JP2007161661A - Cosmetic for decomposing advanced glycation endproducts and method for producing the same - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a means for breaking the C-C bond of an α-diketone and decomposing accumulated advanced glycation endproducts (AGEs) to reduce the AGEs in the skins. <P>SOLUTION: This method for producing a cosmetic comprises extracting the body of Aspalathus linearis plant with a polar solvent to obtain an extract, if desired, subjecting the extract to a fractionation, a purification, and the removal of a solvent, when the product is added to a cosmetic, incubating the extract with 1-phenyl-1,2-propanedione, confirming the amount of the produced benzoic acid, and then adding the extract to the cosmetic. The Aspalathus linearis plant is preferably leaves. The extraction solvent is preferably water-containing ethanol. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

  The present invention relates to a cosmetic and a method for producing the same, and more particularly, to a cosmetic useful for degrading advanced glycation end products related to skin aging and improving aging. .

  Aging is a phenomenon that humans always meet if they live long, and it is said that early signs have already begun in their 30s or 40s. The skin loses its elasticity due to aging, and the skin that is light-skinned is darkened and its appearance is never preferable. It is a feeling that everyone wants to be beautiful, and it can be said that development of a means to resist such aging is desired.

  Regarding aging, even if it is limited to skin aging, many mechanisms have been proposed, and anti-aging means based on each mechanism have been devised. For example, a result obtained by a method of constructing an experimental model by a method of inducing photoaging by cumulatively irradiating light and screening a component that resists this (see, for example, Patent Document 1 and Patent Document 2) Etc. can be exemplified. In such photoaging, it is known that the dermis collagen fibers are ruptured, the dermis collagen fiber bundle structure is broken, and the like, and the dermis elasticity and water retention ability are lost. A method of blending such a component for normalizing dermal collagen fiber bundles with an external preparation for skin is also a stream of development of one effective anti-aging external preparation for skin. (See, for example, Patent Document 3) Other than this, generation of Maillard reaction and subsequent advanced glycation end products (hereinafter sometimes abbreviated as AGEs) are the aging mechanisms that have attracted attention in recent years. Accumulation. Such a reaction is a mechanism in which the skin protein is deprived of its function because it oxidatively denatures the skin protein, and this is reflected in various states of aging. It is said that such AGE generation reaction is an irreversible reaction, and once AGEs are generated, they only accumulate thereafter. Various components have been reported for the suppression of the production of AGEs, but only an olive extract and a yukinoshita extract are known for the degradation of AGEs. (For example, see Patent Document 4 and Patent Document 5) AGEs are products generated as a result of the Maillard reaction, but the Maillard reaction is a Schiff base formed by a non-catalytic condensation reaction between a living amino group and a carbonyl group. The azomethine bond undergoes an Amadori transition, and the Amadori transition product undergoes a complex reaction such as dehydration, condensation, cyclization, and cross-linking, resulting in brown, fluorescence, insolubilization and a later product. Dividing into late stages, AGEs are this final product. These AGEs are usually difficult to decompose, but it is known that they can be decomposed by cleaving the CC bond between the ketones of the α-diketone structure existing in AGEs. However, only N-phenacyl thiazolium bromide is known as such a cleavage-active component, and this substance is a cosmetic component. It is hard to say that it is appropriate in terms of safety.

  On the other hand, rooibos (Aspalathus linearis) is known to have collagen biosynthesis promoting action, antiallergic action, glycation reaction inhibitory action, etc. in its leaf extract (for example, Patent Document 6, Patent Document) 7, see Patent Document 8), but it is not known at all that an action of degrading AGEs exists.

Japanese Patent Laid-Open No. 2005-220043 JP 2004-51580 A Japanese Patent Laid-Open No. 2005-53798 JP 2001-122758 A JP 2001-108622 A JP 2005-255527 A JP-A-2005-247708 JP 2004-250445 A

  The present invention has been made under such circumstances, and an object of the present invention is to provide means for cleaving the CC bond of α-diketone, decomposing accumulated AGEs, and reducing AGEs in the skin. .

Extract the rooibos (Aspalathus linearis) plant with a polar solvent to obtain an extract, and if desired, extract the extract after fractionation, purification and solvent removal, and then include the extract in the cosmetic. Cosmetics produced by incubating the product with 1-phenyl-1,2-propanedione, confirming that the amount of benzoic acid produced is produced, and then incorporating the extract Was found to have such characteristics, and the present invention was completed. That is, the present invention is as follows.
(1) In the case where a plant of rooibos (Aspalathus linearis) is extracted with a polar solvent to obtain an extract, and, if desired, the extract is fractionated, purified, solvent removed and then contained in cosmetics. Incubating the extract with 1-phenyl-1,2-propanedione, confirming that the amount of benzoic acid produced is produced, and then containing the extract. Manufacturing method for cosmetics.
(2) The method for producing a cosmetic according to (1), wherein the rooibos plant is a leaf.
(3) The method for producing a cosmetic according to (1) or (2), wherein the extraction solvent is hydrous ethanol.
(4) The process of extracting rooibos (Aspalathus linearis) plant with polar solvent, obtaining an extract, and, if desired, fractionating, purifying and removing the solvent, rooibos (Aspalathus linearis) plant Is extracted with aqueous ethanol to obtain an extract, from which the extraction solvent is removed, and then ethyl acetate and water are added, liquid-liquid extraction is performed, the ethyl acetate phase is taken, and the solvent of the ethyl acetate phase is removed. It is a process, The manufacturing method of the cosmetics any one of (1)-(3) characterized by the above-mentioned.
(5) Further, the extract of rooibos (Aspalathus linearis) or its fraction purified product is incubated with the advanced glycation end products / bovine serum albumin complex, and after the incubation, the advanced glycation end products / cow Serum albumin complex was quantified, and it was confirmed that the quantified value was reduced compared with the absence of rooibos (Aspalathus linearis) extract or its fraction purified product. The method for producing a cosmetic according to any one of (1) to (4), wherein:
(6) The cosmetics described in any one of (1) to (5), wherein a person who has already formed wrinkles is used for reducing the degree of the wrinkles. Manufacturing method for cosmetics.
(7) Any one of (1) to (6), wherein the reduction of the degree of wrinkles is due to decomposition of Advanced Glycation Endproducts accumulated in the skin. The manufacturing method of cosmetics as described in a term.
(8) A cosmetic comprising a polar solvent of rooibos (Aspalathus linearis) or a fraction / purified product thereof in an amount sufficient to decompose advanced glycation end products.
(9) The leaves of rooibos (Aspalathus linearis) are extracted with 50% aqueous ethanol solution, the solvent is removed, liquid-liquid extraction is performed with ethyl acetate and water, the ethyl acetate phase is removed, and the concentrated fraction is 10 ⁻ Cosmetics containing ⁴ % or more.

  According to the present invention, it is possible to provide means for degrading accumulated AGEs and reducing AGEs in the skin.

  In the method for producing the cosmetic of the present invention, a plant of rooibos (Aspalathus linearis) is extracted with a polar solvent to obtain an extract. If desired, the extract is fractionated, purified, and solvent-removed. In the case of inclusion in cosmetics, the extract and 1-phenyl-1,2-propanedione are incubated to confirm that the amount of benzoic acid produced is produced, and then the extract is used. It is characterized by containing. The plant belonging to the genus Rosaceae is not particularly limited as long as it is a plant belonging to this genus, but rooibos itself, which has been proven as a tea or a herbal medicine, can be preferably exemplified. The plant part used for the production of the plant extract is not particularly limited, and whole plants can be used, but leaves are particularly preferable. Of course, it is also possible to use only parts such as flower ears, flower buds, leaves, stems and roots. In the method for producing the cosmetic of the present invention, a polar solvent is preferable as a solvent used for extraction, water, alcohols such as ethanol and isopropanol, ketones such as acetone and methyl ethyl ketone, nitriles such as acetonitrile, diethyl ether and tetrahydrofuran. Preferred examples include ethers such as ethyl acetate and esters such as ethyl acetate and methyl formate. These may be used alone or in combination. During extraction, 1 to 10 parts by mass of solvent is added to 1 part by mass of the plant body or processed product, and stirring is optionally added for several days at room temperature and for several hours at temperatures near the boiling point. What is necessary is just to immerse. After soaking, the insoluble matter can be removed by filtration or the like, if necessary, and the solvent can be removed if necessary. Furthermore, these can be fractionated and purified by liquid-liquid extraction, chromatography using ion exchange resin or silica gel as a carrier, and the like. The extract thus obtained and its fraction purified product are incubated with 1-phenyl-1,2-propanedione, and the amount of benzoic acid produced by cleaving the CC bond of the α-diketone structure is reduced. The α-diketone carbon-carbon cleaving ability is confirmed by quantification. The blending amount into the cosmetic is determined according to this cutting ability. An example of the method for measuring the cutting ability is as follows.

<Measurement of CC bond cleavage ability of α-diketone>
Mix 1 ml of 22 mM 1-phenyl-1,2-propanedion / MeOH + 0.1 M phosphate buffer (PH 7.4) and 1 ml of the extract of the plant of the genus Potentilla or fractionated purified product, and react at 37 ° C. for 10 hours. The amount of benzoic acid was quantified by HPLC.
(HPLC conditions)
・ Analysis conditions Detector: Ultraviolet absorptiometer (measurement wavelength: 260 nm)
··· Column: Tosoh TSK-ODS80TsQA Column temperature: Room temperature ··· Moving bed: Glacial acetic acid 2g / acetonitrile 500ml + edetate dinaturo : 1ml / min

  In the measurement, when the amount of 1-phenyl-1,2-propanedione is 40% or more, more preferably 45% or more, based on the theoretical amount of benzoic acid produced, the cosmetic of the present invention is used. Judged as an extract suitable for inclusion, and blended into cosmetics. At this time, the extract or fraction purified product is diluted with water, 1,3-butanediol, etc. so that the titer is constant and the amount of benzoic acid produced is 40 to 45%. You can also

  Furthermore, in order to ensure certainty as an effect, in addition to the above evaluation, AGEs actually prepared by incubating glucose and bovine serum albumin can be decomposed and mixed after confirming the amount of decomposition. preferable. An example of AGE resolution evaluation is shown below.

<Measurement of glucose-bovine serum albumin AGE resolution>
The materials used are as follows.
AGE-BSA: Glucose and BSA are incubated at 37 ° C. for 12 weeks or more,
・ ・ ・ ・ ・ ・ ・ ・ PD-10 columns (Amersham Bioscience)
・ ・ ・ ・ ・ ・ ・ ・ Ces 17-0851-1) except for excess glucose ……… primary antibody: Anti-Albumin, Bovine Serum,
... Rabbit-Poly ROCKLAND
... 201-41331 / 20000
Secondary antibody: Goat anti-rabbit IG ghorseradish
・ ・ ・ ・ ・ ・ ・ ・ Peroxidase conjugate Bio RAD
... 170-6515 1/10000
Substrate: TMB solution Wako 546-01911
(procedure)
100 μl of 10 μg / ml AGE-BSA was added to a type I collagen-coated 96-well microplate (Bio Coat 35 4407), (1.0 μg AGE-BSA / well) was left at 37 ° C. for 4 hours, and then 0.05% Wash three times with Tween20 / PBS (−) (shake on a micromixer at room temperature for 3 minutes), add 100 μl of each concentration sample dissolved in PBS (−), and react at 37 ° C. for 10 hours or more. Then, it wash | cleans 3 times by 0.05% Tween20 / PBS (-), 100 microliters / well of primary antibodies are added to each well, and it leaves still at room temperature for 30 minutes. Wash 3 times with 0.05% Tween20 / PBS (−), 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. Add 100 μl / well of 1N HCl, stop the reaction, and measure the absorbance at 450 nm. 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.

  In this evaluation, when the degradation rate of AGEs is 15% or more, it is determined that the extract is suitable for blending into the cosmetic of the present invention or is a fraction-purified product. In blending, if the decomposition rate is adjusted to 15% and used, a component having a stable titer can be contained. The effective concentration is preferably set so as to contain a concentration that is recognized as being effective in this study.

  The cosmetics of the present invention can contain optional components usually used in cosmetics in addition to the rooibos extract or fraction purified product. Such inclusion of optional components may be performed according to a conventional method. Such optional ingredients include, for example, macadamia nut oil, avocado oil, corn oil, olive oil, rapeseed oil, sesame oil, castor oil, safflower oil, cottonseed oil, jojoba oil, coconut oil, palm oil, liquid lanolin, hydrogenated coconut oil Oil, wax, oil such as beeswax, canola wax, carnauba wax, ibotarou, lanolin, reduced lanolin, hard lanolin, jojoba wax, liquid paraffin, squalane, pristane, ozokerite, paraffin, ceresin, petrolatum , Hydrocarbons such as microcrystalline wax; higher fatty acids such as oleic acid, isostearic acid, lauric acid, myristic acid, palmitic acid, stearic acid, behenic acid, undecylenic acid; cetyl alcohol, stearyl alcohol, isostearyl Higher alcohols such as alcohol, behenyl alcohol, octyldodecanol, myristyl alcohol, cetostearyl alcohol; cetyl isooctanoate, isopropyl myristate, hexyldecyl isostearate, diisopropyl adipate, di-2-ethylhexyl sebacate, cetyl lactate, malic acid Diisostearyl, di-2-ethylhexanoic acid ethylene glycol, dicaprate neopentyl glycol, di-2-heptylundecanoic acid glycerin, tri-2-ethylhexanoic acid glycerin, tri-2-ethylhexanoic acid trimethylolpropane, tri Synthetic ester oils such as trimethylolpropane isostearate and pentane erythritol tetra-2-ethylhexanoate; dimethylpolysiloxane, methylphenylpoly Linear polysiloxanes such as oxane and diphenylpolysiloxane; cyclic polysiloxanes such as octamethylcyclotetrasiloxane, decamethylcyclopentasiloxane, and dodecamethylcyclohexanesiloxane; amino-modified polysiloxane, polyether-modified polysiloxane, alkyl-modified polysiloxane, Oil agents such as silicone oils such as modified polysiloxanes such as fluorine-modified polysiloxanes; Anionic surfactants such as fatty acid soap (sodium laurate, sodium palmitate, etc.), potassium lauryl sulfate, triethanolamine ether of alkyl sulfates; Cationic surfactants such as stearyltrimethylammonium, 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) Monostearate, sorbitan sesquioleate, etc.), glycerin fatty acids (glyceryl monostearate, etc.), propylene glycol fatty acid esters (propylene glycol monostearate, etc.), hardened castor oil derivatives, glycerin alkyl ethers, POE sorbitan fatty acid esters (POE sorbitan monooleate, polyoxyethylene sorbitan monostearate, etc.), POE sorbite fatty acid esters (POE-sorbitol monolaurate, etc.), POE glycerin fatty acid ester Tells (POE-glycerol monoisostearate, etc.), POE fatty acid esters (polyethylene glycol monooleate, POE distearate, etc.), POE alkyl ethers (POE2-octyldodecyl ether, etc.), POE alkyl phenyl ethers (POE nonylphenyl) Ethers, etc.), Pluronic types, POE / POP alkyl ethers (POE / POP2-decyltetradecyl ether, etc.), Tetronics, POE castor oil / hardened castor oil derivatives (POE castor oil, POE hardened castor oil, etc.), Nonionic surfactants such as sucrose fatty acid ester and alkyl glucoside; polyethylene glycol, glycerin, 1,3-butylene glycol, erythritol, sorbitol, xylitol, maltitol, propylene Polyhydric alcohols such as recall, dipropylene glycol, diglycerin, isoprene glycol, 1,2-pentanediol, 2,4-hexanediol, 1,2-hexanediol, 1,2-octanediol; sodium pyrrolidonecarboxylate Moisturizing ingredients such as lactic acid and sodium lactate; powders such as mica, talc, kaolin, synthetic mica, calcium carbonate, magnesium carbonate, anhydrous silicic acid (silica), aluminum oxide, barium sulfate, etc. whose surface may be treated Body, the surface may be treated, inorganic pigments such as bengara, yellow iron oxide, black iron oxide, cobalt oxide, ultramarine, bitumen, titanium oxide, zinc oxide; surface may be treated, mica Pearl agents such as titanium, fish phosphorus foil, bismuth oxychloride; red 202 which may be raked, red Color 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 201, purple 201, red 204, etc .; organic powders such as polyethylene powder, polymethyl methacrylate, nylon powder, organopolysiloxane elastomer; para-aminobenzoic acid UV absorbers; anthranils Acid UV absorbers; salicylic acid UV absorbers; cinnamic acid UV absorbers; benzophenone UV absorbers; sugar UV absorbers; 2- (2′-hydroxy-5′-t-octylphenyl) benzo Ultraviolet absorbers such as triazole and 4-methoxy-4′-t-butyldibenzoylmethane; lower grades such as ethanol and isopropanol Alcohols; vitamin A or derivatives thereof, vitamin B6 hydrochloride, vitamin B6 tripalmitate, vitamin B6 dioctanoate, vitamin B2 or derivatives thereof, vitamin B such as vitamin B12, vitamin B15 or derivatives thereof; α-tocopherol, β- Preferred examples include vitamins such as tocopherol, γ-tocopherol, vitamin E acetate and the like, vitamins D, vitamin H, pantothenic acid, panthetin, pyrroloquinoline quinone, and the like; and antibacterial agents such as phenoxyethanol.

  The cosmetic of the present invention is produced according to the method for producing a cosmetic of the present invention, and contains the rooibos extract or fraction purified product in an effective amount for degrading AGEs. . Since the cosmetic of the present invention has an action of decomposing accumulated AGEs, it improves the loss of skin elasticity, dullness of skin, decrease in moisturizing ability, etc. caused by accumulation of the AGEs, and is elastic and dull. It can lead to no, fresh skin. Moreover, since it mix | blends after confirming an effect about such an effect, there is no fluctuation | variation of the titer for every lot and it can be set as biochemically stable cosmetics. Usually, in cosmetics containing herbal medicine extracts and the like, the content of the active ingredient varies depending on the lot, place of origin, and season of the herbal medicine, and thus the physiological effect may vary greatly. The physiological potency is stable even in a form containing a herbal extract as an active ingredient.

  Hereinafter, the present invention will be described in more detail with reference to examples, but it goes without saying that the present invention is not limited to such examples.

  After 100 g of dried dried leaves of rooibos (Aspalathus linearis), 500 ml of 50% ethanol aqueous solution was added and heated under reflux for 3 hours. After cooling, insolubles were removed by filtration, and the filtrate was concentrated under reduced pressure. Subsequently, it was freeze-dried to obtain an extract 1. Thereafter, 200 ml of water and 200 ml of ethyl acetate were added to Extract 1 to perform liquid-liquid extraction, and the ethyl acetate phase was collected and concentrated under reduced pressure to obtain Extract 2. Extract 2 was concentrated under reduced pressure, and then fractionated and purified by silica gel column chromatography. That is, the silica gel was wetted with chloroform, packed in a column, charged with the concentrate of extract 2 dissolved in chloroform, chloroform, 1% methanol-containing chloroform, 5% methanol-containing chloroform, 10% methanol-containing chloroform, then 15% 50 ml of methanol-containing chloroform was allowed to flow, and the effluent was concentrated under reduced pressure. These fractions were designated as Extract 3, Extract 4, Extract 5, Extract 6, and Extract 7 in this order.

  Extracts 1 to 7 were measured for the C—C bond cleavage ability of α-diketone according to the procedure of [0011]. The results are shown in Table 1. From this, it can be seen that the extract 4 is suitable as an extract to be blended in the cosmetic of the present invention.

For extract 4, according to the procedure of [0014], the dose of the extract was shaken to measure glucose-bovine serum albumin AGE resolution. The results are shown in Table 2. From this, it can be seen that the extract 4 effectively decomposes AGEs even at 10 ⁻⁴ %. Accordingly, a cosmetic containing ^10-5 % or more of extract 4 can be said to be a cosmetic of the present invention.

  Using the extract 4, a lotion 1, which is a cosmetic of the present invention, was prepared according to the formulation in Table 3. That is, the prescription ingredients were solubilized by stirring at 80 ° C. and stirred and cooled to obtain a skin lotion 1.

  Using the lotion 1 and the lotion 1 of Comparative Example 1 in which the extract 4 of the lotion 1 was replaced with water, a use test was conducted using a person who has a dull skin age 60 years or older as a panelist. Prepare 10 panelists and divide them into 2 groups of 5 so that there is no variation. 1 group will receive lotion 1 and the remaining 1 group will receive the lotion of Comparative Example 1 and will receive the appropriate amount twice a day for 12 weeks. We had you use continuously in aspect to apply. Before and after the test, the ΔL value with respect to the white plate was measured with a color difference meter manufactured by Konica Minolta Co., Ltd., and the degree of increase in lightness was measured by the equation: ΔL value after test−ΔL before test. As a result, the group of the lotion 1 was 13.9 ± 4.2, the group of the comparative example 1 was −0.9 ± 1.3, and the AGEs were used in the lotion 1 use group which is the cosmetic of the present invention. Is decomposed, and it can be seen that yellowishness and dullness are improved. In addition, the elasticity of the skin was also felt in the skin lotion 1 use group.

  The present invention can be applied to cosmetics.

Claims (9)

Extract the rooibos (Aspalathus linearis) plant with a polar solvent to obtain an extract, and if desired, extract the extract after fractionation, purification and solvent removal, and then include the extract in the cosmetic. And 1-phenyl-1,2-propanedione, and confirms that the amount of benzoic acid produced is produced, and then contains the extract. Manufacturing method. The method for producing a cosmetic according to claim 1, wherein the rooibos plant is a leaf. The method for producing a cosmetic according to claim 1 or 2, wherein the extraction solvent is hydrous ethanol. The process of extracting rooibos (Aspalathus linearis) plant with polar solvent, obtaining an extract, and, if desired, fractionating, purifying and removing the solvent, rooibos (Aspalathus linearis) plant body with hydrous ethanol In this step, an extract is obtained by removing the extraction solvent from this, and then ethyl acetate and water are added, liquid-liquid extraction is performed, the ethyl acetate phase is taken, and the solvent of the ethyl acetate phase is removed. The manufacturing method of the cosmetics of any one of Claims 1-3 characterized by the above-mentioned. Furthermore, rooibos (Aspalathus linearis) extract or its fraction-purified product is incubated with an advanced glycation end product / bovine serum albumin complex, and after incubation, an advanced glycation / end product / bovine serum albumin complex is incubated. The body is quantified, and after confirming that the quantified value is reduced as compared with the absence of rooibos (Aspalathus linearis) extract or its fraction purified product, The method for producing a cosmetic according to any one of claims 1 to 4, wherein the cosmetic is characterized in that 6. The cosmetic production according to any one of claims 1 to 5, wherein the cosmetic is used by a person who has already formed wrinkles to reduce the degree of the wrinkles. Law. The makeup according to any one of claims 1 to 6, wherein the reduction of the wrinkle level is caused by decomposition of advanced glycation end products accumulated in the skin. Manufacturing method. A cosmetic comprising a polar solvent of rooibos (Aspalathus linearis) or a fraction / purified product thereof sufficient to decompose advanced glycation end products. Extract the leaves of rooibos (Aspalathus linearis) with 50% aqueous ethanol solution, remove the solvent, perform liquid-liquid extraction with ethyl acetate and water, take the ethyl acetate phase, and concentrate the fraction to 10 ^-4 % or more Cosmetics containing.