Whitening composition and method for whitening skin using the same

Abstract

To provide a skin whitening composition for mitigating excessive pigmentation of skin.SOLUTION: The skin whitening composition contains as an active ingredient a hydroxy-substituted long-chain unsaturated fatty acid based compound represented by the chemical formula 1-1 in the figure.SELECTED DRAWING: Figure 1

Description

[Technical Field]

[0001] This document relates to a skin whitening composition and a skin whitening method using the same. [Background technology]

[0002] The skin performs a variety of essential functions for human survival. The most representative functions of the skin include its barrier function to maintain homeostasis within the body in response to environmental changes, its sensory function to perceive external changes, and its thermoregulatory function. Among these diverse functions, the skin's barrier function is particularly evident in the stratum corneum, the outermost layer of the skin. The stratum corneum not only functions as a barrier but has also been reported to influence the function, role, and structure of the internal living cell layers, namely the epidermis and dermis, and its importance is steadily increasing. This stratum corneum, composed of dead keratinocytes and intercellular lipids, plays a core role as a protective film, shielding the skin from external stimuli and preventing moisture evaporation from within. Furthermore, keratinocytes in the stratum corneum create the skin barrier through differentiation and keratinization processes.

[0003] While various factors contribute to aging in human skin, ultraviolet (UV) radiation, in particular, causes wrinkle formation, loss of elasticity, pigmentation, and a decrease in skin moisture due to damage to the skin barrier. When UV-induced skin damage reduces the moisture content on the skin surface, the stratum corneum loses its flexibility, causing the skin to dry out and, as a result, the skin can no longer function as a barrier. Therefore, maintaining the skin's ability to retain moisture is of utmost importance in strengthening the skin barrier.

[0004] There are two types of pores in the epidermis associated with water homeostasis: aquaporins (AQP) and tight junctions (TJ). Furthermore, filaggrin is known to play an important role in moisturizing the skin as a precursor protein of natural moisturizing factors (NMF) (Non-Patent Literature 1).

[0005] On the other hand, various inflammatory dermatitiss are caused by IgE-related immune mechanisms, and many reports suggest that a delayed immune response due to T cell abnormalities is involved in these cases. In particular, the infiltration of immune-related cells such as macrophages, Th lymphocytes, and mast cells increases significantly in the areas where atopic dermatitis occurs. In the skin of atopic dermatitis patients, the concentration of IgE in the blood is high because the number of Th2 cells increases, and Th2 cytokines such as IL-4 and IL-13 secreted by these cells stimulate B lymphocytes, promoting IgE secretion. IL-4 and IL-13 play a particularly important role in early-stage atopic dermatitis (Non-Patent Literature 2).

[0006] In inflammation such as atopic dermatitis, it is crucial for the treatment and prevention of inflammation to ensure that anti-inflammatory factors are actively involved. These anti-inflammatory factors are factors that actively participate in the inflammation resolution stage and are naturally produced and secreted by immune cells (neutrophils, macrophages) in tissues during the later stages of the inflammatory response. These anti-inflammatory factors exist in various forms, including lipids, proteins, and gaseous molecules, but research on specialized pro-resolving lipid mediators (SPMs) has recently been actively pursued. These anti-inflammatory lipid mediators are metabolites produced when omega-3 polyunsaturated fatty acids (PUFAs), specifically eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA), are metabolized within cells. While numerous studies have reported the mitigation of inflammatory responses by these anti-inflammatory lipid mediators, their effects on melanin production by melanocytes and their applications for enhancing skin whitening efficacy remain unknown. Therefore, while developing a natural skin whitening agent that is safe for the human body, the inventors confirmed that the anti-inflammatory lipid factor not only has a skin whitening effect in an environment without pigmentation factors, but also suppresses the pigmentation phenomenon caused by pigmentation factors. Furthermore, they confirmed that it has a whitening effect by inhibiting melanin production induction by acne-causing bacteria (Cutibacterium acnes, C. acnes), thus completing the present invention.

[0007] On the other hand, prior art documents related to the present invention include Patent Document 1, among others. [Prior art documents] [Patent Documents]

[0008] [Patent Document 1] Korean Published Patent Publication No. 10-2020-0042285 [Non-patent literature]

[0009] Non-Patent Document 1 J Tabachnich and J H LaBadie, J. Invest. Dermatol. 54, 24-31, 1970 Non-Patent Document 2 Donald Y.M. Leung et al., J Clin Invest. 2004, 113, 651-657 Summary of the Invention Problems to be Solved by the Invention

[0010] One embodiment provides a cosmetic composition capable of improving the hyperpigmentation phenomenon of the skin.

[0011] Another embodiment provides a method for whitening the skin of an individual, which includes the step of administering the cosmetic composition to the individual. Means for Solving the Problems

[0012] According to one embodiment, there is provided a whitening composition containing, as an active ingredient, a compound containing a structural unit represented by the following Chemical Formula A and including one or more hydroxy groups and one or more carboxyl groups.

[0013]

Chemical formula

[0014] The compound contained as the active ingredient may include a compound represented by the following Chemical Formula 1.

[0015]

Chemical formula

[0016] In Chemical Formula 1, R 1 ~R 3 are each independently a hydrogen atom, a hydroxy group or a carboxyl group, and the R1 ~R 3 At least one of them is a hydroxy group, and the said R 1 ~R 3 At least one of them is a carboxyl group.

[0017] The said R 1 and R 2 are each independently a hydroxy group, and the said R 3 may be a carboxyl group.

[0018] The compound represented by Chemical Formula 1 may be contained at a concentration of 0.001 nM to 1 μM with respect to the total amount of the said composition.

[0019] The compound represented by Chemical Formula 1 may be contained at a concentration of 0.01 nM to 100 nM with respect to the total amount of the said composition. <�

[0020] The compound contained as the said active ingredient may include the compound represented by the following Chemical Formula 2. <00001<<END]] The compound contained as the said active ingredient may include the compound represented by the following Chemical Formula 3.

[0022]

Chemical formula

[0023]

Chemical formula

[0024] In the said Chemical Formula 2, R 1 ~R 3 [[ID=<<END]]are each independently a hydrogen atom, a hydroxy group or a carboxyl group, and at least one of the said R 1 ~R[[ID=<<END]] 3 is a hydroxy group, and at least one of the said R 1 ~R 3 is a carboxyl group, In the said Chemical Formula 3, R3 and R 4 Each of these is independently a hydroxyl group or a carboxyl group, and the R 3 and R 4 At least one of them is a hydroxyl group, and the R 3 and R 4 At least one of them is a carboxyl group.

[0025] The aforementioned whitening composition may be a cosmetic composition.

[0026] According to another embodiment, a method for whitening the skin of an individual is provided, comprising the step of administering to the individual a cosmetic composition containing a compound comprising the structural unit represented by the chemical formula A and containing one or more hydroxyl groups and one or more carboxyl groups as an active ingredient.

[0027] Another embodiment provides a compound represented by chemical formula A, comprising one or more hydroxyl groups and one or more carboxyl groups, for use in the production of a whitening composition.

[0028] Another embodiment provides a method for whitening the skin by applying a composition containing an effective amount of the compound represented by chemical formula A (containing one or more hydroxyl groups and one or more carboxyl groups) to the skin.

[0029] The compound and its concentration, which contain one or more hydroxyl groups and one or more carboxyl groups and are represented by chemical formula A, are as described above, and the composition may also contain the compounds represented by chemical formulas 1 to 3, as described above. [Effects of the Invention]

[0030] The composition according to one embodiment not only inhibits the increased protein expression of melanin-producing enzymes (TRP1, TRP2, tyrosinase) in melanocytes caused by the acne-causing bacteria (C. acnes), but also inhibits the increased protein expression of melanin-producing enzymes (TRP2, tyrosinase) in melanocytes even when skin pigmentation occurs unrelated to the acne-causing bacteria, thereby providing an excellent whitening effect to the skin to which the composition is applied. In other words, the composition according to one embodiment not only has skin whitening efficacy in an environment without pigmentation factors, but has also been confirmed to suppress the pigmentation phenomenon caused by pigmentation factors, and further inhibits the induction of melanin production by the acne-causing bacteria (Cutibacterium acnes, C. acnes), thereby providing an excellent whitening effect to the skin to which the composition is applied. [Brief explanation of the drawing]

[0031] [Figure 1] This photograph shows that a composition according to one embodiment inhibits the increased protein expression of the melanogenic enzyme (TRP2, tyrosinase) in normal human melanocytes. [Figure 2] This graph shows that a composition according to one embodiment inhibits the increased protein expression of tyrosinase in normal human melanocytes. [Figure 3] This graph shows that a composition according to one embodiment inhibits the increased protein expression of the melanogenic enzyme (TRP2) in normal human melanocytes. [Figure 4] This photograph shows that a composition according to one embodiment inhibits the increased protein expression of melanin-producing enzyme (TRP2, tyrosinase) caused by a pigmentation factor (α-MSH) that is not the causative agent of acne (C. acnes). [Figure 5]This graph shows that a composition according to one embodiment inhibits the increased protein expression of melanin-producing enzyme (tyrosinase) caused by a pigmentation factor (α-MSH) that is not the causative agent of acne (C. acnes). [Figure 6] This graph shows that a composition according to one embodiment inhibits the increased protein expression of melanin-producing enzyme (TRP2) caused by a pigmentation factor (α-MSH) that is not the causative agent of acne (C. acnes). [Figure 7] This photograph shows that a composition according to one embodiment inhibits the increased protein expression of melanin-producing enzyme (TRP2, tyrosinase) caused by a pigmentation factor (IBMX) that is not the causative agent of acne (C. acnes). [Figure 8] This graph shows that a composition according to one embodiment inhibits the increased protein expression of melanin-producing enzyme (tyrosinase) caused by a pigmentation factor (IBMX) that is not the causative agent of acne (C. acnes). [Figure 9] This graph shows that a composition according to one embodiment inhibits the increased protein expression of melanin-producing enzyme (TRP2) caused by a pigmentation factor (IBMX) that is not the causative agent of acne (C. acnes). [Figure 10] This photograph shows that the acne-causing bacteria (C. acnes) increase the protein expression of melanin-producing enzymes (TRP1, TRP2). [Figure 11] This photograph shows that a composition according to one embodiment inhibits the increased protein expression of melanin-producing enzymes (TRP1, TRP2) caused by acne-causing bacteria (C. acnes). [Figure 12] This graph shows that a composition according to one embodiment inhibits the increased protein expression of melanin-producing enzymes (TRP1, TRP2) caused by acne-causing bacteria (C. acnes). [Modes for carrying out the invention]

[0032] The embodiments of the present invention will be described in detail below so that they can be easily implemented by a person with ordinary skill in the art to which the present invention pertains. However, the present invention can be realized in a variety of different forms and is not limited to the embodiments described herein.

[0033] In this specification, improvement of skin whitening function means that the color of the stratum corneum, located on the outermost layer of the skin, changes to a lighter, whiter color. The stratum corneum, which is the primary protective layer of the skin, is easily damaged by the external environment. In order to impart whitening power to such skin, formulations that involve applying topical skin preparations can solve the problem temporarily, but it is difficult to solve the fundamental problem, and furthermore, many topical skin preparations do not solve the problem at all. They only have the effect of merely concealing dark marks within the skin, so formulations that involve applying topical skin preparations alone cannot fundamentally improve the problem of skin pigmentation. Therefore, the inventors have completed the present invention after confirming that a compound represented by a specific chemical formula constituting the composition according to one embodiment can fundamentally improve the skin whitening efficacy by solving the aforementioned fundamental problem.

[0034] More specifically, a composition according to one embodiment is expected to have a skin whitening effect by regulating signal transduction in relation to the expression of melanin-producing enzymes (TRP1, TRP2, tyrosinase) involved in melanin synthesis.

[0035] Related to this, it is clear that when the intracellular concentration of c-AMP increases, melanin production increases, and when the extracellular signal-regulated kinase (ERK) pathway is activated, melanin production decreases. However, a well-known method for activating the extracellular signal-regulated kinase pathway is to stimulate the signaling pathway that phosphorylates the extracellular signal-regulated kinase. Recently, it has been thought that inhibiting protein phosphatase 2A (PP2A), an enzyme that dephosphorylates extracellular signal-regulated kinase, would activate the extracellular signal-regulated kinase, and as a result, a skin whitening effect due to the degradation of microphthalmia-associated transcription factor (MITF) would be obtained. However, an effective method for inhibiting protein phosphatase 2A has not yet been clarified.

[0036] In connection with this, the inventors have completed the present invention by confirming that when melanocytes are treated with a composition containing a specific compound as an active ingredient (more specifically, a composition containing the specific compound as an active ingredient within a specific concentration range), it has an inhibitory effect on the synthesis of melanin-producing enzymes (TRP1, TRP2, tyrosinase).

[0037] Furthermore, conventional methods that directly inhibit melanin-producing enzymes (TRP1, TRP2, tyrosinase) require high concentrations of these substances, which can cause side effects such as skin irritation. In addition, kojic acid is prohibited from use due to its potential to induce skin cancer. However, the composition according to one embodiment does not contain substances that directly inhibit melanin-producing enzymes (TRP1, TRP2, tyrosinase), so it does not irritate the skin and has virtually no side effects. Moreover, it can produce a much stronger whitening effect by inhibiting the production of melanin-producing enzymes (TRP1, TRP2, tyrosinase).

[0038] In this specification, when a part such as a layer, film, region, or plate is said to be "on top of" another part, this includes not only when it is "immediately above" another part, but also when there is another part in between. Conversely, when a part is said to be "immediately above" another part, it means that there is no other part in between.

[0039] Unless otherwise defined herein, “combination” means mixing or copolymerization. “Copolymer” means block copolymerization or random copolymerization, and “copolymer” means block copolymer or random copolymerization.

[0040] The following describes a skin whitening composition according to one embodiment.

[0041] A skin whitening composition according to one embodiment contains a structural unit represented by the following chemical formula A, and includes a compound containing one or more hydroxyl groups and one or more carboxyl groups as an active ingredient.

[0042] [ka]

[0043] For example, the compound included as the active ingredient may include the compound represented by the following chemical formula 1.

[0044] [ka]

[0045] In the aforementioned chemical formula 1, R 1 ~R 3 Each of these is independently a hydrogen atom, a hydroxyl group, or a carboxyl group, and the R 1 ~R 3 At least one of them is a hydroxyl group, and the R 1 ~R 3 At least one of them is a carboxyl group.

[0046] For example, in the above chemical formula 1, R 1 and R 2 Each of these is independently a hydroxyl group, and R 3 It can be a carboxyl group.

[0047] The compound represented by chemical formula 1, as one of the specialized pro-resolving lipid mediators (SPMs), not only inhibits the increase in the expression of melanin-producing enzymes (TRP1, TRP2) in melanocytes caused by acne-causing bacteria (C. acnes), but also imparts a skin whitening effect to skin that has been pigmented by skin pigmentation factors other than the aforementioned acne-causing bacteria (such as α-MSH and IBMX) by suppressing the increase in the expression of melanin-producing enzymes (TRP2, tyrosinase).

[0048] Hyperpigmentation of the skin can occur due to a variety of factors, including hormonal abnormalities following an inflammatory response in the skin, genetic disorders, and ultraviolet radiation exposure. The main causes include abnormalities in melanin synthesis and distribution.

[0049] The primary function of melanin is to remove oxygen radicals and protect the skin from damage caused by them. Therefore, a high level of melanin means that the skin has an effective defense system to protect itself from physical and chemical toxic substances. This melanin production occurs in melanocytes after tyrosine is converted to dopaquinone by melanogenic enzymes (TRP1, TRP2, tyrosinase), followed by enzymatic action and spontaneous oxidation reactions.

[0050] The methods known to date for suppressing melanin production can be broadly categorized as follows:

[0051] First, there is a method to block ultraviolet rays and eliminate the main cause of melanin production. This method can be achieved by incorporating light scattering agents or light blocking agents into cosmetic compositions.

[0052] Next, melanin production can be suppressed by inhibiting the synthesis of core carbohydrates necessary for the activity of melanin-producing enzymes (TRP1, TRP2, tyrosinase), such as glucosamine.

[0053] Furthermore, kojic acid or arbutin can inhibit the function of melanin-producing enzyme (TRP1), which is involved in melanin production.

[0054] Furthermore, it is also possible to inhibit the division of melanocytes by using substances that have specific toxicity to melanocytes, such as hydroquinone.

[0055] In addition, methods for reducing and decolorizing the generated melanin are also introduced.

[0056] Much of the current research aimed at discovering skin-whitening compositions focuses on substances that directly inhibit melanin-producing enzymes (TRP1, TRP2, tyrosinase) involved in melanin synthesis. However, it has been suggested that skin-whitening effects can also be expected by regulating signal transduction, which is involved in the expression of melanin-producing enzymes (TRP1, TRP2, tyrosinase), in addition to direct inhibition of these enzymes (Briganti S, Camera E, Picardo M. Pigment Cell Res, 2003, 16(2):101-10).

[0057] Furthermore, while it is known that melanin-producing enzymes (TRP1, TRP2, tyrosinase) are produced by the regulation of the transcription factor MITF (microphthalmia-associated transcription factor) when affected by external stimuli or hormones (DS Kim, ES Whang, JE Lee, SY Kim, SB Kwon, and KC Park. J Cell Sci. 2003;116:1699-706), no method has yet been introduced to reduce melanin production by suppressing the expression of MITF.

[0058] The composition according to one embodiment reduces melanin production by suppressing the production of the melanin-producing enzymes (TRP1, TRP2, tyrosinase). Specifically, it is highly effective in inhibiting the increased protein expression of melanin-producing enzymes (TRP1, TRP2, tyrosinase) caused by acne-causing bacteria (C. acnes) in melanocytes. Therefore, when used on skin where hyperpigmentation has been induced by acne-causing bacteria (C. acnes) or other skin pigmentation-inducing factors, it exhibits excellent skin whitening effects. For example, applying the composition according to one embodiment to the skin around acne can be expected to produce excellent skin whitening effects.

[0059] One embodiment provides a skin whitening composition containing the compound represented by chemical formula 1 as an active ingredient, which may contain a pharmaceutically effective amount of the compound represented by chemical formula 1 alone, or may contain one or more pharmaceutically acceptable carriers, excipients, or diluents.

[0060] The compound represented by chemical formula 1 in the composition may be present in concentrations of 0.001 nM to 1 μM relative to the total amount of the composition, for example, 0.01 nM to 100 nM, for example, 1 nM to 100 nM. For example, the compound represented by chemical formula 1 in the composition may be present in concentrations of 0.001 nM or more, 0.01 nM or more, 0.1 nM or more, 1 nM or more, and 1 μM or less, and 100 nM or less, relative to the total amount of the composition. When the compound represented by chemical formula 1 is used at a concentration of less than 0.001 nM, the degree to which it suppresses the phenomenon in which acne-causing bacteria (C. acnes) and skin pigmentation-inducing factors increase the protein expression of melanin-producing enzymes (TRP1, TRP2, tyrosinase) in melanocytes is slight, and it cannot have a skin whitening function improvement effect. Furthermore, using the compound represented by chemical formula 1 at a concentration exceeding 1 μM is undesirable because it can cause cytotoxicity and harm to the human body. While the risk of cytotoxicity is relatively low when used at a concentration exceeding 100 nM, there is no significant difference in skin whitening effect compared to when the compound represented by chemical formula 1 is included at a concentration of 1 nM to 100 nM. On the contrary, the unnecessary excessive inclusion of the compound represented by chemical formula 1 may restrict the roles of other functional components in the composition, which is undesirable.

[0061] For example, the aforementioned whitening composition may contain a compound represented by the following chemical formula 2 as an active ingredient.

[0062] [ka]

[0063] In the aforementioned chemical formula 2, R 1 ~R 3 Each of these is independently a hydrogen atom, a hydroxyl group, or a carboxyl group, and the R 1 ~R 3 At least one of them is a hydroxyl group, and the R 1 ~R 3 At least one of them is a carboxyl group.

[0064] For example, the aforementioned chemical formula 2 is represented by the following chemical formula 2-1, but is not necessarily limited to this.

[0065] [ka]

[0066] For example, the aforementioned whitening composition may contain a compound represented by the following chemical formula 3.

[0067] [ka]

[0068] In the aforementioned chemical formula 3, R 3 and R 4 Each of these is independently a hydroxyl group or a carboxyl group, and the R 3 and R 4 At least one of them is a hydroxyl group, and the R 3 and R 4 At least one of them is a carboxyl group.

[0069] For example, the aforementioned chemical formula 3 is represented by the following chemical formula 3-1, but is not necessarily limited to this.

[0070] [ka]

[0071] In the foregoing, "pharmaceutically effective amount" refers to an amount sufficient to exhibit the desired physiological or pharmacological activity when administered to an animal or human. However, the pharmaceutically effective amount may vary depending on the severity of the symptoms, the patient's age, weight, health condition, sex, route of administration, and duration of treatment.

[0072] Furthermore, "pharmaceutically acceptable" as used above means that it is physiologically acceptable and does not usually cause gastrointestinal disorders, allergic reactions such as dizziness, or similar reactions when administered to humans. Examples of the carriers, excipients, and diluents include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia gum, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methylcellulose, polyvinylpyrrolidone, water, methyl hydroxybenzoate, propyl hydroxybenzoate, talc, magnesium stearate, and mineral oil. They may also further include fillers, anti-coagulants, lubricants, wetting agents, fragrances, emulsifiers, and preservatives.

[0073] For example, the composition may be a cosmetic composition.

[0074] In this specification, "cosmetics" means all substances that have not only cosmetic functions but also additional medical functions in addition to cosmetic functions.

[0075] The dosage form of the cosmetic composition is not particularly limited and can be appropriately selected depending on the purpose.

[0076] For example, the cosmetic composition may be formulated as a solution, suspension, emulsion, paste, gel, cream, lotion, powder, soap, surfactant-containing cleanser, oil, powder foundation, emulsion foundation, wax foundation, and spray, but is not limited thereto. More specifically, it can be formulated as a cosmetic composition such as a cleanser, tonic, hair styling agent, nourishing lotion, essence, serum, treatment, conditioner, shampoo, lotion, hair tonic, or hair dye, or as a basic cosmetic composition such as an oil-in-water (O / W) type or water-in-oil (O / W) type. For example, the composition may have one dosage form selected from the group consisting of skin lotion, skin toner, astringent, lotion, emulsion, moisturizing lotion, nourishing lotion, massage cream, nourishing cream, moisturizing cream, hand cream, ointment, foundation, essence, nourishing essence, pack, soap, cleansing foam, cleansing lotion, cleansing cream, body lotion, body wash, lotion, ointment, gel, cream, patch, and spray. In addition to the essential components described above, a person skilled in the art can easily select and incorporate other optional components into each dosage form of the composition, depending on the type of topical preparation or intended use. For example, it may further contain UV blocking agents, hair conditioning agents, fragrances, etc.

[0077] The cosmetic composition may contain a cosmetically acceptable medium or base. It can be provided in all dosage forms suitable for topical application, for example, in the form of a solution, gel, solid or paste-like anhydrous product, emulsion obtained by dispersing an oily substance in an aqueous solution, suspension, microemulsion, microcapsule, microgranulocyte or ionic (liposome) and / or nonionic vesicle dispersant, or in the form of a cream, skin, lotion, powder, ointment, spray or concealer stick. These compositions can be manufactured by conventional methods of the art.

[0078] When the dosage form of the present invention is a solution or emulsion, a solvent, solubilizer, or emulsifier is used as the carrier component, for example, water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butyl glycol oil, glycerol aliphatic ester, polyethylene glycol, or fatty acid ester of sorbitan.

[0079] When the dosage form of the present invention is a suspension, the carrier component may be a liquid diluent such as water, ethanol, or propylene glycol, a suspending agent such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester, or polyoxyethylene sorbitan ester, or microcrystalline cellulose, aluminum methhydroxyl, bentonite, agar, or tragacanth.

[0080] When the dosage form of the present invention is a paste, cream, or gel, animal oils, vegetable oils, waxes, paraffin, starch, tragacande, cellulose derivatives, polyethylene glycol, silicone, bentonite, silica, talc, or zinc oxide can be used as the carrier component.

[0081] When the dosage form of the present invention is a powder or spray, lactose, talc, silica, aluminum hydroxide, calcium silicate, or polyamide powder may be used as the carrier component, and especially in the case of a spray, it may further contain a propellant such as chlorofluorohydrocarbon, propane / butane, or dimethyl ether.

[0082] In one embodiment of the present invention, the cosmetic composition may further contain a viscosity enhancer. The viscosity enhancer contained in the cosmetic composition of the present invention may be methylcellulose, carboxymethylcellulose, carboxymethylhydroxyguanine, hydroxymethylcellulose, hydroxyethylcellulose, carboxyvinyl polymer, polyquaternium, cetearyl alcohol, stearic acid, carrageenan, etc. Preferably, one or more of carboxymethylcellulose, carboxyvinyl polymer, and polyquaternium may be used, and most preferably carboxyvinyl polymer may be used.

[0083] The cosmetic composition in one embodiment of the present invention may contain various suitable bases and additives as needed, the types and amounts of these components shall be appropriately selected by the inventor. It may also contain acceptable additives as needed, for example, components such as preservatives, dyes, and additives that are common in the industry.

[0084] Examples of preservatives include phenoxyethanol or 1,2-hexanediol, while fragrances include artificial fragrances.

[0085] Furthermore, in one embodiment of the present invention, the cosmetic composition may contain a composition selected from the group consisting of water-soluble vitamins, oil-soluble vitamins, high molecular weight peptides, high molecular weight polysaccharides, sphingolipids, and seaweed extracts. Other ingredients that may be added include oils and fats, moisturizers, emollients, surfactants, organic and inorganic pigments, organic powders, UV absorbers, preservatives, bactericides, antioxidants, plant extracts, pH adjusters, alcohols, dyes, fragrances, blood circulation promoters, cooling agents, antiperspirants, and purified water.

[0086] Furthermore, the ingredients that may be added are not limited to those mentioned above, and any of the aforementioned ingredients can be added within a range that does not impair the purpose and effects of the present invention.

[0087] Furthermore, the cosmetic composition according to one embodiment can be used not only as a pharmaceutical composition as described above, but also as a health functional food. For example, it can be easily used as a main ingredient, auxiliary ingredient, food additive, functional food, or beverage.

[0088] The term "food" as used above means natural products or processed products that contain one or more nutrients, preferably those that have undergone some processing steps and are ready to be eaten directly, and in the usual sense, it includes all foods, food additives, functional foods, and beverages.

[0089] Examples of foods to which the aforementioned food composition can be added include various foods, beverages, gums, teas, vitamin complexes, and functional foods. Furthermore, it includes, but is not limited to, special nutritional foods (e.g., prepared milks, infant food, etc.), processed meat products, fish products, tofu products, jellies (starch gels), noodles (e.g., ramen, udon, etc.), breads, health supplements, seasonings (e.g., soy sauce, miso, gochujang, mixed sauces, etc.), sauces, confectionery (e.g., snacks), candies, chocolates, gums, ice creams, dairy products (e.g., fermented milk, cheese, etc.), other processed foods, kimchi, pickled foods (various types of kimchi, pickled vegetables, etc.), beverages (e.g., fruit drinks, vegetable drinks, soy milk, fermented beverages, etc.), and natural seasonings (e.g., ramen soup, etc.). The aforementioned foods, beverages, or food additives can be manufactured by conventional manufacturing methods.

[0090] Furthermore, the terms "functional food" or "health functional food" refer to a group of foods to which added value has been added using physical, biochemical, or biotechnological methods to act on and express the functions of the food in question for a specific purpose, or foods that have been designed and processed to fully express the internal regulatory functions related to the regulation of biological defense rhythms, disease prevention and recovery, etc., in the body, and specifically may be health functional foods. The functional food may contain food-grade acceptable food additives and may further contain appropriate carriers, excipients, and diluents that are commonly used in the manufacture of functional foods.

[0091] The types of the aforementioned health supplements are not limited to, but may be in the form of powder, granules, tablets, capsules, or beverages.

[0092] Another embodiment provides a method for whitening the skin of an individual, comprising the step of administering the composition to the individual. The composition is the same as described above.

[0093] The administration is carried out by methods known to the art. The administration is carried out directly to the individual by any means, such as via intravenous, intramuscular, oral, transdermal, mucosal, intranasal, intratratracheal, or subcutaneous administration. The administration is carried out systemically or locally. The administration may also be carried out topically to the site where skin aging is present. The administration may be carried out, for example, by topical application. Topical application means all methods of bringing the composition into contact with the skin of the individual in an appropriate manner, thereby allowing the composition to be absorbed into the skin.

[0094] The individual may be a mammal, such as a human, cattle, horse, pig, dog, sheep, goat, or cat. The individual may be one that requires improvement, delay, or suppression of skin hyperpigmentation. The individual may be one that requires suppression of cell death, suppression of tyrosinase protein expression, or increase of antioxidant activity.

[0095] The administration may involve administering the composition according to one embodiment at a dose of 0.01 mg to 10,000 mg, 0.1 mg to 1,000 mg per individual per day, for example, 0.1 mg to 500 mg, 0.1 mg to 100 mg, 0.1 mg to 50 mg, 0.1 mg to 25 mg, 1 mg to 1,000 mg, 1 mg to 500 mg, 1 mg to 100 mg, 1 mg to 50 mg, 1 mg to 25 mg, 5 mg to 1,000 mg, 5 mg to 500 mg, 5 mg to 100 mg, 5 mg to 50 mg, 5 mg to 25 mg, 10 mg to 1,000 mg, 10 mg to 500 mg, 10 mg to 100 mg, 10 mg to 50 mg, or 10 mg to 25 mg. Alternatively, the administration may involve administering the composition according to one embodiment at a working concentration of 0.01-25 μM, 0.05-5 μM, 0.075-3.75 μM, 0.1-2.5 μM, 0.15-2 μM, 0.25-1.5 μM, 0.4-1.25 μM, 0.5-1.2 μM, or 0.75-1.15 μM.

[0096] The advantages and features of the present invention, as well as the methods for achieving them, will become clearer with reference to the examples described below in detail. The present invention will be described in detail below with reference to examples. However, these examples are for illustrative purposes only, and the scope of the present invention is not limited to these examples.

[0097] (Examples) Test Example 1: Confirmation of inhibition of increased protein expression of melanin-producing enzyme (tyrosinase, TRP2) in normal human melanin-producing cells. Human normal melanocytes were laid in a 6-well plate, and the next day the medium was replaced with a melanocyte culture medium that did not contain PMA (phorbol 12-myristate-13-acetate). At this time, the cells were treated with compositions containing the compound represented by chemical formula 1-1 below (Cayman chemical) at concentrations of 0 nM, 0.001 nM, 0.01 nM, 0.1 nM, 1 nM, 10 nM, and 100 nM, respectively (based on the total amount of the composition). After 4 days of culture, the cells were lysed in each well using lysis buffer, and the proteins were separated. From the separated proteins, the relative protein expression levels were measured using antibodies specific to the melanin-producing enzymes tyrosinase and TRP2 (tyrosinase-related protein 2). The expression level of GAPDH was checked as a control group, and the results are shown in Figures 1 to 3.

[0098] [ka]

[0099] Figures 1 to 3 show that when the compound represented by chemical formula 1-1 is included, it effectively inhibits the increase in protein expression of the melanin-producing enzyme (tyrosinase, TRP2) in normal human melanin-producing cells, regardless of C. acnes. In particular, it can be confirmed that the compound represented by chemical formula 1-1 effectively inhibits the increase in tyrosinase protein expression in a concentration-dependent manner.

[0100] Test Example 2: Confirmation of inhibition of increased protein expression of melanin-producing enzyme (tyrosinase, TRP2) by pigmentation inducer (α-MSH). Human normal melanocytes were placed in a 6-well plate, and the next day the medium was replaced with a melanocyte culture medium that did not contain PMA. At this time, the cells were treated with a composition containing 500 nM pigmentation inducer (α-MSH) along with the compound represented by chemical formula 1-1 (Cayman chemical) at concentrations of 0 nM, 0.001 nM, 0.01 nM, 0.1 nM, 1 nM, 10 nM, and 100 nM (based on total composition amount). After 4 days of culture, the cells were lysed in each well using lysis buffer, and the proteins were separated. From the separated proteins, the relative protein expression levels were measured using antibodies specific to the melanin-producing enzymes tyrosinase and TRP2 (tyrosinase-related protein 2). The expression level of GAPDH was checked as a control group, and the results are shown in Figures 4 to 6.

[0101] [ka]

[0102] Figures 4 to 6 show that when the compound represented by chemical formula 1-1 is included, it effectively inhibits the increase in protein expression of the melanin-producing enzyme (tyrosinase, TRP2) induced by the pigmentation inducer (α-MSH).

[0103] Test Example 3: Confirmation of inhibition of increased protein expression of melanin-producing enzyme (tyrosinase, TRP2) by pigmentation inducer (IBMX). Human normal melanocytes were placed in a 6-well plate, and the next day the medium was replaced with a melanocyte culture medium that did not contain PMA. At this time, the cells were treated with a composition containing 100 μM of pigmentation inducer (IBMX) along with the compound represented by chemical formula 1-1 (Cayman chemical) at concentrations of 0 nM, 0.001 nM, 0.01 nM, 0.1 nM, 1 nM, 10 nM, and 100 nM (based on total composition amount). After 4 days of culture, the cells were lysed in each well using lysis buffer, and the proteins were separated. From the separated proteins, the relative protein expression levels were measured using antibodies specific to the melanin-producing enzymes tyrosinase and TRP2 (tyrosinase-related protein 2). The expression level of GAPDH was checked as a control group, and the results are shown in Figures 7 to 9.

[0104] [ka]

[0105] Figures 7 to 9 confirm that when the compound represented by chemical formula 1-1 is included, it effectively inhibits the increase in protein expression of the melanin-producing enzyme (tyrosinase, TRP2) induced by the pigmentation inducer (IBMX).

[0106] Test Example 4: Confirmation of whether C. acnes increases the protein expression of melanin-producing enzymes (TRP1, TRP2). Cutibacterium acnes (C. acnes, ATCC 6919) is inoculated into BHI medium and incubated at 37°C under anaerobic conditions for 72-96 hours, after which the culture medium is collected. The collected culture medium is centrifuged (4°C, 5,000 xg for 10 minutes) to precipitate the bacteria. The precipitated bacteria are washed twice with phosphate-buffered saline (PBS), and then the final concentration is 10. 10Prepare a live C. acnes stock to a concentration of CFU / ml and freeze-store at -80°C. Place normal human melanocytes in a 6-well plate, and the next day replace the medium with a PMA-free melanocyte culture medium. At this time, 10 4 , 10 5 , 10 6 , 10 7 Live C. acnes were treated with CFU / ml. After 2 days of incubation, cells were lysed in each well using lysis buffer, and proteins were separated. Relative protein expression levels were measured from the separated proteins using antibodies specific to the melanin-producing enzymes TRP1 (tyrosinase-related protein 1) and TRP2 (tyrosinase-related protein 2). The expression level of GAPDH was checked as a control group, and the results are shown in Figure 10.

[0107] Figure 10 confirms that the acne-causing bacteria (C. acnes) increase the protein expression of melanin-producing enzymes (TRP1, TRP2) in melanocytes.

[0108] Test Example 5: Confirmation of inhibition of increased protein expression of melanin-producing enzymes (TRP1, TRP2) by C. acnes. Human normal melanocytes are placed in a 6-well plate, and the next day the medium is changed to a melanocyte culture medium that does not contain PMA. At this time, 10 7 C. acnes live bacteria at a concentration of CFU / ml were treated with a composition containing the compound represented by chemical formula 1-1 (Cayman chemical) at concentrations of 1 nM, 10 nM, and 100 nM, respectively (based on the total amount of the composition). After 2 days of incubation, cells were lysed in each well using lysis buffer, and proteins were separated. Relative protein expression levels were measured from the separated proteins using antibodies specific to the melanin-producing enzymes TRP1 (tyrosinase-related protein 1) and TRP2 (tyrosinase-related protein 2). The expression level of GAPDH was checked as a control group, and the results are shown in Figures 11 and 12.

[0109] [ka]

[0110] Figures 11 and 12 confirm that when the compound represented by chemical formula 1-1 is present in a concentration range of 1 nM to 100 nM, it effectively inhibits the increased protein expression of melanin-producing enzymes (TRP1, TRP2) caused by C. acnes.

[0111] 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 that utilize the basic concepts of the present invention as defined in the following claims also fall within the scope of the present invention.

Claims

1. A whitening composition comprising a structural unit represented by the following chemical formula A, and containing a compound represented by the following chemical formula 1 as an active ingredient, 【Chemistry 1】 The compound represented by the chemical formula 1 is contained in the whitening composition at a concentration of 0.001 nM to 1 μM relative to the total amount of the composition; 【Chemistry 2】 In the aforementioned chemical formula 1, Each of R1 to R3 is independently a hydrogen atom, a hydroxyl group, or a carboxyl group, and at least one of R1 to R3 is a hydroxyl group, and at least one of R1 to R3 is a carboxyl group.

2. The aforementioned R １ and R ２ Each of these is independently a hydroxyl group, The aforementioned R ３ The whitening composition according to claim 1, wherein is a carboxyl group.

3. The whitening composition according to claim 1, wherein the compound represented by chemical formula 1 is contained in the composition at a concentration of 0.01 nM to 100 nM relative to the total amount of the composition.

4. The whitening composition according to claim 1, wherein the whitening composition is a cosmetic composition.

5. A method for whitening the skin of an individual, comprising the step of administering to the individual a cosmetic composition containing a structural unit represented by the following chemical formula A and a compound represented by the following chemical formula 1 as an active ingredient, 【Transformation 3】 The compound represented by the chemical formula 1 is contained in the whitening composition at a concentration of 0.001 nM to 1 μM relative to the total amount of the composition; 【Chemistry 4】 In the aforementioned chemical formula 1, Each of R1 to R3 is independently a hydrogen atom, a hydroxyl group, or a carboxyl group, and at least one of R1 to R3 is a hydroxyl group, and at least one of R1 to R3 is a carboxyl group.

6. The aforementioned R １ and R ２ Each of these is independently a hydroxyl group, The aforementioned R ３ The method for whitening the skin of an individual according to claim 5, wherein is a carboxyl group.

7. The method for whitening the skin of an individual according to claim 5, wherein the compound represented by chemical formula 1 is included in the composition at a concentration of 0.01 nM to 100 nM relative to the total amount of the composition.

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