KR20220085074A - Skin anti-pollution composition containing a novel organic compound as an active ingredient - Google Patents

Abstract

The present invention relates to a composition for skin anti-pollution containing a novel organic compound as an active ingredient, which can effectively suppress inflammatory reactions caused by contaminants, and has excellent antioxidant, anti-aging and skin whitening effects. A composition for anti-pollution can be provided.
In addition, it is possible to provide a cosmetic, food and pharmaceutical composition having the above effect.

Description

A composition for skin anti-pollution containing a novel organic compound as an active ingredient {SKIN ANTI-POLLUTION COMPOSITION CONTAINING A NOVEL ORGANIC COMPOUND AS AN ACTIVE INGREDIENT}

The present invention relates to a composition for skin anti-pollution comprising a novel organic compound as an active ingredient. More particularly, it relates to a composition comprising a novel organic compound based on natural products that can suppress skin inflammatory reactions that may be caused by fine dust and the like, and have excellent antioxidant, anti-aging and skin whitening effects.

Recently, as the quality of life is improved due to the extension of average sleep according to the development of medical technology, the desire for a healthy life is increasing, and at the same time, interest in skin beauty is also increasing.

The skin is a part of the body that is directly exposed to the external environment, and it not only acts as a protective film to protect important organs of our body, but also regulates water evaporation and protects the body from external infections. However, no matter how much the skin blocks the penetration of viruses from the outside, external stress such as excessive UV rays and a polluted environment causes skin irritation, which ultimately leads to skin aging.

As we enter the modern society, environmental pollution is getting worse and the concentration of pollutants around our living area is increasing, so the problem of skin protection from pollutants is emerging as a social problem. Examples of these pollutants include formaldehyde, nitrogen oxides, benzopyrene, and the like, and they enter the body and accumulate to cause various diseases.

Meanwhile, one of the causes of skin damage that has been attracting attention in recent years is skin damage caused by fine dust or ultra-fine dust. This means a pollutant having a diameter of 2.5 to 10 μm or a pollutant having a diameter of 2.5 μm or less, and when in contact with the skin, it is known to directly impair the skin barrier function and cause exacerbation of dermatitis.

Since the particle size of fine dust is very small, it can penetrate through the hair follicles to the bottom of the skin, so it can have an effect even if you are not atopic, allergic, or sensitive skin patients. When fine dust penetrates the skin, it produces active oxygen and damages the mitochondria of our skin, reducing collagen synthesis, increasing decomposition, and stimulating melanocytes to cause pigmentation. of skin aging may worsen.

Accordingly, various functional cosmetics are being developed, and in particular, investment and research on skin protection cosmetics with an antipollution function are being actively conducted.

Compared to the effects of pollutants on the skin, the public's awareness of the risks is still low. number is increasing.

Accordingly, the development of cosmetic compositions, detergents, and external preparations having an anti-pollution effect that prevents the environmental pollutants from adhering to the surface of the skin or penetrating into the body through the skin is being actively developed.

However, most of the currently developed products simply remove the contaminants from the skin as well as remove the contaminants that have adhered to or penetrate the skin, and do not fundamentally protect the skin from environmental contaminants. There was a slight problem with the ability to protect the skin from

In particular, since it contains chemicals as a main component, there is a problem that rather acts as a cause of skin troubles and skin diseases. Accordingly, there is a need to develop a composition that is hypoallergenic and has excellent anti-pollution effects on the skin using natural substances.

On the other hand, the bright tone of the skin symbolizes health and youth, and people of all ages are increasingly interested in skin whitening, such as using various cosmetics or receiving skin treatments to have white, clean skin.

Human skin color is influenced by environment, race, gender, etc., but is generally determined by the content of melanin. Melanin pigment is the biggest factor determining the color of a person's skin, and by absorbing or scattering ultraviolet rays, it plays a large role in preventing damage to the skin from ultraviolet rays (Gertrude-E. Costin, et al., The FASED Journal 2001, 21) , 976-994; Yuji Yamaguchi, et al., Journal of Biological Chemistry 2007, 282, 27557-27561).

However, when melanin present in the basal layer of the skin is excessively produced due to various environmental factors such as ultraviolet rays and skin aging, skin pigmentation is increased (Iwata M, et al., J Invest Dermatol 1990, 95, 9-15). Diseases that cause this abnormal skin color cause melasma, freckles, and seborrheic keratosis, and this pigmentation causes health problems such as cosmetic problems, skin aging, and skin cancer ( FR De Gruijl, European Journal of Cancer 1999, 35, 2003-2009; Bruce K. Armstrong, Anne Kricker, Journal of Photochemistry and Photobiology B: Biology 2001, 63, 8-18).

It has already been found that ascorbic acid and hydroquinone have the effect of inhibiting the formation of melanin pigment, and thus it is used as a whitening cosmetic.

Therefore, the most important issue is to develop a whitening material for skin health that can effectively suppress the formation of melanin and is harmless to the human body.

Therefore, in order to solve the above problems, the present applicant confirmed the excellent anti-inflammatory, antioxidant, and skin whitening effects of a novel organic compound based on natural products, and developed a composition for skin anti-pollution containing it as an active ingredient. .

KR 10-1571323 B1 KR 10-1458887 B1

An object of the present invention is to provide a composition for skin anti-pollution comprising a novel organic compound as an active ingredient.

Another object of the present invention is to provide a composition that is a novel organic compound based on natural products, which has excellent anti-inflammatory effects on inflammatory reactions caused by contaminants, and has excellent antioxidant, anti-aging and skin whitening effects.

Another object of the present invention is to provide a cosmetic composition, a food composition and a pharmaceutical composition comprising the composition for skin anti-pollution.

In order to achieve the above object, the composition for skin anti-pollution according to an embodiment of the present invention includes a compound represented by the following formula (1) as an active ingredient, and has excellent anti-inflammatory, antioxidant, anti-aging and skin whitening effects. :

[Formula 1]

here,

L ₁ is a single bond or a substituted or unsubstituted C 1 to C 10 alkylene group,

Ar ₁ is a substituted or unsubstituted cycloalkyl group having 3 to 30 carbon atoms, a substituted or unsubstituted aryl group having 5 to 30 carbon atoms, a substituted or unsubstituted heteroaryl group having 2 to 30 carbon atoms, or a substituted or unsubstituted heteroaryl group having 3 to 30 carbon atoms It is selected from the group consisting of an arylalkyl group, and a substituted or unsubstituted aryloxy group having 6 to 30 carbon atoms,

The substituents of L ₁ and Ar ₁ are hydrogen, deuterium, cyano group, nitro group, halogen group, hydroxyl group, alkyl group having 1 to 30 carbon atoms, alkenyl group having 2 to 30 carbon atoms, alkynyl group having 2 to 24 carbon atoms, and 2 to carbon atoms. A heteroalkyl group having 30, an aralkyl group having 6 to 30 carbon atoms, a cycloalkyl group having 3 to 20 carbon atoms, a heterocycloalkyl group having 3 to 20 carbon atoms, an aryl group having 5 to 30 carbon atoms, a heteroaryl group having 2 to 30 carbon atoms, 3 to carbon atoms substituted with a substituent selected from the group consisting of a heteroarylalkyl group of 30, an alkoxy group of 1 to 30 carbons, an alkylsilyl group of 1 to 30 carbons, an arylsilyl group of 6 to 30 carbons, and an aryloxy group of 6 to 30 carbons, When substituted with a plurality of substituents, they are the same as or different from each other.

The Ar ₁ may be a compound represented by the following Chemical Formula 2 or Chemical Formula 3:

[Formula 2]

[Formula 3]

here,

* means the part to be joined.

The compound represented by Formula 1 may exhibit a first peak at 6.86 to 6.88 ppm and a second peak at 6.85 to 6.87 ppm when ¹ H-NMR spectrum is measured.

The compound represented by Formula 1 may be an active material separated and purified from the extract of sangolchi.

The compound represented by Formula 1 may be an active material obtained by fractionation of the extract of sangolchi with n-BuOH, and separation and purification.

The cosmetic composition for skin anti-pollution according to another embodiment of the present invention may include the composition.

The food composition for skin anti-pollution according to another embodiment of the present invention may include the composition.

The pharmaceutical composition for skin anti-pollution according to another embodiment of the present invention may include the composition.

In the present invention, "hydrogen" is hydrogen, light hydrogen, deuterium or tritium unless otherwise specified.

In the present invention, the “halogen group” is fluorine, chlorine, bromine or iodine.

In the present invention, “alkyl” refers to a monovalent substituent derived from a saturated hydrocarbon having 1 to 40 carbon atoms in a straight or branched chain. Examples thereof include, but are not limited to, methyl, ethyl, propyl, isobutyl, sec-butyl, pentyl, iso-amyl, hexyl, and the like.

In the present invention, “alkenyl” refers to a monovalent substituent derived from a linear or branched unsaturated hydrocarbon having 2 to 40 carbon atoms and having one or more carbon-carbon double bonds. Examples thereof include, but are not limited to, vinyl, allyl, isopropenyl, 2-butenyl, and the like.

In the present invention, “alkynyl” refers to a monovalent substituent derived from a linear or branched unsaturated hydrocarbon having 2 to 40 carbon atoms and having one or more carbon-carbon triple bonds. Examples thereof include, but are not limited to, ethynyl, 2-propynyl, and the like.

In the present invention, “cycloalkyl” refers to a monovalent substituent derived from a monocyclic or polycyclic non-aromatic hydrocarbon having 3 to 40 carbon atoms. Examples of such cycloalkyl include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, norbornyl, adamantine, and the like.

In the present invention, “heterocycloalkyl” means a monovalent substituent derived from a non-aromatic hydrocarbon having 3 to 40 carbon atoms, and at least one carbon in the ring, preferably 1 to 3 carbons, is N, O, S or Se substituted with a hetero atom such as Examples of such heterocycloalkyl include, but are not limited to, morpholine and piperazine.

In the present invention, “aryl” refers to a monovalent substituent derived from an aromatic hydrocarbon having 6 to 60 carbon atoms in which a single ring or two or more rings are combined. In addition, two or more rings may be simply attached to each other (pendant) or condensed form may be included. Examples of such aryl include, but are not limited to, phenyl, naphthyl, phenanthryl, anthryl, fluorenyl, dimethylfluorenyl, and the like.

In the present invention, “heteroaryl” refers to a monovalent substituent derived from a monoheterocyclic or polyheterocyclic aromatic hydrocarbon having 6 to 30 carbon atoms. In this case, one or more carbons in the ring, preferably 1 to 3 carbons, are substituted with a heteroatom such as N, O, S or Se. In addition, a form in which two or more rings are simply attached to each other or condensed may be included, and further, a form condensed with an aryl group may be included. Examples of such heteroaryl include 6-membered monocyclic rings such as pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, triazinyl, phenoxathienyl, indolizinyl, indolyl ( polycyclic rings such as indolyl), purinyl, quinolyl, benzothiazole, and carbazolyl, and 2-furanyl, N-imidazolyl, 2-isoxazolyl , 2-pyridinyl, 2-pyrimidinyl, and the like, but is not limited thereto.

In the present invention, "aryloxy" is a monovalent substituent represented by RO-, wherein R means aryl having 6 to 60 carbon atoms. Examples of such aryloxy include, but are not limited to, phenyloxy, naphthyloxy, diphenyloxy, and the like.

As used herein, "aralkyl" refers to an aryl-alkyl group wherein aryl and alkyl are as described above. Preferred aralkyls include lower alkyl groups. Non-limiting examples of suitable aralkyl groups include benzyl, 2-phenethyl and naphthalenylmethyl. Binding to the parent moiety is through an alkyl.

In the present invention, “alkoxy” may be a straight chain, branched chain or cyclic chain. Although the number of carbon atoms of alkoxy is not particularly limited, it is preferably from 1 to 20 carbon atoms. Specifically, methoxy, ethoxy, n-propoxy, isopropoxy, i-propyloxy, n-butoxy, isobutoxy, tert-butoxy, sec-butoxy, n-pentyloxy, neopentyloxy, Isopentyloxy, n-hexyloxy, 3,3-dimethylbutyloxy, 2-ethylbutyloxy, n-octyloxy, n-nonyloxy, n-decyloxy, benzyloxy, p-methylbenzyloxy, etc. may be, but is not limited thereto.

In the present invention, “alkylsilyl” refers to silyl substituted with alkyl having 1 to 40 carbon atoms, and “arylsilyl” refers to silyl substituted with aryl having 6 to 60 carbon atoms.

In the present invention, "substitution" means that a hydrogen atom bonded to a carbon atom of a compound is replaced with another substituent, and the position to be substituted is not limited as long as the position at which the hydrogen atom is substituted, that is, a position where the substituent is substitutable, is not limited, and when two or more are substituted , two or more substituents may be the same as or different from each other. The substituent is hydrogen, a cyano group, a nitro group, a halogen group, a hydroxy group, an alkyl group having 1 to 30 carbon atoms, an alkenyl group having 2 to 30 carbon atoms, an alkynyl group having 2 to 24 carbon atoms, a heteroalkyl group having 2 to 30 carbon atoms, a heteroalkyl group having 6 to carbon atoms. 30 aralkyl group, C5-30 aryl group, C2-30 heteroaryl group, C3-30 heteroarylalkyl group, C1-30 alkoxy group, C1-C30 alkylamino group, C6-C30 heteroaryl group It may be substituted with one or more substituents selected from the group consisting of a 30 arylamino group, an aralkylamino group having 6 to 30 carbon atoms, and a heteroarylamino group having 2 to 24 carbon atoms, but is not limited thereto.

According to the composition for skin anti-pollution containing the novel organic compound of the present invention as an active ingredient, it is possible to effectively suppress the inflammatory reaction caused by contaminants, as well as to have excellent anti-oxidation, anti-aging and skin whitening effects. A composition for solution can be provided. Furthermore, it is possible to provide a cosmetic, food and pharmaceutical composition having the above effect.

1 is a ¹ H-NMR analysis result of an active material according to an embodiment of the present invention.
2 is a result of ¹³ C-NMR analysis of an active material according to an embodiment of the present invention.
Figure 3 is a cytotoxicity test results of the extract according to an embodiment of the present invention.
4 is an experimental result showing the inhibitory effect on the inflammatory reaction induced by fine dust according to an embodiment of the present invention.
5 is an experimental result showing the inhibitory effect on the inflammatory reaction induced by fine dust according to an embodiment of the present invention.
6 is an experimental result regarding the antioxidant effect according to an embodiment of the present invention.
7 is an experimental result regarding the antioxidant effect according to an embodiment of the present invention.
8 is an experimental result regarding the antioxidant effect according to an embodiment of the present invention.
9 is an experimental result regarding the antioxidant effect according to an embodiment of the present invention.
10 is an experimental result regarding the secretion effect of a nerve cell active material according to an embodiment of the present invention.
11 is an experimental result regarding the secretion effect of a nerve cell active material according to an embodiment of the present invention.
12 is an experimental result regarding the skin whitening effect according to an embodiment of the present invention.

Hereinafter, embodiments of the present invention will be described in detail so that those of ordinary skill in the art can easily carry out the present invention. However, the present invention may be embodied in several different forms and is not limited to the embodiments described herein.

In the present invention, "improvement" may refer to any action that at least reduces a parameter related to alleviation or treatment of a condition, for example, the degree of a symptom.

In the present invention, “skin anti-pollution” refers to improving skin contamination by contaminants such as fine dust, inhibiting skin cell death or skin cell proliferation, or improving skin condition.

The composition for skin anti-pollution of the present invention contains a compound represented by the following formula (1) as an active ingredient, and is excellent in anti-inflammatory, antioxidant, anti-aging and skin whitening improving effects:

[Formula 1]

here,

L ₁ is a single bond or a substituted or unsubstituted C 1 to C 10 alkylene group,

Ar ₁ is a substituted or unsubstituted cycloalkyl group having 3 to 30 carbon atoms, a substituted or unsubstituted aryl group having 5 to 30 carbon atoms, a substituted or unsubstituted heteroaryl group having 2 to 30 carbon atoms, or a substituted or unsubstituted heteroaryl group having 3 to 30 carbon atoms It is selected from the group consisting of an arylalkyl group, and a substituted or unsubstituted aryloxy group having 6 to 30 carbon atoms,

The substituents of L ₁ and Ar ₁ are hydrogen, deuterium, cyano group, nitro group, halogen group, hydroxyl group, alkyl group having 1 to 30 carbon atoms, alkenyl group having 2 to 30 carbon atoms, alkynyl group having 2 to 24 carbon atoms, and 2 to carbon atoms. A heteroalkyl group having 30, an aralkyl group having 6 to 30 carbon atoms, a cycloalkyl group having 3 to 20 carbon atoms, a heterocycloalkyl group having 3 to 20 carbon atoms, an aryl group having 5 to 30 carbon atoms, a heteroaryl group having 2 to 30 carbon atoms, 3 to carbon atoms substituted with a substituent selected from the group consisting of a heteroarylalkyl group of 30, an alkoxy group of 1 to 30 carbons, an alkylsilyl group of 1 to 30 carbons, an arylsilyl group of 6 to 30 carbons, and an aryloxy group of 6 to 30 carbons, When substituted with a plurality of substituents, they are the same as or different from each other.

Specifically, Ar ₁ may be a compound represented by Formula 2 or Formula 3:

[Formula 2]

[Formula 3]

here,

* means the part to be joined.

More specifically, the compound represented by Formula 1 may be a compound represented by Formula 4 or Formula 5 below:

[Formula 4]

[Formula 5]

The composition is characterized in that it has excellent anti-inflammatory effects on inflammatory reactions caused by contaminants, as well as excellent antioxidant, anti-aging and skin whitening improving effects.

In addition, the compound represented by Formula 1 may exhibit a first peak at 6.86 to 6.88 ppm and a second peak at 6.85 to 6.87 ppm when ¹ H-NMR spectrum is measured.

More specifically, the compound represented by Formula 1 exhibits a first peak at 6.86 to 6.88 ppm, a second peak at 6.85 to 6.87 ppm, and a third at 6.58 to 6.60 ppm, when ¹ H-NMR spectrum is measured. A peak may be exhibited, and a fourth peak may be exhibited at 5.78 to 5.80 ppm, a fifth peak may be exhibited at 4.56 to 4.58 ppm, and a sixth peak may be exhibited at 3.73 to 3.75 ppm.

On the other hand, the compound represented by Formula 1 may be an active material separated and purified from the extract of sangolchi.

Specifically, the compound represented by Chemical Formula 1 may be an active material obtained by fractionation of the extract of sangolchi with n-BuOH, and separation and purification.

That is, the compound represented by Formula 1 is a compound isolated from the fraction of the extract of sangolchi.

The mountain chwi (Saussurea neoserrata) grows in a deep mountain and the height is 50 to 110 cm. Stems stand upright and branch out at the top. The base of the leaf flows into the stem and becomes the wing of the stem. The leaves on the root and the leaves on the lower part fall when the flower blooms, and the leaves on the stem are alternate phyllotaxis and are lanceolate or oval-shaped lancets, and are 12 to 15cm long. The tip is pointed and the bottom is narrow. It gets smaller towards the top, curly hairs grow on the back side, and there are sharp sawtooths on the edge. Also, the flowers are purple in August or September. At the end of branches and main stems, two flowers hang in corymbal inflorescences, with a flower diameter of 8 to 10 mm. The gun is cylindrical, 8 to 9 mm long and 4 to 5 mm in diameter. The pieces of cloth are arranged in 4 rows, the edges are purple, and white hairs like cobwebs are formed. The fruit is aqueous, about 5mm long, and has black-brown lines. The crown hair (冠毛) has 2 lines and is brown. Young shoots are edible. This species is endemic to Korea and distributed in the northern regions.

More specifically, the sangolchi may be separated from the compound represented by the formula (1) from the fraction fractionated from the hot water extract extracted by the hot water extraction method.

The hot water extract of sangolchi can be prepared using the same method as the conventional method for preparing a hot water extract.

The hot water extract from Sangolchi was partitioned and extracted with water and ethyl acetate, and the water layer was again partitioned and extracted with n-butanol. Each layer was concentrated under reduced pressure to prepare EtOAc, n-BuOH and H ₂ O fractions.

The compound represented by Formula 1 was identified from the butanol fraction of sangolchi, and the analysis was performed through the NMR data of FIGS. 1 and 2 .

The compound represented by Formula 1 shows a first peak at 6.86 to 6.88 ppm, a second peak at 6.85 to 6.87 ppm, and a third peak at 6.58 to 6.60 ppm, when ¹ H-NMR spectrum is measured, It will be said that it corresponds to a compound characterized in that it exhibits a fourth peak at 5.78 to 5.80 ppm, a fifth peak at 4.56 to 4.58 ppm, and a sixth peak at 3.73 to 3.75 ppm.

The cosmetic composition for skin anti-pollution according to another embodiment of the present invention may include the composition.

'Cosmetics' as used in the present invention is not limited to cosmetics, and is defined to include all external preparations of pharmaceuticals or quasi-drugs.

The cosmetic composition of the present invention may be prepared in any formulation conventionally prepared in the art, for example, a solution, suspension, paste, gel, cream, lotion, powder, soap, surfactant-containing clenosis, oil , powder foundation, emulsion foundation, wax foundation, and spray may be formulated, but are not limited thereto. More specifically, flexible lotion, nourishing lotion, nourishing cream, massage cream, essence, eye cream, cleansing cream, cleansing foam, cleansing water, pack, spray or powder formulation, oil-in-water (O/W) type or water-in-oil It can be prepared as a (W/O) type formulation or ointment.

The cosmetic may be prepared in the form of a supplement that can be applied topically or systemically, which is commonly used in the art, by containing a dermatologically acceptable medium or base in addition to the extract of the present invention.

Suitable cosmetic formulations include, for example, solutions, gels, solid or kneaded dry products, emulsions obtained by dispersing an oil phase in an aqueous phase, suspensions, microemulsions, microcapsules, microgranules or ionic (liposomes), non-ionic It may be provided in the form of a vesicular dispersant, cream, skin, lotion, powder, ointment, spray or in the form of a cone stick. In addition, it may be prepared in the form of a foam or an aerosol composition further containing a compressed propellant.

Products to which the cosmetic composition of the present invention can be added include, for example, cosmetics such as astringent lotion, softening lotion, nutrient lotion, various creams, essence, pack, foundation, etc. and cleansing, face wash, soap, treatment or liquid cosmetics etc. Specific formulations include skin lotion, skin softener, skin toner, astringent, lotion, milk lotion, moisture lotion, nourishing lotion, massage cream, nourishing cream, moisture cream, hand cream, essence, nourishing essence, pack, soap, shampoo, cleansing foam. , cleansing lotion, cleansing cream, body lotion, body cleanser, emulsion, press powder, loose powder or eye shadow formulations.

The food composition for skin anti-pollution according to another embodiment of the present invention may include the composition.

'Food' as used in the present invention includes not only general food and beverage, but also functional food or health functional food.

At this time, the amount of the extract in the food or beverage may be added in an amount of about 0.01 to 15% by weight of the total food weight, and the health drink composition may be added in a ratio of about 0.01 to 10g based on 100 ml, but is not limited thereto. .

When the food composition of the present invention is a beverage composition, there is no particular limitation on other ingredients except for containing the extract as an essential ingredient in the indicated ratio, and it may contain various flavoring agents or natural carbohydrates as additional ingredients like a conventional beverage. can Examples of the above-mentioned natural carbohydrates include monosaccharides such as glucose, fructose and the like; disaccharides such as maltose, sucrose and the like; and polysaccharides such as conventional sugars such as dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol. As flavoring agents other than those described above, natural flavoring agents (taumatin, stevia extract (eg, rebaudioside A, glycyrrhizin, etc.) and synthetic flavoring agents (saccharin, aspartame, etc.) may be used, but are not limited thereto. The proportion of the natural carbohydrate may be generally in the range of about 1 to 20 g per 100 ml of the composition of the present invention, but may not be limited thereto.

In addition to the above, the composition of the present invention contains various nutrients, vitamins, minerals (electrolytes), flavoring agents such as synthetic flavoring agents and natural flavoring agents, coloring agents and thickeners (cheese, chocolate, etc.), pectic acid and its salts, alginic acid and its salts. salts, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohol, carbonation agents used in carbonated beverages, etc., but may not be limited thereto.

In addition, the composition of the present invention may contain natural fruit juice and pulp for the production of fruit juice beverages and vegetable beverages, and these components may be used independently or in combination. The proportion of these additives is not critical, but may be selected from about 0.1 to about 20 parts by weight per 100 parts by weight of the composition of the present invention, but is not limited thereto.

"Functional food" as used in the present invention is a food manufactured and processed by extracting, concentrating, refining, mixing, etc., a specific ingredient as a raw material for the purpose of health supplementation, or including health supplement food. In addition, it is a food designed and processed to sufficiently exert the biological control functions of the food ingredients, such as biological defense, regulation of biological rhythm, prevention and recovery of diseases, and functions related to disease prevention and recovery from diseases. It is assumed to include all that it has.

The health functional food may additionally contain food additives, and the suitability as a "food additive" is determined according to the general rules and general test methods of the Food Additives Code approved by the Food and Drug Administration, unless otherwise specified. and criteria.

As items listed in the "Food Additives Codex", for example, chemical synthetic products such as ketones, glycine, potassium citrate, nicotinic acid, and cinnamic acid, natural additives such as depigmentation, plant extracts, crystalline cellulose, high-cold pigment, and guar gum, L - Mixed preparations such as sodium glutamate preparations, noodle-added alkalis, preservatives, tar dyes, etc. are mentioned.

Carriers, excipients and diluents that may be included in the functional food or health functional food include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia gum, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil. In the case of formulation, it is prepared using commonly used diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrants, and surfactants. Solid preparations for oral administration include tablets, pills, powders, granules, capsules, etc., and these solid preparations include at least one excipient in the extract and its fractions, for example, starch, calcium carbonate, It is prepared by mixing sucrose or lactose, gelatin, etc. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Liquid preparations for oral use include various excipients, such as wetting agents, sweeteners, fragrances, and preservatives, in addition to simple diluents such as water and liquid paraffin, which are commonly used for suspensions, solutions, emulsions, and syrups. have. Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, and suppositories. Non-aqueous solvents and suspending agents include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate. As the base of the suppository, witepsol, macrogol, tween 61, cacao butter, laurin, glycerogelatin, and the like can be used.

The pharmaceutical composition for skin anti-pollution according to another embodiment of the present invention may include the composition.

The pharmaceutical composition is prepared as an oral dosage form or parenteral dosage form according to a conventional method known in the art, including a pharmaceutically acceptable carrier, in addition to including the compound represented by Formula 1 as an active ingredient. can be Here, "pharmaceutically acceptable" means that it does not inhibit the activity of an active ingredient and does not have toxicity beyond what the application (prescription) target can adapt.

In addition, when the pharmaceutical composition is prepared as an oral dosage form, powders, granules, tablets, pills, dragees, capsules, liquids, gels, syrups, suspensions, wafers, etc. according to methods known in the art together with a suitable carrier It can be prepared in a dosage form. Examples of suitable pharmaceutically acceptable carriers include sugars such as lactose, glucose, sucrose, dextrose, sorbitol, mannitol, and xylitol, starches such as corn starch, potato starch, wheat starch, cellulose, methylcellulose, ethylcellulose, Cellulose such as sodium carboxymethylcellulose and hydroxypropylmethylcellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, magnesium stearate, mineral oil, malt, gelatin, talc, polyol, vegetable and oil. In the case of formulation activity, if necessary, the formulation may include a diluent and/or excipient such as a filler, an extender, a binder, a wetting agent, a disintegrant, and a surfactant.

When prepared as a parenteral formulation, it may be formulated in the form of an injection, transdermal administration, nasal inhalation, and suppository together with a suitable carrier according to methods known in the art. In the case of formulation for injection, suitable carriers include sterile water, ethanol, polyols such as glycerol or propylene glycol, or mixtures thereof, preferably Ringer's solution, PBS (phosphate buffered saline) containing triethanolamine, or sterilization for injection. Water, an isotonic solution such as 5% dextrose, etc. may be used. When formulated for transdermal administration, it may be formulated in the form of an ointment, a cream, a lotion, a gel, an external solution, a pasta agent, a liniment agent, an air roll, and the like. In the case of a nasal inhalant, it can be formulated in the form of an aerosol spray using a suitable propellant such as dichlorofluoromethane, trichlorofluoromethane, dichlorotetrafluoroethane, carbon dioxide, and the like. witepsol), tween 61, polyethylene glycols, cacao fat, laurin fat, polyoxyethylene sorbitan fatty acid esters, polyoxyethylene stearate, sorbitan fatty acid esters, etc. may be used.

[Preparation Example: Preparation of extracts from shankol odori]

After hot water extraction of the dried and pulverized mountain odor, the extract was prepared by filtration, and concentrated under reduced pressure at 45 ° C. The concentrate was partitioned and extracted with water and ethyl acetate, and the water layer was again with n-butanol. distribution was extracted. Each layer was concentrated under reduced pressure to prepare EtOAc, n-BuOH and H ₂ O fractions.

Silica gel column (φ5×20cm) chromatography (CHCl ₃ -MeOH = 1:9) was performed on the n-BuOH fraction to obtain a fraction. Among them, silica gel column chromatography (CHCl ₃ -MeOH = 1:9, φ 3×20 cm) was performed on the fraction 2fr. (82 mg) to obtain a fraction. Thereafter, the small fractions were separated and purified. The separated and purified small fraction was purified by Sephadex LH-20 column chromatography (CHCl ₃ :MeOH = 1:9, φ2.5×50 cm) to isolate Compound 1 (10.4 mg).

[Experimental Example 1: Analysis of active substances isolated from mountain odor]

As an analysis method, the active ingredient was analyzed through ¹ H-NMR and ¹³ C-NMR analysis. Analysis was performed using a Bruker AVANCE II 400 ( ¹ H NMR at 400 MHz, ¹³ C NMR at 100 MHz).

The analysis results are shown in FIGS. 1 and 2 .

¹ H-NMR spectrum measurement result, δ _H 6.87 (2H, br.s, H-2,6), δ _H 6.86 (1H, d, J = 15.6 Hz, H-7) and δ _H 6.59 (1H, dt , J = 15.6, 4.8Hz, H-8), the presence of one symmetric tetra-substituted aromatic ring and one trans-double bond was confirmed.

In addition, the presence of one molecule of sugar was confirmed at δ _H 5.79 (1H, d, J = 6.4 Hz, H-1'), and oxygenated methylene at δ _H 4.57 (1H, d, J = 3.8 Hz, H-9) The signal was confirmed, and the methoxy signal was confirmed at δ _H 3.74 (6H, s, H-OCH ₃ ). Through this, the above compound was expected to be an aromatic glycoside derivative.

On the other hand, 17 carbon signals including one molecule of sugar and two methoxy groups were identified in the ¹³ C-NMR spectrum.

In the signal of δc 154.3 (C-3,5), oxygenated olefin quaternary carbon was confirmed, δc 136.4 (C-4), δc 134.4 (C-3), δc 131.6 (C-1), δc 129.8 (C-6) ) and the presence of one symmetric tetra-substituted aromatic ring and one trans-double bond were confirmed through the signals of δc 105.6 (C-2,6).

In the signal of δc 105.3 (C-1'), anomer carbon resulting from carbon 1 of the sugar was confirmed, δc 79.2 (C-3'), δc 78.8 (C-5'), δc 76.5 (C-2') , and glucose structures were determined from the sugar moiety signals of δc 72.0 (C-4') and δc 63.0 (C-6').

In addition, one oxygenated methylene and two methoxy groups were identified through signals of δc 63.2(C-9) and δc 57.0(C-OCH ₃ ).

Based on the analysis results, it was analyzed that Syringin, a compound represented by the following formula (4), corresponds to the active substance:

[Formula 4]

[Experimental Example 2: Materials and Reagents]

1. Sample

Urban particulate matter used as a pollutant was collected from urban air pollutants with an average particle size of 10 μm or less (PM10, Sigma-Aldrich, Darmstadt, Germany). As natural products, sea bamboo shoots obtained by hot water extraction and mountain gourd were used, and the auditory was provided by Kangcos Metique. The compound isolated in Experimental Example 1 was used as a material for identifying mountain odor, and Salidroside, an analogue, was purchased and used.

2. Cell Lines

HaCaT, Raw 264.7, Melan-a, and HDF cell lines used in this experiment were purchased from the Korean Cell Line Bank and used in DMEM medium containing 1% antibiotic-antimycotic and 10% FBS. Incubated in a CO ₂ incubator adjusted to °C, 5% CO ₂ .

[Experimental Example 3: Cytotoxicity test]

1. Cytotoxicity assay (LDH assay)

Cytotoxicity to HaCaT cells was measured using a non-radioactive cytotoxicity assay using lactase dehydrogenase (LDH) release, and Raw264.7 cells and HaCaT cells were placed in a 48-well plate (SPL, Korea) at 1×10 ⁵ cells/ It was inoculated into a well, and after 18 hours of incubation, the hot water extracts from sangolchi were simultaneously treated by concentration and incubated for 24 hours.

45 minutes before recovery of the culture medium, the control cells were treated with 1× lysis buffer (Promega, USA), incubated for 45 minutes, and then the culture medium was centrifuged at 3,000 rpm for 5 minutes. 50 μL of culture medium obtained by centrifugation and 50 μL of reconstituted substrate mix (Promega, USA) were added, and the reaction was stopped at room temperature for 30 minutes, and then 50 μL of stop solution (Promega, USA) was added to stop the reaction. Absorbance was measured at 490 nm using a microplate reader.

The average absorbance value for each sample group was obtained, and cytotoxicity was measured by comparing it with the absorbance value of the control group.

The experimental results are the same as in FIG. 3, and it was confirmed that there was no cytotoxicity of the hot water extract of Sangoschi.

[Experimental Example 4: Anti-inflammatory effect experiment on inflammatory reaction caused by fine dust]

Inflammation expression effect by microparticle PM10 was measured by prostaglandin E2 (PGE ₂ ) expression effect test. Epithelial keratinocyte HaCaT cells were inoculated in a 48-well plate at 1×10 ⁵ cells/well, and after 18 hours of incubation, microparticle PM10 was treated according to concentration and cultured for 24 hours. 45 minutes before recovery of the culture medium, the control cells were treated with 1× lysis buffer (Promega, USA), incubated for 45 minutes, and then the culture medium was centrifuged at 3,000 rpm for 5 minutes. The obtained supernatant was measured for PGE ₂ expression using a PGE ₂ ELISA assay kit (R&D system, USA). All samples were stored frozen at -20 °C or lower until quantification.

Figure 4 confirms the effect of inducing prostaglandin E2 (PGE ₂ ) expression in the inflammatory expression effect of microparticle PM10, and it was confirmed that the effect of inducing PGE ₂ expression was the highest at 25 μg/mL.

Using the 25 μg/mL as a control, PGE ₂ inhibitory effect by microparticle PM10 was confirmed by treatment with 1 μg/mL and 2 μg/mL of sangoschi hot water extract (Saussurea neo serrata), Syringin and Salidroside, respectively.

The experimental results are as shown in FIG. 5, and it was confirmed that the PGE ₂ inhibitory effect was excellent when Syringin and Salidroside, the active substances isolated in Experimental Example 1, were treated alone, compared to the control group.

In light of the experimental results, it will be said that the active material isolated from mountain odor has an excellent inhibitory effect on inflammatory mediators caused by fine dust.

[Experimental Example 5: Intracellular antioxidant effect test]

1. UV B irradiation

UVB irradiation is performed after removing the culture medium, washing the HaCaT cells with PBS, and adding enough PBS to lightly cover the cells. The cells were placed in a UV irradiator, and a wavelength of 275 to 380 nm (up to 290 to 320 nm) was irradiated using a TL 20W/12 RS fluorescent sun lamp (Philips, Netherlands). At this time, a TA 401/407 Kodacel filter (Kodak, USA) was attached to remove UVC emitted from the lamp and the intensity of UV irradiated to the cells was measured with a UV meter (Ultra-Violet Products Ltd., UVP, USA). did.

2. Measurement of the inhibitory effect on the production of free radicals in cells (hydroxyl radical)

In order to measure the inhibitory effect of intracellular hydroxyl radical generation of the extracts from HaCaT according to UVB irradiation, after irradiating with UVB (100 mJ/cm ² ) for 130 min, the fluorescent probe 2',7'-dichlorofluorescein diacetate (DCF-DA: Molecular probe) was used to measure the change in the concentration of hydroxyl radical in the cell.

DCF-DA, which is a non-fluorescent material, is converted into DCF that fluoresces by reacting with hydroxyl radicals and hydrogen peroxide in cells, and shows green fluorescence. ROS can be measured through DCF-DA. 1×10 ⁴ HaCaT cells were inoculated into a 96-well plate (SPL, Korea) and cultured for 18 hours, treated with different concentrations at the same time and cultured for 24 hours. After the culture was completed, the medium was removed and washed twice with PBS. After adding 10 μM DCF-DA to each well and incubating for 90 minutes at 37°C, 5% CO ₂ incubator, the fluorescence intensity was measured through flow cytometry and × using a laser fluorescence microscope (LSM 510, Carl Zeiss, Germany). At 400 magnification, the excitation wavelength was 488 nm (argon laser) and the emission wavelength was 505 nm. After drug administration, changes in fluorescence intensity in cells were observed.

Syringin and Salidroside, which are the active substances isolated from the extract of wild chives, were also treated with 1 mg/mL and 2 mg/mL, respectively, and the efficacy was comparatively analyzed using the same method as in the PGE ₂ inhibitory effect experiment by PM10 microparticles.

The experimental results are shown in FIGS. 6 to 9 . Figure 6 is a control measure the change in fluorescence intensity due to UVB irradiation, and then the reactive oxygen production inhibitory effect for each was tested.

As a result of the experiment, it was confirmed that Syringin and Salidroside, which are the active substances isolated from the extract of wild chives, had an excellent inhibitory effect on the production of active oxygen compared to the control group.

[Experimental Example 6: Nerve cell active substance secretion test]

1. Cell culture

Human-derived dermal fibroblasts use HDF cell line, and cultured in a 10% CO ₂ incubator at 37° C. with 0% FBS, 100 mg/L streptomycin, 100,000 U/L penicillin, and DMEM medium.

2. Extraction sample treatment and UVB irradiation

After stabilizing the cells by dispensing them into a 6-well plate at a density of 5×10 ⁵ cells/well, the extracts were dissolved in serum-free culture medium in each well, treated by concentration, and cultured for 24 hours, then the medium was removed and PBS enough to lightly cover the cells. was added and then UVB was irradiated.

The cells were placed in a UV irradiator, and a wavelength of 275 to 380 nm (up to 290 to 320 nm) was irradiated using a TL 20W/12 RS fluorescent sun lamp (Philips, Netherlands). At this time, a TA 401/407 Kodacel filter (Kodak, USA) was attached to remove UVC emitted from the lamp and the intensity of UV irradiated to the cells was measured with a UV meter (Ultra-Violet Products Ltd., UVP, USA). did

3. Effect on survival and development of nerve cells

After treating the HDF cells with the extraction sample and UVB, incubate for 48 hours, collect the culture medium, collect only the supernatant, and measure the concentration of nerve growth factor-β and neurotrophin-3 production using an enzyme-linked immunosorbent assay (ELISA) kit.

The experimental results are shown in FIGS. 10 and 11 .

As a result of the experiment, it was confirmed that the active substances, Syringin and Salidroside, which were isolated from the extract of sangoschi, exhibited higher concentrations of nerve growth factor-β and neurotrophin-3 compared to the control group.

[Experimental Example 7: Whitening Efficacy Experiment]

1. Cell culture

Melan-a cells were immortalized melanocyte cell line with 10% FBS, 200 nM TPA, 100 mg/L streptomycin, 100,000 U/L penicillin, and RPMI medium and cultured in a 10% CO ₂ incubator at 37°C.

2. Melanin production inhibition test in melanocytes

Dispense to a concentration of 2 X 10 ⁵ cells per well in a 6 well plate, and after 48 hours, the sample was treated for 3 days to harvest the cells, and the amount of melanin produced was prepared by preparing a 10% DMSO solution with 1 N NaOH to dissolve the cells and 475 By measuring the absorbance at nm, the melanin production inhibitory effect of the sample treatment group was expressed as a ratio to the control value.

The experimental results are the same as in FIG. 12, and it can be confirmed that the same or superior melanin production inhibitory effect appears in the active material isolated from the mountain odor, compared to Arbutin, which is known to have an excellent effect on skin whitening. It can be seen that there is

Although preferred embodiments of the present invention have been described in detail above, the scope of the present invention is not limited thereto, and various modifications and improvements by those skilled in the art using the basic concept of the present invention as defined in the following claims are also provided. is within the scope of the

Claims (8)

It contains a compound represented by the following formula (1) as an active ingredient,
Excellent anti-inflammatory, antioxidant, anti-aging and skin whitening effects
Compositions for skin anti-pollution:
[Formula 1]

here,
L ₁ is a single bond or a substituted or unsubstituted C 1 to C 10 alkylene group,
Ar ₁ is a substituted or unsubstituted cycloalkyl group having 3 to 30 carbon atoms, a substituted or unsubstituted aryl group having 5 to 30 carbon atoms, a substituted or unsubstituted heteroaryl group having 2 to 30 carbon atoms, or a substituted or unsubstituted heteroaryl group having 3 to 30 carbon atoms It is selected from the group consisting of an arylalkyl group, and a substituted or unsubstituted aryloxy group having 6 to 30 carbon atoms,
The substituents of L ₁ and Ar ₁ are hydrogen, deuterium, cyano group, nitro group, halogen group, hydroxyl group, alkyl group having 1 to 30 carbon atoms, alkenyl group having 2 to 30 carbon atoms, alkynyl group having 2 to 24 carbon atoms, and 2 to carbon atoms. A heteroalkyl group having 30, an aralkyl group having 6 to 30 carbon atoms, a cycloalkyl group having 3 to 20 carbon atoms, a heterocycloalkyl group having 3 to 20 carbon atoms, an aryl group having 5 to 30 carbon atoms, a heteroaryl group having 2 to 30 carbon atoms, 3 to carbon atoms substituted with a substituent selected from the group consisting of a 30 heteroarylalkyl group, an alkoxy group having 1 to 30 carbon atoms, an alkylsilyl group having 1 to 30 carbon atoms, an arylsilyl group having 6 to 30 carbon atoms, and an aryloxy group having 6 to 30 carbon atoms, When substituted with a plurality of substituents, they are the same as or different from each other. According to claim 1,
Wherein Ar ₁ is a compound represented by the following Chemical Formula 2 or Chemical Formula 3
Compositions for skin anti-pollution:
[Formula 2]

[Formula 3]

here,
* means the part to be joined. According to claim 1,
The compound represented by Formula 1 exhibits a first peak at 6.86 to 6.88 ppm when ¹ H-NMR spectrum is measured,
showing a second peak at 6.85 to 6.87 ppm
A composition for skin anti-pollution. According to claim 1,
The compound represented by Formula 1 is an active material separated and purified from the extract
A composition for skin anti-pollution. 5. The method of claim 4,
The compound represented by Formula 1 is an active material that is separated and purified by fractionating the extract of sangolchi with n-BuOH.
A composition for skin anti-pollution. A composition comprising the composition according to any one of claims 1 to 5
A cosmetic composition for skin anti-pollution. A composition comprising the composition according to any one of claims 1 to 5
A food composition for skin anti-pollution. A composition comprising the composition according to any one of claims 1 to 5
A pharmaceutical composition for skin anti-pollution.

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