WO2006106992A1 - Agent inhibiteur de la production de melanine - Google Patents

Agent inhibiteur de la production de melanine Download PDF

Info

Publication number
WO2006106992A1
WO2006106992A1 PCT/JP2006/306976 JP2006306976W WO2006106992A1 WO 2006106992 A1 WO2006106992 A1 WO 2006106992A1 JP 2006306976 W JP2006306976 W JP 2006306976W WO 2006106992 A1 WO2006106992 A1 WO 2006106992A1
Authority
WO
WIPO (PCT)
Prior art keywords
acid
hibiscus
melanin production
whitening
active ingredient
Prior art date
Application number
PCT/JP2006/306976
Other languages
English (en)
Japanese (ja)
Inventor
Kyoko Ishiguro
Naoe Oku
Naoko Harada
Katsuyuki Fujimura
Original Assignee
Kobayashi Pharmaceutical Co., Ltd.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Kobayashi Pharmaceutical Co., Ltd. filed Critical Kobayashi Pharmaceutical Co., Ltd.
Publication of WO2006106992A1 publication Critical patent/WO2006106992A1/fr

Links

Classifications

    • 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
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/105—Plant extracts, their artificial duplicates or their derivatives
    • 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
    • A61K8/4973—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom

Definitions

  • the present invention relates to a melanin production inhibitor containing hibiscus acids as active ingredients, and a whitening agent, a whitening cosmetic, a whitening food and an oral composition containing the melanin production inhibitor.
  • active oxygen scavengers such as ascorbic acid and tyrosinase activity inhibitors such as kojic acid and arbutin have been proposed as active ingredients for whitening agents! Speak (see Patent Document 1 etc.).
  • the substances proposed as the active ingredients of conventional whitening agents act only on part of the melanin production process, and melanin is also produced by other processes. The power was not satisfactory.
  • the conventional whitening ingredients have not been able to satisfy the viewpoint of sustaining the effect.
  • Patent Document 2 includes 3 hydroxy-3,4 dicarboxy 1,4-butanolide or derivatives thereof. Cosmetics characterized in that they contain a body are described. Patent Document 3 discloses a glycosidase inhibitor and a therapeutic agent for diabetes containing hibiscus acids as active ingredients. However, Hibiscus acids are effective in inhibiting melanin production and whitening! None before had it been known.
  • Patent Document 1 JP-A-1-85907
  • Patent Document 2 Japanese Patent Application Laid-Open No. 200-154134
  • Patent Document 3 Japanese Patent Laid-Open No. 2000-239164
  • the present invention has an excellent melanin production inhibitory action, has a persistent melanin production inhibitory action, and can be used safely, a melanin production inhibitor, a whitening agent, a whitening cosmetic,
  • the main purpose is to provide a food for whitening and a composition for oral cavity.
  • the present invention relates to the following melanin production inhibitor, whitening agent, cosmetic, food and oral composition.
  • a melanin production inhibitor comprising as an active ingredient one or more compounds selected from the group consisting of hibiscus acids represented by the formula (1) and a salt power thereof.
  • Item 2 The melanin production inhibitor according to Item 1, wherein at least one of R 1 and R 2 of the hibiscus acids represented by the formula (1) is a substituted or unsubstituted alkyl group.
  • IT and R 2 each represent a hydrogen atom, a substituted or unsubstituted alkyl group or a benzyl group, and at least one of R 1 and R 2 is a substituted or unsubstituted alkyl group.
  • a melanin production inhibitor comprising as an active ingredient at least one compound selected from the group consisting of bis and biscus acids.
  • a melanin production inhibitor comprising as an active ingredient one or two or more compounds selected from the group power of hibiscus monoalkyl ester and bisbisester dialkyl esterka.
  • melanin production inhibition comprising one or two or more compounds selected from the group power consisting of bismuth acid monomethyl ester, bis, biscus acid monoethyl ester, hibiscus acid dimethyl ester and hibiscus acid dimethyl ester as active ingredients Agent.
  • Item 3 A whitening agent comprising the melanin production inhibitor according to any one of Items 1 to 2 as an active ingredient.
  • Item 4 A whitening cosmetic comprising the melanin production inhibitor according to any one of Items 1 to 2 as an active ingredient.
  • Item 5 A whitening roro comprising the melanin production inhibitor according to any one of Items 1 to 2 as an active ingredient.
  • Item 6 An oral composition comprising the melanin production inhibitor according to any one of Items 12 and 12 as an active ingredient.
  • the melanin production inhibitor of the present invention has the following formula (1)
  • R 1 and R 2 each represent a hydrogen atom, a substituted or unsubstituted alkyl group, or a benzyl group.
  • One or more compounds are active ingredients.
  • the type of the alkyl group is not particularly limited as long as the effect of the present invention is exhibited, and may be linear or branched.
  • the number of carbon atoms of the alkyl group can be set as appropriate within the range in which the effects of the present invention are exerted.
  • alkyl group examples include a methyl group, an ethyl group, a propyl group, a butyl group, an isopropyl group, an isobutyl group, and a hexyl group.
  • the alkyl group or benzyl group may have a substituent, and the type of the substituent may be appropriately set within the range where the effect of the present invention is exerted. And the like.
  • hibiscus acids used in the present invention include, for example, hibiscus acid R 1 and R 2 in the formula are hydrogen atoms, one of R 1 and R 2 in the formula is substituted And Hibiscus acid diester wherein R 1 and R 2 in the formula are both substituted.
  • Hibiscus acid monoesters include, for example, hibiscus monoalkyl esters such as hibiscus monomethyl ester and bisbis monoethyl ester.
  • Hibiscus acid diesters include, for example, bismuth acid dialkyl esters such as bismuth acid dimethyl ester, and biscus acid decyl ester.
  • the salts of hibiscus acids used in the present invention include the above-mentioned salts of hibiscus acids, for example, when R 1 and Z or R 2 are hydrogen atoms, they are monovalent or divalent metal bases. This includes alkali metal salts and alkaline earth metal salts that have been replaced.
  • alkali metal salt examples include sodium salt and potassium salt.
  • alkaline earth metal salts examples include calcium salts and magnesium salts.
  • the salt also includes those forming a complex.
  • an example of a complex is R
  • Examples include alkaline earth metal complexes formed by replacing 1 and Z or R 2 with calcium or magnesium.
  • the means for producing the hibiscus acids and salts thereof used in the present invention are not particularly limited, and may be obtained by force separation such as a plant body or an extract thereof which may be obtained by chemical synthesis. But you can.
  • the ester or salt may be obtained by esterifying a hibiscus acid obtained by separating from a plant or its extract according to a conventional method or reacting with various bases.
  • a method for separating hibiscus acids from a plant body or an extract thereof is not particularly limited, and a known method can be appropriately used.
  • a plant that contains hibiscus acid may be extracted with a suitable extraction solvent and then separated by means such as chromatography.
  • Examples of plants containing hibiscus acids include plants belonging to the genus Fuyu.
  • Examples of plants belonging to the genus Fuyou include the annual annual Roselle (Hibiscus sabdarif fa) native to the tropics and the bushy geese (Hibiscus) of the tropical shrub.
  • Roselle Roselle, Bussouge and Mukuge, and Roselle and Bussouge are particularly preferable.
  • the extraction site of the plant is not particularly limited, and for example, the whole plant of the plant or a part of the plant such as a flower, a bud, a leaf, a stem, a branch, a branch tip, a root, a rhizome, and a seed. Can be mentioned. Among these, Preferably, a flower and a leaf can be mentioned.
  • the extracted raw material may be a pulverized product obtained by using plant bodies as they are, or a product obtained by drying, chopping, crushing, pressing, boiling or fermenting them.
  • the type of the solvent used for extraction can be set as appropriate, and examples thereof include water, various organic solvents, and a mixture of water and an organic solvent.
  • the organic solvent include methanol, ethanol, n -propanol, isopropanol, butanol, isobutanol, hexanol, propylene glycol, 1,3-butylene glycol, acetone, ethyl acetate, black mouth form, pentane, hexane, Including heptane, hydrochloric acid, etc. alone or in combination of two or more.
  • preferable extraction solvents include lower alcohols such as methanol, ethanol, and isopropanol, or a mixture of water and lower alcohols.
  • water can be removed by performing a drying treatment such as reduced-pressure drying or freeze-drying to use as a dried product.
  • Specific conditions for extraction can also be appropriately set according to a conventional method without particular limitation.
  • a dried roselle flower is crushed, and about 10 parts by weight of 1.5% hydrochloric acid-ethanol aqueous solution is added to 1 part by weight of the extraction target, stirred at room temperature, and then solids are removed by filtration.
  • a method of performing purification by HPLC can be mentioned.
  • commercially available bis and ibiscus acids commercially available ones can also be used.
  • the ester can be obtained from commercially available hibiscus acid by subjecting it to esterification according to a known method.
  • the compound used as the active ingredient of the melanin production inhibitor of the present invention may be a single compound selected from the above-mentioned hibiscus acids or a group power of salt power thereof, or a mixture of two or more compound powers. May be.
  • the mixture consisting of two or more kinds of compounds contains biscus acid or biscus acid which may be obtained by mixing various hibiscus acids or salts thereof obtained by synthesis or isolation from plants. It may be a mixture or a fraction obtained from a plant or an extract thereof.
  • the melanin production inhibitor of the present invention contains, as an active ingredient, one or more compounds selected from the group consisting of the above-mentioned hibiscus acids and their salt strength, and preferably a hibiscus monoalkyl ester and hibiscus It contains one or more compounds selected from the group consisting of acid dialkyl esters as active ingredients.
  • it includes one or more compounds selected as an active ingredient, which are selected from bismuth acid monomethyl ester, bis, biscus acid monodimethyl ester, hibiscus acid dimethyl ester, and hibiscus acid dimethyl ester. .
  • the melanin production inhibitor of the present invention contains, as an active ingredient, one or two or more compounds selected from the group consisting of the above-mentioned hibiscus acids and salts thereof, and has a high and sustained tyrosinase activity inhibiting action and a high tyrosinase. It has a production inhibitory action and exhibits an effective and continuous melanin production inhibitory action.
  • the whitening agent of the present invention contains the melanin production inhibitor of the present invention as an active ingredient.
  • the whitening agent of the present invention may consist of the melanin production inhibitor itself, or it may contain other ingredients such as pharmaceutically or sanitary acceptable carriers or additives as an active ingredient. It could be something! /
  • the types and blending amounts of the strong carriers or additives can be appropriately selected and adjusted according to the dosage form of the whitening agent or the application target, as long as the effects of the present invention are not impaired.
  • the form of the whitening agent is not particularly limited, and the dosage form and form of the product to be applied, Depending on the application, etc., it can be arbitrarily prepared into liquids, emulsions, creams, powders, granules, pills, ointments and the like.
  • the whitening agent of the present invention may be an external preparation or an internal preparation.
  • the whitening agent of the present invention inorganic pigments, ultraviolet absorbers, other whitening components, tyrosinase activity inhibitors or melanin dye reducing agents, surfactants, cell activation agents.
  • Additives such as agents, anti-inflammatory agents, antibacterial agents, moisturizers, fragrances, and coloring agents may be added as appropriate.
  • the types of external preparations to which the whitening agent of the present invention can be applied are not particularly limited.
  • external medicines and external quasi drugs skin external preparations, etc.
  • basic cosmetics skin lotion, emulsion, Tarim, ointment, lotion, oil, pack, etc.
  • makeup cosmetics foundation, lipstick, scarlet, mascara, etc.
  • other skin cosmetics face wash, skin cleanser, massage agent, cleansing agent, etc.
  • Oral compositions bath preparations, and the like.
  • the amount of the external preparation varies depending on the compounding target, dosage form, expected effect, etc., and cannot be uniformly defined.
  • Hibiscus acids and salts thereof are 0.00001 to 10% by weight, preferably 0.00005 to 5% by weight, more preferably about 0.0001 to 3% by weight, based on the whole agent.
  • a binder In formulating the whitening agent of the present invention as an internal preparation, a binder, a disintegrant, a lubricant, a wetting agent, a buffering agent, an excipient, an extender, and a preservative are used as necessary. In addition, additives such as fragrances can be combined. In addition, when formulating the whitening agent of the present invention as an internal preparation, other pharmaceutically active ingredients can be further blended.
  • the type of internal preparation to which the whitening agent of the present invention can be applied is not particularly limited, and examples thereof include oral preparations such as powders, tablets, granules, capsules, and syrups.
  • the blending ratio of the internal preparation varies depending on the administration target, dosage form, administration method, etc., and cannot be uniformly defined.
  • the amount of hibiscus acids and salts thereof is 0.00001 to 100% by weight, preferably 0.0001 to 50% by weight, more preferably about 0.001 to 30% by weight, based on the whole internal preparation.
  • the whitening agent of the present invention comprises, as an active ingredient, a melanin production inhibitor containing as an active ingredient one or more compounds selected from the above-mentioned hibiscus acids and the group power of their salt strength.
  • a melanin production inhibitor containing as an active ingredient one or more compounds selected from the above-mentioned hibiscus acids and the group power of their salt strength.
  • it has a continuous and excellent melanin production inhibitory action including a high and sustained tyrosinase activity inhibitory action and a high tyrosinase production inhibitory action, and exhibits a continuous and excellent whitening action.
  • the whitening cosmetic composition of the present invention contains the melanin production inhibitor of the present invention as an active ingredient.
  • the type of cosmetic is not particularly limited, and can be applied to various cosmetics.
  • various types of cosmetics such as rinsing and other hair cosmetics, sarcophagus, beauty nails, eau de cologne, and bath salts.
  • the form of the cosmetic is not particularly limited, either, solution, emulsion, ointment, sol, gel, powder.
  • aqueous component a powder component
  • a moisturizer a surfactant
  • a preservative an increase agent
  • Adhesives ultraviolet absorbers, fragrances and the like can be blended.
  • the method for producing the cosmetic of the present invention is not particularly limited, and can be suitably produced according to a known method.
  • the method of applying the cosmetic composition of the present invention is not particularly limited, but may be applied to, for example, an easily or affected part such as a stain on the face, neck, arm or hand, or freckles, or an easily tanned or tanned part. Apply an appropriate amount once or several times a day.
  • the content ratio of the melanin production inhibitor in the cosmetic of the present invention can be appropriately set within the range in which the effect of the present invention can be exerted.
  • a hibiscus acid and its salt with respect to the entire cosmetic composition 0.00001 -10% by weight, preferably 0.00005-5% by weight, more preferably 0.0001-3% by weight.
  • the whitening cosmetic composition of the present invention includes a melanin production inhibitor containing, as an active ingredient, the above-mentioned hibiscus acid and one or more compounds selected from the group power of its salt strength as an active ingredient, and is high and durable.
  • Tyrosinase activity inhibitory activity and high tyrosiner It has a continuous and excellent melanin production-inhibiting action, including a zeogenesis-inhibiting action, and has a continuous and excellent whitening effect.
  • the whitening food of the present invention contains the melanin production inhibitor of the present invention as an active ingredient.
  • the whitening food of the present invention can be used as, for example, health foods, food additives, functional foods, nutritional functional foods, health functional foods, and the like.
  • the method for producing the whitening food is not particularly limited, and can be suitably produced according to a known method. For example, it can be obtained by mixing the whitening agent with various foods or food materials.
  • the type of food is not particularly limited, and can be appropriately set from various known foods and drinks.
  • it can be used as cookies, cereals, candy, tablets, jelly, marine products, seasonings, bread, soft drinks, carbonated drinks, mineral water, fruit juice drinks, teas, nutrition drinks, drinks, and the like.
  • the food of the present invention can be blended with other components used in ordinary foods and drinks within a range not impairing the effects of the present invention.
  • other ingredients include various vitamins, minerals, animal and plant ingredients, excipients, sweeteners, flavoring agents, coloring agents, preservatives, disintegrating agents, lubricants, wetting agents, bulking agents, and flavoring agents. It is done.
  • the content of the melanin production inhibitor in the food of the present invention can be set as appropriate within the range in which the effects of the present invention can be exerted, but 0.00001 to 10 as hibiscus acids and salts thereof with respect to the entire food composition. % By weight, preferably 0.00005 to 5% by weight, more preferably about 0.0001 to 3% by weight.
  • the amount of intake when eating the whitening food of the present invention can be appropriately set according to the age, weight, symptoms, etc. of the subject of application, but is generally 0.00001 per day for adults as hibiscus acids and salts thereof. About 50 mg, preferably about 0.0001-20 mg, more preferably about 0.001-10 mg.
  • the whitening food of the present invention effectively comprises a melanin production inhibitor containing as an active ingredient one or more compounds selected from the above-mentioned hibiscus acids and the group power of their salt strength. It has a continuous and excellent melanin production inhibitory action including a high and sustained tyrosinase activity inhibitory action and a high tyrosinase production inhibitory action, and has a continuous and excellent whitening action.
  • composition for oral cavity of the present invention contains the melanin production inhibitor of the present invention as an active ingredient.
  • the type of oral composition is not particularly limited, and can be applied to various oral compositions.
  • toothpaste such as toothpaste, mouthwash, mouth rinse, oral paste, troche, gum massage cream and the like.
  • the form of the oral composition is not particularly limited, and can be used in various forms such as a solution, emulsion, ointment, sol, gel, paste, tablet, powder, spray, sheet, and film.
  • composition for oral cavity of the present invention various components generally blended in the composition for oral cavity can be blended within the range where the effects of the present invention are exhibited.
  • Various components include, for example, an adhesive, a refreshing agent, a binder, a sweetener, a flavoring agent, a disintegrant, a lubricant, a colorant, a sustained release regulator, a surfactant, a solubilizer, a wetting agent, and a pH adjuster.
  • An agent etc. can be mentioned.
  • the method for producing the composition for oral cavity of the present invention is not particularly limited, and can be suitably produced according to a known method.
  • the method for applying the oral composition of the present invention is not particularly limited. For example, an appropriate amount may be applied once or several times a day to the affected area or the entire oral cavity.
  • the content ratio of the melanin production inhibitor in the oral composition of the present invention can be appropriately set within the range in which the effect of the present invention can be exerted, but the hibiscus acids and salts thereof with respect to the entire oral composition. As 0.00001 to 10% by weight, preferably 0.00005 to 5% by weight, and more preferably about 0.0001 to 3% by weight.
  • the composition for oral cavity of the present invention includes a melanin production inhibitor containing, as an active ingredient, the above-mentioned hibiscus acids and one or more compounds selected from the group power of its salt strength as an active ingredient, and is high and durable. It has a long-lasting and excellent melanin production-inhibiting action, including a typical tyrosinase activity-inhibiting action and a high tyrosinase-inhibiting action, and is deposited on the gum The pigment
  • a melanin production inhibitor comprising as an active ingredient one or more compounds selected from the group strength of hibiscus acid having a specific structure and its salt strength.
  • the compound as an active ingredient of the melanin production inhibitor of the present invention has an excellent melanin production inhibitory action including a high tyrosinase activity inhibitory action and a high tyrosinase production inhibitory action, and has an excellent whitening effect. It is what you play. Furthermore, the whitening effect is achieved for a long time. However, the compound is also highly safe.
  • the melanin production inhibitor of the present invention comprising such a compound as an active ingredient has an excellent whitening effect and has a long-lasting whitening effect, and is effective in skin cells, oral mucosa and the like. It effectively suppresses the melanin produced and effectively suppresses the deposition of pigments such as spots and freckles. Furthermore, the melanin production inhibitor of the present invention can be used with peace of mind.
  • the melanin production inhibitor can be used as an active ingredient in whitening agents, whitening cosmetics, whitening foods and oral compositions, and has an excellent whitening action according to the present invention.
  • a whitening agent, a whitening cosmetic, a whitening food, and a composition for oral cavity that have a long-lasting whitening effect and can be used safely are also provided.
  • the present invention having such characteristics can be suitably used in the cosmetic industry, the pharmaceutical industry, the food industry, and the like, which have recently been particularly interested in the whitening effect.
  • the obtained fraction is also referred to as “no biscus acid monoethyl ester fraction”.
  • Hibiscus acid obtained in Production Example 1 was dissolved in a mixed solvent of 1.8 ml of methyl-t-butyl ether (MTBE) and 1.8 ml of methanol. This solution was stirred while cooling in an ice-water bath, and 3.5 ml of trimethylsilyl diazomethane 2.0M jetyl ether solution was added little by little. The resulting precipitate was filtered, washed with MTBE, and dried under reduced pressure to obtain 300 mg of bis (bisbisamic acid) dimethyl ester.
  • MTBE methyl-t-butyl ether
  • a biscus extract (extract) was produced by the following method.
  • Mouse-derived B16 melanoma cells (D16, manufactured by Dainippon Pharmaceutical Co., Ltd., B16F0) were cultured for 24 hours in an 8 ml culture medium in a 25 cm 2 flask. Were added at 12.5, 25, 50 or 100 ml, respectively, and cultured for 72 hours.
  • the cells were pulverized to extract proteins, and subjected to electrophoresis.
  • the protein is transferred to a polyvinylidene difluoride membrane (PVDF membrane), reacted with a goat anti-tyrosinase antibody, further reacted with an alkaline phosphatase-labeled anti-goat antibody, and finally a chromogenic substrate is obtained.
  • PVDF membrane polyvinylidene difluoride membrane
  • a goat anti-tyrosinase antibody further reacted with an alkaline phosphatase-labeled anti-goat antibody
  • a chromogenic substrate is obtained.
  • tyrosinase was detected.
  • the same test was carried out using a bismuth acid-free additive.
  • FIG. 1 shows the obtained results.
  • FIG. 1 shows a PVDF membrane image showing the expression level of tyrosinase in B16 melanoma cells cultured in the presence or absence of neubiscus acid.
  • lane I shows no addition of hibiscus acid solution
  • lane II adds 100 ⁇ 1 of 5% hibiscus acid solution
  • lane III adds 50 ⁇ 1 of 5% hibiscus acid solution
  • lane IV shows 5% hibiscus acid solution 25
  • Lane 1 shows the results for a sample with 1 ⁇ l of 5% bismuth acid added.
  • Mouse-derived B16 melanoma cells (D16, manufactured by Dainippon Pharmaceutical Co., Ltd., B16F0) were seeded in a 96-well microphone mouth plate at 5 ⁇ 10 4 cells / well, and cultured in sputum to establish the cells. Next, remove the culture solution from the culture plate with an aspirator, add 1Z Triton X-100-containing PBS (phosphate buffered saline) to lZwell, destroy the cell membrane structure, and remove the crude tyrosinase solution. It was.
  • Control 1 B16 melanoma cell seeding 'Hibiscus acid solution free supplemented solution (PBS added instead)
  • Control 2 B 16 melanoma cell-free seeding 'Hibiscus acid solution free additive (added PBS instead)
  • FIG. Figure 2 illustrates the relationship between the added concentration of bismuth, ibiscus acid and hibiscus extract and the inhibition rate (%) of tyrosinase activity! / Speak.
  • Example 2 the final concentration of bismuth acid monoethyl ester was set to 0.25 by using the bismuth acid monoethyl ester fraction obtained in Production Example 2 instead of bis and biscus acid. Evaluation was performed in the same manner as in Example 2 except that the concentration was adjusted to ⁇ 5 mg / ml.
  • Example 2 As in Example 2, for comparison, instead of the hibiscus monoethyl ester fraction, the hibiscus (Hibiscus sabdarilfa) obtained in Production Example 4 was used.
  • FIG. 3 shows the obtained results.
  • FIG. 3 shows the relationship between the added concentration of the hibiscus monoethyl ester fraction and the nobiscus extract and the inhibition rate (%) of tyrosinase activity.
  • Example 2 instead of bis and biscus acids, the bismuth acid dimethyl ester fraction obtained in Production Example 3 was used, and the final concentration of bismuth acid dimethyl ester was adjusted to 0.25 to 5 mg / ml. Evaluation was performed in the same manner as in Example 2 except that.
  • FIG. Fig. 4 illustrates the relationship between the concentration of bismuth acid dimethyl ester and hibiscus extract and the inhibition rate (%) of tyrosinase activity.
  • the tyrosinase activity inhibition rate (%) was calculated from the measured absorbance value based on the following equation (2).
  • Blank B16 melanoma cell non-seeding: Hibiscus acid solution-free caro
  • Control 2 B 16 melanoma cell-free seeding 'Hibiscus acid solution-free potassium (added PBS instead)
  • Tyrosinase activity inhibition rate 1-(Absorbance of control, Absorbance of control 2 ) ⁇ J 00
  • arbutin-added sample a test was conducted in the same manner except that arbutin was used in place of hibiscus acid, and the tyrosinase activity inhibition rate (%) of arbutin was calculated (hereinafter referred to as an arbutin-added sample).
  • Fig. 5 shows the obtained results.
  • ⁇ and ⁇ indicate the tyrosinase activity inhibition rate (%) of the sample added with hibiscus acid
  • ⁇ and ⁇ indicate the tyrosinase activity inhibition rate (%) of the sample added with arbutin.
  • the dotted line is the measurement result after 20 hours, and the solid line is 108 hours. Later measurement results
  • hibiscus acid has an inhibitory effect on the production of tyrosinase involved in the production of melanin and an inhibitory effect on tyrosinase activity. Even the effect was evaluated.
  • the cells were seeded to 10 5 cellsZwell and cultured overnight to fix the cells. Next, a solution obtained by diluting the nobiscus acid obtained in Production Example 1 with PBS so that the final concentration of the hibiscus acid in the well is 0.2 to 2 mgZml (in the following formula 3, the target sample is also included). ) was added, and after 4 days of culture, the cells were detached using a 0.25% trypsin solution, and the cells were collected by centrifugation. After visually confirming the color difference of the collected cells, the membrane structure of the cells was destroyed with 5N NaOH to elute melanin, and the absorbance at 405 nm was measured.
  • the amount of protein in the sample was measured using a quantification kit, corrected with the amount of unit protein, and the melanin production rate (%) was based on Equation 3 below. Calculated.
  • FIG. Figure 6 shows the melanin production rate (%) at each additive concentration of bis and biscus acids.
  • Example 6 tests and evaluations were performed in the same manner as in Example 6 except that the bisbiscus monoethyl ester fraction obtained in Production Example 2 was used in place of bis and biscus acids.
  • FIG. 7 shows the melanin production rate (%) at each addition concentration of the hibiscus monoethyl ester fraction.
  • Example 6 tests and evaluations were carried out in the same manner as in Example 6 except that the bis-biscus acid dimethyl ester obtained in Production Example 3 was used instead of bis-biscus acid.
  • FIG. 8 shows the obtained results.
  • FIG. 8 shows the melanin production rate (%) at each addition concentration of hibiscus dimethyl ester.
  • the extract obtained from plant power may contain the isomers of bis and biscus acids.
  • the optical isomers of hibiscus acid represented by the following formula (2) galsinic acid represented by the following formula (3) is considered as a naturally occurring one.
  • the cells were seeded to 10 5 cellsZwell and cultured in anther culture to establish the cells. Next, a solution diluted with PBS so that the final concentration of noci, biscus acid or garcinia acid in the well is 0.5 mg / ml (the “target sample” in Equation 4 below). After culturing for 4 days, the cells were detached using a 0.25% tribsin solution, and the cells were collected by centrifugation. After visually confirming the color difference of the collected cells, the membrane structure of the cells was destroyed with 5N NaOH to elute melanin, and the absorbance at 405 nm was measured.
  • non-added sample As a control, the measurement was carried out in the same manner with respect to a system not added with hibiscus acid or garcinia acid (hereinafter referred to as "non-added sample” in formula 4 below).
  • the amount of protein in the sample was measured using a quantification kit, corrected with the amount of unit protein, and the melanin production rate (%) was calculated based on the following equation. .
  • FIG. 9 shows the obtained results.
  • FIG. 9 shows the melanin production rate (%) and the number of cells of garcinia acid and neurobiscus acid at a concentration of 0.5%. BK indicates a blank (no additive sample).
  • the raw materials were blended at the blending ratios shown in the following table, and a lotion was produced according to a conventional method.
  • the raw materials were blended at the blending ratios shown in the table below, and the emulsion was produced according to a conventional method (raw materials) (wt%)
  • Nonfat dry milk 1. 0
  • the ingredients were blended at the blending ratios shown in the table below, and a drink was produced according to a conventional method.
  • the raw materials were blended at the blending ratios shown in the table below, and toothpastes were produced according to conventional methods.
  • the raw materials were blended at the blending ratios shown in the table below, and a mouthwash was produced according to a conventional method.
  • FIG. 1 is a PVDF image showing the expression level of tyrosinase in B16 melanoma cells cultured in Example 1 in the presence or absence of hibiscus acid.
  • Lane I is without hibiscus acid; Lane II is with 5% hibiscus acid solution 100 ⁇ 1; Lane III is with 5% hibiscus acid solution 50 ⁇ 1; Lane IV is 5% hibiscus acid solution 25 ⁇ m
  • Lane 1 is a diagram showing a sample of 12.5 ⁇ l-added 5% biscus acid solution.
  • FIG. 2 shows the concentration of hibiscus acid or hibiscus extract and tyrosin in Example 2. It is a figure which shows the relationship of the enzyme activity inhibition rate (%).
  • FIG. 3 is a graph showing the relationship between the added concentration of hibiscus monoethyl ester fraction or hibiscus extract and the tyrosinase activity inhibition rate (%) in Example 3.
  • FIG. 4 shows the relationship between the concentration of hibiscus dimethyl ester or hibiscus extract and the inhibition rate (%) of tyrosinase activity in Example 4.
  • FIG. 5 is a graph showing the tyrosinase activity inhibition rate (%) in Example 5 after 20 hours and 108 hours of incubation in the hibiscus acid added group and arbutin added group.
  • FIG. 6 is a graph showing the relationship between the concentration of hibiscus acid added and the melanin production rate (%) in Example 6.
  • FIG. 7 is a graph showing the relationship between the added concentration of the hibiscus monoethyl ester fraction and the melanin production rate (%) in Example 7.
  • FIG. 8 shows the relationship between the concentration of bismuth acid dimethyl ester added and the melanin production rate (%) in Example 8.
  • FIG. 9 is a graph showing the number of cells and melanin production rate (%) when the concentration of hibiscus acid and garcinic acid in the well is 0.5 mgZml in a test example.

Landscapes

  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Nutrition Science (AREA)
  • Food Science & Technology (AREA)
  • Polymers & Plastics (AREA)
  • Dermatology (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical & Material Sciences (AREA)
  • Mycology (AREA)
  • Botany (AREA)
  • Birds (AREA)
  • Epidemiology (AREA)
  • Cosmetics (AREA)

Abstract

Les problèmes à résoudre dans la présente invention concernent un agent blanchissant la peau, un produit cosmétique blanchissant la peau, un aliment blanchissant la peau et une composition par voie à orale ayant un effet excellent et soutenu d'inhibition de la production de la mélanine ou de blanchissement de la peau. La solution apportée par l'invention consiste en un agent inhibiteur de la production de la mélanine comprenant un ou plusieurs composés sélectionnés dans un groupe consistant en de l’acide d’hibiscus et des dérivés d’acide d’hibiscus représentés par la formule générale (I) et des sels de cet acide d’hibiscus en tant qu’ingrédient(s) actif(s) ; et en un agent blanchissant la peau, un produit cosmétique blanchissant la peau, un aliment blanchissant la peau ou une composition par voie orale comprenant un agent inhibiteur de la production de la mélanine en tant qu’ingrédient actif. (1) dans laquelle R1 et R2 représentent indépendamment un atome d’hydrogène ou un groupe alkyle substitué ou non substitué ou un groupe benzyle.
PCT/JP2006/306976 2005-03-31 2006-03-31 Agent inhibiteur de la production de melanine WO2006106992A1 (fr)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
JP2005103194 2005-03-31
JP2005-103194 2005-03-31
JP2006-097110 2006-03-31
JP2006097110A JP2006306863A (ja) 2005-03-31 2006-03-31 メラニン生成抑制剤

Publications (1)

Publication Number Publication Date
WO2006106992A1 true WO2006106992A1 (fr) 2006-10-12

Family

ID=37073542

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2006/306976 WO2006106992A1 (fr) 2005-03-31 2006-03-31 Agent inhibiteur de la production de melanine

Country Status (2)

Country Link
JP (1) JP2006306863A (fr)
WO (1) WO2006106992A1 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2016504910A (ja) * 2012-12-24 2016-02-18 エルブイエムエイチ レシェルシェ チロシナーゼの酵素活性を阻害するアプタマー
WO2017019793A1 (fr) * 2015-07-27 2017-02-02 Coty Inc. Triple acide pour micro-administration

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2009019010A (ja) * 2007-07-12 2009-01-29 Sosin:Kk 口腔用組成物
KR101007468B1 (ko) 2008-11-14 2011-01-12 강원대학교산학협력단 양마 추출물을 함유하는 피부 미백용 외용제 조성물
EP3006016A1 (fr) 2014-10-06 2016-04-13 Medical Brands Research B.V. Kit dermatologique comprenant des compositions à base de fleur d'hibiscus et d'huile de buriti
KR102126840B1 (ko) * 2018-07-09 2020-06-25 대한민국 무궁화 꽃잎 추출물의 제조방법, 무궁화 꽃잎 추출물을 유효성분으로 포함하는 피부 미백용 화장료 조성물 및 멜라닌 색소 과다 침착 질환의 예방 또는 개선용 약학조성물
JP7388748B2 (ja) * 2020-11-10 2023-11-29 株式会社デジマ 乳酸菌体のハマボウ抽出物用の呈味改善用添加剤としての使用

Citations (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS5888305A (ja) * 1981-11-19 1983-05-26 Nikko Kemikaruzu Kk 化粧料
EP0425398A1 (fr) * 1989-10-23 1991-05-02 Camille Isnard Eau d'aloès, procédé de préparation et compositions la renfermant
JPH0624937A (ja) * 1992-06-29 1994-02-01 Narisu Keshohin:Kk ムコ多糖類断片化抑制剤、活性酸素消去剤、抗酸化剤および化粧料。
JPH09295928A (ja) * 1996-05-01 1997-11-18 Narisu Keshohin:Kk 老化防止化粧料
JPH11349469A (ja) * 1998-06-08 1999-12-21 Kanebo Ltd 紫外線防御化粧料
JP2000095663A (ja) * 1998-09-24 2000-04-04 Kose Corp 植物抽出物を含有する外用剤
JP2000154134A (ja) * 1998-11-17 2000-06-06 Naris Cosmetics Co Ltd 化粧料
JP2000239164A (ja) * 1999-02-19 2000-09-05 Kikkoman Corp グリコシダーゼ阻害剤
US6127553A (en) * 1998-08-03 2000-10-03 Department Of Science And Technology, Goverment Of India Convenient method for large-scale isolation of hibiscus acid
US20030088110A1 (en) * 2000-10-03 2003-05-08 Saud Ibrahim Ibnu Novel chiral derivatives of hibiscus acid bearing lactone ring moiety, process for preparing the same and a convenient method for the large-scale isolation of hibiscus acid
JP2003171300A (ja) * 2001-09-28 2003-06-17 Kobayashi Pharmaceut Co Ltd メラニン生成抑制剤
JP2004346006A (ja) * 2003-05-22 2004-12-09 Kyoei Kogyosho:Kk 化粧水及びその製造方法

Patent Citations (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS5888305A (ja) * 1981-11-19 1983-05-26 Nikko Kemikaruzu Kk 化粧料
EP0425398A1 (fr) * 1989-10-23 1991-05-02 Camille Isnard Eau d'aloès, procédé de préparation et compositions la renfermant
JPH0624937A (ja) * 1992-06-29 1994-02-01 Narisu Keshohin:Kk ムコ多糖類断片化抑制剤、活性酸素消去剤、抗酸化剤および化粧料。
JPH09295928A (ja) * 1996-05-01 1997-11-18 Narisu Keshohin:Kk 老化防止化粧料
JPH11349469A (ja) * 1998-06-08 1999-12-21 Kanebo Ltd 紫外線防御化粧料
US6127553A (en) * 1998-08-03 2000-10-03 Department Of Science And Technology, Goverment Of India Convenient method for large-scale isolation of hibiscus acid
JP2000095663A (ja) * 1998-09-24 2000-04-04 Kose Corp 植物抽出物を含有する外用剤
JP2000154134A (ja) * 1998-11-17 2000-06-06 Naris Cosmetics Co Ltd 化粧料
JP2000239164A (ja) * 1999-02-19 2000-09-05 Kikkoman Corp グリコシダーゼ阻害剤
US20030088110A1 (en) * 2000-10-03 2003-05-08 Saud Ibrahim Ibnu Novel chiral derivatives of hibiscus acid bearing lactone ring moiety, process for preparing the same and a convenient method for the large-scale isolation of hibiscus acid
JP2003171300A (ja) * 2001-09-28 2003-06-17 Kobayashi Pharmaceut Co Ltd メラニン生成抑制剤
JP2004346006A (ja) * 2003-05-22 2004-12-09 Kyoei Kogyosho:Kk 化粧水及びその製造方法

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2016504910A (ja) * 2012-12-24 2016-02-18 エルブイエムエイチ レシェルシェ チロシナーゼの酵素活性を阻害するアプタマー
WO2017019793A1 (fr) * 2015-07-27 2017-02-02 Coty Inc. Triple acide pour micro-administration
US10470988B2 (en) 2015-07-27 2019-11-12 Coty Inc. Skin improvement formulations

Also Published As

Publication number Publication date
JP2006306863A (ja) 2006-11-09

Similar Documents

Publication Publication Date Title
WO2006106992A1 (fr) Agent inhibiteur de la production de melanine
JP4015792B2 (ja) 美白剤及びそれを有効成分として含有する皮膚外用剤
JP2001026530A (ja) 美白剤
JP2003171300A (ja) メラニン生成抑制剤
KR102425562B1 (ko) 분갈 추출물 또는 이로부터 유래된 화합물을 포함하는 피부 개선용 조성물
KR100755742B1 (ko) 아크릴레이트계 화합물을 포함하는 피부 미백용 조성물
KR20160020253A (ko) 아트락틸레놀라이드 i을 포함하는 피부 미백, 탄력, 주름개선, 또는 보습용 화장료 또는 약학 조성물
KR100982435B1 (ko) （２ｚ，８ｚ）―매트리카리아산 메틸 에스테르를유효성분으로 함유하는 피부 미백용 조성물
KR20080097636A (ko) 산딸나무 추출물 또는 이로부터 분리된 화합물을유효성분으로 함유하는 항노화 및 주름개선용 조성물
JP4902967B2 (ja) メラニン生成抑制剤
KR20160020223A (ko) 샨즈히시드 메틸에스터 또는 이의 약학적으로 허용가능한 염을 포함하는 피부 미백, 탄력, 주름개선, 또는 보습용 화장료 또는 약학 조성물
KR101851928B1 (ko) S-메틸메티오닌 설포늄의 유도체를 유효성분으로 포함하는 피부 미백용 조성물
KR20180061662A (ko) 아네모시드 a3을 포함하는 화장료 조성물
KR20170080074A (ko) 브라시놀라이드를 포함하는 피부상태 개선용 조성물
KR20170080069A (ko) 에스큘렌토사이드 에이를 포함하는 피부상태 개선용 조성물
KR20170078102A (ko) 데메틸웨델로락톤을 포함하는 피부상태 개선용 조성물
KR20170080084A (ko) 네포딘을 포함하는 피부상태 개선용 조성물
JPH05213730A (ja) チロシナーゼ活性抑制剤
KR20160019815A (ko) 에스쿨렌토시드 a 또는 이의 약학적으로 허용가능한 염을 포함하는 피부 미백, 탄력, 주름개선, 또는 보습용 화장료 또는 약학 조성물
KR20160020241A (ko) Prim-O-글루코실시미푸긴 또는 이의 약학적으로 허용가능한 염을 포함하는 피부 미백, 탄력, 주름개선, 또는 보습용 화장료 또는 약학 조성물
KR101289811B1 (ko) 산복숭아꽃 추출물을 유효성분으로 포함하는 피부 주름 개선용 조성물
KR20230018694A (ko) 파이탄트린 a를 포함하는 미백용 조성물
KR20160020250A (ko) 우고노시드 또는 이의 약학적으로 허용가능한 염을 포함하는 피부 미백, 탄력, 주름개선, 또는 보습용 화장료 또는 약학 조성물
JPWO2003047593A1 (ja) エルゴステロール誘導体からなるメラニン生成抑制剤及び美白剤、並びにエルゴステロール誘導体を含有する組成物
JP2006022070A (ja) メラニン生成抑制剤

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application
NENP Non-entry into the national phase

Ref country code: DE

NENP Non-entry into the national phase

Ref country code: RU

122 Ep: pct application non-entry in european phase

Ref document number: 06730924

Country of ref document: EP

Kind code of ref document: A1