JP2013216650A - Skin care preparation and method for suppressing degradation of carotenoid-containing oily component due to ultraviolet ray - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a stabilized skin care preparation containing a carotenoid-containing oily component and a method for suppressing degradation of a carotenoid-containing oily component, especially astaxanthin.SOLUTION: There are provided a skin care preparation containing a carotenoid-containing oily component and resveratrols or derivatives thereof and a method for suppressing light-induced degradation of astaxanthin using resveratrols or derivatives thereof. With such method, the skin care preparation containing a carotenoid-containing oily component is obtained which has excellent stability and an useful effect on the skin such as prevention of aging, prevention and improvement of blems and the like.

Description

  The present invention relates to a skin external preparation characterized by containing a carotenoid-containing oily component and resveratrol or a derivative thereof, and more specifically, decomposition of a carotenoid-containing oily component by ultraviolet rays by resveratrols or a derivative thereof. And a method for inhibiting degradation of carotenoid-containing oily components by resveratrol or derivatives thereof.

Known are polyphenols such as catechin and carotenoids such as astaxanthin, which have useful effects on the skin such as prevention of aging and prevention / improvement of spots. Carotenoids are naturally occurring yellow to red terpenoid pigments that can be found in plants, algae, and bacteria. Astaxanthins (including astaxanthin and esters thereof), which is a kind of carotenoid, are widely distributed in the animal and plant kingdoms in nature, and are mainly used as a color frying agent for farmed fish and chickens. Astaxanthin is also known to have functions such as an antioxidant effect, an anti-inflammatory effect (Patent Documents 1 and 2), and an anti-skin aging effect (Patent Document 3). For this reason, adding astaxanthin to foods, cosmetics, raw materials for pharmaceuticals, processed products thereof, and the like has been studied and implemented.
On the other hand, carotenoids such as astaxanthin are structurally unstable, and are known to be decomposed by heat, light, oxidation, etc., and are difficult to be stably incorporated into preparations. Therefore, in addition to the concomitant use of ascorbic acid and inclusion with hard capsules (see Patent Document 4), a method of combining a specific oil-soluble plant extract, alcohol, nut polyphenol and chelating agent (See Patent Document 5), a method of adding an organic acid to a carotenoid-containing composition (see Patent Document 6), combined use with iron ions, iron chelating agents, dipropylene glycol, and a water-soluble antioxidant (see Patent Document 7) ) And the like, a method for stabilizing carotenoids such as astaxanthin is disclosed.

However, in any of these methods, the stabilizer is expensive, the stabilization effect is not sufficient, or when the stabilizer is a water-soluble component, it is difficult to disperse it in an oil component that dissolves carotenoids such as astaxanthin There was a problem that sufficient effects could not be exhibited. That is, it was not satisfactory from the viewpoint of directly stabilizing carotenoids such as astaxanthin known to have useful effects and sustaining the effects over a long period of time.

JP-A-2-49091 Japanese Patent Laid-Open No. 9-143063 Japanese Patent Application Laid-Open No. 5-15536 JP-A-1-215263 JP 2010-105988 A JP-A-6-264055 JP 2012-31067 A

The problem to be solved by the present invention is to provide an external preparation for skin that directly enhances the stability of carotenoid oil components such as astaxanthin, which are known to be useful for preventing aging, and maintains the effect over a long period of time. And providing a method for stabilizing a carotenoid oil component.

In view of such circumstances, the present inventors have intensively studied to solve the above problems, and as a result, by combining a carotenoid-containing oily component and resveratrols which are a kind of stilbenoid polyphenol or a derivative thereof, a carotenoid-containing oily component. It has been found that it exhibits a remarkable effect in preventing and stabilizing fading caused by ultraviolet rays, that is, the anti-aging effect of a carotenoid-containing oil component such as astaxanthin can be remarkably improved, and the present invention has been completed.

That is, the present invention includes the following components (A) and (B);
(A) A carotenoid-containing oily component (B) A skin external preparation containing resveratrol or a derivative thereof and a method for stabilizing a carotenoid-containing oily component are provided.

  The external preparation for skin and method of the present invention can effectively exhibit the effect of the carotenoid-containing oily component by improving the stability of the carotenoid-containing oily component. Carotenoid-containing oily components such as astaxanthin are effective in preventing and improving rough skin and wrinkles, preventing and improving spots, and are useful for preventing skin aging and whitening. In the present invention, the color of the carotenoid-containing oily component is kept stable for a long period of time, so that it can also be used as a colorant. Furthermore, in combination with resveratrol, the anti-inflammatory action and the like increase synergistically in addition to anti-aging and whitening.

The carotenoid in the carotenoid-containing oily component of the present invention includes those extracted and purified from plants, algae, bacteria and fungi. Moreover, it is not limited to the thing of natural origin, Any thing will be included by the carotenoid in this invention if it can be obtained in accordance with a conventional method.

Examples of carotenoids include hydrocarbons (carotenes), oxidized alcohol derivatives thereof (xanthophylls), and esters thereof.
In the present invention, these compounds are referred to as “carotenoid” unless otherwise specified. Specific examples of the carotenes include α-carotene, β-carotene, γ-carotene, δ-carotene, lycopene and derivatives thereof, but are not limited thereto, and one or two kinds Mixtures of the above can also be used. Examples of xanthophylls include lutein, zeaxanthin, canthaxanthin, fucoxanthin, astaxanthin, and violaxanthin derivatives thereof, but are not limited to these, and one or a mixture of two or more types can also be used. Derivatives include, but are not limited to, esters with fatty acids and sugars, amino acids and proteins that exist in natural products. For example, carotenoids also exist as cartenoprotenes bound to proteins in marine animals, and play an important role in changing the color tone of mimicry. By appropriately using these derivatives, the color tone of external preparations for skin can be adjusted. Is possible.

The carotenoid used in the present invention is preferably xanthophylls from the viewpoint of safety and stability, and particularly preferably has an antioxidant effect, an anti-inflammatory effect, an anti-skin aging effect, a whitening effect, etc., from yellow to red Astaxanthin, also known as a range of colorants.

Astaxanthin is a red pigment having an absorption maximum at 476 nm (ethanol) and 468 nm (hexane), and is classified into xanthophylls, and its chemical structure is 3,3′-dihydroxy-β, β-carotene-4, 4′-dione ( C ₄₀ H ₅₂ 0 ₄ , molecular weight 596.82). Astaxanthin is a 3S, 3S'-form, 3S, 3R'-form (meso-form), 3R in which isomers exist due to the configuration of the hydroxyl group at the 3 (3 ')-position of the ring structure present at both ends of the molecule. , 3R'- isomers, and cis- and trans- isomers of conjugated double bonds at the center of the molecule. For example, all cis-, 9-cis and 13-cis isomers.
A hydroxyl group at the 3,3′-position can form an ester with a fatty acid. Astaxanthin obtained from krill is a diester that is a combination of two fatty acids. , H. pluvialis is obtained from 3S, 3S'- and contains many monoesters with one fatty acid Astaxanthin obtained from Phaffia Rhodozyma has a structure opposite to that of 3S, 3S′-form, which is usually found naturally in 3R, 3R′-form. In the present invention, the term “astaxanthin” includes the above-mentioned derivatives such as astaxanthin and astaxanthin ester unless otherwise specified.

Astaxanthin used in the present invention may be, for example, one extracted from natural products such as krill, salmon, trout, cypress, red yeast, hematococcus algae, or a synthetic product, but extracted from hematococcus algae ( Hereinafter, hematococcus alga extract) is particularly preferable from the viewpoint of quality and productivity. The extraction solvent for obtaining astaxanthin from a natural product may be an aqueous solvent or an organic solvent. As the organic solvent, methanol, ethanol, isopropanol, acetone, 1,3-butylene glycol, ethylene glycol, propylene glycol, glycerin, ethyl acetate, ether, hexane, or the like can be used. Also, carbon dioxide in a supercritical state can be used. These solvents may be used alone or in combination of two or more.

Specific examples of the origin of the Haematococcus alga extract usable in the present invention include Haematococcus pluvialis, Haematococcus lacustris, Haematococcus capensis, Haematococcus capensis, Examples thereof include Haematococcus droebakensis and Haematococcus zimbabwiensis. Further, commercially available Haematococcus algae extract can be used, for example, ASTOTS-S, -5O, -10O, etc. manufactured by Takeda Kaiki Co., Ltd., Asteril manufactured by Fuji Chemical Industry Co., Ltd. Examples thereof include Astaxanthin-5C and 20C manufactured by Oriza Oil and Astabio (registered trademark) AR1 and AR5 manufactured by Biogenic.

In the carotenoid-containing oily component in the present invention, the type of oily component is not limited, and it may be a hydrocarbon, ester oil, higher alcohol, silicone, fluorine-based oil, etc., regardless of the origin of animal oil, vegetable oil, synthetic oil, etc. Either of these is used. A liquid oil that is liquid at 25 ° C. is preferred from the viewpoint of easy production of a skin external preparation. Natural or synthetic glycerides are preferred from the viewpoint of availability, stability, and safety. Particularly preferred are both of these viewpoints, and specific examples include medium chain fatty acid glycerides. The medium-chain fatty acid glyceride refers to a lipid formed by ester-linking a saturated fatty acid having 6 to 12 carbon atoms, specifically, caproic acid, caprylic acid, capric acid, or lauric acid. Any of 1 to 3 of these saturated fatty acids ester-bonded to glycerol may be used.
The carotenoid content in the carotenoid-containing oily component is not particularly limited, but is preferably 0.01 to 50% by mass, more preferably 0.1 to 30% (hereinafter simply referred to as “%”), Especially preferably, it is 1 to 20%.

In addition, the amount of the carotenoid-containing oil component in the external preparation for skin is preferably 0.0001 to 10%, more preferably 0 from the viewpoints of effects on the skin, stability as an external preparation, and colorability as a pigment. 0.0001 to 1%, particularly preferably 0.001 to 0.1%.

On the other hand, resveratrols in the present invention refer to resveratrol monomers and multimers such as dimers and trimers thereof. Resveratrol monomer is also known as 5-parahydroxystyryl resorcinol or 3,4 ', 5-stilbenetriol, and both the stereoisomers trans-resveratrol and cis-resveratrol Including. Pure resveratrol can be obtained commercially from Sigma, Wako Pure Chemical Industries, Ltd., for example. In addition to ε-viniferin and gnetin C, which are dimers, and VITISIN-A and VITISIN-B which are trimers, various oligomers are known as multimers, and some of them are Sigma In addition to being able to obtain pure products from Wako Pure Chemical Industries, Ltd., and including one or more resveratrols including resveratrol monomers, ACTICHEM SA (ACTICHEM), DNP・ International Corporation (DNP
It can be obtained in crude form from raw material manufacturers such as International), Pharma Science, or Madis Botanicals, Sunbright Co., Ltd., and Oriza Yuka Co., Ltd.

In the present invention, a pharmaceutically acceptable salt, ester and / or ether can be used as the resveratrol derivative. Of these, piseed, which is a glycoside, and 3,4′-transdihydroxystilbene, 3-hydroxystilbene, and 3,4-transdihydroxystilbene, which have different coordination and number of OH groups, are preferable, and oxyresvera is particularly preferable. It is a trawl (Stilbene-2,3 ′, 4,5′-tetrol), and one or more of these can be used.

Resveratrols or derivatives thereof may be chemically synthesized, but can also be extracted from plants such as grapes and Japanese knotweed. The extraction method from the plant is not particularly limited, and a general extraction method can be used. Further, the extraction solvent may be an aqueous solvent or an organic solvent. As the organic solvent, methanol, ethanol, isopropanol, acetone, 1,3-butylene glycol, ethylene glycol, propylene glycol, glycerin, ethyl acetate, ether, hexane, or the like can be used. Also, carbon dioxide in a supercritical state can be used. These solvents may be used alone or in combination of two or more. The resveratrols or derivatives thereof used in the present invention may be any of reagents, synthetic products, and those extracted from plants.

  The content of resveratrol or a derivative thereof in the external preparation for skin of the present invention varies depending on the external preparation, the dosage form of cosmetics, the purpose of use, etc., but generally the concentration in the final external preparation for skin is 0. It is preferable that it becomes 00001-2.0%, More preferably, it is 0.0001-1%, Most preferably, it is 0.001-0.1%. When the concentration of resveratrol or a derivative thereof in the external preparation for skin is within this range, an excellent effect of stabilizing a carotenoid-containing oil component such as astaxanthin can be exhibited.

 The formulation form of the external preparation for skin of the present invention is not particularly limited. For example, basic cosmetics such as milky lotion, cream, lotion, cosmetic liquid, pack, cleaning agent, makeup cosmetics such as foundation, blusher, lipstick, and nutrition Any form of hair cosmetics such as hair, hair tonic, shampoo, rinse, etc., dispersion, ointment, liquid, aerosol, patch, poultice, liniment, etc.

In the external preparation for skin of the present invention, as long as it does not impair the effects of the present invention, components used for normal formulation, that is, water (purified water, hot spring water, deep water, etc.), oil agent, Surfactant, metal soap, gelling agent, powder, alcohol, water-soluble polymer, film forming agent, resin, UV protection agent, inclusion compound, antibacterial agent, fragrance, deodorant, salt, pH adjuster , Fresheners, animal / microbe-derived extracts, plant extracts, blood circulation promoters, astringents, antiseborrheic agents, whitening agents, anti-inflammatory agents, active oxygen scavengers, cell activators, moisturizers, chelating agents, keratins Solubilizers, enzymes, hormones, vitamins, etc. can be added.

Hereinafter, the present invention will be described more specifically with reference to Examples and Comparative Reference Examples, but the scope of the present invention is not limited thereto.

Example 1
<Astaxanthin degradation prevention effect (stabilization effect) Test 1>
Oil component containing 5% astaxanthin in tri (capryl / capric acid) glyceride (manufactured by Marine Daio Co., Ltd.) containing 0.005% by volume, ethanol containing 30% by volume, purity 99% resveratrol (Sigma) Was prepared at a concentration of 0.5, 50, and 500 μM. This solution was added to a 24-well plate and irradiated with ultraviolet light. Astaxanthin has light absorption peculiar to a wavelength of 470 nm, and the stability of astaxanthin was evaluated this time using the property that the light absorption at a wavelength of 470 nm decreases when the decomposition of astaxanthin occurs.

Astaxanthin residual rate was measured by measuring the absorbance of each sample at 470 nm (Formula 1)

Astaxanthin residual rate (%) = (A−B) / (C−D) × 100 (1)

A = Absorbance of UV-irradiated astaxanthin-containing system B = Absorbance of UV-irradiated astaxanthin-free system C = Absorbance of UV-unirradiated astaxanthin-containing system D = Absorbance of non-UV-irradiated astaxanthin-containing system

Further, as a comparative example, ascorbic acid-2-glucoside, which is a general antioxidant, or magnesium ascorbate phosphate was added at a concentration of 0.5, 50, and 500 μM, and the same test was performed. The results are shown in Table 1.

  As is clear from Table 1, compared to the general antioxidants ascorbic acid 2-glucoside or ascorbic acid magnesium phosphate, resveratrol reduces the residual rate of astaxanthin, that is, suppresses the degradation of astaxanthin by ultraviolet rays. It was found to be very good and resveratrol was found to have a stabilizing effect on the photodegradation of astaxanthin.

Example 2
<Astaxanthin degradation prevention effect (stabilization effect) Test 2>
Oil component containing 5% of astaxanthin (manufactured by Marine Daio Co., Ltd.) 0.005% by volume, ethanol 30% by volume, resveratrol (Sigma) at concentrations of 0.1, 10, 100 μg / ml An aqueous solution containing was prepared. This solution was added to a 24-well plate and irradiated with ultraviolet light. As in Example 1, the absorbance at 470 nm unique to astaxanthin was measured, and the stability of astaxanthin was evaluated by comparing this with an unirradiated sample.
Further, as a comparative example, turmeric extract and cassis extract known as plant extracts having a high antioxidant effect were added at concentrations of 0.1, 10, and 100 μg / ml, and the same test was performed.
The astaxanthin residual rate was calculated by (Formula 1). The results are shown in Table 2.

  As is clear from Table 2, resveratrol has a reduced residual ratio of astaxanthin, that is, due to the ultraviolet rays of astaxanthin, compared to turmeric extract and cassis extract, which are plant extracts that contain various polyphenols and have a high antioxidant effect. It was found that the effect of suppressing decomposition was very excellent, and resveratrol was found to have a specific stabilizing effect against photodegradation of astaxanthin.

Example 3 <Astaxanthin Degradation Prevention Effect (Stabilization Effect) Test 3>

Resveratrol at the reagent level containing 0.005% by volume of tri (capric acid / caprylic acid) glyceryl and 5% by volume of ethanol containing 5% of astaxanthin derived from Haematococcus algae as a free form of astaxanthin (Sigma) ) Or oxyresveratrol (Tokyo Chemical Industry Co., Ltd.) was prepared at a concentration of 0.01, 0.05, 0.5, 5 mM. This solution was added to a 96-well plate and irradiated with ultraviolet light.
The results are shown in Table 3.
It was found that even carotenoid-containing oily components other than astaxanthin are effective.

Example 5 [Formulation in lotion]
(Ingredient) (mass%)
1 Glycerin 5.0
2 1,3-butylene glycol 5.0
3 Lactic acid 0.05
4 Sodium lactate 0.1
5 Hydrolyzed collagen 0.1
6 Polyoxyethylene (20E.O.) sorbitan monooleate 1.2
7 Ethanol 8.0
8 Resveratrol (Note 1) 0.05
9 ASTOTS-10O (Note 2) 0.001
10 Methyl paraoxybenzoate 0.1
11 Fragrance 0.05
12 Purified water Remaining amount (Note 1) Sigma (Note 2) Takeda Paper device Sunflower oil containing 10% astaxanthin

(Production method)
A: Components (6) to (11) are mixed and dissolved.
B: Components (1) to (5) and (12) are mixed and dissolved.
C: A was added to B and mixed to obtain a skin lotion.

Example 6 [Formulation in emulsion]
(Ingredient) (mass%)
1 Polyoxyethylene monostearate (20E.O.) sorbitan 1.0
2 Polyoxyethylene trioleate (20E.O.) sorbitan 0.5
3 Glyceryl monostearate 1.0
4 Stearic acid 0.5
5 Behenyl alcohol 0.5
6 Squalane 8.0
7 Carboxyvinyl polymer 0.1
8 Methyl paraoxybenzoate 0.1
9 Sodium hydroxide 0.05
10 Purified water remaining 11 Ethanol 5.0
12 Pie Seed (Note 3) 0.01
13 ASTABIO AR1 (Note 4) 0.01
14 Fragrance 0.05
(Note 3) Made by Tokyo Chemical Industry (Note 4) Made by Biogenic
Astaxanthin derived from Haematococcus algae (free body equivalent) content 1%

(Production method)
A: Components (1) to (6) are uniformly mixed at 70 ° C.
B: Components (7) to (10) are uniformly mixed at 70 ° C. C: A is added to B, emulsified, and cooled to room temperature.
D: (11) to (14) were added and mixed uniformly to obtain an emulsion.

Example 7 [Formulation in liquid foundation (oil-in-water cream)]
(Ingredient) (mass%)
1 1,3 Butylene glycol 5.0
2 Hydrogenated soybean phospholipid 0.5
3 Titanium oxide 5.0
4 Bengala 0.1
5 Yellow iron oxide 1.0
6 Black iron oxide 0.05
7 Copolymerization of acrylic acid and alkyl methacrylate (Note 5) 0.5
8 Triethanolamine 1.5
9 Purified water remaining 10 Glycerin 5.0
11 Ethyl paraoxybenzoate 0.1
12 Stearic acid 0.9
13 Glycerol monostearate 0.3
14 cetostearyl alcohol 0.4
15 Polyoxyethylene (20E.O.) sorbitan monooleate 0.2
16 Polyoxyethylene trioleate (20E.O.) sorbitan 0.2
17 2-Ethylhexyl paramethoxycinnamate 5.0
18 ε-viniferin (Note 6) 0.05
19 β-carotene 30% suspension (Note 7) 0.05
20 Perfume 0.02
(Note 5) Pemulen TR-2 (manufactured by NOVEON)
(Note 6) Wako Pure Chemical Industries, Ltd. (Note 7) DSM Nutrition, Inc. Suspended in corn oil

(Production method)
A: Disperse components (1) to (6).
B: Components (7) to (11) are added to A and mixed uniformly at 70 ° C.
C: Components (12) to (17) are uniformly mixed at 70 ° C.
D: B is added to C to emulsify, and cooled to room temperature.
E: Components (18) to (20) were added to D to obtain an oil-in-water cream liquid foundation.

Example 8 [Formulation in sunscreen cosmetic (water-in-oil cream)]
(Ingredient) (mass%)
1 Polyoxyethylene (20E.O.) sorbitan monolaurate 0.2
2 Polyoxyethylene (60) hydrogenated castor oil
0.1
3 Remaining purified water 4 Dipropylene glycol 10.0
5 Magnesium sulfate 0.5
6 Ascorbic acid glucoside 2.0
7 Silicone compound (Note 8) 3.0
8 Decamethylcyclopentasiloxane 20.0
9 Isotridecyl isononanoate 5.0
10 2-Ethylhexyl paramethoxycinnamate 8.0
11 Gnetin C (Note 9) 0.3
12 Zeaxanthin 5% oil (Note 10) 0.01
13 Dimethylstearyl ammonium hectorite 1.2
(Note 8) KF-6028 (manufactured by Shin-Etsu Chemical Co., Ltd.)
(Note 9) Wako Pure Chemical Industries (Note 10) Bioactives Japan

(Production method)
A: Components (1) to (6) are uniformly dispersed.
B: Components (7) to (13) are uniformly dispersed.
C: While stirring B, A was gradually added to emulsify to obtain a water-in-oil cream sunscreen cosmetic.

Example 9 [Formulation in ointment]
(Ingredient) (mass%)
1 Triethanolamine 2.0
2 Glycerin 5.0
3 Dipotassium glycyrrhizinate (Note 11) 0.5
4 Purified water remaining 5 Stearic acid 18.0
6 Cetanol 4.0
7 Resveratrol (Note 1) 0.05
8 Astaxanthin-5C (Note 12) 0.01
9 dl-α-tocopherol acetate 0.2
10 Methyl paraoxybenzoate 0.1

(Note 11) Wako Pure Chemical Industries, Ltd. (Note 12) Oriza Yuka

(Production method)
A. Ingredients (1) to (4) are uniformly dissolved and kept at 75 ° C.
B. Ingredients (5) to (10) are heated and mixed and maintained at 75 ° C.
C. B was gradually added to A to obtain an ointment.

Example 10 [Formulation in lotion preparation]
(Ingredient) (mass%)
1 Polyoxyethylene (20E.O.) sorbitan monolaurate ester 1.2
2 Ethanol 8.0
3 Grape stem extract 0.05
4 Fucoxanthin-5C (Note 14) 0.001
5 Methyl paraoxybenzoate 0.2
6 Glycerin 5.0
7 1,3-butylene glycol 6.5
8 Purified water remaining amount (Note 13) Made by BHN Co., Ltd. Contains 20% of total resveratrol (oligostilbene) (Note 14)

(Production method)
A. Components (1) to (5) are mixed and dissolved.
B. Components (6) to (8) are mixed and dissolved.
C. A and B were mixed and homogenized to obtain a lotion preparation.

The skin external preparation characterized by containing the carotenoid-containing oily component of the present invention and resveratrol or a derivative thereof, and the method for inhibiting the degradation of astaxanthin are stable in the preparation of a carotenoid-containing oily component such as astaxanthin. It is useful not only for improving but also for demonstrating skin effects such as prevention of aging and prevention / improvement of spots.

Claims (6)

A skin external preparation containing a carotenoid-containing oily component and resveratrol or a derivative thereof.
The skin external preparation according to claim 1, which contains a carotenoid-containing oily component stably.
The external preparation for skin according to claim 1 or 2, which suppresses the decomposition of the carotenoid-containing oil component by ultraviolet rays.
The skin external preparation according to any one of claims 1 to 3, wherein the carotenoid-containing oily component is astaxanthin.
A decomposition inhibitor for carotenoid-containing oily components containing resveratrol or a derivative thereof as an active ingredient.
A method for inhibiting decomposition of a carotenoid-containing oily component by resveratrol or a derivative thereof.