JP3480954B2 - 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 external preparation for skin which is excellent in whitening effect and has high stability and safety.

[0002]

2. Description of the Related Art Conventionally, the problems to be solved by the invention
Whitening external preparations are widely used for the purpose of obtaining beauty effects such as preventing skin darkening, spots, freckles, etc.As such whitening external preparations, ascorbic acid, glutathione, colloidal sulfur, etc. are mainly used as whitening agents. It is compounded. However, since ascorbic acid is susceptible to oxidation, it is difficult to expect a certain effect to be exhibited, and glutathione and colloidal sulfur have a drawback that they have a peculiar offensive odor and precipitation.

Therefore, recently, whitening agents have been widely searched from the natural world, for example, screening of plant extracts, and some extracts having the effect have been confirmed.

However, this extract was not sufficiently satisfactory for actual use, since the stability of the product was lowered when it was blended in a high concentration in an external preparation in the expectation of a higher whitening effect. Therefore, there has been a demand for an external preparation for the skin which has excellent whitening effect, stability and safety.

[0005]

Under the circumstances, the present inventor has completed the present invention as a result of earnest research.

[0006] That is, the present invention provides (A ₁ ) squid extract, and (B ₁ ) (i) N, N'-diacetylcystine dimethyl or (b) yokuinin, ibukitoranoo, clara, hawthorn, hops, Neubara and One or two or more kinds of plant extracts selected from white lily; and a whitening skin external preparation characterized by containing: (A ₂ ) one or two kinds of plant extracts selected from mocca and iclinin. And (B ₂ ) one or two or more kinds of plant extracts selected from Yokuinin, Ibukitoranoo, Clara, Hawthorn, Hops, Neubara and Shirayuri, or a whitening skin external preparation. It is provided.

The method for preparing the extract of squid, mocca and iclinin (hereinafter sometimes referred to as Rosaceae plant extract) of the component (A) of the present invention is not particularly limited, but various suitable solvents are used, for example. It is extracted at room temperature to under heating. Examples of the extraction solvent include water; methyl alcohol,
Lower monohydric alcohols such as ethyl alcohol; Liquid polyhydric alcohols such as glycerin, propylene glycol, 1,3-butylene glycol; Lower alkyl esters such as ethyl acetate; Hydrocarbons such as benzene and hexane; Ethers such as diethyl ether 1 type or 2 types or more of these can be used. Particularly, water, ethyl alcohol, glycerin, and a mixed solvent of one or more kinds of 1,3-butylene glycol are 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 of the crude drug, and a temperature of 4 ° C. or higher, particularly 15 to 30 ° C., for 1 hour or longer, particularly for 1 to 3 days. It is preferable to carry out.

The Rosaceae plant extract obtained under the above conditions may be used as it is, but may be subjected to treatment such as concentration and filtration if necessary. These may be used alone or in combination of two or more.

The content of the component (A) is preferably 0.0001 to 10% by weight (hereinafter referred to simply as "%") in terms of dry solid content, and particularly preferably 0.01 to 5%. 0.
If it is less than 0001%, a sufficient effect cannot be obtained, and if it exceeds 10%, the stability over time of the product often decreases, which is not preferable.

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

[0011]

[Chemical 1]

It is known that it is easily absorbed by the skin, converted into cystine and cysteine, and exhibits a skin activating action and a whitening action (Clinical Dermatology 9 (6) p. 444). ). In the present invention, this N,
N'-diacetylcystine dimethyl is preferably contained in the total 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 decreases, which is not preferable.

Among the plant extracts of (B), which is the component (B), Yokuinin extract is a coix (Coix) of the Poaceae family.
lacryma-jobi L. var. ma-yu
en (ROMAN) STAPF) obtained by extracting from seeds and the like excluding the seed coat. Further, the extract of Ibukitoranoo, Clara, hawthorn, hops, Neubara, white lily, the use part of the plant is not particularly limited, and these leaves, branches, stems, flowers, fruits, roots and the like can be extracted. However, among others, rhizomes for Ibukitoranoo, roots for Clara, hawthorn, fruits of hawthorn, fruits for hops, flowers for white lily, and bulbs for white lily are preferable.

The extraction method is not particularly limited, but it can be extracted, for example, 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; carbonization such as benzene and hexane. Hydrogen; one or more ethers such as diethyl ether may be used. Among these, water or a water-soluble solvent, particularly water, ethyl alcohol, glycerin, 1,3-butylene glycol, or a mixed solvent of two or more thereof is preferable.

The plant extract obtained under the above-mentioned conditions may be used as it is as an extracted solution, but if necessary, it may be subjected to treatment such as concentration and filtration, and may be appropriately used.

These plant extracts of the component (B) can be used alone or in combination of two or more kinds, and 0.0001 to 10.0%, particularly 0.001 as solid content in the whole composition.
It is preferable to mix it up to 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. Absent.

Further, the external preparation for skin of the present invention contains, in addition to the above-mentioned essential components, an aqueous component, a powder, a surfactant, which is used in ordinary external preparations for skin, as long as the effects of the present invention are not impaired.
Oil agents, moisturizers, alcohols, pH adjusters, preservatives, pigments, 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 by a conventional method by blending the above components, and can be used as a milky lotion, cream, lotion, beauty essence, cleansing, pack, cleansing agent,
It can be applied as a skin external preparation such as foundation or the like, or other dispersed, granular, ointment, or the like for medicines, quasi-drugs, or cosmetics.

[0019]

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

Test Example 1 Tyrosinase activity inhibition test: <Sample> Mica squid extract: Heat-extracted with 30 V / V% ethyl alcohol, filtered, concentrated under reduced pressure, and allowed to stand in a cool place for aging. About 3% dry solids. Mocca extract: Extracted under reflux with 50 V / V% ethyl alcohol, filtered, concentrated under reduced pressure, and left in a cool place. About 2% dry solids. Iclinin extract: 50V / V% ethyl alcohol was added, and the mixture was extracted at room temperature for 3 days with occasional shaking, and then filtered,
Concentrated under reduced pressure. About 6% dry solids. Yokuinin extract: Yokuinin extract (manufactured by Maruzen Pharmaceutical Co., Ltd.) Ibuquitranoo extract: Ibukitranoo extract (A.
M. Company I) Clara extract: Kujin extract (Maruzen Pharmaceutical Co., Ltd.) Hawthorn extract: Hawthorn extract (Maruzen Pharmaceutical Co., Ltd.) Hop extract: Hop extract (Maruzen Pharmaceutical Co., Ltd.) Neubara extract: Harbex Novara Extract (Koei Kogyo Co., Ltd.) Shirayuri extract: Shirayuri extract GR-327 (Maruzen Pharmaceutical Co., Ltd.)

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

[0022]

[Equation 1]

The results are shown in Tables 1 to 4.

[0024]

[Table 1]

[0025]

[Table 2]

[0026]

[Table 3]

[0027]

[Table 4]

As is clear from Tables 1 to 4, when the components (A) and (B) were combined, the tyrosinase activity inhibitory action was higher than when they were used alone, and a synergistic whitening effect was exhibited. .

Example 1 Emulsion: An emulsion having the composition shown in Table 5 was prepared and evaluated for its whitening effect. The results are shown in Table 6.

[0030]

[Table 5]

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

<Whitening effect test> Females aged 23 to 44 15
Name the panel, and sample 3 after washing the face twice daily in the morning and at night
The use test was conducted by applying an appropriate amount of each of the 0 to 37 emulsions of 4 products to the face for 12 weeks, and evaluated according to the following criteria.

Evaluation criteria; Effective: Blemishes and freckles disappeared. Slightly effective: Spots and freckles are less noticeable. Ineffective: No change.

[0034]

[Table 6]

As is clear from Table 6, the emulsion of the present invention (Samples 35 to 3) prepared by combining the components (A) and (B) in combination.
7) is excellent in the effect of making spots and freckles inconspicuous not only when compared with the sample 30 which does not contain any of these, but also when compared with the samples 31 to 34 in which the component (A) or (B) is blended alone. , Showed a remarkable whitening effect.

Example 2 Cosmetics:

<Table 7><Prescription> (%) (1) Glycerin 5.0 (2) 1,3-butylene glycol 6.5 (3) Polyoxyethylene sorbitan monolaurate ester (20EO) 1.2 (4) ) Ethyl alcohol 8.0 (5) Assemblage extract (as dry solid content) 0.01 (6) Iclinine extract 2.0 (7) Yokuinin extract (as dry solid content) 0.05 (8) Preservative Proper amount (9) Perfume Proper amount (10) Purified water Remaining amount <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.

Example 3 Cream:

<Table 8><Prescription> (%) (1) Beeswax 6.0 (2) Cetanol 5.0 (3) Reduced lanolin 5.0 (4) Squalane 30.0 (5) Glycerin monostearate 4.0 ( 6) Lipophilic glyceryl monostearate 2.0 (7) Polyoxyethylene sorbitan monolaurate ester (20 EO) 2.0 (8) Maika extract 1.0 (9) Yokuinin extract (as dry solids) ) 0.2 (10) Preservative 0.3 (11) Perfume 0.05 (12) Purified water Remaining amount <Production method> A. (1) to (7), (10) and (11) are mixed,
Heat and keep at 70 ° C. B. Mix (8), (9) and (12) and heat to 7
Keep at 0 ° C. C. B was added to A, mixed, and then cooled to obtain a cream.

Example 4 Pack:

<Table 9><Prescription> (%) (1) Polyvinyl alcohol 20.0 (2) Ethanol 20.0 (3) Glycerin 5.0 (4) Kaolin 6.0 (5) Mokka extract 0.1 (6) ) Yokuinin extract 2.0 (7) Preservative 0.3 (8) Perfume 0.1 (9) Purified water Remaining amount <Production method> A. (1), (3) to (6) and (9) are mixed to obtain 70
Heat to ℃ and stir. B. Mix (2), (7) and (8). C. B was added to A, mixed, and then cooled to obtain a pack.

Example 5 Cleaning agent:

<Table 10><Prescription> (%) (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) Perfume 0.1 (8) Preservative 0.2 (9) Glycerin 18.0 (10) Potassium hydroxide 6.0 (11) Mocca extract 0.2 (12) ) Yokuinin extract (as dry solids) 0.01 (13) Purified water Remaining amount <Production method> A. Mix (9), (10) and (13) and heat to 70 ° C. B. Mix (1) to (6) and (8) and heat to 70 ° C. C. B was added to A and maintained at 70 ° C. for a while, and after the saponification reaction was completed, it was cooled to 50 ° C., (7), (11) and (12) were added and cooled to obtain a cleaning agent.

Example 6 An emulsion having the composition shown in Table 11 was produced and evaluated for its whitening effect. The results are shown in Tables 12 and 13.

[0041]

[Table 11]

<Production Method> A. (6) to (9) and (14) are heated and mixed, and the temperature is 70 ° C.
Keep on. B. (1) to (5), (10) and (11) are mixed by heating and kept at 70 ° C. C. B is added to A and mixed, and then (12) is added and uniformly mixed, then (13) is added and uniformly emulsified, and cooled to 30 ° C. to obtain an emulsion.

Test Example 2 The whitening effect of a test substance was examined by utilizing the fact that the back of a colored guinea pig was shaved and irradiated with ultraviolet rays under anesthesia to cause pigmentation. UV irradiation is FL2 made by Toshiba Corporation
Three 0S / BLB lamps and three FL20S / E30 lamps are irradiated at the same time, and the amount of ultraviolet rays is 4.8 × 10 ⁶ erg / cm ²
And 24 hours before UV irradiation, immediately after irradiation, and irradiation 2
After 4 hours, in 4 places (2 x 2 cm) on the back of the guinea pig,
The products 9 to 12 of the present invention were rubbed in 0.2 ml each. However, the application site was thoroughly washed with warm water before irradiation. Seven days after the irradiation, the degree of pigmentation at each site was observed and judged according to the following criteria. The results are shown in Table 12.

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

[0045]

[Table 12]

As is apparent from Table 12, the emulsion of the present invention containing the components (A) and (B) in combination (Sample 41).
Shows a remarkable pigmentation-preventing effect not only when compared with Sample 38 which does not contain any of these, but also when compared with Samples 39 and 40 in which each of them is blended alone.

Test Example 3 Use effect test 15 women aged 23 to 44 years were used as a panel, and the appropriate amount of the milky lotion of Samples 38 to 41 was applied to the face for 12 weeks, twice daily in the morning and at night and after washing the face. According to the above, a usage test was conducted and evaluated according to the following criteria. Evaluation criteria; Effective: Spots and freckles are not noticeable. Slightly effective: Spot freckles are less noticeable. Ineffective: No change.

[0048]

[Table 13]

As is clear from Table 13, the emulsion of the present invention (Sample 41) was not only compared with Sample 38 containing none of these, but also Sample 3 in which each of them was blended alone.
Compared with Nos. 9 and 40, the effect of making spots and freckles inconspicuous was excellent, and a remarkable whitening effect was exhibited.

[0050]

Example 7 Cream:

[Table 1] <Prescription> (%)   (1) Beeswax 6.0   (2) Cetanol 5.0   (3) Reduced lanolin 5.0   (4) Squalane 30.0   (5) Glycerin monostearate 4.0   (6) Lipophilic type glyceryl monostearate 2.0   (7) Polyoxyethylene sorbitan monolauric acid         Ester (20EO) 2.0   (8) Mikaika extract 1.0   (9) N, N'-diacetylcystine dimethyl 1.0 (10) Inositol 0.1 (11) Preservative 0.3 (12) Perfume 0.05 (13) Purified water Remaining amount <Production method> A. (1) to (7), (11) and (12) are mixed, heated and kept at 70 ° C. B. Mix (8) to (10) and (13), heat and keep at 70 ° C. C. B was added to A, mixed, and then cooled to obtain a cream.

[0052]

Example 8 Cleaning agent:

[Table 2] <Prescription> (%)   (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) Perfume 0.1   (8) Preservative 0.2   (9) Glycerin 18.0 (10) Potassium hydroxide 6.0 (11) Micalica extract 0.2 (12) N, N'-diacetylcystine dimethyl 0.1 (13) Purified water Remaining amount <Production method> A. Mix (9), (10) and (13) and heat to 70 ° C. B. Mix (1) to (6) and (8) and heat to 70 ° C. C. Add B to A and keep at 70 ° C for a while until 50 ° C after saponification reaction After cooling, (7), (11) and (12) were added and cooled to obtain a cleaning agent.

[0054]

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

─────────────────────────────────────────────────── ─── Continuation of the front page (72) Inventor Satsuki Kuribayashi 48-18 Sakaemachi, Kita-ku, Tokyo Kose Research Institute Co., Ltd. (72) Keiko Kaizu 48-18 Sakaemachi, Kita-ku, Tokyo Kose Research Co., Ltd. In-house (56) Reference JP-A-3-188011 (JP, A) JP-A-57-35519 (JP, A) JP-A-55-64510 (JP, A) JP-A-60-104005 (JP, A) JP-A-1-26507 (JP, A) JP-A-3-157334 (JP, A) JP-A-3-193712 (JP, A) JP-A-3-127714 (JP, A) JP-B-45-18998 (JP, B2) (58) Fields investigated (Int. Cl. ⁷ , DB name) A61K 7/00 A61K 7/48 A61K 35/78

Claims (2)

(57) [Claims] 1. (A ₁ ) A squid extract, and (B ₁ ) (i) N, N′-diacetylcystine dimethyl or (b) selected from Yokuinin, Ibukitoranoo, Clara, Hawthorn, hops, Neubara and white lily. An external preparation for whitening skin, comprising one or more kinds of plant extracts. 2. One or more kinds of plant extracts selected from (A ₂ ) mocca and iclinin, and a plant selected from (B ₂ ) Yokuinin, Ibukitoranoo, Clara, Hawthorn, Hop, Neubara and Shirayuri. An external preparation for whitening skin, comprising one or more kinds of the extract of