KR102588652B1 - Composition for improving skin conditions comprising Dehydrotumulosic acid - Google Patents

Abstract

The present invention relates to cosmetic compositions, pharmaceutical compositions, and health foods that have excellent effects on anti-glycation, darkening, wrinkle improvement, elasticity improvement, skin moisturizing, or anti-inflammatory effects on the skin. The composition of the present invention has excellent effects on skin or hair darkening, skin elasticity improvement, skin wrinkle improvement, skin moisturization, or skin anti-inflammation. The compound of Chemical Formula 1, which is the active ingredient of the composition of the present invention, can be used as a cosmetic raw material, pharmaceutical ingredient, or health food raw material that is safe for the skin and has excellent skin condition improvement effects.

Description

Composition for improving skin conditions comprising Dehydrotumulosic acid}

The present invention relates to a composition that has excellent effects in improving skin condition, and more specifically, to a cosmetic composition, pharmaceutical composition and health that has excellent effects in anti-glycation, darkening, wrinkle improvement, elasticity improvement, skin moisturizing or anti-inflammatory effects of the skin. It's about food.

As cultural standards improve due to economic growth, interest in not only health but also appearance is increasing, and the desire to take care of one's skin and keep it healthy is also increasing. Recently, the use of self-tanning products not only to maintain healthy skin but also to make the skin look healthy has been increasing. Interest in self-tanning is increasing because it can avoid photoaging caused by overexposure to ultraviolet rays and can produce a tanning effect even in seasons when the sun does not shine. Recently used self-tanning products, such as Erythrulose or Dihydroxyacetone, are used to temporarily dye the skin by combining it with keratin in the stratum corneum of the skin. However, in the case of dihydroxyacetone, the skin tone is often uneven depending on the method of use, and there is a problem in that the skin appears stained as dead skin cells peel off. Erythrulose produces a more even skin tone, but the color development is too weak. There is. Additionally, it has been reported that exposure to ultraviolet rays within 24 hours after application to the skin promotes the production of active oxygen in the skin.

Additionally, gray hair generally occurs as one ages, giving a feeling of old age, and gray hair, especially at a young age, is a cause of stress. White hair appears more clearly in Asians with dark hair than in Caucasians with light hair, and is a subject of research in health, beauty, and psychological aspects. Melanin is divided into red-yellow Pheomelanin and black-brown Eumelanin. Melanin in hair is an important factor in determining the color of hair. Melanin produced within melanocytes present at the top of the hair forms the hair. After being delivered to the cortical cells keratinocytes, it moves upward along with hair growth. Gray hair, which is recognized as a phenomenon of physiological aging, is caused by a decrease in the number of hair melanocytes and a decrease in melanin production due to decreased function of melanocytes. Currently, dyeing is being used as a solution to gray hair, but dyeing is a temporary method and requires re-dying due to the growth of gray hair, and the ingredients contained in the dye of hair dye become irritants, causing contact dermatitis or skin allergies. It is becoming a problem.

Collagen is a major matrix protein produced by skin fibroblasts and exists in the extracellular matrix. Its important functions include mechanical rigidity of the skin, connective tissue resistance and tissue adhesion, support for cell adhesion, and cell division and differentiation. Induction (during the growth of organisms or wound healing) is known. Collagen decreases due to age and photoaging caused by ultraviolet irradiation, and collagen reduction is promoted by collagenase enzyme activity that decomposes collagen. This is known to be closely related to the formation of wrinkles on the skin.

In addition, elastin fibers form cross-links with collagen and are an important skin component in wrinkle formation, which is involved in skin elasticity. Deficiency and aggregation of elastin fibers and a significant increase in the activity of elastase, an elastin decomposing enzyme, have been found to be one of the factors causing skin wrinkles. Elastase is the only enzyme that can decompose elastin, and its inhibition is known to fundamentally reduce the improvement of skin wrinkles.

Meanwhile, collagen and elastin fibers are matrix proteins that play an important role in retaining moisture in the dermal layer. These matrix proteins absorb moisture and increase the moisture retention capacity within the structure they form, allowing the skin to maintain an appropriate moisture content. It is known to be involved in maintaining skin elasticity.

In addition, elastic fibers produced from skin fibroblasts form cross-links with collagen and are an important skin component in wrinkle formation, which is involved in skin elasticity. Deficiency and decomposition of elastic fibers have been found to be one of the main factors in the formation of skin wrinkles and loss of elasticity.

Currently, retinoids, adenosine, protein derived from animal placenta, and chlorella extract are known as wrinkle-improving cosmetics. The most well-known retinol is a substance that promotes collagen synthesis and inhibits the elastase enzyme, but it is unstable and its usage is limited due to safety issues such as irritation and redness when applied to the skin. It is known that it is difficult to expect a wrinkle improvement effect.

Glycation generally refers to a reaction in which a simple sugar such as glucose or fructose forms a covalent bond with a protein or fat without the involvement of enzymes. Glycation occurs through a series of complex chemical reactions known as Amadori rearrangement and Maillard reaction, resulting in the production of advanced glycation endproducts (AGEs).

Meanwhile, the glycation process of proteins occurs slowly because enzyme action is not involved, and as a result, it has a greater effect on proteins with a long half-life, such as collagen. Analysis of advanced glycation end products showed that glycated collagen accumulates with age. Accumulation of advanced glycation end products changes proteins into a harder and more brittle state, and glycated collagen is stored in the extracellular matrix of the dermal layer. By preventing collagen from forming an appropriate structure, it causes the skin to lose elasticity and promotes the formation of wrinkles (Dyer, DG et al. , The Journal of Clinical Investigation, 9, p. 2463, 1993).

Aminoguanidine, Pyridoxamine, and Aspirin are known as substances that inhibit glycation, but these substances have limits on the amount of use due to safety issues on the skin, or their effects are so minimal that they are practically effective. There is a problem that cannot be expected.

Inflammation is the body's immune response to wounds or diseases, and oxidative stress such as ultraviolet rays, active oxygen, and free radicals activate inflammatory factors, causing various diseases and skin aging. Vasoactive polypeptides such as Kinin, Plasmin, and Complement have vasodilation and constriction and chemotaxis effects, and lymphocytes such as interleukin-6 (IL-6) Phosphorus and arachidonic acid are responsible for the inflammatory response. Arachidonic acid is metabolized through two pathways, cyclooxygenase or lipooxygenase, into prostaglandins or leukotrienes, which are inflammatory mediators, and mediates various inflammatory reactions.

Meanwhile, anti-inflammatory agents act to eliminate inflammation by removing the inflammatory source and reducing biological reactions and symptoms. Substances currently used for anti-inflammatory purposes include non-steroids such as Flufenamic acid, Ibuprofen, Benzydamine, and Indomethacin, and steroids such as Prednisolone. , Dexamethasone, etc. In addition, allantoin, Azn, hydrocortisone, etc. are known to be effective in improving inflammation, but the amount of these substances is limited due to safety issues on the skin, or the effect is so minimal that a practical inflammation-relieving effect cannot be expected. there is.

Therefore, it is safe for the body, the active ingredient is safe for the skin, has high stability, and above all, it is more effective in anti-glycation, darkening, wrinkles, and anti-glycation than substances known previously to have anti-glycation, darkening, wrinkle improvement, elasticity improvement, or anti-inflammatory effects on the skin. There is an urgent need for the development of ingredients for skin improvement, elasticity improvement, or anti-inflammatory properties.

Therefore, the problem to be solved by the present invention is to solve the above problems and to create a new active ingredient that has fewer side effects, is safe for the human body, and has excellent anti-glycation, darkening, wrinkle improvement, elasticity, or anti-inflammatory effects of the skin. It serves a useful purpose.

In other words, the problem to be solved by the present invention is to provide a composition containing the above-mentioned active ingredient with excellent efficacy as an active ingredient.

In order to solve the above problems, the present invention provides a cosmetic composition or pharmaceutical composition containing dehydromethylammonium acid or a pharmaceutically or cosmetically acceptable salt thereof as an active ingredient.

In addition, the present invention provides a product containing Dehydrotumulosic acid or a pharmaceutically or cosmetically acceptable salt thereof as an active ingredient for darkening skin or hair, improving skin elasticity, improving skin wrinkles, and moisturizing the skin. A composition for use or anti-inflammatory skin, preferably a cosmetic composition, pharmaceutical composition or health food, is provided.

That is, the present invention relates to the use of dehydroturic acid or a pharmaceutically or cosmetically acceptable salt thereof as a cosmetic composition or pharmaceutical composition, for darkening the skin or hair, for improving skin elasticity, for improving skin wrinkles, and for skin moisturizing. It offers new uses such as skin treatment or anti-inflammatory use.

The inventors of the present invention completed the present invention after discovering that dehydroturic acid has the effect of improving wrinkles and elasticity of the skin by promoting the production of collagen in the skin and inhibiting the activity of elastase. In addition, it was confirmed that the dehydroturose acid increases the total amount of melanin, thereby exhibiting a darkening effect on the skin or hair, and also exhibits an anti-inflammatory effect by inhibiting NO production. In addition, the dehydroturic acid exhibits an anti-glycation effect, and may play a synergistic effect by playing an auxiliary role in improving skin wrinkles and skin elasticity.

In the present invention, the 'blackening effect' refers to an increase in the colored pigment of the skin or hair, and in particular, may refer to a phenomenon in which the amount of melanin pigment increases, causing the skin or hair to appear dark in color. The invention is not limited by this mechanism.

In the present invention, 'improving elasticity or skin elasticity' means alleviating the degree of sagging or sagging skin. In addition, the elasticity means maintaining the elasticity of the skin in the presence of sufficient elastin and collagen.

In the present invention, 'wrinkle improvement' refers to preventing, suppressing, or inhibiting the formation of wrinkles on the skin, or alleviating wrinkles that have already been formed.

In the present invention, 'moisturizing or skin moisturizing' means increasing moisture in the skin and maintaining a moist state. The skin moisturizing effect can help improve skin wrinkles and increase elasticity.

In the present invention, the term 'anti-inflammatory effect' refers to suppressing inflammation, and the inflammation is one of the defense responses of biological tissue to a certain stimulus, and occurs in three ways: tissue deterioration, circulatory failure and exudation, and tissue proliferation. Refers to a complex lesion. More specifically, inflammation is part of innate immunity, and as in other animals, human innate immunity recognizes patterns on the cell surface that are specific to pathogens. Phagocytes recognize cells with such a surface as non-self and attack the pathogen. If pathogens break through the body's physical barriers, an inflammatory response occurs. The inflammatory response is a non-specific defense function that creates a hostile environment for microorganisms invading the wound area. In an inflammatory response, when a wound occurs or an external infectious agent enters the body, white blood cells responsible for the initial immune response flock in and express cytokines. Therefore, the expression level of intracellular cytokines becomes an indicator of inflammatory response activation. Examples of skin diseases related to inflammation include atopic dermatitis, psoriasis, erythematous diseases triggered by radiation, chemicals, burns, etc., acid burns, bullous dermatoses, lichenoid diseases, itching due to allergies, seborrheic eczema, rosacea acne, etc. Examples include, but are not limited to, pemphigus vulgaris, erythema multiforme exudative, erythema nodosum, balanitis, vulvitis, inflammatory hair loss such as alopecia areata, and cutaneous T-cell lymphoma.

In the present invention, the 'anti-glycation' effect refers to preventing glycation of collagen in the extracellular matrix of the dermal layer, thereby improving skin elasticity and preventing wrinkles. In addition, the anti-glycation effect suppresses the production of advanced glycation end products that accumulate in the upper dermal layer as the skin ages. Therefore, in the present invention, the anti-glycation effect can produce a synergistic effect in improving skin elasticity and improving wrinkles.

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

[Formula 1]

The compound represented by Formula 1 has the molecular formula C ₃₁ H ₄₈ O ₄ and molecular weight: 484, and is named Dehydrotumulosic acid.

The present invention is not particularly limited to the method of obtaining the dehydrohydrochemical acid, and it can be chemically synthesized by a method known in the field to which the present invention pertains, or a commercially available material can be used.

In the cosmetic composition, pharmaceutical composition and health food according to the present invention, the content of the dehydroturose acid or a pharmaceutically or cosmetically acceptable salt thereof is 0.00001 to 0.00001 based on the total weight of the cosmetic composition, pharmaceutical composition and health food. It is preferably 10% by weight.

In the present invention, the dehydroturose acid used as an active ingredient may be used in the form of a “pharmaceutically or cosmetically acceptable salt.” The “pharmaceutically or cosmetically acceptable salt” of the dehydroturonic acid may include salts prepared by adding a base to the dehydroturonic acid. Addition salts that can be used to prepare the pharmaceutically or cosmetically acceptable salts include, but are not limited to, one or more salts selected from the group consisting of sodium, potassium, calcium, ammonium, magnesium, and organic aminos. .

The dehydrohydrochemical acid of the present invention may exist in solvated form, including hydrate, ethanolate, etc., as well as in unsolvated form. The dehydrotopolymer acid of the present invention may exist in crystalline or amorphous form, and all such physical forms are included within the scope of the present invention.

The composition according to the present invention for darkening skin or hair, improving skin elasticity, improving skin wrinkles, moisturizing skin, or anti-inflammatory skin includes solutions, external ointments, creams, foams, nourishing lotions, softening lotions, packs, softening water, and emulsions. , makeup base, essence, soap, liquid cleanser, bath salt, sunscreen cream, sun oil, suspension, emulsion, paste, gel, lotion, powder, soap, surfactant-containing cleansing, oil, powder foundation, emulsion foundation , it can be manufactured in a formulation selected from the group consisting of wax foundation, patch, and spray, but is not limited thereto.

In addition, the cosmetic composition of the present invention may additionally include one or more types of cosmetically acceptable carriers that are blended with general skin cosmetics, and common ingredients include, for example, oil, water, surfactant, moisturizer, lower alcohol, Thickeners, chelating agents, pigments, preservatives, fragrances, etc. may be appropriately mixed, but are not limited thereto.

Cosmetically acceptable carriers included in the cosmetic composition of the present invention vary depending on the formulation. When the formulation of the present invention is an ointment, paste, cream or gel, the carrier ingredient may include animal oil, vegetable oil, wax, paraffin, starch, tracant, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc, zinc oxide or Mixtures of these can be used.

When the formulation of the present invention is a powder or spray, lactose, talc, silica, aluminum hydroxide, calcium silcate, polyamide powder, or mixtures thereof may be used as the carrier component, and especially in the case of a spray, chlorochloride may be added. May contain propellants such as fluorohydrocarbons, propane/butane or dimethyl ether.

When the formulation of the present invention is a solution or emulsion, a solvent, solubilizing agent, or emulsifying agent is used as the carrier component, such as water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl benzoate, propylene glycol, 1,3 -Butyl glycol oils, especially cottonseed oil, peanut oil, corn germ oil, olive oil, castor oil and sesame oil, aliphatic esters of glycerol, fatty acid esters of polyethylene glycol or sorbitan.

When the formulation of the present invention is a suspension, the carrier components include water, liquid diluents such as ethanol or propylene glycol, suspending agents such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester and polyoxyethylene sorbitan ester, and miso. Crystalline cellulose, aluminum metahydroxide, bentonite, agar, or tracant may be used.

When the formulation of the present invention is soap, alkali metal salts of fatty acids, fatty acid hemiester salts, fatty acid protein hydrolysates, isethionates, lanolin derivatives, fatty alcohols, vegetable oils, glycerol, sugars, etc. may be used as carrier ingredients. You can.

The present invention also provides a method for darkening the skin or hair, improving skin elasticity, improving skin wrinkles, moisturizing the skin, or Provides an anti-inflammatory method for the skin. The subject includes mammals, including rats, livestock, humans, etc., without limitation.

According to another embodiment of the present invention, the present invention provides a product for darkening skin or hair, improving skin elasticity, and improving skin wrinkles, containing the compound of Formula 1 or a pharmaceutically or cosmetically acceptable salt thereof as an active ingredient. , and provides a pharmaceutical composition for skin moisturizing or skin anti-inflammation.

The composition containing the compound of the present invention may be in various oral or parenteral formulations, but is preferably a parenteral formulation. When formulated, it is prepared using diluents or excipients such as commonly used fillers, extenders, binders, wetting agents, disintegrants, and surfactants. Solid preparations for oral administration include tablets, pills, powders, granules, capsules, etc. These solid preparations contain one or more compounds and at least one excipient, such as starch, calcium carbonate, sucrose, or lactose ( It is prepared by mixing lactose, gelatin, etc. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Liquid preparations for oral administration include suspensions, oral solutions, emulsions, and syrups. In addition to the commonly used simple diluents such as water and liquid paraffin, various excipients such as wetting agents, sweeteners, fragrances, and preservatives may be included. there is. Preparations for parenteral administration include sterilized aqueous solutions, non-aqueous solvents, suspensions, and emulsions. Non-aqueous solvents and suspensions may include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, and injectable ester such as ethyl oleate.

The present invention also provides a product for darkening skin or hair, improving skin elasticity, improving skin wrinkles, moisturizing skin, or anti-inflammatory skin, comprising the compound of Formula 1 or a pharmaceutically or cosmetically acceptable salt thereof as an active ingredient. It can be provided in the form of an external skin preparation.

When the compound of Formula 1 or a pharmaceutically or cosmetically acceptable salt thereof is used as an external skin agent, fatty substances, organic solvents, solubilizers, thickeners and gelling agents, softeners, antioxidants, suspending agents, and stabilizers are added. , foaming agents, fragrances, surfactants, water, ionic or non-ionic emulsifiers, fillers, sequestering agents and chelating agents, preservatives, vitamins, blocking agents, wetting agents, essential oils, dyes, pigments, hydrophilic or It may contain adjuvants commonly used in the field of dermatology, such as lipophilic active agents, lipid vesicles or any other ingredients commonly used in topical preparations for the skin. Additionally, the ingredients may 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 in a formulation for external application to the skin, it may have a formulation such as an ointment, patch, gel, cream, or spray, but is not limited thereto.

The pharmaceutical composition of the present invention can be particularly preferably used as a parenteral preparation. For example, the external preparation for skin may include a suitable pharmaceutically acceptable base such as vaseline or stearyl alcohol; Suitable pharmaceutically acceptable surfactants such as polysorbate and sorbitan sesquioleate; Suitable pharmaceutically acceptable moisturizers such as glycerin; A suitable pharmaceutically acceptable solvent; And it can be prepared by a conventional skin external preparation method of homogeneously mixing flavoring agents, colorants, stabilizers, viscosifiers, etc.

In addition, when the compound of Formula 1 of the present invention or a pharmaceutically or cosmetically acceptable salt thereof is used as a pharmaceutical, it may additionally contain one or more active ingredients exhibiting the same or similar functions. For example, it may include known ingredients for darkening skin or hair, improving skin elasticity, improving skin wrinkles, moisturizing skin, or anti-inflammatory skin. When additional ingredients for darkening skin or hair, improving skin elasticity, improving skin wrinkles, moisturizing skin, or anti-inflammatory skin are included, the composition of the present invention can darken skin or hair, improve skin elasticity, improve skin wrinkles, and moisturize skin. Alternatively, the skin anti-inflammatory effect may be further enhanced. When adding the above ingredients, skin safety due to combined use, ease of formulation, and stability of the active ingredients can be taken into consideration.

In one embodiment of the present invention, the composition includes skin elasticity or wrinkle improvement ingredients known in the art, such as retinoic acid, TGF, protein from animal placenta, betulinic acid, and chlorella extract; Anti-inflammatory ingredients known in the art include COX-2 inhibitors, prednisolone, and allantoin; Moisturizing ingredients known in the art include petrolatum (vaseline), mineral oil, silicon, neutral fat, essential fatty acids (e.g. gamma-linolenic acid (evening primrose oil)), GGF, amino acids, provitamin B5, hyaluronic acid, poly- γ-Glutamic acid, Lipidure PMB, ceramides, cholesterol, fatty acids; and one or two or more ingredients selected from the group consisting of their derivatives and various plant extracts. 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 range may be adjusted according to requirements such as skin safety and ease of formulation of the compound of Formula 1.

The pharmaceutical composition of the present invention, when it contains an effective amount of the compound of formula 1 or a pharmaceutically or cosmetically acceptable salt thereof, has desirable skin or hair darkening, skin elasticity enhancement, skin wrinkle improvement, skin moisturizing, or skin anti-inflammatory effects. can be provided. In the present invention, 'effective amount' refers to the amount of a compound that can sufficiently exhibit skin or hair darkening, skin elasticity enhancement, skin wrinkle improvement, skin moisturizing, or skin anti-inflammatory effects.

The effective amount of the compound of Formula 1 or a pharmaceutically or cosmetically acceptable salt thereof included in the composition of the present invention will vary depending on the form in which the composition is manufactured, the method in which the compound is applied to the skin, and the time it remains on the skin. For example, when the composition is commercialized as a pharmaceutical, it may contain the compound of Formula 1 at a higher concentration than when it is commercialized as a cosmetic that is routinely applied to the skin. Therefore, 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, and 1 to 60 mg/kg per day. Can be administered 6 times.

According to another embodiment of the present invention, a product containing the compound of Formula 1 or a pharmaceutically or cosmetically acceptable salt thereof is used for darkening skin or hair, improving skin elasticity, improving skin wrinkles, moisturizing skin, or treating skin. Provides health foods for inflammation.

In this specification, 'health food' refers to a compound of Formula 1 or a pharmaceutically or cosmetically acceptable salt thereof added to food materials such as beverages, teas, spices, gum, confectionery, etc., or in capsules, powders, suspensions, etc. It is a food manufactured from , which means that when consumed, it brings about a specific health effect. However, unlike general drugs, it has the advantage of not having any side effects that may occur when taking the drug for a long period of time as it is made from food. The health food of the present invention obtained in this way can be consumed on a daily basis, so it is very useful as it can be expected to have excellent effects on darkening of the skin or hair, improvement of skin elasticity, improvement of skin wrinkles, skin moisturizing, or skin anti-inflammation.

When using the compound of Formula 1 or a pharmaceutically or cosmetically acceptable salt thereof as a food additive, the compound of Formula 1 or a pharmaceutically or cosmetically acceptable salt thereof is added as is or mixed with other foods or food ingredients. They can be used together, and can be used appropriately according to conventional methods. The mixing amount of the active ingredient can be appropriately determined depending on the purpose of use (prevention, health, or therapeutic treatment). Generally, when producing a food or beverage, the composition of the present invention is added in an amount of 15 parts by weight or less, preferably 10 parts by weight or less, based on the raw materials. However, in the case of long-term intake for the purpose of health and hygiene or health control, the amount may be below the above range, and since there is no problem in terms of safety, the active ingredient may be used in an amount above the above range. . There are no special restrictions on the types of foods above. Examples of foods to which the above substances can be added include meat, sausages, bread, chocolate, candies, snacks, confectionery, pizza, ramen, other noodles, gum, dairy products including ice cream, various soups, beverages, tea, drinks, etc. These include alcoholic beverages and vitamin complexes, and include all health foods in the conventional sense. The health drink composition of the present invention may contain various flavoring agents or natural carbohydrates as additional ingredients like conventional drinks. The above-mentioned natural carbohydrates include monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, polysaccharides such as dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol. As a sweetener, natural sweeteners such as thaumatin and stevia extract or synthetic sweeteners such as saccharin and aspartame can be used. The proportion 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 includes various nutrients, vitamins, electrolytes, flavors, colorants, pectic acid and its salts, alginic acid and its salts, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, and alcohol. , may contain carbonating agents used in carbonated drinks, etc. In addition, the health food of the present invention may contain pulp for the production of natural fruit juice, fruit juice drinks, and vegetable drinks. These ingredients can be used independently or in combination. The ratio of these additives is not very important, 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.

Although not limited thereto, in one embodiment of the present invention, the composition may include the compound of Formula 1 or a pharmaceutically or cosmetically acceptable salt thereof in an amount of 0.00001% to 10% by weight based on the total weight of the composition. there is.

The composition containing dehydroturonic acid of the present invention exhibits excellent effects on skin or hair darkening, skin elasticity improvement, skin wrinkle improvement, skin moisturization, or skin anti-inflammation.

The composition containing dehydroturonic acid of the present invention can be used as a cosmetic ingredient, pharmaceutical ingredient, or health food ingredient that is safe for the skin and has excellent skin condition improvement effects.

Hereinafter, in order to explain the present invention in more detail, the following examples will be given. However, the embodiments according to the present invention may be modified into various other forms and the scope of the present invention should not be construed as being limited to the embodiments described in detail below. Embodiments of the present invention are provided as examples to aid detailed understanding of the present invention.

Reference example One: Dehydro-to-water formula Exceed ( Dehydrotumulosic acid) substance information

[Formula 1]

Substance name: Dehydrotumulosic acid

CAS No. :6754-16-1

Molecular formula: C ₃₁ H ₄₈ O ₄

Molecular Weight: 484

Where to buy: Shanghai Taut Biotech Co., Ltd.

Experiment example 1: Effect of promoting type I collagen synthesis in human-derived fibroblasts

The compound of Formula 1 was added to the culture medium of human-derived fibroblasts, and the effect of promoting type 1 collagen synthesis was confirmed at the cellular level. The synthesized collagen was quantified using the 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 the fibroblast culture medium (DMEM medium), cultured for 48 hours, and then the culture medium was taken and the degree of type 1 collagen synthesis at each concentration was measured using a spectrophotometer using a PICP EIA kit. and measured at 450 nm.

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

Collagen synthesis promoting effect of the compound of Formula 1 (number of repetitions = 4)

sample Type 1 collagen production (ng/ml) Increase rate (%) Negative control group 140.3 - Positive control group (vitamin C, 52.85ppm) 215.1 53.3 Compound of Formula 1 (1ppm) 182.1 29.8 Compound of Formula 1 (10ppm) 209.9 49.6

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

Experimental Example 2: Elastase activity inhibition effect

The effect of inhibiting the activity of Elastase, an enzyme that decomposes elastin, was confirmed as follows.

Elastase derived from human white blood cells was used, and the synthetic substrate MeOSuc-Ala-Ala-Pro-Val-pNA was used as the elastase substrate. A 100mM Tris (pH 7.5) solution was used as the buffer solution. Elastase was used in a final amount of 0.2 mU using a buffer solution. In addition, the synthetic substrate of elastase was made into a 100mM solution using DMSO and then diluted using a buffer solution to reach a final concentration of 0.5mM. At this time, the positive control was set to contain quercetin, known as an elastase inhibitor, at a concentration of 10 ppm. Elastase inhibition candidates were added to final concentrations of 10 and 20 ppm. The reaction was carried out in a 96-well plate and reacted at room temperature for 20 minutes. Absorbance was measured at 405 nm at 1-minute intervals using a spectrophotometer, and the slope of absorbance versus time was determined to determine enzyme activity. The elastase inhibition rate was calculated as follows.

Elastase activity inhibition effect of the compound of Formula 1 (number of repetitions = 3)

sample enzyme activity Inhibition rate (%) Compound of Formula 1 (20ppm) 3.9 62.5 Compound of Formula 1 (10ppm) 4.6 55.77 Positive control group (Quercetin, 10ppm) 4.9 53.19 Control (DMSO, 20ppm) 10.4 -

As can be seen from the results in Table 2, the compound of Formula 1 showed a better elastase activity inhibition effect than quercetin at a concentration of 20 ppm, confirming that the compound of Formula 1 had an excellent elastase activity inhibition effect. Therefore, it was found that the compound of Formula 1 can be effectively used to improve skin elasticity and wrinkles.

Experiment example 3: Glycosylation Inhibition (anti- glycation ) effect

To confirm the anti-glycation effect, the anti-glycation activity was measured using L-arginine and glucose.

First, 1M L-arginine and 1M glucose were prepared by dissolving them in 1M phosphate buffer solution (pH 7.4), and the samples were diluted to 50 and 100ppm using 1M phosphate buffer solution. 1M L-arginine and 1M phosphate buffer solution were mixed in a ratio of 1 to 4, and then 80 μl each was dispensed into a 96-well plate. Here, 100 μl of samples diluted to 50 and 100 ppm, respectively, and 0.01 M aminoguanidin to be used as a positive control were added. After mixing these samples well, glucose diluted with 1M phosphate buffer solution was added so that the final concentration of glucose was 0.1M, and then reacted at 70°C for 4 hours. The degree of glycosylation was measured by measuring the absorbance of the 96-well plate at 420 nm using a spectrophotometer.

The Glycation experimental group shown below is an experimental group in which 1M L-arginine and 1M glucose were added to induce glycation. To measure the absorbance of the sample itself, only 1M L-arginine and the sample were added without adding glucose, and the absorbance was measured at 420 nm. Glycosylation inhibition activity can be calculated using the following formula.

Anti-glycation effect of compounds of formula 1

sample Inhibition rate (%) Control (DMSO, 50ppm) - Positive control (Aminoguanidine, 55ppm) 56.21 Compound of Formula 1 (50ppm) 71.34 Compound of Formula 1 (25ppm) 40.97

As can be seen from the results in Table 3, the compound of Formula 1 was found to have a more excellent anti-glycation effect compared to aminoguanidine, a known anti-glycation substance. That is, the compound of Formula 1 exhibits an excellent anti-glycation effect, and in improving skin wrinkles and elasticity, the anti-glycation effect acts as an auxiliary role, so a synergistic effect can be expected.

Experiment example 4: blackening Effect - Effect of increasing the total amount of melanin

The darkening effect was confirmed by adding the compound of Formula 1 to the culture medium of B-16 mouse melanoma cells and measuring the total amount of melanin at the cellular level (Lotan R., Lotan D. Cancer Res . 40: 3345-3350, 1980). Before the experiment, toxicity was evaluated for rat melanoma cells, a non-toxic concentration was selected, and blackening evaluation was performed.

The compound of Formula 1 was added to the culture medium at a final concentration of 1 ppm and 10 ppm, and Forskolin, a control, was added to the medium at a concentration of 10 ppm, treated with B-16 melanoma cells, and cultured for 3 days.

Afterwards, the cells were treated with trypsin, removed from the culture vessel, centrifuged, and melanin was extracted. To the removed cells, 1 ml of sodium hydroxide solution (1N concentration) was added and boiled for 10 minutes to dissolve the melanin. The amount of melanin produced was measured by measuring the absorbance at 400 nm using a spectrophotometer.

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

Effect of increasing total melanin amount at the cellular level depending on concentration

sample Melanin production amount
(abs) Increase rate (%) Control (DMSO, 10ppm) 0.321 - Positive control group (Forskolin, 10ppm) 0.413 28.6 Formula 1 (10ppm) 0.475 48.0 Formula 1 (1ppm) 0.398 24.0

As can be seen from the results in Table 4, the compound of Formula 1 shows a significantly superior effect of increasing the total amount of melanin even at 10 ppm when compared to forskolin, which is a positive control, and can be used for blackening of skin or hair. there was.

Experimental Example 5: Anti-inflammatory effect-NO production inhibition effect

To confirm the anti-inflammatory effect and skin trouble alleviation effect of the compound of Formula 1, a nitric oxide (NO) formation inhibition test was conducted using the GRISESS method using RAW264.7 cell line (ATCC number: CRL-2278).

Specifically, RAW264.7 cells, which are mouse macrophages, were subcultured several times, placed in a 24-well plate at 3×10 ⁵ cells per well, and cultured for 24 hours. Subsequently, the cell medium was replaced with a cell medium in which the compound of Formula 1 was diluted to final concentrations of 1, 10, and 100 ppm. At this time, L-NMMA (L-NG-Monomethylarginine), an NO-production inhibitor, was treated as a positive control and cultured for 30 minutes, and LPS (Lipopolysaccharide) was treated as a stimulant at 1 μg each and cultured for 24 hours. . Take 100 μl of the supernatant and transfer it to a 96-well plate, add 100 μl of GRIESS solution each, react at room temperature for 10 minutes, and measure the absorbance at 540 nm to determine the NO inhibition effect of the compound of Formula 1, and the results is shown in Table 5 below.

sample NO production inhibition rate (%) Control (DMSO, 10ppm) - L-NMMA (positive control, 10 ppm) 49.36 Compound of Formula 1 (1ppm) 11.79 Compound of Formula 1 (10ppm) 17.31 Compound of Formula 1 (100ppm) 47.98

As can be seen from the results in Table 5, the compound of Formula 1 showed a significant NO production inhibition rate as a natural substance compared to L-NMMA, a representative anti-inflammatory drug. Therefore, it was confirmed that Chemical Formula 1 can be effectively used for skin anti-inflammatory and skin trouble improvement purposes. In addition, the anti-inflammatory effect can be expected to have a synergistic effect by playing an auxiliary role in improving skin elasticity or wrinkles.

Claims (13)

A cosmetic composition for skin or hair darkening comprising a compound represented by the following formula (1) or a cosmetically acceptable salt thereof as an active ingredient.
[Formula 1]
A cosmetic composition for improving skin elasticity comprising a compound represented by the following formula (1) or a cosmetically acceptable salt thereof as an active ingredient.
[Formula 1]
A cosmetic composition for improving skin wrinkles comprising a compound represented by the following formula (1) or a cosmetically acceptable salt thereof as an active ingredient.
[Formula 1]
A cosmetic composition for moisturizing skin containing a compound represented by the following formula (1) or a cosmetically acceptable salt thereof as an active ingredient.
[Formula 1]
delete delete The cosmetic composition according to any one of claims 1 to 4, wherein the compound represented by Formula 1 or a cosmetically acceptable salt thereof is contained in an amount of 0.00001 to 10% by weight based on the total weight of the cosmetic composition. The method of any one of claims 1 to 4, wherein the compound of Formula 1 or a cosmetically acceptable salt thereof contained in the cosmetic composition also exhibits an anti-glycation effect. Cosmetic composition. A health food composition for skin or hair darkening comprising a compound represented by the following formula (1) or a pharmaceutically acceptable salt thereof as an active ingredient.
[Formula 1]
A health food composition for improving skin elasticity comprising a compound represented by the following formula (1) or a pharmaceutically acceptable salt thereof as an active ingredient.
[Formula 1]
A health food composition for improving skin wrinkles, comprising a compound represented by the following formula (1) or a pharmaceutically acceptable salt thereof as an active ingredient.
[Formula 1]
A health food composition for skin moisturizing comprising a compound represented by the following formula (1) or a pharmaceutically acceptable salt thereof as an active ingredient.
[Formula 1]
The health food according to any one of claims 9 to 12, wherein the compound represented by Formula 1 or a pharmaceutically acceptable salt thereof is contained in an amount of 0.00001 to 10% by weight based on the total weight of the health food composition. Composition.