JP2006241033A - Skin care preparation for external use for amelioration of skin somberness - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a skin care preparation for external use effective for amelioration of skin troubles accompanied by aging such as skin somberness or the like. <P>SOLUTION: The invention relates to the skin care preparation for external use (1) for amelioration of skin somberness comprising following (A)-(D). (A) An extract of Mori Cortex. having a tyrosinase activity inhibiting action. (B) A cell-activating agent. (C) An active oxygen scavenger. (D) An estrogenic agent. (2) The cell-activating agent (B) comprises at least one selected from a deoxyribonucleic acid salt, disodium adenosine triphosphate, yeast extract, carrot extract, garlic extract and chlorella vulgaris extract, and the active oxygen scavenger (C) comprises at least one selected from Sanguisorba officinalis extract, tea extract, Moutan Cortex extract and Olea europaea leaf extract, and the estrogenic agent (D) comprises at least one selected from soy Glycine maxes extract, Puerariae Radix extract, Pueraria mirifica extract and Trifolium pretense extract. <P>COPYRIGHT: (C)2006,JPO&NCIPI

Description

  The present invention relates to a skin cosmetic useful for improving skin troubles associated with age-related changes such as dullness. More specifically, the present invention relates to a skin external preparation for dullness improvement comprising (A) an extract of Sakuhakaku having a whitening effect, (B) a cell activator, (C) an active oxygen scavenger and (D) an estrogen-like agent. .

  It is said that the cause of skin trouble accompanying aging changes such as dullness is a synergistic result of melanin overproduction and skin shape change. Regarding the mechanism of skin blotting, it is considered that melanin pigments are formed due to the stimulation of ultraviolet rays from sunlight and hormonal abnormalities, resulting in abnormal deposition in the skin. Melanin pigments are produced in melanosomes within melanocytes. In melanocytes, tyrosine, an essential amino acid, becomes dopaquinone by the action of tyrosinase, which changes to black melanin through a red pigment and a colorless pigment by enzymatic or non-enzymatic oxidation. Hydroquinone is a compound that suppresses the production of melanin, but it cannot generally be used because of its sensitization. Derivatives such as higher fatty acid monoesters and alkyl ethers have been studied, but are not sufficient for safety. Therefore, kojic acid, ellagic acid, arbutin, various plant extracts and the like have been studied as those derived from natural products (Non-patent Document 1, Patent Document 1, Patent Document 2, Patent Document 3, Patent Document 4, Patent (Refer to Literature 5, Patent Literature 6, and Patent Literature 7).

Skin is the organ most exposed to active oxygen because it is in contact with air and irradiated with ultraviolet rays as well as oxygen stress caused by the body. On the skin surface, active oxygen oxidizes sebum and is the starting point for deterioration of the skin surface condition. In the dermis, it is said that the active oxygen causes cross-linking of collagen and elastin, which are constituent components, causing a decrease in elasticity, and hyaluronic acid is reduced in molecular weight to cause a decrease in moisturizing ability. Such changes in the dermal component have been proposed as a cause of wrinkles. In addition, active oxygen is considered to be deeply involved in the generation of spots, and thus is presumed to be the main cause of various skin aging. For this reason, cosmetics that protect the skin from active oxygen have been developed so far.
In particular, active oxygen scavengers have been developed from natural products such as sesaminol in sesame oil, sesamol, tocopherol in rice germ, oryzanol, caffeic acid in coffee beans, carnosol in rosemary, rosemary acid, turmeric. There is curcumin inside. Moreover, active oxygen scavenging ability was discovered and used for many plant extracts (refer nonpatent literature 2, patent document 8, patent document 9).

On the other hand, it is known that estrogens and estrogenic compounds increase skin layer thickness and reduce wrinkle formation in aging skin. Changes in the skin, such as skin dryness, skin elasticity and loss of bulges that occur after menopause are due to a lack of estrogen production. Estrogen therapy prevents or delays many of these changes associated with aging skin.
Therefore, compounds having an estrogen-like action have been studied from plant extracts (Non-patent Document 3, Patent Document 10, and Patent Document 11).

  Various studies have also been made on enhancing the effect of an active ingredient by incorporating an active ingredient and a cell activator into an external preparation for skin (Patent Document 12).

However, many of these products are mainly for individual usefulness and formulation into skin preparations, and there are problems in terms of effectiveness, safety, cost, etc. in terms of prevention of aging, especially in terms of dullness improvement. It was still not fully satisfactory. Conventional publicly known documents are listed below.

Noriyuki Omori, FRAGRANCE JOURNAL Extraordinary, No. 14, 1995, 118-126 Jin Masaki, FRAGRANCE JOURNAL, Vol. 32, No. 4, 2004, 26-32 Creid et al., Effect of a conjugated estrogen cream on aging facial skin, Maturitas, 19, p. 211, 1994 JP-A-8-48621 JP-A-8-283143 JP-A-9-315928 JP 2000-109476 A JP2001-2558 JP 2002-114626 A JP2003-104835 JP 2004-168732 A JP 2004-238310 A JP2002-29980 JP-A-2004-67590 JP-A-8-99860

This invention makes it a subject to provide the skin external preparation useful for improving the skin trouble accompanying the splendor changes, such as dullness.

  In view of such a situation, the present inventor has conducted extensive research on an external preparation for skin effective for improving skin troubles associated with age-related changes such as dullness. One or more kinds selected from deoxyribonucleic acid salt, adenosine triphosphate disodium, yeast extract, carrot extract, garlic extract, chlorella extract, etc. having an activating action, mainly having an active oxygen scavenging action From at least one selected from the group consisting of soy extract, tea extract, button pipi extract, olive leaf extract, and the like, and having an estrogenic action, mainly from soybean extract, cuckoo extract, Pueraria myrifica extract, red clover extract, etc. Discovered an excellent dullness-improving effect on a topical skin preparation containing one or more selected ingredients and completed the invention It came to that.

The present invention is constituted by the following claims 1 to 4.
[1] A skin external preparation for dullness improvement comprising the following (A) to (D):
(A) Sakuhakuhi extract having tyrosinase activity inhibiting action (B) Cell activator (C) Reactive oxygen scavenger (D) Estrogen-like agent Claim 2: Cell activator is deoxyribonucleic acid salt, adenosine triphosphate diphosphate The skin external preparation for dullness improvement according to claim 1, which is at least one selected from sodium, yeast extract, carrot extract, garlic extract and chlorella extract.
[3] The skin external preparation for dullness improvement according to [1], wherein the active oxygen scavenger is at least one selected from a bitumen extract, a tea extract, a button pi extract and an olive leaf extract.
[4] The skin external preparation for dullness improvement according to [1], wherein the estrogen-like agent is at least one selected from soybean extract, cuckoo extract, Pueraria myrifica extract, and red clover extract.

By blending the four essential ingredients of the present invention, the extract of Sakuhakuhi, cell activator, active oxygen scavenger and estrogen-like agent, skin troubles associated with age-related changes such as dullness due to their synergistic effect It has the effect that it can provide a skin external preparation useful for improving the skin.
Hereinafter, the present invention will be described in detail.

As used in the present invention, the Sakuhakuhi is the root bark of Moraceae, Morus and Morus alba L., which is widely cultivated in East Asia. It is widely known that the extract of Sakuhakuhi has an inhibitory effect on tyrosinase activity. It is preferable to use the extract of Sakuhakuhi used in the present invention, in particular, having enhanced tyrosinase activity inhibitory action.

(Manufacture example 1) Manufacture of an extract of Sakuhakuhi 3000g of 30vol% ethanol solution is added to 300g of Sakuhakuhi, extracted for 8 hours at 50 ° C, filtered, and the filtrate is concentrated to about 500g under reduced pressure. The concentrated solution is passed through a column packed with synthetic adsorbent Diaion HP-20. After washing with 30 vol% ethanol solution, elution was performed with 50 vol% ethanol solution, and the eluate was dried under reduced pressure, and 100 g of 50% 1,3-butylene glycol solution was added and dissolved to produce a Sakuha extract. The product evaporation residue was 3.1%.

(Reference Example 1) A test sample for inhibiting tyrosinase activity of Sakuhakuhi extract was prepared by using a dry solid before dissolution in 50% 1,3-butylene glycol solution in Production Example 1, diluted with purified water, and 0.01 mg The concentration was / mL. Using MEM (Gibco) containing 10% FBS (fetal bovine serum; purchased from Nikkyo) and theophylline (0.09 mg / mL), mouse-derived B16 melanoma cultured cells were placed in a 96-well plate at 5 × 10 ⁴ cells / well. After seeding at a density and culturing at 37 ° C. and 5% CO _{2 for} 24 hours, each concentration of the test sample was added, and the cells were further cultured at 37 ° C. and 5% CO _{2 for} 3 days. Prior to measurement of tyrosinase activity, the medium in the wells was removed and washed twice with 100 μL of PBS. PBS containing 45 μLk 1% tryin X (Rohm and House) was added to each well, the plate was shaken for 1 minute to break the cell membrane, and the absorbance at a wavelength of 475 nm was measured with a microplate reader. Absorbance in minutes. Thereafter, 5 μL of 10 mM L-DOPA solution was quickly added and incubated at 37 ° C. for 60 minutes. After shaking the plate for 1 minute, the absorbance was measured in the same manner as the absorbance at 60 minutes. The ratio of the difference in absorbance of the test sample to the difference in absorbance at 0 minutes and 60 minutes when no test sample was added (control) was defined as the tyrosinase activity inhibition rate. The inhibition rate of tyrosinase activity was 78.6%.

In addition, about 10 times as many difference in inhibitory activity appeared in the extract of Sakuhakaku extract which does not perform the column process of the said manufacture example 1 and the Sakuhakaku extract which processed the column.

The cell activator used in the present invention is mainly selected from deoxyribonucleic acid, adenosine triphosphate disodium, yeast extract, carrot extract, garlic extract, chlorella extract, and has a cell activation effect. Widely known and generally commercially available products can be used.

The active oxygen scavenger used in the present invention is generally expected to have a widely used active oxygen scavenging action, and is highly effective and safe. Things are the main thing.

The bittersweet used in the present invention is the rhizome of the Rosaceae genus Sanguisorba (Sanguisorba officinalis).

The button pi used in the present invention is a root bark of a button family (Paeoniaceae) button genus (Paeonia) or button (Paeonia suffruticosa).

The olive used in the present invention is a leaf of the family Oleaceae, the olive genus (Olea), or the olive (Olea europaea).

Examples of teas used in the present invention include green tea (sencha, roasted tea, gyokuro, kabuse tea, tencha, etc.), oolong tea, non-fermented tea such as black tea, semi-fermented tea, and fermented tea.

(Manufacture example 2) The manufacturing method of a bittersweet extract 1000g of 50vol% ethanol solutions are added to 100g of bittersweet, and it extracts at room temperature for 3 days. This is filtered, and the filtrate is concentrated to dryness under reduced pressure. The dried product is dissolved in 1000 g of 30% 1,3-butylene glycol, and then filtered to produce the extract. The product evaporation residue was 1.74%.

(Manufacture example 3) The manufacturing method of a button pie extract The 2000g of 50% ethanol solutions are added to 100g of button pie, and it extracts at room temperature for 3 days. This is filtered, and the filtrate is concentrated to dryness under reduced pressure. The dried product is dissolved in 1000 g of 30% 1,3-butylene glycol and filtered to produce a button pi extract. The evaporation residue of the product was 1.13%.

(Manufacture example 4) The manufacturing method of an olive leaf extract 2000g of 50vol% ethanol solutions are added to 100g of olive leaves, and it extracts at 50 degreeC for 8 hours. This is filtered, and the filtrate is concentrated to dryness under reduced pressure. The dried product is dissolved in 1000 g of 30% 1,3-butylene glycol and filtered to produce an olive leaf extract. The product evaporation residue was 1.52%.

(Manufacture example 5) The manufacturing method of a tea extract Add 2000g of 50vol% ethanol to 100g of green tea, and this is filtered for 3 days at room temperature. The filtrate is concentrated to dryness under reduced pressure. The dried product is dissolved in 1000 g of 30% 1,3-butylene glycol and then filtered to obtain a tea leaf extract. Product evaporation residue was 1.95%

(Reference Example 2)
The active oxygen scavenging ability was measured by measuring the SOD-like activity and DPPH radical scavenging ability using the extracts of Production Examples 5-8. SOD-like activity was according to the NBT method (Beauchamps et al. Method Anal. Bioche., 44, 279-287, 1971 in combination with the XOD system). DPPH radical (diphenylpicrylhydrazyl radical) scavenging ability was measured by dissolving DPPH radical (Sigma) in ethanol to make a 0.1 mM solution, taking 3 mL of 0.1 mM DPPH radical solution in a test tube, and adding each concentration to purified water. After adding 0.5 mL of the diluted test solution and allowing to stand at room temperature for 10 minutes, the absorbance was measured at a wavelength of 517 nm. The test results are shown in Table 1.

The estrogen-like agent used in the present invention may generally be one widely used as having a female hormone-like action, and is mainly soybean extract, cuckoo extract, Pueraria myrifica extract, red clover extract. As an extraction method, an extract having an increased isoflavonoid content is used. The extraction method is not particularly defined, but the one produced by the following method was used.

The soybean extract used in the present invention is an extract of seeds of leguminosae, Glycine soybean (Glycine max). It is widely known that a soybean extract contains isoflavonoids such as daidzin and genistin and has an estrogenic action. It is preferred to use an extract that has been column treated to increase the isoflavone concentration.

  The cuckoo extract used in the present invention is an extract of the roots of leguminosae, genus Pueraria and pueraria lobata. It is well known that the cuckoo extract contains isoflavones such as puerarin and daidzein and has an estrogenic action. It is preferred to use an extract that has been column treated to increase the isoflavone concentration.

  The Pueraria myrifica extract used in the present invention is an extract of the roots of leguminosae, pueraria, and pueraria milifica. It is widely known that the Pueraria myrifica extract contains isoflavonoids such as puerarin, daidzin and daidzein and has an estrogenic action. It is preferred to use an extract that has been column treated to increase the isoflavone concentration.

  Red clover (Trifolium pretense) used in the present invention is a kind of legume, called red clover in Japan, and its component contains isoflavone which is a kind of polyphenol and is known to have high estrogenic action. It is what.

(Production Example 6) Production of soybean extract After adding 1000 g of purified water to 100 g of soybean and leaving it to stand overnight, 2000 g of purified water is further added, extracted at 80 ° C. for 8 hours, cooled and then filtered. The filtrate is concentrated under reduced pressure to 100 g. Add 1000 mL of ethanol to the concentrate, stir and dissolve, then filter. The ethanol solution is concentrated to dryness, 200 g of 50% 1,3-butylene glycol solution is added and dissolved, and then filtered to produce a soybean extract. The product evaporation residue was 0.56%.

(Manufacture example 7) Manufacture of a konkon extract To 100 g of konkon, 2000 mL of absolute ethanol is added and extracted at room temperature for 5 days. This is filtered, and the filtrate is concentrated to dryness under reduced pressure. After adding and dissolving 200 g of 50% 1,3-butylene glycol solution, the filtrate is filtered to produce a cuckoo extract. The product evaporation residue was 1.53%.

Production Example 8 Production of Pueraria Myrifica Extract To 100 g of Pueraria myrifica, 2000 g of a 30 vol% ethanol solution is added and extracted at room temperature for 3 days. This is filtered, and the filtrate is concentrated to 200 g under reduced pressure. The concentrated solution is passed through a column packed with synthetic adsorbent Diaion HP-20. After washing with 30 vol% ethanol solution, elution was performed with 70 vol% ethanol solution, the eluate was dried under reduced pressure, and the dried product was dissolved in 300 g of 50% 1,3-butylene glycol, followed by filtration to Pueraria myrifica. Make an extract. The evaporation residue of the product was 1.31%.

(Manufacture example 9) The manufacturing method of a red clover extract 2,000 g of 30 vol% ethanol solutions are added to 100 g of red clovers, and it extracts at 50 degreeC for 8 hours. This is filtered, and the filtrate is concentrated to dryness under reduced pressure. The dried product is dissolved in 200 g of 50% 1,3-butylene glycol and filtered to produce a red clover extract. The evaporation residue of the product was 1.84%.

The estrogen-like action was measured by a method of examining the effect of estrogen-like activity on the growth of estrogen-dependent cells (In vitro cell. Dev. Biol. 28A, 595-602, 1992). MCF-7 cells derived from human breast cancer cells were suspended at a density of 5 × 10 ⁴ cells / mL using Eagles MEM (phenol red removed) containing 5% FBS (charcoal dextran treatment) and 1 mM sodium pyruvate. The cell suspension (0.1 mL) was seeded on a 96-well microculture plate and cultured at 37 ° C. under 5% CO ₂ for 24 hours. Thereafter, samples of various concentrations were added to the culture plate and cultured for 6 days. After culturing, the cell concentration was measured by the MTT reduction method to obtain an estrogen-like action. High estrogen-like action was confirmed in the soybean extract, cuckoo extract, Pueraria myrifica extract, and red clover extract used in the present invention.

The skin external preparation for dullness improvement of the present invention includes the above-mentioned extract of Sorakuhi which is a tyrosinase activity inhibitor, deoxyribonucleic acid which is a cell activator, disodium adenosine triphosphate, yeast extract, carrot extract, garlic One or more selected from an extract, a chlorella extract, etc., one or more selected from an active oxygen scavenger extract, a tea extract, a button extract, an olive leaf extract, and the like, and an estrogen agent And at least one selected from a soybean extract, a cuckoo extract, a Pueraria myrifica extract, a red clover extract, and the like. The total amount of the essential components is not particularly limited, but is generally 0.0001 to 10.0% by weight, preferably 0.001 to 5.0% by weight in terms of dry solid based on the total amount of the external preparation for skin. %, Particularly preferably 0.005 to 3.0% by weight. If the blending amount is less than 0.0001% by weight, the whitening effect of the external preparation for the skin tends to be poor, and conversely, even if it exceeds 5.0% by weight, the increase in the effect is practically not expected. It tends to be difficult.

The skin external preparation of this invention can contain the arbitrary components used with a normal skin external preparation other than the said essential component. For example, oils, wetting agents, UV inhibitors, antioxidants, surfactants, preservatives, moisturizers, fragrances, water, alcohol, thickeners, sebum secretion regulators, anti-inflammatory agents, astringents, antioxidants Furthermore, animal and plant extracts having physiological activity, and extracts and fractions and purified products thereof are appropriately blended as necessary, and can be produced by a conventional method according to the dosage form.

The dosage form of the external preparation for skin of the present invention is arbitrary, and any of those used for conventional external preparations for skin such as a solubilizing system such as a lotion, an emulsifying system such as an emulsion or cream, or an ointment, a dispersion or a powder system. The dosage form is acceptable. Moreover, it is not limited to general skin cosmetics, but includes pharmaceuticals, quasi-drugs, medicinal cosmetics and the like. The use is not limited to basic cosmetics such as lotions, emulsions, creams and packs, makeup cosmetics such as foundations, toiletries such as shampoos, rinses, soaps and body shampoos, and bath preparations.

Hereinafter, the present invention will be described in more detail with reference to examples, but the present invention is not limited only to these examples.

(Examples 1-2)
A lotion was prepared according to the following formulation. That is, the prescription ingredients were stirred at room temperature and solubilized to obtain a lotion.
(Ingredient) (wt%)
(1) 1,3-butylene glycol 6.0%
(2) Glycerin 5.0%
(3) Essential component and comparative component 5.0%
(4) Pentylene glycol 3.0%
(5) Phenoxyethanol 0.5%
(6) Purified water residue

(Example 3)
Using a dull model using brown guinea pigs (30 weeks old), dullness improvement was tested using the lotions of Examples 1 and 2 and Comparative Examples 1 to 7 as specimens. The back of five brown guinea pigs was shaved and irradiated with 0.5 × MED (minimum erythema concentration) ultraviolet rays for 5 days to create a soot model. An application site of 2 cm × 2 cm on the back of the guinea pig was provided, and 0.01 mL / dose / day of the sample was applied for 8 weeks. As a control example, an essential component of the example skin lotion was replaced with purified water. The effect of improving dullness was compared with the average dullness of the control group 24 hours after the last application, +: markedly improved, +: clearly improved, ±: slightly improved,-: not improved Determination was made for each guinea pig. The results are shown in Table 3. Thereby, it turns out that the lotion of Example 1 and 2 which is the skin external preparation for dullness improvement of this invention is excellent in the dullness improvement effect with respect to a comparative example.

Example 4
A panel of 20 people from Haneda who suffered from dullness in Haneda with a grant of 40 years of age or older was collected, and a total of 80 people were collected, and the skin lotion of Examples 1 and 2 and Comparative Examples 4 and 6 was evaluated for dullness improvement. . Panelists asked to use it twice a day for 8 weeks, and evaluated skin dullness improvement on the basis of ++: markedly improved, +: clearly improved, ±: slightly improved,-: no improvement I got it. The results are shown in Table 3 as the number of appearance examples. Thereby, it was confirmed that the skin external preparation of this invention showed the remarkable improvement effect with respect to the skin which the dullness accumulated by the aging change, and was excellent in the effect | action which makes healthy youthful skin.

Furthermore, the formulation example of this invention is shown below.
(Example 5) Cream The following components (1) to (11), and separately the following components (12) to (24) are heated and dissolved at 75 ° C. to obtain A solution and B solution, respectively. Liquid B was added to liquid A, emulsified, and cooled with stirring to prepare a cream.
(Ingredient) (wt%)
(1) 3.0% olive oil
(2) Squalane 2.0%
(3) Methyl polysiloxane 0.5%
(4) Stearyl alcohol 0.5%
(5) Cetyl alcohol 0.5%
(6) Tri (capryl / capric acid) glyceryl 12.5%
(7) Glyceryl monostearate 5.0%
(8) 1.5% diglyceryl monostearate
(9) Decaglyceryl monostearate 3.0%
(10) Acetic acid dl-α-tocophenol 0.05%
(11) Preservative appropriate amount (12) Xanthan gum 0.1%
(13) α-Arbutin 0.3%
(14) Sohakuhi extract 3.0%
(15) Adenosine triphosphate disodium 0.05%
(16) Garlic extract 0.35%
(17) Chlorella extract 1.0%
(18) Button pi extract 1.0%
(19) Cuckoo extract 1.0%
(20) 1.0% soybean extract
(21) 1,3-butylene glycol 3.0%
(22) Glycerol 1.0%
(23) Preservative appropriate amount (24) Purified water residue

(Example 6) Emulsion The following components (1) to (10), and separately (11) to (19) are heated and dissolved at 75 ° C. to make A liquid and B liquid, respectively. The mixture was cooled with stirring to prepare an emulsion.
(Ingredient) (wt%)
(1) 1.0% olive oil
(2) Squalane 2.0%
(3) Behenyl alcohol 1.0%
(4) Tri (capryl / capric acid) glyceryl 2.0%
(5) Tetraglycerin condensed silinoleic acid 0.1%
(6) Propylene glycol monooleate 0.5%
(7) Glycerol monostearate 1.0%
(8) Hexaglyceryl monomyrestate 1.0%
(9) Decaglyceryl monomyristate 0.5%
(10) Preservative appropriate amount (11) Sakuhakuhi extract 2.0%
(12) Chlorella extract 1.0%
(13) Button pi extract 1.0%
(14) Aloe vera extract 2.0%
(15) 1.0% olive leaf extract
(16) Cuckoo extract 2.0%
(17) 1,3-butylene glycol 3.0%
(18) Preservative appropriate amount (19) Purified water residue

Claims (4)

The skin external preparation for dullness improvement characterized by containing the following (A)-(D).
(A) Sakuhakuhi extract having tyrosinase activity inhibitory action (B) Cell activator (C) Reactive oxygen scavenger (D) Estrogen-like agent The skin external preparation for dullness improvement according to claim 1, wherein the cell activator is at least one selected from deoxyribonucleic acid salt, disodium adenosine triphosphate, yeast extract, carrot extract, garlic extract and chlorella extract. 2. The skin external preparation for dullness improvement according to claim 1, wherein the active oxygen scavenger is one or more selected from a bitter melon extract, a tea extract, a button pi extract, and an olive leaf extract. The skin external preparation for dullness improvement according to claim 1, wherein the estrogen-like agent is at least one selected from soybean extract, cuckoo extract, Pueraria myrifica extract, and red clover extract.