JP2003335668A - Oral agent for beautiful skin - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To obtain an oral agent for beautiful skin, and a food containing the oral agent for the beautiful skin. <P>SOLUTION: The oral agent for the beautiful skin has a formulation comprising 1-5 pts.wt. astaxanthin and 10-100 pts.wt. tocotrienol. The food contains the oral agent for the beautiful skin. A state of the skin is kept good, for example, a water content of the skin (at a corner of the eye), a liver spot, a freckle, a pimple, a boil, a shadow, smoothness, moist feeling and tenseness are introduced to a good state and kept at the state, by ingesting the formulation. The food is useful as a health assistant food having skin care activities. <P>COPYRIGHT: (C)2004,JPO

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to an oral skin beautifying agent containing an astaxanthin-tocotrienol blend and a food containing the skin beautifying agent.

[0002]

BACKGROUND OF THE INVENTION Astaxanthin is a carotenoid that is the same as β-carotene, and it is used for crustaceans such as shrimp and crab, salmon,
It is a red pigment that is widely distributed in nature, especially in the ocean, such as fish from Thailand, and has a good food experience. Recently, astaxanthin is 100 to 1,000 times as much as vitamin E (α-tocopherol), β
-Astaxanthin has now been expected as a large health food material from the industry since the time when it was found to have a powerful antioxidant activity about 40 times that of carotenes and it was conventionally treated as a simple pigment. Other functional properties of astaxanthin include anti-inflammatory action, anti-arterial action action, action against diabetes, retinal protection action against light damage, diurnal rhythm control action, immunostimulatory action, anti-stress action, muscle endurance improving action, sperm Many reports have been made on the quality-improving effect of bladder cancer and suppression of bladder cancer induction. Further, as effects on the skin, effects of suppressing pigmentation, suppressing melanin production and suppressing photoaging are reported.
The present inventors have applied for a patent for the effect of removing wrinkles on the outer corners of the eyes.

Examples of cosmetics using astaxanthin include (1) a component for absorbing visible light in a sunscreen cosmetic (JP-A-63-83017), (2)
A cosmetic or pharmaceutical composition in which a peroxidase capable of reducing organic peroxide and an antioxidant capable of neutralizing singlet oxygen (astaxanthin is an example of an antioxidant capable of neutralizing singlet oxygen) are combined (special feature: (Kaihei 6-227961), (3) Concentrated phaffia dye oil (the main component of the dye is astaxanthin) -containing cosmetics (JP-A-7-101827).
Gazette), (4) stable cosmetics that can be stored for a long period of time,
A highly unsaturated fatty acid that is easily oxidized and unstable can be stably incorporated in a cosmetic composition, and the effect of the highly unsaturated fatty acid can be expected to the maximum (Japanese Patent Laid-Open No. 8-245335), (5) 100 parts by weight of phospholipid, Carotenoid pigment 0.01-0.
1 part by weight, tocopherol 0.1 to 1.0 part by weight. Useful as an antioxidant composition for use in cosmetics (JP-A-9-1
10888), (6) (A) lipoic acid, and (B) carotenoid-containing external preparations improve active oxygen species scavenging action, rough skin caused by oxidative stress, and wrinkles and spots (skin aging). , An external preparation for skin excellent in prevention and whitening action, stability, and safety (JP-A-10-007541),
(7) Carotenoid-colorant containing an aggregate. Colorants for food products, cosmetics and pharmaceutical compositions / stable to light and oxygen (JP-A-11-285359),
(8) A skin external preparation. (A) Metal chelating agent, (B) UV protection agent, (C) Active oxygen scavenger (astaxanthin), antioxidant. Fully exhibiting the effect of each medicinal agent / prevents skin disorders such as skin roughness, wrinkles, sagging, and yellowing of skin due to chronic UV exposure, and has an effect of preventing photoaging (Japanese Patent Laid-Open No. 2000-136123). )
And so on.

Tocotrienol is a compound related to vitamin E contained in wheat, rice bran, palm oil and the like, and has a structure having three double bonds in the side chain of tocopherol. This is also a natural product with abundant food experience similar to the above-mentioned astaxanthin. As for the physiological activity of tocotrienol, it has the same antioxidant effect as astaxanthin. Its action is said to be 40 to 60 times that of tocopherol. Tocotrienol has been reported to have other effects such as blood pressure lowering action, cholesterol lowering action, arterial effect improving action, breast cancer cell growth inhibiting action, etc., and most recently, angiogenesis inhibiting action,
New functionalities not found in tocopherol such as whole blood flow improving action have been discovered. In Europe and the United States, it is widely used as a next-generation vitamin E for external use such as cosmetics. This tocotrienol can be obtained by a method such as pressing a natural product, extracting from a natural product, or synthesizing. Generally, it is extracted from the peel and / or seed of a palm plant. Tocotrienols obtained from natural product extracts are a mixture of multiple tocotrienol isomers. These have been applied to food additives, cosmetics, etc. by utilizing their antioxidant effect.

Regarding the use of tocotrienols in cosmetics, for example, vitamin E (including α, β, γ, δ-tocotrienol) is widely used as an antioxidant in the fields of medicine, food and cosmetics. In addition, it is added to foods to enhance the nutrition of the foods (Japanese Patent Laid-Open No. 58-9602).
No. 1), a hair nourishing agent, a hair nourishing agent, a skin cream, a hair cream containing tocotrienol as an active ingredient,
Hair tonic, whole body lotion, hair lotion, jell, shampoo, conditioner, sculptonic, skull lotion, hair liquid, face lotion, body lotion, lotion (JP-A-8-12532), tocotrienol esters (C7-25) Cosmetics containing a fatty acid ester group as a cell activating agent (hair nourishing agent, skin cream, hair cream, hair tonic, hair lotion, shampoo, rinse, oral hygiene product, nutritional drink, food, powder, tablet, capsule (JP-A-61-183206), an external preparation for skin containing tocotrienols as an active ingredient.The whitening effect and the content in cosmetics are 0.01 to 1 based on the total weight of the composition.
0% by weight, preferably 0.05 to 1%
No. 92062), a bio-aging agent comprising a root extract of Choleus forskolin and tocotrienol (JP-A-8-176005), a skin external preparation composition (vitamin E is contained as one component of the composition) ) Tocotrienol can also be used (JP-A-10-7541), and a skin external preparation comprising creatinine and / or creatine and a medicinal substance and / or a physiologically active substance (antioxidant, containing tocotrienol) (JP-A 2000-2478).
No. 66) has been reported. However, all of the conventional agents are external preparations, and astaxanthin-
There is no report on an oral skin beautifying agent containing a tocotrienol compound as an active ingredient.

[0006]

SUMMARY OF THE INVENTION It is an object of the present invention to provide an oral skin beautifying agent containing an astaxanthin-tocotrienol blend and a food containing the skin beautifying agent.

[0007]

Means for Solving the Invention The present inventors have found that astaxanthin and tocotrienol, which have excellent antioxidative action, have different antioxidative actions, specifically, astaxanthin has singlet oxygen scavenging and lipid peroxides. Focusing on the suppression, tocotrienol shows an antioxidant effect by capturing lipid peroxyl radicals,
Even if the astaxanthin-tocotrienol composition is taken orally, the results have been earnestly studied in view of synergistically showing a beautiful skin effect on the skin, and as a result, an excellent skin-beautifying effect is obtained when the astaxanthin and tocotrienol composition is orally taken. Found to show. The present invention has been completed based on such findings. That is, the present invention provides (1) an oral skin beautifying agent containing an astaxanthin-tocotrienol blend as an active ingredient, and (2) a blend containing 1 to 1 of astaxanthin.
It is a food containing the oral skin beautifying agent according to the above (1) consisting of 5 parts by weight and 10 to 100 parts by weight of tocotrienol, and (3) the oral beautifying agent containing the astaxanthin-tocotrienol blend as an active ingredient.

[0008]

BEST MODE FOR CARRYING OUT THE INVENTION An oral skin beautifying agent comprising the astaxanthin-tocotrienol blend of the present invention will be specifically described below.

The astaxanthin used in the skin-care agent of the present invention can be obtained by extraction from plants, yeasts of the genus Phaffia, algae, bacteria, crustaceans or by chemical synthesis according to known methods. Among them, the method for obtaining astaxanthin from the green alga Hematococcus is in a very advantageous position as a method for supplying naturally-occurring astaxanthin, because a method for culturing a large amount and stable of hematococcus containing astaxanthin at a high concentration was developed. . As a culture method for obtaining a high astaxanthin content of Haematococcus green algae, for example, culture is carried out using a culture medium having a closed dome-shaped, conical or cylindrical culture device and a gas discharge device movable within the device. A method is disclosed (International Publication No. WO9
9/50384).

Astaxanthin can be extracted from this Haematococcus alga by a known method. Since Haematococcus is covered with a flexible and sticky cell wall, the cell wall of algae is destroyed before extraction. As a method of destroying the cell wall, a method of destroying the cell wall of the alga body enzymatically, chemically or physically is known.

It is known that tocotrienols can be obtained by a method such as squeezing, extracting or synthesizing natural products such as plants. Generally the peels of palms and /
Or extracted from seeds. For example, in the case of producing palm palm, water is added to the extract to separate it, and the oil layer is separated and purified by column chromatography, and if necessary, tocotrienols containing no tocopherols or containing traces of tocopherols. Can be prepared. Tocotrienols contained in extracts from this natural product are usually
It contains one or more of α-tocotrienol, β-tocotrienol, γ-tocotrienol and δ-tocotrienol. These tocotrienols have D-, L-, and DL-type isomers, but any of them can be used in the present invention. The ratio and content of each tocotrienol isomer can be determined according to a conventional method, for example,
It can be measured by liquid chromatography (HPLC) or the like.

When the tocotrienol is one or a mixture of two or more selected from α-tocotrienol, β-tocotrienol, γ-tocotrienol and δ-tocotrienol, other components such as water and palm oil are optional. It may be included in a ratio. For example,
The composition ratio of α-, β-, γ-, and δ-tocotrienol in tocotrienol is α-tocotrienol 18.
9%, γ-tocotrienol 22.6%, δ-tocotrienol 1.2%, α-tocopherol 0.0%, other 45.3% (mainly water or palm oil) and the like can be mentioned. .

The tocotrienol extracted and concentrated by the above-mentioned method is further subjected to column chromatography, if necessary, to obtain α-tocotrienol, β-tocotrienol,
Each component of γ-tocotrienol and δ-tocotrienol can be isolated and purified.

Each isomer of tocotrienol is commercially available as α-tocotrienol, β-tocotrienol, γ-tocotrienol, δ-tocotrienol.

The tocotrienol may be in the form of an ester with a known saturated or unsaturated fatty acid capable of releasing tocotrienol in vivo.

The astaxanthin-tocotrienol composition of the present invention can be manufactured by the following method.

The content of astaxanthin used in the preparation of the astaxanthin-tocotrienol blend is astaxanthin monoester or diester contained in the raw materials.
Astaxanthins such as a free form (astaxanthin) can be obtained by quantifying according to a conventional method, for example, by HPLC or the like, and then converting to a free form. Similarly, the tocotrienol content in the formulation can be determined by converting the tocotrienols contained in the raw material into the free form (tocotrienol) after quantifying the tocotrienols contained in the raw materials according to a conventional method, for example, by HPLC. By the above-mentioned operation, a mixture containing astaxanthin and tocotrienol in an arbitrary ratio can be prepared.

The amount of astaxanthin blended in the above-mentioned astaxanthin-tocotrienol blend is about 0.5 to 10 mg, preferably 1 mg to 5 per day for an adult.
mg, and the amount of tocotrienol is 5 mg to 200
mg, preferably 10 mg to 100 mg, more preferably 20 mg to 80 mg.

The method for confirming the skin beautifying effect of the astaxanthin-tocotrienol blend of the present invention and the results thereof are shown below.

Effect of Long-term Ingestion of Astaxanthin-Tocotrienol Blend (4 Weeks) Preparation Method of Astaxanthin-Tocotrienol Blend Soft capsules were prepared according to a conventional method by the method of Reference Example 1 below.

1-1. Preparation of Samples (Compounds) Production Example 1 Hematococcus alga extract containing 5% soft capsule astaxanthin [trade name Astaryl Oil 50F, Fuji Chemical Industry Co., Ltd.]
Manufactured] and a palm oil extract containing 37.5% tocotrienol (trade name: Tocomin 50%, manufactured by Carotech),
Soft capsules having the following composition containing 2 mg of astaxanthin and 45 mg of tocotrienol per capsule were prepared.

Samples for administration to control groups (placebo)
As the soft capsules of Production Example 1 above, rapeseed oil was used instead of astaxanthin and tocotrienol to produce soft capsules of only rapeseed oil having the following composition.

[0023]

EXAMPLES The present invention will be described more concretely in the following examples. In the following examples, astaxanthin 2 of Production Example 1
Astaxanthin-tocotrienol combination drug containing mg + 45 mg of tocotrienol was administered as an adult / day / tablet. Sample (placebo) as a control for comparison
Was administered.

1-2. Test Subject A test was conducted on 16 healthy women (M1 to M16) with dry skin who agreed to participate in the present study, around 40 years old. Considering all attributes such as age, physique, skin quality, and physical constitution, and after the skin measurement in advance, the test group and the placebo group were divided into two groups (8 persons each) so that both groups would be uniform. The attributes of the subjects are shown in Tables 1 and 2. The test groups in Table 1 include M1, M4, M5, M7, M10, M11, M1.
3, M16, and in the placebo group of Table 2, M2, M3,
M6, M8, M9, M12, M14, M15 belong.

[0025]

[Table 1]

[0026]

[Table 2]

1-3. Test period and test method From January 15, 2002, the test group was ingested with one tablet of the astaxanthin-tocotrienol composition every evening in the evening.
The control group received the sample (placebo). The test period is 4 weeks. The measurement of each test item was performed three times at the start, two weeks later, and four weeks later. All tests were carried out using the double blind method.

1-4. Measurement conditions 1 after washing the face in an environmental test room adjusted to 20 ° C and 65% humidity
The measurement was performed after resting for 5 minutes in a sitting position.

1-5. Measurement item

1-5-1. Questionnaire collection Skin condition and skin diary were conducted by a questionnaire of Fuji TV Product Research Laboratory model described later.

1-5-2. Visual inspection and palpation by a beauty specialist It was conducted with the Fuji Television Products Research Laboratory model described later.

1-5-3. Moisture content Electric conductivity type SKICON-200 (manufactured by IBS) was used to measure the right corner of the eye and the cheek.

1-5-4. Measurement of the amount of sebum The left forehead and the cheeks were measured using a transmitted light ratio type sebometer.

1-5-5. Skin enlargement photography Photographed with Medical Nikkor (manufactured by Nikon Corporation).

2. Result 2-1. The amount of change in skin condition by self-assessment after 2 weeks and 4 weeks after the start of self-reported skin condition is shown in FIGS. 1 and 2.

With respect to the average value of 8 persons, the test group showed a good tendency in all evaluation items after 2 weeks and after 4 weeks. A statistically significant difference was observed between "spots and freckles" after 2 weeks and "acne / fukimono" after 4 weeks.

2-2. 3 and 4 show the amount of change in skin condition due to visual inspection / palpation after two weeks and four weeks after the start of visual inspection / palpation by a beauty expert.

Among the average values of 8 persons, the items in which the test group tended to have a better tendency were, after 2 weeks, visual inspection "bear (significantly different)", "oiliness", "forehead / eyebrow". No wrinkles, sagging under the eyes, palpation "smoothness (with significant difference)", "moisturizing", "goodness of elasticity". Four weeks later, a physical examination "Kuma", "Absurdness", "Glossy", "Acne / bukimonomono", "Texture",
The results were “slack under the eyes”, “slack in the mouth”, palpation “smoothness (with significant difference)”, “moistness (with significant difference)”, “wellness (with significant difference)”.

2-3. Changes in water content after 2 weeks and 4 weeks based on the start of water content are shown in FIGS. 5 and 6. The water content in the outer corners of the eyes was significantly higher than that at the start of the test group after 4 weeks (p <0.05)
Was rising to. A slightly good moisturizing effect was also observed on the cheeks, although it was not significant. On the other hand, the placebo group is
It was not significant in the cheeks, but it tended to decrease gradually. Regarding the amount of change after 4 weeks, a significant difference (p <0.05) was observed between the test group and the placebo group.

2-4. Changes in the amount of sebum after 2 weeks and 4 weeks based on the start of the amount of sebum are shown in FIGS. 7 and 8. No change in the forehead or cheek was observed in the test group. On the other hand, it decreased in the placebo group. Considering from the time of conducting the test, it can be said that the skin condition tends to be better in the test group.

2-5. Skin surface observation Example of improvement in wrinkle condition (M4 and M11)
Enlarged photographs of the above are shown in FIGS. 9 and 10. Overall, the test group tended to have better skin condition.

The effects of astaxanthin and tocotrienol, which have strong antioxidant effects, on the skin by internal use were evaluated by a clinical test using a double blind system. As a result, it was significant in skin water content (extremity of eyes), subject's self-skin diagnosis (for spots, freckles, acne and wipes), and visual inspection and palpation by beauty specialists (bear, smoothness, moistness, goodness of elasticity). Improvement was noted. All of these items are important items showing the skin condition. Moreover, it should be taken into account that the test period was in a bad environment for the skin.

From the above, it was confirmed that the combined administration of astaxanthin and tocotrienol had an excellent skin-beautifying effect.

In this study, the skin beautifying effect of astaxanthin and tocotrienol was confirmed. However, considering the already reported beauty effects of astaxanthin when used externally, further skin beautifying effect is obtained by internal and external use. Can be expected.

The composition of the present invention has an excellent skin beautifying effect and is therefore useful as a dietary supplement. The mixed food can be used in various forms, for example, can be produced by uniformly mixing with a carrier generally used in the food field. In particular,
Can be manufactured using sugars such as sucrose, sorbitol and fructose, glycols such as polyethylene glycol and propylene glycol, oils such as sesame oil, rapeseed oil, olive oil and soybean oil, and flavors such as strawberry flavor and peppermint. . In the form of powders, pills, capsules, tablets, excipients such as lactose, glucose, sucrose, and mannitol, disintegrants such as starch and sodium alginate, lubricants such as magnesium stearate and talc, polyvinyl alcohol. , Hydroxypropyl cellulose, a binder such as gelatin, a surfactant such as a fatty acid ester, and a plasticizer such as glycerin. Tablets and capsules are preferred as they are easier to ingest.

Production Examples of Compounds Production Examples 2 to 6 In the same manner as in the preparation method of Production Example 1 above, asturyl oil 50F and tocomin 50% were blended as shown in the following table to prepare 220 mg of rapeseed oil. After that, soft capsules composed of gelatin and glycerin were prepared.

[0047]

[Table 3]

Astaryl oil 50F and Tocomin 50
The composition of% is shown below. Astaryl oil 50F Astaxanthin (free conversion) 5% Vegetable oil and fat 95% Tocomin 50% Tocotrienol 37.5% Tocopherol 12.5% Palm-derived oil and fat 50%

Production Example 7 A tablet having the following composition is prepared by a conventional method. Astaxanthin (converted to free form) 2mg Tocotrienol (converted into free form) 20 mg Lactose 60mg Potato starch 40mg Polyvinyl alcohol 2 mg Magnesium stearate 1 mg

[0050]

Industrial Applicability According to the present invention, it is possible to provide an oral skin beautifying agent containing an astaxanthin-tocotrienol blend and a food containing the skin beautifying agent.
The astaxanthin-tocotrienol composition of the present invention, when ingested, leads to good condition of skin moisture content (eye corners), spots / freckles, acne / blister, bear, smoothness, moistness, and elasticity. The skin condition can be maintained in good condition such as being maintained. Therefore, it is useful as a health supplement having a skin beautifying effect. Despite the skin measurement in a long-term monitor test, and as in this time, we divided into two groups (test group and placebo group) with the same actual age and skin age, and even though the measurement was done with strict double blind, The fact that a statistically significant difference was revealed in many items showing the skin condition could confirm that the skin beautifying effect of the test product intake was confirmed. Items that were significantly different this time were skin water content (outside the eyes), self-diagnosis on the monitor (for spots, freckles, acne and wipes), and visual inspection and palpation by a beauty specialist (bear, smoothness, moistness). However, all of these items are important items that indicate the skin condition. In particular, the fact that the amount of change in water content before and after the test and the results of visual inspection and palpation were confirmed confirmed that the test product, astaxanthin-tocotrienol, had an excellent skin-beautifying effect. In addition, the concept of "cosmetics for drinks" like inner cosmetics is drawing attention in the field of health foods. The present inventors have already been able to confirm that astaxanthin and tocotrienol, which are effective for external use, show a skin-beautifying effect on the skin when used internally and in combination.

[Brief description of drawings]

FIG. 1 shows changes in skin condition by self-report after 2 weeks, based on the start time. The item names in the figure are, from the left end of the figure, moisturized, smooth, oily, smoothness, gloss, acne and wipes, dull skin, spots / freckles, redness, forehead and brows. Wrinkles, fine wrinkles around the corners of the eyes, sagging under the eyes, sagging around the mouth, glue, makeup sticky and comprehensive evaluation are shown.

[FIG. 2] FIG. 2 shows changes in skin condition by self-report after 4 weeks from the start. Item names in the figure are the same as those in FIG.

[Fig. 3] Fig. 3 shows the results of visual inspection and palpation by a beauty expert two weeks after the start.
The item names in the figure are, in order from the left edge of the figure, the skin color for inspection, the stain,
Freckles, dull skin, dark circles, oily, lustrous, acne / blank, redness, wrinkles on the outer corners of the eyes, wrinkles on the forehead / brow, texture, sagging under the eyes, slackness on the palate, palpability, moistness Shows dryness, firmness and firmness.

FIG. 4 shows the results of visual inspection and palpation by a beauty expert after 4 weeks from the start.
Item names in the figure are the same as those in FIG.

FIG. 5 shows changes in the amount of water in the outer corners of the eyes. The water content in the outer corner of the eye was significantly increased in the test group after 4 weeks. The vertical axis in the figure indicates the amount of change (μS).

FIG. 6 shows changes in water content in the cheeks. The amount of water on the cheek was not significant, but a slightly good moisturizing effect was observed. The vertical axis in the figure indicates the amount of change (μS).

FIG. 7 shows changes in the amount of sebum on the forehead. The forehead increased for the test group, although there was no significant difference.
On the other hand, it decreased in the placebo group. The vertical axis in the figure represents the amount of change (sebum level).

FIG. 8 shows changes in the amount of sebum on the cheeks. The vertical axis in the figure represents the amount of change (sebum level).

FIG. 9 is an enlarged photograph of the outer corner of the eye of a subject (M4). Improvement of wrinkles is recognized.

FIG. 10 is an enlarged photograph of the outer corner of the eye of a subject (M11). Improvement of wrinkles is recognized.

Front page continuation (51) Int.Cl. ⁷ Identification code FI theme code (reference) A61K 7/48 A61K 7/48 31/122 31/122 A61P 17/16 A61P 17/16 F term (reference) 4B018 MD48 MD74 ME14 4C083 AA112 AA122 AC122 AC422 AC491 AC492 AD661 AD662 CC01 CC50 DD14 EE12 4C086 AA01 AA02 BA09 MA02 MA04 MA37 MA52 NA14 ZA89 4C206 AA01 AA02 CB25 MA02 MA04 MA57 MA72 ZA89

Claims (3)

[Claims] 1. An oral skin beautifying agent comprising an astaxanthin-tocotrienol blend as an active ingredient. 2. The oral skin beautifying agent according to claim 1, wherein the composition comprises 1 to 5 parts by weight of astaxanthin and 10 to 100 parts by weight of tocotrienol. 3. A food containing an oral skin beautifying agent containing an astaxanthin-tocotrienol blend as an active ingredient.