Formula 1]

In the composition for improving skin condition of the present invention, the "myrcene" is a substance having a chemical formula of C ₁₀ H ₁₆ and having a molecular weight of about 136.239, preferably represented by the following formula (1) .

[Chemical Formula 1]

The chlorogenic acid and the myrcene proposed in the present invention include both chlorogenic acid salts, myrcene salts and optical isomers thereof, unless otherwise mentioned, and can be used as a material for improving the skin condition of acne skin. When the chlorogenic acid and the myrcene are used in the form of a salt, it is preferable to select a salt which is acceptable as an antibacterial agent, an antifungal agent, a food preservative additive, or a cosmetic additive in a salt with respect to chlorogenic acid and myrcene which are effective ingredients. Typically, the salt includes an acid addition salt of an inorganic acid such as a hydrochloride, a sulfate, a nitrate, a phosphate, a hydrobromide, and a hydroiodide, or an acetate, an oxalate, a malate, a bathate, a marine phosphate, a fumarate, And addition salts of organic acids such as malic acid salt, citric acid salt, tartaric acid salt, methanesulfonic acid salt and ethanesulfonic acid salt. The use of chlorogenic acid and myrcene in the human body is known to be toxic to humans through the use of analgesics and antipyretics, antioxidants, leukemia, diabetes, and cardiovascular diseases through prior arts. (See Fig. 1).

In the composition for improving the skin condition of the present invention, the chlorogenic acid, the myrcene, and the mixture thereof are characterized by inhibiting the growth of a strain of Propionibacterium , which is a cause of acne, and more particularly, Propionibacterium acnes ) strain or an antibiotic resistant propionibacterium acnes ( Propionibacterium acnes ) has an antibacterial activity. In a preferred embodiment of the present invention, the group treated with the chlorogenic acid, the myrcene and the mixture thereof of the present invention effectively inhibited the growth of the pathogenic bacterium, Propionibacterium acnes, and the antibiotic-resistant strain thereof, even at a very low concentration , And can be used to improve acne skin.

In addition, in the composition for improving the skin condition of the present invention, the chlorogenic acid, the myrcene, and the mixture thereof may be used not only as a causative agent of acne but also as an agent for increasing the inflammation occurrence site and affecting the worsening of acne, And has an antimicrobial effect on the cells. Examples of the above-mentioned skin-bearing bacterium include Staphylococcus aureus , Staphylococcus epidermidis , and purulent streptococci ( Sreptococcus pyogenes ), but the present invention is not limited thereto.

In addition, in the composition for improving skin condition of the present invention, the chlorogenic acid, myrcene, and mixtures thereof promote the synthesis of collagen protein in skin tissues damaged by acne causative bacteria and skin flora, and promote the regeneration of skin tissue .

Collagen of skin cells may be directly related to restoration or regeneration of tissue during skin regeneration, skin elasticity, wrinkle formation and skin damage. That is, when the synthesis of collagen or procollagen of skin cells is promoted, it is possible to obtain effects such as skin regeneration, wound healing caused by acne, restoration and regeneration of damaged skin tissue, prevention of skin aging, And it positively affects the state improvement.

In a preferred embodiment of the present invention, it was confirmed that when damaged chondrogenic acid, myrcene, and a mixture thereof were treated on damaged skin cells, regeneration of damaged skin cells was directly promoted. It was also observed that the regenerated skin cells morphologically showed the same growth as normal skin cells. Based on the above results, when chlorogenic acid, myrcene, and a mixture thereof are applied to the symptom of acne, the regenerated skin tissue does not differ from the surrounding normal skin tissue. Therefore, (Fig. 2 and Fig. 3). Fig. 2 shows the effect of stimulating the regeneration of skin cells.

Further, in the composition for improving skin condition of the present invention, the above-mentioned chlorogenic acid, myrcene, and mixtures thereof are characterized by inhibiting the production of nitric oxide and inhibiting the expression of IL-6 protein.

Acne caused by acne causative bacteria and skin fungus is further enlarged through the inflammatory reaction, and clinical symptoms of acne tend to deteriorate through skin eruption, skin irritation, or photoreceptor reaction. Therefore, early interception of the inflammatory reaction is very important for effective improvement of acne-causing skin condition.

In a preferred embodiment of the present invention, the production of LPS-induced nitric oxide and IL-6 protein is inhibited in the treatment of chlorogenic acid, myrcene, and mixtures thereof. Such nitric oxide secretion and IL-6 protein expression Was dose-dependent. Accordingly, the composition of the present invention effectively inhibits the production of nitric oxide and IL-6 protein, which are inflammation mediators, effectively blocks the inflammatory reaction around the acne-causing skin, thereby effectively improving the condition of acne skin.

In the composition for improving the skin condition of the present invention, the chlorogenic acid, the myrcene, and the mixture thereof may be formulated as an external preparation for skin, which can be applied to the skin, such as cream, gel, patch, spray, ointment, , Pasta or cataplasma, but the present invention is not limited thereto.

According to another aspect of the present invention, there is provided a cosmetic composition for improving the skin condition of acne skin containing, as an active ingredient, at least one compound selected from chlorogenic acid and a myrcene compound.

When the composition for improving the skin condition of the present invention is used as a cosmetic composition, it may further contain water-soluble vitamins, fat-soluble vitamins, polymer peptides, polymeric polysaccharides, sphingoglyphs and seaweed extracts.

The water-soluble vitamin may be any vitamin B, vitamin B2, vitamin B6, pyridoxine, pyridoxine hydrochloride, vitamin B12, pantothenic acid, nicotinic acid, nicotinic acid amide, folic acid, vitamin C, vitamin H (Sodium thiamine hydrochloride, sodium ascorbate, etc.) and derivatives (sodium ascorbic acid-2-phosphate, magnesium ascorbic acid-2-phosphate etc.) can also be used in the present invention It is included in water-soluble vitamins. The water-soluble vitamin can be obtained by a conventional method such as a microorganism conversion method, a purification method from a culture of a microorganism, an enzymatic method, or a chemical synthesis method.

The fat-soluble vitamin may be vitamin A, carotene, vitamin D2, vitamin D3, vitamin E (d1-alpha tocopherol, d-alpha tocopherol, d-alpha tocopherol) And their derivatives (such as palmitic acid ascorbin, stearic acid ascorbin, dipalmitic acid ascorbin, dl-alpha tocopheryl acetate, dl-alpha tocopherol nicotinate E, DL-pantothenyl alcohol, D-pantothenyl alcohol, Pantothenyl ethyl ether, etc.) and the like are also included in the fat-soluble vitamins used in the present invention.

The polymeric peptide may be any compound as long as it can be compounded in cosmetics, preferably collagen, hydrolyzed collagen, gelatin, elastin, hydrolyzed elastin, keratin and the like. The polymeric peptide can be obtained by a conventional method such as purification from a culture broth of a microorganism, an enzymatic method, or a chemical synthesis method, or purified from natural products such as ducks such as pigs and cows and silk fiber of silkworms .

The polymeric polysaccharide may be any compound as long as it can be incorporated in cosmetics, and examples thereof include hydroxyethyl cellulose, xanthan gum, chondroitin sulfate or a salt thereof (sodium salt, etc.). For example, chondroitin sulfate or a salt thereof can be usually purified from mammals or fish.

The sphingogly lipids may be any of those which can be incorporated in cosmetics, and examples thereof include ceramides, phytosphingosine and sphingoglycolipids. The sphingogly lipids can be purified from ordinary mammals, fish, shellfish, yeast or plants by a conventional method or can be obtained by chemical synthesis.

The seaweed extract may be any of those which can be incorporated in cosmetics. Preferably, the seaweed extract is selected from the group consisting of algae extract, red tiger extract, green algae extract, and the like. Sodium, potassium alginate and the like are also included in the seaweed extract used in the present invention. Seaweed extract can be obtained from seaweed by a conventional method.

The cosmetic of the present invention may contain, in addition to the above-mentioned essential ingredients, other ingredients usually added to cosmetics, if necessary.

Examples of the compounding ingredients that may be added include a preservative component, a moisturizer, an emollient, an ultraviolet absorber, a pH adjuster, a flavor, a blood circulation accelerator, a cold agent, a limiting agent and purified water.

Examples of the above-mentioned sustaining component include ester-based oils, hydrocarbon-based oils, silicone-based oils, fluorine-based oils, animal oils, and plant oils.

Examples of the ester-based oil include glyceryl tri-2-ethylhexanoate, cetyl 2-ethylhexanoate, isopropyl myristate, butyl myristate, isopropyl palmitate, ethyl stearate, octyl palmitate, isostearyl isostearate, Butyl stearate, ethyl linoleate, isopropyl linoleate, ethyl oleate, isosilyl myristate, isostearic acid isostearyl, isostearyl palmitate, octyldodecyl myristate, isosertyl isostearate, diethyl sebacate, (Capryl, capric acid) glyceryl, tri-2-ethylhexanoic acid trimethylol propane, triisostearic acid trimethylol propane, tetra 2-ethylhexanoic acid pentaerythritol But are not limited to, lactose, lactate, caprylylsacetyl, lauric acid decyl, hexyl laurate, myristyl dicyl, myristyl myristate, myristyl acid stearyl, stearyl stearate, decyl oleate, But are not limited to, cetyl, lauric acid, isostearyl, isostearyl isostearyl, isostearyl isostearate, isostearyl isostearate, isostearyl palmitate, octyl stearate, isostearyl stearate, isodecyl oleate, octyldodecyl oleate, octyldodecyl linoleate, Ethylhexanoate, stearyl 2-ethylhexanoate, stearyl 2-ethylhexanoate, hexyl isostearate, ethylene glycol dioctanoate, ethylene glycol dioleate, propylene glycol dicaprate, di (capryl, capric acid) propylene glycol, Propylene glycol dicaprylate, propylene glycol dicaprylate, neopentyl glycol dicaprate, neopentyl glycol dioctanoate, glyceryl tricarboxylate, glyceryl triunsaturated acid, glyceryl triisopalmitate, glyceryl triisostearate, octyl dodecanoate Wherein the octanoic acid is selected from the group consisting of octanoic acid, octanoic acid, octanoic acid, octanoic acid, octanoic acid, octanoic acid, octanoic acid, octanoic acid, octanoic acid, octanoic acid, octanoic acid, octanoic acid, , Octyldecyl isostearate, polyglycerin oleic acid ester, polyglycerin isostearic acid ester, triisocetyl citrate, triisolealkyl citrate, triisooctyl citrate, lauryl lactate, myristyl lactate, cetyl lactate, octyldecyl lactate, citric acid But are not limited to, triethyl citrate, acetyltriethyl citrate, acetyl tributyl citrate, trioctyl citrate, diisostearyl malate, 2-ethylhexyl hydroxystearate, di-2-ethylhexyl succinate, diisobutyl adipate, diisopropyl sebacate , Dodecyl sebacate, stearic acid cholesteryl, isostearic acid cholesteryl, hydroxystearic acid cholesteryl, oleic acid cholesteryl, oleic acid dihydrocholesteryl, isostearic acid pitostearyl, oleic acid pitostearyl , 12-stearoylhydroxystearic acid isostearyl, 12-stearoyl stearyl hydroxystearate, 12-stearoyl stearoyl stearate, Roil-hydroxy stearic acid and the like esters such as cetearyl source.

Examples of the hydrocarbon-based oil include hydrocarbons such as squalene, liquid paraffin, alpha-olefin oligomer, isoparaffin, ceresin, paraffin, floating isoparaffin, polybutene, microcrystalline wax and vaseline.

Examples of the silicone-based oil include polymethyl silicone, methylphenyl silicone, methyl cyclopolysiloxane, octamethyl polysiloxane, decamethyl polysiloxane, dodecamethyl cyclosiloxane, dimethyl siloxane methyl cetyloxysiloxane copolymer, dimethylsiloxane methyl stearoxysiloxane copolymer , An alkyl-modified silicone oil, and an amino-modified silicone oil.

Examples of the fluorine-based oil include perfluoropolyether and the like.

Examples of the animal or plant oil include avocado oil, almond oil, olive oil, sesame oil, rice bran oil, fresh flower oil, soybean oil, corn oil, rapeseed oil, goat oil, palm kernel oil, palm oil, castor oil, sunflower oil, It is also possible to use an oil-in-water emulsion which contains at least one component selected from the group consisting of cottonseed oil, palm oil, cucumber oil, wheat germ oil, rice germ oil, shea butter, Canned wax, carnauba wax, liquid lanolin, hardened castor oil, and the like.

Examples of the moisturizing agent include water-soluble low-molecular moisturizing agents, oil-soluble molecular moisturizing agents, water-soluble polymers, and oil-soluble polymers.

Examples of the water-soluble low molecular weight moisturizer include serine, glutamine, sorbitol, mannitol, sodium pyrrolidone-carboxylate, glycerin, propylene glycol, 1,3-butylene glycol, ethylene glycol, polyethylene glycol B Polypropylene glycol (polymerization degree n = 2 or more), polyglycerin B (polymerization degree n = 2 or more), lactic acid, lactic acid salt and the like.

Examples of the lipid-soluble low-molecular moisturizing agent include cholesterol and cholesterol ester.

Examples of the water-soluble polymer include carboxyvinyl polymer, polyaspartic acid, tragacanth, xanthan gum, methylcellulose, hydroxymethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, carboxymethylcellulose, water-soluble chitin, chitosan, dextrin .

Examples of the oil-soluble polymer include a polyvinylpyrrolidone / eicosene copolymer, a polyvinylpyrrolidone / hexadecene copolymer, nitrocellulose, a dextrin fatty acid ester, and a polymeric silicone.

Examples of the emollients include long chain acyl glutamic acid cholesteryl ester, hydroxystearic acid cholesteryl, 12-hydroxystearic acid, stearic acid, rosin acid, and lanolin fatty acid cholesteryl ester.

Examples of the ultraviolet absorber include para-aminobenzoic acid, ethyl paranobenzoate, amyl paranobenzoate, octyl paranobenzoate, ethylene glycol salicylate, phenyl salicylate, benzyl salicylate, benzyl salicylate, butylphenyl salicylate, homomenthyl salicylate, Benzyl cinnamate, 2-ethoxyethyl paratomethoxy cinnamate, octyl paratomethoxy cinnamate, mono-2-ethylhexane glyceryl diflamamethoxycinnamate, isopropyl paratumoxycinnamate, diisopropyl-diisopropyl cinnamate ester mixture , Urocannic acid, ethyl urocanoate, hydroxymethoxybenzophenone, hydroxymethoxybenzophenone sulfonic acid and salts thereof, dihydroxymethoxybenzophenone, sodium dihydroxymethoxybenzophenone disulfonate, dihydroxy Benzophenone, tetrahydroxybenzophenone, 4-tert-butyl-4'-methoxydibenzoylmethane, 2,4,6-trianylino-p- (carbo-2'-ethylhexyl- -1,3,5-triazine, 2- (2-H And the like can be mentioned hydroxy-5-methylphenyl) benzotriazole.

Examples of the pH adjusting agent include citric acid, sodium citrate, malic acid, sodium malate, fumaric acid, sodium fumarate, succinic acid, sodium succinate, sodium hydroxide, sodium monohydrogenphosphate and the like.

In addition, any of the above components may be blended within the range not impairing the objects and effects of the present invention, but it is preferably 0.01 to 5 parts by weight, more preferably 0.01 to 5 parts by weight, Preferably 0.01 to 3 parts by weight.

The cosmetic preparation prepared by containing the composition of the present invention may take the form of a solution, an emulsion, a viscous mixture or the like.

In addition, the components contained in the cosmetic composition of the present invention may contain, as an active ingredient, the components commonly used in cosmetic compositions in addition to the above components, for example, conventional additives such as stabilizers, pigments and natural flavors, And may further comprise a carrier.

The composition of the present invention can be used variously in cosmetics or cleansers for improving the skin condition of acne skin.

Examples of products to which the composition of the present invention can be added include a skin lotion, a skin softener, a skin toner, an astringent, a lotion, a milk lotion, a moisturizing lotion, a nutrition lotion, a massage cream, Cosmetics such as foundation, essence, nutrition essence, pack, soap, cleansing foam, cleansing lotion, cleansing cream, body lotion and body cleanser.

When the formulation of the present invention is a paste, cream or gel, animal fiber, plant fiber, wax, paraffin, starch, tracant, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc or zinc oxide may be used as the carrier component .

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.

In the case of the solution or emulsion of the present invention, a solvent, a solvent or an emulsifier is used as a carrier component, and examples thereof include water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, , 3-butyl glycol oil, glycerol aliphatic ester, polyethylene glycol or sorbitan fatty acid esters.

When 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.

According to another aspect of the present invention, there is also provided a pharmaceutical composition for improving the skin condition of acne skin comprising, as an active ingredient, at least one compound selected from chlorogenic acid and a myrcene compound.

The pharmaceutical compositions of the present invention may further comprise suitable carriers, excipients and diluents conventionally used in the manufacture of pharmaceutical compositions.

The pharmaceutical dosage forms of the compositions of the present invention may be used in the form of their pharmaceutically acceptable salts and may also be used alone or in combination with other pharmaceutically active compounds.

Examples of carriers, excipients and diluents that can be included in the composition of the present invention include lactose, dextrose, sucrose, oligosaccharide, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium Silicates, cellulose, methylcellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil.

When the composition of the present invention is formulated, it is prepared using diluents or excipients such as fillers, extenders, binders, humectants, disintegrants, and surfactants which are generally used.

The composition of the present invention can be applied to the skin and is directly applied to the skin in the form of external preparation for skin such as cream, gel, patch, spray, ointment, warning agent, lotion, liniment, pasta or cataplasma But is not limited thereto.

The preferred dosage of the mixed composition of the present invention varies depending on the condition and the weight of the patient, the degree of disease, the type of drug, the route of administration and the period of time, but may be suitably selected by those skilled in the art, Lt; RTI ID = 0.0 > g / ml. ≪ / RTI > External administration may be administered once a day or divided into several doses.

INDUSTRIAL APPLICABILITY The composition for improving the skin condition of the present invention has an antibacterial effect against Propionibacterium acnes bacteria and skin supplements which cause acne, promotes the synthesis of collagen proteins, promotes regeneration of damaged skin, It is expected that the effect of improving the skin condition of acne skin can be further improved because it has an effect of suppressing the inflammation reaction in the skin tissue damaged by the supernatant.

The features and advantages of the present invention are summarized as follows:

(I) The composition of the present invention is an antimicrobial effect against Propionibacterium acnes , which is a causative agent of acne, and Staphylococcus aureus, Staphylococcus epidermidis and purulent streptococci, which are skin-damaging bacteria that affect the worsening of acne when acne occurs .

(Ii) The composition of the present invention promotes the regeneration of skin tissue by increasing collagen synthesis in damaged skin cells due to the development of acne.

(Iii) In addition, the composition of the present invention effectively inhibits the production of nitric oxide and IL-6 protein which are inflammation mediators, effectively blocks the inflammation reaction around the acne-causing skin, and effectively works to improve the condition of acne skin.

1 is a graph showing changes in cell survival rate upon treatment of chlorogenic acid, myrcene, and mixtures thereof in human dermal keratinocytes.
FIG. 2 is a graph showing the expression pattern of type 1 procollagen protein upon treatment with chlorogenic acid, myrcene, and mixtures thereof in human dermal keratinocytes.
FIG. 3 shows the cell regeneration effect by treatment of chlorogenic acid, myrcene, and mixtures thereof in injured human fibroblasts.
4 is a graph showing the production of nitrogen oxide by treatment with chlorogenic acid, myrcene, and a mixture thereof in a mouse macrophage cell line.
5 is a graph showing changes in the expression of IL-6 protein following treatment with chlorogenic acid, myrcene, and mixtures thereof in mouse macrophage cells.

Hereinafter, the present invention will be described in more detail with reference to Examples. These embodiments are only for illustrating the present invention, and thus the scope of the present invention is not construed as being limited by these embodiments.

Example 1 Measurement of antimicrobial activity

1-1. Measurement of antimicrobial activity against aerobic skin bacteria

In order to search for candidate substances that have antimicrobial activity among natural substances and can be used to improve the condition of acne skin, firstly, an experiment for measuring the antimicrobial activity against aerobic dermatophytes was carried out.

The skin flora was selected on Muller-Hiton broth from Staphylococcus aureus (ATCC 25923), Staphylococcus epidermidis (ATCC 12228) and Purified Streptococcus pyogenes (ATCC 12353) , And cultured for 18 hours, and S. pyogenes was cultured in a CO ₂ incubator.

Each inoculum was incubated with the candidate material at a concentration of 2 × 10 ⁶ CFU / well for 18 hours. After incubation, the growth of the bacteria was observed with a naked eye and a microscope, and the absorbance at an absorption wavelength of 600 nm was measured to determine the minimum inhibitory concentration, which was the same as the absorbance value of the pure culture liquid.

As a result, in the group treated with the sample of chlorogenic acid, myrcene, and a mixture thereof (1: 1 by weight) as shown in Table 1 below, the growth of the skin flora was suppressed even at a low concentration (쨉 g / Appeared to be suitable candidates for use in the improvement of acne skin.

[Table 1]

1-2. Verification of antimicrobial activity against acne causing bacteria

The chlorogenic acid and the myrcene selected as candidates for the composition for improving the condition of acne skin of the present invention have a direct antimicrobial activity against the causative agent of acne by comparing Propionibacterium acnes and Antibiotic clindamycin clindamycin), a resistant strain of P. acnes .

For the verification, the minimum growth inhibitory concentration (MIC) of P. acnes and its resistant strains was determined by liquid culture dilution method.

First, Propionibacterium acnes and its resistant strains were cultured in a TS (trypticase strain) broth supplemented with 5% sheep blood at 35 ° C for 48 hours under anaerobic conditions and then used in the test.

Propionibacterium acnes and its resistant strains were inoculated at a concentration of 2 × 10 ⁶ CFU / well and cultured for 24 hours with a sample of chlorogenic acid, myrcene, and a mixture thereof (1: 1 weight ratio) The growth of bacteria was observed, and the absorbance at 600 nm of absorbance was measured to determine the minimum inhibitory concentration (see Table 2), which was the same as the absorbance of the pure culture medium.

[Table 2]

As a result, in the group treated with the chlorogenic acid, the myrcene and the mixture thereof, as shown in Table 2, even at a very low concentration (less than 41 / / ml unit), the bacterium acne causing P. bacterium acnes and its antibiotic resistance The growth of the strain was effectively inhibited and it was found that it was more suitable as a candidate substance that can be used for the improvement of acne skin.

Example  2: Skin cell  Verification of efficacy associated with growth and collagen protein expression

It is one of the important requirements to exhibit antimicrobial activity against skin-causing bacteria and acne causing bacteria for use as a substance for improving the condition of acne skin. However, in order to be used as a composition for improving skin condition used for the improvement of damaged acne skin caused by acne, regeneration of damaged skin cells and collagen synthesis should be sufficiently performed.

The effects of chlorogenic acid and myrcene selected as candidates for skin condition improvement of acne skin on the growth of human epidermal keratinocyte (HEK) in order to examine the effect of skin cell growth and collagen protein expression on the growth of human epidermal keratinocyte And confirmed by the same method.

First, keratinocytes were inoculated in DMEM (Dulbeccos modified Eagles medium), a medium containing 10% FBS (fetal bovine serum, Cambrex), at a concentration of 1.2 × 10 ⁵ in a 40 mm cell culture dish, , And cultured at 37 占 폚 and 5% CO ₂ wetting conditions. Thereafter, chlorogenic acid, myrcene and a mixture thereof (1: 1 weight ratio) diluted with serum-free DMEM medium were treated with concentration (0.1, 1, 10 / /)) and cultured for 48 hours. After 72 hours, 1 mg / mL of MTT was treated and 2 hours later, the formazan produced by MTT treatment was dissolved in DMSO and the absorbance was measured at 570 nm (FIG. 1).

In addition, the expression level of collagen protein was analyzed by an enzyme-linked immunosorbent assay (ELISA) method using a collagen assay kit (Fig. 2).

As a result, it was confirmed that when human keratinocytes were treated with chlorogenic acid, myrcene, and a mixture thereof, chlorogenic acid, myrcene, and a mixture thereof did not significantly affect cell viability (see FIG. 1) Myrcene, and mixtures thereof did not show toxicity to human dermal keratinocytes.

Further, as can be seen from FIG. 2, the synthesis of collagen protein is increased in a concentration-dependent manner due to the treatment of chlorogenic acid, myrcene, and a mixture thereof in the keratinocytes.

These results indicate that chlorogenic acid, myrcene, and mixtures thereof promote the regeneration of skin tissue by increasing collagen synthesis in damaged skin cells due to the development of acne.

Example  3. Cells from skin wound models With the refresh rate  Validation of related efficacy

Cell culture When NHDF (normal human dermal fibroblast) cells, which are primary cultured skin cells, were proliferated by 80% in a 100 mm dish, skin cells were wound using a tip of sterilized tip (200 ul), and chlorogenic acid, (1: 1 weight ratio) were injected at a concentration of 0.01 to 10 μg / ml, respectively, and cell regeneration effect was confirmed.

At this time, cell proliferation was confirmed by microscopic examination after cell staining using MTT (methylthiazole-2-yl-2.5-diphenyl tetrazolium bromide) analysis method and Diff quic stain method (FIG.

As a result, as shown in FIG. 3, it was confirmed that when damaged chondrogenic acid, myrcene, and a mixture thereof were treated on damaged skin cells, regeneration of damaged skin cells was directly promoted. It was also observed that the morphological shape of the regenerated skin cells was the same as that of normal skin cells.

Based on the above results, when chlorogenic acid, myrcene, and a mixture thereof are applied to the symptom of acne, the regenerated skin tissue does not differ from the surrounding normal skin tissue. Therefore, It was found that there was an effect of promoting the regeneration of skin cells while not overcharging.

Example  4. Verification of effect on skin immunity activity

Acne caused by acne causative bacteria and skin fungus is further enlarged through the inflammatory reaction, and clinical symptoms of acne tend to deteriorate through skin eruption, skin irritation, or photoreceptor reaction. Therefore, early interception of the inflammatory reaction is a very important factor in the treatment of acne symptoms for effective improvement of acne-causing skin condition.

The effects of chlorogenic acid, myrcene, and mixtures thereof, selected as candidates for improving skin condition, on inflammatory and immune activity were tested in the following manner.

4-1. The inflammatory mediator, nitric oxide ( nitric oxide , NO ) Secretion suppression effect

Mouse macrophage RAW264.7 cells were prepared and treated with LPS (1 ㎍ / ㎖) as a cell activation and inflammation inducer in all groups except for the normal group. Cells were cultured for 24 hours, Respectively.

Nitric oxide donor and griess reagent were treated together and nitric oxide (NO) appeared after the lapse of time.

In order to quantify the amount of nitric oxide observed at the designated time, chlorogenic acid, myrcene and mixtures thereof were treated for each concentration, incubated at 37 ° C for 2 hours, The absorbance was measured at 540 nm by mixing the reagent, the Greek reagent.

As a result, it was shown that the production of LPS-induced nitric oxide was inhibited when chlorogenic acid, myrcene, and a mixture thereof were treated, and this nitric oxide secretion inhibitory ability was found to be concentration-dependent.

4-2. IL -6 protein expression inhibitory effect

In the inflammatory response mechanism caused by skin cell damage, inflammatory mediators such as IL-6 are involved, and the inflammatory response is amplified by the action of inflammatory mediators. In the case of inhibiting the expression of IL-6, It can be effectively blocked.

To examine the effect of chlorogenic acid, myrcene, and a mixture thereof on the expression of IL-6 protein, mouse macrophage RAW264.7 cells were tested. RAW264.7 cells were inoculated at a concentration of 1.0 × 10 ⁵ in a 96-well plate and cultured for 24 hours at 37 ° C and 5% CO2 wet condition. After washing with PBS solution, 1 ㎍ / ㎖ of LPS was treated with each sample alone or in various concentrations and cultured for 24 hours. The normal control group was treated with bacillus.

After the incubation, the supernatant was taken and the amount of IL-6 protein produced was analyzed using an enzyme-linked immunosorbent assay (ELISA) kit.

As a result, it was shown that the production of IL-6 protein induced by LPS was inhibited when chlorogenic acid, myrcene, and a mixture thereof were treated.

These results show that chlorogenic acid, myrcene, and mixtures thereof effectively inhibit the production of nitric oxide and IL-6 protein, which are inflammatory mediators, and effectively block the inflammatory reaction around the acne-causing skin, It was found that it works effectively for improvement.

While the present invention has been particularly shown and described with reference to exemplary embodiments thereof, it is to be understood that the same is by way of illustration and example only and is not to be construed as limiting the scope of the present invention.

Accordingly, the actual scope of the present invention will be defined by the appended claims and their equivalents.

Claims (8)

A composition for improving the skin condition of acne skin containing a myrcene compound as an active ingredient. delete The method according to claim 1,
Wherein the myrcene is a compound represented by the following formula (2)
(2)

. The method according to claim 1,
Wherein said composition inhibits the growth of a Propionibacterium acnes strain. The method according to claim 1,
Wherein said composition promotes the synthesis of collagen protein, inhibits the production of nitric oxide, and inhibits the expression of IL-6 protein. 6. The method according to any one of claims 1 to 5,
Wherein the composition is an external preparation for skin. 6. The method according to any one of claims 1 to 5,
Wherein the composition is a pharmaceutical composition. 6. The method according to any one of claims 1 to 5,
Wherein the composition is a cosmetic composition.

Images