JP2011246354A5 - - Google Patents

Description

The present invention, cosmetics (including quasi-drugs) relates suitable skin external preparation etc., particularly, 1) Advanced Gurike Activation End Products (AGEs: Advanced glycation
The present invention relates to an external preparation for skin containing End-products) decomposition agent and 2) anti-wrinkle agent.

Wrinkles, age spots, dullness, aging skin, including slack, in addition to the accumulation of useless over di due to physical stimulation over the years, such as temperature changes and exposure to ultraviolet light, manifested with age by genetic factors . Wrinkles, sagging, skin aging phenomena such as dullness is a decrease and change in the skin structure by modification of the components, such as collagen fibers (Kola progestogen) and elastic fibers present in the skin (elastin), beams of skin loss At the same time, it is known to occur due to a decline in the motor function of facial muscles that create facial expressions. Furthermore, the skin aging phenomenon that progresses over a long time generally appears in a complicated form in which a plurality of aging symptoms are accumulated rather than single. For this reason, the deterioration of skin symptoms due to aging is a major concern for those who are concerned about keeping the beauty of the skin beautiful. Various researches are still being conducted in search of means for preventing or improving such deterioration of skin aging symptoms and regaining youthful skin.

With regard to prevention or improvement of wrinkle and sagging formation, analysis of the mechanism of action of wrinkle or sagging formation, and further research and development of anti-wrinkle agents and anti-aging agents based on information on the elucidated mechanism of action Has been done. The mechanism of action of wrinkle formation, exposure to ultraviolet rays cells Apoptosis over cis is enhanced by it and cell damage due to, matrix metalloproteinase protease (MMP) Kola progestogen by enhanced expression of the protease, such as such as It has already been reported that the fiber component is hydrolyzed, and further that the bundle of fibers is disrupted by the enhancement of cytokines. Many anti-wrinkle agents (see, for example, Patent Document 1 and Patent Document 2) have been developed based on information obtained by analyzing the mechanism of action of wrinkle formation. In particular, retinoic acid (see, for example, Non-Patent Document 1) is well known as a component having an effect of preventing or improving wrinkle formation. Retinoic acid has been approved as a therapeutic drug for wrinkles and acne in the United States, and its effectiveness has been proven . However, retinoic acid is not approved in Japan because there are major problems in terms of safety, including irritation to the skin. Also, pre Bomata against wrinkle formation than retinoic acid as the component having improved activity, anti-wrinkle agents (e.g., see Patent Document 3), Kola progestogen production promoter (e.g., see Patent Document 4), Hyaluronic acid production promoters (see, for example, Patent Document 5) are known. Further, triterpene acids, or, it is attached to the benzyl derivative, to wrinkles formed by the collapse of the dermis Kola progestogen fiber bundle caused by light irradiation, and rebuild the dermal Kola progestogen fiber bundle structure, the improvement It is known to show (see, for example, Patent Document 6). However, some of the above-mentioned ingredients having a preventive or ameliorating effect on wrinkle formation have problems in terms of stability, safety, etc. in addition to their medicinal properties, and in reality, sufficient preventive or ameliorating effects cannot be obtained. Also exist. For this reason, in addition to the creation of components that prevent or improve the formation of new wrinkles or sagging, there are expectations for components that enhance the effects of existing anti-wrinkle agents. In recent years, in view of the situation where it is difficult to create new active ingredients, it is desired to develop ingredients and formulation techniques that effectively enhance the action of anti-wrinkle agents and the like. Also attached to the sheet ring formation, also with the accumulation of AGEs, are Ime chromatography di these phenomena give the appearance impression of the skin increases, these factors, while relevant, is independent part Considering the existence of the skin, it is desired to improve both of these two factors to realize beautiful skin. Furthermore, the appearance of a component that can dramatically improve the appearance of skin symptoms by simultaneously improving the worsening of other skin symptoms as well as prevention or improvement of wrinkle formation is eagerly desired.

On the other hand, in 1912, L. C. Advanced glycation end-products (AGEs), which are final products generated by non-enzymatic condensation reactions of amino acids and reducing sugars, discovered by Mallard, have several tens of compounds (for example, Crosslin, pyropyridine, pentosidine, pyralin, carboxymethyllysine, etc.) exist and are known to exhibit various properties. Diseases AGEs is implicated, diabetic vascular complications, arteriosclerosis, there are known various diseases such as Alzheimer's disease (e.g., see Non-Patent Document 2). Regarding skin, the presence of AGEs in the epidermis (for example, see Patent Document 7) and dermis (for example, see Patent Document 8) is already known. Furthermore, it is known that an effect of preventing or improving skin aging by suppressing the production of dermal AGEs (see, for example, Patent Document 9) is obtained, but AGEs are present in the stratum corneum, and The work was not known at all. Furthermore, it is possible to prevent or improve wrinkle formation by including an AGE decomposition agent, in particular, an ingredient having an action of reducing the amount of AGEs present in the epidermis and / or dermis, and an anti-wrinkle agent in an external preparation for skin. It has not been known at all to improve the appearance of the skin by improving the skin aging phenomenon such as the transparency of the skin. Further, a method of measuring AGEs in the skin using fluorescence is known (see, for example, Patent Document 10).

Development technology for anti-aging, whitening and moisturizing cosmetics, CM Publishing, supervised by Masato Suzuki Edited by Shoichi Yamagishi, forefront of AGEs research Current status of glycated protein-related disease research (Medical Review, P231, (2004)

The present invention has been made under such circumstances, have the effect of significantly improving the appearance Ime over di-, and to provide a suitable topical skin preparation for beautiful skin.

In view of such circumstances, the present inventors have seeking composition suitable for beautiful skin, a result of repeated extensive studies, 1) Advanced Gurike Activation End Products (AGEs: Advanced Glycation End-products It has been found that a composition comprising a) a degrading agent and 2) an anti-wrinkle agent is excellent in skin beautifying action, and has completed the present invention. The present invention is as follows.
<1> 1) Advanced Gurike Activation End Products (AGEs: Advanced Glycation and End-products) decomposer, 2), characterized in that it contains an anti-wrinkle agent, a skin external preparation.
<2> The skin external preparation according to claim 1, wherein the AGEs decomposing agent comprises the following plant extract.
(Plant) Oleaceae olive genus, Saxifragaceae Saxifraga, Rosaceae Potenchira genus, Rosaceae Potentilla, leguminous asparagus-to-scan genus Rosaceae filipendula, Asteraceae Artemisia, and legume Astragalus plants belonging to <3> said of Oleaceae olive genus, Saxifragaceae Saxifraga, Rosaceae Potenchira genus, Rosaceae Potentilla, leguminous asparagus-to-scan genus Rosaceae filipendula, Asteraceae Artemisia, and plants belonging to the legume Astragalus There, each Oleaceae olive species olive, Saxifragaceae Saxifraga saxifrage, Rosaceae Potenchira genus Torumenchira, Rosaceae Potentilla Kawarasaiko, Rosaceae Potenchira genus Miyama Kinbae, leguminous asparagus-to-scan genus rooibos, Rosaceae filipendula Shimotsukesou , Asteraceae mugwort genus mugwort, and leguminous genus The external preparation for skin according to <1> or <2>, characterized in that it is a gypsum.
<4> The external preparation for skin according to any one of <1> to <3>, wherein the AGEs degrading agent has a degrading action of AGEs present in the horny layer of the skin.
<5> The anti-wrinkle agent, vitamin A, its derivatives and pharmaceutically acceptable salts thereof pharmacologically, triterpenic acids, their derivatives and pharmaceutically acceptable salts thereof pharmacologically and dermal Kola progestogen fibers The skin external preparation according to any one of <1> to <4>, wherein the skin external preparation is at least one selected from the group consisting of plant extracts having a bundle restructuring action.
<6> Vitamin A or a derivative of it, retinol Lumpur, retinal Lumpur, retinoic acid, tretinoin, isotretinoin, retinoic acid tocopherol Lumpur, palmitate retinol Lumpur, acetate retinoic Lumpur, and hydrogenated Retino over The external preparation for skin according to <5> , wherein the external preparation is one or more selected from the above.
<7> triterpene acid residue of the triterpene acids and derivatives thereof are, Urso Lumpur acid,
It is betulinic acid or the residue of those acids, The skin external preparation as described in <5> characterized by the above-mentioned. <8> The topical skin preparation according to <7>, wherein the triterpenic acid and a derivative thereof are triterpenic acid, triterpenic acid benzyl ester, or triterpenic acid phosphoric ester.
<9> plant extracts with dermal Kola progestogen fascicles restructuring action of said, characterized in that at one of two or more selected from plant extracts shown below, according to <5> Topical skin preparation.
<Plant extract having a dermal Kola progestogen fiber bundle reconstruction action>
A plant extract obtained from the Myrtaceae spp. family Hypericum plant extract obtained from Tomoesou, plant extract obtained from Caprifoliaceae Sambucus Sambucus nigra, plant extract obtained from Asteraceae centaurea cornflower, and plant extracts obtained from Labiatae rosemary Shokuro over Zumari over Item <10> The skin external application according to any one of <1> to <9>, wherein the AGEs decomposing agent is contained in an amount of 0.0001% by mass to 10% by mass with respect to the total amount of the external preparation for skin. Agent.
<11> The skin external preparation according to any one of <1> to <10>, wherein the anti-wrinkle agent is contained in an amount of 0.00001% by mass to 15% by mass with respect to the total amount of the external preparation for skin. .
<12> The external preparation for skin according to any one of <1> to <11>, which is for beautiful skin.
<13> The skin external preparation according to <12>, wherein the skin beautifying action is an action for preventing or improving sagging or wrinkle formation.
<14> The external preparation for skin according to <12>, wherein the skin beautifying effect is an effect of improving skin transparency.
<15> The skin external preparation according to any one of <1> to <14>, which is in the form of a water-in-oil emulsifier .
<16 > In the skin of a person who should use cosmetics, when the fluorescence generated from the skin by excitation light is measured and the amount of AGEs in the skin estimated from the fluorescence intensity is large, it should be used by that person The external preparation for skin according to any one of <1> to < 15 >, which is a cosmetic. < 17 > In the skin of a person who should use cosmetics, when a replica of the skin surface is prepared and the shape of the skin groove and skin is analyzed, the difference between the skin groove and skin is small, and the skin is severely disconnected. The skin external preparation according to any one of <1> to < 15 >, which is a cosmetic to be used by the person having the characteristics described above.
< 18 > The skin external preparation described in any one of <1> to < 17 >, which is used in the following mode.
(1) than people trying to use the cosmetics, the corneocytes taken by tape over TOPS stripping method, irradiated with excitation light, the intensity of fluorescence produced is measured, the AGEs amount of the stratum corneum intracellular Estimate and discriminate whether the amount is larger or smaller than the average amount.
(2) From the person who wants to use cosmetics, make a replica of the skin surface, analyze the shape of the skin groove and skin, and the difference between the skin groove and skin is small, and there is a large disconnection. In this case, it is a candidate for a cosmetic user.
(3) A person who is a candidate for both (1) and (2) is a cosmetic user.

<AGEs decomposition agent of the present invention>
Meira over de reaction is a reaction for amino acid and reducing sugar brown pigment produced by heating. Glycation, the amino group of the carbonyl group and the amino acid of reducing sugars after the formation of the Schiff base, via the enamino Lumpur, an initial step of generating a stable Amadori compound Amadori rearrangement, later, dehydration, hydrolysis Decomposition and cleavage between carbons produce α-dicarbonyl compounds, then saccharification by decomposition of α-dicarbonyl compounds, Schiff bases, Amadori compounds, aldehydes derived from lipid peroxidation, and auto-oxidation and decomposition of sugars It can be categorized into the late stage in which final products (AGEs) are generated. AGEs is a general term for products generated as a result of the saccharification reaction, and does not mean a single compound. In addition, the saccharification reaction causes a physical or physiological change by forming a disordered cross-linking structure between the protein in the body and the molecule or in the molecule in the process leading to the generation of AGEs of the final product. It is known that the saccharification reaction is deeply involved in factors such as dullness of skin color, elasticity, skin beautification such as skin texture, and whitening factors. For this reason, a component having a dermal AGEs degrading action has an action of preventing or improving skin symptoms involving pigmentation such as dullness by suppressing the saccharification reaction.

The external preparation for skin of the present invention is characterized by containing 1) an AGEs degrading agent and 2) an anti-wrinkle agent. As the AGEs decomposing agent of the present invention, any component having an action of reducing the amount of AGEs can be applied without particular limitation, and more preferably, it has an action of reducing the amount of AGEs present in the stratum corneum. The component which has can be illustrated suitably. The AGEs decomposing agent of the present invention includes components having an action of suppressing the production of AGEs produced by a saccharification reaction, in addition to components having an action of degrading the produced AGEs. As the AGEs decomposing agent of the present invention, for example, measurement of the CC bond cleavage ability of AGEs decomposition evaluation (alpha-diketones as described in JP-A-2007-161662, glucose - bovine serum albumin AGEs resolution The component which shows AGEs decomposition | disassembly action in measurement) can illustrate suitably. The component having AEGs decomposing action in the AGEs decomposing action evaluation is calculated from the amount of 1-phenyl-1,2-propanedione in the measurement evaluation of CC bond cleavage ability of α-diketones in the AEGs degrading action evaluation. theoretical amount of acid relative to that, the amount of acid that is actually generated, material is 40% or more, or, glucose - in the measurement evaluation of bovine serum albumin AGEs resolution, with AGEs decomposition rate of 15% or more It means a substance. According to the present inventors, as a component having a AGEs decomposing action in such evaluation systems, Oleaceae olive genus, Saxifragaceae Saxifraga, Rosaceae Potenchira genus, Rosaceae Potentilla, leguminous asparagus toe scan genus, Rosaceae filipendula, Asteraceae Artemisia plant extract obtained from leguminous Astragalus belongs plants can preferably exemplified, more preferably, Oleaceae olive genus olive, Saxifragaceae Saxifraga saxifrage, Rosaceae Potenchira genus Torumenchira Preferable examples include plant extracts obtained from rosaceae genus Kawara psycho, rosaceae potentia spp. Further, among the components having the AGEs decomposition action, a horny layer AGEs decomposition agent can be preferably exemplified as a more preferable one. As the stratum corneum AGEs decomposing agent, for example, a component having an AGEs decomposing action in the human stratum corneum or a component having an action of suppressing the production of AGEs in the human stratum corneum can be suitably exemplified. The component having a AGEs decomposition present in such human stratum corneum in, for example, in AGEs decomposition evaluation in human stratum corneum in Japanese Patent Application No. 2009-154495, the stratum corneum samples taken from panelists over, It reacts with anti-AGE antibodies, detects the reaction sites, and has the action of decomposing AGEs present in the stratum corneum when there are clearly fewer reaction sites in the presence of AGEs-decomposing agent than in the absence of coexistence. It can be called an ingredient. As the component having the effect of inhibiting the formation of AGEs in such human stratum corneum in, in AGEs formation inhibitory evaluation in human stratum corneum in, allowed to horny layer specimen at 37 ° C. is immersed in glucose solution When AGEs are generated, a component having an action of suppressing the generation of AGEs in the stratum corneum when there are clearly fewer reaction sites in the coexistence with the AGEs decomposing agent than in the non-coexistence is preferable. I can do it. According to the study of the present inventor, the component having an action of degrading AGEs in the human stratum corneum or the component having an action of suppressing the production of AGEs in the human stratum corneum is obtained from a plant belonging to the leguminous genus genus. The plant extract obtained from leguminous genus Astragalus can be preferably exemplified.

The AGEs decomposing agent of the present invention means a simple chemical substance or an extract obtained from an animal or a plant, and the skin external preparation can contain only one kind of such ingredients, or two or more kinds. It can also be contained in combination. Here, the plant extract of the present invention means a general term for the extract itself, the fraction of the extract, the purified fraction, the extract or fraction, and the solvent-removed product of the purified product. Examples of such AGEs decomposing agent, according to the study by the present inventors, Oleaceae olive genus, Saxifragaceae Saxifraga, Rosaceae Potenchira genus, Rosaceae Potentilla, leguminous asparagus-to-scan genus Rosaceae filipendula, Asteraceae Artemisia, leguminous Astragalus belongs can preferably exemplified plant extract obtained from plants, and more preferably, Oleaceae olive genus olive, Saxifragaceae Saxifraga saxifrage, Rosaceae Potenchira genus Torumenchira, Rosaceae A plant extract obtained from the genus Alaska spp., Rosaceae Potentilla spp., Rabbits Aspartus rooibos, Roses Psyllium spp., Chrysanthemum spp., Leguminous genus Astragalus, and more preferably Legumes Astragalus The plant extract obtained more can be suitably exemplified, and further Preferably, the plant extract obtained from the leguminous genus Astragalus can be illustrated suitably. The plant extract obtained from the leguminous genus Astragalus is superior in AGEs degrading action, in particular, epidermal AGEs degrading action.

Among plant extracts with AGEs decomposition of the, Oleaceae olive genus olive is evergreen tree of North Africa native, fruits are used as a cage over Buoiru and pickles. In Japan, it is cultivated on Shodoshima in Kagawa Prefecture. Yukinosita is a evergreen perennial plant originating in China and Japan and is used as a folk medicine. In Japan, it is cultivated in a wide area from Hokkaido to Kyushu. Rosaceae Potenchira genus Torumenchira is a perennial that is distributed to the yaw Europe, there is an effect and antibacterial action to tighten the skin. The rose family Potentilla spp. Is a perennial alpine plant that grows in China's native gravel and grassland. In Japan, it grows in the north of Honshu, Hokkaido, the Kuril Islands, etc. In Japan, the Rosaceae is a perennial that grows on sunny rivers and sands in Honshu, Shikoku, and Kyushu. The whole plant is called whitening herb and the root is red saiko, and it is used as an antipyretic medicine. Legume asparagus-to-scan genus rooibos is a plant with a conifer-like leaves that grows naturally only in Sedaruba Hague Mountains zone that extends to the north of Nishike-loop State of the Republic of South Africa, the leaves are dried used in the health tea. Rosaceae is a perennial small shrub native to Japan and China, and is native to Honshu, Shikoku, and Kyushu west of Kanto. Asteraceae Artemisia is a cold-tolerant perennial plant native to Europe and North Africa, and has long been used in Japan, such as grassy mochi and rice cake mushrooms. In Japan, it grows in a wide range from Honshu to Kyushu and Okinawa. The leguminous genus Astragalus is a biennial plant native to China and is known to have diuretic and antipyretic effects. It is cultivated throughout Japan.

As the extraction solvent used for producing the plant extract, preferably a polar solvent, water, ethanol, isopropyl alcohol, alcohol such as butanol, 1,3-butanediol Lumpur polyhydric alcohol such as polypropylene glycol, ketones such as acetone and methyl ethyl ketone, diethyl chromatography ether, one to be selected from the error over ethers, such as tetrahydrofuran 2 or more kinds suitably be exemplified.

Ingredients having AGEs-degrading action obtained from the above-mentioned plant extract in the present invention may be prepared by using plants grown in Japan or grown in Japan, as well as Japanese herbal medicine raw materials. It is also possible to purchase and use commercially available extracts sold by companies that handle plant extracts such as Maruzen Pharmaceutical Co., Ltd. In the extraction, it is preferable to process the plant body, the above-ground part or the tree trunk part in advance so as to improve the extraction efficiency by crushing or chopping. For the extract, 1 to 30 parts by mass of a solvent is added to 1 part by mass of the plant body, the above-ground part or its dried product, and immersed for several days at room temperature and for several hours at a temperature near the boiling point. After the immersion, the solution can be cooled to room temperature, insoluble matter can be removed if desired, and then the solvent can be removed by concentration under reduced pressure. Thereafter, fractionated purified such by column chromatography packed with silica gel or ion exchange resin, it is possible to obtain the desired extract.

<Method for Oleaceae olive genus cage over Buyori resulting extract of the present invention>
Was added 50% ethanol aqueous solution 5L leaves 3kg of olive, heated under reflux for 2 hours, and concentrated under vacuum to give remove insolubles by filtration, the sediment over Buyori plant extract obtained according to the present invention was obtained 44 g.

<The manufacturing method of the plant extract obtained from the saxifrage family Yukinosita genus Yukinoshita of this invention>
Leaves 3.5kg of saxifrage 50% ethanol aqueous solution 6L added, heated under reflux for 2 hours,
Insoluble matter was removed by filtration and the filtrate was concentrated under reduced pressure to obtain 41 g of a plant extract obtained from Yukinoshita of the present invention.

<The manufacturing method of the plant extract obtained from the rose family Potentilla genus Tormentilla of this invention>
The dried product 100g of whole plant of the Rosaceae family Potenchira genus Torumenchira After minced, 3 hours by addition of 50% ethanol solution of 500 mL, heated to reflux, after removing insoluble matter by cooling after filtration, vacuum Concentrated and then freeze-dried to obtain plant extract 1. Thereafter, 200 mL of water and 200 mL of ethyl acetate are added to the plant extract 1, liquid-liquid extraction is performed, the ethyl acetate phase is taken and concentrated under reduced pressure, and the plant extract obtained from the Rosaceae Potentilla Tormensilla of the present invention is obtained. Obtained.

<The manufacturing method of the plant extract obtained from the rosaceae genus Kawara-saiko of the present invention>
The dried product 100g of whole plant of the family Rosaceae Potentilla Kawarasaiko After minced, 3 hours by addition of 50% ethanol solution of 500 mL, heated to reflux, after removing insoluble matter by cooling after filtration, vacuum Concentrated and then lyophilized to obtain plant extract 2. Thereafter, 200 mL of water and 200 mL of ethyl acetate are added to the plant extract 2, liquid-liquid extraction is performed, the ethyl acetate phase is taken and concentrated under reduced pressure, and the plant extract obtained from the Rosaceae genus Kawarasaico of the present invention is obtained. Obtained.

<The manufacturing method of the plant extract obtained from the rose family Potentilla spp.
The dried product 100g of whole plant of the Rosaceae family Potenchira genus Miyamakinbai After minced, 3 hours by addition of 50% ethanol solution of 500 mL, heated to reflux, after removing insoluble matter by cooling after filtration, vacuum Concentrated and then freeze-dried to obtain plant extract 3. Thereafter, 200 mL of water and 200 mL of ethyl acetate are added to the plant extract 3, liquid-liquid extraction is performed, the ethyl acetate phase is taken and concentrated under reduced pressure, and the plant extract obtained from the Rosaceae potentia spp. Obtained.

<The manufacturing method of the plant extract obtained from the leguminous aspartus genus rooibos of this invention>
The dried product 100g leaves legume asparagus toe scan genus rooibos, after minced, 3 hours by addition of 50% ethanol solution of 500 mL, heated to reflux, after removing insoluble matter by cooling after filtration, vacuum Concentrated and then lyophilized to obtain Extract 4. After that, 200 mL of water and 200 mL of ethyl acetate are added to the extract 4, liquid-liquid extraction is performed, the ethyl acetate phase is taken and concentrated under reduced pressure, and the plant extract obtained from the leguminous Aspartus rooibos of the present invention is obtained. Obtained.

<The manufacturing method of the plant extract obtained from the Rosaceae genus Shimoke of the present invention>
The dried product 100g of whole plant of the Rosaceae family Potenchira genus Shimotsukesou After minced, 3 hours by addition of 50% ethanol solution of 500 mL, heated to reflux, after removing insoluble matter by cooling after filtration, vacuum Concentrated and then lyophilized to obtain Extract 5. Thereafter, 200 mL of water and 200 mL of ethyl acetate are added to the extract 5, liquid-liquid extraction is performed, and the ethyl acetate phase is taken and concentrated under reduced pressure to obtain a plant extract obtained from the genus Rosaceae of the present invention. It was.

<The manufacturing method of the plant extract obtained from the asteraceae Artemisia mugwort of this invention>
The dried product 100g of whole plant of the family Asteraceae Artemisia Artemisia, after minced, 3 hours by addition of 50% ethanol solution of 500 mL, heated to reflux, after removing insoluble matter by cooling after filtration, vacuum Concentrated and then lyophilized to obtain Extract 6. Thereafter, 200 mL of water and 200 mL of ethyl acetate are added to the extract 6, liquid-liquid extraction is performed, and the ethyl acetate phase is taken and concentrated under reduced pressure to obtain a plant extract obtained from the asteraceae Artemisia sp. It was.

<The manufacturing method of the plant extract obtained from the leguminous genus Astragalus of this invention>
The dried product 1 kg of whole plant and seeds of Leguminosae Astragalus Rengesou chopped, 10 L ethanol was added and was immersed overnight at 50 ° C. below the temperature, removing the insolubles by filtration by obtain an extract which is ethanol solution extract.

<Test Example 1: AGEs degradation action evaluation 1 (measurement of CC bond cleavage ability of α-diketone)>
22 mM 1-phenyl-1,2-propane dione / methanol + 0.1 M phosphate buffer (pH 7.4) and 1 mL, plant extracts of the invention (Oleaceae olive genus cage over Buyori resulting plant Extracts, plant extracts obtained from the genus Yukinosita, Yukinosita, plant extracts obtained from the genus Rosaceae, Tormentilla, plant extracts obtained from the moss, Pseudosidae, plant extracts obtained from the genus Rosaceae , Plant extract obtained from leguminous aspartus rooibos, plant extract obtained from rosaceae genus genus shimoke, plant extract obtained from asteraceae genus mugwort, plant extract obtained from legume genus genus 1 mL was mixed and reacted at 37 ° C. for 10 hours, and the amount of benzoic acid was determined by HPLC. It was quantified.
(HPLC conditions)
Analysis conditions Detector: Ultraviolet absorptiometer (measurement wavelength: 260 nm)
Column: Tosoh over TSK-ODS80TsQA
Column temperature: room temperature moving bed: glacial acetic acid 2 g / acetonitrile 500 mL + edetate disodium solution (1 → 250) 500 mL
Flow rate: 1 mL / min

With the AGEs decomposing agent of the present invention described above, AGEs decomposing action evaluation (measurement of CC bond cleavage ability of α-diketone) was performed according to the method described in Test Example 1. Cutting ability of plant extracts with AGEs decomposition of the present invention, Oleaceae olive genus cage over Buyori plant extract obtained (29%), plant extracts obtained from Saxifragaceae Saxifraga saxifrage (35% ), A plant extract (32%) obtained from the rose family Potentilla genus Tormentilla, a plant extract (29%) obtained from the Rosaceae genus Kawara Psycho, a plant extract (34%) obtained from the Rosaceae Potentilla spp. Plant extract obtained from leguminous aspartus rooibos (25%), plant extract obtained from rosaceae spruce spruce (37%), plant extract obtained from asteraceae mugwort mugwort, legumes It was a plant extract (43%) obtained from the genus Astragalus. The AGEs decomposing agent of the present invention was found to have an excellent AGEs decomposing action.

<Test Example 2: AGEs decomposition Evaluation 2 (glucose - measured in bovine serum albumin AGEs resolution)
>
AGEs decomposition action evaluation was implemented using the following test materials.
AGE-BSA: glucose and bovine serum albumin (BSA) and incubate preparative least 12 weeks at 37 ℃, PD-10 columns ( Amersham Biosciences 17-0851-01) at extra <br/> glucose Primary antibody: Anti-Albumin, Bovine Serum, Rabbit-Poly ROCKLAND 201-41331 / 20000, secondary antibody: Goat anti-rabbit IgG horseradish peroxidase conjugate BioRAD 170-65151 / 10000, substrate: TMB solution Wako 546-01911
(procedure)
Type I Kola over Genko and reports open 96-well microplate over preparative (Bio Coat 35 4407)
100 μL of 10 μg / mL AGE-BSA was added to the sample, and 1.0 μg (AGE-BSA / well) was allowed to stand at 37 ° C. for 4 hours, and then washed three times with 0.05% Tween 20 / PBS (−) (micro room temperature on a mixer, 3 minutes shaken), PBS (- samples) were dissolved in a concentration (1 × 10 ^-4%) 100
Add μL and react at 37 ° C. for 10 hours or longer. Thereafter, 0.05% Tween 20 / PBS (−)
After washing 3 times, add 100 μL / well of the primary antibody to each well and let stand at room temperature for 30 minutes. Wash 3 times with 0.05% Tween20 / PBS (−) and add 100 μL / well of secondary antibody.
And let stand at room temperature for 30 minutes. Wash 3 times with 0.05% Tween20 / PBS (−), add 100 μL / well of TMB, and react at room temperature for 15 minutes. 1N hydrochloric acid is added at 100 μL / well, the reaction is stopped, and the absorbance at 450 nm is measured. The amount of AGEs was changed, a calibration curve was drawn, and the amount of residual AGEs was quantified from this calibration curve. The AGEs decomposition rate was calculated by subtracting the remaining AGEs from the added AGEs, dividing by the added AGEs, and multiplying by 100.

With the AGEs decomposer of the present invention described above, AGEs decomposition evaluation according to the method described in Test Example 2 - it was carried out (glucose measurements of bovine serum albumin AGEs resolution). Glucose plant extracts with AGEs decomposition of the present invention - bovine serum albumin AGEs resolution, Oleaceae olive genus cage over Buyori plant extract obtained (25%), obtained from Saxifragaceae Saxifraga saxifrage Plant extract (28%), plant extract (24%) obtained from the rose family Potentilla genus Tormentilla, plant extract (28%) obtained from the rose family Potato genus Kawara psycho, plant obtained from the Rosaceae potentia genus Extract (31%), plant extract obtained from leguminous aspartus rooibos (24%), plant extract obtained from rosaceae spruce spruce (32%), plant extract obtained from Asteraceae mugwort (33%), a plant extract (37%) obtained from leguminous genus Astragalus. The AGEs decomposing agent of the present invention was found to have an excellent AGEs decomposing action.

<Test Example 3: Evaluation of AGEs production inhibitory action in human stratum corneum>
AGEs in the stratum corneum can be detected as follows. Performed corneum collected by tape over TOPS stripping using commercially available adhesive tape or the like from the skin, was treated half a day with a solvent to remove the adhesive tape portion. The obtained stratum corneum is subjected to immunohistochemical staining, and the stained stratum corneum specimen is observed under a microscope. The results are shown in FIG. Preferred examples of the solvent include organic solvents, particularly xylene. As conditions for immunohistochemical staining, primary antibody (anti AGE monocronal antibody (mouse) TransGenic KH001), biotinylated secondary antibody (Biotin-Rabbit Anti Mouse IGg conjugate ZYMED 81-6740), ABC reagent (RTU VECTASTAIN Elite ABC REAGENT BECTOR PK -7100) and AEC substrates (ENVISION kit / HRP (AEC) Dako K3464). As a control, it was prepared immersed corneum sample 70% ethanol solution. The stratum corneum samples are immersed in 70% ethanol solution of 100mM glucose. Further, AGEs were detected after standing for 8 days at 37 ° C. in the presence or absence of 0.1% plant extract obtained from the leguminous genus Astragalus, which is the AGEs decomposing agent of the present invention. In the non-presence of a plant extract obtained from Leguminosae Astragalus Rengesou clearly reaction site compared to the control lot, AGEs by glucose was found to have produced. In the presence of 0.1% plant extract obtained from the leguminous genus Astragalus, there are clearly fewer reaction sites than in the absence, and the plant extract obtained from the leguminous genus Astragalus AGEs in the human stratum corneum It was found to have a production inhibitory effect. This degree can be quantified by the ratio of the existing area of the label, and the existing ratio of the label can be easily quantified by a score or the like as will be described later. The results are shown in FIG.

<Anti-wrinkle agent of the present invention>
The external preparation for skin of the present invention is characterized by containing 1) an AGEs degrading agent and 2) an anti-wrinkle agent. The anti-wrinkle agent of the present invention can be applied without particular limitation as long as it has a preventive or ameliorating action against wrinkle formation, and more preferably vitamin A or a derivative thereof and / or their pharmacology acceptable salts, triterpenic acids or triterpene acid derivatives and / or their pharmacologically acceptable salts, furthermore, such a plant extract having a dermal Kola progestogen fascicles reconstruction action appropriately illustrated can . The preventive or ameliorating action for wrinkle formation possessed by the anti-wrinkle agent of the present invention includes a preventive or ameliorating action for wrinkles that are formed or wrinkles that are in the process of formation, in addition to the improving action for wrinkles that have already been formed. The As the mode of action anti-wrinkle agent of the present invention has, hyaluronic acid production promoting action, Kola progestogen production promoting action, matrix metalloproteinase protease inhibitory effect, acting through the dermis Kola progestogen fascicles restructuring action and the like The mechanism is estimated. The AGEs decomposition agent is added to the skin external preparation together with the anti-wrinkle agent, thereby enhancing the prevention or improvement action against wrinkle formation of the anti-wrinkle agent, and at the same time, improving skin symptoms such as skin transparency. Overall, it is excellent in action to prevent or improve skin aging symptoms. Any anti-wrinkle agent having a preventive or ameliorating action against wrinkle formation can be included in the external preparation for skin of the present invention. from the surface to improve the overall skin aging by improving skin conditions such as transparency, particularly preferred are anti having an action of preventing or ameliorating the disorder of the collapse or the structure of the dermis Kola progestogen fiber bundles wrinkle agent, specifically, acceptable salt triterpenic acid or triterpene acid derivatives and / or their pharmacologically, plant extracts having dermal Kola progestogen fascicles reconstruction action suitably be exemplified.

With regard to the anti-wrinkle agent of the present invention, vitamin A, its derivatives and / or their pharmacologically acceptable salts, triterpenic acid or triterpenic acid derivatives and / or their pharmacologically acceptable ones are particularly preferred. salts, such as plant extracts having dermal Kola progestogen fascicles reconstruction action suitably be exemplified. The vitamin A, among the derivatives and / or a pharmaceutically acceptable salt thereof pharmacologically, as is preferred, retinoic Lumpur, its derivatives and / or their pharmacologically acceptable salts, retinal Lumpur , Its derivatives and / or their pharmacologically acceptable salts, retinoic acid, their derivatives and / or their pharmacologically acceptable salts, etc. if, retinoic Lumpur, the derivatives and / or a pharmaceutically acceptable salt thereof pharmacologically, retinoic Lumpur, acetate retinoic Lumpur, propionic acid retinol Lumpur, butyric retinoic Lumpur, octylate retinol Lumpur, laurate retinol Lumpur, palmitate retinol Lumpur, retinoic stearate Lumpur, myristic acid retinol Lumpur, oleic acid retinol Lumpur, linolenic acid retinol Lumpur, Reno Lumpur acid retinol Lumpur etc. Of retinol Lumpur fatty acid ester and / or their pharmacologically acceptable salts, hydrogenated retinol Lumpur and / or a pharmaceutically acceptable salt thereof pharmacologically etc. can preferably exemplified, retinal Lumpur, its derivatives and / or a pharmaceutically acceptable salt thereof pharmacologically, retinal Lumpur and / or a pharmacologically acceptable salt thereof can be preferably exemplified, retinoic acid, a derivative thereof and / or their pharmacologically to acceptable salts, retinoic acid, tretinoin (O Lumpur trans retinoic acid), isotretinoin (13-cis - retinoic acid), methyl retinoic acid, ethyl retinoic acid, retinoic acid retinol Lumpur, tocopheryl retinoic acid (The tocopheryl residue may have any chemical structure of α, β, γ, and δ) and / or their pharmacologically acceptable salts. Can. Of these, particularly preferred are retinol Lumpur, retinal Lumpur, retinoic acid, tretinoin, isotretinoin, tocopheryl retinoic acid, palmitic acid retinol Lumpur, acetate retinol Lumpur and / or tolerance their pharmacologically Suitable salts can be exemplified. Also, salts of vitamin A derivative and / or tolerance their pharmacologically use in the present invention, for example, Sigma-Aldrich, were purchased from reagents sales menu over mosquitoes over such Nikko Chemical Co., Ltd., using I can do it.

Further, the triterpenic acid, its derivative and / or pharmacologically acceptable salt thereof will be described. As the above-mentioned triterpenic acid, its derivatives and / or pharmacologically acceptable salts thereof, any triterpenic acid can be used without particular limitation as long as it is used in the field of cosmetics and the like. as a specific example of ursodeoxycholic Lumpur acid, Oreano Lumpur acid and betulinic acid can be preferably exemplified, in particular, Urso Lumpur acid. Further, as the triterpenic acid derivative, an aliphatic hydrocarbon ester having 1 to 20 carbon atoms of triterpenic acid, a hydrocarbon ester having 1 to 4 carbon atoms substituted by an aromatic group of triterpenic acid, a phosphate ester of triterpenic acid And / or pharmacologically acceptable salts thereof can be preferably exemplified. Examples of the aliphatic hydrocarbon ester having 1 to 20 carbon atoms include methyl ester, ethyl ester, hexyl ester, cyclohexyl ester, octyl ester, isooctyl ester, lauryl ester, cetyl ester, stearyl ester, isostearyl ester, oleyl ester and the like. The aliphatic ester is preferably exemplified. Examples of the C1-C4 hydrocarbon ester substituted with the aromatic group include benzyl ester, phenylethyl ester, phenylpropyl ester, and phenylbutyl ester, and benzyl ester is particularly preferable. . Among the anti-wrinkle agent as described above, particularly preferable ones include ursodeoxycholic Lumpur acid and / or a pharmacologically acceptable salt thereof, ursodeoxycholic Lumpur benzyl and / or a pharmacologically acceptable salt thereof (e.g. , JP see JP 2000-302659), 3-position hydroxyl group of ursodeoxycholic Lumpur acid phosphate ester ursodeoxycholic Lumpur acid phosphorylated and / or a pharmacologically acceptable salt thereof suitably be exemplified. The anti-wrinkle agent of the present invention described above contains an excellent skin beautifying effect when it is added to the external preparation for skin together with the AGEs decomposing agent, specifically, the enhancement of the prevention or improvement effect against wrinkle formation in combination with the AGEs decomposing agent. At the same time as strengthening, the effect of improving the overall skin condition by improving skin symptoms such as improvement of skin transparency is exhibited.

ウルソール酸ベンジル

Urso Lumpur benzyl

ウルソール酸リン酸エステル

Urso Lumpur acid phosphate ester

The anti-wrinkle agent can be synthesized by the following method, or can be purchased as a commercially available reagent. Among the above-mentioned anti-wrinkle agents, C1-C20 aliphatic hydrocarbon esters of triterpenic acid and C1-C4 hydrocarbon esters substituted with an aromatic group of triterpenic acid include the corresponding triterpenic acid. It can be obtained by treating with sodium hydride to obtain a sodium salt, and then adding a halogenated hydrocarbon to this to react. The reaction temperature and time may be one to 12 hours at room temperature or under reflux conditions. The phosphate ester of triterpenic acid can be derived from triterpenic acid, for example, according to the method described in Table No. 2006-132033. Specifically, triterpenic acid phosphate esters, presence tetrazole Lumpur commercial triterpenic acids, from 1 to 3 equivalents of dimethyl -N, treated with N- diethyl phosphoramidite de chromatography preparative, t- butyl hydroperoxide the path over oxide reacted, after a Mechiruhosufe over bets triterpenic acids, may further be synthesized by the action of trimethylsilyl bromide.

The above-mentioned anti-wrinkle agent can be used as an anti-wrinkle agent as it is, but it can also be treated with a pharmacologically acceptable acid or base, converted into a salt form, and used as a salt. For example, mineral salts such as hydrochloride, sulfate, nitrate, phosphate, carbonate, maleate, fumarate, oxalate, citrate, lactate, tartrate, methanesulfonate, para toluenesulfonate, organic acid salts such as benzenesulfonate, sodium salt, alkali metal, calcium salts, alkaline earth metals such as magnesium salt metal, triethylamine salt and potassium salt, triethanolamine over triethanolamine salts, ammonium salts, monoethanolamine over Preferred examples include organic amine salts such as ruamine salt and piperidine salt, and basic amino acid salts such as lysine salt and alginate.

Among the anti-wrinkle agent of the present invention is described with the plant extract with a dermal Kola progestogen fascicles reconstruction action. As a component having a dermal Kola progestogen fascicles reconstruction operation of the present invention can be accommodated without particular limitation as long as components having Kola progestogen fascicles reconstruction action. Examples of such components, for example, in the Kola progestogen fascicles reconstruction action evaluation using dermal fibroblasts hairless mice described in JP 2002-104921, Kola progestogen fiber bundle of photographs taken component Kola progestogen reconstruction action is observed by determining the state suitably be exemplified. The component having such Kola progestogen fascicles restructuring action, plant extracts obtained from Myrtaceae Myrtaceae genus Choujinoki, plant extract obtained from hypericaceae Hypericum Hypericum, obtained from hypericaceae Hypericum Hypericum perforatum Plant extract, plant extract obtained from Hypericaceae sp. , Plant extract obtained from rose family peach genus, plant extract obtained from buckthorn family jujube jujube, plant extract obtained from honeysuckle family elderberry genus elderberry, cornaceae cornflower cornflower The plant extract, a plant extract obtained from the Labiatae family Ibuki musk genus time, Lamiaceae Rosmarinus officinalis Shokuro over Zumari plant extract obtained from chromatography, plant extract obtained from Labiatae Salvia Shokuse over di-, Shisoka perilla A plant extract obtained from the genus Perilla, a plant extract obtained from the Labiatae pertussis, a plant extract obtained from the Labiatae mint genus can be suitably exemplified, and among these, more preferable are: A plant extract obtained from the Myrtaceae spp. Hypericum Plant extracts obtained from layers, plant extract obtained from Caprifoliaceae Sambucus Sambucus nigra, plant extract obtained from Asteraceae Centaurea cornflower, plant extract preferably obtained from Labiatae rosemary Shokuro over Zumari over It can be illustrated. Component having a dermal Kola progestogen fascicles restructuring action of said, together with the AGEs decomposer, excellent skin-beautifying effect by containing the skin external preparation, specifically, for wrinkle formation by combination with AGEs decomposers It enhances and enhances the preventive or ameliorating action, and at the same time exhibits the effect of improving the overall skin condition by improving the skin symptoms such as improvement of skin transparency.

Plant extracts with dermal Kola progestogen fascicles reconstruction operation of the present invention, if the plant extract with a dermal Kola progestogen fascicles restructuring action, can be adapted without particular limitation. The plant extract in the present invention refers to a plant body itself, a processed product obtained by drying, shredding, pulverizing the plant body, a solvent extract obtained by adding a solvent to the plant body or the processed product, and an extract. solvent removal of the extract solvent removal means collectively including their purified products such as column chromatography or liquid-liquid extraction. As a plant to be applied to the plant extract of the present invention, a plant extract obtained from the genus Hydrangeaceae, a plant extract obtained from Hypericumaceae, a plant extract obtained from Hypericum pertussis, a plant extract obtained from Hypericum pertussis, Hypericum perforatum, Hypericaceae family plant extract obtained from Hypericum spp., Hypericumaceae family Hypericum spp., Plant extract obtained from Papaveraceae spp. Plant extract obtained from Peach genus Peach, Plant extract obtained from Chrysanthemum family Jujube jujube, Plant extract obtained from Honeysuckle family Elderberry genus Elderberry, Plant extract obtained from Cornaceae cornflower , Plant extracts obtained from the Labiatae family Ibuki musk genus time, Lamiaceae Rosmarinus officinalis Shokuro over Zumari plant extract obtained from chromatography, plant extract obtained from Labiatae Salvia Shokuse chromatography di, obtained from Shisoka Perilla genera perilla The plant extract obtained from the plant extract obtained, the plant extract obtained from the Labiatae genus Olysium, and the plant extract obtained from the Labiatae family mint genus can be illustrated suitably. As the plant part used for the preparation of the plant extract of the present invention, any part of the plant body can be used, but a particularly preferable one is a dried whole plant. This is because is contained many components to reconstruct the dermis Kola progestogen fiber bundles at this site. As the plant extract of the present invention, the polar solvent extract or a solvent removal thereof is possible exemplary particularly preferred, the polar solvent, alcohol such as ethanol or methanol, ethyl acetate and methyl formate esters such as, ketones such as acetone or methylethylketone, et chromatography ethers such as diethyl over ether and tetrahydrofuran, halogenated hydrocarbons such as chloroform and methylene chloride, one selected from water and the like or may have two or more Preferred examples can be given. Of these, particularly preferred are one or selected from water and alcohol is 2 or more. Such an extract or its solvent-removed product is soaked in a plant or processed product by 1 to 10 times the amount of solvent and immersed for several days at room temperature or for several hours at a temperature near the boiling point. That's fine. The solvent can be removed by evaporation to dryness, concentration under reduced pressure, or lyophilization. Most preferred are vacuum concentration and lyophilization.

<Manufacture example 1: The manufacturing method of the plant extract obtained from Myrtaceae cinnamon>
Myrtaceae flower buds Choujinoki those dried 500 g of methanol 5 L of added and immersed for one week at room temperature, filtered, and concentrated under reduced pressure, the plant extract obtained from Myrtaceae Choujinoki of the present invention 35 g was obtained.

<Production Example 2: Method for producing a plant extract obtained from Hypericumaceae Hypericum Hypericum>
Hypericaceae Hypericum whole herbs of Hypericum to 500 g which was dried 5 L methanol was added and immersed for one week at room temperature, it is filtered and concentrated in vacuo to give from hypericaceae Hypericum Hypericum of the present invention 22 g of plant extract was obtained. According to the same procedure, a plant extract obtained from Hypericum perforatum Hypericum perforatum, a plant extract obtained from Hypericum pertussis spp., And a plant extract obtained from Hypericum perforatum was obtained.

<Production Example 3: Method for producing plant extract obtained from honeysuckle family Elderberry>
Caprifoliaceae Sambucus oilseed refluxed elderflower 1 kg to 10 L 2 hours added ethanol of take filtered filtrate, which was collected by filtration once added deposited precipitate in water 3 L, honeysuckle invention 19 g of a plant extract obtained from the family Elderberry was obtained.

<Manufacture example 4: The manufacturing method of the plant extract obtained from a asteraceae cornflower genus cornflower>
Asteraceae Centaurea refluxed whole plant 1 kg 2 hour addition of ethanol of 10 L to the cornflower, take filtered filtrate, which was collected by filtration once added deposited precipitate in water 3 L, chrysanthemum present invention 12 g of a plant extract obtained from the family cornflower genus cornflower was obtained.

<Production Example 5: production method of plant extract obtained from Labiatae rosemary Shokuro over Zumari over>
B over Zumari over 1 kg to refluxed for 2 hours added ethanol of 10 L, takes a filtered filtrate to give it was concentrated under reduced pressure crude extract 1213 g. Ethanol The crude extract 1 100 g of 600 mL
The resulting precipitate was added to 200 mL of water all at once, and the deposited precipitate was collected by filtration to obtain 42 g of a crude extract 2. The 100 g of crude extract 2 was dissolved in Norumarubutano Lumpur 500 mL, a 500 mL of water was added thereto, and liquid extraction took butanol phase. Repeat this process three times, to give Lamiaceae Rosmarinus officinalis Shokuro over Zumari plant extract obtained from over 27 g of concentrated under reduced pressure present invention combined butanol phases.

In addition, in the preparation of a skin external preparation containing 1) AGEs degrading agent and 2) anti-wrinkle agent of the present invention, it is an option used in the preparation of normal pharmaceuticals, quasi drugs, cosmetics, etc. Ingredients can be included. As the skin external preparation of the present invention, pharmaceuticals, quasi-drugs, cosmetics and the like can be suitably exemplified, and since they can be taken on a daily basis, it is preferable to apply to cosmetics, quasi-drugs and the like. The administration route is preferably such that these components are administered continuously, or transdermally in consideration of safety. The external skin preparation of the present invention can be used without particular limitation as long as it is applied externally to the skin, for example, cosmetics, skin external medicine, skin external goods and the like can be suitably exemplified, It is particularly preferable to apply to cosmetics. This is because the external preparation for skin of the present invention has an unparalleled feeling of use and is particularly suitable for cosmetics where the feeling of use is important. As the external preparation for skin of the present invention, for example, B Activation of such cosmetics, milky lotion, essence, creams, face pack, face wash cosmetic, cleansing cosmetics can be preferably exemplified. Still the dosage form, as long as it is known in the cosmetic area particular limitation is no B Activation formulations, oil-in-water emulsion formulations, water-in-oil emulsion formulation, preferably exemplified composite emulsion emulsifying formulations, etc. it can.

The external preparation for skin of the present invention can contain, in addition to such components, optional components that are usually used in external preparations for skin. Examples of such optional components, e.g., macadamia nut oil, Abou transient oil, corn oil, olive oil, rapeseed oil, sesame oil, castor oil, safflower over oil, cottonseed oil, jojoba oil, coconut oil, palm oil , Liquid lanolin, hydrogenated coconut oil, hydrogenated oil, molasses, hydrogenated castor oil, beeswax, candelilla wax, carnauba wax, ibota wax, lanolin, reduced lanolin, hard lanolin, jojoba oil, waxes; liquid paraffin, squalane, pristane, ozokerite, paraffin, ceresin, vaseline, hydrocarbons such as microcrystalline wax; oleic acid, isostearic acid, lauric acid, myristic acid, palmitic acid, stearic acid, behenic acid, higher fatty acids such as undecylenic acid; Sechiruaruko Lumpur, stearyl alcohol, Isosuteari Alcohol, behenyl alcohol, octyl dodecanoate Lumpur, myristyl alcohol, higher alcohols such as cetostearyl alcohol; isooctane cetyl, isopropyl myristate, isostearate hexyl decyl, diisopropyl adipate, sebacic acid di-2-ethylhexyl, cetyl lactate, diisostearyl malate, di-2-ethyl hexanoate of ethylene glycol, neopentyl glycol dicaprate, glyceryl di-2-heptylundecanoate, tri-2-ethylhexanoate glycerin , tri-2-ethylhexanoate trimethylol over trimethylolpropane triisostearate trimethylol over trimethylolpropane, synthetic ester oils such as tetra-2-ethylhexanoate pentane pentaerythritol; dimethyl polysiloxane, methylphenyl Rokisan, linear polysiloxanes such as diphenyl polysiloxane; octamethylcyclotetrasiloxane, decamethylcyclopentasiloxane, cyclic polysiloxanes such as dodeca methylcyclohexane siloxane; amino-modified polysiloxane, polyether chromatography ether-modified polysiloxane, alkyl-modified polysiloxane , oils such silicone over emissions oils of modified polysiloxanes and fluorine-modified polysiloxane; fatty acid soap (sodium laurate, sodium palmitate), potassium lauryl sulfate, alkyl sulfate triethanol over Ruamin'e chromatography ether such anionic surfactants Agents; cationic surfactants such as stearyltrimethylammonium chloride, benzalkonium chloride, laurylamine oxide; imidazoline-based amphoteric surfactants (2-cocoyl-2-imida) Zolinium hydroxide-1-carboxyethyloxy disodium salt, etc.), betaine surfactants (alkyl betaine, amide betaine, sulfobetaine, etc.), and amphoteric surfactants such as acylmethyltaurine; sorbitan fatty acid esters (sorbitan) Monosuteare over DOO, sorbitan sesquioleate etc.), glycerol fatty acids (glycerol monostearate, etc.), propylene glycol fatty acid esters (monostearate propylene glycol, etc.), hardened castor oil derivatives, glycerin alkyl error over ether , POE sorbitan fatty acid esters (POE sorbitan monooleate over preparative, polio monostearate key sorbitan, etc.), POE sorbitol fatty acid esters (POE- sorbit monolaurate over preparative etc.), POE glycerin fatty et Ethers (POE- glyceryl monoisostearyl array over preparative etc.), POE fatty acid esters (polyethylene glycol Rumonoore over preparative, POE Jisuteare over preparative etc.), POE alkyl ether over ethers (POE2- octyldodecyl error over ether, etc.), POE alkylphenyl et chromatography ethers (POE nonylphenyl error over ether, etc.), Pluronic type compound, POE-POP alkyl ether over ethers (POE-POP2- decyltetradecyl et chromatography ether, etc.), Tetronic compounds, POE castor oil, Hardened castor oil derivatives (POE castor oil, POE hardened castor oil, etc.), nonionic surfactants such as sucrose fatty acid ester, alkyl glucoside; moisturizing ingredients such as sodium pyrrolidone carboxylate, lactic acid, sodium lactate; surface treatment may be, mica, talc, kaolin, synthetic mica, Calcium, magnesium carbonate, silicic anhydride (silica), aluminum oxide powder such as barium sulfate; may be surface treated, red iron oxide, yellow iron oxide, black iron oxide, cobalt oxide, ultramarine, iron blue, titanium oxide, inorganic pigments zinc oxide; may be surface treated mica titanium, Sakanarinhaku, Pas Lumpur agent such as bismuth oxychloride; les over key of which may be red No. 202, Red 228, Red 226, Yellow 4, Blue 404, Yellow 5, Red 505, Red 230, Red 223, Orange 201, Red 213, Yellow 204, Yellow 203, Blue 1 No., green No. 201, purple No. 201, organic dyes red No. 204, etc., polyethylene powder, polymethyl methacrylate, nylon powder, organic powders such as organopolysiloxane elastomers; Pas Laaminobenzoic acid UV absorbers; Anthranilic acid UV absorbers; Salicylic acid UV absorbers; Cinnamic acid UV absorbers ; Benzophenone UV absorbers; Sugar UV absorbers; 2- (2'-hydroxy-5 ' -t- octylphenyl) benzotriazole, 4-methoxy-4'-t-butyl-dibenzo yl ultraviolet absorbers such as methane; ethanol, lower alcohols such as isopropanol Lumpur; vitamin a or a derivative thereof, vitamin B ₆ hydrochloride, vitamin B ₆ Toriparumite over preparative, vitamin B ₆ Jiokutanoe over preparative, vitamin B ₂ or derivatives thereof, vitamin B _12, vitamin B such as vitamin B ₁₅ or a derivative thereof; alpha-tocopherol Lumpur, beta- tocopherol Lumpur, .gamma. tocopherol Lumpur, vitamin E such as vitamin E Asete over preparative, vitamin D, vitamin H, pantothenic acid , Pantethine, vitamins such as pyrroloquinoline quinone and the like; antibacterial agents such as phenoxyethanol Lumpur; hectorite, and organic-modified clay minerals such as dimethyl distearyl ammonium modified hectorite may be preferably exemplified.

The external preparation for skin of the present invention contains the above-mentioned essential components. The external preparation for skin of the present invention, as long as it is known in the cosmetic area particular limitation is no emulsifier b Activation formulations, oil-in-water emulsion formulations, water-in-oil emulsion formulation, to a composite emulsion emulsifying formulations, etc. The form may be either a water-in-oil emulsifier form or an oil-in-water emulsifier form, but the water-in-oil emulsifier form is particularly preferred. Here, the water-in-oil emulsifier type is a word called comprehensively the emulsifier shape with the oil phase to the Foreign Minister, may also contain an aqueous phase to the internal phase, have the emulsion, such as oil-in-water emulsions You may do it.

The skin external preparation of the present invention can contain a non-surfactant used in skin external preparations such as ordinary cosmetics. Furthermore, it is also preferred to incorporate an alkyl-modified carboxyvinyl polymer over and / or salt thereof in the sense to maintain the emulsified state stably. The preferable content of such components is 0.01 to 0.5 mass%, more preferably 0.05 to 0.3 mass%, based on the total amount of the external preparation for skin. Such a component is preferably contained also in that sense because it forms a composite film with the essential ingredient amodimethicone after administration to the skin and enhances the effect of amodimethicone. For such alkyl-modified carboxyvinyl polymer over commercial products resides, it can be used to purchase such commercially. Preferred commercially available from Nippon support over Fakutanto Industrial Co., alkyl denaturated with an alkyl group having 10 to 30 carbon atoms "Pemulen (PEMUREN; R) TR-1", "Pemulen (PEMUREN; Registration R) TR-2 ", BF Goodrich (USA)" mosquito turbo port Lumpur available from (CARBOPOL; registered trademark) 1382 "include, as the carboxyvinyl polymers over that are not alkyl-modified, BF Goodrich is commercially available from (US) "mosquito turbo port Lumpur (CARBOPOL; registered trademark) Ultrez10", "Carbopol (CARBOPOL; registered trademark) 940", and the like. Such hydrophilic polymers may be used alone or in combination of two or more. The oil-in-water emulsified skin external preparation of the present invention preferably contains 0.05 to 1% by mass of such hydrophilic polymer, more preferably 0.08 to 0.5% by mass. When less than this, an emulsification system will become unstable, and when more than this, the viscosity of a system will become high too much and applicability | paintability will worsen.

<Production Example 1: Production 1 of the skin external preparation of the present invention>
Skin external preparations (cosmetics 1 to 7) comprising the formulation components described in Tables 1 and 2 were prepared. That is, ingredients A), heat b) and c) to 70 ° C., respectively, and neutralized by adding b) to i), this was emulsified slowly c) was added, trimmed emulsified particles with a homogenizer over The mixture was stirred and cooled to obtain a skin external preparation (cosmetics 1 to 7). At the same time, Comparative Example 1 in which the “AGEs decomposing agent of the present invention” was replaced with “water” in the prescription components of Table 1, Comparative Example 2 in which “Anti-wrinkle agent of the present invention” was replaced with “Water”, “This Comparative Example 3 was prepared by substituting “water” for both the “AGEs decomposing agent of the invention” and the “anti-wrinkle agent of the present invention”.

<Test Example 4: Wrinkle improvement effect evaluation 1 using the skin external preparation of the present invention>
Regarding the skin external preparations (cosmetics 1 to 7) produced according to the method described in Example 1 and Comparative Examples 1 to 3, the wrinkle improvement effect was examined according to the following test method. In other words, the panelists over the crow's feet is a concern (female, age 40 to 60 years of age) in the group consisting of each group of five, the external preparation for skin (cosmetics 1 to 7), pass the Comparative Examples 1 to 3, 1 Used twice a day in the morning and every day for 8 weeks, score 0: no improvement, score 1: feels a little improved, score 2: feels improved, score 3: clearly improved, score 4 : Score evaluation was performed according to the criteria of marked improvement. The results are shown in Table 3 as the number of appearances. From this, it can be seen that the skin external preparations (cosmetics 1 to 7) containing 1) AGEs decomposing agent and 2) anti-wrinkle agent of the present invention are excellent in wrinkle improvement effect. Moreover, the higher skin wrinkle improvement effect was recognized in the skin external preparation containing the plant extract obtained from the leguminous genus Astragalus which has a stratum corneum AGE decomposition | disassembly effect | action, and an anti-wrinkle improving agent.

<Production Example 2: Production 2 of the skin external preparation of the present invention>
As a skin external preparation of the present invention, the production of Table 1 and to a cosmetic 1 described in Table 2, the formulation components "Pemulen TR-2" substitution skin external preparation "carboxyvinyl polymers over" (cosmetic 8) However, emulsification could not be carried out, and the external preparation for skin (Cosmetic 8) could not be produced.

<Test Example 5: Skin transparency improving effect evaluation 1 using the external preparation for skin of the present invention>
The skin external preparations (cosmetics 1 to 8) described in Example 1 and Comparative Examples 1 to 3 were evaluated for improving skin transparency. The people who have trouble in transparent feeling to the skin of up to 59 years of age and panelists over, was carried out using test. Panelists over the variation grouped one by each group of five as not, to each group cosmetics 1-7, passing the cosmetics of Comparative Examples 1 to 3, applying the appropriate amount twice a month morning and evening We had you use continuously in aspect. Pre-test and a questionnaire by the awareness carried out after the end, a sense of transparency, 1: very feel, 2: feel pretty, 3: feel, 4: I feel slightly, 5: I do not feel too much, 6: almost no feeling, of The evaluation was made in 6 stages, and the value obtained by subtracting the evaluation value after use from the evaluation value before use was defined as the degree of improvement. The results are shown in Table 4.

Claims (18)

1) Advanced Gurike Activation End Products (AGEs: Advanced Glycation and End-products) decomposer, 2), characterized in that it contains an anti-wrinkle agent, a skin external preparation. The skin external preparation according to claim 1, wherein the AGE decomposition agent comprises the following plant extract.
(Plant) Oleaceae olive genus, Saxifragaceae Saxifraga, Rosaceae Potenchira genus, Rosaceae Potentilla, leguminous asparagus-to-scan genus Rosaceae filipendula, Asteraceae Artemisia, and plants belonging to the legume Astragalus Said of Oleaceae olive genus, Saxifragaceae Saxifraga, Rosaceae Potenchira genus, Rosaceae Potentilla, leguminous asparagus-to-scan genus Rosaceae filipendula, Asteraceae Artemisia, and plants belonging to the legume Astragalus is, each Oleaceae olive species olive, Saxifragaceae Saxifraga saxifrage, Rosaceae Potenchira genus Torumenchira, Rosaceae Potentilla Kawarasaiko, Rosaceae Potenchira genus Miyama Kinbae, leguminous asparagus-to-scan genus rooibos, Rosaceae filipendula Shimotsukesou, chrysanthemum wherein the family Artemisia Artemisia, and leguminous Astragalus Rengesou skin external preparation according to claim 1 or 2. The external preparation for skin according to any one of claims 1 to 3, wherein the AGEs decomposing agent has an action of decomposing AGEs present in the horny layer of the skin. Anti-wrinkle agent of the can, vitamin A, its derivatives and their pharmacologically acceptable salts, triterpenic acids, their derivatives and their pharmacologically acceptable salts, as well as dermal Kola progestogen fiber bundle reconstruction It is 1 or more types selected from the group which consists of a plant extract which has an effect | action, The skin external preparation as described in any one of Claims 1-4 characterized by the above-mentioned. Vitamin A or a derivative of said can, retinoic Lumpur, retinal Lumpur, retinoic acid, tretinoin, isotretinoin, retinoic acid tocopherol Lumpur, palmitate retinol Lumpur, acetate retinoic Lumpur, and hydrogenated retinol over Ruyori selected The skin external preparation according to claim 5 , wherein the skin external preparation is one type or two or more types. Triterpene acid residue of triterpenic acids and derivatives thereof of the can, Urso Lumpur acid, characterized in that it is a betulinic acid or residue of these acids, skin external preparation according to claim 5. The topical skin preparation according to claim 7, wherein the triterpenic acid and a derivative thereof are triterpenic acid, triterpenic acid benzyl ester, or triterpenic acid phosphoric ester. Plant extracts with dermal Kola progestogen fascicles restructuring action of said, characterized in that at one of two or more selected from plant extracts shown below, external skin of claim 5 Agent. <Plant extract having a dermal Kola progestogen fiber bundle reconstruction action>
A plant extract obtained from the Myrtaceae spp. family Hypericum plant extract obtained from Tomoesou, plant extract obtained from Caprifoliaceae Sambucus Sambucus nigra, plant extract obtained from Asteraceae centaurea cornflower, and plant extracts obtained from Labiatae rosemary Shokuro over Zumari over object The skin external preparation according to any one of claims 1 to 9, wherein the AGEs decomposing agent is contained in an amount of 0.0001 mass% to 10 mass% with respect to the total amount of the external preparation for skin. The skin external preparation according to any one of claims 1 to 10, wherein the anti-wrinkle agent is contained in an amount of 0.00001 to 15% by mass based on the total amount of the external preparation for skin. The skin external preparation according to any one of claims 1 to 11, wherein the preparation is for beautiful skin. The skin external preparation according to claim 12, wherein the skin beautifying action is an action for preventing or improving sagging or wrinkle formation. The skin external preparation according to claim 12, wherein the skin beautifying effect is an effect of improving skin transparency. The skin external preparation according to any one of claims 1 to 14, which is in the form of a water-in-oil emulsifier. In the skin of a person who should use cosmetics, the fluorescence generated from the skin by excitation light is measured, and when the amount of AGEs in the skin estimated from the fluorescence intensity is large, the cosmetics to be used by the person The external preparation for skin according to any one of claims 1 to 15 , wherein the preparation is external. In the skin of a person who should use cosmetics, when the skin surface replica is made and the shape of the skin groove and the skin is analyzed, the difference between the skin groove and the skin is small, and there is a feature that a large disconnection exists. The skin external preparation according to any one of claims 1 to 15 , which is a cosmetic to be used by the person when having a skin. The skin external preparation according to any one of claims 1 to 17 , which is used in the following mode.
(1) than people trying to use the cosmetics, the corneocytes taken by tape over TOPS stripping method, irradiated with excitation light, the intensity of fluorescence produced is measured, the AGEs amount of the stratum corneum intracellular Estimate and discriminate whether the amount is larger or smaller than the average amount. (2) From the person who wants to use cosmetics, make a replica of the skin surface, analyze the shape of the skin groove and skin, and the difference between the skin groove and skin is small, and there is a large disconnection. In this case, it is a candidate for a cosmetic user.
(3) A person who is a candidate for both (1) and (2) is a cosmetic user.