JP3072584B2 - Skin stratum corneum water content increasing agent - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an agent for increasing the water content of the stratum corneum of the skin and a composition containing the same, and more particularly, to a water content of the skin stratum corneum containing gingerol and ginger contained in a ginger extract as active ingredients. The present invention relates to an amount increasing agent and a composition containing the same.

[0002]

2. Description of the Related Art Normal skin stratum corneum usually contains 10 to 30%.
Moisture, and the elasticity and flexibility are maintained, but when this becomes 10% or less due to changes in environmental conditions such as age, wind, humidity, etc., it becomes a so-called dry skin It is known that skin loses elasticity and causes various troubles.

[0003] In order to prevent this dry skin, attempts have conventionally been made to replenish moisture to the stratum corneum of the skin using cosmetics and the like containing various components to regulate the physiological action of the skin.

[0004] These substances acting from the outside of the skin are required to have not only an excellent moisturizing effect, but also a refreshing feeling of use, a beautiful transparent appearance, and no load on the skin. However, none of these characteristics are sufficiently satisfied.

[0005] In recent years, the usefulness of so-called functional foods has been pointed out, but there is no known food having an effect of increasing the water content of the stratum corneum of the skin. The condition of the stratum corneum of the skin is closely related to the state of health, and human health largely depends on eating habits. Therefore, it is considered desirable to enhance the moisturizing mechanism of the skin from the inside with food and to guide it to a healthy stratum corneum. Therefore, a functional food having an effect of increasing the water content of the stratum corneum of the skin and a substance increasing the water content of the skin stratum corneum which realizes this are desired.

On the other hand, it has been known that ginger has an effect of improving blood circulation, prompting sweating, suppressing vomiting, and increasing appetite. In addition, ginger essential oil is known to promote peripheral blood circulation, warm the whole body after taking it, cause sweating, increase gastric juice secretion, enhance gastrointestinal peristalsis, and excrete gas, etc. ing. Furthermore, the platelet aggregation inhibitory action (Japanese Unexamined Patent Publication No.
No. 72625), an anti-inflammatory effect (JP-A-61-2639)
No. 09), a whitening effect (JP-A-61-50909), a cardiotonic effect (JP-A-57-59809), an analgesic effect (JP-B-59-1684) and the like are also known. In addition, 6-gingerolol, a component contained in ginger, is used.
l) and 6-shogaol have an analgesic effect (JP-B-59-1684) and a cardiotonic effect (JP-B 64-92).
No. 1), platelet aggregation inhibitory action (Japanese Patent Application Laid-Open No. 62-28392)
No. 2) and an antiparasitic effect (Japanese Patent Application Laid-Open No. 2-4711).

[0007] However, it is not known that the above compounds have an effect of increasing the water content of the stratum corneum of the skin. Utilizing these compounds, the water content of the stratum corneum of the skin is increased, the rough skin due to drying is prevented, and the skin is moistened fresh. No attempt has been made to make the skin softer.

[0008]

DISCLOSURE OF THE INVENTION The present invention has been made in view of the above, and has a sufficient effect of increasing the water content of the stratum corneum of the skin, and is a highly safe skin stratum corneum water content increasing agent. It is an object to provide a composition containing the same.

[0009]

Means for Solving the Problems The present inventors have conducted intensive studies in order to solve the above problems, and as a result, gingerol or gingerol contained in the ginger extract has an effect of increasing the water content of the stratum corneum of the skin. Heading that
The present invention has been reached.

[0010] That is, the present invention is a skin stratum corneum water content increasing agent containing a compound represented by the structural formula as an active ingredient, and a composition containing the same.

[0011]

Embedded image

However, in Chemical Formula 4, R represents a group represented by Chemical Formula 5 or Chemical Formula 6 (n represents 4, 6, or 8 in both formulas).

[0013]

Embedded image

[0014]

Embedded image

Hereinafter, the present invention will be described in detail. The skin horny layer water content increasing agent of the present invention contains one or more compounds represented by the above formula (4) as active ingredients. Incidentally, in Chemical Formula 4,
Those in which R is represented by Chemical Formula 5 are called gingerols, and those in which R is represented by Chemical Formula 6 are called shogaols. Among these, 6-shogaol wherein n is 4 in Chemical Formula 5, and 6-gingerol wherein n is 4 in Chemical Formula 6 are particularly preferred in the present invention.

The above compound can be obtained, for example, from ginger (ginger) which is a plant of the ginger family as follows. The extract obtained by extracting the dried ginger rhizome with ether is concentrated and subjected to, for example, column chromatography using silica gel and eluted with a concentration gradient of hexane and ether.
Ginger mainly in the fraction eluted at 3: 1
Gingerol is mainly obtained in the fraction eluted with ether. These can be further purified by preparative thin-layer chromatography or the like.

In addition to the above method, isolation and purification can be performed by high performance liquid chromatography or the like. In the present invention, besides the above-mentioned purified compound, a ginger extract and those at each production stage can be used as well. The ginger extract is commercially available as ginger extract, and may be used as it is or after purification.

The skin stratum corneum water content increasing agent of the present invention can be obtained by mixing the above compound or ginger extract with a base. The base is preferably an oral base such as a tablet, capsule or drink.

The dosage of the skin stratum corneum water content increasing agent of the present invention is not particularly limited, but it is usually 0.1 mg or more, preferably 1 to 1 mg per day for an adult.
0 mg. By using in this range, expected effects can be expected.

Further, the composition of the present invention is obtained by blending the above-mentioned water content increasing agent for the stratum corneum of the skin with various compositions, for example, foods and drinks, pharmaceuticals, quasi-drugs and the like. The amount of the skin stratum corneum water content increasing agent in these compositions is usually
The amount of the compound is 0.1 mg or more, preferably 1 to 10 mg per adult per day. In particular, ginger has been used for food and medicine for a long time, and long-term continuous use is possible.

[0021]

Embodiments of the present invention will be described below. First, production examples of the compound used in the present invention will be described.

[0022]

[Preparation Example 1] 1 kg of "Kyokyo" from the Japanese Pharmacopoeia was reflux-extracted with 10 l of hot water for 3 hours, the extract was filtered, and the filtrate was freeze-dried to obtain 114 g of a hot water extract. This hot water extract was combined with 1 L of a large network-structured synthetic adsorbent XAD-2.
After passing through a column filled with (manufactured by Organo Co., Ltd.), the non-adsorbed fraction was thoroughly washed with water, and the adsorbed fraction was washed with 2 liters of 99.5.
Elution was performed with vol% ethanol. The solvent was distilled off from the column adsorption fraction under reduced pressure to obtain 7.3 g of a solid.

The solid was separated from a preparative reverse phase column (μBONDASPHERE 5 μC18-100 angstrom 19 mm × 1 mm, manufactured by Millipore).
5 cm) and fractionated by high performance liquid chromatography using water: acetonitrile in a mixing ratio of 3: 2 as a solvent,
The fraction containing 6-gingerol was collected and the solvent was distilled off under reduced pressure to obtain 330 mg of 6-gingerol.

The detection of 6-gingerol is performed by thin-layer chromatography using n-hexane: ethyl acetate = 2: 1 as a developing solvent, or high performance liquid chromatography (column: Millipore Co., Ltd., μBONDASPHERE 5 μC18-100 Å, 3.9 mm × 15 cm, elution solvent: water: acetonitrile with a mixing ratio of 3: 2, flow rate: 1 ml / min, detection wavelength: 210 n
m). Under these conditions, Rf is eluted at around Rf = 0.6 in thin layer chromatography and around Rt = 11.1 minutes in high performance liquid chromatography.

[0025]

[Preparation Example 2] 1 kg of "Shokyo" of the Japanese Pharmacopoeia was refluxed and extracted with 10 l of ethanol for 3 hours, the extract was filtered, and the filtrate was concentrated under reduced pressure to obtain 41 g of an ethanol extract. This ethanol extract was suspended in 1 liter of ethyl acetate, and 1 liter of water was added for liquid-liquid extraction. The ethyl acetate layer was separated, and the solvent was distilled off under reduced pressure to obtain 33.6 g of a solid. .

This solid was fractionated by high performance liquid chromatography in the same manner as in Production Example 1, a fraction containing 6-gingerol was collected, and the solvent was distilled off under reduced pressure to obtain 2.2.
g of 6-gingerol were obtained.

The fact that the sample obtained in Preparation Examples 1 and 2 is 6-gingerol is compared with a commercially available sample by nuclear magnetic resonance (NMR) spectroscopy, high performance liquid chromatography and thin layer chromatography. Was performed. Below is the proton NMR of the sample (in γ-acetone-d ₆ )
The spectrum of is shown.

[0028] 0.88 [3H, triplet, J = 6 _{Hz, - (CH 2) 4 -C} H 3] 1.34 ( center) [8H, multiplet, -CH (OH) -
_{(C H 2) 4 -CH 3} ] 2.50 [2H, doublet, J = 7 Hz, -C0-C H ₂ -CH
(OH) -] 2.77 [4H , _{singlet, Ar-C H 2 -C H} 2 -] 3.81 [3H, _{singlet, -OC H 3 -] 4.00 [} 1H, multiplet, -C H (OH)-] 6.62-6.82 [3H, multiplet, 3x aromatic H]

The acute toxicity to male mice was 100 mg / kg or more by oral administration. It is also known that 6-shogaol has extremely low acute toxicity (Japanese Patent Publication No. 59-1684, etc.).

[0030]

Example 1 15 mg of 6-gingerol was dissolved in 50 ml of a 1% aqueous solution of sodium carboxymethylcellulose (cmc-Na) to prepare a skin horny layer water content increasing agent.

Next, the effects of the skin stratum corneum water content increasing agent will be described. 19 male hairless mice (weight about 35 g,
(25 weeks old) was left for 1 hour in a room adjusted to 23.0 ± 1.0 ° C. and 50 ± 5% humidity to adjust to this environment, and then the water content of the horny layer of the thoracic skin was measured. Thereafter, 10 mice were orally administered with 0.5 ml of the above-mentioned skin stratum corneum water content increasing agent, and the remaining 9 animals were orally administered with 0.5 ml of a 1% aqueous solution of sodium carboxymethylcellulose as a comparative example. The water content of the stratum corneum of the thoracic skin at 7 hours after the administration was measured over time (15
Minutes, 30 minutes, 45 minutes, 1 hour, 1.5 hours, 3 hours, 5
Time, 7 hours).

The amount of water in the stratum corneum of the thoracic skin was measured by holding the mouse in a supine position and applying a low-frequency type stratum corneum moisture meter (Courage + Khazaka electronic Co. Corneometer C) to the skin of the sternum body.
M820PC). Further, in order to eliminate individual differences, the percentage (%) of the au value after the sample administration with respect to the au value was determined based on the arbitrary units (au) value before the sample administration, and data processing was performed using the percentage. In addition, the significant difference test was performed by the Student's t test.

FIG. 1 shows the average value of the percentage (%) of the au value after the sample administration to the au value before the sample administration for each group (administration group and control group) together with the standard deviation. In the figure, * indicates that the risk rate is less than 5%, and ** indicates that the risk rate is less than 1%, each of which has a significant difference.

From these results, it can be seen that the hairless mice to which the agent of the present invention was administered had a significantly higher skin horny layer water content for about 45 minutes to about 1 hour after administration than the hairless mice to which only the aqueous solution of sodium carboxymethylcellulose was administered. It is clear that has increased. Since the hairless mouse has no sweat glands, the amount of water detected in the above test is not due to sweating, but is considered to be due to an increase in water in the stratum corneum of the skin.

[0035]

EFFECTS OF THE INVENTION The agent for increasing the water content of the stratum corneum of the present invention and the composition containing the same are excellent in the action of increasing the water content of the stratum corneum of the skin and have high safety.

[Brief description of the drawings]

BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is a graph showing the change over time in the mean value and the standard deviation of the percentage (%) of hairless mouse horny skin stratum corneum after administration compared to before administration.

[Explanation of symbols]

In the figure, the symbol * indicates that the risk factor is less than 5%, and the symbol ** indicates that the risk factor is less than 1%, each of which has a significant difference.

──────────────────────────────────────────────────続 き Continuation of front page (56) References JP-A-6-239758 (JP, A) JP-A-6-239736 (JP, A) JP-A-6-183959 (JP, A) 207256 (JP, A) JP-A-1-96121 (JP, A) JP-A-59-106277 (JP, A) (58) Fields investigated (Int. Cl. ⁷ , DB name) A61K 31/12-31 / 125 A61K 7/00-7/48 A61K 35/78 CA (STN) CAOLD (STN)

Claims (2)

(57) [Claims] 1. An agent for increasing the water content of the stratum corneum of the skin, comprising a compound represented by the structural formula 1 as an active ingredient. Embedded image Here, in Chemical formula 1, R represents a group represented by Chemical formula 2 or Chemical formula 3 (n represents 4, 6, or 8 in both formulas). Embedded image Embedded image 2. A composition comprising the skin stratum corneum water content increasing agent according to claim 1.