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WO2020241972A1 - Composition cosmétique comprenant de la substance p pour le blanchiment de la peau - Google Patents

Composition cosmétique comprenant de la substance p pour le blanchiment de la peau Download PDF

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Publication number
WO2020241972A1
WO2020241972A1 PCT/KR2019/012400 KR2019012400W WO2020241972A1 WO 2020241972 A1 WO2020241972 A1 WO 2020241972A1 KR 2019012400 W KR2019012400 W KR 2019012400W WO 2020241972 A1 WO2020241972 A1 WO 2020241972A1
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WIPO (PCT)
Prior art keywords
substance
composition
present
whitening
skin
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Ceased
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PCT/KR2019/012400
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English (en)
Korean (ko)
Inventor
김다정
이정선
장송선
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Biosolution Co ltd
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Biosolution Co ltd
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Filing date
Publication date
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Publication of WO2020241972A1 publication Critical patent/WO2020241972A1/fr
Anticipated expiration legal-status Critical
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/64—Proteins; Peptides; Derivatives or degradation products thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/046—Tachykinins, e.g. eledoisins, substance P; Related peptides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/46—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing sulfur
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/46—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing sulfur
    • A61K8/463—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing sulfur containing sulfuric acid derivatives, e.g. sodium lauryl sulfate
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
    • A61K8/4993—Derivatives containing from 2 to 10 oxyalkylene groups
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
    • A61K8/73—Polysaccharides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
    • A61K8/73—Polysaccharides
    • A61K8/731—Cellulose; Quaternized cellulose derivatives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A61Q19/02—Preparations for care of the skin for chemically bleaching or whitening the skin

Definitions

  • the present invention relates to a cosmetic composition for skin whitening comprising a substance P (substance P) as an active ingredient, and more specifically, a composition comprising a substance P, an antioxidant, a surfactant and a thickener of the present invention, a cosmetic composition, It can be usefully used as quasi-drug composition, pharmaceutical composition and health functional food composition.
  • Human skin color is genetically determined according to the concentration and distribution of melanin in the skin, but is also affected by environmental or physiological conditions such as solar ultraviolet rays, fatigue, and stress.
  • melanin which determines the color of the skin
  • melanocytes which are melanocytes, protect cells from ultraviolet rays in the intracellular organelle called melanosomes. After synthesizing melanin having a protective function, it is known that the melanin migrates from melanocytes to keratinocytes, and it is reported that the melanin transferred to the keratinocytes determines the skin color.
  • tyrosine is converted to dihydroxyphenylalanine (DOPA), and then finally converted to melanin through a substance called dopaquinone.
  • DOPA dihydroxyphenylalanine
  • melanin-forming enzymes include tyrosinase (TYR), tyrosinase-related protein 1 (TRP-1), and tyrosinase-related protein 2 (tyrosinase-related protein).
  • TRP-1 tyrosinase-related protein 1
  • tyrosinase-related protein 2 tyrosinase-related protein 2
  • TRP-2/DOPA chrome tautomerase
  • MITF microphthalmia-associated transcription factor
  • Tyrosinase which plays an important role in the melanin synthesis pathway, converts L-tyrosine to L-DOPA (L-3,4-dihydroxyphenylalanine), and rapidly converts the generated L-DOPA to L-dopaquinone, Through subsequent reactions, it eventually forms melanin.
  • L-DOPA L-3,4-dihydroxyphenylalanine
  • Melanin synthesized by tyrosinase darkens the skin color, and research on a skin whitening method to brighten the skin color by inhibiting the melanin synthesis due to health or beauty requirements is actively underway.
  • a commonly known whitening ingredient arbutin, kojic acid (kojic acid), azelaic acid, aloesin, 4-butylresorcinol, resveratrol, ceramide, sphingosine-1-phosphate, sphingosyl which inhibit tyrosinase enzyme activity
  • substances such as phosphorylcholine and the like, and hydroquinone (Korean Patent Application Publication No. 2016-0014271).
  • These whitening components inhibit the synthesis of melanin pigment, thereby brightening the skin tone to realize skin whitening, or to improve skin hyperpigmentation such as spots and freckles caused by ultraviolet rays, hormones, or genetics.
  • Substance P is a peptide consisting of 11 amino acids and is a neurotransmitter scattered in nervous tissue. It has been known for a long time that it is involved in the activity of various cells in the body such as nerve cells, blood cells, and epithelial cells, and recently, the scope of application is wide enough to be known to act on anti-inflammatory and angiogenesis. The present inventors confirmed the skin whitening effect of the substance P.
  • the present inventors have made diligent efforts to increase the stability of the substance P.
  • the composition comprising the substance P, an antioxidant, a surfactant and a thickener has a better skin whitening effect compared to the use of substance P alone. It was confirmed that the present invention was completed.
  • One object of the present invention is to provide a cosmetic composition for skin whitening comprising a substance P, an antioxidant, a surfactant and a thickener.
  • Another object of the present invention is to provide a quasi-drug composition for skin whitening comprising a substance P, an antioxidant, a surfactant and a thickener.
  • Another object of the present invention is to provide a pharmaceutical composition for the prevention or treatment of whitening-related diseases comprising a substance P, an antioxidant, a surfactant, and a thickener.
  • the present invention relates to a cosmetic composition for skin whitening comprising a substance P, an antioxidant, a surfactant, and a thickener as active ingredients, and reduces melanocyte activity and total melanin production, decreases MITF transcription factor mRNA, tyrosinase mRNA and activity It provides skin whitening effect through reduction.
  • 1 is a photograph showing activated melanocytes under a fluorescence microscope through HMB45 antibody staining for gp100, a melanosome-specific protein, after co-culture with skin keratinocytes and melanocytes to treat a composition containing substance P.
  • Figure 2a is a graph of measuring the amount of extracellular melanin production after treating a composition containing a substance P by co-culturing skin keratinocytes and melanocytes.
  • Figure 2b is a graph of measuring the amount of melanin production in cells after treating a composition containing substance P by co-culturing skin keratinocytes and melanocytes.
  • 3A is a photo of an agarose gel band confirming the amount of mRNA production of MITF, tyrosinase, and GAPDH through PCR after co-culture of skin keratinocytes and melanocytes to treat a composition containing substance P.
  • Figure 3b is a graph obtained by co-culturing skin keratinocytes and melanocytes to treat a composition including substance P, and then quantifying the amount of mRNA of MITF through PCR.
  • 3C is a graph in which keratinocytes and melanocytes are co-cultured to treat a composition including substance P, and then the amount of tyrosinase mRNA produced is quantified through PCR.
  • FIG. 4 is a graph showing the quantification of tyrosinase activity by co-culture of skin keratinocytes and melanocytes to treat a composition containing substance P, and then treatment with L-DOPA, a substrate of tyrosinase.
  • One aspect for achieving the above object is to provide a cosmetic composition for skin whitening comprising a substance P, an antioxidant, a surfactant, and a thickener.
  • the present invention relates to a novel cosmetic composition for improving the insignificant effect of skin whitening effect due to the instability of the existing substance P.
  • the present inventors have developed components and contents of the composition that enable the optimal skin whitening effect to appear when the substance P is applied.
  • composition comprising substance P means a composition comprising substance P, an antioxidant, a surfactant and a thickener.
  • the present invention provides a cosmetic composition for skin whitening comprising a substance P, sodium thiosulfate, polysorbate-80, and hydroxyethylcellulose.
  • composition comprising the substance P, an antioxidant, a surfactant, and a thickener has a skin whitening effect by reducing the total amount of melanocytes and melanin production, reducing MITF transcription factor mRNA, reducing tyrosinase mRNA and activity. And completed the present invention.
  • the substance P refers to a neuropeptide consisting of the amino acid "Arg- Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met-NH 2 "of SEQ ID NO: 1.
  • the concentration of the substance P included in the composition of the present invention may be 1 to 5 ⁇ g/ml.
  • the composition containing the substance P having a concentration of 1 to 5 ⁇ g/ml has excellent skin whitening effect (Fig. 1).
  • the cosmetic composition of the present invention when the concentration of the substance P is included in the range of 1 to 5 ⁇ g/ml, it was confirmed that the cosmetic composition of the present invention has an excellent skin whitening effect.
  • pigmentation when the substance P is contained at a high concentration, pigmentation may occur.
  • the "antioxidant” acts on free groups or peroxides generated in the process of oxidation of the active ingredient by oxygen in the air to stop the chain reaction of oxidation, prevent the progress of oxidation, and deteriorate the active ingredient. It means a substance added for the purpose of preventing.
  • the antioxidant can prevent deterioration of the skin whitening effect of the cosmetic composition containing the substance P.
  • the antioxidant can be used without limitation, conventional antioxidants that can be used in the art, specifically beta-mercaptoethanol ( ⁇ -mercaptoethanol, ⁇ -ME), glutathione (Glutathione, GSH), ascorbic acid ( ascorbic acid), vitamin E, beta carotene, lycopene coenzyme Q-10, selenium, chromium, magnesium, taurine, hypotaurine, or trehalose, etc. It is not limited.
  • the antioxidant may be sodium thiosulfate.
  • the content of the antioxidant is not particularly limited as long as the whitening function is not altered, but may be 0.01 to 1% by weight, and specifically 0.1 to 1% by weight, based on the total weight of the composition of the present invention.
  • the "surfactant” refers to a substance that uses a lipophilic oil component to maintain a uniform liquid composition.
  • the surfactant may be a general surfactant used in the manufacture of cosmetic compositions such as anionic, cationic, nonionic, or amphoteric surfactants.
  • the surfactant may be polysorbate 80.
  • the content of the surfactant may be 0.001 to 0.1% by weight based on the total weight of the composition of the present invention, and specifically 0.006 to 0.1% by weight, may be 0.01 to 0.1% by weight.
  • the "thickener” is a thickener added to impart viscosity.
  • the thickener of the present invention may be hydroxyethylcellulose.
  • the content of the thickener may be 1 to 5% by weight based on the total weight of the composition of the present invention, and specifically 1.5 to 5% by weight, 2 to 5% by weight, and 3 to 5% by weight. If the content of the thickener is 1% by weight or less with respect to the total weight of the composition, there may be a problem in the stability of the cosmetic composition, and if it is 5% by weight or more, the viscosity of the cosmetic composition may be too high, resulting in a composition not suitable for mixing. .
  • the term “skin whitening” refers to brightening skin tone by inhibiting the synthesis of melanin pigment and/or inhibiting tyrosinase activity.
  • the skin whitening includes improving the deposition of skin hyperpigmentation such as spots, freckles, age spots, blemishes or melanoma caused by ultraviolet rays, hormones or genetics.
  • the melanin is a pigment of dark brown particles, and is produced by an organelle called melanosomes in melanocytes. Melanin exists in the skin, hair, and eyes, and the skin color is determined by the amount of melanin. The higher the amount of melanin, the darker the skin color is.
  • the composition may be characterized by a skin whitening effect that suppresses melanin production.
  • the skin whitening may be achieved by a tyrosinase inhibitory effect
  • the tyrosinase inhibitory effect may be an effect exhibited by a composition containing the substance P.
  • the term "cosmetic composition" of the present invention can be prepared in the form of a general emulsified formulation and a solubilized formulation.
  • the emulsified formulation includes nutrient lotion, cream, essence, and the like, and the solubilized formulation includes softening lotion.
  • the cosmetic composition is a formulation selected from the group consisting of a solution, a suspension, an emulsion, a paste, a gel, a cream, a lotion, a powder, a soap, a surfactant including cleansing, an oil, an ampoule, a powder foundation, an emulsion foundation, a wax foundation, and a spray. It can be manufactured by, but is not limited thereto. Specifically, hypoallergenic cosmetic skin protectant, flexible lotion, nutrient lotion, nutrition cream, massage cream, essence, eye cream, serum, cleansing cream, cleansing foam, cleansing water, pack, cream, essence, stray or powder formulation Can be.
  • the cosmetic composition may additionally include one or more cosmetically acceptable carriers blended in general skin cosmetics, and as common ingredients, for example, oil, water, surfactants, moisturizers, lower alcohols, thickeners, A chelating agent, a colorant, a preservative, a fragrance, and the like may be appropriately blended, but the present invention is not limited thereto.
  • one or more cosmetically acceptable carriers blended in general skin cosmetics, and as common ingredients, for example, oil, water, surfactants, moisturizers, lower alcohols, thickeners, A chelating agent, a colorant, a preservative, a fragrance, and the like may be appropriately blended, but the present invention is not limited thereto.
  • the cosmetically acceptable carrier included in the cosmetic composition varies depending on the formulation.
  • the formulation of the cosmetic composition is an ointment, paste, cream or gel, as a carrier component, animal oil, vegetable oil, wax, paraffin, starch, tracant, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc, zinc oxide Or a mixture thereof may be used.
  • lactose When the formulation of the cosmetic composition is a powder or spray, lactose, talc, silica, aluminum hydroxide, calcium silicate, polyamide powder, or a mixture thereof may be used as a carrier component, and in particular, in the case of a spray, additionally Propellants such as chlorofluorohydrocarbons, propane/butane or dimethyl ether.
  • a solvent, a solubilizing agent or an emulsifying agent is used as a carrier component, such as water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol , 1,3-butylglycol oil may be used, and in particular cottonseed oil, peanut oil, corn germ oil, olive oil, castor oil and sesame oil, glycerol aliphatic ester, polyethylene glycol or fatty acid ester of sorbitan may be used.
  • a solvent, a solubilizing agent or an emulsifying agent is used as a carrier component, such as water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol , 1,3-butylglycol oil may be used, and in particular cottonseed oil,
  • the formulation of the cosmetic composition is a suspension
  • a liquid diluent such as water, ethanol or propylene glycol, an ethoxylated isostearyl alcohol, a suspending agent such as polyoxyethylene sorbitol ester and polyoxyethylene sorbitan ester, Microcrystalline cellulose, aluminum metahydroxide, bentonite, agar or tracant, and the like may be used.
  • an alkali metal salt of a fatty acid, a fatty acid hemiester salt, a fatty acid protein hydrolyzate, isethionate, a lanolin derivative, an aliphatic alcohol, vegetable oil, glycerol, sugar, etc. are used as a carrier component.
  • an alkali metal salt of a fatty acid, a fatty acid hemiester salt, a fatty acid protein hydrolyzate, isethionate, a lanolin derivative, an aliphatic alcohol, vegetable oil, glycerol, sugar, etc. are used as a carrier component.
  • Another aspect of the present invention is to provide a quasi-drug composition for skin whitening comprising a substance P, an antioxidant, a surfactant, and a thickener.
  • the substance P, antioxidant, surfactant, and thickener are as described above.
  • the term "quasi-drug” refers to items that are less effective than pharmaceuticals among items used for the purpose of diagnosing, treating, improving, alleviating, treating or preventing diseases of humans or animals.
  • the Korean Pharmacological Law Quasi-drugs exclude items used for pharmaceutical purposes, and include products used for the treatment or prevention of diseases of humans and animals, and products with minor or no direct action on the human body.
  • the quasi-drug composition of the present invention may be prepared in a form selected from the group consisting of a body cleanser, foam, soap, mask, ointment, cream, lotion, essence, and spray, but is not limited thereto.
  • the composition containing the substance P, an antioxidant, a surfactant, and a thickener of the present invention is added as it is or It can be used together with other quasi-drugs or quasi-drug ingredients, and can be used appropriately according to conventional methods.
  • Another aspect of the present invention is to provide a pharmaceutical composition for the prevention or treatment of whitening-related diseases, comprising a substance P, an antioxidant, a surfactant and a thickener.
  • another aspect of the present invention is to provide a use for the prevention or treatment of whitening-related diseases, including the substance P, an antioxidant, a surfactant, and a thickener.
  • the substance P, antioxidant, surfactant, and thickener are as described above.
  • the term "whitening-related disease” refers to a disease having symptoms in which pigment is excessively deposited on the skin, and specifically, the whitening-related disease may be spots, freckles, age spots, blemishes, or melanoma.
  • prevention means any action in which the composition of the present invention inhibits or delays the occurrence of whitening-related diseases.
  • treatment refers to any action that makes the pharmaceutical composition of the present invention ameliorate or benefit the symptoms of whitening-related diseases.
  • the pharmaceutical composition may further include a pharmaceutically acceptable carrier.
  • the term "pharmaceutically acceptable carrier” refers to a carrier or diluent that does not irritate an organism and does not inhibit the prophylactic or therapeutic activity and properties of whitening-related disease symptoms of the present composition.
  • acceptable pharmaceutical carriers for compositions formulated as liquid solutions, sterilization and biocompatible ones saline, sterile water, Ringer's solution, buffered saline, albumin injection solution, dextrose solution, maltodextrin solution, glycerol, ethanol And one or more of these components may be mixed and used, and other conventional additives such as antioxidants, buffers, and bacteriostatic agents may be added as needed.
  • the pharmaceutically acceptable carrier of the present invention may include a non-natural carrier.
  • the pharmaceutical composition of the present invention may be administered singly or multiple times in a pharmaceutically effective amount.
  • the term "pharmaceutically effective amount” refers to an amount sufficient to prevent or treat a disease at a reasonable benefit/risk ratio applicable to medical prevention or treatment, and the effective dose level is the severity of the disease, the activity of the drug , Including the patient's weight, health, sex, sensitivity to the patient's drugs, the time of administration of the composition of the present invention used, the route of administration and the rate of excretion, the duration of treatment, and drugs used in combination or concurrent with the composition of the present invention used Factors and other factors well known in the medical field can be determined.
  • Another aspect of the invention provides a method of whitening skin comprising administering to a subject in need thereof a composition comprising Substance P, an antioxidant, a surfactant and a thickener.
  • composition and whitening including the substance P, an antioxidant, a surfactant, and a thickener are as described above.
  • Administration of the present invention may be a method, including application to the skin.
  • a composition comprising Substance P, an antioxidant, a surfactant and a thickener can be administered to a subject in need thereof in an effective amount.
  • the level of effective dose can be determined by a person skilled in the art based on common knowledge to the extent that the desired skin whitening effect is exhibited.
  • Another aspect of the present invention is to provide a health functional food for skin whitening comprising a substance P, an antioxidant, a surfactant, and a thickener.
  • the present invention is as described above with respect to the composition and whitening containing the substance P, an antioxidant, a surfactant and a thickener.
  • the term "health functional food” refers to a food manufactured and processed in the form of tablets, capsules, powders, granules, liquids and pills using raw materials or ingredients having useful functions for the human body.
  • the term "functionality" means obtaining a useful effect for health purposes such as controlling nutrients or physiological effects on the structure and function of the human body.
  • the health functional food of the present invention can be prepared by a method commonly used in the art, and at the time of manufacture, it can be prepared by adding raw materials and ingredients commonly added in the art.
  • the formulation of the health functional food may be prepared without limitation as long as it is a formulation recognized as a health functional food.
  • the health functional food of the present invention can be prepared in various forms of formulation, and unlike general drugs, it has the advantage of not having side effects that may occur when taking the drug for a long time by using food as a raw material, and is excellent in portability. Health functional foods can be consumed as a supplement to enhance the skin whitening effect.
  • the health functional food of the present invention may contain various flavoring agents or natural carbohydrates as additional ingredients.
  • the natural carbohydrates described above are monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, polysaccharides such as dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol.
  • sweetener natural sweeteners such as taumatin and stevia extract, or synthetic sweeteners such as saccharin and aspartame can be used.
  • the health functional food of the present invention includes various nutrients, vitamins, electrolytes, flavors, coloring agents, pectic acid and salts thereof, alginic acid and salts thereof, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohols, Carbonating agents used in carbonated beverages may be contained. These components may be used independently or in combination. Although the ratio of these additives is not very important, it is generally selected from 0.000001 to 0.1 parts by weight per 100 parts by weight of the health food of the present invention, but is not particularly limited thereto.
  • Example 1 Preparation of a cosmetic composition for whitening containing substance P
  • a novel formulation was prepared in which sodium thiosulfate as an antioxidant, polysorbate 80 as a surfactant, and hydroxyethylcellulose as a thickener were added to the substance P.
  • Material P was synthesized through a solid/solution phase using Fmoc-chemistry, a peptide synthesis technology, and purified through high performance liquid chromatography, and finally, a purity of 85% or more was used.
  • composition comprising substance P Composition of the composition content Substance P 5 ⁇ g/ml Sodium thiosulfate 0.1% Polysorbate 80 0.006% Hydroxyethyl cellulose 1.5%
  • composition containing a substance P prepared as shown in Table 1 in the co-cultured cells (substance P, 5 ⁇ g/ml), a composition obtained by diluting it five times (substance P, 1 ⁇ g/ml) and a phosphoric acid substance
  • a composition in which P was dissolved in a buffer solution (PBS) (material P, 5 ⁇ g/ml) was treated on the co-cultured cells, respectively.
  • PBS buffer solution
  • the degree of reduction of activated melanocytes was confirmed through HMB45 antibody staining for gp100, a melanosome-specific protein inside the activated melanin.
  • a melanocyte stimulating hormone ( ⁇ -MSH) 150 nM and a phosphate buffer (PBS) as a negative control were treated with 10 ⁇ g/ml of arbutin as a positive control to reduce fluorescence. The degree was observed through a fluorescence microscope.
  • Example 3 Confirmation of the effect of the composition containing the substance P on the production of extracellular and intracellular melanin
  • composition containing a substance P prepared as shown in Table 1 under the conditions of 5:1 co-cultivation of skin keratinocytes and melanocytes constructed for an environment similar to human skin tissue (substance P, 5 ⁇ g/ml)
  • a composition obtained by diluting it 5 times (substance P, 1 ⁇ g/mL) and as a comparative example, substance P dissolved in phosphate buffer solution (PBS) (substance P, 5 ⁇ g/mL) was applied to cells under co-culture conditions for up to 48 hours. After that, the supernatant of the cells was collected and the amount of melanin outside the cells was measured at 405 nm absorbance. In addition, the amount of melanin inside the cells was measured at 405 nm absorbance after washing the cells with PBS and centrifuging, dissolving the cells with 1N sodium hydroxide containing 10% DMSO for 1 hour at 80°C.
  • the group treated with the substance P-containing composition (substance P, 5 ⁇ g/ml) with ⁇ -MSH confirmed that the amount of melanin production was reduced by 54%p to 100%, which was 3 times higher than that of treatment with substance P alone. It was found that it showed an effect of reducing abnormal melanin production. In addition, this showed a decrease in the amount of melanin production to the same level as when not treated with ⁇ -MSH, and it was confirmed that the effect was superior to that of the group treated with arbutin, a positive control (FIG. 2B).
  • the composition containing the substance P of the present invention shows a better effect of reducing melanin production outside and inside the cell, even when the substance P is used in a smaller dose than when the substance P is treated alone, and the same amount is used. In the case, it was confirmed that there is a better effect of reducing melanin production.
  • Example 4 Confirmation of the effect of reducing MITF transcription factor and tyrosinase mRNA of a composition containing substance P
  • the amount of reduction in the production of MITF transcription factor and tyrosinase mRNA was confirmed through the co-cultured cell experiment.
  • the co-cultured cell conditions and material treatment were the same as those mentioned in Example 1, and the experiment was a composition containing the substance P of Table 1 under the co-culture conditions of skin keratinocytes and melanocytes 5:1 (substance P , 5 ⁇ g/ml), a composition obtained by diluting it 5 times (material P, 1 ⁇ g/ml) and material P dissolved in a phosphate buffer solution (PBS) as a comparative example (substance P, 5 ⁇ g/ml) under co-culture conditions. After applying to the cells for up to 48 hours, the cells were extracted and proceeded.
  • a composition containing the substance P of Table 1 under the co-culture conditions of skin keratinocytes and melanocytes 5:1 (substance P , 5 ⁇ g/ml)
  • a composition obtained by diluting it 5 times material P, 1 ⁇ g/ml
  • material P dissolved in a phosphate buffer solution (PBS) a phosphate buffer solution (P
  • the cells were extracted by directly treating the cells with the RiboEx (cell lysate) reagent in the GeneAll Hybrid-R kit (Cat no. 305-101) and then suspending them. After separating the RNA inside the extracted cells with RNases-free water in the Hybrid-R kit, cDNA is synthesized using reverse transcriptase, and the amount of mRNA produced by MITF transcription factor and tyrosinase is reverse transcriptase chain It was confirmed through the reaction (RT-PCR: reverse transcription PCR) (Fig. 3a).
  • the amount of mRNA production of the MITF transcription factor decreased to 1.3, similar to that of the case without treatment with ⁇ -MSH. It was confirmed that the mRNA reduction effect of the MITF transcription factor was shown. In addition, it was confirmed that this was similar to the group treated with the positive control, arbutin (Fig. 3b).
  • the composition containing the substance P of the present invention has a similar or superior level of MITF transcription factor and tyrosinase mRNA reduction effect, even when a dose of 1/5 of the substance P is used than when the substance P is treated alone.
  • a dose of 1/5 of the substance P is used than when the substance P is treated alone.
  • Example 5 Confirmation of the effect of reducing tyrosinase activity of a composition comprising substance P
  • PBS phosphate buffer solution
  • the remaining cells were lysed using a buffer mixed with 1% sodium dodecyl sulfate and 0.5% Triton x-100, and the lysed cells were centrifuged at 12,000 rpm for 30 minutes, and a supernatant was obtained.
  • the total amount of protein was adjusted to 50 ⁇ g, and 2 mg/ml of L-DOPA, a substrate of tyrosinase, was mixed for 1 hour under dark conditions, and the amount of melanin changed in L-DOPA was measured at 475 nm. The activity of tyrosinase was quantified.
  • composition containing the substance P of the present invention shows a better effect of reducing tyrosinase activity even when the amount of substance P is used 1/5 than when the substance P is treated alone, and when the same amount is used, It was confirmed that there is a better effect of reducing tyrosinase activity.

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Abstract

La présente invention concerne une composition cosmétique comprenant de la substance P en tant que principe actif pour le blanchiment de la peau. Plus particulièrement, une composition comprenant de la substance P, un antioxydant, un tensioactif et un épaississant selon la présente invention peut être avantageusement utilisée en tant que composition cosmétique, que composition quasi-médicamenteuse, que composition pharmaceutique et que composition alimentaire fonctionnelle pour la santé. La présente invention concerne une composition cosmétique comprenant de la substance P en tant que principe actif pour le blanchiment de la peau, qui produit un effet de blanchiment de la peau par le biais d'une réduction de l'activité mélanocytaire et de la quantité totale de production de mélanine, dans le niveau d'ARNm du facteur transcriptionnel MITF, et dans le niveau d'ARNm et l'activité de la tyrosinase.
PCT/KR2019/012400 2019-05-28 2019-09-24 Composition cosmétique comprenant de la substance p pour le blanchiment de la peau Ceased WO2020241972A1 (fr)

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WO2025134152A1 (fr) * 2023-12-21 2025-06-26 L'oreal Composition cosmétique comprenant des composés de thiopyridinone, agent réducteur et acide aminé

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KR101056656B1 (ko) * 2008-11-26 2011-08-16 (주)아모레퍼시픽 신경 전달 물질 분비 억제를 통한 피부 미백 화장료 조성물
KR20170115357A (ko) * 2016-04-07 2017-10-17 주식회사 바이오솔루션 물질 p를 포함하는 상처치유용 약학 조성물
KR20180136301A (ko) * 2017-06-14 2018-12-24 주식회사 바이오솔루션 물질 p를 포함하는 주름 개선 또는 항염증 화장료 조성물

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KR101056656B1 (ko) * 2008-11-26 2011-08-16 (주)아모레퍼시픽 신경 전달 물질 분비 억제를 통한 피부 미백 화장료 조성물
KR20170115357A (ko) * 2016-04-07 2017-10-17 주식회사 바이오솔루션 물질 p를 포함하는 상처치유용 약학 조성물
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WO2025134152A1 (fr) * 2023-12-21 2025-06-26 L'oreal Composition cosmétique comprenant des composés de thiopyridinone, agent réducteur et acide aminé

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