WO2006106992A1 - Melanin production inhibitory agent - Google Patents

Abstract

[PROBLEMS] To provide a skin-whitening agent, a skin-whitening cosmetic, a skin-whitening food and a composition for oral use having sustained, excellent melanin production inhibitory effect or skin whitening effect. [MEANS FOR SOLVING PROBLEMS] A melanin production inhibitory agent comprising one or more compounds selected from the group consisting of hibiscus acid and hibiscus acid derivatives represented by the general formula (1) and salts thereof as the active ingredient(s); and a skin-whitening agent, a skin-whitening cosmetic, a skin-whitening food or a composition for oral use comprising the melanin production inhibitory agent as the active ingredient. (1) wherein R1 and R2 independently represent a hydrogen atom, a substituted or unsubstituted alkyl group or a benzyl group.

Description

 Melanin production inhibitor

 Technical field

 TECHNICAL FIELD [0001] 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.

 Conventionally, it is known that the deposition of pigments such as stains and freckles is caused by the formation and accumulation of melanin in skin cells. In addition, when melanin is generated not only in the skin but also in the mucous membrane of the oral cavity, it will be broken!

 [0003] The production process of melanin has not yet been fully elucidated, but the following process has become clear as one of its main production processes. That is, (1) active oxygen is generated in the epidermis cells of the skin when the skin is exposed to ultraviolet rays, (2) cells are damaged by active oxygen, and various information-transmitting substances are generated and released, (3) Various signaling substances cause the promotion and activation of tyrosinase and produce melanin.

 [0004] Therefore, in order to suppress the production of melanin and keep the skin white, it is effective to eliminate active oxygen on the skin, inhibit the production of tyrosinase, or inhibit tyrosinase activity. It is considered as

 [0005] To date, 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.). However, 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. Furthermore, the conventional whitening ingredients have not been able to satisfy the viewpoint of sustaining the effect.

[0006] On the other hand, cosmetics and pharmaceuticals containing hibiscus acids are known. For example, 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! Never 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

 Disclosure of the invention

 Problems to be solved by the invention

[0007] 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.

 Means for solving the problem

[0008] As a result of intensive studies aimed at solving the above-mentioned problems, the present inventors have found that a compound having a specific structure has an excellent melanin production inhibitory effect, and further intensive studies. The present invention has been completed.

[0009] That is, the present invention relates to the following melanin production inhibitor, whitening agent, cosmetic, food and oral composition.

[0010] Item 1: Formula (1) below

[0011] [Chemical 1]

(Where R ¹ and R ² are each a hydrogen atom, a substituted or unsubstituted alkyl group, or A benzyl group is shown. 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.

[0013] 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.

 [0014] Preferably, the following formula (1)

[0015] [Chemical 2]

(In the formula, 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.

 [0017] Preferably, 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.

 [0018] More preferably, 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.

 [0019] Item 3: A whitening agent comprising the melanin production inhibitor according to any one of Items 1 to 2 as an active ingredient.

 [0020] 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. [0022] Item 6: An oral composition comprising the melanin production inhibitor according to any one of Items 12 and 12 as an active ingredient.

 [0023] Hereinafter, the present invention will be described in more detail.

[0024] Melanin production inhibitor

 The melanin production inhibitor of the present invention has the following formula (1)

[0025] [Chemical 3]

[0026] (In the formula, 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.

[0027] 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.

[0028] 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.

[0029] Specific examples of the alkyl group include a methyl group, an ethyl group, a propyl group, a butyl group, an isopropyl group, an isobutyl group, and a hexyl group.

[0030] 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.

[0031] Specific examples of 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. [0032] Hibiscus acid monoesters include, for example, hibiscus monoalkyl esters such as hibiscus monomethyl ester and bisbis monoethyl ester.

 [0033] Hibiscus acid diesters include, for example, bismuth acid dialkyl esters such as bismuth acid dimethyl ester, and biscus acid decyl ester.

[0034] 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.

 [0035] Examples of the alkali metal salt include sodium salt and potassium salt. Examples of alkaline earth metal salts include calcium salts and magnesium salts. The salt also includes those forming a complex. For example, 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.

 [0036] 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. In addition, 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.

 [0037] 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. For example, a plant that contains hibiscus acid may be extracted with a suitable extraction solvent and then separated by means such as chromatography.

 [0038] Examples of plants containing hibiscus acids include plants belonging to the genus Fuyu.

 [0039] 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.

rosa- sinensis L.), Chinese mugwort (Hibiscus syriacus L.), African native kenaf (Hibiscus cannabinus) L.), North American-grown Momiji (Hibiscus coccineus L.), Japanese-grown hawk (Hibiscus hamabo), Chinese-grown Fuyou (H¾iscus

 mutabilis L.). Of these, it is preferable to use Roselle, Bussouge and Mukuge, and Roselle and Bussouge are particularly preferable.

 [0040] 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.

 [0041] 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.

[0042] 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. Examples of 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. Among these, preferable extraction solvents include lower alcohols such as methanol, ethanol, and isopropanol, or a mixture of water and lower alcohols.

 [0043] After extraction, various chromatographies such as dissolution, re-extraction, separation, gradient, filtration, concentration, distillation, sublimation, crystallization, thin-layer chromatography, column chromatography, gas chromatography, and high-performance liquid chromatography. Various methods such as separation using a graph can be purified appropriately, alone or in combination.

 [0044] Further, if necessary, water can be removed by performing a drying treatment such as reduced-pressure drying or freeze-drying to use as a dried product.

[0045] Specific conditions for extraction can also be appropriately set according to a conventional method without particular limitation. For example, 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. Furthermore, a method of performing purification by HPLC can be mentioned. [0046] In addition, as commercially available bis and ibiscus acids, commercially available ones can also be used. Further, the ester can be obtained from commercially available hibiscus acid by subjecting it to esterification according to a known method.

 [0047] 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.

 [0048] 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.

 [0049] 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.

 [0050] Further, more preferably, 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. .

 [0051] 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.

 [0052]

 The whitening agent of the present invention contains the melanin production inhibitor of the present invention as an active ingredient.

[0053] 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! /

[0054] 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.

[0055] Further, 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.

 [0056] Further, the whitening agent of the present invention may be an external preparation or an internal preparation.

[0057] In formulating the whitening agent of the present invention as an external preparation, if necessary, 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.

 [0058] The types of external preparations to which the whitening agent of the present invention can be applied are not particularly limited. For example, 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.

 [0059] When the whitening agent of the present invention is formulated as an external preparation, 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.

 [0060] 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.

 [0061] 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.

 [0062] When the whitening agent of the present invention is formulated as an internal preparation, 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.

[0063] 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. In addition, 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.

 [0064] & m ^ M

 The whitening cosmetic composition of the present invention contains the melanin production inhibitor of the present invention as an active ingredient.

 [0065] The type of cosmetic is not particularly limited, and can be applied to various cosmetics. For example, creams, emulsions, lotions, knocking agents, facial cleansers, various basic cosmetics such as powders, foundations, cheeks, white powders, makeup products, hair washing products, hair nourishing agents, shampoos, etc. It can be applied to various types of cosmetics such as rinsing and other hair cosmetics, sarcophagus, beauty nails, eau de cologne, and bath salts.

 [0066] The form of the cosmetic is not particularly limited, either, solution, emulsion, ointment, sol, gel, powder.

, Sprays, sheets, films, and the like.

[0067] In the cosmetic of the present invention, various components that are generally blended in cosmetics, for example, an aqueous component, a powder component, a moisturizer, a surfactant, a preservative, an increase agent, within the scope of the effects of the present invention. Adhesives, ultraviolet absorbers, fragrances and the like can be blended.

[0068] The method for producing the cosmetic of the present invention is not particularly limited, and can be suitably produced according to a known method.

 [0069] 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.

 [0070] 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. However, as 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.

[0071] 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.

 [0072] Food for whitening

 The whitening food of the present invention contains the melanin production inhibitor of the present invention as an active ingredient.

[0073] 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.

[0074] 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.

 [0075] The type of food is not particularly limited, and can be appropriately set from various known foods and drinks. For example, 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.

 [0076] In addition, 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. Examples of 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.

[0077] 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.

 [0078] 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.

[0079] 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.

 [0080] Oral composition

 The composition for oral cavity of the present invention contains the melanin production inhibitor of the present invention as an active ingredient.

 [0081] The type of oral composition is not particularly limited, and can be applied to various oral compositions.

[0082] For example, it can be applied to various oral compositions such as toothpaste such as toothpaste, mouthwash, mouth rinse, oral paste, troche, gum massage cream and the like.

[0083] 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.

 [0084] In the 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.

 [0085] 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.

 [0086] 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.

 [0087] 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.

[0088] 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 | dye which carried out is removed and there exists an outstanding whitening effect | action.

 The invention's effect

 [0089] According to the present invention, there is provided 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.

 [0090] 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.

 [0091] 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.

[0092] 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. In addition, 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.

 [0093] 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. BEST MODE FOR CARRYING OUT THE INVENTION

 [0094] Hereinafter, the present invention will be described in detail with reference to Examples, Production Examples, and Test Examples, but the present invention is not limited thereto.

 [0095] Example 1 (Hibiscus acid)

800 g of dried Hibiscus sabdariffa L. flowers were pulverized with a mill, and 8 L of 1.5% hydrochloric acid-methanol aqueous solution was added thereto, followed by extraction treatment with stirring at room temperature for 3 hours. Subsequently, the solid content was removed by filtration, and the filtrate was concentrated with an evaporator (45 ° C.). This filtrate was purified and concentrated by ΗΡ-20 (φ = 70 mm, h = 500 mm) column chromatography to obtain 118 g of a crude product. It was.

 [0096] The obtained crude product was purified and concentrated several times by ODS (φ = 110 mm, h = 1200 mm) column chromatography, and then crystallized to obtain 34.8 g of biscus acid.

 [0097] The substance obtained for confirmation was analyzed. As a result, the molecular weight according to the mass spectrum was 190. Proton NMR was as follows.

[0098] Proton NMR ^ vector (400MHz) (acetone d6) δ (ppm): 5.35 (1H, S), 3.26 (1H, d, J = 17.2Hz), 2.78 (1H, d, J = 17.2Hz) ₀

 These values were consistent with the values for bis and biscus acids reported by Boll et al. (Acta Chemica Scandinavica, 1969, Vol. 23, pp. 286-293).

 [0099] Example 2 (Nobiscus monoethyl ester)

 100 g of dried Hibiscus sabdariffa L. flowers were pulverized with a mill, added with 500 mL of 30% aqueous ethanol, and extracted for 3 days with stirring at room temperature. Next, extraction with ethyl acetate was performed, and the obtained aqueous layer was further extracted with butanol, and then purified with silica gel chromatography (eluent: ethyl acetate-methanol solution) to obtain a fraction. .

 [0100] When the obtained fraction was analyzed, the molecular weight was 218 according to the mass spectrum. In proton NMR, several overlapping signals were observed, and the existence of several isomers was expected. In addition, one of the compounds considered to have one of the following signals was recognized.

[0101] Proton NMR ^ vector (500MHz) (CDC13) δ (ppm): 5.23 (1H, S), 3.20 (1H, d, J = 17.4Hz), 2.90 (1H, d, J = 17.4Hz), 4.29 (2H, m), 1.37 (3H, t, J = 7.4Hz) ₀

 [0102] From the above analysis results and the fact that Hibiscus sabdariffa contained a large amount of hibiscus acid, it was presumed that the fraction contained hibiscus monoethyl ester and isomers thereof.

 [0103] The structures of the nobis, bisbisic acid monoethyl ester and isomers thereof are presumed to be the following (a) and (b).

[0104] [Chemical 4] H o 0 (b)

, HC ₂ H ₅ 0 H

 O

Hereinafter, the obtained fraction is also referred to as “no biscus acid monoethyl ester fraction”.

[0106] Example 3 (Hibiscus acid dimethyl ester)

 450 mg of 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.

 [0107] When the substance obtained for confirmation was analyzed, the molecular weight by mass spectrum was 218. Proton NMR was as follows.

[0108] Proton NMR ^ vector (400 MHz) (black mouth form dl) δ (ppm): 5.11 (1H, S), 3.08 (1H, d, J = 17.5Hz), 2.88 (1H, d, J = 17.2Hz ), 3.80 (1H, S), 3.84 (3H, S), 3.96 (3H, S

).

 [0109] These values were consistent with those of hibiscus acid dimethyl ester reported by IBnusaud et al. (Tetrahedron, 2002, Vol. 58, 4887-4892).

[0110] Production Example 4 Lebiscus extract)

 For use as a comparison, a biscus extract (extract) was produced by the following method.

[0111] 100 g of dried Hibiscus sabdariffa L. flower was pulverized with a mill, and 500 mL of a 30% aqueous ethanol solution was added to this and extracted for 3 days with stirring at room temperature. Next, the solid content was removed by filtration, and the filtrate was concentrated under reduced pressure, and then freeze-dried to obtain 15 g of Hibkmi Ssabdariffa L. extract.

[0112] ¾ application {line ί tyrosinase ¾ flat In order to evaluate the inhibitory effect of bis and ibiscus acid on the production of tyrosinase, we stamped lots as follows.

[0113] 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.

 [0114] After completion of the culture, the cells were pulverized to extract proteins, and subjected to electrophoresis. Next, 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. As a result, tyrosinase was detected. For comparison, the same test was carried out using a bismuth acid-free additive.

 [0115] 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.

 [0116] In the figure, lane I shows no addition of hibiscus acid solution, lane II adds 100 μ1 of 5% hibiscus acid solution, lane III adds 50 μ1 of 5% hibiscus acid solution, lane IV shows 5% hibiscus acid solution 25 Lane 1 shows the results for a sample with 1 μl of 5% bismuth acid added.

 [0117] As is apparent from the thickness of the band shown in Fig. 1, the cultures added with no, ibiscus acid and those added with no, ibiscus acid increased with the increase of the concentration. Thus, it was confirmed that the expression of tyrosinase tends to be suppressed.

 As a result, it has been clarified that bis and ibiscus acid have a tyrosinase production inhibitory effect.

 Example 2 Tyrosinase Activity V. Evaluation of Harmful Effect (Hibiscus Acid)

 In order to evaluate the activity inhibitory effect of tyrosinase of bis and biscus acids, the following tests were conducted.

[0120] 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.

 Next, a solution obtained by diluting the nobiscus acid obtained in Production Example 1 with PBS so that the final concentration of hibiscus acid in the well becomes 0.3 to 2.5 mg / ml (in the following formula 1, the hibiscus acid is used). (Also referred to as an added sample) was added at 50 lZwell. Thereafter, 50 / zL of 0.1% dopa solution diluted with PBS was added and immediately incubated at 37 ° C for 4 hours, and then the absorbance at 405 nm was measured using a microplate reader.

 [0121] As a control, the following conditions were also measured in the same manner.

[0122] Based on the measured absorbance value, the tyrosinase activity inhibition rate (%) was calculated based on Equation 1 below.

 • Blank: B 16 melanoma cells unseeded: Hibiscus acid solution-free caro

 • Hibiscus acid added sample: B 16 melanoma cell seeding · Hibiscus acid solution added caro

• 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)

 [0123] [Equation 1]

 (Absorbance of hibiscus acid added sample

 Tyrosinase activity inhibition rate (X): Absorbance of one blank)

 X 100

(Control 1 absorbance vs. Control 2 absorbance)

[0124] For comparison, a test was carried out in the same manner as above except that the biscus acid (Hibi scus sabdariffa L.) extract obtained in Production Example 4 was used instead of hibiscus acid, and the tyrosinase activity of The inhibition rate (%) was also calculated.

 [0125] The obtained results are shown in 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.

 [0126] From these results, it was confirmed that bis and biscus acid have a higher tyrosinase activity inhibitory action than hibiscus extract, and that the effect is enhanced in a concentration-dependent manner.

 Example 3 Tyrosinase Activity V. Evaluation of Harmful Effect (Hibiscus Acid

In 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.

[0128] As in Example 2, for comparison, instead of the hibiscus monoethyl ester fraction, the hibiscus (Hibiscus sabdarilfa) obtained in Production Example 4 was used.

 The same test was conducted except that the extract was used, and the tyrosinase activity inhibition rate (%) of the hibiscus extract was also calculated.

[0129] 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.

 [0130] From this result, it was confirmed that the hibiscus acid monoethyl ester fraction had a higher tyrosinase activity inhibitory effect than that of biscus ibis extract, and that the effect increased in a concentration-dependent manner. It was.

 [0131] u tyrosinase activity 評. Evaluation of harmful effects (Dimethyl Hibiscusate ヱ)

 In 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.

 [0132] For comparison, in the same manner as in Example 2, a test was conducted in the same manner except that the Hibiscus sabdarilfa L. extract obtained in Production Example 4 was used instead of Hibiscus acid dimethyl ester. The tyrosinase activity inhibition rate (%) of the extract was also calculated.

 [0133] The obtained results are shown in FIG. Fig. 4 illustrates the relationship between the concentration of bismuth acid dimethyl ester and hibiscus extract and the inhibition rate (%) of tyrosinase activity.

[0134] From these results, it was confirmed that bismuth acid dimethyl ester has a tyrosinase activity inhibitory action equivalent to that of biscus ibis extract and that the effect is enhanced in a concentration-dependent manner.

 [0135] Example 5 Tyrosinase activity 評 価. Evaluation of sustained effects of harmful effects (Hibiscus acid)

 In order to evaluate the persistence of the inhibitory effect of bismuth acid and bismuth acid on melanin production, a test for confirming the persistence of the tyrosinase activity inhibitory effect was performed according to the following method.

[0136] Mouse-derived B16 melanoma cells (Dainippon Pharmaceutical, B16F0) in a 96-well microphone mouthplate The cells were seeded at 5 × 10 ⁴ cells / well and cultured in a sputum to establish the cells. Next, the culture solution on the culture plate was removed with an aspirator, and 50 μl ZweU of PBS (phosphate buffered saline) containing 1% Triton X-100 was added to disrupt the cell membrane structure to obtain a crude tyrosinase solution.

 Next, a solution obtained by diluting the nobiscus acid obtained in Production Example 1 with PBS so that the final concentration of hibiscus acid in the well was 0.3 to 10 mg / mL was added with 50 lZwell (hereinafter referred to as Hibiscus). (It is also referred to as acid-added sample.) O After that, 50 μL of 0.1% dopa solution diluted with PBS was added and incubated at 37 ° C immediately.

[0137] The absorbance at 405 nm was measured using a microplate reader 20 hours and 108 hours after the initiation of incubation.

[0138] As a control, the following conditions were also measured in the same manner.

[0139] The tyrosinase activity inhibition rate (%) was calculated from the measured absorbance value based on the following equation (2).

 [0140] · Blank: B16 melanoma cell non-seeding: Hibiscus acid solution-free caro

 • Hibiscus acid added sample: B16 melanoma cell seeding • Hibiscus acid solution added caro • Control 1: B16 melanoma cell seeded 'Hibiscus acid solution not added (PBS added instead)

 • Control 2: B 16 melanoma cell-free seeding 'Hibiscus acid solution-free potassium (added PBS instead)

[0141] [Equation 2]

"(Absorbance of Hibiscus acid added sample-Absorbance of blank)

Tyrosinase activity inhibition rate 1-(Absorbance of control, Absorbance of control ₂ ) ^ J ⁰⁰

[0142] For comparison, 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).

[0143] Fig. 5 shows the obtained results. In FIG. 5, 〇 and 參 indicate the tyrosinase activity inhibition rate (%) of the sample added with hibiscus acid, and △ 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

 Show.

 As is clear from FIG. 5, in the measurement results after 20 hours, biscus acid and biscus acid showed a higher tyrosinase inhibitory effect than arbutin. Further, in the measurement result after 108 hours, the sample added with biscus acid maintained a high tyrosinase inhibitory effect.

 [0145] In contrast, in the arbutin-added sample, a significant decrease in the inhibition rate of tyrosinase activity was observed after 108 hours compared to 20 hours later.

 [0146] From these results, it was suggested that bis and biscus acid have a high and sustained tyrosinase activity inhibitory effect and can maintain a high whitening effect over a long period of time.

 [0147] me melanin cattle ¾ effect (Hibiscus coffee)

 From the above results, it has been clarified that 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.

 [0148] The evaluation test was performed according to the following method.

 [0149] Mouse-derived B16 melanoma cells (Dainippon Pharmaceutical Co., Ltd., B16F0) were placed on a 6-well plate at about 1 X

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.

 [0150] As a control, the same measurement was performed on a system not added with hibiscus acid (hereinafter referred to as an additive-free sample in Formula 3 below).

 [0151] Furthermore, in order to correct errors during preparation of the solution, 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.

 [0152] [Equation 3] Nin production rate (¾) = (Absorbance of target sample) No (Amount of protein in target sample) X

(Absorbance of additive-free sample) Z (protein amount of additive-free sample) [0153] The obtained results are shown in FIG. Figure 6 shows the melanin production rate (%) at each additive concentration of bis and biscus acids.

 [0154] As a result, it was confirmed that the addition of hibiscus acid significantly suppressed the production of melanin, and it became clear that it was useful as a hibiscus acid lanine production inhibitor.

 Example 7 Inhibitory Effect of Melanin Formation (Ibiscus acid monoethyl ester)

 In 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.

[0156] The obtained results are shown in FIG. FIG. 7 shows the melanin production rate (%) at each addition concentration of the hibiscus monoethyl ester fraction.

[0157] As a result, it was confirmed that the addition of the bismuth acid monoethyl ester fraction significantly suppressed the production of melanin, and the bismuth acid monoethyl ester carbonate production was suppressed. It became clear that it was useful as an agent.

 [0158] ms Melayun cattle growth control effect (Hibiscus acid dimethyl ester)

 In 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.

[0159] Fig. 8 shows the obtained results. FIG. 8 shows the melanin production rate (%) at each addition concentration of hibiscus dimethyl ester.

[0160] As a result, it was confirmed that the addition of bismuth acid dimethyl ester significantly suppressed the production of melanin, and it was clear that it was useful as an inhibitor of bismuth acid dimethyl ester power lanine production. became.

[0161] Test example

 Since the optical isomers of bis and ibiscus acids exist, the extract obtained from plant power may contain the isomers of bis and biscus acids. Among 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.

[0162] [Chemical 5]

 [0163] Therefore, in order to confirm whether the whitening action was characteristic of the three-dimensional structure of hibiscus acid, a test on the melanin production inhibitory action of hibiscus acid and garcinia acid was performed according to the following procedure. In addition, cytotoxicity was also evaluated to confirm the safety of hibiscus acid.

 [0164] The melanin production inhibitory action was tested as follows.

 [0165] Mouse-derived B16 melanoma cells (B16F0, manufactured by Dainippon Pharmaceutical Co., Ltd.)

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.

 [0166] 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).

 [0167] Furthermore, in order to correct errors during solution preparation, 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. .

[0168] [Equation 4] Meller, 'Production rate = (Absorbance of target sample) z (Protein amount of target sample) X _{1 00}

 (Absorbance of additive-free sample) / (protein amount of additive-free sample)

[0169] Regarding cytotoxicity, the collected culture was stained with trypan blue, and the number of viable cells was measured with a hemocytometer. [0170] 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).

 [0171] As a result, it was found that neutral biscus acid had an inhibitory effect on melanin production and low cytotoxicity.

 [0172] On the other hand, it has been clarified that garcinia acid is highly cytotoxic with almost no inhibitory effect on melanin production.

 [0173] From this, it was suggested that the steric strength of hibiscus acid is important for the melanin production inhibitory effect.

[0174] Formulation example

 Hereinafter, the present invention will be described in more detail with reference to formulation examples of the present invention, but the present invention is not limited thereto.

[0175] <Prescription Example 1> Lotion

 The raw materials were blended at the blending ratios shown in the following table, and a lotion was produced according to a conventional method.

 (Raw material) (wt%)

 Neubiscus acid 0.5

 Ascorbic acid magnesium phosphate 3.0

 Polypropylene glycol 2.0

 Oxybenzone 3.0

 Paraxybenzoate ester 0.5

 Quenic acid

 Perfume

 Purified water mm _

 Total 100. 0

 [0176] <Prescription Example 2> Cosmetic cream

Ingredients are blended in the proportions shown in the table below, and cosmetic creams are produced according to conventional methods. Hibiscus acid monomethyl ester 0.

Ascorbic acid monostearate 3

 Ten

Stearyl Arco 5.0

Stearic acid 8.0

Screen 10.0

Self-emulsifying glyceryl monostearate 3.0

Polyoxyethylene cetyl ether (20E. 0) 1.0

Propylene glycol 5.0

Potassium hydroxide 0.3

Fragrance

Preservative

Total 100. 0

 <Formulation example 3> Emulsion

 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%)

Monobiscusic acid monomethylenoestenole 1. 0

Nobisci acid monoethino estenole 1. 0

Skulun 8.0

Vaseline 2.0

Beeswax 0.5

Sonorebitan Sesquitoate 0.8

Polyoxyethylene oleyl ether (20E. 0) 1.2

Canoleboxyvininole polymer 0.2

Propylene glycol 0.5

Potassium hydroxide 0.1

Ethanol 7.0 Fragrance

 Preservative

 Summary 7k

 Total 100. 0

 [0178] <Prescription Example 4> Bread

The raw materials were blended in proportions shown in the following table according to a conventional method, to produce bread _c

(Raw material) (wt%)

flour

 Sugar 3.0

 Salt 1. 0 〇

 No, biscus acid 0.5

 Nonfat dry milk 1. 0

 Oils and fats 3.1

 East Food 0.1

 East 1.0

 The rest

 A

 O Doo B I 100. 0

 [0179] <Prescription Example 5> Tablet

 Ingredients were blended in the proportions shown in the table below, and tablets were produced according to conventional methods (raw materials) (wt%)

 Neubiscus acid 5

 Nobiscus acid monoethinore estenore 5

 Ascorbic acid phosphate magnesium 10

 Placenta extract 10

 Collagen 20

 Crystalline cellulose 20

 Dextrin 14

Glycerin fatty acid ester 6 Vaginal form 10

 Total 100

 [0180] <Prescription Example 6> Drink

 The ingredients were blended at the blending ratios shown in the table below, and a drink was produced according to a conventional method.

(material)

 No, biscus acid 0.5

 Fructose glucose 20. 0

 Chenic acid 0.50

 Sodium quenate 0. 10

 Asconolevic acid 0.20

 Fragrance

 Spirit

 Total 100. 0

 [0181] <Prescription Example 7> Toothpaste A

 Ingredients were blended in the proportions shown in the table below, and toothpastes were produced according to conventional methods (raw materials) (wt%)

 Dicalcium phosphate 30. 00

 Sejin 10. 00

 Sonorbitol 20.00

 Sodium carboxymethylcellulose 1.00

 Sodium lauryl sulfate 1. 50

 Carrageenan 0.50

 Saccharin sodium 0. 10

 Fragrance 1.00

 Sodium benzoate 0. 30

 /, Biscus acid 0. 10

 Purified water

A DOO 100. 0 [0182] <Prescription Example 8> Toothpaste B

 The raw materials were blended at the blending ratios shown in the table below, and toothpastes were produced according to conventional methods.

(Raw material) (wt%)

 Sodium lauryl sulfate

 Lauric acid diethanolamide 1. 00

 Propylene glycol

 60% sorbite 35. 00

 Methylparaben

 Butylparaben 〇 〇 〇

 〇 〇 ο οO C0 00

 Saccharin sodium 〇 ο 〇 〇 〇

 ○ ○ ○ ○ ○ 1—

 Gelatin

 Fragrance

 Sodium alginate

 Sodium benzoate

 Aluminum hydroxide 45. 00

 Sodium monofluorate

 No, biscus acid

Total 100. 0

 [0183] <Prescription Example 9> Mouthwash

 The raw materials were blended at the blending ratios shown in the table below, and a mouthwash was produced according to a conventional method.

(Raw material) (wt%)

 Ethanor 10.00

 Glycerin 5.00

 Quenic acid 0. 01

 Sodium quenate 0. 10

 Polyoxyethylene hydrogenated castor oil 0.50

Methyl paraoxybenzoate 0. 10 Fragrance 0. 20

No, biscus acid 0.1

Purified water

Total 100. 0

 <Prescription Example 10> Oral Pasta

 Ingredients were blended at the blending ratios shown in the table below, and oral pasta was produced according to conventional methods.

(Raw material) (wt%)

Liquid paraffin 13.00

Cetanore 10.00

Glycerin 25. 00

Sorbitan monopalmitate 0.60

Polyoxyethylene sorbitan monostearate 5. 00

Sodium lauryl sulfate 0. 10

Benzotonium chloride 0. 10

Methyl salicylate 0. 10

Saccharin 0.20

Fragrance 0. 25

No, biscus acid 0.50

Purified water

Total 100. 0

Brief Description of Drawings

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. In the figure, Lane I is without hibiscus acid; Lane II is with 5% hibiscus acid solution 100 μ1; Lane III is with 5% hibiscus acid solution 50 μ1; Lane IV is 5% hibiscus acid solution 25 μm Lane 1 is a diagram showing a sample of 12.5 μl-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.

Claims

Claim [1] The following formula (1)

 [Chemical 1]

(In the formula, R ¹ and R ² each represent a hydrogen atom, a substituted or unsubstituted alkyl group or a benzyl group.) Hibiscus acids represented by A melanin production inhibitor containing at least one kind of compound as an active ingredient.

[2] The melanin production inhibitor according to claim 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.

 [3] A whitening agent comprising the melanin production inhibitor according to any one of claims 1 to 2 as an active ingredient

[4] A whitening cosmetic comprising the melanin production inhibitor according to any one of claims 1 to 2 as an active ingredient.

 [5] For whitening comprising the melanin production inhibitor according to any one of claims 1 to 2 as an active ingredient

 TOo

 [6] An oral composition comprising the melanin production inhibitor according to any one of claims 1 to 2 as an active ingredient.