WO2011074275A1

WO2011074275A1 - Skin barrier function promoter

Info

Publication number: WO2011074275A1
Application number: PCT/JP2010/050470
Authority: WO
Inventors: 久美富永; 信子本江; 栄次山下
Original assignee: 富士化学工業株式会社
Priority date: 2009-12-18
Filing date: 2010-01-18
Publication date: 2011-06-23
Also published as: JP2011126820A; JP5912215B2

Abstract

Disclosed are a preparation for external application and a preparation for internal application both of which are effective on the promotion of a skin barrier function. Also disclosed is a combination of the preparation for external application and the preparation for internal application. The preparation for external application and the preparation for internal application are characterized by comprising one or both of tocopherol and a glyceride represented by general formula (1) and astaxanthin. (In the formula, R₁, R₂ and R₃ may be the same as or different from one another and independently represent a linear or branched saturated or unsaturated alkyl group having 8 to 22 carbon atoms.)

Description

Skin barrier function promoter

The present invention relates to an external preparation and an internal preparation effective for improvement by improvement of the skin barrier function and improvement of the skin barrier function (hereinafter collectively referred to as skin barrier function promotion) and a combination thereof.

Skin tissue is an important tissue that protects a living body from external chemical or physical stimuli.
Such a skin barrier function is said to be normal when a stratum corneum cell is matured, sufficiently flattened, and a structure in which cells having a sufficiently large surface area are layered is formed.

For the purpose of improving and promoting the skin barrier function, for example, Patent Documents 1 to 4 are known, but it is still not sufficient.
On the other hand, the applicant of the present application has been conducting research and product development on astaxanthin so far, and it has been clarified that the skin barrier function is promoted by combining astaxanthin with a predetermined other component. Invented.
Patent Document 5 discloses a cosmetic obtained by purifying a krill solvent extract.
However, from the content of the test results of the stratum corneum improvement effect, the test method evaluates the decrease in the amount of exfoliated corneocytes due to tape peeling, and it is not necessarily clear whether the skin barrier function has been improved.

JP 2007-14294 A Japanese Patent Application Laid-Open No. 2005-119995 Japanese Patent Laid-Open No. 2007-1914 JP 2004-51543 A Japanese Patent Laid-Open No. 5-15536

The present invention aims to provide an external preparation and an internal preparation effective for promoting the skin barrier function and a combination thereof.

The present invention is characterized by an external preparation applied to the skin and an oral preparation by oral administration, and particularly when the external preparation and the internal preparation are used in combination, a significant improvement in the recovery of the skin barrier function or an improvement in the skin barrier function is observed. .

1stly, the skin barrier function promotion external preparation as an external preparation which concerns on this invention is characterized by containing one or both and astaxanthin among tocopherol and the glyceride represented by following General formula (1).

However, R ₁ , R ₂ and R ₃ are each a linear or branched saturated or unsaturated alkyl group having 8 to 22 carbon atoms, which may be the same or different.

Secondly, the internal preparation for promoting skin barrier function according to the present invention contains one or both of tocopherol and glyceride represented by the following general formula (1) and astaxanthin.

However, R ₁ , R ₂ and R ₃ are each a linear or branched saturated or unsaturated alkyl group having 8 to 22 carbon atoms, which may be the same or different.
That is, the combination of one or both of the glyceride and tocopherol represented by the general formula (1) with the astaxanthin according to the present invention can be used as an external preparation or an internal preparation, thereby improving the skin barrier function. Or improve.

Here, tocopherol is also called vitamin E and is a methylated derivative of tocol.
There are four types of α, β, γ, and δ depending on the position of the methyl group, and D-α-tocopherol exists widely in nature.
In the present invention, the tocopherol may be any of the above, or a mixed tocopherol mixed.

Astaxanthin is a kind of carotenoid classified into xanthophylls.
The IUPAC name is 3,3′-dihydroxy-β, β-carotene-4,4′dione, depending on the position of the hydroxy group at the 3 and 3 ′ positions, (3R, 3′R), (3R, 3 ′S) ) (Meso) and (3S, 3 ′S) isomers, and has cis-trans isomers of conjugated double bonds.
In the present invention, any astaxanthin may be used.
Moreover, it can exist as a free type, a monoester type, and a diester type.
Examples of those derived from natural products include microalgae such as green algae Hematococcus, yeasts such as red yeast Phaffia, arthropods such as shrimp, krill, crab and daphnia, molluscs such as squid and octopus Viscera and gonads, various seafood skins, petals of the genus Fuchsia such as Natsuzaki Fukujusou, Paracoccus sp. N81106, Brevundimonas sp. SD212, Erythrobacter sp. Α-proteobacteria such as PC6, Gordonia sp. Gordonia, such as KANMONKAZ-1129, Schizophytrium sp. Examples thereof include those obtained from Labyrinthulas (particularly Yabetaceae) such as KH105 and astaxanthin-producing genetically modified organisms.
Natural extracts and chemically synthesized products are commercially available and are readily available.

In the present invention, the trifatty acid glyceride may be an ester of glycerin and a linear or branched fatty acid having 8 to 22 carbon atoms, and these may be saturated or unsaturated fatty acids.
An ester with a medium chain fatty acid having 8 to 12 carbon atoms is preferred.
Examples of the medium chain fatty acid include glyceryl tricaprylate, glyceryl tri-2-ethylhexanoate, glyceryl tri (capryl / capric acid), glyceryl triundecylate, glyceryl triisopaltiminate, and particularly preferably tri (capryl / Capric acid) glyceryl.

In the external preparation according to the present invention, it is possible to add known components in addition to the above astaxanthin, tocopherol and fatty acid ester with glycerin as long as these blending effects are not impaired.
The form of the external preparation includes, but is not particularly limited to, the form of a skin external preparation for pharmaceuticals and cosmetics. For example, milky lotion, cream, lotion, pack, dispersion liquid, cleaning agent, makeup cosmetics, scalp / hair products. And cosmetics such as ointments, creams, and liquids for external use.
In addition to the above components, components commonly used in skin external preparations such as cosmetics and pharmaceuticals, such as whitening agents, moisturizers, various skin nutritional components, ultraviolet absorbers, antioxidants, oily components, surfactants, thickeners , Alcohols, coloring agents, water, preservatives, fragrances and the like can be appropriately blended as necessary.
More specifically, examples include components described in Japanese Patent Application Laid-Open No. 2003-55188 filed earlier by the present applicant.

In the oral preparation according to the present invention, it should be used as supplements, health foods, health functional foods such as nutritional functional foods and foods for specified health use, special purpose foods, general foods, quasi drugs, and supplements for sports. Since it is easy to decide and easy to determine the amount of intake, supplements, sports supplements, functional health foods, special-purpose foods are preferred, the same form as the above-mentioned pharmaceuticals, tablets, intraoral rapidly disintegrating tablets, capsules, It can be taken in solid dosage forms such as granules, fine granules, and liquid dosage forms such as solutions, drinks, syrups and suspensions.

In the present invention, although the effect of improving the skin barrier function is recognized even when only the above-mentioned external preparation or the internal preparation is used alone, when the external preparation and the internal preparation are used in combination, the skin barrier function is further improved.

In the external preparation and the internal preparation according to the present invention, an excellent improvement effect of the skin barrier function is recognized by blending one or both of tocopherol and the glyceride represented by the following general formula (1) with astaxanthin.

However, R ₁ , R ₂ and R ₃ are each a linear or branched saturated or unsaturated alkyl group having 8 to 22 carbon atoms, which may be the same or different.
Furthermore, when these external preparations and internal preparations are used in combination, a skin barrier function improving effect is further recognized.

8 shows changes in transepidermal water transpiration (TEWL) due to combined use of internal and external preparations for 8 weeks. The change of the stratum corneum cell area (μm ² ) due to the internal and external use is shown for 8 weeks. The grouping in application | coating of an external preparation is shown. In Test Example 2, the change rate of TEWL after 6 weeks due to the use of the external preparation shown in Example 2 (S group) and Comparative example 2 (C group) is shown. In Test Example 2, the change rate of TEWL after 6 weeks due to the use of the internal preparation shown in Example 1 (Group A) and Comparative Example 1 (Group P) is shown. Use in four groups combining Example 1 (Group A) and Comparative Example 1 (Group P) as internal preparations and Example 2 (Group S) and Comparative Example 2 (Group C) as external preparations in Test Example 2 The change rate of TEWL 3 weeks after the start is shown. Use in four groups combining Example 1 (Group A) and Comparative Example 1 (Group P) as internal preparations and Example 2 (Group S) and Comparative Example 2 (Group C) as external preparations in Test Example 2 The change rate of TEWL 6 weeks after the start is shown. In Test Example 2, the change ratio of the stratum corneum cell area after 6 weeks due to the use of the external preparation shown in Example 2 (S group) and Comparative Example 2 (C group) is shown. In Test Example 2, the change rate of the stratum corneum cell area after 6 weeks due to the use of the internal preparation shown in Example 1 (Group A) and Comparative Example 1 (Group P) is shown. Use in four groups combining Example 1 (Group A) and Comparative Example 1 (Group P) as internal preparations and Example 2 (Group S) and Comparative Example 2 (Group C) as external preparations in Test Example 2 The change rate of the stratum corneum cell area 6 weeks after the start is shown.

The combined use effect of the external preparation and the internal preparation according to the present invention was verified in a monitor test as Test Example 1, and further, the effects of the external preparation and internal use according to the present invention were grouped as Test Example 2 and compared with Comparative Examples. Therefore, although it demonstrates concretely, this invention is not limited to this.

<Test Example 1>
For 30 women, 200 mg capsules of the component ratio shown in Example 1 of Table 1 were taken as internal preparations by 1 capsule each morning and evening (2 capsules per day). At that time, it was shown in Example 2 of Table 2 0.5 ml (1 ml per day) of the external preparation at the blending ratio was applied to the face.
The Haematococcus alga extract shown in Table 1 contains 10 to 12% of diester type astaxanthin in terms of free type.
In this example, tri (capryl / capric acid) glyceryl is contained 10 times or more of astaxanthin as an internal preparation.

In Table 2, Biocera G is a product of Dainippon Kasei Co., Ltd. and is a blend of glycerin, sphingomonas extract and tocopherol.
Biocera G contains 0.02% of tocopherol, and in Comparative Example 2, the value is 0.0002%.
The external preparation in this invention exists in the point which mix | blended astaxanthin, tocopherol, and tri (capryl capric acid) glyceryl.
When formulated as an external preparation, the oxidation of astaxanthin may be affected by other additive components, and tocopherol acts as an antioxidant for astaxanthin and is not effective for other external components to be formulated as an external preparation. Also functions as an oxidant.
The amount of tocopherol is required to be at least 0.1 times the amount of astaxanthin (in terms of free form) in the following mass, preferably 0.3 times the amount or more, but depending on other additive components, 1.5 times the amount. In some cases, it may be more than the amount, preferably more than twice, more preferably more than 5 times.
In the external preparation according to the present invention, tri (capryl / capric acid) glyceryl is an oily component and has an action of diluting and stabilizing astaxanthin.
In the formulation of external preparations, this tri (caprylic / capric acid) glyceryl may not be an essential component, but in this example, tri (caprylic / capric acid) glyceryl is contained in an amount of 10.4 times that of astaxanthin. It is.
Moreover, when the compounding quantity of astaxanthin becomes less than 0.0042% of a present Example, it may exceed 10 times amount relatively and may become a 100 times amount level or more.
As evaluation of the skin barrier function, transepidermal water transpiration (TEWL) and stratum corneum cell area (μm ² ) were measured and evaluated.
The measurement methods are shown below.

[Measurement method of transepidermal water transpiration (TEWL)]
<Measurement environment>
Room set to room temperature: 20 ± 2 ° C, humidity: 40 ± 10% <Measurement method>
(1) The subject washed the face after entering the room with the above environment.
(2) After washing the face, it was allowed to acclimate to the measurement environment by waiting for 20 minutes indoors.
(3) After acclimatization for 20 minutes, the amount of transepidermal transpiration at a specified site on the subject's face was measured using a transepidermal water transpiration meter (Cyclone moisture transpiration monitor AS-CT1: manufactured by Asahi Biomed Co., Ltd.). It was measured.

[Measuring method of stratum corneum cell area (μm ² )]
<Measurement environment>
Room set to room temperature: 20 ± 2 ° C, humidity: 40 ± 10% <Measurement method>
(1) The subject washed the face after entering the room with the above environment.
(2) After washing the face, it was kept indoors for 20 minutes and acclimated to the stratum corneum collection environment.
(3) The stratum corneum cells were collected by tape stripping method from a specified site different from the transepidermal water transpiration amount measurement site on the subject's face.
(4) The collected horny layer cells were stained with a hematoxylin / eosin staining method (Mayers Hematoxylin Solution, 1% EosinY Solution: manufactured by Wako Pure Chemical Industries, Ltd.).
(5) Microscopic images of stained horny layer cells were analyzed by image processing software (ImageJ: developed by National Institutes of Health), and the area of horny layer cells was measured. At that time, approximately 30 stratum corneum cells per subject were randomly selected and the area was averaged to obtain the stratum corneum cell area for each subject.

After using the internal preparation of Example 1 (2 capsules / day) and the external preparation of Example 2 (0.5 ml × 2/1 day) at the start of the test (0 week) and 8 weeks (8 weeks) FIG. 1 shows a graph of the TEWL value of).
Moreover, the graph of the value of a stratum corneum cell area is shown in FIG.
In addition, a value shows the average value of 30 women.
The TEWL value greatly decreased. When the difference between the mean values was t-tested, it became highly significant at a risk rate of 1%, and the stratum corneum cell area increased and became significant at a risk rate of 5%.
Thereby, it became clear that a skin barrier function improves by using the internal preparation and external preparation which concern on this invention together.

<Test Example 2>
First, 37 males were divided into 18 Active group (Group A) and 19 Placebo group (P group), and A group was given one capsule (1 mg / day) 2 capsules per day), and 200 mg capsules shown in Comparative Example 1 were similarly taken in the morning and evening (2 capsules per day) in the P group.
As shown in FIG. 3, the topical preparation of Example 2 shown in Table 2 above as the Subject group (S group) was applied to the A group and the P group on the face half as shown in FIG. The external preparation of Comparative Example 2 was applied twice in the morning and evening twice as a Compared group (Group C) to the remaining half of the face.

Since the TEWL value and the stratum corneum cell area value were measured and evaluated in the same manner as in Test Example 1, the results will be described below.
The graph shown in FIG. 4 excludes one of the group C [A / C + P / C (37 persons)] and the group S [A / S + P / S (37 persons)] to investigate the effect of the external preparation. The change ratio (average value) after 6 weeks of use of the TEWL value of N = 36 persons with respect to the start of the test is shown.
The graph shown in FIG. 5 shows N = 36 out of the P group [P / S + P / C (38 persons)] and the A group [A / S + A / C (36 persons)] in order to investigate the influence of the internal medicine. The change ratio (average value) 6 weeks after the start of use of the TEWL value is shown.
As a result, it was determined that the t-test was 1% significant in the internal preparation example 1 according to the present invention and the comparative example 1 which did not contain astaxanthin or the like.
The graph shown in FIG. 6 shows P / C (N = 18), P / S (N = 18), A / C (N = 18), A / S (N = 18) shows the ratio of change in TEWL value after 3 weeks of use relative to the start of each test in the case of four groups, and the graph shown in FIG. 7 shows the change in TEWL value after 6 weeks of use relative to the start of the test. Indicates the ratio.
As a result, the external preparation and the internal use according to the present invention both in the presence / absence of use of the external preparation according to the present invention (comparison between the S group and the C group) and the use or non-use of internal use (comparison between the A group and the P group). Although the TEWL value is decreased by the use of the agent, as shown in FIGS. 6 and 7, the TEWL value of the A / S group in which the external preparation and the internal preparation according to the present invention are used together is the largest decrease.
Therefore, it has been clarified that the external preparation and the internal preparation according to the present invention have a skin barrier function promoting effect even when used alone, and when both are used in combination, there is a greater effect.

Next, the evaluation result of the stratum corneum cell area will be described.
The graph shown in FIG. 8 shows the difference in the external preparation, the sixth week of use relative to the start of the test between group C [A / C + P / C (37 persons)] and group S [A / S + P / S (37 persons)]. The change rate of the stratum corneum cell area is shown, and the graph shown in FIG. 9 shows the difference in the internal use, group P [P / S + P / C (38 persons)] and group A [A / S + A / C (36 persons)]. The change ratio of the stratum corneum cell area after 6 weeks of use relative to the start of the test is shown.
The graph shown in FIG. 10 shows the stratum corneum at the 6th week of use at the start of each of four groups, P / C, P / S, A / C, and A / S, in which external preparations and internal preparations are combined. The cell area change ratio is shown.
As a result, for the stratum corneum cell area, the use effect of the external preparation according to the present invention is greatly expressed as shown in FIG. 8, and the internal preparation and external preparation according to the present invention are used in combination as shown in FIG. The A / S group showed the largest area improvement change.

The present invention is an external preparation or internal preparation effective for recovery and improvement of the skin barrier function.
Examples of the external preparation include skin external preparations for pharmaceuticals and cosmetics, and examples of internal preparations include supplements, health foods, nutritional functional foods, quasi drugs, and general foods. .

Claims

One or both of tocopherol and glycerides represented by the following general formula (1) and astaxanthin are used, and the skin barrier function-promoting external preparation.

(However, R 1 , R 2 , and R 3 are each a linear or branched saturated or unsaturated alkyl group having 8 to 22 carbon atoms, which may be the same or different.)
The external preparation for promoting skin barrier function according to claim 1, wherein the glyceride is an ester with a fatty acid having 8 to 12 carbon atoms.
One or both of tocopherol and the glyceride represented by the following general formula (1) and astaxanthin are contained, and the oral preparation for promoting skin barrier function is characterized.

(However, R 1 , R 2 , and R 3 are each a linear or branched saturated or unsaturated alkyl group having 8 to 22 carbon atoms, which may be the same or different.)
4. The oral preparation for promoting skin barrier function according to claim 3, wherein the glyceride is an ester with a fatty acid having 8 to 12 carbon atoms.
A skin barrier function promoter comprising a combination of the external preparation for promoting skin barrier function according to claim 1 or 2 and an internal preparation for promoting skin barrier function according to claim 3 or 4.