JP2005255529A - Skin care preparation for external use - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a skin care preparation for external use excellent in bleaching and/or antiaging effect. <P>SOLUTION: This skin care preparation for external use comprises an extract of Tithonia diversifolia (Hemsl) A. Gray as an active ingredient, particularly as a bleaching agent or an antioxidant. The skin care preparation for external use can be supplied to various kinds of applications, e.g. cosmetics, quasi-drugs and external medicines. Since the skin care preparation for external use is excellent in bleaching effect and/or antiaging effect, the preparation is particularly useful as a cosmetic. <P>COPYRIGHT: (C)2005,JPO&NCIPI

Description

  The present invention relates to an external preparation for skin using an extract of Asteraceae Nitobegiku.

  Conventionally, in skin external preparations, various natural product-derived components such as plant extracts have been used as active ingredients. For example, Yokuinin extract or Asteraceae chamomile extract is known to have a whitening effect, and cosmetics containing the extract have been proposed. However, the effects of conventional medicinal agents are insufficient, and a new natural product-derived medicinal agent that exhibits a more excellent whitening effect or the like is demanded.

  This invention makes it a subject to provide the skin external preparation which is excellent in the medicinal effect at the time of applying to skin, especially the whitening effect and / or the anti-aging effect, and favorable stability.

The present invention provides an external preparation for skin containing nitobegiku extract as an active ingredient. In the present invention, the nitobegiku extract is contained in a skin external preparation as a whitening agent and / or as an anti-aging agent.
From another point of view, according to the present invention, a melanin production inhibitor composed of a nitrite extract; a reactive oxygen trap comprising a nitrite extract; a melanin production inhibition method comprising applying a nitrite extract; A method for eliminating active oxygen comprising: applying a nitrite extract; a method for whitening the skin; applying a nitrite extract; and a skin comprising adding a nitrite extract. A method for producing an external preparation is provided.

  ADVANTAGE OF THE INVENTION According to this invention, the skin external preparation with favorable stability excellent in various medicinal effects, especially the whitening effect and / or anti-aging effect can be provided.

Hereinafter, the present invention will be described in detail.
The external preparation for skin of the present invention contains an extract of the asteraceae Nitobegiku (scientific name: Tithonia diversifolia (Hemsl) A. Gray) as an active ingredient. Extracts of various parts such as leaves, stems, roots, flowers, etc. can be used, but it is preferable to use leaf extracts. In the present invention, extracts obtained from two or more parts of the nitrite may be mixed and used, or two or more extracts extracted from two or more parts with different solvents may be mixed. May be used.

  The method for preparing the nitobegiku extract is not particularly limited, and can be prepared using a general extraction method. For example, it can be prepared by immersing Nitobegi leaves in a solvent at 50 to 100 ° C. for a predetermined time. Although it does not specifically limit as an extraction solvent, For example, Water; Lower monohydric alcohols, such as methyl alcohol and ethyl alcohol; Liquid polyhydric alcohols, such as glycerol, propylene glycol, and 1, 3- butylene glycol; Ketones, such as acetone; Ethyl One or more of ethers such as ether; esters such as ethyl acetate; and the like can be used. Among these, water is preferable, and it is preferable to extract by dipping in hot water (50 to 100 ° C.). Moreover, it is preferable to use about 2-8 times as much mass as an extraction solvent with respect to the leaf etc. of a nitrite. Although the preferable range of the extraction time varies depending on the type of solvent or the extraction temperature, it is generally preferably 60 to 100 minutes.

  The nitobegiku extract may be used as it is in a skin external preparation, or may be used after being left to mature for an appropriate period. If necessary, it can be used after being subjected to a purification treatment such as deodorization and decolorization by filtration or ion exchange resin within a range that does not affect the effect of the present invention. Further, a fraction having high activity can be taken out and used by using a separation means such as liquid chromatography.

  The extract of nitobegiku may be in any form such as liquid, paste or gel. The liquid extract containing the extraction solvent can also be used after it is solidified by drying under reduced pressure or freeze drying. It can also be dried by spray drying or the like and used as a powder.

  The skin external preparation of this invention has the outstanding whitening effect and / or antiaging effect which are show | played by the said nitobegiku extract which is an active ingredient. In the present specification, “anti-aging” means an anti-aging action on living cell tissues. In particular, “anti-aging” for skin means wrinkles and sagging of skin (including scalp, lips and mucous membranes) caused by aging, UV exposure, etc., reduced tension and elasticity, and reduced water retention capacity of skin It means an anti-aging action such as prevention or improvement of skin aging such as. As long as these actions are exhibited, there is no particular limitation on the mechanism that exhibits the anti-aging action. For example, the effects exhibited by “antioxidant effect” and “cell activation effect” are also included in the range of “anti-aging”. Further, in the present specification, the term “whitening” is used to include not only the positive effect of whitening the skin but also the negative effect of suppressing the blackening of the skin. For example, it includes not only the effect of improving pigmentation such as spots and freckles but also the effect of suppressing pigmentation.

  The content of the nitobegiku extract (dry solid) in the external preparation for skin of the present invention is preferably 0.00001 to 5% by mass (hereinafter simply referred to as “%”), more preferably 0.0001 to 2%. %. If it is in this range, the above-mentioned nitrite extract can be blended stably, and a high whitening effect or anti-aging effect can be exhibited. When the extract is used as a solution, the concentration of the extract is not limited as long as the content of the dry solid content as a solute is within the above range.

  In the external preparation for skin of the present invention, as long as the effects of the present invention are not impaired, components, water (purified water, hot spring water, deep layer water) that are usually used in preparations such as cosmetics, quasi drugs, and external medicines are used. Etc.), oil agent, surfactant, metal soap, gelling agent, powder, alcohol, water-soluble polymer, film-forming agent, resin, inclusion compound, antibacterial agent, fragrance, deodorant, salt, pH adjustment Agents, fresheners, extracts from plants, animals and microorganisms, active oxygen scavengers, blood circulation promoters, astringents, antiseborrheic agents, moisturizers, chelating agents, keratolytic agents, enzymes, hormones, vitamins, etc. Can be added as needed.

  Alcohol is used for the purpose of dissolution, refreshing feeling, antiseptic, moisturizing and the like. Examples of alcohols that can be used in the present invention include lower alcohols such as ethanol; and various alcohols such as glycerin, diglycerin, ethylene glycol, diethylene glycol, propylene glycol, dipropylene glycol, 1,3-butylene glycol, and polyethylene glycol. And the like.

  The oil is used as a component of the base or for the purpose of improving usability or feeling of use. Any of those used in normal cosmetics can be used, such as whether it is a natural oil or a synthetic oil, or whether it is a solid, semi-solid, liquid, etc. It doesn't matter about the properties. In the present invention, hydrocarbons, waxes, fatty acids, higher alcohols, ester oils, silicone oils, fluorine oils and the like can be used. More specifically, hydrocarbons such as liquid paraffin, squalane and petrolatum, synthetic ester oils such as cetyl tri-2-ethylhexanoate and pentaerythritol tetra-2-ethylhexanoate, olive oil, castor oil, jojoba oil, mink Oil, macadamia nut oil, apricot oil, persic oil, safflower oil, sunflower oil, avocado oil, medhome oil, camellia oil, almond oil, egoma oil, sesame oil, borage oil, shea butter, etc. Oils, beeswax, carnauba wax, candelilla wax, gaywax and other waxes can be used.

  Examples of UV protection agents that can be used include para-methoxycinnamate-2-ethylhexyl, 2-hydroxy-4-methoxybenzophenone, 2-hydroxy-4-methoxybenzophenone-5 sodium sulfate, 4-butyl-4 ′ -Methoxydibenzoylmethane, 2-phenyl-benzimidazole-5-sulfuric acid, titanium oxide, zinc oxide and the like.

  The water-soluble polymer is used for stabilizing the system, improving usability or feeling of use, and also for obtaining a moisturizing effect. Examples of water-soluble polymers that can be used include plant polymers such as carrageenan, pectin, agar, locust bean gum, microbial polymers such as xanthan gum, animal polymers such as gelatin, and starch-based polymers such as starch. Examples include molecules, cellulosic polymers such as methylcellulose, carboxymethylcellulose, and hydroxypropylcellulose, alginic acid polymers such as sodium alginate, vinyl polymers such as carboxyvinyl polymer, and the like.

  Examples of antiseptics and antibacterial agents include benzoic acid, sodium benzoate, paraoxybenzoic acid ester, benzalkonium chloride, phenoxyethanol, isopropylmethylphenol, and the like.

  Nitobegiku extract alone has an excellent whitening effect, but in order to further improve the effect of the present invention, a conventionally known whitening agent may be used in combination. The whitening agent is used for the purpose of preventing skin blackening caused by sunburn and the like, spots such as spots and freckles caused by pigmentation. Examples of other whitening agents that can be used include arbutin, ellagic acid, linoleic acid, vitamin C and its derivatives, vitamin E and its derivatives, glycyrrhizic acid and its derivatives, tranexamic acid, placenta extract, chamomile extract, licorice Extract, Ages extract, Ogon extract, Seaweed extract, Kujin extract, Caiket extract, Gokahi extract, Rice bran extract, Wheat germ extract, Saisin extract, Hawthorn extract, Sunpens extract, Shirayuri extract , Peonies extract, Sempukuka extract, soybean extract, tea extract, molasses extract, sandalwood extract, grape extract, hop extract, micaika extract, mokka extract, yukinoshita extract, Yokuinin extract, etc. Is included.

  Anti-inflammatory agents are used for the purpose of suppressing inflammation such as hot flashes and erythema after sunburn. Examples of anti-inflammatory agents that can be used in the present invention include sulfur and its derivatives, glycyrrhizic acid and its derivatives, glycyrrhetinic acid and its derivatives, aloe extract, artea extract, ashitaba extract, arnica extract, inchinkou extract , Nettle extract, duckweed extract, hypericum extract, chamomile extract, goldfish extract, watercress extract, comfrey extract, salvia extract, lion extract, perilla extract, birch extract, gentian extract, etc. Is included.

  Nitobegi extract has an excellent cell activation effect by itself, but in order to further improve the effect of the present invention, a conventionally known cell activation agent may be used in combination. The cell activator is used for the purpose of improving rough skin. Examples of cell activators that can be used in the present invention include caffeine, chicken crown extract, shell extract, shell extract, royal jelly, silk protein and its degradation product or derivatives thereof, lactoferrin or its degradation product, chondroitin Mucopolysaccharides such as sulfuric acid and hyaluronic acid or salts thereof, collagen, yeast extract, lactic acid bacteria extract, bifidobacteria extract, fermentation metabolic extract, ginkgo biloba extract, barley extract, assembly extract, thymus extract, Examples include carrot extract, rosemary extract, organic acids such as glycolic acid, citric acid, lactic acid, malic acid, tartaric acid, succinic acid, and derivatives thereof.

  Nitobegiku extract alone has an excellent active oxygen scavenging ability, but in order to further improve the effects of the present invention, a conventionally known active oxygen remover may be used in combination. The active oxygen scavenger is used for the purpose of suppressing oxidative damage such as lipid peroxide production suppression. Examples of active oxygen scavengers that can be used in the present invention include superoxide dismutase, mannitol, quercetin, catechin and derivatives thereof, rutin and derivatives thereof, bopi extract, yashajitsu extract, melissa extract, rahan extract, retinol And derivatives thereof, vitamin A such as carotenoid, thiamine and derivative thereof, riboflavin and derivative thereof, pyridoxine and derivative thereof, vitamin B such as nicotinic acid and derivative thereof, vitamin E such as tocopherol and derivative thereof, dibutylhydroxytoluene And butylhydroxyanisole.

  Examples of humectants that can be used in the present invention include proteins such as elastin and keratin or derivatives thereof, hydrolysates and salts thereof, amino acids such as glycine, serine, aspartic acid, glutamic acid, arginine, and theanine, and their Derivatives, sorbitol, erythritol, trehalose, inositol, glucose, sucrose and derivatives thereof, dextrin and derivatives thereof, saccharides such as honey, D-pantenol and derivatives thereof, urea, phospholipid, ceramide, auren extract, shobu extract, Examples of the present invention include terrestrial extract, nematode extract, mallow extract, gypsophila extract, dokudami extract, hamamelis extract, bodaige extract, maronier extract, quince extract and the like.

  Examples of the form of the external preparation for skin of the present invention are not particularly limited. For example, emulsions, creams, lotions, packs, cosmetics, cleansing agents, makeup cosmetics, dispersions, ointments, liquids, aerosols, patches It may be any form of cosmetic such as a cloth, a poultice, a liniment or the like, or an external medicine.

  The present invention will be described more specifically with reference to the following examples. However, the scope of the present invention is not limited to the following examples.

[Example 1: Preparation of nitobegiku extract]
3 liters of water was placed in 500 g of dried Nitobegiku (Tithonia diversifolia (Hemsl) A. Gray), extracted in hot water, concentrated under reduced pressure, and lyophilized to obtain 70 g of extract.
[Example 2: Preparation of sample for comparison (chamomile extract and yokoinin extract)]
50 mL of 1,3-butylene glycol was added to each 10 g of a mixture of flowers of the genus Camellia chamomile L., and the mixture was extracted with stirring at room temperature for 10 days, filtered, and filtrated (camomile extraction). Product). The dry solid content of the chamomile extract was 0.35%.
To 10 g of Yokuinin (JP), 100 mL of 70 vol% water-containing ethyl alcohol was added, extracted at room temperature for 3 days, and then filtered to obtain a Yokuinin extract. The dry solid content of the Yokuinin extract was 0.8%.

[Example 3: Suppression of melanin production and cell viability test by cultured cells]
B16 melanoma cultured cells derived from mice were used. An appropriate amount of 10% FBS-containing MEM medium was taken in two 6-well plates, seeded with B16 melanoma cells, and allowed to stand at 37 ° C. in a carbon dioxide concentration of 5 vol%. On the next day, the sample preparation solution was added to and mixed with the nitobegiku extract obtained in Example 1 so that the final solid concentration would be the concentration shown in Table 1. On day 5 of the culture, the medium was changed, and the sample preparation solution was added again. The medium was removed the next day, and the cells were collected after washing with a phosphate buffer (pH 7) on one plate, and the whitening degree of B16 melanoma cultured cells was evaluated according to the following criteria. The results are shown in Table 1.
Moreover, the same test was evaluated and evaluated about the chamomile extract which belongs to the Asteraceae prepared in Example 2, and the Yokuinin extract already prepared in Example 2 that is known to have a melanin production inhibitory effect. The results are also shown in Table 1.

(Criteria)
Judgment Description ++: Extremely white compared to the control.
+: Clearly white relative to the control.
±: Slightly white with respect to the control.
-: The same black color as the control.

  As is clear from the results in Table 1, it was recognized that the nitrite extract has a high ability to suppress melanin production at a low concentration as compared with the chamomile extract and the yokoinin extract. Therefore, by applying an external preparation for skin containing nitobegiku extract to the skin, it exerts an excellent melanin production inhibitory effect, effectively suppresses skin blackening, spots, freckles, etc. due to sunburn, whitening The effect can be expected.

  Furthermore, among the plates prepared for the evaluation of the melanin production inhibitory ability, the remaining one plate was fixed with formalin and then stained with 1% crystal violet solution. The cell viability for each sample concentration was measured with a monocerator (Olympus). The cell growth rate at a concentration at which melanin production-inhibiting ability was observed was 93% for the nitrite extract (10 μg / L), and for the chamomile extract (100 μg / L), for each of the nitrite extract, chamomile extract, and yokuinin extract. 83%, and 99% for Yokuinin extract (1000 μg / L), and Nittobegi extract should show good safety equivalent to or higher than that of conventional whitening agents at concentrations where melanin production inhibitory activity is observed. I understood.

[Example 4: Evaluation of antioxidant effect by measuring DPPH radical scavenging ability]
Antioxidant ability was evaluated based on the rate at which the maximum absorption at 517 nm of 1,1-Diphenyl-2-picrylhydrazyl (hereinafter abbreviated as DPPH) having a stable radical was reduced when the sample was added.
A sample solution was prepared by diluting the nitrite extract obtained in Example 1 with 5 mmol / L acetic acid buffer so that the solid concentration would be 0.01, 0.02, 0.1%. After adding 1 mL of the sample solution to 0.5 mL of 0.5 mmol / L DPPH solution and 1 mL of ethanol and reacting at room temperature for 20 minutes, absorbance at 517 nm (Abs (S)) was measured. At this time, the final solid content concentrations of the nitrite extract were 0.0004, 0.002, 0.004, and 0.02%, respectively. Absorbance (Abs (C)) was measured in the same manner using DPPH solution (0.5 mL), ethanol (1 mL), and acetate buffer (1 mL) as control solutions. The radical scavenging rate was determined by Equation 1.
(Formula 1)
Radical scavenging rate = [Abs (C) −Abs (S)] / Abs (C) × 100
The radical scavenging rate is represented by a value from 0 to 100. Here, the antioxidant ability was evaluated by the solid content concentration IC50 of the sample having a radical scavenging rate of 50. It can be said that the lower the IC50, the higher the antioxidant capacity of the sample. The results are shown in Table 2 below.

  A similar test was also conducted on chamomile extract, which has a known antioxidant effect. For the evaluation, the chamomile extract prepared in Example 2 was used. The results are also shown in Table 2 below.

  As is clear from the results in Table 2, the IC50 of the nitrite extract was lower than the IC50 of the chamomile extract and was found to have a high radical scavenging ability. Therefore, it can be expected that nitobegiku extract is applied to the skin as an antioxidant component to prevent and improve skin wrinkles, sagging, gloss, reduction of elasticity, and the like caused by aging, ultraviolet exposure, and the like.

[Example 5: Evaluation of cell activation by cultured cells]
Human neonatal fibroblasts NB1RGB were used. An appropriate amount of medium was taken in a 24-well plate, seeded with fibroblasts NB1RGB, and allowed to stand at 37 ° C. in a carbon dioxide concentration of 5 vol%. The sample preparation liquid was added and mixed so that the final solid content concentration was 0 (control) and 1 μg / mL, respectively, for the nitrite extract obtained in Example 1. On day 4 of the culture, the medium was changed, and the sample preparation solution was added again. On the next day, the medium was removed, the cells were washed with a phosphate buffer and then collected, and the number of fibroblasts NB1RGB grown in each specimen preparation solution was evaluated as the cell growth rate compared to the control. Moreover, the same test was done by making the soybean extract known to have a cell activation effect into the comparative product 3. The soybean extract was obtained by adding 100 mL of 70 vol% hydrous ethyl alcohol to 10 g of soybean seeds, performing extraction at room temperature for 3 days, and then filtering. At this time, the dry solid content of the soybean extract was 0.5%.

(Evaluation criteria)
The number of cells was counted using a hemocytometer. The number of cells grown by adding each sample preparation solution was compared with the number of control cells, and the cell activation effect was evaluated using the cell proliferation rate as an index. These results are shown in Table 3.

(result)

  As is clear from the results in Table 3, it was confirmed that the extract of nitobegiku has a high cell activation ability equivalent to that of the soybean extract with respect to human neonatal fibroblast NB1RGB. Therefore, it can be expected that nitobegiku extract is applied to the skin as a cell activation component to prevent and improve skin wrinkles, sagging, gloss, reduction of elasticity, and the like caused by aging, ultraviolet exposure, and the like.

[Example 6: lotion]
A solution in which the following components (3) to (5) and (9) to (11) are mixed and dissolved; and a solution in which the components (1), (2), (6) to (8) and (12) are mixed and dissolved; Were mixed to obtain a skin lotion.
(Prescription) (%)
(1) Glycerin 5.0
(2) 1,3-butylene glycol 6.5
(3) Polyoxyethylene (20E.O.) sorbitan 1.2
Monolaurate (4) Ethyl alcohol 8.0
(5) Nitobegi extract * 1 0.005
(6) Magnesium L-ascorbate phosphate * 2 0.5
(7) Lactic acid 0.05
(8) Sodium lactate 0.1
(9) Paramethoxycinnamic acid-2-ethylhexyl 3.0
(10) Preservative Appropriate amount (11) Fragrance Appropriate amount (12) Purified water Remaining amount * 1 Made in Example 1 * 2 Sigma

[Example 7: Latex]
The following components (1) to (6) and (10) and (13) were heated and mixed to prepare a mixture 1 maintained at 70 ° C. A part of components (12) and (14) was heated and mixed to prepare a mixture 2 kept at 70 ° C. A mixture 3 was prepared by dissolving the components (7) to (9) with the remainder of the component (14). The mixture 2 was added to the mixture 1 and mixed, and the mixture was uniformly emulsified. Furthermore, after cooling this emulsion, the mixture 3 was added and mixed uniformly. (11) was added to this mixture, and it fully stirred, and also (15) was added and mixed uniformly to obtain an emulsion.
(Prescription) (%)
(1) Polyoxyethylene (10E.O.) sorbitan 1.0
Monostearate (2) Polyoxyethylene (60EO) Sorbit 0.5
Tetraoleate (3) Glyceryl monostearate 1.0
(4) Stearic acid 0.5
(5) Behenyl alcohol 0.5
(6) Squalane 8.0
(7) Dipotassium glycyrrhizinate * 1 0.3
(8) Nitobegi extract * 2 0.02
(9) Daylily extract * 3 0.1
(10) Preservative 0.1
(11) Carboxyvinyl polymer 0.1
(12) Sodium hydroxide 0.05
(13) Ethyl alcohol 5.0
(14) Purified water Remaining amount (15) Fragrance Appropriate amount * 1 Made by Sigma * 2 Made in Example 1 * 3 Maruzen Pharmaceutical Co., Ltd.

  Both the lotion prepared in Example 6 and the emulsion prepared in Example 7 were excellent cosmetics that, when applied to the skin, whitened the skin and gave the skin a gloss and gloss. Moreover, the stability of these lotions and emulsions was also good.

  The external preparation for skin of the present invention can be used for various applications such as cosmetics, quasi drugs, and external medicines. Especially, since it is excellent in the whitening effect and / or the anti-aging effect, it is particularly useful as a cosmetic.

Claims (3)

An external preparation for skin containing nitobegiku extract as an active ingredient. The skin external preparation of Claim 1 which contains the said nitobegiku extract as a whitening agent. The skin external preparation of Claim 1 which contains the said nitobegiku extract as an anti-aging agent.