KR20170076374A - Composition for improving skin conditions comprising hupehenine - Google Patents

Abstract

The present invention relates to a cosmetic composition, a pharmaceutical composition and a health food which have excellent effects on skin antiheration, whitening, wrinkle improvement, elasticity improvement or anti-inflammation in the skin. The composition of the present invention exhibits excellent effects on skin whitening, skin elasticity enhancement, skin wrinkle improvement, skin moisturization or skin anti-inflammation. The compound of Chemical Formula (1), which is an active ingredient of the composition of the present invention, can be used as a cosmetic raw material, a pharmaceutical ingredient or a health food raw material which is safe for skin and has excellent skin condition improving effect.

Description

BACKGROUND OF THE INVENTION 1. Field of the Invention [0001] The present invention relates to a composition for improving skin condition,

More particularly, the present invention relates to a cosmetic composition, a pharmaceutical composition and a health food which have excellent effects on skin antihalation, whitening, wrinkle improvement, elasticity improvement or anti-inflammation will be.

It is a common desire to have white skin. The color or brightness of the skin is genetically determined by the concentration and distribution of melanin in the human skin, but is also influenced by environmental or physiological conditions such as sun UV, fatigue or stress. Melanin is produced by a nonenzymatic oxidation reaction of tyrosine, which is a kind of amino acid, by the enzyme tyrosinase, which is converted to DOPA and Dopaquinone. The pathway for the formation of melanin is known, but the mechanism by which the melanin synthesis induces tyrosinase is not yet elucidated.

On the other hand, commonly known whitening ingredients include substances that inhibit tyrosinase enzyme activities such as kojic acid or arbutin, and also include hydroquinone, L-ascorbic acid or derivatives thereof And various plant extracts are known to have whitening effect. By inhibiting the synthesis of melanin pigment, they can lighten skin tone to realize whitening of skin, and it is possible to improve skin hypercholesterolemia such as stain or freckles due to ultraviolet ray, hormone or oil field. However, when applied to skin, there is a problem that the use amount is limited due to safety problems such as irritation and redness, or the effect is insignificant, so that a practical effect can not be expected.

Collagen is a major substrate protein produced in the fibroblasts of the skin and exists in extracellular epilepsy. Its important functions are mechanical durability of the skin, resistance of connective tissues and binding force of tissues, support of cell adhesion, cell division and differentiation (Induction of growth of an organism or wound healing) are known. Such collagen is reduced by photoaging by age and ultraviolet irradiation, and collagenase activity, which degrades collagen, promotes collagen reduction. This is known to be closely related to the formation of wrinkles in the skin.

In addition, Elastin fiber forms crosslinks with collagen and is a skin constituent important for wrinkle formation involved in skin elasticity. The deficiency and aggregation of elastin fibers and the marked increase in the activity of the elastin degrading enzyme Elastase have been found to be one of the causes of skin wrinkles. It is known that Elastase is the only enzyme capable of degrading elastin, and its inhibition can fundamentally reduce the wrinkles of the skin.

On the other hand, collagen and elastin fibers are substrate proteins that play an important role in water retention in the dermal layer. These protein proteins adsorb moisture and increase the water holding capacity inside the structure, thereby allowing the skin to maintain proper moisture content. And it is known to be involved in maintaining the elasticity of the skin.

In addition, the elastic fiber produced in the fibroblast of the skin forms a cross-link with collagen, and is a skin constituent important for wrinkle formation which is involved in skin elasticity. Deficiency and decomposition of elastic fibers were found to be one of the main factors of skin wrinkle formation and elasticity reduction.

Presently, retinoids, adenosine, animal placenta-derived proteins, chlorella extract, and the like are known to improve wrinkles. The best known retinol promotes collagen synthesis and inhibits elastase enzymes, but it is unstable. When applied to the skin, it has a limited use due to safety problems such as irritation and redness, and chlorella extract has little effect, It is known that it is difficult to expect a wrinkle-improving effect.

Glycation generally refers to a reaction in which a simple sugar such as glucose or fructose forms a covalent bond to a protein or fat that occurs without involvement of the enzyme. Saccharification takes place through a series of complex chemical reactions known as Amadori rearrangement, Maillard reaction, which results in the formation of advanced glycation endproducts (AGEs).

On the other hand, the glycation process of the protein does not involve the enzymatic action, so it occurs slowly, and as a result, the protein having a longer half-life such as collagen has more influence. Analysis of the final glycation products revealed that the more aged the glycated collagen was accumulated, the accumulation of the final glycated product changed the protein to a harder and more brittle state, and the glycated collagen was found in the extracellular matrix of the dermal layer (Dyer, DG et al. , The Journal of Clinical Investigation, 9, p. 2463, 1993), by inhibiting collagen from forming a proper structure and thereby reducing skin elasticity and promoting wrinkle formation.

Also, it is known that the final saccharification product produced by saccharification is a brownish substance and accumulates on the dermal layer as the skin ages. It is believed that as the aging of the skin progresses gradually, the face light turns yellow and it is known that the reflection light reflected from the skin decreases as the specific final saccharification product accumulates. While the amount of melanin pigment in the skin is weakly related to skin aging, the final glycation product accumulated in the dermal layer of the skin gradually increases in amount as the skin ages, and the skin color becomes dull (Hiroshi, O. et al . Skin Research and Technology, 15, p. 496, 2009).

Aminoguanidine, pyridoxamine, and aspirin are known to inhibit glycosylation. However, these substances are limited in their use due to the safety of the skin, There is a problem that can not be expected.

Inflammation is the immune response of the body in response to a wound or disease. Oxidative stresses such as ultraviolet rays, active oxygen, and free radicals activate inflammatory factors and cause aging of various diseases and skin. The vasoactive polypeptides Kinin, Plasmin and Complement have vasodilatation, contraction and chemotaxis, and also include lymphokines such as interleukin-6 (IL-6) Phosphorus and arachidonic acid are responsible for inflammation. Arachidonic acid is metabolized through the two pathways of cyclooxygenase or lipoxygenase and is metabolized to inflammation mediator Prostaglandin or Lukotriene to mediate various inflammatory responses.

On the other hand, in order to eliminate inflammation, elimination of inflammation source, reduction of vital reaction and symptoms is called anti-inflammatory. Flutenamic acid, Ibuprofen, Benzydamine, Indomethacin, and Prednisolone have been used for antiinflammatory purposes to date. Nonsteroidal antiinflammatory agents include fluthenic acid, , And dexamethasone. It is also known that allantoin, azene, hydrocortisone, etc. are effective in improving inflammation. However, these substances have problems in that their use is limited due to the safety of the skin, or the effects thereof are insignificant, have.

Therefore, it is possible to provide a pharmaceutical composition which is safe and biologically safe, effective for skin, safe and high in stability, and exhibits antihalation, whitening, wrinkle improvement, elasticity improvement, Improvement of elasticity, or development of a component for anti-inflammation is strongly desired.

Accordingly, a problem to be solved by the present invention is to solve the above-mentioned problems, and to provide a new active ingredient which is safe to human body and has little side effects and is excellent in antihalation, whitening, wrinkle improvement, elasticity improvement or anti- To provide useful applications.

In other words, a problem to be solved by the present invention is to provide a composition comprising an active ingredient having excellent efficacy as an active ingredient.

In order to solve the above-described problems, the present invention provides a skin whitening agent for skin whitening, skin elasticity enhancement, skin wrinkle improvement, skin moisturizing or skin whitening comprising, as an active ingredient, Hupehenine or a pharmacologically or cosmetically acceptable salt thereof, A composition for skin inflammation, preferably a cosmetic composition, a pharmaceutical composition or a health food.

That is, the present invention relates to the use of a pharmaceutical or cosmetically acceptable salt thereof as a cosmetic composition or a pharmaceutical composition, and to a skin whitening agent, a skin elasticity improving agent, a skin wrinkle improving agent, a skin moisturizing agent or a skin anti- It provides a new use.

The inventors of the present invention have found that the hufenhenin promotes the collagen production of the skin and inhibits the activity of the elastase, thereby improving the wrinkles and elasticity of the skin, thus completing the present invention. In addition, it was confirmed that the above-mentioned triphenyin decreased the total amount of melanin to exhibit a skin whitening effect, inhibited NO production, and also exhibited anti-inflammatory effects. In addition, the above-mentioned triphenyin exhibits an antihyperglycemic effect, and can act synergistically by acting as an auxiliary for skin whitening, skin wrinkles and skin elasticity improvement.

In the present invention, the 'whitening effect' refers to not only brightening the skin tone but also improving skin hypercholesterolemia such as stain or freckles due to ultraviolet rays, hormones or heredity. This whitening effect can be achieved, for example, by reducing the total amount of melanin pigment, but the present invention is not limited by this mechanism.

In the present invention, the term 'improving elasticity or skin elasticity' means reducing the degree to which the skin is stuck or stretched. In addition, the elasticity means that elasticity of the skin is maintained in a state where elastin and collagen are sufficiently present.

In the present invention, "improving wrinkles" refers to preventing, suppressing or inhibiting the generation of wrinkles on the skin, or alleviating wrinkles that have already been formed.

In the present invention, the term 'moisturizing or skin moisturizing' means increasing the skin moisture and maintaining a moist state. Skin moisturizing effect can help to improve wrinkles and elasticity of skin.

In the present invention, the term 'anti-inflammatory effect' refers to inhibition of inflammation. The inflammation is one of defensive responses of biological tissues to certain stimuli, and involves three types of tissue degeneration, circulatory disorder, exudate, and tissue proliferation Complex lesions. More specifically, inflammation is part of congenital immunity and, like in other animals, human congenital immunity recognizes a pattern of cell surfaces that are specifically present in a pathogen. Phagocytes recognize cells with such surfaces as non-magnetic and attack pathogens. If pathogens break through the physical barriers of the body, an inflammatory reaction occurs. Inflammation is a nonspecific defense that creates hostile environments for microorganisms entering the wound. In the inflammatory response, white blood cells that are responsible for the early stage of immune response, when wounded or infected, enter the body to express cytokines. Therefore, the expression level of intracellular cytokine is an index of inflammatory response activation. Examples of skin diseases associated with inflammation include atopic dermatitis, psoriasis, radiation, chemical substances, inflammatory diseases caused by burns, acid burns, vesicular dermatosis, visceral type diseases, itching due to allergies, seborrheic eczema, rose acne, Inflammatory hair loss such as pemphigus vulgaris, polymorphous exudative erythema, erythema nodosum, erythematosus, pharyngitis, alopecia areata, skin T-cell lymphoma, and the like.

In the present invention, the 'antagonism' effect means preventing the collagen from being saccharified in the extracellular matrix of the dermal layer, thereby enhancing elasticity of the skin and preventing wrinkle formation. In addition, the antihalation effect can help skin whitening by inhibiting the production of final glycation products accumulated on the dermal layer according to skin aging. Therefore, in the present invention, the anticarcinogenic effect can not only enhance skin elasticity and wrinkle but also produce a synergistic effect on skin whitening.

In order to solve the above-mentioned problems and to achieve the object of the present invention, the present invention provides a composition comprising a compound represented by the following Chemical Formula 1, or a pharmaceutically or cosmetically acceptable salt thereof.

[Chemical Formula 1]

The compound represented by the formula (1) has the molecular formula C ₂₇ H ₄₅ NO ₂ , the molecular weight is 415.65, and is named Hupehenine.

The present invention is not particularly limited to the method for obtaining the above-described triphenyin, and may be chemically synthesized by a known method in the field of the present invention, or a commercially available material may be used.

In the cosmetic composition, the pharmaceutical composition and the health food according to the present invention, the amount of the above-mentioned humectant or its pharmaceutically or cosmetically acceptable salt may be 0.00001 to 10% by weight based on the total weight of the cosmetic composition, .

In the present invention, the above-mentioned triphenynes used as an active ingredient can be used in the form of a "pharmaceutically or cosmetically acceptable salt ". "Pharmaceutically or cosmetically acceptable salts " of the above-described triphenyenes refer to salts prepared using less or less toxic organic acids or inorganic acids with respect to the hufenhenin.

The organic acid may be selected from the group consisting of formic acid, acetic acid, propionic acid, lactic acid, butyric acid, isobutyric acid, trifluoroacetic acid, malic acid, maleic acid, malonic acid, fumaric acid, succinic acid, succinic acid monoamide, glutamic acid, , Glycolic acid, glucuronic acid, ascorbic acid, benzoic acid, phthalic acid, salicylic acid, anthranilic acid, dichloroacetic acid, aminooxyacetic acid, benzenesulfonic acid, p-toluenesulfonic acid and methanesulfonic acid-based salts, , Bromic acid, sulfuric acid, phosphoric acid, nitric acid, carbonic acid and boric acid-based salts.

The above-mentioned acid addition salts may be obtained by a) directly mixing the compound of formula 1 and an acid, or b) dissolving and mixing one of them in a solvent or a water solvent, or c) Lt; RTI ID = 0.0 > acid < / RTI > in a solvent and mixing them.

In addition to the above, additionally saltable forms include, but are not limited to, the salts of gabapentin, pregabalin, nicotinate, adipate, hemimarate, cysteine, acetylcysteine, methionine, arginine, Aspartate and the like.

The triphenynes of the present invention may exist in solvated as well as unsolvated forms, including forms such as hydrates, ethanolates, and the like. The present invention can be present in crystalline or amorphous form, and all such physical forms are included within the scope of the present invention.

The composition for skin whitening, skin elasticity enhancement, skin wrinkle improvement, skin moisturizing or skin antiinflammation according to the present invention can be used as a solution, an external ointment, a cream, a foam, a nutrition lotion, a softening water, a pack, Base, essence, soap, liquid cleansing agent, bath salts, sunscreen cream, sun oil, suspension, emulsion, paste, gel, lotion, powder, soap, surfactant-containing cleansing oil, powder foundation, emulsion foundation wax But are not limited to, a formulation selected from the group consisting of a foundation, a patch, and a spray.

In addition, the cosmetic composition of the present invention may further comprise at least one cosmetically acceptable carrier incorporated in a cosmetic composition for general skin, and examples thereof include oil, water, a surfactant, a moisturizer, a lower alcohol, A thickening agent, a chelating agent, a coloring matter, an antiseptic, a perfume, and the like may be appropriately compounded, but the present invention is not limited thereto.

The cosmetically acceptable carrier to be contained in the cosmetic composition of the present invention varies depending on the formulations. When the formulation of the present invention is an ointment, a paste, a cream or a gel, the carrier component may be an animal oil, a vegetable oil, a wax, a paraffin, a starch, a tracer, a cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc, zinc oxide Mixtures of these may be used.

When the formulation of the present invention is a powder or a spray, lactose, talc, silica, aluminum hydroxide, calcium silicate, polyamide powder or a mixture thereof may be used as the carrier component, Propellants such as fluorohydrocarbons, propane / butane or dimethyl ether.

When the formulation of the present invention is a solution or an emulsion, a solvent, a solubilizing agent or an emulsifying agent is used as a carrier component, and examples thereof include water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl benzoate, -Butyl glycol oil, and in particular fatty acid esters of cottonseed oil, peanut oil, corn oil, olive oil, castor oil and sesame oil, glycerol aliphatic ester, polyethylene glycol or sorbitan.

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 suspension such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester and polyoxyethylene sorbitan ester, Crystalline cellulose, aluminum metahydroxide, bentonite, agar or tracant, etc. may be used.

When the formulation of the present invention is a soap, alkali metal salts of fatty acids, fatty acid hemiesters, fatty acid protein hydrolizates, isethionates, lanolin derivatives, aliphatic alcohols, vegetable oils, glycerol, sugars and the like are used as carrier components .

The present invention also relates to a method for improving skin whitening, improving skin elasticity, improving skin wrinkles, skin moisturizing or skin nourishment, which comprises applying a compound represented by Formula 1 or a pharmaceutically or cosmetically acceptable salt thereof to an individual's skin Provides an inflammation method. The subject includes, without limitation, mammals including rats, livestock, humans, and the like.

According to another embodiment of the present invention, the present invention provides a method for skin whitening, skin elasticity enhancement, skin wrinkle improvement, and skin whitening comprising the compound of Chemical Formula 1 or a pharmaceutically or cosmetically acceptable salt thereof as an active ingredient There is provided a pharmaceutical composition for moisturizing or skin anti-inflammation.

The composition comprising the compound of the present invention may be various oral or parenteral formulations, but may preferably be a parenteral agent. In the case of formulation, a diluent or excipient such as a filler, an extender, a binder, a wetting agent, a disintegrant, or a surfactant is usually used. Solid formulations for oral administration include tablets, pills, powders, granules, capsules, and the like, which may contain one or more excipients such as starch, calcium carbonate, sucrose or lactose lactose, gelatin and the like. In addition to simple excipients, lubricants such as magnesium stearate, talc, and the like are also used. Liquid preparations for oral administration include suspensions, solutions, emulsions, syrups and the like. Various excipients such as wetting agents, sweeteners, fragrances, preservatives and the like may be included in addition to water and liquid paraffin, which are simple diluents commonly used. have. Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solutions, suspensions, and emulsions. Examples of the non-aqueous solvent and the suspending agent include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, and injectable ester such as ethyl oleate.

The present invention also relates to the use of a compound of formula (I) or a pharmaceutically or cosmetically acceptable salt thereof as an active ingredient for skin whitening, skin elasticity enhancement, skin wrinkle improvement, skin moisturizing or skin anti- Can be provided.

When the compound of Chemical Formula 1 or a pharmaceutically or cosmetically acceptable salt thereof is used as an external preparation for skin, it may further contain a fatty substance, an organic solvent, a solubilizing agent, a thickening agent and a gelling agent, a softening agent, an antioxidant, a suspending agent, A foaming agent, a fragrance, a surfactant, water, an ionic or nonionic emulsifier, a filler, a sequestering and chelating agent, a preservative, a vitamin, a barrier, a wetting agent, A lipophilic active agent, a lipid vesicle or any other ingredient conventionally used in external preparations for skin. The components can also be introduced in amounts commonly used in the field of dermatology.

When the compound of Formula 1, or a pharmaceutically or cosmetically acceptable salt thereof, is provided as an external dermal preparation, it may have a formulation such as, but not limited to, ointments, patches, gels, creams or sprays.

The pharmaceutical composition of the present invention is particularly preferably used as a parenteral preparation. For example, the external preparation for skin may be a pharmaceutically acceptable base such as vaseline or stearyl alcohol; Suitable pharmaceutically acceptable surfactants such as polysorbate, sorbitan sesquioleate, and the like; A suitable pharmaceutically acceptable humectant such as glycerin; A suitable pharmaceutically acceptable solvent; And a conventional external preparation for skin preparation in which a flavoring agent, a coloring agent, a stabilizer, a tackifier and the like are homogeneously mixed.

When the compound of Formula 1 of the present invention or its pharmaceutically or cosmetically acceptable salt is used as a medicament, it may further contain one or more active ingredients showing the same or similar functions. For example, it may contain known ingredients for skin whitening, skin elasticity enhancement, skin wrinkle improvement, skin moisturizing or skin antiinflammation. When the composition contains the ingredients for further skin whitening, skin elasticity enhancement, skin wrinkle improvement, skin moisturizing, or skin antiinflammation, the skin whitening, skin elasticity improvement, skin wrinkle improvement, skin moisturization, The effect can be further enhanced. When the above ingredients are added, skin safety, easiness of formulation, and stability of effective ingredients can be considered according to the combined use.

In one embodiment of the invention, the composition is a skin elasticity or wrinkle improving ingredient known in the art and includes retinoic acid, TGF, animal placenta-derived proteins, betulinic acid and chlorella extract; As a whitening ingredient known in the art, a substance that inhibits tyrosinase enzyme activity such as kojic acid, arbutin, etc., hydroquinone, L-ascorbic acid; Anti-inflammatory components known in the art include, but are not limited to, COX-2 inhibitors, prednisolone and allantoin; Examples of moisturizing ingredients known in the art include petrolatum, mineral oil, silicone, triglycerides, essential fatty acids such as gamma linolenic acid (evening primrose oil), GGF, amino acids, provitamin B5, hyaluronic acid, γ-glutamic acid, Lipidure PMB, ceramide, cholesterol, fatty acids; And derivatives thereof, and various plant extracts. ≪ Desc / Clms Page number 2 > The additional ingredients may be included in an amount of 0.0001 to 10% by weight based on the total weight of the composition, and the content may be adjusted according to requirements such as skin safety, ease of formulation of the compound of Formula 1, and the like.

The pharmaceutical composition of the present invention provides desirable skin whitening, skin elasticity enhancement, skin wrinkle improvement, skin moisturizing or skin anti-inflammatory effects when the compound of the above formula 1 or its pharmaceutically or cosmetically acceptable salt is contained in an effective amount can do. In the present invention, the term "effective amount" means the amount of a compound capable of sufficiently exhibiting skin whitening, skin elasticity improvement, skin wrinkle improvement, skin moisturizing or skin anti-inflammatory effect.

The effective amount of the compound of formula (I) or a pharmaceutically or cosmetically acceptable salt thereof contained in the composition of the present invention will vary depending on the form in which the composition is produced, the manner in which the compound is applied to the skin, and the time on the skin. For example, when the composition is commercialized as a pharmaceutical product, the compound of Formula 1 may be contained at a higher concentration than that of a cosmetic product that is routinely applied to skin. Accordingly, the daily dosage is 0.1 to 100 mg / kg, preferably 30 to 80 mg / kg, more preferably 50 to 60 mg / kg, based on the amount of the compound of formula (1) 6 times a day.

According to another embodiment of the present invention, there is provided a pharmaceutical composition for skin whitening, skin elasticity enhancement, skin wrinkle improvement, skin moisturizing, or skin antiinflammation comprising the compound of Chemical Formula 1 or a pharmaceutically or cosmetically acceptable salt thereof Provide health food.

In the present specification, the term 'health food' is intended to include a compound of the above formula (1) or a pharmaceutically or cosmetically acceptable salt thereof to a food material such as a beverage, a tea, a spice, a gum or a confectionery, or to encapsulate, , Which means that it has a certain health effect when ingested. However, unlike general medicines, there is an advantage that there is no side effect that may occur when a drug is taken for a long time by using a food as a raw material. Since the health food of the present invention thus obtained can be routinely ingested, it can be expected to exert excellent effects on skin whitening, skin elasticity enhancement, skin wrinkle improvement, skin moisturization or skin anti-inflammation.

When the compound of Chemical Formula 1, or a pharmaceutically or cosmetically acceptable salt thereof, is used as a food additive, the compound of Chemical Formula 1 or a pharmaceutically or cosmetically acceptable salt thereof may be directly added, Can be used together, and can be suitably used according to a conventional method. The amount of the active ingredient to be mixed can be suitably determined according to its intended use (prevention, health or therapeutic treatment). Generally, the composition of the present invention is added in an amount of not more than 15 parts by weight, preferably not more than 10 parts by weight, based on the raw material, when the food or beverage is produced. However, in the case of long-term consumption intended for health and hygiene purposes or for health control purposes, the amount may be less than the above range, and since there is no problem in terms of safety, the active ingredient may be used in an amount exceeding the above range . There is no particular limitation on the kind of the food. Examples of the food to which the above substance can be added include dairy products including meat, sausage, bread, chocolate, candy, snack, confectionery, pizza, ramen, other noodles, gums, ice cream, various soups, drinks, tea, Alcoholic beverages, and vitamin complexes, all of which include healthy foods in a conventional sense. The health beverage composition of the present invention may contain various flavors or natural carbohydrates as an additional ingredient such as ordinary beverages. Such natural carbohydrates are monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, and polysaccharides such as dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol and erythritol. Examples of sweeteners include natural sweeteners such as tau martin and stevia extract, synthetic sweeteners such as saccharin and aspartame, and the like. The ratio of the natural carbohydrate is generally about 0.01 to 0.04 g, preferably about 0.02 to 0.03 g per 100 mL of the composition of the present invention. In addition to the above, the health food of the present invention may contain various nutrients, vitamins, electrolytes, flavors, colorants, pectic acids and salts thereof, alginic acid and its salts, organic acids, protective colloid thickeners, pH adjusters, stabilizers, preservatives, , A carbonating agent used in carbonated drinks, and the like. In addition, the health food of the present invention may contain flesh for the production of natural fruit juice, fruit juice drink and vegetable drink. These components may be used independently or in combination. The proportion of such additives is not critical, but is generally selected in the range of 0.01 to 0.1 parts by weight per 100 parts by weight of the composition of the present invention.

In one embodiment of the present invention, but not limited thereto, the composition may comprise 0.00001% to 10% by weight of the compound of Formula 1 or a pharmaceutically or cosmetically acceptable salt thereof, based on the total composition weight have.

The composition containing the humectanthene of the present invention exhibits excellent effects on skin whitening, skin elasticity enhancement, skin wrinkle improvement, skin moisturization or skin anti-inflammation.

The composition containing the humectanthene of the present invention can be used as a cosmetic raw material, a pharmaceutical ingredient, or a raw material for health food, which is safe for skin and has excellent skin condition improving effect.

Hereinafter, the present invention will be described in more detail with reference to the following examples. However, the embodiments according to the present invention can be modified into various other forms, and the scope of the present invention should not be construed as being limited to the embodiments described below. The embodiments of the present invention are provided by way of example to facilitate a specific understanding of the present invention.

Reference Example  One: Hufenhenine ( Hupehenine ) Material information

[Chemical Formula 1]

Material name: Hupehenine

CAS No. : 98243-57-3

Molecular formula: C ₂₇ H ₄₅ NO ₂

Molecular weight: 415.65

Where to buy: Shanghai Tauto Biotech Co., Ltd

Experimental Example  1: promoting the synthesis of type I collagen in human fibroblasts

The compound of Chemical Formula 1 was added to the culture medium of human-derived fibroblasts to confirm the promoting effect of type I collagen synthesis at the cellular level. The synthesized collagen was quantitated using a PICP EIA kit (Procollagen Type I C-Peptide Enzyme Immuno Assay Kit). To measure the amount of collagen synthesis, the compound of formula (1) was added to a culture medium of fibroblasts (DMEM medium) and cultured for 48 hours. The culture broth was taken and the degree of type 1 collagen synthesis was measured by a PICP EIA kit using a spectrophotometer And measured at 450 nm.

For the comparison of the effects, the degree of collagen synthesis was measured in the same manner for the samples in which the culture medium of the untreated fibroblasts (negative control) and vitamin C (positive control) were added to a final concentration of 52.85 / / ml. The increase rate of collagen production was calculated as a ratio of relative collagen production to the control group, and the results are shown in Table 1 below.

Promoting collagen synthesis of the compound of formula (1) (number of repeats = 4)

sample Type 1 collagen synthesis (ng / ml) Growth rate (%) Negative control group 150.2 - Positive control group
(Vitamin C, 52.85ppm) 246.8 64.3 The compound of formula (1) (1 ppm) 177.1 17.94 The compound of formula (1) (10 ppm) 213.5 42.15

As can be seen from the results of Table 1, when the compound of Chemical Formula 1 was treated, the amount of collagen synthesis was increased in a concentration-dependent manner, and the similar collagen synthesis effect was lower than that of vitamin C, which is generally known to induce collagen synthesis But showed excellent collagen synthesis effect.

Experimental Example  2: Elastase  Active inhibitory effect

The activity inhibitory effect of Elastase, an enzyme that degrades elastin, was confirmed as follows.

Elastase used Elastase from human leukocyte cells and MeOSuc-Ala-Ala-Pro-Val-pNA as synthetic substrate for Elastase. The buffer solution used was 100 mM Tris (pH 7.5) solution. Finally, 0.2 mU was used for the ELASTASES using a buffer solution. In addition, the synthetic substrate of Elastase was diluted with buffer solution to make a final concentration of 0.5 mM by making a 100 mM solution using DMSO. At this time, the positive control group was set to contain 10 ppm of quercetin, which is known as an ELASTIC inhibitor. Ella stase inhibition candidates were added to give a final concentration of 10, 20 ppm. The reaction was carried out in a 96-well plate and allowed to react at room temperature for 20 minutes. Absorbance was measured at 405 nm using a spectrophotometer at intervals of 1 minute, and the slope of the absorbance versus time was determined as the activity of the enzyme. Ella stasis inhibition rates were calculated as follows.

Inhibitory effect of the compound of formula (1) on elastase activity (number of repeats = 3)

sample Enzyme activity Inhibition rate (%) The compound of formula (1) (20 ppm) 2.8 73.08 The compound of formula (1) (10 ppm) 5.5 46.94 The positive control (Quercetin, 10 ppm) 4.2 59.43 The control (DMSO, 20 ppm) 10.4 -

As can be seen from the results of the above Table 2, the compound of Chemical Formula 1 showed a high level of inhibition of elastase activity at a concentration of 10 ppm, corresponding to quercetin as a positive control, and at a concentration of 20 ppm, And the compound of the formula (1) was found to be excellent in the elastase activity inhibitory effect. Thus, it has been found that the compound of formula (I) can be effectively used for skin elasticity and wrinkle improvement.

Experimental Example  3: Glycation  The anti- glycation ) effect

In order to confirm the anti-glycation effect, the saccharification inhibitory activity was measured using L-arginine and glucose.

First, 1 M L-arginine and 1 M glucose were prepared by dissolving 1 M phosphoric acid buffer (pH 7.4) and diluted to 50 ppm and 100 ppm using 1M phosphate buffer solution. 1M L-arginine and 1M phosphate buffer solution were mixed at a ratio of 1: 4, and then 80 [mu] l each was added to a 96-well plate. To each sample, 100 μl of 0.01 M aminoguanidine to be used as a positive control and a sample diluted to 50 ppm and 100 ppm, respectively, were added. These samples were mixed well and finally glucose diluted with 1M phosphate buffer solution was added to the final concentration of glucose to 0.1 M and reacted at 70 ° C for 4 hours. The degree of saccharification was measured by measuring the absorbance of the 96-well plate at 420 nm using a spectrophotometer.

Glycation group of the following formula was an experimental group in which 1M L-arginine and 1M glucose were added to induce glycation. To measure the absorbance of the sample itself, absorbance was measured at 420 nm by adding 1M L-arginine and sample without glucose . The saccharide inhibitory activity can be obtained by the following formula.

The antagonism effect of the compound of formula (1)

sample Inhibition rate (%) The control (DMSO, 50 ppm) - The positive control (Aminoguanidine, 55 ppm) 54.89 The compound of formula (1) (50 ppm) 50.64 The compound of formula (1) (25 ppm) 29.79

As can be seen from the results shown in Table 3, the compound of Chemical Formula 1 has similar anticarcinogenic effect to aminoguanidine, which is known as an anticarious substance. That is, the compound of formula (I) exhibits an excellent antihyperglycosylation effect, and antihalation effect plays an auxiliary role in skin whitening, skin wrinkle, and elasticity improvement, and a synergistic effect can be expected.

Experimental Example  4: whitening effect - melanin total amount reduction effect

The compound of Chemical Formula 1 was added to the culture solution of mouse B-16 mouse melanoma cells to determine the whitening effect by measuring the total amount of melanin at the cellular level (Lotan R., Lotan D. Cancer Res . 40: 3345-3350, 1980). To evaluate the toxicity of melanoma cells in rats before the experiment, whitening evaluation was performed by selecting a concentration that is not toxic.

The compound of formula (I) was added to the culture medium to a final concentration of 1 ppm or 10 ppm, and the control group, arbutin, was added to the medium to 100 ppm, and treated with B-16 melanoma cells for 3 days.

Cells were then trypsinized, detached from the culture, centrifuged, and then melanin was extracted. The removed cells were incubated with 1 ml of sodium hydroxide solution (1N concentration), boiled for 10 minutes to dissolve melanin, and the absorbance was measured at 400 nm using a spectrophotometer to measure the amount of melanin produced.

The amount of melanin was measured by an absorbance of 1 × 10 ⁶ cells per unit cell, and the total amount of melanin relative to the control group was calculated as the inhibition rate (%). The results are summarized in Table 4 below.

Reduction of total melanin levels at the cellular level by concentration

sample Melanin production (abs) Inhibition rate (%) Control group (DMSO, 10 ppm) 0.33 - Positive control (arbutin, 100 ppm) 0.228 31.06 The compound of formula (1) (10 ppm) 0.189 42.61 The compound of formula (1) (1 ppm) 0.240 27.23

As can be seen from the results in Table 4, the compound of Chemical Formula 1 showed a remarkably superior melanin total reducing effect even at 10 ppm as compared with the positive control arbutin, and thus it could be used for whitening purposes.

Experimental Example  5: Anti-inflammatory effect -NO generation inhibitory effect

In order to confirm the anti-inflammatory effect and the skin trouble relieving effect of the compound of formula (1), nitrite oxide (NO) formation inhibition test was carried out by the GRIESS method using RAW264.7 cell line (ATCC number: CRL-2278).

Specifically, RAW264.7 cells, macrophages of mice, were subcultured several times, placed in 24-well plates at 3 × 10 ⁵ per well, and cultured for 24 hours. Subsequently, the compound of formula (1) was replaced with a diluted cell culture medium at a final concentration of 1, 10 and 100 ppm. At this time, L-NMMA (L-NG-Monomethylarginine), which is an inhibitor of NO production, was treated together as a positive control, and cultured for 30 minutes. Lipopolysaccharide (LPS) . 100 μl of the supernatant was transferred to a 96-well plate, and 100 μl of the GRIESS solution was added thereto at room temperature for 10 minutes, and the absorbance at 540 nm was measured to determine the NO inhibitory effect of the compound of formula (1) Are shown in Table 5 below.

sample NO production inhibition rate (%) Control group (DMSO, 10 ppm) - L-NMMA (positive control, 10 ppm) 41.02 The compound of formula (1) (1 ppm) 15.72 The compound of formula (1) (10 ppm) 20.13 The compound of formula (1) (100 ppm) 38.05

As can be seen from the results of Table 5, the compound of Chemical Formula 1 showed a significant inhibition of NO production as a natural substance when compared with L-NMMA which is a representative anti-inflammatory drug substance. Accordingly, it has been confirmed that the compound of formula (1) can be effectively used for improving skin inflammation and skin troubles. In addition, the anti - inflammatory effect acts as an auxiliary to the skin whitening or wrinkle improvement, and a synergistic effect can be expected.

Claims (10)

A composition for skin whitening comprising a compound represented by the following formula (1) or a pharmaceutically or cosmetically acceptable salt thereof as an active ingredient.
[Chemical Formula 1]

A composition for promoting skin elasticity comprising a compound represented by the following formula (1) or a pharmaceutically or cosmetically acceptable salt thereof as an active ingredient.
[Chemical Formula 1]

A composition for improving skin wrinkles comprising a compound represented by the following formula (1) or a pharmaceutically or cosmetically acceptable salt thereof as an active ingredient.
[Chemical Formula 1]

1. A skin moisturizing composition comprising a compound represented by the following formula 1 or a pharmaceutically or cosmetically acceptable salt thereof as an active ingredient.
[Chemical Formula 1]

1. A composition for skin inflammation comprising a compound represented by the following formula 1 or a pharmaceutically or cosmetically acceptable salt thereof as an active ingredient.
[Chemical Formula 1]

6. The composition according to any one of claims 1 to 5, wherein the composition is used as a cosmetic composition, a pharmaceutical composition or a health food. The composition according to any one of claims 1 to 5, wherein the compound represented by the formula (1) or a pharmaceutically or cosmetically acceptable salt thereof is contained in an amount of 0.00001 to 10% by weight based on the total weight of the composition . The composition according to any one of claims 1 to 5, wherein the compound of formula (I) or a pharmaceutically or cosmetically acceptable salt thereof contained in the composition exhibits an anti-glycation effect . 1. A cosmetic composition comprising a compound represented by the following formula (1) or a cosmetically acceptable salt thereof as an active ingredient.
[Chemical Formula 1]

1. A pharmaceutical composition comprising, as an active ingredient, a compound represented by the following formula (1) or a pharmaceutically acceptable salt thereof.
[Chemical Formula 1]