JP3170070B2 - External preparation for skin - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a novel skin external preparation having excellent whitening effect, high stability and high safety.

[0002]

2. Description of the Related Art
Whitening cosmetics are widely used for the purpose of obtaining cosmetic effects such as prevention of skin darkening, spots, freckles, etc. Such whitening external preparations mainly include ascorbic acid, glutathione, colloidal sulfur, etc. as whitening agents. It is blended. However, ascorbic acid is susceptible to oxidation, so that it is difficult to expect a certain effect, and glutathione and colloidal sulfur have disadvantages such as peculiar off-odor and precipitation.

[0003] For this reason, recently, whitening agents have been widely searched for from the natural world, for example, screening of plant extracts has been carried out, and some extracts having the effect have been confirmed.

[0004] However, this extract was not sufficiently satisfactory for practical use, for example, when the extract was formulated in a high concentration in an external preparation in expectation of a higher whitening effect, the stability of the product was lowered. For this reason, there has been a demand for an external preparation for skin which is excellent in whitening effect and high in stability and safety.

[0005]

Under such circumstances, the present inventors have conducted intensive studies and completed the present invention.

That is, the present invention provides the following components (A) and (B): (A) an asparagus extract; (B) (A) N, N'-diacetylcystine dimethyl;
Or (b) a skin external preparation for whitening, characterized by containing one or more plant extracts selected from yoquinin, Ibukitranoo, Clara, hawthorn, hops, wild rose and shirayuri. It is.

[0007] The asparagus extract used in the external preparation for skin of the present invention is asparagus (Asparagus of asparagus).
ficinalis L. ), Obtained by extracting from the stem, rhizome, leaves, flowers, etc., and its preparation method is not particularly limited. For example, the extraction is carried out at room temperature to heating using various appropriate solvents. Examples of the extraction solvent include water; lower monohydric alcohols such as methyl alcohol and ethyl alcohol; liquid polyhydric alcohols such as glycerin, propylene glycol and 1,3-butylene glycol; lower alkyl esters such as ethyl acetate; benzene, hexane and the like. Or one or more of ethers such as diethyl ether. In particular, one or a mixture of two or more of water, ethyl alcohol, glycerin, and 1,3-butylene glycol is preferable. As the extraction conditions, a solvent is used in a volume ratio of 1 to 1000 times, particularly 5 to 100 times the volume ratio of asparagus, and 4 ° C. or more, particularly 15 to 100 times.
It is preferably carried out at a temperature of 30 ° C. for 1 hour or more, particularly 1 to 3 days.

[0008] The extract obtained under the above conditions may be used as it is as an extracted solution, but if necessary, a concentrate, filtration and the like may be used as appropriate.

The amount of asparagus extract in the external preparation for skin of the present invention is 0.0001 in terms of dry solids.
To 10.0% by weight (hereinafter simply referred to as "%"), and particularly preferably 0.01 to 5.0%. If the content is less than 0.0001%, the effect is not sufficiently exhibited, and if it exceeds 10.0%, no further increase in the effect is observed.

In the component (B) of the present invention, the N, N'-
Diacetylcystine dimethyl has the following structural formula

[0011]

Embedded image

It is known that it is easily absorbed by the skin, converted to cystine and cysteine, and has a skin activating effect and a whitening effect (Clinical Dermatology 9 (6) p. 444). ). In the present invention, this N,
N'-Diacetylcystine dimethyl is preferably contained in the entire composition in an amount of 0.0001 to 5%, particularly 0.01 to 3.0%. If it is less than 0.0001%, a sufficient whitening effect cannot be obtained, and if it exceeds 5%, the stability of the product is undesirably reduced.

Among the plant extracts (B) of the component (B) of the present invention, the yokuinin extract is obtained from the cotyledon (Coto
ix lacryma-jobi L. var. ma-
yuen (ROMAM) STAPF), which is obtained by extracting from seeds and the like from which the seed coat has been removed. In addition, the extracts of Ibukitranoo, Clara, Hawthorn, Hops, Noibara, and Shirazuri are not particularly limited in the use parts of the plants, and can be extracted using their respective leaves, branches, stems, flowers, fruits, roots, and the like. Among them, especially preferred are rhizomes for Ibukitranoo, roots for Clara, fruits for hawthorn and wild rose, flowers for hops, and bulbs for lily lily.

The extraction method is not particularly limited. For example, extraction can be performed at room temperature or under heating using various suitable solvents. Examples of the extraction solvent include water; lower monohydric alcohols such as methyl alcohol and ethyl alcohol; liquid polyhydric alcohols such as propylene glycol and 1,3-butylene glycol; lower alkyl esters such as ethyl acetate; and carbonization such as benzene and hexane. Hydrogen; one or more kinds of ethers such as diethyl ether can be used. Among these, water or a water-soluble solvent, particularly one or a mixture of two or more of water, ethyl alcohol, glycerin, and 1,3-butylene glycol are preferable.

The plant extract obtained under the above-mentioned conditions may be used as it is as an extracted solution. However, if necessary, those which have been subjected to treatments such as concentration and filtration may be appropriately used.

These plant extracts of the component (B) can be used alone or in combination of two or more, and the solid content in the total composition is 0.0001 to 10.0%, particularly 0.001 to 10.0%.
It is preferable to mix 5.0%. If it is less than 0.0001%, a sufficient whitening effect cannot be obtained, and if it exceeds 10.0%, the effect does not increase, and depending on the extract, problems such as coloring of the product may occur, which is preferable. Absent.

Further, the external preparation for skin of the present invention may further contain, in addition to the essential components, aqueous components, powders, surfactants, oils and the like used in usual external preparations for skin, as long as the effects of the present invention are not impaired. , Humectants, alcohols, pH adjusters, preservatives,
Dyes, antioxidants, ultraviolet absorbers, thickeners, fragrances, cosmetic ingredients, and the like can be appropriately added as necessary.

The external preparation for skin of the present invention can be produced according to a conventional method by blending the above-mentioned essential components (A) and (B), and can be produced according to a conventional method. It can be applied as a cleansing, pack, cleansing agent, foundation, and other external, pharmaceutical, quasi-pharmaceutical, or cosmetic skin preparations such as dispersions, granules, and ointments.

[0019]

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

Test Example 1 Tyrosinase activity inhibition test: <Sample> Asparagus extract: As a raw material, 23650 g (as a fresh weight) of the raw white asparagus root portion was weighed.
Then, ethanol was added after adjusting the alcohol concentration to 60%. These were pulverized using a food mixer (National MX-M3) to obtain a mixture. Next, the mixture composed of these raw materials and the solvent was placed in a polybucket, and allowed to stand at room temperature for 24 hours to perform extraction. The extract was collected by suction filtration in a suction filtration bottle. To the extraction residue, 25 l of 60% ethanol was again added, and the above operation was repeated. Then, about 66 l of the extract was concentrated by a rotary evaporator, and the solvent was distilled off to obtain 10 parts of a brown concentrated extract.
00 g (dry solid content: 4%) was obtained (first step).

Then, until all the concentrated extracts are dissolved, n
-Add a mixed solvent of butanol and water (1: 1), shake well, and centrifuge at 10,000 rpm for 30 minutes with a centrifuge to extract and separate saponin components and the like into n-butanol layer. (Second step). Next, the n-butanol layer was concentrated by a rotary evaporator and the solvent was distilled off to obtain about 110 g of an extract (third step).

Next, water and benzene were added to the extract in an equivalent amount and suspended to obtain a milky white solution. This solution is centrifuged at 10,000 rpm for 30 minutes using a centrifugal separator, and the separated benzene layer is tilted by a centrifugal tube to discard the upper layer of benzene, or by sucking and removing only the upper layer with a pipette tube. The lipid component in the extract was removed, and the same operation was performed by adding the same amount of fresh benzene to the remaining aqueous layer. In the degreasing step, only benzene alone may be added, but it has been confirmed that efficient degreasing can be performed by using another solvent such as chloroform or ether (fourth step).

Next, water was concentrated from the obtained aqueous layer portion by a rotary evaporator and dried, and then n-
About 1 liter of a mixed solvent of butanol and water (1: 1) was added to dissolve the extract, and the mixture was allowed to stand in a separating funnel for 24 hours to extract the saponin component into the butanol layer. Next, the butanol layer was concentrated and dried by a rotary evaporator to obtain about 18 g of an extract (brown extract) (fifth step).

Next, 300 ml of methanol was added to the brown extract to dissolve it, and 75 ml of the solution was slowly added dropwise to a separately prepared ethyl ether (2 l) using an injection needle to form a white precipitate. After that, most of the ether was removed by the decantation method, and the precipitate was collected by suction filtration. The precipitate was washed several times with fresh ether from above the precipitate to wash away the ether in which the impurities were dissolved. The substantially white precipitate obtained by such an operation was dried in a vacuum desiccator and then pulverized in a mortar to obtain about 11 g of asparagus saponin powder (sixth step).

In this test example, the asparagus extract obtained in the first step was used.

Yokuinin extract: Yokuinin extract (manufactured by Maruzen Pharmaceutical Co., Ltd.) Ibukitranoo extract: Ibukitranoo extract (A.
M. Clara extract: Kujin extract (Maruzen Pharmaceutical) Hawthorn extract: Hawthorn extract (Maruzen Pharmaceutical) Hop extract: Hop extract (Maruzen Pharmaceutical) Neubara extract: Harbex nobara Extract (produced by Koei Kogyo Co., Ltd.) Shiraturi extract: White lily extract GR-327 (produced by Maruzen Pharmaceutical Co., Ltd.)

<Measurement method> An enzyme solution [10 mg of tyrosinase of 28,000 units, manufactured by Sigma Co.,
Dissolved in 20 ml of phosphate buffer (pH 6.8)]
Add 1 ml, and further add 0.1 M phosphate buffer (pH 6.8)
Was added to make 4 ml, which was incubated at 25 ° C. for 10 minutes. To this was added 198.0 mg of a substrate solution [L-DOPA (Tokyo Kasei) 198.0 mg.
Dissolved in 100 ml of 1M phosphate buffer (pH 6.8)], and allowed to react for 10 minutes. Then 4
The absorbance at 75 nm (OD _s ) was measured. Further, the absorbance (OD _HE ) and the absorbance (OD _B ) when no sample was added were measured in the same manner using the enzyme inactivated by heating, and the activity inhibition rate of tyrosinase activity was calculated from the following equation.

[0028]

(Equation 1)

The results are shown in Tables 1 and 2.

[0030]

[Table 1]

[0031]

[Table 2]

As is clear from Tables 1 and 2, when the components (A) and (B) were combined, the tyrosinase activity inhibitory activity was higher than when each was used alone, and a synergistic whitening effect was exhibited. .

Example 1 Emulsion: An emulsion having the composition shown in Table 3 was prepared and evaluated for its whitening effect. Table 4 shows the results.

[0034]

[Table 3]

<Production Method> (6) to (11), (15) and (16) are mixed by heating and maintained at 70 ° C. B. (1) to (5), (12) and (13) are mixed by heating and maintained at 70 ° C. C. B is added to A and mixed, and then (14) is further added, uniformly emulsified, and cooled to 30 ° C. to obtain an emulsion.

<Whitening Effect Test> Female 15 between 23 and 44 years old
Named as a panel, sample 1 twice daily, morning and night, after face washing
A use test was carried out by applying an appropriate amount of the emulsion of each of 6 to 23 to the face of each of the four products for 4 weeks, and evaluated according to the following criteria.

Evaluation criteria: Efficient: Spots and freckles became inconspicuous. Somewhat effective: spots, freckles are less noticeable. Ineffective: No change.

[0038]

[Table 4]

As is clear from Table 4, the emulsion of the present invention (samples 21 to 2) was prepared by combining components (A) and (B).
3) is excellent in the effect of making the spots and freckles inconspicuous not only when compared with Sample 16 which does not contain any of these, but also when compared with Samples 17 to 20 which contain the component (A) or (B) alone. , Showed a pronounced whitening effect.

[0040]

Example 2 Cosmetic: <Formulation> (%) (1) Glycerin 5.0 (2) 1,3-butylene glycol 6.5 (3) Polyoxyethylene sorbitan monolaurate (20E.O.) 1.2) (4) Ethyl alcohol 8.0 (5) Assembly extract (as dry solids) 0.01 (6) Asparagus extract ^{* 1} 2.0 (7) Yoquinin extract ^{* 2} (dry solids) 0.05) (8) Preservative appropriate amount (9) Flavor appropriate amount (10) Purified water balance

<Production Method> A. (3), (4), (8) and (9) are mixed and dissolved. B. (1), (2), (5) to (7) and (10) are mixed and dissolved. C. A and B were mixed and made uniform to obtain a lotion.

[0042]

Table 3 Example 3 Cream: <Formulation> (%) (1) Beeswax 6.0 (2) Cetanol 5.0 (3) Reduced Lanolin 5.0 (4) Squalane 30.0 (5) Glycerin Monostea Rate 4.0 (6) Lipophilic glyceryl monostearate 2.0 (7) Polyoxyethylene sorbitan monolaurate (20EO) 2.0 (8) Asparagus extract ^{* 1} 1.0 (9) Yokuinin extract ^{* 2} (as dry solids) 0.2 (10) Preservative 0.3 (11) Fragrance 0.05 (12) Purified water balance

<Production Method> A. (1) to (7), (10) and (11) are mixed,
Heat and maintain at 70 ° C. B. (8), (9) and (12) are mixed and heated to 7
Keep at 0 ° C. C. B was added to A, mixed, and cooled to obtain a cream.

[0044]

Example 7 Pack: <Formulation> (%) (1) Polyvinyl alcohol 20.0 (2) Ethanol 20.0 (3) Glycerin 5.0 (4) Kaolin 6.0 (5) Asparagus extraction Material ^{* 1} 0.1 (6) Yokuinin extract ^{* 2} 2.0 (7) Preservative 0.3 (8) Fragrance 0.1 (9) Purified water

<Production Method> A. (1), (3) to (6) and (9) are mixed,
Heat to 0 ° C and stir. B. (2), (7) and (8) are mixed. C. B was added to A, mixed, and cooled to obtain a pack.

[0046]

Example 5 Cleaning agent: <Formulation> (%) (1) Stearic acid 10.0 (2) Palmitic acid 8.0 (3) Myristic acid 12.0 (4) Lauric acid 4.0 (5) ) Oleyl alcohol 1.5 (6) Purified lanolin 1.0 (7) Fragrance 0.1 (8) Preservative 0.2 (9) Glycerin 18.0 (10) Potassium hydroxide 6.0 (11) Asparagus Extract ^{* 1} 0.2 (12) Yokuinin extract ^{* 2} (as dry solids) 0.01 (13) Purified water

<Production Method> (9), (10) and (13) are mixed and heated to 70 ° C. B. (1) to (6) and (8) are mixed and heated to 70 ° C. C. B was added to A, and the mixture was kept at 70 ° C. for a while. After the saponification reaction was completed, the mixture was cooled to 50 ° C., and (7), (11) and (12) were added.

Example 6 An emulsion having the composition shown in Table 9 was prepared and evaluated for the whitening effect. The results are shown in Tables 10 and 11.

[0049]

[Table 9]

<Production Method> A. (6) to (9) and (14) are heated and mixed at 70 ° C.
To keep. B. (1) to (5), (10) and (11) are mixed by heating and maintained at 70 ° C. C. B is added to A, mixed, further added (12) and uniformly mixed, and then (13) is added to emulsify uniformly, and cooled to 30 ° C. to obtain an emulsion.

Test Example 2 The back of a colored guinea pig was shaved, and the whitening effect of the test substance was examined by utilizing the fact that ultraviolet irradiation under anesthesia caused pigmentation. UV irradiation is performed by FL2 manufactured by Toshiba Corporation.
Irradiate three 0S • BLB lamps and three FL20S • E30 lamps at the same time, and the amount of ultraviolet rays is 4.8 × 10 ⁶ erg / cm ^2.
And 24 hours before and immediately after UV irradiation and irradiation 2
Four hours later, in four places (2 x 2 cm) on the back of the guinea pig,
Samples 24 to 27 were rubbed well by 0.2 ml. However,
Before irradiation, the application site was thoroughly washed with warm water. Seven days after the irradiation, the degree of pigmentation at each site was observed and judged according to the following criteria. Table 10 shows the results.

<Evaluation Criteria> Pigmentation score: 0: No pigmentation was observed. 1: Very slight pigmentation is observed. 2: Pigmentation was observed, but the boundary with the non-irradiated part was unclear. 3: Pigmentation was observed, and the boundary with the non-irradiated part was clear. Whitening effect; 8 or more of 10 guinea pigs with a pigmentation score of 1 or less: excellent 6 or more: effective 4 or more: slightly effective 3 or less: ineffective

[0053]

[Table 10]

As is clear from Table 10, the emulsion of the present invention (sample 27) containing the components (A) and (B) in combination.
Showed a remarkable pigmentation-preventing effect not only when compared with Sample 24 which did not contain any of these, but also when compared with Samples 25 and 26 each of which alone was blended.

Test Example 3 Use Effect Test Fifteen females aged 23 to 44 were used as panels, and the appropriate amount of each of the emulsions of Samples 24 to 27 was applied to the face for 12 weeks after washing the face twice daily in the morning and evening. A use test was performed according to the following criteria. Evaluation criteria: Effective: Stain and freckles became inconspicuous. Moderately effective: The spots and freckles are less noticeable. Ineffective: No change.

[0056]

[Table 11]

As is clear from Table 11, the emulsion of the present invention (Sample 27) was not only compared with Sample 24 containing no emulsion but also Sample 2 containing each of them alone.
Compared with Nos. 5 and 26, the effect of making spots and freckles less noticeable was excellent, and a remarkable whitening effect was exhibited.

[0058]

Example 7 Lotion: <Formulation> (%) (1) Glycerin 5.0 (2) 1,3-butylene glycol 6.5 (3) Polyoxyethylene sorbitan monolaurate (20E.O.) 1.2) (4) Ethyl alcohol 8.0 (5) Assembly extract (as dry solids) 0.01 (6) Asparagus extract ^{* 1} 2.0 (7) N, N'-diacetylcystine dimethyl 0.2 (8) Preservative appropriate amount (9) Flavor appropriate amount (10) Purified water

<Production Method> A. (3), (4), (8) and (9) are mixed and dissolved. B. (1), (2), (5) to (7) and (10) are mixed and dissolved. C. A and B were mixed and made uniform to obtain a lotion.

[0060]

Example 8 Cream: <Formulation> (%) (1) Beeswax 6.0 (2) Cetanol 5.0 (3) Reduced Lanolin 5.0 (4) Squalane 30.0 (5) Glycerin Monostea Rate 4.0 (6) Lipophilic glyceryl monostearate 2.0 (7) Polyoxyethylene sorbitan monolaurate (20EO) 2.0 (8) Asparagus extract ^{* 1} 1.0 (9 ) N, N'-diacetylcystine dimethyl 1.0 (10) inositol 0.1 (11) preservative 0.3 (12) fragrance 0.05 (13) purified water

<Production Method> A. (1) to (7), (11) and (12) are mixed,
Heat and maintain at 70 ° C. B. (8)-(10) and (13) are mixed and heated to 70 ° C. C. B was added to A, mixed, and cooled to obtain a cream.

[0062]

Example 9 Pack: <Formulation> (%) (1) Polyvinyl alcohol 20.0 (2) Ethanol 20.0 (3) Glycerin 5.0 (4) Kaolin 6.0 (5) Rosemary extraction Liquid (manufactured by Maruzen Pharmaceutical Co., Ltd.) (as dry solid content) 0.02 (6) Asparagus extract ^{* 1} 0.1 (7) N, N'-diacetylcystine dimethyl 0.2 (8) Preservative 0.3 (9) Fragrance 0.1 (10) Remaining amount of purified water

<Production Method> (1), (3) to (7) and (10) are mixed,
Heat to 0 ° C. and stir. B. (2), (8) and (9) are mixed. C. B was added to A, mixed, and cooled to obtain a pack.

[0064]

Example 10 Cleaning agent: <Formulation> (%) (1) Stearic acid 10.0 (2) Palmitic acid 8.0 (3) Myristic acid 12.0 (4) Lauric acid 4.0 (5) ) Oleyl alcohol 1.5 (6) Purified lanolin 1.0 (7) Fragrance 0.1 (8) Preservative 0.2 (9) Glycerin 18.0 (10) Potassium hydroxide 6.0 (11) Asparagus Extract ^{* 1} 0.2 (12) N, N'-diacetylcystine dimethyl 0.1 (13) Purified water

<Production Method> (9) to (10) and (13) are mixed and heated to 70 ° C. B. (1) to (6) and (8) are mixed and heated to 70 ° C. C. B was added to A, and the mixture was kept at 70 ° C. for a while. After the saponification reaction was completed, the mixture was cooled to 50 ° C., and (7), (11) and (12) were added.

[0066]

As described in detail above, the external preparation for skin of the present invention has an excellent whitening effect, and is effective for blackening the skin due to sunburn, preventing and improving spots and freckles, and the like. Furthermore, since the skin external preparation of the present invention is stable and safe, it can be used with confidence.

────────────────────────────────────────────────── ─── Continued on the front page (51) Int.Cl. ⁷ identification code FI A61K 35/78 A61K 35/78 C (58) Field surveyed (Int.Cl. ⁷ , DB name) A61K 7/00-7 / 50 A61K 35/78

Claims (1)

(57) [Claims] 1. The following components (A) and (B): (A) an asparagus extract; (B) (A) N, N'-diacetylcystine dimethyl;
Or (b) one or more extracts of a plant selected from yoquinin, Ibukitranoo, Clara, hawthorn, hops, wild rose, and white lily.