JP2007191438A - Desmosome degradation-promoting agent - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a means for efficiently promoting the peeling of skin horny in a short time to improve drabness, because the sufficient peeling of the skin horny layers is difficult to cause the drabness in many cases, when the activity of a desmosome degradation enzyme on skin is deteriorated. <P>SOLUTION: This desmosome degradation-promoting agent of the present invention is characterized by containing the extract of one or more plants selected from Zizyphus jujuba var. inermis Rehd, Saxifraga stolonifera L., and Rubus idaeus L. The external preparation for skin is characterized by containing the extract of one or more plants selected from Zizyphus jujuba var. inermis Rehd, Saxifraga stolonifera L., and Rubus idaeus L., and granules. The desmosome degradation-promoting agent has a desmosome degradation enzyme activity-promoting effect and further an excellent horny keratinocyte-removing effect, and therefore prevents the thickening of horny layer and prevents and improves the drabness of skin. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

  The present invention relates to a desmosome degradation promoter and an external preparation for skin.

  One of the causes of dullness is known to be a decrease in transparency due to stratum corneum thickening, and it has been found that dullness can be prevented by suppressing the thickening of the stratum corneum. For these reasons, one of the major objectives required for skin preparations such as cosmetics is the effect of removing the old stratum corneum.

In order to achieve this object, conventionally, raw materials having an exfoliating effect such as AHA (α-hydroxy acid) (Japanese Patent Laid-Open No. 58-8007), scrub (Japanese Patent Publication No. 5-7362) have been blended. It was. However, it has been reported that AHA adversely affects the skin depending on the person. As the scrub agent, walnut shell, polyethylene powder or the like is used, but it is considered that the skin may be damaged unless the scrub particles are spherical.
JP 58-8007 JP 5-7362

The thickening of the stratum corneum occurs because the detachment of the horny cells misses the time of detachment, and one of them involves the activity of the desmosome degrading enzyme, a substance that adheres between the cells of the horny cells. Has been reported.
Arch. Dermatol. Res. 286, 249-255, 1994.

  Activating the desmosome-degrading enzyme activity is expected to lead to prevention or elimination of dullness by normalizing or promoting skin turnover or actively removing the dysfunctional stratum corneum.

  When the enzyme activity of desmosome-degrading enzyme is reduced on the skin, it is often difficult to remove the stratum corneum sufficiently with AHA or scrub agents, and more effectively, in a short time, It would be desirable to provide a means for promoting stratum corneum peeling.

  As a result of intensive studies to solve such problems, the present inventors have found that one or more plant extracts selected from jujube, yukinoshita, and raspberry significantly promote desmosome-degrading enzyme activity. confirmed. In addition, it was confirmed that by further adding granules to the skin external preparation containing these plant extracts, the peeling effect of the stratum corneum was further improved and dullness was improved, and the present invention was completed. It was.

    The jujube used in the present invention belongs to the family Oleaceae, and is a jujube (scientific name: Zizyhus jujuba var. Inermis Rehd) or a related plant thereof, and is a deciduous tree that originates from North America to western Europe. The dried fruit (herbal medicine name: Daegu) can be used.

  Yukinosita used in the present invention belongs to the family Yukinosita, and the scientific name: Saxifraga stolonifera L. et al. It is a perennial herb distributed in Japan and China. Whole grass can be used.

  The raspberry used in the present invention belongs to the Rosaceae family and is a European raspberry (scientific name: Rubus idaeus L.) or a related species thereof, and is widely cultivated as a fruit tree. Raspberry (fruit) can be used.

  The extraction method of the extract of jujube, yukinoshita and raspberry of the present invention is not particularly limited, and for example, it may be extracted by heating, or it may be extracted at room temperature or low temperature. Examples of the extraction solvent include water, lower monohydric alcohols (methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, 2-butanol, etc.), liquid polyhydric alcohol (1,3-butylene glycol). , Propylene glycol, etc.), hydrocarbons (hexane, pentane, etc.), ketones (acetone, methyl ethyl ketone, etc.), ethers (ethyl ether, tetrahydrofuran, propyl ether, etc.), acetonitrile and the like. These solvents may be used alone or in combination of two or more. Preferably, one or two or more solvents among water or a water-soluble solvent (solvent that can be mixed with water in an arbitrary ratio. For example, ethanol, 1,3-butylene glycol, propylene glycol, etc.) may be used. . The extract may be used as it is, or a part or all of the solvent may be distilled off.

  The extract may be used as it is, or may be used after concentration, dilution, filtration, decolorization with activated carbon, deodorization, or the like, if necessary. Further, the extracted solution may be used as a dried product after being concentrated and dried, spray dried, freeze dried, etc., or may be used after concentrating or isolating the active ingredient by performing column purification or the like. good.

  As the desmosome degradation promoter and the external preparation for skin of the present invention, the jujube extract, the yukinoshita extract and the raspberry extract may be used as they are. Fats and oils, waxes, hydrocarbons, fatty acids, alcohols, esters, surfactants, metal soaps, pH adjusters, preservatives, fragrances, moisturizers, powders, UV absorbers, increase Components such as a sticking agent, a pigment, an antioxidant, a whitening agent, and a chelating agent can be blended.

  The desmosome degrading agent and the external preparation for skin used in the present invention can be used in any of cosmetics, quasi-drugs, and pharmaceuticals. Examples of the dosage form include lotions, creams, emulsions, gels, and aerosols. , Ointments, poultices, pastes, plasters, essences, packs, cleaning agents, bath preparations, foundations, powders, lipsticks and the like.

  Although the compounding quantity of the jujube extract used in this invention, a Yukinoshita extract, and a raspberry extract is not specifically limited, 0.0001-10 weight% is preferable as a dry product, More preferably, it is 0.001-5 weight%. is there. If it is 0.0001% by weight or less, the effect is low, and even if it exceeds 10% by weight, the effect is hardly increased and is not efficient. In addition, the addition method may be added in advance or during the production, and may be appropriately selected in consideration of workability.

  The granule used in the present invention may be any granule as long as it can be usually blended into a skin external preparation, a cleaning material, a cosmetic material, a massage material, or the like, but preferably Japanese Patent Publication No. 5-7362. The hydrogenated jojoba oil described, the scrub granules described in Japanese Patent No. 3242742, and the like can be used.

  The present invention has an effect of promoting desmosome-degrading enzyme activity, and is further excellent in the effect of removing keratinocytes.

  Next, in order to describe the present invention in detail, examples of production of the extract used in the present invention, formulation examples and experimental examples will be given as examples, but the present invention is not limited thereto. The compounding amount shown in the examples indicates% by weight.

Production Example 1 Hot water extract of jujube 800 ml of purified water was added to 20 g of dried jujube fruits, extracted at 95-100 ° C. for 2 hours, filtered, the filtrate was concentrated, freeze-dried and hot water extract of jujube 3.3 g of product was obtained.

Production Example 2 30% 1,3-butylene glycol extract of jujube 280 g of purified water and 120 g of 1,3-butylene glycol were added to 20 g of dried jujube fruits, extracted at room temperature for 7 days, filtered, and 30% of jujube 330 g of 1,3-butylene glycol extract was obtained.

Production Example 3 50% ethanol extract of jujube 400 ml of purified water and 400 ml of ethanol were added to 40 g of dried jujube fruits, extracted at room temperature for 7 days, filtered, the filtrate was concentrated to dryness, and jujube 50% ethanol was extracted. 2.4 g of product was obtained.

Production Example 4 Yukinoshita Hot Water Extract 800 ml of purified water was added to 30 g of dried Yukinoshita whole plant, extracted at 95-100 ° C. for 2 hours, filtered, and the filtrate was concentrated and freeze-dried to obtain the heat of Yukinoshita. 6.2 g of water extract was obtained.

Production Example 5 30% 1,3-Butylene Glycol Extract of Yukinoshita 280 g of purified water and 120 g of 1,3-butylene glycol were added to 20 g of dried leaves of Yukinoshita, extracted at room temperature for 7 days, filtered, and 50% of Yukinoshita 330 g of 1,3-butylene glycol extract was obtained.

Production Example 6 50% Ethanol Extract of Yukinoshita 400 ml of purified water and 400 ml of ethanol were added to 40 g of dried Yukinoshita whole plant, extracted at room temperature for 7 days, filtered, and the filtrate was concentrated to dryness to obtain 50% of Yukinoshita. 4.5 g of ethanol extract was obtained.

Production Example 7 Hot Water Extract of Raspberry Extracted from 60 g of frozen raspberry fruits, 600 mL of purified water was added, extracted at 95-100 ° C. for 2 hours, filtered, the filtrate was concentrated, freeze-dried and extracted with ripe strawberries. 2.4 g of product was obtained.

Production Example 8 30% 1,3-butylene glycol extract of raspberry Add 280 g of purified water and 120 g of 1,3-butylene glycol to 20 g of freeze-dried fruit of raspberry, extract at room temperature for 7 days, filter, and extract 30 raspberry 330 g of% 1,3-butylene glycol extract was obtained.

Manufacture example 9 50% ethanol extract of raspberry Add 1 L of purified water and 1 L of ethanol to 100 g of frozen raspberry fruits, extract for 7 days at room temperature, filter, concentrate the filtrate to dryness, extract 50% ethanol of raspberry 2.0 g of product was obtained.

  Next, the prescription of the Example which concerns on this invention is shown.

Formulation Example 1 Cream 1
Formulation amount (% by weight)
1. Hot water extract of jujube (Production Example 1) 0.6
2. Squalane 5.5
3. Olive oil 3.0
4). Stearic acid 2.0
5). Beeswax 2.0
6). Octyldodecyl myristate 3.5
7). Polyoxyethylene cetyl ether (20E.O.) 3.0
8). Behenyl alcohol 1.5
9. Glycerol monostearate2.5
10. Fragrance 0.1
11.1,3-butylene glycol 8.5
12 Ethyl paraoxybenzoate 0.05
13. Methyl paraoxybenzoate 0.2
14 Purified water 67.55
[Production Method] Components 2 to 9 are heated and mixed, and kept at 70 ° C. to obtain an oil phase. Ingredients 1 and 11 to 14 are dissolved by heating and mixed, and kept at 75 ° C. to form an aqueous phase. The aqueous phase is added to the oil phase to emulsify, and the mixture is cooled while stirring. The component 10 is added at 45 ° C., and further cooled to 30 ° C. to obtain a product.

Formulation Example 2 Cream 2
In Formulation Example 1, cream 2 was obtained by replacing the hot water extract of jujube with the hot water extract of Yukinoshita (Production Example 4).

Formulation Example 3 Cream 3
In Formulation Example 1, cream 3 was obtained by replacing the hot water extract of jujube with the hot water extract of raspberry (Production Example 7).

Formulation Example 4 Cream 4
Formulation amount (% by weight)
1. Hot water extract of jujube (Production Example 1) 0.2
2. Yukinoshita hot water extract (Production Example 4) 0.2
3. Raspberry hot water extract (Production Example 7) 0.2
4). Squalane 5.5
5). Olive oil 3.0
6). Stearic acid 2.0
7). Beeswax 2.0
8). Octyldodecyl myristate 3.5
9. Polyoxyethylene cetyl ether (20E.O.) 3.0
10. Behenyl alcohol 1.5
11. Glycerol monostearate2.5
12 Fragrance 0.1
13.1,3-Butylene glycol 8.5
14 Ethyl paraoxybenzoate 0.05
15. Methyl paraoxybenzoate 0.2
16. Purified water 67.55
[Manufacturing method] Components 4 to 11 are heated and mixed to maintain an oil phase at 70 ° C. Ingredients 1 to 3 and 13 to 16 are dissolved by heating and mixed, and kept at 75 ° C. to obtain an aqueous phase. The aqueous phase is added to the oil phase to emulsify, and the mixture is cooled while stirring. The component 12 is added at 45 ° C., and further cooled to 30 ° C. to obtain a product.

Formulation Example 5 Cream 5
Formulation amount (% by weight)
1. Hot water extract of jujube (Production Example 1) 0.2
2. Yukinoshita hot water extract (Production Example 4) 0.2
3. Raspberry hot water extract (Production Example 7) 0.2
4). Squalane 5.5
5). Olive oil 3.0
6). Stearic acid 2.0
7). Beeswax 2.0
8). Octyldodecyl myristate 3.5
9. Polyoxyethylene cetyl ether (20E.O.) 3.0
10. Behenyl alcohol 1.5
11. Glycerol monostearate2.5
12 Fragrance 0.1
13.1,3-Butylene glycol 8.5
14 Ethyl paraoxybenzoate 0.05
15. Methyl paraoxybenzoate 0.2
16. Purified water 66.05
17. Granule 1 (particle size 0.105 to 2 mm) 0.75
18. Granule 2 0.75
[Manufacturing method] Components 4 to 11 are heated and mixed to maintain an oil phase at 70 ° C. Ingredients 1 to 3 and 13 to 16 are dissolved by heating and mixed, and kept at 75 ° C. to obtain an aqueous phase. The aqueous phase is added to the oil phase to emulsify, and the mixture is cooled while stirring. The component 12 is added at 45 ° C., and further cooled to 30 ° C., and then components 17 and 18 are uniformly dispersed to obtain a product. The granule 1 is a hydrogenated jojoba oil described in Japanese Patent Publication No. 5-7362, and the granule 2 is a scrub granule described in Japanese Patent No. 3242742.

Comparative Example 1 Conventional cream 1
In Formulation Example 1, a hot cream extract of jujube replaced with purified water was used as a conventional cream.

Comparative Example 2 Conventional Cream 2
In the formulation example 5, the hot water extract of jujube, the hot water extract of Yukinoshita, and the hot water extract of raspberry were replaced with purified water to obtain conventional cream 2.

Formulation Example 6 Lotion Formulation Amount (% by weight)
1. 30% jujube 1,3-butylene glycol
Extract (Production Example 2) 1.0
2. 30% 1,3-butylene glycol of Yukinoshita
Extract (Production Example 5) 1.0
3. 30% 1,3-butylene glycol of raspberry
Extract (Production Example 8) 1.0
4.1,3-Butylene glycol 8.0
5). Glycerin 2.0
6). Xanthan gum 0.02
7). Citric acid 0.01
8). Sodium citrate 0.1
9. Ethanol 5.0
10. Methyl paraoxybenzoate 0.1
11. Polyoxyethylene hydrogenated castor oil (40E.O.) 0.1
12 Fragrance 0.1
13. Purified water 81.57
[Production Method] Components 1 to 8 and 13 and Components 9 to 12 are uniformly dissolved, mixed and filtered to obtain a product.

Formulation Example 7 Emulsion Formulation Amount (% by weight)
1. Jujube 50% ethanol extract (Production Example 3) 0.05
2. 50% ethanol extract of Yukinoshita (Production Example 6) 0.05
3. 50% ethanol extract of raspberry (Production Example 9) 0.05
4). Squalane 5.0
5). Olive oil 5.0
6). Jojoba oil 5.0
7). Cetanol 1.5
8). Glycerol monostearate 2.0
9. Polyoxyethylene cetyl ether (20E.O.) 3.0
10. Polyoxyethylene sorbitan monooleate 2.0
11. Fragrance 0.1
12 Propylene glycol 1.0
13. Glycerin 2.0
14 Methyl paraoxybenzoate 0.2
15. Purified water 73.05
[Manufacturing method] Components 4 to 10 are heated and dissolved, mixed, and kept at 70 ° C to obtain an oil phase. Ingredients 1 to 3 and 12 to 15 are dissolved by heating and mixed, and kept at 75 ° C. to obtain an aqueous phase. The aqueous phase is added to the oil phase to emulsify, and the mixture is cooled while stirring. The component 11 is added at 45 ° C., and further cooled to 30 ° C. to obtain a product.

Formulation Example 8 Ointment Formulation Amount (% by weight)
1. Jujube extract from hot water (Production Example 1) 0.5
2. Yukinoshita hot water extract (Production Example 4) 0.5
3. Raspberry hot water extract (Production Example 7) 0.5
4). Polyoxyethylene cetyl ether (30E.O.) 2.0
5). Glycerol monostearate 10.0
6). Liquid paraffin 5.0
7). Cetanol 6.0
8). Methyl paraoxybenzoate 0.1
9. Propylene glycol 10.0
10. Purified water 65.4
[Manufacturing method] Components 4 to 7 are dissolved by heating and mixed, and kept at 70 ° C to obtain an oil phase. Ingredients 1 to 3 and 8 to 10 are dissolved by heating and mixed, and kept at 75 ° C. to obtain an aqueous phase. The aqueous phase is added to the oil phase to emulsify, and the mixture is cooled to 30 ° C. with stirring to obtain a product.

Formulation Example 9 Foundation Formulation Amount (% by weight)
1. Jujube hot water extract (Production Example 1) 0.5
2. Yukinoshita hot water extract (Production Example 4) 0.5
3. Raspberry hot water extract (Production Example 7) 0.5
4). Stearic acid 2.4
5). Polyoxyethylene sorbitan monostearate 1.0
(20 EO)
6). Polyoxyethylene cetyl ether (20E.O.) 2.0
7). Cetanol 1.0
8). Liquid lanolin 2.0
9. Liquid paraffin 3.0
10. Isopropyl myristate 6.5
11. Butyl paraoxybenzoate 0.1
12 Sodium carboxymethylcellulose 0.1
13. Bentonite 0.5
14 Propylene glycol 4.0
15. Triethanolamine 1.1
16. Methyl paraoxybenzoate 0.2
17. Titanium dioxide 8.0
18. Talc 4.0
19. Bengala 1.0
20. Yellow iron oxide 2.0
21. Fragrance 0.1
22. Purified water 59.5
[Manufacturing method] Components 4 to 11 are dissolved by heating and kept at 80 ° C to obtain an oil phase. Swell component 12 well in component 22, then add components 1-3 and 13-16 and mix uniformly. To this, components 17 to 20 pulverized and mixed with a pulverizer are added, stirred with a homomixer and kept at 75 ° C. to obtain an aqueous phase. The oil phase is added to this aqueous phase with stirring, cooled, component 21 is added at 45 ° C., and cooled to 30 ° C. with stirring to give a product.

Formulation Example 10 Bath preparation formulation Formulation amount (% by weight)
1. Hot water extract of jujube (Production Example 1) 5.0
2. Yukinoshita Hot Water Extract (Production Example 4) 5.0
3. Raspberry hot water extract (Production Example 7) 5.0
4). Sodium bicarbonate 50.0
5). Yellow No. 202 (1) 0.05
6). Fragrance 0.25
7). Anhydrous sodium sulfate 34.7
[Production Method] Components 1 to 7 are uniformly mixed to obtain a product.

  Next, experimental examples will be given to explain the effects of the present invention in detail.

Experimental Example 1 Desmosome-degrading enzyme activity promoting action The surface of the back skin of a white Hartley female guinea pig that had been cut and shaved was shaved with a scalpel to obtain a keratinocyte powder. It was suspended and dispersed at 10 mg / mL in 0.2 M Tris-HCl buffer (pH 9.0) containing 0.1% Triton X-100, homogenized, and centrifuged at 1500 rpm for 10 minutes. Obtained. This was used as a crude enzyme solution of desmosome-degrading enzyme. The desmosome-degrading enzyme was measured as a serine protease activity using a synthetic substrate (Boc-Phe-Ser-Arg-MCA; manufactured by Peptide Institute). That is, 0.05 mL of a 10 mg / mL sample was added to 0.45 mL of the crude enzyme solution and incubated at 37 ° C. for 1 hour. Thereafter, 0.04 mL of 5 mM synthetic substrate was added and incubated at 37 ° C. for 90 minutes to decompose the synthetic substrate. Immediately after completion of the reaction, the fluorescence intensity (Ex / Em = 380/460) was measured with a fluorescence spectrophotometer. The result of activity measurement was expressed as 100% when no sample was added.

  The test results are shown in Table 1. As a result, an excellent desmosome-degrading enzyme activity promoting effect was observed in the extracts of jujube, yukinoshita and raspberry.

Experimental Example 2 Removal of keratinocytes When the creams of Formulation Examples 1 to 4 and the conventional cream 1 of Comparative Example 1 are applied to human skin and washed after standing for a certain period of time, the feeling of use is good and the keratinocytes are removed. It was tested for effects.

  After washing the face, 1 mL of the cream containing the plant extract was applied to one cheek of a human who had been kept quiet without touching with a hand for a certain time, and the same amount of conventional cream was applied to the other cheek. The position of application was 2 cm square at the same position in the center of both cheeks. After 8 hours from the application, both cheeks were similarly washed with water, the adhesive tape was affixed to the applied part, the tape was stained by the eosin method, and the number of cells stained within 1 cm square was counted.

  These results are summarized in Table 3. The creams of Formulation Examples 1 to 4 showed an excellent keratinocyte removal effect. In addition, the effect of removing keratinocytes was synergistically promoted by combining the extract of jujube, the extract of Yukinoshita and the extract of raspberry.

Experimental Example 3 Dullness Improvement Test Using the creams of Examples 4 and 5 and the conventional creams 1 and 2 of Comparative Examples 1 and 2, a dullness improvement test was conducted on 10 women (21 to 46 years old) who suffered from dullness. It was.

  1 mL of cream containing a plant extract on one cheek and the same amount of conventional cream on the other cheek were applied and massaged for 5 minutes. The position of application was 2 cm square at the same position in the center of both cheeks. A color pigment meter (manufactured by Minolta, CR-200) was used for the determination, and the face was washed before applying the cream and after the massage, and the color change at the test site was measured. In the measurement method, the brightness of the test site and the adjacent site was measured, and the brightness index was obtained by subtracting the brightness of the measured test site and the adjacent site. In addition, the dullness improvement effect was determined from each lightness index according to the evaluation criteria shown in Table 3 below.

  These results are summarized in Table 4. The creams of Formulation Examples 4 and 5 were found to have excellent dullness improving effects. It was also confirmed that the effect of improving dullness was further improved by blending the granules.

Experimental Example 4 Usage Test Using the creams of Formulation Examples 1 to 4 for 30 months (21 to 46 years old) as a control, a usage test was conducted for 3 months. There was no problem.

As an application example of the present invention, it can be used for any of cosmetics, quasi drugs, and pharmaceuticals. Examples of the dosage form include lotions, creams, emulsions, gels, aerosols, ointments, poultices, pastes, plasters, essences, packs, detergents, bath preparations, foundations, powders, lipsticks, etc. By activating the desmosome-degrading enzyme activity, it is possible to prevent keratin thickening and prevent or improve skin dullness.

Claims (3)

A desmosome degradation promoter comprising one or more plant extracts selected from jujube, saxifrage, and raspberry. An external preparation for skin, comprising the desmosome degradation promoter according to claim 1. The external preparation for skin according to claim 2, comprising granules.