JPH10279468A - Skin preparation for external use - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a skin preparation for external use having excellent preventing effects on skin aging, reducing effects on skin roughening and humectant effects by including a lignan glycoside and an antiinflammatory agent. SOLUTION: This preparation for external use is obtained by including a lignan glycoside represented by the formula [R is a glycosyl; (n) is 0 or 1] and an antiinflammatory agent such as glycyrrhizic acid, indomethacin, allantoin, guaiazulene, derivatives thereof and salts thereof, zinc oxide, an extract from aloe, an extract from Lithospermi Radix, an extract from Matricaria chachamomille L., an extract from Hypericium erectum Thunb. or an extract from Spindus mukurossi Gaertn. as active indredients. The lignan glycoside is a hydrous lower alcohol extract from a sesame seed, a humidified substance thereof, a germinated substance thereof, a pulverized substance or a defatted substance thereof. Since efficacies essentially possessed by the pharmacodynamically effective ingredient can sufficiently be manifested, the preparation is effective in preventing the occurrence of a burning sensation due to sunburn, erythema due to irradiation of ultraviolet rays, preventing the occurrence or reducing pigmentation, etc., and is useful for the beauty culture and medicine.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to an external preparation for skin containing a lignan glycoside and a specific medicinal ingredient, and more particularly, to an external preparation for skin having excellent skin aging prevention, skin roughness improvement and moisturizing effects. Agent.

[0002]

2. Description of the Related Art Conventionally, cosmetics such as milky lotions, creams, lotions, packs, dispersions, and detergents, and dermatological external preparations such as ointments, creams, and liquids for external use have been used for these purposes. A medicinal component is added for the purpose of imparting a predetermined medicinal effect to the drug. For example, for the purpose of calming inflammation such as hot skin and erythema of the skin after sunburn and suppressing pigmentation, medicinal ingredients such as glycyrrhizic acid, indomethacin, zinc oxide, aloe extract and chamomile extract are added. I have.

[0003]

However, an external preparation for skin containing these medicinal components does not have sufficient effect of the medicinal components, or lacks stability when used in an amount sufficient to obtain the medicinal effects. There has been a demand for an improvement, for example, in that the use feeling is impaired.

[0004]

Means for Solving the Problems The present inventors have conducted intensive studies to improve the effect of a medicinal component, and as a result, when a lignan glycoside is combined with a specific medicinal component, the original medicinal component has the medicinal component. The present inventors have found that the action is sufficiently exerted and completed the present invention.

That is, the present invention relates to the following components (A) and (B): (A) a lignan glycoside represented by the structural formula (I);

Embedded image The present invention provides an external preparation for skin containing the following lignan glycosides represented by the following structural formulas (II-a) and (II-
Preferably, one or more of the lignan glycosides represented by b) or (II-c) is contained as a main component, and in a preferred embodiment, the lignan glycoside is sesame seed or a humidified product thereof. Alternatively, it is a hydrated lower alcohol extract of a germinated body.

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[0006]

BEST MODE FOR CARRYING OUT THE INVENTION The lignan glycoside, which is the component (A) of the present invention, is represented by the above general formula (I). That is, the lignan glycoside according to the present invention comprises 2
The aglycone portion has a methylenedioxyphenyl group and a sugar portion in which one to four sugar residues of glucose, galactose or fructose are bonded to the hydroxyl group.

[0007] The lignan glycoside is preferably glucoside lignan in which the sugar residue in the structural formula (I) is a diglucoside residue and / or a triglucoside residue, and still more preferably the structural formula (II) −
One, two or more of the compounds represented by a), (II-b) or (II-c), or those containing these as main components. Further, the method for preparing the same is not particularly limited.
No. 228793).

The amount of the lignan glycoside in the external preparation for skin of the present invention cannot be uniformly defined by the difference in the content of each component of the lignan glycoside.
In the case of a water-containing lower alcohol extract prepared by the method disclosed in Japanese Patent No. 8793, it is 0.05 to 20% by weight (hereinafter simply referred to as "%"), preferably 0.1 to 10%. 0.01-10 when glycosides are blended
%, Preferably 0.05 to 5%, and a highly purified product (the above-mentioned structural formulas (I), (II-a) and (II-b)
Or, at least about one or more of the lignan glycosides represented by (II-c) are contained in a total amount of about 60% or more. )
0.001 to 5%, preferably 0.01%
~ 1%.

On the other hand, examples of the anti-inflammatory agent as the component (B) of the present invention include the following.

That is, glycyrrhizic acid, glycyrrhetinic acid, mefenamic acid, phenylbutazone, indomethacin, ibuprofen, ketoprofen, allantoin,
Guaiazulene, D-panthenol and their derivatives and their salts, ε-aminocaproic acid, zinc oxide,
Diclofenac sodium, aloe extract, sicon extract, salvia extract, soybean extract, perilla extract,
Scallop extract, Dutch mustard extract, cattail extract, sambucus elder extract, filet extract, arnica extract, oak extract, chamomile extract, birch extract, hypericum extract, eucalyptus extract, sapling extract, etc. And one or two of them
More than one kind may be appropriately selected.

Among these anti-inflammatory agents, particularly preferred are glycyrrhizinic acid, indomethacin, allantoin, guaiazulene and derivatives thereof, salts thereof, zinc oxide, aloe extract, sicon extract, chamomile extract and hypericum extract. Products and sapling extract. The origin of each of these components is not particularly limited, and may be any of animal origin, microorganism origin, and synthetic products. Further, there is no particular limitation on the production method such as the extraction method and the purification treatment method.

In the external preparation for skin of the present invention, the component (B) may be appropriately selected from one or more of them, and the amount thereof is not particularly limited. 0.0001 to 10%, more preferably 0.01 to 5%. Within this range, the lignan glycoside is more stable over time than when used alone, and exhibits a sufficiently high drug effect.

The external preparation for skin of the present invention is prepared by blending the essential components (A) and (B) with various types of bases known as normal external preparations for skin in accordance with a conventional method. Can be.

The form of the external preparation for skin is not particularly limited, and examples thereof include skin care cosmetics such as milky lotions, creams, lotions, packs, and cleansers, makeup cosmetics such as lipsticks and foundations, cosmetics for the scalp, and the like. Ointments, dispersions,
Pharmaceutical products such as creams and liquids for external use can be prepared.

The external preparation for skin of the present invention includes, in addition to the above-mentioned essential components, components to be added to ordinary external preparation for skin, for example,
Oils, powders, surfactants, purified water, lower alcohols, high molecular compounds, gelling agents, ultraviolet absorbers, ultraviolet scattering agents,
Antioxidants, dyes, preservatives, fragrances, cosmetic ingredients, and the like can be appropriately selected and used within a range that does not impair the effects of the present invention.

[0016]

EXAMPLES Next, the present invention will be described in more detail with reference to Reference Examples, Test Examples and Examples, but the present invention is not limited thereto.

Reference Example 1 Production of aqueous methanol extract Pre-sterilized quartz sand was spread on a stainless steel vat of 300 cm ² , and 10 g of Chinese sesame seeds were sprinkled thereon. And germinated for 2 days in a constant temperature bath. The germination rate was 89% or more. A certain amount of germinated material having a similar germination state was ground with a blender together with 100 ml of hydrated methanol (80% (v / v)). The residue was filtered, and the filtrate was concentrated to dryness to obtain a methanol extract. Then, the extract was washed by extraction with n-hexane to remove fat-soluble substances, thereby obtaining a water-containing methanol extract. The aqueous methanol extract was redissolved in 100 ml of aqueous methanol (80% (v / v)) and subjected to high performance liquid chromatography (HPLC) to analyze the composition.

The HPLC conditions were as follows: a pump (CCPM, manufactured by Tosoh Corporation) was used and a column (Soken Pak ODS-W5) was used.
μ, 10 mmΦ × 250 mm), UV absorption detector (U
V-8000, manufactured by Tosoh Corporation), elution was performed using a linear gradient of water: methanol starting at 90:10 (v: v) and 60:60 minutes later at 10:90 (v: v). The flow rate was 1 ml / min, and the detection wavelength was 280 nm.

As a result of HPLC analysis, the composition and content of the lignan glycoside in the aqueous methanol extract were determined using sesamin as an external standard.
a)), SG-3 (Structural Formula (II-b)) and SG-5
(Structural formula (II-c)) are the main components, and 115 mg of these are present in the aqueous methanol extract. The composition is 30% for SG-1, 40% for SG-3, and SG-5. Was 30%.

The chemical structure of each lignan glycoside component was confirmed by the following method using each purified product purified to a single component by preparative HPLC under the same conditions as described above. That is, 1N hydrochloric acid was added to each purified product, hydrolyzed at 100 ° C. for 30 minutes, extracted with ethyl acetate, and separated into an ethyl acetate layer and an aqueous layer. The ethyl acetate layer was concentrated to dryness at 40 ° C. or lower, subjected to trimethylsilylation treatment with TMS-PZ (manufactured by Tokyo Chemical Industry Co., Ltd.), and subjected to gas chromatography (GLC) to quantitatively analyze lignan (external standard: sesamin).

The GLC conditions are as follows. GLC apparatus: Hewlett-Packard 5890, column: D
B-17HT (15mx0.319mm, film t
kickness: 0.15 μm, J & W SCIEN
TIFIC), injection method: split method (split ratio 1/10), column temperature: 270 ° C., carrier gas:
helium.

The aqueous layer was subjected to a pretreatment filter for HPLC (pore size: 0.2 μm, Meishoridisk W-13).
2, Tosoh Corporation), add 5 ml of acetone to the filtrate, concentrate under reduced pressure to dryness, and then TMS-PZ (same as above)
And subjected to GLC for quantitative analysis of sugars (external standard: glucose, galactose,
Fructose).

The GLC conditions are as follows: Column: DB-170
1 (15m x 0.25mm, film thickne
ss: 1.0 μm, manufactured by J & W SCIENTIFIC) Injection method: split method (split ratio 1/5)
0), except that the column temperature was set to 180 ° C.

Reference Example 2 Production of Crude Lignan Glycoside A hydrous methanol extract obtained in the same manner as in Reference Example 1
Dispersed in 100 ml of 0 mM acetate buffer (pH 5.0), 200 mg of β-glucosidase (Funakoshi),
1 g of cellulase (manufactured by Boehringer Mannheim) and 1 g of amylase (manufactured by Wako Pure Chemical Industries) were added, and the mixture was shaken at 50 ° C. for 15 hours. The same volume of n-hexane was added to the reaction solution and vigorously shaken. This extraction operation was repeated three times to remove fat-soluble substances. To the residual solution from which the n-hexane layer was completely removed, the same volume of n-butanol which had been saturated with water in advance was added, and the mixture was vigorously shaken. This extraction operation was repeated twice to remove water-soluble substances. After washing the n-butanol layer twice with the same volume of water,
It was concentrated to dryness under reduced pressure to obtain a crude lignan glycoside.

HPLC analysis by the method described in Reference Example 1 revealed that the lignan glycoside in the crude lignan glycoside was SG-
1, SG-3 and SG-5 are the main components, and these are present in the crude lignan glycoside in an amount of 150 mg.
-1 was 24%, SG-3 was 43%, and SG-5 was 33%.

Reference Example 3 Production of Highly Purified Lignan Glycoside The crude lignan glycoside obtained by the method described in Reference Example 2 was
The product was subjected to partition chromatography using octadecyl silica (ODS) as a carrier. YMC-GEL ODS-A
(Manufactured by Yamamura Chemical Co., Ltd.) 60 g with a diameter of 3 cm and a length of 50 c
m glass column and equilibrated by flowing water.
To this, 1 g of the crude lignan glycoside was loaded on the top of the column. The fraction components were eluted by a step elution method in which the methanol concentration was sequentially increased from water. 30-60% (v
/ V) The fractions eluted with methanol were collected and concentrated under reduced pressure to obtain about 100 mg of a column fraction.

This was repeatedly subjected to preparative HPLC, and purification was performed until each lignan glycoside component became single.
As a result, 5 to 10 mg of each of the purified lignan glycosides of SG-1, SG-3 and SG-5 was obtained. The content of these total lignan glycoside components was 2.
5% (wt / wt), 5 per hydrated methanol extract.
It was 0% (wt / wt).

Reference Example 4 Production of chamomile extract 20 g of dried chamomile flowers were finely chopped, 100 ml of 1,3-butylene glycol was added, the mixture was extracted for 5 days at room temperature with occasional stirring, and filtered to remove the chamomile extract. Obtained.

Test Example 1 Erythema Inhibition Test The back of a colored guinea pig (15 animals in each group) was shaved and irradiated with ultraviolet light under anesthesia. UV irradiation is performed by FL2 manufactured by Toshiba Corporation.
Irradiate three lamps of 0S · BLB and three lamps of FL20S · E30 at the same time.
cm ² . Twenty-four hours before, immediately after, and 12 hours after and 24 hours after the ultraviolet irradiation, 0.2 ml of each sample having the composition shown in Table 1 was applied to four places on the back of the guinea pig. However, before irradiation, the application site was thoroughly washed with warm water. Irradiation 2
The degree of erythema was observed 4 hours later, and the degree of pigmentation was observed 7 days later, and evaluated according to the following criteria. The results are also shown in Table 1.

[0030]

[Table 1] * 1: Manufactured in Reference Example 3 * 2: Manufactured by Sigma * 3: Manufactured in Reference Example 4

(Evaluation Criteria for Erythema Inhibition Effect) <Evaluation> <Contents> Excellent Erythema is not observed at all. Effective Very little erythema is observed. Slightly effective Erythema is observed, but the boundary with the non-irradiated part is unclear. Ineffective Erythema was observed, and the boundary with the non-irradiated part was clear.

(Evaluation Criteria for Pigmentation Inhibition Effect) <Evaluation> <Contents> Excellent No pigmentation was observed at all. Effective Very slight pigmentation is observed. Slightly effective pigmentation is observed, but the boundary with the non-irradiated part is unclear. Ineffective Pigmentation was observed, and the boundary with the non-irradiated part was clear.

As shown in the results of Table 1, the composition of the present invention in which purified lignan glycoside represented by the product 1 of the present invention is combined with glycyrrhizic acid and high purity represented by the product 2 of the present invention It was found that the light composition of the present invention, in which a purified lignan glycoside and a chamomile extract were combined, effectively suppressed erythema and pigmentation caused by ultraviolet rays when applied to the skin.

Example 1: Cream (Component) (%) (1) Polyoxyethylene monostearate (40EO) 2.0 (2) Glyceryl monostearate 5.0 (3) Stearic acid 5.0 ( 4) Behenyl alcohol 0.5 (5) Squalane 15.0 (6) Cetyl isooctanoate 5.0 (7) Preservative appropriate amount (8) 1,3-butylene glycol 5.0 (9) Hydrous methanol extract * 1 10 0.0 (10) Dipotassium glycyrrhizinate * 2 1.0 (11) Remaining amount of purified water (12) Appropriate amount of perfume * 1 Produced in Reference Example 1 * 2 Wako Pure Chemical Industries, Ltd.

(Production method) Mix components (1)-(7), heat to 70 ° C. and stir. B. Mix components (8)-(11) and heat to 70 ° C.
Stir. C. After B was added to A and mixed, the mixture was cooled and (12) was added to obtain a cream.

The cream of Example 1 was applied to the skin to suppress erythema due to ultraviolet irradiation and effectively prevent pigmentation due to inflammation.

Example 2: Emulsion (Component) (%) (1) Polyoxyethylene sorbitan monostearate (10 EO) 1.0 (2) Polyoxyethylene sorbite tetraoleate (60 EO) 0 5.5 (3) Glyceryl monostearate 1.0 (4) Stearic acid 0.5 (5) Behenyl alcohol 0.5 (6) Purified avocado oil 4.0 (7) Glyceryl tri-2-ethylhexanoate 4.0 ( 8) Preservative appropriate amount (9) Crude lignan glycoside * 1 0.01 (10) Guaiazulene * 2 0.2 (11) Carboxyvinyl polymer 0.07 (12) 1,3-butylene glycol 5.0 (13) ) Sodium hydroxide 0.025 (14) Remaining amount of purified water (15) Appropriate amount of fragrance * 1 Produced in Reference Example 2 * 2 Sigma

(Production method) Components (1) to (10) are heated and dissolved at 70 ° C. B. The components (11) and (12) are heated and dissolved at 70 ° C. C. A is added to B, mixed uniformly, and cooled.
3) to (15) were added and uniformly mixed to obtain an emulsion.

The emulsion of Example 2 was applied to the skin to calm down hot flashes due to sunburn and to effectively suppress pigmentation.

Example 3: Lotion (Ingredient) (%) (1) Polyoxyethylene hydrogenated castor oil (60EO) 1.0 (2) Suitable amount of fragrance (3) Ethanol 10.0 (4) Preservative (5) ε-aminocaproic acid * 1 0.3 (6) citric acid 0.1 (7) sodium citrate 0.3 (8) 1,3-butylene glycol 5.0 (9) high-purity lignan glycoside Purified body * 2 0.01 (10) Remaining purified water * 1 Sigma * 2 Manufactured in Reference Example 3

(Production method) Heat and dissolve components (1) to (5) at 70 ° C. B. B. Dissolve components (6) to (10) by heating at 70 ° C. B was added to A and mixed evenly to obtain a lotion

The lotion of Example 3 was applied to the skin to soothe hot flashes due to sunburn and to suppress the formation of erythema.
It effectively prevented pigmentation.

[0043]

EFFECT OF THE INVENTION The skin external preparation of the present invention can sufficiently exhibit the inherent effects of the active ingredient by blending the lignan glycoside with the anti-inflammatory agent. That is, since it has a stable and excellent anti-inflammatory action, it is effective for preventing and improving the occurrence of hot flashes due to sunburn and erythema due to ultraviolet irradiation, or the occurrence of pigmentation and the like, and is extremely useful in beauty and medicine. Things.

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[Procedure amendment]

[Submission date] February 6, 1998

[Procedure amendment 1]

[Document name to be amended] Statement

[Correction target item name] 0029

[Correction method] Change

[Correction contents]

Test Example 1 Erythema Inhibition Test The back of a colored guinea pig (15 animals in each group) was shaved and irradiated with ultraviolet light under anesthesia. UV irradiation is performed by FL2 manufactured by Toshiba Corporation.
Irradiate three lamps simultaneously with the OSS / BLB lamp and FL20S / E30 lamp, and the amount of ultraviolet rays is 4.8 × 10 ⁶ erg /
cm ² . Twenty-four hours before, immediately after, and 12 hours after and 24 hours after the ultraviolet irradiation, 0.2 ml of each sample having the composition shown in Table 1 was applied to four places on the back of the guinea pig. However, before irradiation, the application site was thoroughly washed with warm water. Irradiation 2
The degree of erythema was observed 4 hours later, and the degree of pigmentation was observed 7 days later, and evaluated according to the following criteria. The results are also shown in Table 1.

[Procedure amendment 2]

[Document name to be amended] Statement

[Correction target item name] 0033

[Correction method] Change

[Correction contents]

As shown in the results of Table 1, the composition of the present invention in which purified lignan glycoside represented by the product 1 of the present invention is combined with glycyrrhizic acid and high purity represented by the product 2 of the present invention It was found that the composition of the present invention in which the purified lignan glycoside and the chamomile extract were combined effectively suppressed erythema and pigmentation due to ultraviolet rays by applying them to the skin.

Continued on the front page (51) Int.Cl. ⁶ Identification code FI A61K 7/40 ADA A61K 7/40 ADA (72) Inventor Kumi Kameyama 4-11-9-512 Kamiikebukuro, Toshima-ku, Tokyo

Claims (5)

[Claims] 1. An external preparation for skin, comprising one or more of the following components (A) and (B): (A) a lignan glycoside (B) an anti-inflammatory agent. 2. A lignan glycoside having the following structural formula (I):
The external preparation for skin according to claim 1, which is a lignan glycoside represented by the formula: Embedded image 3. A lignan glycoside having the following structural formula (II)
The external preparation for skin according to claim 1 or 2, which is a lignan glycoside comprising one or more of the lignan glycosides represented by -a), (II-b) or (II-c). . Embedded image Embedded image Embedded image 4. The lignan glycoside is a hydrated lower alcohol extract of sesame seeds, humidified or germinated bodies thereof, crushed products thereof, or defatted products thereof.
4. The external preparation for skin according to 2 or 3. 5. An anti-inflammatory agent comprising glycyrrhizic acid, glycyrrhetinic acid, mefenamic acid, phenylbutazone, indomethacin, ibuprofen, ketoprofen, allantoin, guaiazulene, D-panthenol and derivatives thereof and salts thereof, ε-aminocaproic acid , Zinc oxide, diclofenac sodium, aloe extract, siconium extract, salvia extract, soybean extract, perilla extract, sagebrush extract, Dutch mustard extract, cattail extract, western elderberry extract, filet extract, arnica The external use for skin according to claim 1, 2, 3 or 4, wherein the extract is one or two or more kinds selected from an extract, oak extract, chamomile extract, birch extract, hypericum extract, eucalyptus extract and sapling extract. Agent.