JP2008303180A - Skin-lightening agent, skincare preparation for external use, and functional oral composition - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a skin-lightening agent synergistically improved in skin-lightening effect, thus exhibiting high skin-lightening effect. <P>SOLUTION: The skin-lightening agent having the advantage is provided, through compounding, as active ingredients, glutathione and one or more plants selected from those belonging to the genus Psidium or extract thereof. <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

The present invention relates to a whitening agent, an external preparation for skin, and a functional oral composition that synergistically improve the whitening effect and exhibit a high whitening effect. More specifically, the present invention relates to a whitening agent, an external preparation for skin, and a functional oral composition containing one or more plants selected from glutathione and Psidium plants or extracts thereof as active ingredients.

  Tyrosinase is an oxidase that uses various catechol derivatives as substrates. Most of them have monophenol monooxygenase activity, and mono-phenol is used as a substrate to produce ortho-diphenol, which is further oxidized to ortho-quinones. This oxidase is widely distributed in nature, and is present in pigment cells of plants and animals such as mushrooms, potatoes and apples. Oxidizing enzymes in animals exhibit high activity especially against tyrosine and dopa, and are deeply involved in melanin biosynthesis. Melanin is produced from tyrosine in the process of L-dopa, dopaquinone, dopachrome, 5,6 dihydroxyindole, indole-5,6-quinone and melanin, and tyrosinase is involved in the oxidation process of tyrosine to L-dopa and dopaquinone. ing. Melanin is a pigment that determines the color of hair and skin. In the skin, this pigment is produced in response to light and ultraviolet rays in melanocytes existing in the basal layer of the epidermis. Melanin production in the skin plays a role in protecting humans from the adverse effects of ultraviolet rays and the like. However, when there is a stimulus such as exposure to a large amount of light or ultraviolet rays, the melanin generating function is locally maintained, and the skin of that part is darkened. As a result, pigmentation will form spots and freckles, which eventually promote skin aging. Conventionally, tyrosinase activity inhibitors have been used for the purpose of promoting whitening. Known examples of tyrosinase activity inhibitors include vitamin C (see Patent Document 1), arbutin, extracts extracted from plants and the like (see Patent Document 2), and sulfites.

  However, vitamin C is easily oxidized due to its own reducing action and is unstable, and has a storage problem. Arbutin also has a problem in heat resistance stability, which also has a problem in handling. Sulfites are recognized as a skin irritation to the human body and have safety problems.

JP-A-2-45408 Japanese Patent Laid-Open No. 6-40896

  The object of the present invention is to solve the above-mentioned problems and to obtain a whitening agent exhibiting a high whitening effect in which the whitening effect is synergistically improved.

  In order to solve the above-mentioned problems, various studies have been conducted. By using glutathione and a specific plant component in combination, the whitening effect is synergistically improved, the safety to the human body is high, and the whitening effect is high. An activity inhibitor was found and the present invention was completed.

That is, the present invention relates to a whitening agent comprising as an active ingredient one or more plants selected from glutathione and Psidium plants, or an extract thereof.

Another invention relates to a skin external preparation characterized by containing one or more plants selected from glutathione and Psidium plants or extracts thereof.

Yet another invention relates to a functional oral composition comprising one or more plants selected from glutathione and Psidium plants or extracts thereof.

ADVANTAGE OF THE INVENTION According to this invention, the whitening agent which has the outstanding effect can be provided by using as an active ingredient the 1 type, or 2 or more types of plant chosen from glutathione and the genus Psidium, or its extract. .

  By blending these whitening agents into a topical skin preparation and a functional oral composition, it is possible to provide various compositions that exhibit excellent effects in improving pigmentation symptoms such as remarkable spots and buckwheat. .

  Glutathione is a tripeptide composed of amino acids such as glutamic acid, cysteine, and glycine, and is contained in a large amount in living cells. In the present invention, glutathione may be used as it is, but due to problems such as odor, glutathione-containing yeast cell powder and glutathione-containing yeast cell extract may be used in addition to these.

The genus Psidium is an evergreen shrub or tree of the Myrtaceae family, distributed from the tropical to the warm Americas. As for the genus Vanjiro, tropical green American shrubs are the origin, tropical guava ( Psidium guajava ) spreading from the tropical to the subtropical zone of the world, Psidium guineense ( Psidium guineense ) considered to be the origin of African guinea, Psidium cattleianum, a shrub that is lower than guava, is known.

  These plants can be used alone or in combination of two or more.

The present invention is not particularly limited as long as it is a plant belonging to the genus Banjiro, but guava ( P. guajava ) is mentioned as a suitable one because of its relatively easy availability.

  There are no particular restrictions on the site of use of these genus plants, and any part such as roots, stems, trunks, leaves, and flowers can be used. A plurality of parts may be used in combination.

  They can be pulverized as they are, but it is preferable to use an extract from those parts.

  For extraction, any part of the plant belonging to the genus Bansirou may be used, but for easy use, whole grass, roots, leaves, flowers, etc. may be used. In that case, you may make it obtain an extract using a some site | part. Further, two or more kinds of extracts extracted using different solvents may be mixed and used.

  In the extraction, the plant may be used as it is, but considering the extraction efficiency, it is preferable to perform the extraction after performing processing such as shredding, drying, and pulverization.

  The extraction can be performed by immersing in an arbitrary extraction solvent for a predetermined time. The extraction solvent may be heated as necessary. Alternatively, extraction can be performed using a supercritical fluid or a subcritical fluid. In order to increase the extraction efficiency, stirring or homogenization in an extraction solvent may be performed. The extraction temperature is suitably about 5 ° C. to the boiling point of the extraction solvent. The extraction time varies depending on the type of extraction solvent and the extraction temperature, but is suitably about 1 hour to 14 days.

  As an extraction solvent, in addition to water, lower alcohols such as methanol, ethanol, propanol and isopropanol; polyhydric alcohols such as 1,3-butylene glycol, propylene glycol, dipropylene glycol and glycerin; ethers such as ethyl ether and propyl ether Solvents such as esters; esters such as butyl acetate and ethyl acetate; ketones such as acetone and ethyl methyl ketone can be used. These may be used alone or in combination of any two or more. Saline, phosphate buffer, phosphate buffered saline, and the like may be used. Furthermore, you may use 1 type, or 2 or more types of supercritical liquids and subcritical liquids, such as water, a carbon dioxide, ethylene, propylene, ethanol, methanol, ammonia.

  An extract of the above-mentioned banjiro genus plant with the above solvent can be used as it is, but it may be left to mature for a certain period of time, or it may be used after ripening, and the concentrated and dried product is dissolved again in water or a polar solvent. Can also be used. Alternatively, it may be used after performing purification treatment such as decolorization, deodorization, desalting, etc., or fractionation treatment by column chromatography or the like, as long as these physiological functions are not impaired. The said extract of a genus genus genus, its processed material, and a fraction can also be lyophilized | freeze-dried after each process and fractionation, and can also be used after melt | dissolving in a solvent at the time of use. It can also be used by encapsulating in vesicles such as liposomes or microcapsules.

  A whitening agent containing one or two or more plants selected from glutathione and vanilla species or an extract thereof as an active ingredient has an excellent inhibitory effect on tyrosinase activity of human epidermal melanocytes, including pigmentation, spots, freckles Prevents and improves, etc., and exhibits an excellent whitening effect.

  These whitening agents can be blended into an external preparation for skin or a functional oral composition to provide various forms of compositions, and can be used as it is for external use or oral use.

  As long as the whitening agent contains one or two or more plants selected from glutathione and Banjiro plants or an extract thereof as an active ingredient, the form and the presence or absence of other ingredients are not limited. As for the form, any form such as liquid, paste, gel, solid, powder, etc. can be selected according to its use and the like, vehicle (excipient), solvent, Other general additives (antioxidants, colorants, dispersants, etc.) can optionally be included.

  A whitening agent containing one or two or more plants selected from glutathione and vanilla species or an extract thereof as an active ingredient has an excellent inhibitory effect on tyrosinase activity of human epidermal melanocytes, including pigmentation, spots, freckles Etc. are prevented and improved to have an excellent whitening action, and by blending this, an external skin preparation or a functional oral composition having an excellent effect can be provided.

  Here, the external preparation for skin means all external compositions for external use on the skin or hair, such as cosmetics, quasi-drugs, and external medicines. The functional oral composition also means all compositions that are taken orally regardless of the type of pharmaceuticals, foods, beverages and the like. The function of the oral composition is preferably whitening.

  The dosage form of the external preparation for skin is arbitrary, and can be provided, for example, as a solubilizing system such as lotion, a dispersion system such as calamine lotion, or an emulsifying system such as cream or emulsion. Further, it can be provided in various dosage forms such as an aerosol form, an ointment, and a poultice filled with a propellant.

  Specifically, various cosmetics such as emulsions, creams, lotions, lotions, packs, cosmetic liquids, cleaning agents, makeup cosmetics, etc .; liquids, ointments, powders, granules, aerosols, patches, poultices, etc. Various forms of cosmetics, quasi drugs, topical medicines, and the like can be exemplified.

  The form of the functional oral composition is also arbitrary and is not particularly limited. Specifically, general foods including beverages; health foods (supplements) such as tablets, capsules, granules, powders or functional foods; oral drugs such as tablets, capsules, granules, powders, syrups, extracts Etc. can be exemplified.

  Various skins such as spots and dullness can be obtained by blending one or more kinds of plants selected from glutathione and banjirou plants or extracts thereof into cosmetics, external medicines, quasi drugs, and other skin external preparations. It is possible to obtain a skin external preparation that exhibits an excellent effect in preventing and improving symptoms. Therefore, for example, it can be preferably used as a skin whitening external preparation for whitening.

  In addition to one or two or more plants selected from glutathione and Vanjirou plants or extracts thereof, the topical skin preparation or functional oral composition includes pharmaceuticals and quasi drugs as required. , Optional ingredients usually incorporated into skin cosmetics, hair cosmetics and detergents, such as water, oily ingredients, moisturizers, powders, pigments, emulsifiers, solubilizers, gelling agents, detergents, UV rays Absorbers, anti-inflammatory agents, thickeners, pH adjusters, chelating agents, drugs (medicinal ingredients), fragrances, resins, fungicides, fungicides, antioxidants, alcohols, and the like can be appropriately blended. Furthermore, in the range which does not impair the effect of this invention, combined use with another whitening agent is also possible.

  In the case of functional oral compositions such as foods and drinks, there is no particular limitation in combination with various components that are usually used for oral use.

  The amount of glutathione added to the external preparation for skin or functional oral composition can be adjusted depending on the purpose, etc., but from the point of effect and stability, 0.0001 to 20.0% by mass is the total amount. More preferably, it is 0.001-10.0 mass%, More preferably, it is 0.01-10 mass%, More preferably, it is 0.1-10 mass%.

  The blending amount of the plant of the genus Vanjiro or its extract into the topical skin preparation or functional oral composition can be adjusted depending on the type, purpose, etc., but from the standpoint of effects and stability, In terms of minutes, it is preferably 0.0001 to 20.0% by mass, more preferably 0.001 to 10.0% by mass, still more preferably 0.01 to 10% by mass, and still more preferably 0.00. 1 to 10% by mass.

In the following, preparation examples of plant extracts of the genus Pangium ( Psidium ), test methods for evaluating the whitening effect of glutathione and plants of the genus Bungilow, prescription examples as external preparations for skin, functional oral compositions, and usage tests are described in more detail As will be described, the technical scope of the present invention is not limited thereby.

[Preparation Method 1]
20 kg of 50% by weight ethanol aqueous solution was added to 1 kg of dried pulverized guava ( P. guajava ) leaves, and immersed for 7 days at room temperature. The extract was collected by filtration, and after removing the solvent, 25 g of a banjillo plant extract was obtained.

[Preparation Method 2]
20 liters of water was added to 1 kg of dried pulverized guava leaves, and the mixture was extracted by refluxing at 90 ° C. for 6 hours. The extract was collected by filtration, and after removing the solvent, 20 g of a banjillo plant extract was obtained.

[Preparation Method 3]
20 kg of methanol was added to 1 kg of dried and ground guava leaf and immersed for 7 days at room temperature. The extract was collected by filtration and after removing the solvent, 40 g of a banjillo plant extract was obtained.

[Preparation Method 4]
A supercritical extraction apparatus was charged with 100 g of a dry pulverized guava leaf and extracted with a supercritical fluid of carbon dioxide at 40 ° C. under an atmospheric pressure of 15 Mpa. The extract was recovered to obtain 5 g of an extract of the genus Vanilla.

<Evaluation of whitening action (tyrosinase activity inhibitory action)>
Evaluation of the tyrosinase activity inhibitory action of glutathione and the extract of the genus Vanilla was performed by the following method. As a sample, glutathione was a commercially available product, and an extract produced by Preparation Method 1 was used as the extract of the genus Vanilla.

Normal human epidermal melanocytes manufactured by Kurabo Industries Co., Ltd. were seeded in a 96-well microplate so as to be 3.0 × 10 ⁴ cells per well. As a seeding medium, Medium154S manufactured by Kurabo Industries Co., Ltd. was used. After 24 hours, the medium was replaced with a sample-added medium adjusted to each concentration shown in Table 1 with Medium 154S, and further cultured for 48 hours. Next, the cells were completely lysed by exchanging with 75 μL of 1% by weight Triton-X-containing phosphate buffer, and 50 μL of the cells was used as a crude enzyme solution. To the crude enzyme solution, 50 μL of 0.05% by mass L-dopa-containing phosphate buffer serving as a substrate was added and allowed to stand at 37 ° C. for 2 hours. The absorbance at 405 nm was measured immediately after the addition of the substrate and at the end of the reaction with a microplate reader, and the amount of produced dopamelanin was determined by introducing each measured value into equation (1).

Formula (1): Amount of produced dopamelanin = {(405 nm value after reaction−405 nm value before reaction)} − 2.166 / 5.238
Further, the amount of protein in each well was measured by BCA Protein Assay Kit manufactured by PIERCE, and the amount of dopamelanin produced per unit protein amount was determined. Table 1 shows the relative values when the amount of dopamelanin produced when no sample was added as a control was taken as 100.

  As shown in Table 1, in Example 1 in which glutathione and a banjillo genus plant extract were used in combination, a clear decrease in melanin production was observed as compared with Comparative Examples 1 and 2 blended alone. From this, it was found that the use of glutathione and a banjillo genus plant extract together has an excellent tyrosinase activity inhibitory action.

  From the above, it has been clarified that glutathione and an extract of the genus Banjiro are used in combination to have an excellent whitening effect.

  Next, the formulation example of the skin external preparation which is this invention is shown.

[Example 2, Comparative Example 3] Cosmetic liquid (1) Glyceryl tri-2-ethylhexanoate 7.8 (% by mass)
(2) Polyglyceryl distearate 2.4
(3) Hydrogenated soybean phospholipid 0.4
(4) Batyl alcohol 0.1
(5) The balance (6) of purified water 100 Glycerin 7.5
(7) Xanthan gum 0.4
(8) Diethylenetriaminepentaacetic acid pentasodium 0.2
(9) 1,3-butylene glycol 2.5
(10) Methyl paraoxybenzoate 0.1
(11) Ethanol 4.0
(12) Fragrance 0.1
(13) Glutathione 0.5
(14) Guava leaf extract [Preparation method 1] 0.5
Production method: The oil phase components (1) to (4) are mixed, dissolved, and heated to 75 ° C. On the other hand, the aqueous phase components (5) to (10) are mixed and dissolved and heated to 75 ° C. Subsequently, after adding an oil phase component to the said water phase component and pre-emulsifying, it emulsifies uniformly with a homomixer. The mixture was cooled with stirring, (11) to (14) were added at 40 ° C., mixed and homogenized to obtain a cosmetic liquid. In this case, Comparative Example 3 was obtained by replacing (13) and (14) with sodium lactate.

Example 3 Emulsion (1) Squalane 6.0 (mass%)
(2) Methylphenylpolysiloxane 4.0
(3) Hydrogenated palm kernel oil 0.5
(4) Polyoxyethylene monostearate
Sorbitan (20E.O.) 1.5
(5) Sorbitan monostearate 1.0
(6) Glycerin 10.0
(7) Methyl paraoxybenzoate 0.1
(8) 1 mass% carboxyvinyl polymer aqueous solution 15.0
(9) 10% by mass L-arginine aqueous solution 1.0
(10) Glutathione 1.0
(11) Guava leaf extract [Preparation method 2] 1.0
(12) Refining water 100: The rest of the production method: (1) to (5) oil phase components and (6) to (8) added to (12) water phase components are heated and homogenized at 80 ° C. To do. Next, the oil phase component is added to the water phase component and stirred uniformly. Next, (9) is added, and the mixture is uniformly emulsified by a homogenizer, then cooled, and (10) and (11) are added at 45 ° C. to make the mixture uniform.

<Use test of topical skin preparation>
About Example 2 and Comparative Example 3 of this invention, the improvement effect of the pigmentation symptom was evaluated. The effect of improving pigmentation symptom is a group of 20 female panelists who have pigmentation symptom, such as remarkable blotch and buckwheat, and each group uses the example or comparative example twice a day for 2 months blindly. Then, the pigmentation state of the skin after 2 months was observed and evaluated in comparison with before use. The pigmentation state was evaluated according to the criteria shown in Table 2, and the average value of 20 people was calculated and shown in Table 3.

  As is apparent from Table 3, in Example 2 in which glutathione according to the present invention and the extract of the genus Vanjiro were used in combination, a marked improvement in pigmentation was observed, and mild pigmentation was observed after the end of the use test. The symptoms were improved to such a degree that only whitening was observed, and the whitening effect was comparable or higher than that of Comparative Example 3 in which sodium lactate, which has been conventionally known as a whitening agent, was blended.

  In addition, about the Example of this invention, the state change of a formulation, such as precipitation of a content component, isolation | separation, aggregation, odor change, and discoloration, was not seen at all during the said use test period. Moreover, in each Example use group, the paneler which showed skin irritation reaction and skin sensitization reaction did not exist.

  Next, the formulation example of the functional oral composition which is this invention is shown.

[Example 4, Comparative Example 4] Tablet (1) Corn starch 44.0 (mass%)
(2) Remainder made of crystalline cellulose 100 (3) Carboxymethylcellulose calcium 5.0
(4) Silicic anhydride 0.5
(5) Magnesium stearate 0.5
(6) Glutathione 10.0
(7) Guava leaf extract [Preparation method 1] 10.0
Production method: (1) to (7) were uniformly mixed, and compression-molded with a tableting machine to obtain one tablet of 200 mg. In this case, Comparative Example 4 was obtained by replacing (7) with glutathione.

[Example 5] Powder (1) Magnesium aluminate silicate 40.0 (% by mass)
(2) Carboxymethylcellulose calcium 100 The remainder (3) Glutathione-containing yeast cell extract 20.0
(4) Guava leaf extract [Preparation method 2] 5.0
Production method: After mixing the powders (1) to (4), they are pulverized by a pulverizer and uniformly dispersed.

<Use test of functional oral composition>
For Example 4 and Comparative Example 4 of the present invention, the effect of improving pigmentation symptoms was evaluated. The effect of improving pigmentation symptom is a group of 20 female panelists having pigmentation symptom such as remarkable blotch, buckwheat, etc., and each group is allowed to ingest 1 g daily for 4 weeks in each of the examples or comparative examples, The pigmentation state of the skin after 4 weeks was observed and evaluated as compared with before use. The state of pigmentation was evaluated according to the criteria shown in Table 2, and the average value of 20 people was calculated and shown in Table 4.

  As is apparent from Table 4, Example 4, which uses glutathione according to the present invention and the extract of the genus Vanjiro, has a marked improvement in pigmentation symptoms as compared with Comparative Example 4 in which glutathione is added twice. After the use test, the symptoms were improved to such an extent that only slight pigmentation was observed.

  From the above, it has been clarified that the use of glutathione and an extract of the genus Vanjiro has an excellent whitening effect.

Claims (3)

A whitening agent comprising one or more plants selected from glutathione and Psidium plants or an extract thereof as an active ingredient. An external preparation for skin, comprising one or more plants selected from glutathione and Psidium plants or extracts thereof. A functional oral composition comprising one or more plants selected from glutathione and Psidium plants, or an extract thereof.