JP6533639B2 - Skin external preparation and method for suppressing decomposition of carotenoid-containing oily component by ultraviolet light - Google Patents

Description

  The present invention relates to an external preparation for skin comprising a carotenoid-containing oily component and resveratrols or a derivative thereof, and more specifically, the ultraviolet-induced degradation of a carotenoid-containing oily component with resveratrols or a derivative thereof The present invention relates to an external preparation for skin which is inhibited, and a method for inhibiting the decomposition of a carotenoid-containing oily component by resveratrols or a derivative thereof.

As polyphenols such as catechin and carotenoids such as astaxanthin, those having useful effects on the skin such as antiaging, prevention and improvement of stains and the like are known. 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 are a type of carotenoid, are widely distributed in the animal and plant kingdom in the natural world, and are mainly used as a color-deepening agent for cultured fish and poultry. Astaxanthin is also known to have functions such as an antioxidant effect, an anti-inflammatory effect (Patent Document 1, Patent Document 2), a skin anti-aging effect (Patent Document 3), and the like. Therefore, it has been studied and implemented to add astaxanthin to raw materials of foods, cosmetics, pharmaceuticals and processed products thereof.
On the other hand, carotenoids such as astaxanthin are structurally unstable, and are known to accelerate decomposition by heat, light, oxidation and the like, and it is difficult to stably blend them into preparations. Therefore, in addition to the combination with ascorbic acid and the inclusion with a hard capsule, etc. have been devised (see Patent Document 4), a method of combining a specific oil-soluble plant extract with an alcohol and a nut polyphenol and a chelating agent (See Patent Document 5) or a method of adding an organic acid to a carotenoid-containing composition (see Patent document 6), iron ion, iron chelating agent, dipropylene glycol, combined use with a water-soluble antioxidant (see Patent Document 7) Methods of stabilizing carotenoids such as astaxanthin, etc.).

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

JP-A-2-49091 JP-A-9-143063 JP-A-5-155736 Unexamined-Japanese-Patent No. 1-215263 Unexamined-Japanese-Patent No. 2010-105988 Japanese Patent Application Laid-Open No. 6-264055 JP, 2012-31067, A

The problem to be solved by the present invention is to provide a skin external preparation which directly enhances the stability of a carotenoid oil component such as astaxanthin which is known to be useful for preventing aging, and maintains its effect for a long time It is another object of the present invention to provide a method for stabilizing a carotenoid oily component.

In view of such circumstances, the inventor of the present invention has intensively studied to solve the above-mentioned problems, and as a result, a carotenoid-containing oily component is obtained by combining a carotenoid-containing oily component with resveratrols which is one of stilbenoid polyphenols or derivatives thereof. It has been found that it exerts a remarkable effect on the prevention and stabilization of discoloration by ultraviolet light, that is, the antiaging effects of carotenoid-containing oily components such as astaxanthin can be dramatically enhanced, and the present invention has been completed.

That is, the present invention provides the following components (A) and (B):
(A) Carotenoid-Containing Oily Component (B) The present invention provides a skin external preparation containing resveratrols or a derivative thereof and a method of stabilizing a carotenoid-containing oil component.

  The skin external preparation and method of the present invention can effectively exhibit the effect of the carotenoid-containing oil component by improving the stability of the carotenoid-containing oil component. Carotenoid-containing oily components such as astaxanthin are effective in preventing and improving rough skin and wrinkles, and preventing and improving stains, and are useful in preventing skin aging and whitening. Further, in the present invention, since the color of the carotenoid-containing oily component is stably maintained for a long time, it can also be used as a coloring agent. Furthermore, by using resveratrols in combination, in addition to anti-aging and whitening synergistically, anti-inflammatory action and the like are enhanced.

Carotenoids in the carotenoid-containing oily component of the present invention include those extracted and purified from plants, algae and any of bacteria and fungi. Further, the present invention is not limited to naturally occurring ones, and any one obtained according to a conventional method is included in the carotenoid in the present invention.

Carotenoids include hydrocarbons (carotenes) and their oxidized alcohol derivatives (xanthophylls) and their esters.
In the present invention, unless otherwise specified, these compounds are collectively referred to as "carotenoids". Specific examples thereof include α-carotene, β-carotene, γ-carotene, δ-carotene, lycopene and derivatives thereof as carotenes, but are not limited to these, and one or two kinds Mixtures of the above may also be used. Examples of xanthophylls include lutein, zeaxanthin, canthaxanthin, fucoxanthin, astaxanthin, violaxanthin and the like, but are not limited thereto, and one or a mixture of two or more can also be used. The derivatives include, but are not limited to, esters with fatty acids, sugars, amino acids, proteins and the like which are present in natural products. For example, carotenoids are also present as cartenoproteins bound to proteins in marine animals and play an important role in the change in color tone of mimicry, and it is possible to adjust the color tone of the external preparation for skin by appropriately using these derivatives. It is possible.

As the carotenoid used in the present invention, xanthophylls are preferable from the viewpoint of safety and stability, and particularly preferably having an antioxidant effect, an anti-inflammatory effect, an anti-skin aging effect, a whitening effect, etc. 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 an isomer exists 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 in the center of the molecule. For example, all cis-, 9-cis and 13-cis.
The hydroxyl group at the 3,3'-position can form an ester with a fatty acid. Astaxanthin obtained from krill is a diester in which two fatty acids are linked , And H. pluvialis, which is obtained from 3S, 3S'-form, contains a large amount of monoester bound with one fatty acid. Astaxanthin obtained from Phaffia Rhodozyma has a structure opposite to that of 3S, 3S'- which is usually found naturally in 3R, 3R'-form. In the present invention, unless otherwise specified, the above astaxanthin and derivatives such as astaxanthin ester and the like are referred to as "astaxanthin".

The astaxanthin used in the present invention may be, for example, extracts from natural products such as krill, salmon, trout, adonis, red yeast, Haematococcus alga etc. or synthetic products, but those extracted from Haematococcus alga ( Hereinafter, the Haematococcus alga extract is also particularly preferable in terms 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 and the like can be used. In addition, carbon dioxide in a supercritical state can also be used. These solvents may be used alone or in combination of two or more.

Specific examples of the source of the Haematococcus alga extract that can be used in the present invention include Haematococcus pluvialis, Haematococcus lacustris, Haematococcus capensis, Haematococcus. Haematococcus droebakensis, Haematococcus zimbabensis, etc. are mentioned. In addition, Hematococcus alga extract that is widely marketed can be used, for example, ASTATEL-S, -5O, -10O, etc. made by Takeda Paper Inc., Astarille, made by Fuji Chemical Industry Co., Ltd. Oils 50F, 5F, etc., astaxanthin-5C, 20C manufactured by Oryza Oil Co., Ltd., Astabio (registered trademark) AR1, AR5 manufactured by Biogenic, etc. may be mentioned.

In the carotenoid-containing oily component in the present invention, the type of oily component is not limited, and hydrocarbons, ester oils, higher alcohols, silicones, fluorinated oils, etc. regardless of the origin of animal oil, vegetable oil, synthetic oil etc. Any of these is used. Preferably, a liquid oil which is liquid at 25 ° C. is preferable from the viewpoint of easy production of a skin external preparation. In addition, natural or synthetic glycerides are preferable in terms of availability, stability and safety. Particularly preferred are both of these viewpoints, and specific examples include medium-chain fatty acid glycerides. Medium-chain fatty acid glyceride refers to a lipid composed of saturated fatty acid having 6 to 12 carbon atoms, specifically caproic acid, caprylic acid, capric acid or lauric acid, which is esterified with glycerol. Any one of these saturated fatty acids esterified with glycerol may be used.
The content of the carotenoid in the carotenoid-containing oily component is not particularly limited, but is preferably 0.01 to 50% by mass, and more preferably 0.1 to 30% (hereinafter simply referred to as "%"), Particularly preferably, it is 1 to 20%.

In addition, the amount of the carotenoid-containing oily component in the external preparation for skin is preferably 0.00001 to 10%, more preferably 0, from the viewpoint of the effect on the skin, the stability as the external preparation, and the coloring property as a pigment. .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 thereof such as dimers and trimers. The resveratrol monomer is also known as 5-parahydroxystyryl resorcinol or 3,4 ', 5-stilbentriol, and both of the stereoisomers trans-resveratrol and cis-resveratrol are Including. Pure resveratrol can be obtained commercially, for example, from Sigma, Wako Pure Chemical Industries, Ltd. Further, as multimers, various oligomers are known in addition to the dimer ε-viniferin, gunetin C, trimers VITISIN-A and VITISIN-B, and some of these oligomers are from Sigma Co. In addition to being able to obtain pure products from Wako Pure Chemical Industries, Ltd. (Sigma), and containing one or more resveratrols, including resveratrol monomers, Aktekem SA (ACTICHEM), DNP・ International (DNP)
They can be obtained in crude form from raw material manufacturers such as International), Pharma Science, or Madis Botanicals, Sun Bright Inc., Oryza Oil Co., Ltd.

In the present invention, pharmaceutically acceptable salts, esters and / or ethers can be used as resveratrol derivatives. Among them, Piseed which is a glycoside, 3,4'-transdihydroxystilbene having different OH group coordination and number, 3-hydroxystilbene and 3,4-transdihydroxystilbene 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.

In addition, resveratrols or derivatives thereof may be chemically synthesized, but can also be used by extracting from plants such as grapes and Japanese knotweed. The extraction method from plants is not particularly limited, and general extraction methods 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 and the like can be used. In addition, carbon dioxide in a supercritical state can also be used. These solvents may be used alone or in combination of two or more. As the resveratrols or derivatives thereof used in the present invention, any of reagents, synthetic products and those extracted from plants can be used.

  Although the content of resveratrols or derivatives thereof in the external preparation for skin of the present invention varies depending on the external preparation, the dosage form of the cosmetic preparation, the purpose of use, etc., the concentration in the final external preparation for skin is generally 0. The content is preferably 00001 to 2.0%, more preferably 0.0001 to 1%, and particularly preferably 0.001 to 0.1%. If the concentration of resveratrols or derivatives thereof in the external preparation for skin is within this range, it is possible to exert an excellent stabilizing effect of a carotenoid-containing oily component such as astaxanthin.

 The formulation form of the external preparation for skin of the present invention is not particularly limited, and, for example, basic cosmetics such as milk, cream, lotion, beauty liquid, pack, cleansing agent, foundation, makeup cosmetic such as blush, lipstick, etc. It may be in the form of hair, hair tonic, shampoo, rinse etc. hair cosmetic, dispersion, ointment, solution, aerosol, patch, patch, liniment and the like.

The external preparation for skin of the present invention is a component used for ordinary formulation, that is, water (refined water, hot spring water, deep water, etc.), oil agent, to the extent that the effect of the present invention is not impaired as needed. Surfactants, metal soaps, gelling agents, powders, alcohols, water-soluble polymers, film-forming agents, resins, UV protection agents, inclusion compounds, antibacterial agents, fragrances, deodorants, salts, pH adjusters , Refresh agent, extract derived from animal or microorganism, plant extract, blood circulation promoting agent, astringent, antiseborrhoeic agent, whitening agent, anti-inflammatory agent, active oxygen scavenging agent, cell activator, moisturizer, chelating agent, keratin Solubilizers, enzymes, hormones, vitamins etc can be added.

Hereinafter, the present invention will be more specifically described by way of examples and comparative reference examples, but the scope of the present invention is not limited to these.

Example 1
<Analysis effect of astaxanthin (stabilizing effect) test 1>
It contains 0.005% by volume of an oily component (manufactured by Marin Daio Co., Ltd.) containing 5% of astaxanthin in tri (caprylic / capric acid) glyceride and 30% by volume of ethanol and has a purity of 99% resveratrol (Sigma) Were prepared at concentrations of 0.5, 50 and 500 μM. This solution was added to a 24-well plate and irradiated with ultraviolet light. Astaxanthin has a specific light absorption at a wavelength of 470 nm, and the stability of astaxanthin was evaluated at this time by utilizing the property that light absorption at a wavelength of 470 nm decreases when astaxanthin decomposition occurs.

Astaxanthin retention rate measures the absorbance at 470 nm of each sample, (Equation 1)

Astaxanthin residual rate (%) = (A-B) / (C-D) x 100 (1)

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

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

  As is clear from Table 1, resveratrol has a lower residual rate of astaxanthin, that is, an effect of suppressing the degradation of astaxanthin by ultraviolet light, as compared with ascorbic acid 2 glucoside or magnesium ascorbate phosphate which is a general antioxidant. It was found to be very good and resveratrol was found to have a stabilizing effect on the photodegradation of astaxanthin.

Example 2
<Anti-degradation effect of Astaxanthin (stabilizing effect) test 2>
0.005% by volume of an oily component (manufactured by Marin Daio Co., Ltd.) containing 5% of astaxanthin, 30% by volume of ethanol, and resveratrol (Sigma) at concentrations of 0.1, 10 and 100 μg / ml The contained aqueous solution 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 specific to astaxanthin was measured, and the stability of astaxanthin was evaluated by comparing this with an unirradiated sample.
As a comparative example, a curcuma extract known as a plant extract having a high antioxidative effect and a cassis extract were added at concentrations of 0.1, 10 and 100 μg / ml to conduct the same test.
The astaxanthin residual rate was calculated by (Equation 1). The results are shown in Table 2.

  As is clear from Table 2, resveratrol has a reduction in the remaining rate of astaxanthin, that is, ultraviolet rays of astaxanthin, as compared with turmeric extract and cassis extract which are plant extracts having various antioxidants and having high antioxidant effects. It was found that the effect of suppressing degradation was very excellent, and resveratrol was found to have a stabilizing effect on the photodegradation of astaxanthin specifically.

Example 3 <The effect of preventing decomposition of astaxanthin (stabilizing effect) test 3>

Resveratrol (Sigma) containing 0.005% by volume of tri (capric acid / caprylic acid) glyceryl containing 5% of astaxanthin derived from Haematococcus algae in terms of free form of astaxanthin and 25% by volume of ethanol Or an aqueous solution containing oxyresveratrol (Tokyo Chemical Industry Co., Ltd.) 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 has been found that even carotenoid-containing oily components other than astaxanthin have similar effects.

Example 5 [blending into a lotion]
(Component) (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 Monooleic acid polyoxyethylene (20E.O.) sorbitan 1.2
7 Ethanol 8.0
8 Resveratrol (Note 1) 0.05
9 ASTOTS-10 O (Note 2) 0.001
10 Methyl parahydroxybenzoate 0.1
11 perfume 0.05
12 Purified water Remaining amount (Note 1) Made by Sigma (Note 2) Takeda Paper Container Astaxanthin 10% sunflower oil content

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

Example 6 [blending into emulsion]
(Component) (mass%)
1 Polyoxyethylene (20E.O.) sorbitan monostearate 1.0
2 Trioleic acid polyoxyethylene (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 parahydroxybenzoate 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 perfume 0.05
(Note 3) Tokyo Chemical Industry Co., Ltd. (Note 4) Biogenic
Hematococcus alga-derived astaxanthin (free form equivalent) content 1%

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

Example 7 [Formulation to liquid foundation (oil-in-water cream-like)]
(Component) (mass%)
1 1,3 butylene glycol 5.0
2 Hydrogenated soybean phospholipids 0.5
3 Titanium oxide 5.0
4 bengara 0.1
5 Yellow iron oxide 1.0
6 Black iron oxide 0.05
7 Acrylic acid · alkyl methacrylate copolymer (Note 5) 0.5
8 Triethanolamine 1.5
9 Purified water remaining amount 10 Glycerin 5.0
11 Ethyl parahydroxybenzoate 0.1
12 stearic acid 0.9
13 Glycerin monostearate 0.3
14 cetostearyl alcohol 0.4
15 polyoxyethylene monooleate (20E.O.) sorbitan 0.2
16 Trioleic acid polyoxyethylene (20E.O.) sorbitan 0.2
17 Paramethoxycinnamic acid 2-ethylhexyl 5.0
18 ε-Vinipherin (Note 6) 0.05
19 β-carotene 30% suspension (Note 7) 0.05
20 perfumes 0.02
(Note 5) Pemulen TR-2 (made by NOVEON)
(Note 6) Wako Pure Chemical Industries (Note 7) Suspended in corn oil made by DSM Nutrition

(Production method)
A: The components (1) to (6) are dispersed.
B: Add components (7) to (11) to A and mix uniformly at 70 ° C.
C: Ingredients (12) to (17) are uniformly mixed at 70 ° C.
D: Add B to C, emulsify, and cool to room temperature.
E: Add ingredients (18) to (20) to D to obtain an oil-in-water cream liquid foundation.

Example 8 [Formulation into sunscreen cosmetic (water-in-oil cream-like)]
(Component) (mass%)
1 Monolaurate polyoxyethylene (20E.O.) sorbitan 0.2
2 Polyoxyethylene (60) hydrogenated castor oil
0.1
3 Purified water remaining amount 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 Isotrinodecyl isononanoate 5.0
10 2-Methylhexyl paramethoxycinnamate 8.0
11 Gunetin C (Note 9) 0.3
12 Zeaxanthin 5% oil (Note 10) 0.01
13 Dimethyl stearyl 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: The components (1) to (6) are uniformly dispersed.
B: The components (7) to (13) are uniformly dispersed.
C: While stirring B, A was gradually added and emulsified to obtain a water-in-oil type cream sunscreen cosmetic.

Example 9 [blending into an ointment]
(Component) (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 Settanol 4.0
7 Resveratrol (Note 1) 0.05
8 Astaxanthin-5C (Note 12) 0.01
9 Acetic acid dl-α-tocopherol 0.2
10 Methyl parahydroxybenzoate 0.1

(Note 11) Wako Pure Chemical Industries, Ltd. (Note 12) Oryza Oil

(Production method)
A. Dissolve components (1) to (4) uniformly and keep at 75 ° C.
B. Ingredients (5)-(10) are heat mixed and kept at 75 ° C.
C. To A was gradually added B to obtain an ointment.

Example 10 [blending into a lotion]
(Component) (mass%)
1 polyoxyethylene (20E.O.) sorbitan monolaurate 1.2
2 ethanol 8.0
3 grape stem extract 0.05
4 Fucoxanthin-5C (Note 14) 0.001
5 Methyl parahydroxybenzoate 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. 20% as total resveratrol (oligostilbene) (Note 14)

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

The external preparation for skin comprising the carotenoid-containing oily component of the present invention and resveratrols or a derivative thereof, and the method for suppressing the degradation of astaxanthin, the stability of the carotenoid-containing oily component such as astaxanthin in the preparation of It is useful not only to improve but also to exert effects on the skin such as antiaging and prevention / improvement of stains.

Claims (2)

Inhibitor of ultraviolet light degradation of astaxanthin in skin external preparations containing astaxanthin, which comprises resveratrol or oxyresveratrol as an active ingredient (except those containing gliadin-coated melon SOD active extract). A method for suppressing the degradation of astaxanthin by ultraviolet light in an external skin preparation containing astaxanthin by resveratrol or oxyresveratrol (except for the method for suppressing the degradation by gliadin-coated melon SOD active extract).