WO2021215709A1 - Whitening cosmetic composition comprising sodium pyruvate as active ingredient - Google Patents

Whitening cosmetic composition comprising sodium pyruvate as active ingredient Download PDF

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WO2021215709A1
WO2021215709A1 PCT/KR2021/004377 KR2021004377W WO2021215709A1 WO 2021215709 A1 WO2021215709 A1 WO 2021215709A1 KR 2021004377 W KR2021004377 W KR 2021004377W WO 2021215709 A1 WO2021215709 A1 WO 2021215709A1
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sodium pyruvate
composition
pigmentation
skin
hydroquinone
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PCT/KR2021/004377
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French (fr)
Korean (ko)
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최선국
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주식회사 엘지생활건강
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/33Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/36Carboxylic acids; Salts or anhydrides thereof
    • A61K8/365Hydroxycarboxylic acids; Ketocarboxylic acids
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/21Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/22Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/70Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7028Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
    • A61K31/7034Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/33Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/35Ketones, e.g. benzophenone
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/33Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/35Ketones, e.g. benzophenone
    • A61K8/355Quinones
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/60Sugars; Derivatives thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/60Sugars; Derivatives thereof
    • A61K8/602Glycosides, e.g. rutin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/0012Galenical forms characterised by the site of application
    • A61K9/0014Skin, i.e. galenical aspects of topical compositions
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00Preparations for care of the skin
    • A61Q19/02Preparations for care of the skin for chemically bleaching or whitening the skin

Definitions

  • the present invention relates to a cosmetic composition for whitening comprising sodium pyruvate as an active ingredient.
  • Skin color is determined by melanin, hemoglobin, carotene, etc. Among them, melanin plays the most important role. In addition to determining a person's skin color, melanin also performs skin protection functions such as UV absorption and free radical scavengers. However, when melanin is excessively generated by external environmental changes such as excessive exposure to ultraviolet rays, air pollution, stress, etc., it causes pigmentation in the skin, which causes skin blackening (melanism), blemishes, freckles, and the like. Blackening of the skin is caused by the reaction of skin cells to internal and external factors, and a representative factor is due to UV exposure.
  • melanin when the skin is exposed to ultraviolet rays, tyrosinase is activated, and the tyrosinase acts on tyrosine present in the skin tissue to produce dopa (DOPA) and dopaquinone (dopaquinone) by an oxidation process,
  • DOPA dopa
  • dopaquinone dopaquinone
  • a polymer called melanin is synthesized from melanosomes in melanocytes, which are skin pigment cells, and this melanin is transferred to keratinocytes, which are keratinocytes of the skin, and reaches the skin surface through the keratinization process. It protects the skin from UV rays.
  • melanin when melanin is locally synthesized excessively or the physiological function of the skin is deteriorated due to skin lesions and aging, melanin is deposited on the skin surface, causing melasma, freckles and various pigmentation.
  • melanocyte precursor cells (melanoblasts) are stored in the hair follicle epithelium, especially in the bulge (Nishimura et al, Science. 2005, 307(5710):720-4), and the epidermis between the hair follicles ( When melanocytes are removed from the basal layer of the interfollicular epidermis, melanocyte precursor cells migrate to this area, and at this time, not only UV rays but also adjacent cutaneous cells such as keratinocytes, fibroblasts or inflammatory cells Interaction between melanin synthesis (melanogenesis) and dendrite outgrowth required to move melanin granules to keratinocytes occurs and final differentiation occurs.
  • a-melanocyte-stimulating hormone is a melanocyte differentiation-promoting material secreted from UV-exposed keratinocytes. It promotes the proliferation of melanocyte precursor cells and the M promoter of microphtalmia-associated transcription factor (Mitf) in melanocytes. ), increases the expression of enzymes that cause pigment formation mechanisms such as tyrosinase, and causes melanosome formation and dendrite elongation. As such, the molecular mechanisms involved in the differentiation of melanocytes are precisely regulated.
  • substances having an inhibitory effect on the activity of tyrosinase, an enzyme involved in the skin blackening process are compounded, or melanin
  • a method of reducing the production of melanin by inhibiting some reactions in the production process is generally used.
  • Representative materials used for this purpose include chemical substances such as ascorbic acid, kojic acid, and hydroquinone, and plant extracts such as epiphyllum extract and licorice extract.
  • ascorbic acid lacks tyrosinase activity inhibitory effect and is not suitable as a melanogenesis inhibitor due to low safety of the molecule itself, and kojic acid has excellent inhibitory activity of tyrosinase, Therefore, not only there is a problem in safety such as a decrease in potency, but there is a limitation in use due to large skin irritation, and hydroquinone is limited in use in cosmetics due to skin irritation and safety problems. restricted to contain.
  • Another object of the present invention is a cosmetic composition for whitening comprising sodium pyruvate as an active ingredient; pharmaceutical compositions for the treatment of pigmentation; A composition for external application for skin for the treatment of pigmentation, and a whitening method using the composition, a method for treating pigmentation, and use for manufacturing a whitening cosmetic; and to provide a use for the manufacture of a therapeutic agent for pigmentation.
  • Another object of the present invention is sodium pyruvate and hydroquinone; sodium pyruvate and arbutin; Or a cosmetic composition for whitening comprising sodium pyruvate, hydroquinone and arbutin; pharmaceutical compositions for the treatment of pigmentation; Or a composition for external application to the skin for the treatment of pigmentation; And a whitening method using the composition, a method for treating hyperpigmentation, a use for manufacturing a whitening cosmetic; and to provide a use for the manufacture of a therapeutic agent for pigmentation.
  • a cosmetic composition for whitening comprising sodium pyruvate as an active ingredient.
  • compositions for whitening further comprising one or more selected from the group consisting of hydroquinone and arbutin.
  • the cosmetic composition in the present invention may be in the form of a lotion, essence, lotion, cream, pack, gel, powder, foundation or detergent.
  • a pharmaceutical composition for treating hyperpigmentation comprising sodium pyruvate as an active ingredient.
  • compositions for the treatment of pigmentation further comprising one or more selected from the group consisting of hydroquinone and arbutin.
  • composition for external application for skin for the treatment of pigmentation comprising sodium pyruvate as an active ingredient.
  • compositions for external application to the skin for the treatment of pigmentation further comprising one or more selected from the group consisting of hydroquinone and arbutin.
  • composition for external application for skin in the present invention may be in the form of an ointment, patch, gel, cream or spray.
  • a whitening method comprising the step of treating the skin with a composition comprising sodium pyruvate as an active ingredient.
  • a method for treating pigmentation comprising the step of treating the skin with a composition comprising sodium pyruvate as an active ingredient.
  • composition may further include one or more selected from the group consisting of hydroquinone and arbutin.
  • composition comprising sodium pyruvate for the preparation of a therapeutic agent for pigmentation.
  • composition comprising sodium pyruvate for preparing an external preparation for the treatment of pigmentation.
  • composition may further include one or more selected from the group consisting of hydroquinone and arbutin.
  • the cosmetic composition for whitening, the pharmaceutical composition for the treatment of pigmentation, and the composition for external application to the skin for the treatment of pigmentation of the present invention can overcome the disadvantages of safety and apoptosis, which are disadvantages of conventional tyrosinase activity inhibitory compounds.
  • compositions comprising sodium pyruvate, hydroquinone, and arbutin as an active ingredient has the effect of inhibiting the differentiation of melanocytes, has the effect of inhibiting melanin synthesis, and reduces the apoptosis and skin safety problems of hydroquinone and arbutin with sodium pyruvate. It was confirmed that it was possible to overcome when used together. Accordingly, an improved whitening effect can be provided, and the composition of the present invention can be effectively used in cosmetics, medicines, external preparations, and the like.
  • the present invention provides a cosmetic composition for whitening comprising sodium pyruvate as an active ingredient.
  • composition for whitening further comprising one or more selected from the group consisting of hydroquinone and arbutin.
  • composition for the treatment of pigmentation disorder comprising sodium pyruvate as an active ingredient.
  • compositions for the treatment of pigmentation further comprising one or more selected from the group consisting of hydroquinone and arbutin.
  • composition for external application to the skin for the treatment of pigmentation comprising sodium pyruvate as an active ingredient.
  • composition for external application for skin for the treatment of pigmentation further comprising one or more selected from the group consisting of hydroquinone and arbutin.
  • a whitening method using a composition comprising sodium pyruvate as an active ingredient a method for treating pigmentation, use for preparing a whitening cosmetic; and for the manufacture of a therapeutic agent for pigmentation.
  • sodium pyruvate and hydroquinone sodium pyruvate and arbutin; or a whitening method using a composition comprising sodium pyruvate, hydroquinone, and arbutin, a method for treating pigmentation disorders, and use for preparing a whitening cosmetic; and for the manufacture of a therapeutic agent for pigmentation.
  • a whitening method comprising the step of treating the skin with a composition comprising sodium pyruvate as an active ingredient.
  • a method for treating pigmentation comprising the step of treating the skin with a composition comprising sodium pyruvate as an active ingredient.
  • composition may further include one or more selected from the group consisting of hydroquinone and arbutin.
  • composition comprising sodium pyruvate for the manufacture of a therapeutic agent for pigmentation.
  • composition comprising sodium pyruvate for preparing an external preparation for the treatment of pigmentation.
  • composition may further include one or more selected from the group consisting of hydroquinone and arbutin.
  • Sodium pyruvate of the present invention is represented by the following [Formula 1] and is another salt form of pyruvic acid, which is one of a-keto acids.
  • pyruvate is an intermediate in many metabolic pathways, sodium pyruvate is widely used to provide more energy in many experiments involving cell culture.
  • pyruvic acid not only suppresses melasma, solar lentigine, acne, and warts, but also promotes collagen synthesis and improves skin elasticity. (50 ⁇ 100%), since it is an effect due to chemical exfoliation, you may feel a stinging or burning sensation while using pyruvic acid, and excessive exfoliation of dead skin cells or inflammatory blisters may be accompanied.
  • the human efficacy at low concentrations in which chemical exfoliation does not occur is unknown.
  • “Hydroquinone (HQ)” of the present invention is represented by [Formula 2], also known as benzene-1,4-diol or quinol. It is an aromatic organic compound that is a type of phenol.
  • Hydroquinone is used for topical application for skin whitening, but its use is limited because it can irritate the skin when used in high concentrations.
  • Alkaolin of the present invention is represented by [Formula 3].
  • glucoside As a type of glucoside, it is a glycosylated hydroquinone extracted from bearberry of the genus Arctostaphylos of the Azalea family.
  • Arbutin is used for skin whitening treatment, but like hydroquinone, arbutin can irritate the skin when used in high concentrations, so special attention is required.
  • the "skin whitening effect" of the present invention not only brightens the skin tone by inhibiting the synthesis of melanin pigment and the differentiation of melanocytes, but also makes the skin tone or complexion uniform, UV rays, hormonal or genetic blemishes, hyperpigmentation after inflammation It refers to, but is not limited to, improving pigmentation, changes in pigmentation due to skin aging, age spots or brown spots, freckles, and hyperpigmentation.
  • cosmetics prepared by containing the compounds and mixtures as active ingredients can be prepared in the form of general emulsified formulations or solubilized formulations. have.
  • a lotion such as a softening lotion or a nourishing lotion
  • Emulsion such as facial lotion or body lotion, cream such as nourishing cream, moisture cream or eye cream, essence, cosmetic ointment, spray, gel, pack, sunscreen, makeup base, liquid type, solid type or spray type foundation
  • Powders, cleansing creams, cleansing lotions, make-up removers such as cleansing oils, cleansing foams, soaps, body washes, and the like may have formulations.
  • composition of the present invention comprises a fatty substance, an organic solvent, a solubilizer, a thickening agent, a gelling agent, an emollient, an antioxidant, a suspending agent, a stabilizer, a foaming agent, a fragrance, a surfactant, water, an ionic emulsifier, a nonionic Additional additives commonly used in the cosmetic field, such as emulsifiers, fillers, sequestering agents, chelating agents, preservatives, vitamins, blocking agents, wetting agents, essential oils, dyes, pigments, hydrophilic active agents, lipophilic active agents or lipid vesicles may contain.
  • the composition may include sodium pyruvate in an amount of 0.001 to 5% (w/w) based on the total weight of the composition.
  • the composition of the present invention contains less than 0.001% (w/w) of sodium pyruvate, a sufficient skin whitening effect cannot be expected.
  • the sodium pyruvate is preferably 0.005 to 4% (w/w), more preferably 0.01 to 2% (w/w), and most preferably 0.05 to 1% (w/w) based on the total weight of the composition. can be included as
  • the composition may include hydroquinone in an amount of 0.001 to 6% (w/w) based on the total weight of the composition.
  • hydroquinone in an amount of 0.001 to 6% (w/w) based on the total weight of the composition.
  • the hydroquinone is 0.005 to 6% (w / w), 0.01 to 5% (w / w), 0.05 to 4% (w / w), or 0.1 to 2% (w / w) based on the total weight of the composition.
  • the composition may include arbutin in an amount of 0.001 to 10% (w/w) based on the total weight of the composition.
  • arbutin in an amount of 0.001 to 10% (w/w) based on the total weight of the composition.
  • the arbutin is included in 0.005 to 10% (w/w), 0.01 to 6% (w/w), 0.05 to 5% (w/w), or 0.1 to 2% (w/w) by weight of the total composition can do.
  • the composition includes active ingredients sodium pyruvate and hydroquinone; or sodium pyruvate and arbutin; Or sodium pyruvate, hydroquinone and arbutin based on the total weight of the composition 0.002 to 10% (w / w), 0.005 to 6% (w / w), 0.01 to 5% (w / w), 0.05 to 4% ( w/w), or 0.1 to 3% (w/w).
  • active ingredient of the present invention is included in less than 0.002% (w/w), a sufficient skin whitening effect cannot be expected, and when it contains more than 10% (w/w), unwanted reactions such as allergies occur. Or there may be a problem with skin safety.
  • the 'pharmaceutical composition' of the present invention can be administered orally or parenterally, and when sodium pyruvate, sodium pyruvate and hydroquinone or sodium pyruvate and arbutin are used as pharmaceutical compositions, the form of a generic pharmaceutical preparation, For example, it can be administered in various oral and parenteral dosage forms during clinical administration. When formulated, it can be prepared using diluents or excipients such as commonly used fillers, extenders, binders, wetting agents, disintegrants, surfactants, etc. can, but is not limited thereto.
  • Solid preparations for oral administration include tablets, pills, powders, granules, capsules, etc., and these solid preparations include at least one excipient in the pharmaceutical composition of the present invention, for example, starch, calcium carbonate, It may be prepared by mixing sucrose or lactose, gelatin, etc., but is not limited thereto.
  • lubricants such as magnesium stearate talc are also used.
  • Liquid formulations for oral use include suspensions, solutions, emulsions, syrups, etc.
  • various excipients such as wetting agents, sweeteners, fragrances, preservatives, etc. may be included. not limited
  • the 'composition for external application to the skin' of the present invention may be used as an external preparation for skin, but is not limited thereto.
  • sodium pyruvate, sodium pyruvate and hydroquinone, and sodium pyruvate and arbutin are used as external preparations for skin, fat substances, organic solvents, solubilizers, thickening and gelling agents, emollients, antioxidants, suspending agents, and stabilizing agents are additionally used.
  • Agents foaming agents, fragrances, surfactants, water, ionic or nonionic emulsifiers, fillers, sequestering and chelating agents, preservatives, vitamins, blocking agents, wetting agents, essential oils, dyes, pigments, hydrophilicity 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 external preparations for skin. In addition, the ingredients may be introduced in an amount generally used in the field of dermatology. When provided as an external preparation for skin, it may have a formulation such as, but not limited to, an ointment, a patch, a gel, a cream, or a spray.
  • a formulation such as, but not limited to, an ointment, a patch, a gel, a cream, or a spray.
  • each of the above-mentioned components included in the composition according to the present invention may preferably be included in the composition of the present invention within a range not exceeding the maximum amount specified in the norms stipulated by the respective national governments.
  • it may be included in the present invention within the scope of the manufacturing method, properties, amount of use, etc. specified in the Pharmacopoeia or drug collection prescribed in Korea, the United States, Europe, Germany, Japan, China, etc. .
  • the cosmetic composition of the present invention may be included in the cosmetic composition of the present invention to the extent that it does not exceed the maximum amount specified in the Cosmetic Safety Act stipulated by each country or the “Cosmetic Safety Technical Specification” stipulated by the Chinese government. can
  • B16F10 cells (ATCC, catalog number CRL-6475) were first aliquoted in a 6-well plate at a concentration of 1 x 10 5 cells/well and cultured for 24 hours. .
  • 10 nM of ⁇ -MSH ⁇ -Melanocytes Stimulating Hormone
  • the experimental group was treated with 10 nM of ⁇ -MSH and 10 mM sodium pyruvate in the cells. After 48 hours in both control and experimental groups, the length of dendrites was measured under a microscope (EVOS FL auto 2, Termo Fisher Scientific).
  • B16F10 cells were aliquoted in a 96-well plate at a concentration of 2 x 10 3 cells/well and cultured in DMEM medium containing 10% FBS and 1% penicillin/streptomycin for 24 hours at 37°C and 5% CO 2 condition.
  • sodium pyruvate or hydroquinone (HQ) was treated for 48 hours at each concentration, and then cytotoxicity was tested by CCK-8 assay, and the results are shown in Table 2.
  • the negative control group was a condition in which neither sodium pyruvate nor HQ was treated, and the cell viability of the experimental group treated with sodium pyruvate or hydroquinone (HQ) was calculated as a percentage compared to the negative control group, and is shown in Table 2.
  • B16F10 cells were dispensed in a 6-well plate at a concentration of 1 x 10 5 cells/well, and DMEM medium containing 10% FBS and 1% penicillin/streptomycin for 24 hours at 37°C and 5% CO 2 conditions. cultured in Then, the cells were treated with ⁇ -MSH 10 nM and sodium pyruvate or hydroquinone (HQ) at different concentrations as shown in Table 3 for 48 hours. After harvesting the cells, 100 ⁇ l of lysis buffer (lysis buffer, 1N NaOH, 10% DMSO) was added and reacted at 90° C. for 20 minutes, and then the amount of melanin was measured at 405 nm (EPOCH, Biotek). Table 3 shows the relative amount (%) of melanin compared to the negative control group as a negative control when sodium pyruvate and HQ were not treated.
  • lysis buffer lysis buffer, 1N NaOH, 10% DMSO
  • the inhibition rate (%) of melanin production in Table 3 was calculated by subtracting the amount of melanin production (%) from the negative control group (100) compared to the negative control group, and was calculated according to Equation 1 below.
  • Example 1 50 - 104.9 Comparative Example 1 - 2.5 87.3
  • Example 2 100 - 110.5 Comparative Example 2 - 5 59.8
  • Example 3 50 2.5 92
  • Example 4 100 2.5 97.1
  • the melanogenesis inhibition rate of HQ also increased from 53.7% when treated with HQ 2.5 ppm alone (Comparative Example 1) to 83.6% and 95.7% when treated with sodium pyruvate 50ppm and 100ppm (Examples 3 and 4), respectively. did. This is a higher efficacy than 67.1% when HQ 5ppm (Comparative Example 2) is treated alone, and it can be confirmed that there is a melanin production inhibitory effect as a very high synergistic effect because the cytotoxicity is also significantly lower. Accordingly, the composition according to one aspect of the present invention will exhibit remarkable skin whitening, melanogenesis inhibition or pigmentation inhibition effects.
  • the melanin content was measured by combining the cell viability and melanogenesis inhibition rate of sodium pyruvate and arbutin, which is a sugar derivative of hydroquinone, according to the same experimental method as in Experimental Example 2.
  • the inhibition rate (%) of melanin production in Table 5 is a value obtained by subtracting the amount of melanin production (%) from the negative control group (100) compared to the negative control group, and was calculated according to Equation 1 below.
  • Example 1 50 - 104.9 Comparative Example 3 - 50 98.2
  • Example 2 100 - 110.5 Comparative Example 4 - 100 87.9
  • Example 5 20 80 95
  • Example 6 50 98.7
  • Example 7 80 20 99.4
  • Example 1 50 - 74.4 25.6 Comparative Example 3 - 50 80.6 19.4 Example 2 100 - 65 35 Comparative Example 4 - 100 72.4 27.6
  • Example 5 20 80 68.3 31.7
  • Example 6 50 50 42.6 57.4
  • Example 7 80 20 55.1 44.9
  • Example 4 100ppm of sodium pyruvate and arbutin in B16F10 cells compared to the control showed cell viability of 110.5% (Example 2) and 87.9% (Comparative Example 4), respectively.
  • Example 5 when the weight ratio is 2:8, 95% (Example 5), 5:5, 98.7% (Example 6), and 8:2, 99.4% ( Example 7) showed the cell viability.

Abstract

The present invention relates to a whitening use of a composition that comprises: as active ingredients, sodium pyruvate, sodium pyruvate and hydroquinone, sodium pyruvate and arbutin, or sodium pyruvate, hydroquinone and arbutin. The whitening effect of sodium pyruvate was confirmed, and the disadvantages associated with skin safety, including apoptosis from hydroquinone and arbutin as compounds for skin whitening, can be overcome when applied together with sodium pyruvate, thereby providing an improved whitening effect. Therefore, the composition can be effectively used in cosmetics, medicines, external preparations, and the like.

Description

소듐 피루베이트를 유효성분으로 하는 미백 화장료 조성물Whitening cosmetic composition containing sodium pyruvate as an active ingredient
본 발명은 소듐 피루베이트를 유효성분으로 포함하는 미백용 화장료 조성물에 관한 것이다.The present invention relates to a cosmetic composition for whitening comprising sodium pyruvate as an active ingredient.
피부색은 멜라닌, 헤모글로빈(hemoglobin), 카로틴(carotene) 등에 의해 결정되는데 이중에서도 멜라닌이 가장 중요한 역할을 한다. 멜라닌은 사람의 피부색을 결정하는 것 이외에도 자외선 흡수 작용, 자유 라디칼 소거제(free radical scavenger) 등과 같은 피부 보호 작용을 수행한다. 그러나 자외선의 과다 노출, 대기 오염, 스트레스 등과 같은 외부의 환경 변화에 의하여 멜라닌이 과다하게 생성되면 피부 내에서 색소 침착 현상을 일으켜 피부의 흑화(melanism) 또는 기미, 주근깨 등의 원인이 된다. 피부의 흑화는 내적 및 외적 요인에 대한 피부 세포의 반응에 의하여 발생하는 것으로, 대표적인 요인은 자외선 노출로 인한 것이다. 즉, 피부가 자외선에 노출되면 티로시나아제(tyrosinase)가 활성화되는데, 상기 티로시나아제가 피부조직에 존재하는 티로신에 작용하여 도파(DOPA) 및 도파퀴논(dopaquinone)을 생성시키는 산화 과정에 의하여, 피부 색소 세포인 멜라노사이트(melanocyte) 내의 멜라노좀(melanosome)에서 멜라닌이라는 중합체가 합성되며, 이러한 멜라닌이 피부의 각질 형성 세포인 케라티노사이트(keratinocyte)로 전달되고 각질화 과정에 의해 피부 표면에 도달하여 자외선으로부터 피부를 보호하게 된다. 그러나 멜라닌이 국소적으로 과도하게 합성되거나, 피부 병변 및 노화에 따른 피부의 생리 기능이 떨어지게 되면, 멜라닌이 피부 표면에 침착되어 기미, 주근깨 및 다양한 색소 침착을 유발하게 된다. Skin color is determined by melanin, hemoglobin, carotene, etc. Among them, melanin plays the most important role. In addition to determining a person's skin color, melanin also performs skin protection functions such as UV absorption and free radical scavengers. However, when melanin is excessively generated by external environmental changes such as excessive exposure to ultraviolet rays, air pollution, stress, etc., it causes pigmentation in the skin, which causes skin blackening (melanism), blemishes, freckles, and the like. Blackening of the skin is caused by the reaction of skin cells to internal and external factors, and a representative factor is due to UV exposure. That is, when the skin is exposed to ultraviolet rays, tyrosinase is activated, and the tyrosinase acts on tyrosine present in the skin tissue to produce dopa (DOPA) and dopaquinone (dopaquinone) by an oxidation process, A polymer called melanin is synthesized from melanosomes in melanocytes, which are skin pigment cells, and this melanin is transferred to keratinocytes, which are keratinocytes of the skin, and reaches the skin surface through the keratinization process. It protects the skin from UV rays. However, when melanin is locally synthesized excessively or the physiological function of the skin is deteriorated due to skin lesions and aging, melanin is deposited on the skin surface, causing melasma, freckles and various pigmentation.
한편, 사람의 피부는 멜라노사이트 전구체 세포(melanoblasts)를 모낭 상피, 특히 팽윤부(bulge)에 저장하고 있다가(Nishimura et al, Science. 2005, 307(5710):720-4) 모낭 사이 표피(interfollicular epidermis) 기저층에서 멜라노사이트가 탈락되면 이 부분으로 멜라노사이트 전구체 세포가 이동하고, 이 때 자외선 뿐만 아니라 케라티노사이트(keratinocytes), 섬유아세포(fibroblasts) 또는 염증 세포와 같이 인접한 피부 세포(cutaneous cells) 간의 상호작용에 의해 멜라닌 합성(melanogenesis) 및 멜라닌 과립을 케라티노사이트로 이동시킬 때 필요한 수상 돌기의 신장(dendrite outgrowth)이 일어나며 최종 분화(terminal differentiation) 된다. 대표적으로 a-melanocyte-stimulating hormone (MSH)는 UV에 노출된 케라티노사이트에서 분비되는 멜라노사이트 분화 촉진 소재로서 멜라노사이트 전구체 세포의 증식을 촉진하며 멜라노사이트 내 M promoter of microphtalmia-associated transcription factor(Mitf)의 발현을 증가시킴으로써 타이로시나아제 등 색소 형성 기작을 일으키는 효소들의 발현을 높이며 멜라노좀(melanosome) 형성 및 수상 돌기 신장을 일으킨다. 이처럼 멜라노사이트의 분화와 관련된 분자 기전은 정교하게 조절되고 있다. On the other hand, in human skin, melanocyte precursor cells (melanoblasts) are stored in the hair follicle epithelium, especially in the bulge (Nishimura et al, Science. 2005, 307(5710):720-4), and the epidermis between the hair follicles ( When melanocytes are removed from the basal layer of the interfollicular epidermis, melanocyte precursor cells migrate to this area, and at this time, not only UV rays but also adjacent cutaneous cells such as keratinocytes, fibroblasts or inflammatory cells Interaction between melanin synthesis (melanogenesis) and dendrite outgrowth required to move melanin granules to keratinocytes occurs and final differentiation occurs. Typically, a-melanocyte-stimulating hormone (MSH) is a melanocyte differentiation-promoting material secreted from UV-exposed keratinocytes. It promotes the proliferation of melanocyte precursor cells and the M promoter of microphtalmia-associated transcription factor (Mitf) in melanocytes. ), increases the expression of enzymes that cause pigment formation mechanisms such as tyrosinase, and causes melanosome formation and dendrite elongation. As such, the molecular mechanisms involved in the differentiation of melanocytes are precisely regulated.
상기한 바와 같이 피부 흑화의 원인과 기작이 밝혀지면서, 미백 화장료 또는 색소 침착 개선 의료용 조성물의 제조에 있어 피부 흑화 과정에 관여하는 효소인 티로시나아제의 활성 저해 효과를 갖는 물질들을 배합하거나, 또는 멜라닌 생성 과정 중에서 일부 반응을 저해함으로써 멜라닌의 생성을 감소시키는 방법이 일반적으로 사용되고 있다. 이러한 목적을 위해 사용되고 있는 대표적인 물질로는 아스코르브산(ascorbic acid), 코직산(kojic acid), 하이드로퀴논(hydroquinone) 등의 화학 물질과 상백피 추출물, 감초 추출물 등의 식물 추출물이 있다. 하지만, 아스코르브산은 티로시나아제 활성 저해 효과가 부족할 뿐만 아니라 분자 자체의 안전성이 낮아서 멜라닌 생성 억제제로 적합하지 않으며, 코직산은 티로시나아제의 저해활성이 우수하지만, 화장료에 배합할 때 변색되고 경시 변화에 따라서 역가가 저하되는 등의 안전성에 문제가 있을 뿐만 아니라, 피부 자극이 커서 사용상 한계가 있고, 하이드로퀴논은 피부 자극 및 안전성 문제로 인하여 화장료에서의 사용이 제한되고 있으며 일반 의약품으로는 6% 미만을 함유하도록 제한하고 있다. As the cause and mechanism of skin blackening are revealed as described above, in the preparation of a whitening cosmetic or a pigmentation improvement medical composition, substances having an inhibitory effect on the activity of tyrosinase, an enzyme involved in the skin blackening process, are compounded, or melanin A method of reducing the production of melanin by inhibiting some reactions in the production process is generally used. Representative materials used for this purpose include chemical substances such as ascorbic acid, kojic acid, and hydroquinone, and plant extracts such as epiphyllum extract and licorice extract. However, ascorbic acid lacks tyrosinase activity inhibitory effect and is not suitable as a melanogenesis inhibitor due to low safety of the molecule itself, and kojic acid has excellent inhibitory activity of tyrosinase, Therefore, not only there is a problem in safety such as a decrease in potency, but there is a limitation in use due to large skin irritation, and hydroquinone is limited in use in cosmetics due to skin irritation and safety problems. restricted to contain.
이러한 배경 하에서, 안전성 및 안전성이 우수하며 효과적인 미백 성분의 개발에 대한 관심이 집중되고 있다.Under this background, attention is focused on the development of effective whitening ingredients with excellent safety and safety.
상기한 목적을 달성하기 위해, 예의 연구 노력한 결과, 소듐 피루베이트와 기존의 티로시나아제 활성 억제 화합물인 하이드로퀴논 혹은 알부틴을 저농도로 복합 적용할 시에 멜라닌 생성 억제 효능의 시너지가 있으며, 세포 사멸 억제 효과까지 보이는 것을 확인함으로써, 본 발명을 완성하게 되었다.In order to achieve the above object, as a result of intensive research efforts, there is a synergistic effect of inhibiting melanin production when sodium pyruvate and hydroquinone or arbutin, which are conventional tyrosinase activity inhibitory compounds, are combined at low concentrations, and apoptosis inhibition By confirming that even an effect is seen, this invention was completed.
본 발명의 목적은 피부 미백에 관한 효능 및 피부의 안전성에 문제가 없으면서, 우수한 멜라닌 생성 억제 효과를 갖는 미백용 화장료 조성물을 제공하는 것이다.It is an object of the present invention to provide a cosmetic composition for whitening that has an excellent melanin production inhibitory effect while not having problems with skin whitening efficacy and skin safety.
본 발명의 다른 목적은 소듐 피루베이트를 유효성분으로 포함하는 미백용 화장료 조성물; 색소 침착증 치료용 약학적 조성물; 색소 침착증 치료용 피부 외용제 조성물, 그리고 상기 조성물을 이용한 미백 방법, 색소 침착증 치료방법, 미백 화장료 제조를 위한 용도; 및 색소 침착증 치료제 제조를 위한 용도를 제공하는 것이다.Another object of the present invention is a cosmetic composition for whitening comprising sodium pyruvate as an active ingredient; pharmaceutical compositions for the treatment of pigmentation; A composition for external application for skin for the treatment of pigmentation, and a whitening method using the composition, a method for treating pigmentation, and use for manufacturing a whitening cosmetic; and to provide a use for the manufacture of a therapeutic agent for pigmentation.
본 발명의 또 다른 목적은 소듐 피루베이트와 하이드로퀴논; 소듐 피루베이트와 알부틴; 또는 소듐 피루베이트와 하이드로퀴논 및 알부틴을 포함하는 미백용 화장료 조성물; 색소 침착증 치료용 약학적 조성물; 또는 색소 침착증 치료용 피부 외용제 조성물; 그리고 상기 조성물을 이용한 미백 방법, 색소 침착증 치료방법, 미백 화장료 제조를 위한 용도; 및 색소 침착증 치료제 제조를 위한 용도를 제공하는 것이다.Another object of the present invention is sodium pyruvate and hydroquinone; sodium pyruvate and arbutin; Or a cosmetic composition for whitening comprising sodium pyruvate, hydroquinone and arbutin; pharmaceutical compositions for the treatment of pigmentation; Or a composition for external application to the skin for the treatment of pigmentation; And a whitening method using the composition, a method for treating hyperpigmentation, a use for manufacturing a whitening cosmetic; and to provide a use for the manufacture of a therapeutic agent for pigmentation.
상기 목적을 달성하기 위하여, 소듐 피루베이트를 유효성분으로 포함하는 미백용 화장료 조성물을 제공한다.In order to achieve the above object, there is provided a cosmetic composition for whitening comprising sodium pyruvate as an active ingredient.
또한, 하이드로퀴논 및 알부틴으로 이루어진 군에서 선택되는 하나 이상을 더 포함하는, 미백용 화장료 조성물을 제공한다.In addition, it provides a cosmetic composition for whitening, further comprising one or more selected from the group consisting of hydroquinone and arbutin.
본 발명에서의 화장료 조성물은 화장수, 에센스, 로션, 크림, 팩, 젤, 파우더, 파운데이션 또는 세정제의 제형일 수 있다.The cosmetic composition in the present invention may be in the form of a lotion, essence, lotion, cream, pack, gel, powder, foundation or detergent.
상기 목적을 달성하기 위하여, 소듐 피루베이트를 유효성분으로 포함하는 색소 침착증 치료용 약학적 조성물을 제공한다.In order to achieve the above object, there is provided a pharmaceutical composition for treating hyperpigmentation comprising sodium pyruvate as an active ingredient.
또한, 하이드로퀴논 및 알부틴으로 이루어진 군에서 선택되는 하나 이상을 더 포함하는, 색소 침착증 치료용 약학적 조성물을 제공한다.In addition, it provides a pharmaceutical composition for the treatment of pigmentation, further comprising one or more selected from the group consisting of hydroquinone and arbutin.
상기 목적을 달성하기 위하여, 소듐 피루베이트를 유효성분으로 포함하는 색소 침착증 치료용 피부 외용제 조성물을 제공한다.In order to achieve the above object, there is provided a composition for external application for skin for the treatment of pigmentation comprising sodium pyruvate as an active ingredient.
또한, 하이드로퀴논 및 알부틴으로 이루어진 군에서 선택되는 하나 이상을 더 포함하는, 색소 침착증 치료용 피부 외용제 조성물을 제공한다.In addition, it provides a composition for external application to the skin for the treatment of pigmentation, further comprising one or more selected from the group consisting of hydroquinone and arbutin.
본 발명에서의 피부 외용제 조성물은 연고, 패취, 겔, 크림 또는 분무제의 제형일 수 있다.The composition for external application for skin in the present invention may be in the form of an ointment, patch, gel, cream or spray.
상기 목적을 달성하기 위하여, 소듐 피루베이트를 유효성분으로 포함하는 조성물을 피부에 처리하는 단계를 포함하는, 미백 방법을 제공한다.In order to achieve the above object, there is provided a whitening method comprising the step of treating the skin with a composition comprising sodium pyruvate as an active ingredient.
상기 목적을 달성하기 위하여, 소듐 피루베이트를 유효성분으로 포함하는 조성물을 피부에 처리하는 단계를 포함하는, 색소 침착증 치료방법을 제공한다.In order to achieve the above object, there is provided a method for treating pigmentation, comprising the step of treating the skin with a composition comprising sodium pyruvate as an active ingredient.
상기 조성물은 하이드로퀴논 및 알부틴으로 이루어진 군에서 선택되는 하나 이상을 더 포함할 수 있다.The composition may further include one or more selected from the group consisting of hydroquinone and arbutin.
상기 목적을 달성하기 위하여, 미백 화장료를 제조하기 위한 소듐 피루베이트를 포함하는 조성물의 용도를 제공한다.In order to achieve the above object, there is provided the use of a composition comprising sodium pyruvate for preparing a whitening cosmetic.
상기 목적을 달성하기 위하여, 색소 침착증 치료제를 제조하기 위한 소듐 피루베이트를 포함하는 조성물의 용도를 제공한다.In order to achieve the above object, there is provided the use of a composition comprising sodium pyruvate for the preparation of a therapeutic agent for pigmentation.
상기 목적을 달성하기 위하여, 색소 침착증 치료용 외용제를 제조하기 위한 소듐 피루베이트를 포함하는 조성물의 용도를 제공한다.In order to achieve the above object, there is provided the use of a composition comprising sodium pyruvate for preparing an external preparation for the treatment of pigmentation.
상기 조성물은 하이드로퀴논 및 알부틴으로 이루어진 군에서 선택되는 하나 이상을 더 포함할 수 있다. The composition may further include one or more selected from the group consisting of hydroquinone and arbutin.
본 발명의 미백용 화장료 조성물, 색소 침착증 치료용 약학적 조성물 및 색소 침착증 치료용 피부 외용제 조성물은, 기존의 티로시나아제 활성 억제 화합물의 단점인 안전성 및 세포사멸 단점을 극복할 수 있다.The cosmetic composition for whitening, the pharmaceutical composition for the treatment of pigmentation, and the composition for external application to the skin for the treatment of pigmentation of the present invention can overcome the disadvantages of safety and apoptosis, which are disadvantages of conventional tyrosinase activity inhibitory compounds.
소듐 피루베이트; 또는 소듐 피루베이트와 하이드로퀴논; 또는 소듐 피루베이트와 알부틴; 또는 소듐 피루베이트와 하이드로퀴논 및 알부틴을 유효성분을 포함하는 조성물은 멜라노사이트의 분화 억제 효능을 가지며, 멜라닌 합성 저해 효능을 지니고 있고, 하이드로퀴논과 알부틴의 세포사멸 및 피부안전성 문제를 소듐 피루베이트와 함께 사용할 시 극복이 가능함을 확인하였다. 이에 따라 향상된 미백 효과를 제공할 수 있어, 본 발명의 조성물은 화장품, 의약, 외용제 등에 효과적으로 활용될 수 있다.sodium pyruvate; or sodium pyruvate and hydroquinone; or sodium pyruvate and arbutin; Alternatively, a composition comprising sodium pyruvate, hydroquinone, and arbutin as an active ingredient has the effect of inhibiting the differentiation of melanocytes, has the effect of inhibiting melanin synthesis, and reduces the apoptosis and skin safety problems of hydroquinone and arbutin with sodium pyruvate. It was confirmed that it was possible to overcome when used together. Accordingly, an improved whitening effect can be provided, and the composition of the present invention can be effectively used in cosmetics, medicines, external preparations, and the like.
도 1은 소듐 피루베이트의 B16F10 세포 내 수상 돌기 신장 억제 효능 결과이다.1 is a result of the inhibitory effect of sodium pyruvate on dendrite elongation in B16F10 cells.
이하 본 발명을 상세하게 설명한다.Hereinafter, the present invention will be described in detail.
하나의 양태로서, 본 발명은 소듐 피루베이트를 유효성분으로 포함하는 미백용 화장료 조성물을 제공한다.In one aspect, the present invention provides a cosmetic composition for whitening comprising sodium pyruvate as an active ingredient.
다른 양태로서, 하이드로퀴논 및 알부틴으로 이루어진 군에서 선택되는 하나 이상을 더 포함하는, 미백용 화장료 조성물을 제공한다.In another aspect, it provides a cosmetic composition for whitening, further comprising one or more selected from the group consisting of hydroquinone and arbutin.
다른 양태로서, 소듐 피루베이트를 유효성분으로 포함하는 색소 침착증 치료용 약학적 조성물을 제공한다.In another aspect, there is provided a pharmaceutical composition for the treatment of pigmentation disorder comprising sodium pyruvate as an active ingredient.
다른 양태로서, 하이드로퀴논 및 알부틴으로 이루어진 군에서 선택되는 하나 이상을 더 포함하는, 색소 침착증 치료용 약학적 조성물을 제공한다.In another aspect, it provides a pharmaceutical composition for the treatment of pigmentation, further comprising one or more selected from the group consisting of hydroquinone and arbutin.
다른 양태로서, 소듐 피루베이트를 유효성분으로 포함하는 색소 침착증 치료용 피부 외용제 조성물을 제공한다.In another aspect, there is provided a composition for external application to the skin for the treatment of pigmentation comprising sodium pyruvate as an active ingredient.
다른 양태로서, 하이드로퀴논 및 알부틴으로 이루어진 군에서 선택되는 하나 이상을 더 포함하는, 색소 침착증 치료용 피부 외용제 조성물을 제공한다.In another aspect, there is provided a composition for external application for skin for the treatment of pigmentation, further comprising one or more selected from the group consisting of hydroquinone and arbutin.
다른 양태로서, 소듐 피루베이트를 유효성분으로 포함하는 조성물을 이용한 미백 방법, 색소 침착증 치료방법, 미백 화장료 제조를 위한 용도; 및 색소 침착증 치료제 제조를 위한 용도를 제공한다.In another aspect, a whitening method using a composition comprising sodium pyruvate as an active ingredient, a method for treating pigmentation, use for preparing a whitening cosmetic; and for the manufacture of a therapeutic agent for pigmentation.
다른 양태로서, 소듐 피루베이트와 하이드로퀴논; 소듐 피루베이트와 알부틴; 또는 소듐 피루베이트와 하이드로퀴논 및 알부틴을 포함하는 조성물을 이용한 미백 방법, 색소 침착증 치료방법, 미백 화장료 제조를 위한 용도; 및 색소 침착증 치료제 제조를 위한 용도를 제공한다.In another aspect, sodium pyruvate and hydroquinone; sodium pyruvate and arbutin; or a whitening method using a composition comprising sodium pyruvate, hydroquinone, and arbutin, a method for treating pigmentation disorders, and use for preparing a whitening cosmetic; and for the manufacture of a therapeutic agent for pigmentation.
다른 양태로서, 소듐 피루베이트를 유효성분으로 포함하는 조성물을 피부에 처리하는 단계를 포함하는, 미백 방법을 제공한다.In another aspect, there is provided a whitening method comprising the step of treating the skin with a composition comprising sodium pyruvate as an active ingredient.
다른 양태로서, 소듐 피루베이트를 유효성분으로 포함하는 조성물을 피부에 처리하는 단계를 포함하는, 색소 침착증 치료방법을 제공한다.In another aspect, there is provided a method for treating pigmentation, comprising the step of treating the skin with a composition comprising sodium pyruvate as an active ingredient.
상기 조성물은 하이드로퀴논 및 알부틴으로 이루어진 군에서 선택되는 하나 이상을 더 포함할 수 있다.The composition may further include one or more selected from the group consisting of hydroquinone and arbutin.
다른 양태로서, 미백 화장료를 제조하기 위한 소듐 피루베이트를 포함하는 조성물의 용도를 제공한다.In another aspect, there is provided the use of a composition comprising sodium pyruvate for preparing a whitening cosmetic.
다른 양태로서, 색소 침착증 치료제를 제조하기 위한 소듐 피루베이트를 포함하는 조성물의 용도를 제공한다.In another aspect, there is provided the use of a composition comprising sodium pyruvate for the manufacture of a therapeutic agent for pigmentation.
다른 양태로서, 색소 침착증 치료용 외용제를 제조하기 위한 소듐 피루베이트를 포함하는 조성물의 용도를 제공한다.In another aspect, there is provided the use of a composition comprising sodium pyruvate for preparing an external preparation for the treatment of pigmentation.
상기 조성물은 하이드로퀴논 및 알부틴으로 이루어진 군에서 선택되는 하나 이상을 더 포함할 수 있다. The composition may further include one or more selected from the group consisting of hydroquinone and arbutin.
본 발명의 "소듐 피루베이트(sodium pyruvate)"는 하기 [화학식 1]로 표현되며 a-keto acid 중 하나인 피루브산(pyruvic acid)의 다른 염 형태이다."Sodium pyruvate" of the present invention is represented by the following [Formula 1] and is another salt form of pyruvic acid, which is one of a-keto acids.
[화학식 1][Formula 1]
Figure PCTKR2021004377-appb-img-000001
Figure PCTKR2021004377-appb-img-000001
피루베이트는 많은 대사 경로에서 중간체이기 때문에, 소듐 피루베이트는 세포 배양과 관련된 많은 실험에서 더 많은 에너지를 제공 하는데 널리 사용되고 있다. 기존 연구에 의하면 피루브산은 기미(melasma), 검버섯(solar lentigine), 여드름(acne), 사마귀(wart)를 억제하는 것뿐 만 아니라 콜라겐(collagen) 합성을 촉진하며, 피부 탄력을 증진 시키나 이는 피루브산 고농도 (50~100%)에서 화학적 박리에 기인한 효능이기 때문에 피루브산 사용 중 따갑거나 열감을 느낄 수 있으며 과도한 각질 박리 혹은 염증성 수포가 동반될 수 있다. 화학적 박리가 일어나지 않는 저농도에서의 인체 효능은 알려진 바 없다. 최근 연구 결과에 의하면 0.055%의 피루브산을 세포에 처리 시 멜라닌 합성 억제 효능이 있음을 in vitro 실험을 통해 확인하였으나, 소듐 피루베이트의 멜라닌 합성 억제 효능은 없다고 보고되었다.Because pyruvate is an intermediate in many metabolic pathways, sodium pyruvate is widely used to provide more energy in many experiments involving cell culture. According to previous studies, pyruvic acid not only suppresses melasma, solar lentigine, acne, and warts, but also promotes collagen synthesis and improves skin elasticity. (50~100%), since it is an effect due to chemical exfoliation, you may feel a stinging or burning sensation while using pyruvic acid, and excessive exfoliation of dead skin cells or inflammatory blisters may be accompanied. The human efficacy at low concentrations in which chemical exfoliation does not occur is unknown. According to the results of a recent study, it was confirmed through an in vitro experiment that when 0.055% pyruvic acid was treated in cells, it had the effect of inhibiting melanin synthesis, but it was reported that sodium pyruvate had no effect on inhibiting melanin synthesis.
본 발명의 "하이드로퀴논(Hydroquinone, HQ)"은 [화학식 2]로 표현되며, 벤젠-1,4-디올 혹은 퀴놀로도 알려져 있다. 페놀의 일종인 방향족 유기 화합물이다."Hydroquinone (HQ)" of the present invention is represented by [Formula 2], also known as benzene-1,4-diol or quinol. It is an aromatic organic compound that is a type of phenol.
[화학식 2][Formula 2]
Figure PCTKR2021004377-appb-img-000002
Figure PCTKR2021004377-appb-img-000002
하이드로퀴논은 피부 미백에 국소 적용으로 사용되나 고농도로 사용할 시에 피부에 자극을 줄 수 있어 사용이 제한되고 있는 실정이다. Hydroquinone is used for topical application for skin whitening, but its use is limited because it can irritate the skin when used in high concentrations.
본 발명의 "알부틴(Arbutin)"은 [화학식 3]으로 표현된다. 글루코사이드의 일종으로 진달래과 Arctostaphylos 속의 베어베리(bearberry)에서 추출한 글리코실레이티드 하이드로퀴논이다."Arbutin" of the present invention is represented by [Formula 3]. As a type of glucoside, it is a glycosylated hydroquinone extracted from bearberry of the genus Arctostaphylos of the Azalea family.
[화학식 3][Formula 3]
Figure PCTKR2021004377-appb-img-000003
Figure PCTKR2021004377-appb-img-000003
알부틴은 피부 미백 치료에 사용되고 있으나, 하이드로퀴논과 마찬가지로 알부틴도 고농도로 사용할 시에 피부에 자극을 줄 수 있어 각별한 주의가 필요하다.Arbutin is used for skin whitening treatment, but like hydroquinone, arbutin can irritate the skin when used in high concentrations, so special attention is required.
본 발명에서 하이드로퀴논 및 알부틴을 피부에 적용할 시 문제되는 세포독성 또는 피부세포사멸 등의 안전성에 대한 문제점을 소듐 피루베이트와 함께 적용하여 극복하였다. 특히, 소듐 피루베이트와 하이드로퀴논 및/또는 알부틴을 함께 사용하는 경우, 성분 간의 시너지 효과에 의하여 낮은 농도에서도 충분한 멜라닌 색소 합성 저해 효과를 제공할 수 있다. In the present invention, when hydroquinone and arbutin are applied to the skin, safety problems such as cytotoxicity or skin cell death, which are problematic, are overcome by applying together with sodium pyruvate. In particular, when sodium pyruvate and hydroquinone and/or arbutin are used together, it is possible to provide sufficient melanin synthesis inhibitory effect even at a low concentration due to the synergistic effect between the components.
본 발명의 "피부 미백 효과"는 멜라닌 색소의 합성 저해 및 멜라노사이트 분화를 억제함으로써 피부 톤을 밝게 할 뿐만 아니라, 피부 톤이나 안색의 균일, 자외선, 호르몬 또는 유전에 기인한 기미, 염증 후 과색소 침착, 피부 노화로 인한 색소 침착 변화, 검버섯 또는 갈색 반점, 주근깨, 및 과색소 침착 등을 개선하는 것을 말하나 이에 제한되는 것은 아니다.The "skin whitening effect" of the present invention not only brightens the skin tone by inhibiting the synthesis of melanin pigment and the differentiation of melanocytes, but also makes the skin tone or complexion uniform, UV rays, hormonal or genetic blemishes, hyperpigmentation after inflammation It refers to, but is not limited to, improving pigmentation, changes in pigmentation due to skin aging, age spots or brown spots, freckles, and hyperpigmentation.
상기 소듐 피루베이트, 소듐 피루베이트와 하이드로퀴논 또는 소듐 피루베이트와 알부틴을 화장품으로 사용하는 경우, 상기 화합물 및 혼합물들을 유효성분으로 함유하여 제조되는 화장품은 일반적인 유화 제형 또는 가용화 제형의 형태로 제조할 수 있다. 예컨대, 유연 화장수 또는 영양 화장수 등과 같은 화장수; 훼이셜 로션 또는 바디로션 등과 같은 유액, 영양 크림, 수분 크림 또는 아이 크림 등과 같은 크림, 에센스, 화장연고, 스프레이, 젤, 팩, 선 스크린, 메이크업 베이스, 액체 타입, 고체 타입 또는 스프레이 타입 등의 파운데이션, 파우더, 클렌징 크림, 클렌징 로션, 클렌징 오일과 같은 메이크업 제거제, 클렌징 폼, 비누, 바디 워시 등과 같은 세정제 등의 제형을 가질 수 있다. When the sodium pyruvate, sodium pyruvate and hydroquinone or sodium pyruvate and arbutin are used as cosmetics, cosmetics prepared by containing the compounds and mixtures as active ingredients can be prepared in the form of general emulsified formulations or solubilized formulations. have. For example, a lotion such as a softening lotion or a nourishing lotion; Emulsion such as facial lotion or body lotion, cream such as nourishing cream, moisture cream or eye cream, essence, cosmetic ointment, spray, gel, pack, sunscreen, makeup base, liquid type, solid type or spray type foundation; Powders, cleansing creams, cleansing lotions, make-up removers such as cleansing oils, cleansing foams, soaps, body washes, and the like may have formulations.
또한 본 발명의 조성물은 지방 물질, 유기 용매, 용해제, 농축제, 겔화제, 연화제, 항산화제, 현탁화제, 안정화제, 발포제(foaming agent), 방향제, 계면활성제, 물, 이온형 유화제, 비이온형 유화제, 충전제, 금속이온봉쇄제, 킬레이트화제, 보존제, 비타민, 차단제, 습윤화제, 필수 오일, 염료, 안료, 친수성 활성제, 친유성 활성제 또는 지질 소낭 등 화장품 분야에서 통상적으로 사용되는 보조제를 추가로 함유할 수 있다.In addition, the composition of the present invention comprises a fatty substance, an organic solvent, a solubilizer, a thickening agent, a gelling agent, an emollient, an antioxidant, a suspending agent, a stabilizer, a foaming agent, a fragrance, a surfactant, water, an ionic emulsifier, a nonionic Additional additives commonly used in the cosmetic field, such as emulsifiers, fillers, sequestering agents, chelating agents, preservatives, vitamins, blocking agents, wetting agents, essential oils, dyes, pigments, hydrophilic active agents, lipophilic active agents or lipid vesicles may contain.
상기 조성물은 소듐 피루베이트를 전체 조성물 중량에 대하여 0.001 내지 5%(w/w)로 포함할 수 있다. 본 발명의 조성물이 소듐 피루베이트를 0.001%(w/w) 미만으로 포함할 경우에는 충분한 피부 미백 효과를 기대할 수 없다.The composition may include sodium pyruvate in an amount of 0.001 to 5% (w/w) based on the total weight of the composition. When the composition of the present invention contains less than 0.001% (w/w) of sodium pyruvate, a sufficient skin whitening effect cannot be expected.
상기 소듐 피루베이트는 전체 조성물 중량에 대하여 바람직하게는 0.005 내지 4%(w/w), 보다 바람직하게는 0.01 내지 2%(w/w), 제일 바람직하게는 0.05 내지 1%(w/w)로 포함할 수 있다. The sodium pyruvate is preferably 0.005 to 4% (w/w), more preferably 0.01 to 2% (w/w), and most preferably 0.05 to 1% (w/w) based on the total weight of the composition. can be included as
상기 조성물은 하이드로퀴논을 전체 조성물 중량에 대하여 0.001 내지 6%(w/w)로 포함할 수 있다. 본 발명의 조성물이 하이드로퀴논을 0.001%(w/w) 미만으로 포함할 경우에는 충분한 피부 미백 효과를 기대할 수 없고, 6%(w/w)를 초과하여 포함할 경우에는 알러지 등 원치 않는 반응이 발생하거나 피부 안전성에 문제가 있을 수 있다.The composition may include hydroquinone in an amount of 0.001 to 6% (w/w) based on the total weight of the composition. When the composition of the present invention contains less than 0.001% (w/w) of hydroquinone, a sufficient skin whitening effect cannot be expected, and when it contains more than 6% (w/w), unwanted reactions such as allergies may occur. It may occur or there may be problems with skin safety.
상기 하이드로퀴논은 전체 조성물 중량에 대하여 0.005 내지 6%(w/w), 0.01 내지 5%(w/w), 0.05 내지 4%(w/w), 또는 0.1 내지 2%(w/w)로 포함할 수 있다. The hydroquinone is 0.005 to 6% (w / w), 0.01 to 5% (w / w), 0.05 to 4% (w / w), or 0.1 to 2% (w / w) based on the total weight of the composition. may include
상기 조성물은 알부틴을 전체 조성물 중량에 대하여 0.001 내지 10%(w/w)로 포함할 수 있다. 본 발명의 조성물이 알부틴을 0.001%(w/w) 미만으로 포함할 경우에는 충분한 피부 미백 효과를 기대할 수 없고, 5%(w/w)를 초과하여 포함할 경우에는 알러지 등 원치 않는 반응이 발생하거나 피부 안전성에 문제가 있을 수 있다.The composition may include arbutin in an amount of 0.001 to 10% (w/w) based on the total weight of the composition. When the composition of the present invention contains less than 0.001% (w/w) of arbutin, a sufficient skin whitening effect cannot be expected, and when it contains more than 5% (w/w), unwanted reactions such as allergies occur. Or there may be a problem with skin safety.
상기 알부틴은 전체 조성물 중량에 대하여 0.005 내지 10%(w/w), 0.01 내지 6%(w/w), 0.05 내지 5%(w/w), 또는 0.1 내지 2%(w/w)로 포함할 수 있다. The arbutin is included in 0.005 to 10% (w/w), 0.01 to 6% (w/w), 0.05 to 5% (w/w), or 0.1 to 2% (w/w) by weight of the total composition can do.
상기 조성물은 유효성분인 소듐 피루베이트와 하이드로퀴논; 혹은 소듐 피루베이트와 알부틴; 혹은 소듐 피루베이트와 하이드로퀴논 및 알부틴을 전체 조성물 중량에 대하여 0.002 내지 10%(w/w), 0.005 내지 6%(w/w), 0.01 내지 5%(w/w), 0.05 내지 4%(w/w), 또는 0.1 내지 3%(w/w)로 포함할 수 있다. 상기 본 발명의 유효성분을 0.002%(w/w) 미만으로 포함할 경우에는 충분한 피부 미백 효과를 기대할 수 없고, 10%(w/w)를 초과하여 포함할 경우에는 알러지 등 원치 않는 반응이 발생하거나 피부 안전성에 문제가 있을 수 있다.The composition includes active ingredients sodium pyruvate and hydroquinone; or sodium pyruvate and arbutin; Or sodium pyruvate, hydroquinone and arbutin based on the total weight of the composition 0.002 to 10% (w / w), 0.005 to 6% (w / w), 0.01 to 5% (w / w), 0.05 to 4% ( w/w), or 0.1 to 3% (w/w). When the active ingredient of the present invention is included in less than 0.002% (w/w), a sufficient skin whitening effect cannot be expected, and when it contains more than 10% (w/w), unwanted reactions such as allergies occur. Or there may be a problem with skin safety.
본 발명의 '약학적 조성물'은 경구 또는 비경구로 투여할 수 있으며, 상기 소듐 피루베이트, 소듐 피루베이트와 하이드로퀴논 또는 소듐 피루베이트와 알부틴을 약학적 조성물로 사용하는 경우, 일반 의약품 제제의 형태, 예를 들어, 임상 투여 시 경구 및 비경구의 여러 가지 제형으로 투여될 수 있는데, 제제화할 경우에는 보통 사용하는 충진제, 증량제, 결합제, 습윤제, 붕해제, 계면활성제 등의 희석제 또는 부형제를 사용하여 조제될 수 있으나 이에 제한되지 않는다.The 'pharmaceutical composition' of the present invention can be administered orally or parenterally, and when sodium pyruvate, sodium pyruvate and hydroquinone or sodium pyruvate and arbutin are used as pharmaceutical compositions, the form of a generic pharmaceutical preparation, For example, it can be administered in various oral and parenteral dosage forms during clinical administration. When formulated, it can be prepared using diluents or excipients such as commonly used fillers, extenders, binders, wetting agents, disintegrants, surfactants, etc. can, but is not limited thereto.
경구투여를 위한 고형제제에는 정제, 환제, 산제, 과립제, 캡슐제 등이 포함되며, 이러한 고형제제는 본 발명의 약학적 조성물에 적어도 하나 이상의 부형제 예를 들면, 전분, 칼슘카보네이트(Calcium carbonate), 수크로스(Sucrose) 또는 락토오스(Lactose), 젤라틴 등을 섞어 조제될 수 있으나 이에 제한되지 않는다.Solid preparations for oral administration include tablets, pills, powders, granules, capsules, etc., and these solid preparations include at least one excipient in the pharmaceutical composition of the present invention, for example, starch, calcium carbonate, It may be prepared by mixing sucrose or lactose, gelatin, etc., but is not limited thereto.
단순한 부형제 이외에 마그네슘 스티레이트 탈크 같은 윤활제들도 사용된다. 경구를 위한 액상 제제로는 현탁제, 내용액제, 유제, 시럽제 등이 해당되는데 흔히 사용되는 단순희석제인 물, 리퀴드 파라핀 이외에 여러가지 부형제, 예를 들면 습윤제, 감미제, 방향제, 보존제 등이 포함될 수 있으나 이에 제한되지 않는다.In addition to simple excipients, lubricants such as magnesium stearate talc are also used. Liquid formulations for oral use include suspensions, solutions, emulsions, syrups, etc. In addition to water and liquid paraffin, which are commonly used simple diluents, various excipients such as wetting agents, sweeteners, fragrances, preservatives, etc. may be included. not limited
본 발명의 '피부 외용제 조성물'은 피부 외용제로 사용될 수 있으나 이에 제한되는 것은 아니다. 상기 소듐 피루베이트, 소듐 피루베이트와 하이드로퀴논 및 소듐 피루베이트와 알부틴을 피부 외용제로 사용하는 경우, 추가로 지방 물질, 유기 용매, 용해제, 농축제 및 겔화제, 연화제, 항산화제, 현탁화제, 안정화제, 발포제(foaming agent), 방향제, 계면활성제, 물, 이온형 또는 비이온형 유화제, 충전제, 금속이온봉쇄제 및 킬레이트화제, 보존제, 비타민, 차단제, 습윤화제, 필수 오일, 염료, 안료, 친수성 또는 친유성 활성제, 지질 소낭 또는 피부용 외용제에 통상적으로 사용되는 임의의 다른 성분과 같은 피부 과학 분야에서 통상적으로 사용되는 보조제를 함유할 수 있다. 또한 상기 성분들은 피부 과학 분야에서 일반적으로 사용되는 양으로 도입될 수 있다. 피부 외용제 제형으로 제공될 경우, 이에 제한되는 것은 아니나, 연고, 패취, 겔, 크림 또는 분무제와 같은 제형을 가질 수 있다.The 'composition for external application to the skin' of the present invention may be used as an external preparation for skin, but is not limited thereto. When sodium pyruvate, sodium pyruvate and hydroquinone, and sodium pyruvate and arbutin are used as external preparations for skin, fat substances, organic solvents, solubilizers, thickening and gelling agents, emollients, antioxidants, suspending agents, and stabilizing agents are additionally used. Agents, foaming agents, fragrances, surfactants, water, ionic or nonionic emulsifiers, fillers, sequestering and chelating agents, preservatives, vitamins, blocking agents, wetting agents, essential oils, dyes, pigments, hydrophilicity 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 external preparations for skin. In addition, the ingredients may be introduced in an amount generally used in the field of dermatology. When provided as an external preparation for skin, it may have a formulation such as, but not limited to, an ointment, a patch, a gel, a cream, or a spray.
본 발명에 따른 조성물에 포함되는 상기 언급된 성분들 각각은 바람직하게는 각 국 정부에 의해 규정된 규범에 명시된 최대 사용량을 초과하지 않는 범위 내에서 본 발명의 조성물에 포함될 수 있다. 예를 들어, 약학 조성물을 제공하는 경우, 대한민국, 미국, 유럽, 독일, 일본, 중국 등에서 규정하는 약전(Pharmacopoeia) 또는 의약품집에 명시된 제법, 성상, 사용량 등의 범위 내에서 본 발명에 포함될 수 있다. 또한, 화장료 조성물을 제공하는 경우 각 국 정부에서 규정하는 화장품 안전에 관한 법률 또는 중국 정부에서 규정하는 《화장품 안전 기술 사양》, 에 명시된 최대 사용량을 초과하지 않는 범위 내에서 본 발명의 화장료 조성물에 포함될 수 있다. Each of the above-mentioned components included in the composition according to the present invention may preferably be included in the composition of the present invention within a range not exceeding the maximum amount specified in the norms stipulated by the respective national governments. For example, in the case of providing a pharmaceutical composition, it may be included in the present invention within the scope of the manufacturing method, properties, amount of use, etc. specified in the Pharmacopoeia or drug collection prescribed in Korea, the United States, Europe, Germany, Japan, China, etc. . In addition, in the case of providing a cosmetic composition, the cosmetic composition of the present invention may be included in the cosmetic composition of the present invention to the extent that it does not exceed the maximum amount specified in the Cosmetic Safety Act stipulated by each country or the “Cosmetic Safety Technical Specification” stipulated by the Chinese government. can
이하, 본 발명을 하기 실험예에 의해 상세히 설명한다. 단, 하기 실험예는 본 발명을 예시하는 것일 뿐, 본 발명의 내용이 하기 실험예에 의해 제한되는 것은 아니다. 또한, 이들 실험예는 본 발명에 대한 이해를 돕기 위한 목적일 뿐이므로, 어떤 의미로든 본 발명의 범위가 이들에 의해 제한되는 것은 아니다.Hereinafter, the present invention will be described in detail by the following experimental examples. However, the following experimental examples are merely illustrative of the present invention, and the content of the present invention is not limited by the following experimental examples. In addition, since these experimental examples are only for the purpose of helping the understanding of the present invention, the scope of the present invention is not limited thereto in any sense.
실험예 1: 소듐 피루베이트에 의한 멜라노사이트 분화 억제 여부 확인Experimental Example 1: Confirmation of inhibition of melanocyte differentiation by sodium pyruvate
소듐 피루베이트에 의해 멜라노사이트의 수상 돌기 신장이 억제 되는지 확인하기 위해, 먼저 6well plate에 B16F10 세포 (ATCC, 카탈로그넘버 CRL-6475)를 1 x 10 5 cells/well 농도로 분주하고 24시간 동안 배양하였다. 멜라닌 합성 촉진 모델을 만들기 위해서, 배양 후 대조군 세포에 α-MSH (α-Melanocytes Stimulating Hormone) 10nM를 처리했고, 실험군은 세포에 α-MSH 10nM와 소듐 피루베이트 10mM를 함께 처리했다. 대조군과 실험군 모두 48시간 후에 수상 돌기의 길이를 현미경 (EVOS FL auto 2, Termo Fisher Scientific)으로 측정하였다.In order to check whether the dendrite elongation of melanocytes is inhibited by sodium pyruvate, B16F10 cells (ATCC, catalog number CRL-6475) were first aliquoted in a 6-well plate at a concentration of 1 x 10 5 cells/well and cultured for 24 hours. . To create a model for promoting melanin synthesis, 10 nM of α-MSH (α-Melanocytes Stimulating Hormone) was treated in the control cells after culture, and the experimental group was treated with 10 nM of α-MSH and 10 mM sodium pyruvate in the cells. After 48 hours in both control and experimental groups, the length of dendrites was measured under a microscope (EVOS FL auto 2, Termo Fisher Scientific).
첨가 화합물additive compound 수상돌기의 길이 (μm)Length of dendrites (μm)
소듐 피루베이트sodium pyruvate 25.7 ± 16.525.7 ± 16.5
대조군(α-MSH 처리군)Control group (α-MSH treatment group) 69.8 ± 29.569.8 ± 29.5
그 결과, 표 1 및 도 1에 개시된 바와 같이 대조군에서는 분화 인자에 의해 수상 돌기가 평균 69.8 μm로 신장되어 있지만, 소듐 피루베이트를 처리한 군에서의 수상 돌기는 평균 25.6 μm로 신장이 억제되어 있는 것을 알 수 있다. 멜라노사이트 수상 돌기 신장 억제를 통해서 본 발명 소듐 피루베이트가 멜라닌 합성 및 분비를 억제시킬 수 있음을 알 수 있다. As a result, as shown in Table 1 and Figure 1, in the control group, dendrites were elongated to an average of 69.8 μm by the differentiation factor, but in the group treated with sodium pyruvate, the elongation was inhibited to an average of 25.6 μm. it can be seen that It can be seen that the sodium pyruvate of the present invention can inhibit melanin synthesis and secretion by inhibiting melanocyte dendrite elongation.
실험예 2: 소듐 피루베이트와 하이드로퀴논의 시너지 효능Experimental Example 2: Synergistic effect of sodium pyruvate and hydroquinone
B16F10 세포를 96-well plate에 2 x 10 3 cells/well 농도로 분주 하고 37℃, 5% CO 2 조건에서 24시간 동안 10% FBS, 1% penicillin/streptomycin을 함유한 DMEM 배지에서 배양했다.이어 표 2에서처럼 소듐 피루베이트 또는 하이드로퀴논(HQ)을 농도 별로 48시간 동안 처리한 후, CCK-8 assay 로 세포독성검사를 실시하여 그 결과를 표 2에 나타내었다. 음성대조군은 소듐 피루베이트와 HQ를 모두 처리하지 않은 조건이며, 소듐 피루베이트나 하이드로퀴논(HQ)을 처리한 실험군의 세포 생존율은 음성대조군 대비 %로 계산하여, 표 2에 나타내었다. B16F10 cells were aliquoted in a 96-well plate at a concentration of 2 x 10 3 cells/well and cultured in DMEM medium containing 10% FBS and 1% penicillin/streptomycin for 24 hours at 37°C and 5% CO 2 condition. As shown in Table 2, sodium pyruvate or hydroquinone (HQ) was treated for 48 hours at each concentration, and then cytotoxicity was tested by CCK-8 assay, and the results are shown in Table 2. The negative control group was a condition in which neither sodium pyruvate nor HQ was treated, and the cell viability of the experimental group treated with sodium pyruvate or hydroquinone (HQ) was calculated as a percentage compared to the negative control group, and is shown in Table 2.
멜라닌 함량 측정을 위해, 먼저 6well plate에 B16F10 세포를 1 x 10 5 cells/well 농도로 분주하고 37℃, 5% CO 2 조건에서 24시간 동안 10% FBS, 1% penicillin/streptomycin을 함유한 DMEM 배지에서 배양하였다. 이어서 세포를 α-MSH 10nM 과 함께 표 3에서와 같이 소듐 피루베이트 또는 하이드로퀴논(HQ)을 농도별로 48시간 동안 처리했다. 이 세포를 수확하여 라이시스 버퍼(lysis buffer, 1N NaOH, 10% DMSO) 100μl를 넣고 90℃에서 20분 동안 반응시킨 다음 405 nm(EPOCH, Biotek)에서 멜라닌 양을 측정하였다. 소듐 피루베이트와 HQ를 처리하지 않은 경우를 음성대조군으로 하여 음성대조군 대비 상대적인 멜라닌 양(%)을 표 3에 나타내었다. To measure melanin content, first, B16F10 cells were dispensed in a 6-well plate at a concentration of 1 x 10 5 cells/well, and DMEM medium containing 10% FBS and 1% penicillin/streptomycin for 24 hours at 37°C and 5% CO 2 conditions. cultured in Then, the cells were treated with α-MSH 10 nM and sodium pyruvate or hydroquinone (HQ) at different concentrations as shown in Table 3 for 48 hours. After harvesting the cells, 100 μl of lysis buffer (lysis buffer, 1N NaOH, 10% DMSO) was added and reacted at 90° C. for 20 minutes, and then the amount of melanin was measured at 405 nm (EPOCH, Biotek). Table 3 shows the relative amount (%) of melanin compared to the negative control group as a negative control when sodium pyruvate and HQ were not treated.
표 3의 멜라닌 생성 억제율(%)은 음성대조군(100)에서 음성대조군 대비 멜라닌 생성량(%)를 뺀 값으로, 다음 식 1에 따라 계산하였다. The inhibition rate (%) of melanin production in Table 3 was calculated by subtracting the amount of melanin production (%) from the negative control group (100) compared to the negative control group, and was calculated according to Equation 1 below.
식 1: [(음성대조군의 멜라닌 합성량 - 실험군의 멜라닌 합성량) / 음성대조군의 멜라닌 합성량] x 100Formula 1: [(Negative control group melanin synthesis amount - experimental group melanin synthesis amount) / negative control group melanin synthesis amount] x 100
샘플명sample name 소듐 피루베이트 농도 (ppm)Sodium Pyruvate Concentration (ppm) 하이드로퀴논(HQ) 농도 (ppm)Hydroquinone (HQ) concentration (ppm) 음성 대조군 대비 세포 생존율 (%)Cell viability (%) compared to negative control
음성대조군negative control -- -- 100100
실시예 1Example 1 5050 -- 104.9104.9
비교예 1Comparative Example 1 -- 2.52.5 87.387.3
실시예 2Example 2 100100 -- 110.5110.5
비교예 2Comparative Example 2 -- 55 59.859.8
실시예 3Example 3 5050 2.52.5 9292
실시예 4Example 4 100100 2.52.5 97.197.1
표 2에 나타낸 바와 같이, 세포 생존율은 B16F10 세포에 HQ 2.5ppm 단독 처리시(비교예 1) 12.7%, 5ppm 처리시(비교예 2) 40.2%의 세포 독성을 나타내나 HQ 2.5ppm과 소듐 피루베이트 50ppm, 100ppm(실시예 3 및 4) 과 함께 처리시 세포 독성이 8%, 2.9%로 감소하였다. As shown in Table 2, cell viability showed cytotoxicity of 12.7% and 40.2% when treated with HQ 2.5ppm alone (Comparative Example 1) and 40.2% when treated with HQ 2.5ppm (Comparative Example 2), but with HQ 2.5ppm and sodium pyruvate. When treated with 50 ppm and 100 ppm (Examples 3 and 4), the cytotoxicity was reduced to 8% and 2.9%.
샘플명sample name 소듐 피루베이트 농도 (ppm)Sodium Pyruvate Concentration (ppm) 하이드로퀴논(HQ) 농도 (ppm)Hydroquinone (HQ) concentration (ppm) 음성대조군 대비 멜라닌 생성량 (%)Amount of melanin production compared to negative control (%) 멜라닌 생성 억제율 (%)Melanin production inhibition rate (%)
음성대조군negative control -- -- 100100 00
실시예 1Example 1 5050 -- 74.474.4 25.625.6
비교예 1Comparative Example 1 -- 2.52.5 42.742.7 53.753.7
실시예 2Example 2 100100 -- 6565 3535
비교예 2Comparative Example 2 -- 55 32.932.9 67.167.1
실시예 3Example 3 5050 2.52.5 16.416.4 83.683.6
실시예 4Example 4 100100 2.52.5 4.34.3 95.795.7
표 3에서 HQ의 멜라닌 생성 억제율도 HQ 2.5 ppm 단독 처리(비교예 1) 했을 때 53.7%에서 소듐 피루베이트 50ppm, 100ppm과 같이 처리한 경우(실시예 3 및 4) 83.6%, 95.7%로 각각 증가하였다. 이는 HQ 5ppm(비교예 2) 단독 처리했을 때의 67.1% 보다 높은 효능이며 세포 독성 또한 현저히 낮기 때문에 매우 높은 시너지 효과로서 멜라닌 생성 억제 효과가 있음을 확인할 수 있다. 따라서, 본 발명의 일 측면에 따른 조성물은 현저한 피부 미백, 멜라닌 생성 억제 또는 색소 침착 억제의 효과를 나타낼 것이다. In Table 3, the melanogenesis inhibition rate of HQ also increased from 53.7% when treated with HQ 2.5 ppm alone (Comparative Example 1) to 83.6% and 95.7% when treated with sodium pyruvate 50ppm and 100ppm (Examples 3 and 4), respectively. did. This is a higher efficacy than 67.1% when HQ 5ppm (Comparative Example 2) is treated alone, and it can be confirmed that there is a melanin production inhibitory effect as a very high synergistic effect because the cytotoxicity is also significantly lower. Accordingly, the composition according to one aspect of the present invention will exhibit remarkable skin whitening, melanogenesis inhibition or pigmentation inhibition effects.
실험예 3: 소듐 피루베이트와 알부틴의 시너지 효능Experimental Example 3: Synergistic effect of sodium pyruvate and arbutin
실험예 2와 같은 실험법으로 소듐 피루베이트와 하이드로퀴논의 당유도체인 알부틴의 세포 생존율과 멜라닌 생성 억제율을 농도 별로 조합하여 멜라닌 함량을 측정하였다. 표 5의 멜라닌 생성 억제율(%)은 음성대조군(100)에서 음성대조군 대비 멜라닌 생성량(%)를 뺀 값으로, 다음 식 1에 따라 계산하였다. The melanin content was measured by combining the cell viability and melanogenesis inhibition rate of sodium pyruvate and arbutin, which is a sugar derivative of hydroquinone, according to the same experimental method as in Experimental Example 2. The inhibition rate (%) of melanin production in Table 5 is a value obtained by subtracting the amount of melanin production (%) from the negative control group (100) compared to the negative control group, and was calculated according to Equation 1 below.
식 1: [(음성대조군의 멜라닌 합성량 - 실험군의 멜라닌 합성량) / 음성대조군의 멜라닌 합성량] x 100Formula 1: [(Negative control group melanin synthesis amount - experimental group melanin synthesis amount) / negative control group melanin synthesis amount] x 100
샘플명sample name 소듐 피루베이트 농도 (ppm)Sodium Pyruvate Concentration (ppm) 알부틴 농도 (ppm)Arbutin Concentration (ppm) 음성 대조군 대비 세포 생존율 (%)Cell viability (%) compared to negative control
음성대조군negative control -- -- 100100
실시예 1Example 1 5050 -- 104.9104.9
비교예 3Comparative Example 3 -- 5050 98.298.2
실시예 2Example 2 100100 -- 110.5110.5
비교예 4Comparative Example 4 -- 100100 87.987.9
실시예 5Example 5 2020 8080 9595
실시예 6Example 6 5050 5050 98.798.7
실시예 7Example 7 8080 2020 99.499.4
샘플명sample name 소듐 피루베이트 농도 (ppm)Sodium Pyruvate Concentration (ppm) 알부틴 농도 (ppm)Arbutin Concentration (ppm) 음성대조군 대비 멜라닌 생성량(%)Amount of melanin production compared to negative control (%) 멜라닌 생성 억제율(%)Melanin production inhibition rate (%)
음성대조군negative control -- -- 100100 00
실시예 1Example 1 5050 -- 74.474.4 25.625.6
비교예 3Comparative Example 3 -- 5050 80.680.6 19.419.4
실시예 2Example 2 100100 -- 6565 3535
비교예 4Comparative Example 4 -- 100100 72.472.4 27.627.6
실시예 5Example 5 2020 8080 68.368.3 31.731.7
실시예 6Example 6 5050 5050 42.642.6 57.457.4
실시예 7Example 7 8080 2020 55.155.1 44.944.9
표 4에 따르면, B16F10 세포에서 대조군 대비 100ppm의 소듐 피루베이트와 알부틴은 각각 110.5%(실시예 2), 87.9%(비교예 4)의 세포 생존율을 나타내었다. 이 때, 소듐 피루베이트와 알부틴의 병용 처리시에는 그 중량비가 2:8인 경우 95%(실시예 5), 5:5인 경우 98.7%(실시예 6), 8:2인 경우 99.4%(실시예 7)의 세포 생존율을 보였다. 또한, 표 5에서 볼 수 있듯이, 대조군 대비 100ppm의 소듐 피루베이트와 알부틴은 각각 35%(실시예 2), 27.6%(비교예 4)의 멜라닌 생성 억제 효율을 나타내며, 소듐 피루베이트와 알부틴의 병용 처리시에는 그 중량비가 2:8인 경우 31.7%(실시예 5), 5:5인 경우 57.4%(실시예 6), 8:2인 경우 44.9%(실시예 7)의 멜라닌 생성 억제 효율을 보였다. 이러한 결과는 두 물질을 함께 처리하는 경우에는 더욱 현저하게 좋은 효과를 나타냄을 알 수 있었으며, 특히 병용 처리에서도 중량비가 5:5인 경우에 멜라닌 생성 억제 효과가 가장 뛰어났다.According to Table 4, 100ppm of sodium pyruvate and arbutin in B16F10 cells compared to the control showed cell viability of 110.5% (Example 2) and 87.9% (Comparative Example 4), respectively. At this time, in the case of the combined treatment of sodium pyruvate and arbutin, when the weight ratio is 2:8, 95% (Example 5), 5:5, 98.7% (Example 6), and 8:2, 99.4% ( Example 7) showed the cell viability. In addition, as can be seen in Table 5, 100 ppm of sodium pyruvate and arbutin compared to the control showed melanin production inhibition efficiency of 35% (Example 2) and 27.6% (Comparative Example 4), respectively, and the combination of sodium pyruvate and arbutin In the case of treatment, the weight ratio of 31.7% (Example 5) of 2:8, 57.4% (Example 6) of 5:5, and 44.9% (Example 7) of 44.9% (Example 7) when the weight ratio is seemed These results show that when the two substances are treated together, it can be seen that a more remarkably good effect is exhibited, and in particular, the melanin production inhibitory effect is the most excellent in the case of a weight ratio of 5:5 even in the combined treatment.

Claims (17)

  1. 소듐 피루베이트를 유효성분으로 포함하는 미백용 화장료 조성물.A cosmetic composition for whitening comprising sodium pyruvate as an active ingredient.
  2. 제 1항에 있어서,The method of claim 1,
    상기 조성물은 하이드로퀴논 및 알부틴으로 이루어진 군에서 선택되는 하나 이상을 더 포함하는, 미백용 화장료 조성물.The composition further comprises one or more selected from the group consisting of hydroquinone and arbutin, cosmetic composition for whitening.
  3. 제 1항에 있어서,The method of claim 1,
    상기 화장료는 화장수, 에센스, 로션, 크림, 팩, 젤, 파우더, 파운데이션 또는 세정제의 제형인 미백용 화장료 조성물.The cosmetic composition for whitening is the formulation of a lotion, essence, lotion, cream, pack, gel, powder, foundation or detergent.
  4. 소듐 피루베이트를 유효성분으로 포함하는 색소 침착증 치료용 약학적 조성물.A pharmaceutical composition for treating hyperpigmentation comprising sodium pyruvate as an active ingredient.
  5. 제 4항에 있어서,5. The method of claim 4,
    상기 조성물은 하이드로퀴논 및 알부틴으로 이루어진 군에서 선택되는 하나 이상을 더 포함하는, 색소 침착증 치료용 약학적 조성물.The composition further comprises one or more selected from the group consisting of hydroquinone and arbutin, a pharmaceutical composition for the treatment of pigmentation.
  6. 제 4항에 있어서,5. The method of claim 4,
    색소 침착증은 기미, 염증 후 과색소 침착, 피부 노화로 인한 색소 침착, 검버섯, 갈색 반점, 주근깨, 및 과색소 침착으로 이루어진 군에서 선택된 하나 이상인, 색소 침착증 치료용 약학적 조성물.Pigmentation is at least one selected from the group consisting of melasma, hyperpigmentation after inflammation, pigmentation due to skin aging, age spots, brown spots, freckles, and hyperpigmentation, a pharmaceutical composition for treating pigmentation.
  7. 소듐 피루베이트를 유효성분으로 포함하는 색소 침착증 치료용 피부 외용제 조성물.A composition for external application for the treatment of pigmentation comprising sodium pyruvate as an active ingredient.
  8. 제 7항에 있어서,8. The method of claim 7,
    상기 조성물은 하이드로퀴논 및 알부틴으로 이루어진 군에서 선택되는 하나 이상을 더 포함하는, 색소 침착증 치료용 피부 외용제 조성물.The composition further comprises one or more selected from the group consisting of hydroquinone and arbutin.
  9. 제 7항에 있어서,8. The method of claim 7,
    상기 외용제는 연고, 패취, 겔, 크림 또는 분무제의 제형인 색소 침착증 치료용 피부 외용제 조성물.The external application is an ointment, a patch, a gel, a cream or a spray formulation for the treatment of pigmentation external application for the skin.
  10. 제 7항에 있어서,8. The method of claim 7,
    색소 침착증은 기미, 염증 후 과색소 침착, 피부 노화로 인한 색소 침착, 검버섯, 갈색 반점, 주근깨, 및 과색소 침착으로 이루어진 군에서 선택된 하나 이상인, 색소 침착증 치료용 피부 외용제 조성물.Pigmentation is at least one selected from the group consisting of melasma, hyperpigmentation after inflammation, pigmentation due to skin aging, age spots, brown spots, freckles, and hyperpigmentation, a composition for external application for the treatment of pigmentation.
  11. 소듐 피루베이트를 유효성분으로 포함하는 조성물을 피부에 처리하는 단계를 포함하는, 미백 방법.A whitening method comprising the step of treating the skin with a composition comprising sodium pyruvate as an active ingredient.
  12. 소듐 피루베이트를 유효성분으로 포함하는 조성물을 피부에 처리하는 단계를 포함하는, 색소 침착증 치료 방법.A method for treating pigmentation, comprising the step of treating the skin with a composition comprising sodium pyruvate as an active ingredient.
  13. 제 11항 또는 제 12항 중 어느 한 항에 있어서, 상기 조성물은 하이드로퀴논 및 알부틴으로 이루어진 군에서 선택되는 하나 이상을 더 포함하는 방법.The method according to any one of claims 11 to 12, wherein the composition further comprises at least one selected from the group consisting of hydroquinone and arbutin.
  14. 미백 화장료를 제조하기 위한 소듐 피루베이트를 포함하는 조성물의 용도.Use of a composition comprising sodium pyruvate for the manufacture of a whitening cosmetic.
  15. 색소 침착증 치료제를 제조하기 위한 소듐 피루베이트를 포함하는 조성물의 용도.Use of a composition comprising sodium pyruvate for the manufacture of a treatment for pigmentation.
  16. 색소 침착증 치료용 외용제를 제조하기 위한 소듐 피루베이트를 포함하는 조성물의 용도.Use of a composition comprising sodium pyruvate for preparing an external preparation for the treatment of pigmentation disorders.
  17. 제 14항 내지 제 16항 중 어느 한 항에 있어서, 상기 조성물은 하이드로퀴논 및 알부틴으로 이루어진 군에서 선택되는 하나 이상을 더 포함하는 용도.17. The use according to any one of claims 14 to 16, wherein the composition further comprises at least one selected from the group consisting of hydroquinone and arbutin.
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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0345082A2 (en) * 1988-06-02 1989-12-06 Kabushiki Kaisha Hayashibara Seibutsu Kagaku Kenkyujo Enzyme formation suppressing agent
US6086789A (en) * 1996-03-18 2000-07-11 Case Western Reserve University Medical uses of pyruvates
JP2003026528A (en) * 2001-07-10 2003-01-29 Dhc Co Bleaching cosmetic

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0345082A2 (en) * 1988-06-02 1989-12-06 Kabushiki Kaisha Hayashibara Seibutsu Kagaku Kenkyujo Enzyme formation suppressing agent
US6086789A (en) * 1996-03-18 2000-07-11 Case Western Reserve University Medical uses of pyruvates
JP2003026528A (en) * 2001-07-10 2003-01-29 Dhc Co Bleaching cosmetic

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
CHOI SEON-GUK, JIN-HYUN KIM, SEONG-HEON HONG, OUN YOUNG LEE, NAE-GYU KANG: "Exogenous pyruvate alleviates UV-induced hyperpigmentation via restraining dendrite outgrowth and Rac1 GTPase activity", JOURNAL OF DERMATOLOGICAL SCIENCE, vol. 101, no. 2, 1 February 2021 (2021-02-01), pages 101 - 106, XP055860390, DOI: 10.1016/j.jdermsci.2020.11.006 *
ZHOU SIQI, SAKAMOTO KAZUICHI: "Pyruvic acid/ethyl pyruvate inhibits melanogenesis in B16F10 melanoma cells through PI3K/AKT, GSK3β, and ROS-ERK signaling pathways", GENES TO CELLS, WILEY-BLACKWELL PUBLISHING LTD., GB, vol. 24, no. 1, 1 January 2019 (2019-01-01), GB , pages 60 - 69, XP055860388, ISSN: 1356-9597, DOI: 10.1111/gtc.12654 *

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