JP2003002819A - Skin care composition - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain an 8-OHdG production inhibiting agent which can prevent or improve the formation of fine wrinkles and blots by restraining the production of 8-OHdG. SOLUTION: One or more 8-OHdG (8-hydroxydeoxyguanosine) production- inhibiting agents selected from the group consisting of a catechin and/or its glycosides, a flavone and/or its glycosides, a flavonol and/or its glycosides, a flavanone and/or its glycosides, an isoflavone and/or its glycosides, a coumarin and/or its glycosides and the extracts of plants selected from the genera Vitis, Plantago, Linum, Carthamus, Gossypium, Rosemary, Eucalyptus, Gnaphalium, Thymus, Syringa and Pinus and Banzakuro assort of pomegranate are characteristically compounded in cosmetics. The 8-OHdG production-inhibiting agent inhibits the production of 8-OHdG in DNA of cells by ultraviolet rays, and prevents or improves the formation of the fine wrinkles and blots.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention has an inhibitory action on 8-hydroxydeoxyguanosine (hereinafter abbreviated as 8-OHdG) production and prevents skin aging such as spots and wrinkles by preventing DNA damage due to ultraviolet rays. Or to improve cosmetics.

[0002]

2. Description of the Related Art Ultraviolet rays are deeply involved in the aging of the skin and are considered to be the cause of spots and wrinkles. That is,
It is considered that melanin is produced in the skin tissue of the skin by external stimuli such as ultraviolet rays, which promotes blackening of the skin and causes symptoms such as spots and freckles. Skin fibroblasts are damaged by active oxygen generated by ultraviolet rays and the production of collagen and hyaluronic acid is suppressed, causing wrinkles. As a method for confirming the skin whitening effect, it has been proposed to suppress the activity of tyrosinase involved in the production of melanin. Conventionally, as a substance that suppresses the activity of tyrosinase, an extract of a natural product such as a crude drug has been blended into cosmetics for whitening cosmetics. In addition, compounds such as ascorbic acid derivatives, glutathione, and colloidal sulfur are blended, and such whitening cosmetics have been used to obtain cosmetic effects such as preventing dark skin, stains and freckles on the skin. Further, α-hydroxy acids such as glycolic acid and crude drugs having a collagen production promoting action on fibroblasts have been incorporated into cosmetics for the prevention and improvement of wrinkles.

[0003]

However, the ascorbic acid derivative, which is expected to improve spots, is not easily expected to exhibit its effect because it is easily oxidized.
The blended cosmetics change color and odor over time. In addition, glutathione and colloidal sulfur have problems with their unique odor and stability, which hinders their commercialization. On the other hand, crude drugs are expected to be useful because of their high safety,
The whitening effect was still insufficient in many cases. Further, α-hydroxy acids such as glycolic acid, which is added in the hope of improving wrinkles, has strong skin irritation and it has been difficult to add a sufficient amount.

[0004]

Means for Solving the Problems As a result of intensive research to prevent and improve skin aging such as spots and wrinkles due to ultraviolet rays, the present inventor has suppressed the DNA damage of cells due to ultraviolet rays to We have found that it is possible to achieve the purpose. That is, 8-OHdG in the DNA base generated by ultraviolet rays acts on melanocytes to promote melanin production. Therefore, melanin production is suppressed by suppressing the production of 8-OHdG by ultraviolet irradiation. It was also discovered that suppressing the production of 8-OHdG would suppress the damage of DNA in cells to that extent and promote the production of collagen in fibroblasts, leading to the improvement of wrinkles. did. The present inventor, in order to solve the above problems, as a result of examining the 8-OHdG production inhibitory effect on various substances and plant extracts, catechins and / or glycosides thereof, flavones and / or glycosides thereof Body, flavonols and / or glycosides thereof, flavanones and / or glycosides thereof, isoflavones and / or
Or a glycoside thereof, a coumarin and / or a glycoside thereof,
Vitis genus, Plantago genus, Linum genus, Carthamus genus, Gossypium genus, rosemary (Rosmarinus) genus,
Genus Psidium, Eucalyptus
Genus, Gnaphalium, Thym
It has been found that the extract of plants belonging to the genus us), genus Syringa and genus Pinus has a desired effect,
The present invention has been completed.

That is, the present invention relates to catechins and / or glycosides thereof, flavones and / or glycosides thereof, flavonols and / or glycosides thereof, flavanones and / or glycosides thereof, isoflavones. And / or its glycoside, coumarins and / or its glycoside, Vitis (Vi
tis genus, Plantago genus, Linum
Genus, Carthamus, Gossypi
um), Rosemary (Rosmarinus), Pomedium (Psidium), Eucalyptus (Eucalyptus), Gnaphalium (Gnaphalium), Thymus (Thymus), Syringa (Syringa), and Pinus (Pinus) An extract containing one or more kinds of plants selected from the group consisting of extracts as an active ingredient 8-
An OHdG production inhibitor is provided.

The substances and plant extracts that can be used in the present invention are not particularly limited, and catechins and / or glycosides thereof include catechin, epicatechin, epigallocatechin, epigallocatechin gallate and the like.

Examples of flavones and / or their glycosides include luteolin, flavones and apigenin.

Examples of flavonols and / or their glycosides include quercetin, myricetin, kaempferol, quercitrin, rutin and the like.

Examples of flavanones and / or glycosides thereof include naringenin, hesperidin and naringin.

The isoflavones and / or their glycosides include genistein, daidzein, genistin and the like.

Coumarins and / or glycosides thereof include esculetin and the like.

[0012] Examples of plants belonging to the genus Vitis include grapes (Vitis vinifera L.).

Plantago genus plant (Plantago major L. var. Asiatica Q _ECAISNE ),
Ezo plantain (Plantago camtschatica Cham.Ex Lin
k) and the like.

As a plant of the genus Linum, flax (Linum)
usitatissimum L.) and the like.

Examples of plants belonging to the genus Carthamus include safflower (Carthamus tinctorius L.).

Cotton (Gossypium herbaceumL _INNAEUS ) and the like can be mentioned as a plant of the genus Gossypium.

As a plant belonging to the genus Rosemary (Rosmarinus), rosemary (Rosmarinus officinalis L.)
Etc.

Examples of plants belonging to the genus Psidium include guava (Psidium guajava L.) and the like.

Examples of plants belonging to the genus Eucalyptus include Eucalyptus globules L _ABILL .

Everlasting (Gnaphalium uliginosu) is a plant belonging to the genus Gnaphalium.
m L.) and the like.

[0021] Examples of plants belonging to the genus Thymus include wild thyme (Thymusserpyllum L.) and mussel (Thymus quinquecostatus Celak.).

Examples of plants belonging to the genus Syringa include lilac (Syringa vulgaris).

Examples of plants belonging to the genus Pinus include Pinus pinaster.

Catechins and / or glycosides thereof, flavones and / or glycosides thereof, flavonols and / or glycosides thereof, flavanones and / or glycosides thereof, isoflavones and As the glycoside, the coumarin and / or the glycoside thereof, commercially available reagents can be used. In addition, various solvents such as water; lower monohydric alcohols such as methyl alcohol and ethyl alcohol, from plants containing a large amount of these compounds;
Liquid polyhydric alcohols such as glycerin, propylene glycol and 1,3-butylene glycol; ketones such as acetone and methyl ethyl ketone; alkyl esters such as ethyl acetate; hydrocarbons such as benzene and hexane; ethers such as diethyl ether; dichloromethane, chloroform It is possible to use by extracting with one or more kinds of halogenated alkanes and the like, and then purifying and using it, and it is also possible to use those prepared from the above compound by chemical synthesis.

[0025] Also, the genus Vitis, plantago (P
genus lantago, genus Linum, Cartha
genus mus), genus Gossypium, genus Rosemarinus, genus Psidium, eucalyptus, Gnaphalium
Genus, Thymus genus, Syringa genus,
The part to be used of the plant belonging to the genus Pinus is not particularly limited, and each leaf, branch, stem, flower, fruit, root, seed, etc. or whole grass should be extracted using raw or dried ones. You can, but above all, Plantago
Genus, Linum genus, Carthamus genus,
Seeds are particularly suitable for the genus Gossypium, and bark is particularly suitable for the genus Pinus.

The preparation of the plant extract is not particularly limited,
For example, various suitable organic solvents can be used for extraction from a low temperature to a high temperature. As the extraction solvent, for example,
Water; lower monohydric alcohols such as methyl alcohol and ethyl alcohol; glycerin, propylene glycol, 1,
Liquid polyhydric alcohols such as 3-butylene glycol; ketones such as acetone and methyl ethyl ketone; alkyl esters such as ethyl acetate; hydrocarbons such as benzene and hexane; ethers such as diethyl ether; halogenated alkanes such as dichloromethane and chloroform One kind or two or more kinds can be used. Among them, water, ethyl alcohol, 1,3-butylene glycol, one or two
Mixtures of one or more solvents are particularly suitable.

The extraction method is not particularly limited, but if each plant is appropriately finely pulverized and dried, for example, it is 1 to 1000 times the weight ratio, particularly 10 to 10 times.
In the case of extraction at room temperature using 0 times the amount of solvent, 0 ° C or higher,
It is particularly preferable to carry out the treatment at 20 ° C. to 40 ° C. for 1 hour or longer, particularly 3 to 7 days. Moreover, you may heat-extract at 60-100 degreeC for 1 hour.

Each of the above-mentioned extracts obtained under the above conditions may be used as it is as an extracted solution, but if necessary, it may be subjected to a treatment such as filtration, concentrated and powdered to be used properly. Can be used.

The amount of the extract compounded in the cosmetic composition of the present invention is preferably 0.00001 to 20.0% by weight in terms of evaporative dry matter, and most preferably 0.01 to 10.0% by weight. is there.

The cosmetic composition of the present invention comprises, in addition to the above essential ingredients,
Aqueous component, oil component, plant extract, animal extract, powder,
Excipients, surfactants, oils, alcohols, pH adjusters,
Preservatives, antioxidants, thickeners, sweeteners, dyes, flavors and the like are mixed as necessary and prepared. The dosage form of the cosmetic of the present invention is not particularly limited, and a lotion,
Emulsion, cream, pack, powder, spray, ointment,
It can be made into various dosage forms such as a dispersion and a cleaning agent.

[0031]

[Examples] Hereinafter, test examples relating to the 8-OHdG production inhibitory effect of various extracts according to the present invention will be shown, and examples of application prescriptions to cosmetics using the materials will be described. It goes without saying that it is not limited to the examples.

(1) Preparation of sample solution and culture solution As sample solutions, catechin, epicatechin, epigallocatechin, epigallocatechin gallate, luteolin, flavone, apigenin, quercetin, myricetin, kaempferol, quercitrin, rutin, Naringenin,
Commercially available purchased reagents were used for hesperidin, naringin, genistein, daidzein, genistin, and esculetin. Grapes, plantain, psyllium, flax, safflower,
Cotton seeds, rosemary, guava, eucalyptus,
For everlasting, wild thyme, mussels and lilac, dried plant bark and bark of French coastal pine were powdered and soaked and extracted with 50% ethanol aqueous solution at 37 ° C. for one week. Dimethyl sulfoxide (DMS) was added to 100 mg of these reagents and the dried extract.
500 μl of O) and 9.5 ml of PBS (−) were added and dissolved to prepare a sample solution.

(2) Preparation of cells Human fetal skin keratinocytes (Clonetic) were used as cells.
The medium was cultured in a synthetic medium for keratinocytes manufactured by sigma. Human skin keratinocyte cells were cultured in a petri dish (50 cm ² ) having a diameter of 8 cm until confluent. The sample whose efficacy is to be measured is added at a pre-measured non-cytotoxic concentration and incubated for 3 hours. After 3 hours, the medium was removed and well washed with PBS (-) solution. After washing, 2 ml of PBS (-) was added, and the cells were irradiated with 20 mJ / cm ² of ultraviolet light. After irradiation, the cells are collected in an Eppendorf tube by trypsinization.

(3) Extraction of DNA from cells The DNA in the recovered cells was used as DNAExtr from Wako Pure Chemical Industries, Ltd.
Extracted by actor WB kit. 75 μl of distilled water was added to the extract, and the mixture was left at 4 ° C. for one day. After that, the solution was heated at 95 ° C for 5 minutes and then rapidly cooled, and 2M-sodium acetate buffer (PH4.
5) 1 μl and nuclease P ₁ 5 μl (10 units) were added and left at 37 ° C. for 1 hour. Next, 8 μl of 1M-Tris-HCl (PH7.5),
2 μl of alkaline phosphatase was added and left at 37 ° C. for 1 hour. After that, centrifugation was performed at 15,000 rpm for 3 minutes, and the supernatant was used as a sample for HPLC.

(4) Detection of 8-OHdG and 2-deoxyguanosine by HPLC A mobile phase was prepared by adding 80 ml of methanol and 50 ml of 0.2M sodium dihydrogen phosphate and adjusting the volume to 1 L with distilled water. Column is DAISOPAK (SP-120-5-ODS-BP) 150 mm ×
Using 6 mm, 8-OHdG was detected by an ESD detector under the following conditions. In addition, the detection of 2-deoxyguanosine is 290 nm
UV detector.

ECD detection conditions GUARD CELL INSTALLED E: 350mV CH 1: E150mV, R100μA, FILTER 2 SEC, OUTPUT   1 V, OFFSET 0% CH 2: E300mV, R 50nA, FILTER 10 SEC, OUTPUT 100mV, OFFSET 0%

[0037]

[Table 1] shows the results of suppressing the production of 8-OHdG by ultraviolet rays of various components. The production rate (%) of 8-OHdG was calculated by the following calculation.

[0038]

[Chemical 1]

[0039]

As shown in [Table 1], epicatechin, epigallocatechin gallate, flavone, myricetin, kaempferol,
Naringenin, naringin, genistein, genistin, esculetin, and grape, psyllium, psyllium, flax, safflower, cotton seed, rosemary, guava, eucalyptus, everlasting, wild time,
The extract of bark of Pleurotus cornucopiae, Lilac and French pine pine all showed a high inhibitory effect on 8-OHdG production.

[0040]

[Table 1]

Next, examples of formulation of cosmetics containing various components of the present invention will be shown, but the present invention is not limited thereto. Cosmetic prescription example

(1) Cosmetic cream (% by weight) a) Beeswax ... 2.0 b) Stearyl alcohol ... 5.0 c) Stearic acid ... 8.0 d) Squalane ... 10.0 e) Self-emulsifying glyceryl monostearate ... 3.0 f) Polyoxy Ethylene cetyl ether (20 E.O.)… 1.0 g) Grape (leaf) aqueous extract… 3.0 h) Kaempferol… 0.5 i) 1,3-butylene glycol… 5.0 j) Potassium hydroxide… 0.3 k) Preservatives Antioxidant: Appropriate amount l) Purified water: Remaining manufacturing method a) to f) are dissolved by heating and kept at 80 ° C. g) to l) are heated and dissolved, kept at 80 ° C, added to a) to f) and emulsified to 40
Cool to 0 ° C with stirring.

(1) Cosmetic cream (% by weight) a) Beeswax ... 2.0 b) Stearyl alcohol ... 5.0 c) Stearic acid ... 8.0 d) Squalane ... 10.0 e) Self-emulsifying glyceryl monostearate ... 3.0 f) Polyoxy Ethylene cetyl ether (20E.O.)… 1.0 g) Kaempferol… 0.5 h) 1,3-butylene glycol… 5.0 i) Potassium hydroxide… 0.3 j) Preservatives / antioxidants… Appropriate amount k) Purified water… The balance Processes a) to g) are dissolved by heating and kept at 80 ° C. h) to k) are melted by heating, kept at 80 ° C., added to a) to g) and emulsified,
Cool to 40 ° C with stirring.

(2) Emulsion (% by weight) a) Beeswax ... 0.5 b) Vaseline ... 2.0 c) Squalane ... 8.0 d) Sorbitan sesquioleate ... 0.8 e) Polyoxyethylene oleyl ether (20 E.O.) ... 1.2 f ) Epigallocatechin gallate ... 0.5 g) Guava (leaf) 50% 1,3-butylene glycol aqueous solution extract ... 2.0 h) 1,3-butylene glycol ... 7.0 i) Carboxyvinyl polymer ... 0.2 j) Potassium hydroxide ... 0.1 k) Purified water: the rest l) Preservative / antioxidant ... Appropriate amount m) Ethanol: 7.0 Dissolve by heating process a) to e) and keep at 80 ° C. f) to l) are melted by heating, kept at 80 ° C, added to a) to e) and emulsified to 50
Cool to 0 ° C with stirring. M) at 50 ℃, add 40 ℃
Cool down.

(2) Emulsion (% by weight) a) Beeswax ... 0.5 b) Vaseline ... 2.0 c) Squalane ... 8.0 d) Sorbitan sesquioleate ... 0.8 e) Polyoxyethylene oleyl ether (20 E.O.) ... 1.2 f ) French coastal pine (root) aqueous solution extract… 2.0 g) 1,3-butylene glycol… 7.0 h) Carboxyvinyl polymer… 0.2 i) Potassium hydroxide… 0.1 j) Purified water… balance k) Preservatives / antioxidants … Appropriate amount l) Ethanol… 7.0 Dissolve by heating process a) to e) and keep at 80 ℃. f) to k) are melted by heating, kept at 80 ° C, added to a) to e) and emulsified.
Cool to 0 ° C with stirring. L) at 50 ℃, add 40 ℃
Cool down.

(3) Lotion (% by weight) a) Everlasting (whole grass) 50% glycerin aqueous solution extract 1.0 b) Wild thyme (flower) 20% propylene glycol aqueous solution extract 1.0 c) Glycerin 5.0 d) Polyoxyethylene sorbitan monolaurate (20E.
O.)… 1.0 e) Ethanol… 6.0 f) Perfume… Appropriate amount g) Preservative / antioxidant… Appropriate amount h) Purified water… The rest of the manufacturing methods a) to h) are mixed and uniformly dissolved.

(3) Lotion (% by weight) a) Lilac (root) 20% ethyl acetate aqueous solution extract ... 1.0 b) Glycerin ... 5.0 c) Polyoxyethylene sorbitan monolaurate (20E.
O.) ... 1.0 d) Ethanol ... 6.0 e) Perfume ... Appropriate amount f) Preservative / antioxidant ... Appropriate amount g) Purified water ... Remaining manufacturing method a) to g) are mixed and uniformly dissolved.

(4) Packing agent (% by weight) a) Myricetin ... 1.0 b) Rosemary (stem) 20% ethanol aqueous solution extract ... 2.0 c) Vinyl acetate resin emulsion ... 15.0 d) Polyvinyl alcohol ... 10.0 e) Olive oil ... 3.0 f) Glycerin… 5.0 g) Titanium oxide… 8.0 h) Kaolin… 7.0 i) Ethanol… 8.0 j) Perfume… Appropriate amount k) Preservatives / antioxidants… Appropriate amount l) Purified water… Remaining process a) to l) Are mixed and well stirred and dispersed to homogenize.

(4) Packing agent (% by weight) a) Myricetin ... 1.0 b) Ethanol ... 8.0 c) Vinyl acetate resin emulsion ... 15.0 d) Polyvinyl alcohol ... 10.0 e) Olive oil ... 3.0 f) Glycerin ... 5.0 g) Titanium oxide … 8.0 h) Kaolin… 7.0 i) Perfume… Appropriate amount j) Preservative / antioxidant… Appropriate amount k) Purified water… The rest of the processes a) to k) are mixed, and well stirred and dispersed to homogenize.

[0050]

[Effect confirmation test] (1) Effect confirmation test on humans by application As test subjects, 15 women aged 20 to 50 years twice a day (morning, night) for 2 consecutive months, each of the invention product and the comparative product The state of the application site was compared before and after the test, and the improvement effect was investigated. For this test,

Using the cosmetics shown in, the comparative example

Grape (leaf) extract from the cosmetics shown in
A cosmetic excluding kaempferol was prepared and the effect of its application was investigated. While applying the cosmetic containing the active ingredient of the present invention every day, the pigmentation state and wrinkle state of the skin were summarized by questionnaires before the start of application and after 2 months of application to confirm the effect. Result is

[Table 2] shows.

[0051]

[Judgment criteria]

Marked effect: Skin spots and wrinkles were remarkably improved as compared with those before the start of application. Effective: Skin stains and wrinkles were improved compared to before application. Slightly effective: Skin stains / wrinkles were slightly improved compared to before application. Ineffective: There was no change compared to before application.

[0052]

[Table 2]

[0053]

As is clear from [Table 2], higher effects were observed in all cases as compared with the control product.

[0054]

As described in detail above, the cosmetic of the present invention has an excellent effect of suppressing 8-OHdG production, and is effective in preventing spots and wrinkles on the skin.

Continued front page    F-term (reference) 4C083 AA082 AA111 AA112 AB032                       AB052 AB242 AB442 AC012                       AC022 AC072 AC102 AC122                       AC182 AC242 AC422 AC442                       AC841 AC842 AD092 AD112                       BB51 CC04 CC05 CC07 DD23                       DD31 EE01 EE06 EE07 EE10                       EE16 EE17

Claims (4)

[Claims] 1. Catechins and / or glycosides thereof, flavones and / or glycosides thereof, flavonols and / or glycosides thereof, flavanones and / or glycosides thereof, isoflavones and / or A glycoside, coumarin and / or one or more glycosides 8-
A cosmetic comprising an OHdG (8-hydroxydeoxyguanosine) production inhibitor. 2. A genus of Vitis, Plantag
o) Genus, Linum genus, Carthamus
Genus, Gossypium, Rosemary
rinus), Pomedium (Psidium), Eucalyptus (Euca)
lyptus genus, Gnaphalium genus, Thymus genus, Syringa genus, Pinus (Pinu)
s) 1 or 2 or more extracts of plants belonging to the genus 8
A cosmetic composition comprising a -OHdG (8-hydroxydeoxyguanosine) production inhibitor. 3. Catechins and / or glycosides thereof are catechin, epicatechin, epigallocatechin, epigallocatechin gallate, flavones are luteolin, flavones, apigenin and / or glycosides thereof, and flavonols are quercetin, Myricetin, kaempferol and / or its glycosides, flavanones are naringenin, flavanones, hesperidin and / or its glycosides, isoflavones are genistein, daidzein and / or their glycosides, coumarins are esculetins and / or their The cosmetic according to claim 1, which is a glycoside. 4. A plant of the genus Vitis is grape (Vitis v).
inifera L.), Plantago genus plants are plantain (Plantagomajor L. var. asiatica Q _ECAISNE ), Ezo plantain (Plantago camtschaticaCham. Ex Lin
k), Linum plants are flax (Linumusitatissim)
um L.), Carthamus plant is safflower (Cart
hamus tinctorius L.), Gossypium plants are cotton (Gossypium _herbaceum L _INNAEUS ), and rosemary (Rosmarinus) plants are rosemary (Ro
smarinusofficinalis L.), plants belonging to the genus Psidium are guava (Psidium guajava L.), and plants belonging to the genus Eucalyptus are eucalyptus (Eucalypt).
usglobules L _ABILL .), Gnaphalium
Plants belonging to the genus Everlasting (Gnaphaliumulig
inosum L.), plants belonging to the genus Thymus are wild thyme (Thymus serpyllum L.), plants belonging to the genus Thymus quinquecostatus Celak., and syringa (Syringa).
lgaris), one or two plant extracts whose plants belonging to the genus Pinus are French coastal pines (Pinus pinaster)
The cosmetic composition according to claim 2, comprising at least one kind.