JP2008214250A - Maillard reaction inhibitor - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an excellent Maillard reaction inhibitor, an external preparation for skin containing the Maillard reaction inhibitor as an active component, an agent for the prevention and treatment of diabetic complications, and foods and drinks containing the inhibitor. <P>SOLUTION: The invention provides a Maillard reaction inhibitor containing cultured cell extract of a plant of the genus Lithospermum or its treated material as an active component, a Maillard reaction inhibitor containing a caffeic acid polymer as an active component, an external preparation for skin containing the Maillard reaction inhibitor as an active component, a Maillard reaction inhibitor composition containing (A) a pharmaceutical component selected from the cultured cell extract of a plant of the genus Lithospermum, its treated material and a caffeic acid polymer and (B) a pharmaceutical component selected from skin lightening agents, antioxidation agents, antiinflammatory agents, antibacterial agents, cell activation agents, humectants and peripheral vessel flow accelerator, an agent for the prevention and treatment of diabetic complications containing one or more agents selected from the Maillard reaction inhibitors, and foods and drinks containing one or more agents selected from the Maillard reaction inhibitors. <P>COPYRIGHT: (C)2008,JPO&INPIT

Description

  TECHNICAL FIELD The present invention relates to a cultured cell extract of Murasaki spp. Or a processed product thereof and a Maillard reaction inhibitor containing caffeic acid polymer as active ingredients, such as pharmaceuticals, quasi drugs, cosmetics, foods, and beverages. Used in the field.

  The progress of aging due to aging is an unavoidable event for all humans, but in recent years, the progress of aging tends to be further promoted due to causes such as an increase in stress caused by changes in the social life environment. On the other hand, the number of elderly people is increasing due to advances in medical technology and ensuring good nutrition, and the proportion of elderly people in the total population is steadily increasing along with the declining birthrate. Therefore, to suppress the progression of aging induced by various factors is not only strongly desired as an individual, but also from a social viewpoint.

  Aging, which means deterioration of the body's function, is thought to be caused by defects in the regulation of gene expression or abnormalities in the proteins responsible for the normal function of the body. Proteins are deeply involved in aging. Is clear.

  The Maillard reaction is a non-enzymatic reaction between an amino group in amino acid or protein and an aldehyde group of a reducing sugar to produce glycated end products called AGEs (Advanced glycation endproducts) via Schiff base and Amadori rearrangement products. It is a reaction that leads to protein cross-linking and denaturation. In vivo, it is known that the progress of Maillard reaction leads to protein cross-linking and degeneration, and AGEs cause vascular disorders such as cataracts and diabetic complications such as arteriosclerosis (Non-patent Document 1), Alzheimer's disease, etc. It has been revealed that it is involved in neurodegenerative diseases (Non-Patent Document 2-4), malignant tumor growth, metastasis, invasion (Non-Patent Document 5) and the like. In addition, it is considered that wrinkles, dullness, sagging, and the like are observed due to cross-linking and denaturation of dermal constituent proteins such as collagen and elastin as the Maillard reaction proceeds in the skin (Patent Document 1). Further, in the food field, it is recognized as an important reaction particularly in terms of quality control because it causes coloring and aroma components generated during processing and storage of food. Therefore, the development of compounds that inhibit the Maillard reaction is expected in the fields of pharmaceuticals, quasi drugs, cosmetics, foods, beverages and the like.

  AGEs have properties such as specific fluorescence, browning, intramolecular and intermolecular crosslink formation, and pentosidine, croslin, fluorolink, etc. are known as AGEs. Carboxymethyllysine, pyralin, imidazolone, etc. that do not have this feature have been considered to be included in the concept of AGEs, but for carboxymethyllysine, the main source in vivo is due to lipid peroxidation, which is due to saccharification It has been reported that it is not a thing (Non-Patent Document 6), and is considered as an oxidative stress marker rather than AGEs. In recent years, it has been reported that AGEs are generated not only from glucose but also from dicarbonyl compounds such as 3-deoxyglucosone, glyoxal, and methylglyoxal generated from glucose autooxidation and degradation products (Non-patent Document 7). -9). In particular, 3-deoxyglucosone is significantly higher in the blood of uremic patients than in healthy individuals, and is reported to be even higher when combined with diabetes (Non-Patent Document 10). Therefore, 3-deoxyglucosone is considered to be related not only in diabetes but also in the development of diabetic complications. Measurement of 3-deoxyglucosone concentration in serum and plasma is useful because it is useful to determine the effects of 3-deoxyglucosone in vivo in diabetes, diabetic complications, and protein glycation reaction inhibitors. Is used as a test index related to diabetes.

From such a background, development of substances that inhibit the Maillard reaction has been attempted, including aminoguanidine, metformin, OPB-9195, ALT-462, olmesartan, camosin, tenilcetam, 2,3-diaminophenazone, Various basic compounds such as pioglitazone, ALT-486, temocaprilato, pyridoxine, pyridoxamine, pyridoxal, pyridoxal phosphate, thiamine, thiamine monophosphate, thiamine pyrophosphate, adenine, and kinetin are known to have similar activities. (Patent Document 2-28). In addition, many oxidation reactions are involved in the late stage of AGE production, and various antioxidants are known to suppress the progress of late stage reaction and become Maillard reaction inhibitors. Examples include mannitol, dihydrolipoic acid, α-lipoic acid, N-acetylcysteine, cemothiazyl, gliclazide, pentoxifylline, nifedipine, isradipine, rasidipine, benzoic acid, alpha-ketoglutaric acid, pyruvic acid, (+)-rutin, tyrone Nitecapone, diosmin, curcumin, vitamin E, troglitazone, 17β-estradiol, butylated hydroxytoluene, inositol and the like (Patent Documents 29-38). In addition, Maillard reaction inhibitory activity is also known for plant extracts, such as Asunaro, Asenyaku, Japanese knotweed, Ichiyakuso, Apricot, Kankanka, Hakukayumatou, Birch, Hawthorn, Achillea millefolium, Tarayou, Dokudami, Torumenchira, Bakumondou , Hiba, grape, sweet willow, mugwort, mocca, litchi, Roman chamomile extract (Patent Document 39), American witch hazel, apricot, Ichiyakuso, waurusushi, auren, giant clam, gambir, genus shoko, kohone, pomegranate, peonies, natto Xanthou, daiou, chanoki, chojinoki, chinneberry senna, tencha, tokkuri strawberry, tormentilla, rose, button, salamander, yachabushi, bayberry Extract of eucalyptus tree, logwood, bitumen (patent document 40), akebi, aloe, apricot, hippopotamus, kyoukou, trash, sanchinin ginseng, taukogi, narukoyuri, chickweed, hamadisha, bukuryo, yuzu extract (patent document 41), Examples include extracts of calcade, hibiscus, chazenshi, tonin, maroni, cinnamon, trash, shikon, senna, toshishi, and sandalwood (Patent Document 42). However, when considering the use as a preventive and therapeutic agent for diabetic complications, an external preparation for skin, and food and drink, it is expected that maintenance of effective blood concentration by long-term use is necessary. For example, aminoguanidine provided for clinical trials The effective blood concentration of is relatively high, and a large amount of administration is necessary to maintain the blood concentration, and there are concerns about side effects. On the other hand, natural antioxidants and plant extracts have also been shown to be effective, but no substances have been found that are significantly effective at low concentrations compared to aminoguanidine.
JP-A-62-249909 JP 2003-300961 A JP 2002-302472 A JP 2001-64158 A JP 2000-32273 A JP 2000-256259 A JP-A-11-106371 JP 11-49740 A Japanese Patent Laid-Open No. 10-324629 Japanese Patent Laid-Open No. 10-182460 JP-A-10-175554 Japanese Patent Laid-Open No. 10-167965 JP-A-10-158244 Japanese Patent Laid-Open No. 9-212473 JP-A-9-212427 Japanese Patent Laid-Open No. 9-124471 Japanese Patent Laid-Open No. 9-59258 Japanese Patent Laid-Open No. 9-59233 Japanese Patent Laid-Open No. 9-40626 JP 7-133264 A JP-A-6-305964 JP-A-6-298738 JP-A-6-298737 JP-A-6-287180 JP-A-6-287179 Japanese Patent Laid-Open No. 6-192089 JP-A-6-135968 JP-A-5-255130 JP 2003-212774 A Japanese Patent Laid-Open No. 10-36257 JP 9-315960 A JP-A-9-241165 JP-A-9-221667 JP-A-9-40519 JP-A-8-59485 Japanese Patent Laid-Open No. 7-324025 JP 7-109215 A JP-A-6-336430 JP 2003-221770 A JP 2002-241299 A JP 2002-241293 A JP-A-11-106336 Vlassara, H. et al., Lab. Invest., 70, 138-151 (1994) Sasaki, N. et al., Brain Res., 888, 256-262 (2001) Sasaki, N. et al., Neurosci. Lett., 326, 117-120 (2002) Kikuchi, S. et al., Amyotroph. Lateral Scler. Other Motor Neuron Disord., 3, 63-68 (2002) Abe, R. et al., J. Invest. Dermatol., 122, 461-467 (2004) Fu, MX. Et al., J. Biol. Chem., 271, 9982-9986 (1996) Glomb, MA. Et al., J. Biol. Chem., 270, 10017-10026 (1995) Wells-Knecht, KJ. Et al., Biochemistry, 34, 3702-3709 (1995) Thornalley, PJ. Et al., Biochem. J., 344, 109-116 (1999) Niwa, T. et al., Nephron, 69, 438 (1995).

  An object of the present invention is to provide an excellent Maillard reaction inhibitor, an external preparation for skin containing the Maillard reaction inhibitor as an active ingredient, a preventive and therapeutic agent for diabetic complications, and a food and drink.

The gist of the present invention is as follows.
(1) Maillard reaction inhibitor containing cultured cell extract of Murasaki genus plant or processed product thereof as an active ingredient.
(2) Maillard reaction inhibitor containing a caffeic acid polymer as an active ingredient.
(3) The caffeic acid polymer is one or more selected from rosmarinic acid or a salt thereof, lysospermic acid or a salt thereof, lysospermic acid B or a salt thereof, and epilabdocin or a salt thereof. Maillard reaction inhibitor.
(4) An external preparation for skin comprising the Maillard reaction inhibitor according to any one of (1) to (3) as an active ingredient.
(5) Maillard reaction inhibitor composition containing the following components (A) and (B).
(A) One or more medicinal components selected from the group consisting of a cell extract extracted from a plant of the genus Murasaki, a processed product thereof, or a caffeic acid polymer, and (B) a whitening agent, an antioxidant, and an anti-inflammatory agent One or more medicinal components selected from the group consisting of an antibacterial agent, a cell activator, a moisturizer, and a peripheral blood flow promoter.
(6) A preventive and therapeutic agent for diabetic complications, comprising one or more selected from the Maillard reaction inhibitor according to any one of (1) to (3).
(7) Food / beverage products containing 1 type, or 2 or more types chosen from the Maillard reaction inhibitor in any one of said (1)-(3).

  ADVANTAGE OF THE INVENTION According to this invention, the outstanding Maillard reaction inhibitor, the skin external preparation which uses this Maillard reaction inhibitor as an active ingredient, the prevention and treatment agent of diabetic complication, and food-drinks can be provided.

  Hereinafter, the present invention will be described in detail.

  The method for preparing the extract of the cell extract of the genus Murasaki used in the present invention is not particularly limited, but the cultured cell is established from a part of the plant body such as a leaf, root, or stem of the genus Lithospermum. The cells, the culture solution, or a mixture thereof can be dried and then extracted. Examples of the plants of the genus Lithospermum that serve as raw materials for establishing cultured cells include purple (Lithospermum erythrorhizon et. Lithospermum zollingeri A.DC.) and the like. Among them, purple (Lithospermum erythrorhizon et. Zucc.) Is preferable. In addition, the production area of these genus plants is not particularly limited. The roots of purple are called purple roots, and it is known in Kampo that the extract has anti-inflammatory, anti-edema and anti-tumor effects.

  Although it is not particularly limited as a method for establishing the cultured cells of the genus Murasaki and the established cultured cells, as an example of preferred culture, callus is aseptically obtained from a part of the tissue of the genus Murasaki, for example, cotyledons, Furthermore, a strain in which the content of p-O-β-D-glucosylbenzoic acid (PHBOG) is maintained at a high level is obtained, and the cells are subcultured every 14 days to proliferate the cells. Examples thereof include a method of obtaining a cell line having a high content of caffeic acid polymer, which is cultured in a caffeic acid polymer production induction medium, for example, a liquid medium of M-9 and does not exhibit a purple color derived from naphthoquinone. The extract prepared from the cell line having a high content of caffeic acid polymer obtained by the above method is clearly different from the extract extracted from purple root containing naphthoquinone and showing purple, in terms of components, color tone, etc. It could not be assumed that the extract extracted from the cell line exhibited a Maillard reaction inhibitory action.

  Examples of the extraction solvent used in preparing an extract from Murasaki plant culture cells include water and lower monohydric alcohols (methyl alcohol, ethyl alcohol, 1-propanol, 2-propanol, 1-butanol, 2-butanol, etc.). Liquid polyhydric alcohols (glycerin, propylene glycol, 1,3-butylene glycol, etc.), lower alkyl esters (ethyl acetate, etc.), hydrocarbons (benzene, hexane, pentane, etc.), ketones (acetone, methyl ethyl ketone, etc.), ethers (Diethyl ether, tetrahydrofuran, dipropyl ether, etc.), acetonitrile and the like can be mentioned, and one kind or two or more kinds can be used.

  As an example of a preferable extraction method, water, ethyl alcohol, or a mixed solvent thereof is used, extracted at room temperature or heated for 1 to 5 days, filtered, and the obtained filtrate is further filtered for 1 week. There is a method in which the mixture is allowed to stand for aging and then filtered again. The mixing ratio (volume%) of the mixed solvent of water and ethyl alcohol can be appropriately selected depending on the extraction material, the extraction conditions, and the like.

  The extract thus obtained can be used as it is as an active ingredient such as the Maillard reaction inhibitor of the present invention. In addition, the extract is treated by various purification means such as ion exchange chromatography, gel filtration chromatography, dialysis, etc., and is used as a processed product with further enhanced activity by obtaining an active fraction using Maillard reaction inhibitory activity as an index. Also good.

  The caffeic acid polymer of the present invention is a compound containing a structure in which two or more molecules of caffeic acid are polymerized and a salt thereof, and preferably a caffeic acid polymer in which caffeic acid is polymerized from two to four molecules. Examples thereof include, but are not particularly limited to, for example, rosmarinic acid, lysospermic acid, lysospermic acid B, epilabdocin, lysospermic acid magnesium salt, lysospermic acid B magnesium salt, lysospermic acid ammonium / potassium salt, lysospermic acid B Examples include calcium / magnesium salts.

  The Maillard reaction inhibitor of the present invention contains a cultured cell extract of Murasaki spp. Or a processed product thereof as an active ingredient, and if necessary, at least one of a carrier for a formulation and a diluent, and further various additives, May be prepared as a Maillard reaction inhibitor composition. Moreover, the ratio of the component (A) and the component (B) in the one containing the component (A) and the component (B) mentioned above as the Maillard reaction inhibitor composition of the present invention is not particularly limited and is in a wide range. Usually, the component (A) may be 0.001 to 10% by weight, preferably 0.01 to 5% by weight, and the component (B) is 0% based on the total weight of the composition. 0.01 to 10% by weight, preferably 0.1 to 5% by weight.

  The Maillard reaction inhibitor of the present invention is not limited as long as it inhibits the Maillard reaction. For example, in the comparison of the presence / absence conditions of the test sample, the inhibitor of AGEs generation intermediate compounds and AGEs generated by the progress of the Maillard reaction are used. It is specified by a method of measuring and calculating and comparing, or a method of detecting fluorescence that is a feature of AGEs and calculating a generation suppression degree thereof, and its shape is not particularly limited.

  In addition to the Maillard reaction inhibitor of the present invention, the external preparation for skin, the preventive and therapeutic agent for diabetic complications comprising the Maillard reaction inhibitor of the present invention as an active ingredient, and the food and drink, a carrier ordinarily used in pharmaceuticals and cosmetics, etc. Components as diluents, for example, powder components, liquid fats and oils, solid fats and oils, waxes, hydrocarbon oils, higher fatty acids, ester oils, silicone oils, anionic surfactants, cationic surfactants, amphoteric surfactants, nonionic interfaces Activators, water-soluble polymers, thickeners, UV absorbers, sequestering agents, alcohols, sugars, amino acids, organic amines, polymer emulsions, pH adjusters, vitamins, antioxidants, antioxidant aids, A moisturizer, water, whitening agent, anti-inflammatory agent, antibacterial agent, cell activator, peripheral vascular blood flow promoter, etc. are appropriately blended as necessary, in the form of a solution, gel, emulsion, solid, powder ,pace Jo, film-like, aerosol-like cosmetics, can be prepared by generally known methods depending on the dosage form intended. Specific ingredients that can be blended are listed below, and the Maillard reaction inhibitor of the present invention and any one or more of the following ingredients are blended to prepare the topical skin preparation of the present invention and prevent diabetic complications. And a therapeutic agent and food-drinks can be prepared.

  Examples of the powder component include inorganic powders (for example, talc, kaolin, mica, sericite (sericite), muscovite, phlogopite, synthetic mica, saucite, biotite, permiculite, magnesium carbonate, calcium carbonate, silicic acid. Aluminum, barium silicate, calcium silicate, magnesium silicate, strontium silicate, metal tungstate, magnesium, silica, zeolite, barium sulfate, calcined calcium sulfate (baked gypsum), calcium phosphate, fluorine apatite, hydroxyapatite, ceramic powder Organic powder (eg, polyamide resin powder (nylon powder), polyethylene powder, polymethyl methacrylate powder, polystyrene powder, copolymer resin powder of styrene and acrylic acid, benzoguanamine resin powder, poly-4 Ethylene powder, cellulose powder, metal soap (eg, zinc myristate, calcium palmitate, aluminum stearate); inorganic white pigment (eg, titanium dioxide, zinc oxide, etc.); inorganic red pigment (eg, iron oxide) (Bengara), iron titanate, etc.); inorganic brown pigments (eg, γ-iron oxide, etc.); inorganic yellow pigments (eg, yellow iron oxide, ocher, etc.); inorganic black pigments (eg, black iron oxide, Low-order titanium oxide, etc.); inorganic purple pigments (eg, manganese violet, cobalt violet, etc.); inorganic green pigments (eg, chromium oxide, chromium hydroxide, cobalt titanate, etc.); inorganic blue pigments (eg, ultramarine blue) Pearl pigments (eg, titanium oxide coated mica, titanium oxide coated bismuth oxychloride, titanium oxide coated) Lac, colored titanium oxide coated mica, bismuth oxychloride, fish scale foil, etc.); metal powder pigments (eg, aluminum powder, copper powder, etc.); organic pigments such as zirconium, barium, or aluminum lake (eg, red 201, red 202) No., Red No. 204, Red No. 205, Red No. 220, Red No. 226, Red No. 228, Red No. 405, Orange No. 203, Orange No. 204, Yellow No. 205, Yellow No. 401, Blue No. 404, Red No. 3, Red 104, Red 106, Red 227, Red 230, Red 401, Red 505, Orange 205, Yellow 4, Yellow 5, Yellow 202, Yellow 203, Green 3 and Blue 1 Etc.); natural pigments (for example, chlorophyll, β-carotene, etc.) and the like.

  Examples of liquid oils include avocado oil, camellia oil, turtle oil, macadamia nut oil, corn oil, mink oil, olive oil, rapeseed oil, egg yolk oil, sesame oil, persic oil, wheat germ oil, southern castor oil, castor oil, linseed oil , Safflower oil, cottonseed oil, eno oil, soybean oil, peanut oil, tea seed oil, kaya oil, rice bran oil, cinnagiri oil, Japanese kiri oil, jojoba oil, germ oil, triglycerin and the like.

  Examples of the solid fat include cacao butter, coconut oil, hardened coconut oil, palm oil, palm kernel oil, owl kernel oil, hardened oil, owl, and hardened castor oil.

  As the wax, for example, beeswax, candelilla wax, cotton wax, carnauba wax, bayberry wax, ibota wax, whale wax, montan wax, nuka wax, lanolin, kapok wax, liquid lanolin, sugar cane wax, lanolin fatty acid isopropyl, lauryl hexyl, reduced lanolin, jojoba wax, Examples include hard lanolin, shellac wax, POE lanolin alcohol ether, POE lanolin alcohol acetate, POE cholesterol ether, lanolin fatty acid polyethylene glycol, POE hydrogenated lanolin alcohol ether, and the like.

  Examples of the hydrocarbon oil include liquid paraffin, ozokerite, squalane, pristane, paraffin, ceresin, squalene, petrolatum, microcrystalline wax, and the like.

  Examples of higher fatty acids include lauric acid, myristic acid, palmitic acid, stearic acid, behenic acid, oleic acid, undecylenic acid, tall oil fatty acid, isostearic acid, linoleic acid, linolenic acid, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) etc. are mentioned.

  Examples of ester oils include isopropyl myristate, cetyl octanoate, octyldodecyl myristate, isopropyl palmitate, butyl stearate, hexyl laurate, myristyl myristate, decyl oleate, hexyl decyl dimethyloctanoate, cetyl lactate, lactic acid Myristyl, lanolin acetate, isocetyl stearate, isocetyl isostearate, cholesteryl 12-hydroxystearate, ethylene glycol di-2-ethylhexanoate, dipentaerythritol fatty acid ester, n-alkyl glycol monoisostearate, neopentyl glycol dicaprate, Diisostearyl malate, glycerin di-2-heptylundecanoate, trimethylolpropane tri-2-ethylhexanoate, triiso Trimethylolpropane teaate, pentaerythritol tetra-2-ethylhexanoate, glycerin tri-2-ethylhexanoate, glyceryl trioctanoate, glyceryl triisopalmitate, trimethylolpropane triisostearate, cetyl 2-ethylhexanoate, 2-ethylhexyl palmitate, glyceryl trimyristate, glyceride tri-2-heptylundecanoate, castor oil fatty acid methyl ester, oleyl oleate, acetoglyceride, 2-heptylundecyl palmitate, diisobutyl adipate, N-lauroyl-L -Glutamic acid-2-octyldodecyl ester, di-2-heptylundecyl adipate, ethyl laurate, di-2-ethylhexyl sebacate, 2-hexyl myristate Rudeshiru, palmitic acid 2-hexyl decyl, 2-hexyldecyl adipate, diisopropyl sebacate, 2-ethylhexyl succinate, and triethyl citrate.

  Examples of the silicone oil include linear polysiloxanes (for example, dimethylpolysiloxane, methylphenylpolysiloxane, diphenylpolysiloxane, etc.); cyclic polysiloxanes (for example, octamethylcyclotetrasiloxane, decamethylcyclopentasiloxane, dodecamethylcyclohexyl). And silicone resins that form a three-dimensional network structure, various modified polysiloxanes (amino-modified polysiloxane, polyether-modified polysiloxane, alkyl-modified polysiloxane, fluorine-modified polysiloxane, etc.) It is done.

  Anionic surfactants include, for example, fatty acid soaps (eg, sodium laurate, sodium palmitate, etc.); higher alkyl sulfates (eg, sodium lauryl sulfate, potassium lauryl sulfate, etc.); alkyl ether sulfates (eg, POE-lauryl sulfate triethanolamine, POE-sodium lauryl sulfate, etc.); N-acyl sarcosine acid (eg, sodium lauroyl sarcosine, etc.); higher fatty acid amide sulfonates (eg, sodium N-myristoyl-N-methyl taurate, palm Oil fatty acid methyl taurine sodium, lauryl methyl taurine sodium, etc .; Phosphate ester salt (POE-oleyl ether sodium phosphate, POE-stearyl ether phosphate, etc.); Sulfosuccinate (for example, Sodium di-2-ethylhexyl sulfosuccinate, sodium monolauroyl monoethanolamide polyoxyethylene sodium sulfosuccinate, sodium lauryl polypropylene glycol sulfosuccinate, etc .; alkyl benzene sulfonates (eg, sodium linear dodecyl benzene sulfonate, triso linear dodecyl benzene sulfonate) Ethanolamine, linear dodecyl benzene sulfonic acid, etc.); higher fatty acid ester sulfates (for example, hydrogenated coconut oil fatty acid sodium glycerin sulfate, etc.); N-acyl glutamate (for example, monosodium N-lauroyl glutamate, di-N-stearoyl glutamate) Sodium, N-myristoyl-L-monosodium glutamate, etc.); sulfated oil (eg funnel oil); POE-A Kill ether carboxylic acid; POE-alkyl allyl ether carboxylate; α-olefin sulfonate; higher fatty acid ester sulfonate; secondary alcohol sulfate ester; higher fatty acid alkylolamide sulfate ester; lauroyl monoethanolamide succinic acid Sodium; N-palmitoyl aspartate ditriethanolamine; sodium caseinate and the like.

  Examples of the cationic surfactant include alkyltrimethylammonium salts (eg, stearyltrimethylammonium chloride, lauryltrimethylammonium chloride, etc.); alkylpyridinium salts (eg, cetylpyridinium chloride, etc.); distearyldimethylammonium dialkyldimethylammonium chloride; Poly (N, N′-dimethyl-3,5-methylenepiperidinium chloride); alkyl quaternary ammonium salt; alkyldimethylbenzylammonium salt; alkylisoquinolinium salt; dialkyl morpholinium salt; POE-alkylamine; Examples include alkylamine salts; polyamine fatty acid derivatives; amyl alcohol fatty acid derivatives; benzalkonium chloride; benzethonium chloride and the like.

  Examples of amphoteric surfactants include imidazoline-based amphoteric surfactants (eg, 2-undecyl-N, N, N- (hydroxyethylcarboxymethyl) -2-imidazoline sodium, 2-cocoyl-2-imidazolinium hydroxide). Side-1-carboxyethyloxy disodium salt, etc.); betaine surfactants (for example, 2-heptadecyl-N-carboxymethyl-N-hydroxyethylimidazolinium betaine, lauryldimethylaminoacetic acid betaine, alkylbetaine, amide betaine) , Sulfobetaine, etc.).

  Examples of the lipophilic nonionic surfactant include sorbitan fatty acid esters (for example, sorbitan monooleate, sorbitan monoisostearate, sorbitan monolaurate, sorbitan monopalmitate, sorbitan monostearate, sorbitan sesquioleate, Sorbitan trioleate, diglycerol sorbitan penta-2-ethylhexylate, diglycerol sorbitan tetra-2-ethylhexyl); glycerin polyglycerin fatty acids (for example, mono-cotton oil fatty acid glycerin, mono-erucic acid glycerin, sesquioleate glycerin, monostearin) Glycerin acid, α, α′-oleic acid pyroglutamate glycerin, monostearate glycerin malate, etc.); propylene glycol fatty acid esters (for example, Nosutearin propylene glycol, etc.); hydrogenated castor oil derivatives; glycerol alkyl ethers, and the like.

  Examples of the hydrophilic nonionic surfactant include POE-sorbitan fatty acid esters (for example, POE-sorbitan monooleate, POE-sorbitan monostearate, POE-sorbitan monooleate, POE-sorbitan tetraoleate, etc.); POE sorbite fatty acid esters (eg, POE-sorbite monolaurate, POE-sorbite monooleate, POE-sorbite pentaoleate, POE-sorbite monostearate, etc.); POE-glycerin fatty acid esters (eg, POE-glycerin) Monostearate, POE-glycerol monoisostearate, POE-monooleate such as POE-glycerol triisostearate, etc.); POE-fatty acid esters (eg, POE-distearate, PO Monodiolates, ethylene glycol distearate, etc.); POE-alkyl ethers (eg POE-lauryl ether, POE-oleyl ether, POE-stearyl ether, POE-behenyl ether, POE-2-octyldecyl ether, POE-cholestanol) Ethers, etc.); Pluronic types (for example, Pluronic etc.); POE • POP-alkyl ethers (for example, POE • POP-cetyl ether, POE • POP-2-decyltetradecyl ether, POE • POP-monobutyl ether, POE) POP-hydrogenated lanolin, POE / POP-glycerin ether, etc.) Tetra POE / tetra-POP-ethylenediamine condensates (eg, Tetronic etc.); POE-castor oil hydrogenated castor oil derivative ( For example, POE-castor oil, POE-hardened castor oil, POE-hardened castor oil monoisostearate, POE-hardened castor oil triisostearate, POE-hardened castor oil monopyroglutamic acid monoisostearic acid diester, POE-hardened castor Oil maleic acid, etc.); POE-beeswax lanolin derivatives (eg POE-sorbite beeswax etc.); alkanolamides (eg coconut oil fatty acid diethanolamide, lauric acid monoethanolamide, fatty acid isopropanolamide etc.); POE-propylene glycol fatty acid Examples include esters; POE-alkylamines; POE-fatty acid amides; sucrose fatty acid esters; alkyl ethoxydimethylamine oxides;

  Examples of natural water-soluble polymers include plant-based polymers (for example, gum arabic, gum tragacanth, galactan, guar gum, carob gum, caraya gum, carrageenan, pectin, agar, quince seed (malmello), alge colloid (guckweed extract), starch (Rice, corn, potato, wheat), glycyrrhizic acid); microbial polymer (eg, xanthan gum, dextran, succinoglucan, pullulan, etc.); animal polymer (eg, collagen, casein, albumin, gelatin, etc.), etc. Is mentioned.

  Semi-synthetic water-soluble polymers include, for example, starch polymers (eg, carboxymethyl starch, methylhydroxypropyl starch, etc.); cellulose polymers (methylcellulose, ethylcellulose, methylhydroxypropylcellulose, hydroxyethylcellulose, sodium cellulose sulfate) Hydroxypropylcellulose, carboxymethylcellulose, sodium carboxymethylcellulose, crystalline cellulose, cellulose powder and the like); alginic acid polymers (for example, sodium alginate, propylene glycol alginate, etc.) and the like.

  Synthetic water-soluble polymers include, for example, vinyl polymers (eg, polyvinyl alcohol, polyvinyl methyl ether, polyvinyl pyrrolidone, carboxyvinyl polymer); polyoxyethylene polymers (eg, polyethylene glycol 20,000, 40). , 000, 60,000 polyoxyethylene polyoxypropylene copolymer, etc.); acrylic polymers (for example, sodium polyacrylate, polyethyl acrylate, polyacrylamide, etc.); polyethyleneimine; cationic polymers, and the like.

  Examples of the thickener include gum arabic, carrageenan, caraya gum, gum tragacanth, carob gum, quince seed (malmello), casein, dextrin, gelatin, sodium pectate, sodium alginate, methylcellulose, ethylcellulose, CMC, hydroxyethylcellulose, hydroxypropyl Cellulose, PVA, PVM, PVP, sodium polyacrylate, carboxyvinyl polymer, locust bean gum, guar gum, tamarind gum, cellulose dialkyldimethylammonium sulfate, xanthan gum, magnesium aluminum silicate, bentonite, hectorite, AlMg silicate (Beegum), Examples thereof include laponite and silicic anhydride.

Examples of the ultraviolet absorber include the following compounds.
(1) Benzoic acid ultraviolet absorbers, for example, paraaminobenzoic acid (hereinafter abbreviated as PABA), PABA monoglycerin ester, N, N-dipropoxy PABA ethyl ester, N, N-diethoxy PABA ethyl ester, N, N-dimethyl PABA ethyl ester, N, N-dimethyl PABA butyl ester, N, N-dimethyl PABA ethyl ester and the like.
(2) Anthranilic acid-based ultraviolet absorbers such as homomenthyl-N-acetylanthranilate.
(3) Salicylic acid ultraviolet absorbers such as amyl salicylate, menthyl salicylate, homomenthyl salicylate, octyl salicylate, phenyl salicylate, benzyl salicylate, p-isopropanol phenyl salicylate, and the like.
(4) Cinnamic acid-based ultraviolet absorbers For example, octyl cinnamate, ethyl-4-isopropyl cinnamate, methyl-2,5-diisopropyl cinnamate, ethyl-2,4-diisopropyl cinnamate, methyl-2,4- Diisopropyl cinnamate, propyl-p-methoxycinnamate, isopropyl-p-methoxycinnamate, isoamyl-p-methoxycinnamate, octyl-p-methoxycinnamate (2-ethylhexyl-p-methoxycinnamate), 2-ethoxy Ethyl-p-methoxycinnamate, cyclohexyl-p-methoxycinnamate, ethyl-α-cyano-β-phenylcinnamate, 2-ethylhexyl-α-cyano-β-phenylcinnamate, glyceryl mono-2-ethylhexanoyl -Diparamet Such as Shishin'nameto.
(5) Triazine-based ultraviolet absorber, for example, bisresorcinyl triazine. More specifically, bis {[4- (2-ethylhexyloxy) -2-hydroxy] phenyl} -6- (4-methoxyphenyl) 1,3,5-triazine, 2,4,6-tris { 4- (2-ethylhexyloxycarbonyl) anilino} 1,3,5-triazine and the like.
(6) Other ultraviolet absorbers For example, 3- (4′-methylbenzylidene) -d, l-camphor, 3-benzylidene-d, l-camphor, 2-phenyl-5-methylbenzoxazole, 2-hydroxy -4-methoxyphenylbenzotriazole, 2- (2'-hydroxy-5'-t-octylphenyl) benzotriazole, 2- (2-hydroxy-5-methylphenyl) benzotriazole, dibenzalazine, dianisoylmethane, 4- Pyridazine derivatives such as methoxy-4′-t-butyldibenzoylmethane, 5- (3,3-dimethyl-2-norbornylidene) -3-pentan-2-one, dimorpholinopyridazinone and the like.

  Examples of the sequestering agent include 1-hydroxyethane-1,1-diphosphonic acid, 1-hydroxyethane-1,1-diphosphonic acid tetrasodium salt, disodium edetate, trisodium edetate, and tetrasodium edetate. Sodium citrate, sodium polyphosphate, sodium metaphosphate, gluconic acid, phosphoric acid, citric acid, ascorbic acid, succinic acid, edetic acid, trisodium ethylenediaminehydroxyethyl triacetate and the like.

  Examples of the lower alcohol include ethanol, propanol, isopropanol, isobutyl alcohol, t-butyl alcohol and the like.

  Examples of the polyhydric alcohol include divalent alcohols (for example, ethylene glycol, propylene glycol, trimethylene glycol, 1,2-butylene glycol, 1,3-butylene glycol, tetramethylene glycol, 2,3-butylene glycol, Pentamethylene glycol, 2-butene-1,4-diol, hexylene glycol, octylene glycol, etc.); trivalent alcohol (for example, glycerin, trimethylolpropane, 1,2,6-hexanetriol, etc.); tetravalent Alcohol (eg, pentaerythritol); pentavalent alcohol (eg, xylitol); hexavalent alcohol (eg, sorbitol, mannitol, etc.); polyhydric alcohol polymer (eg, diethylene glycol, dipropylene glycol, trie) Ren glycol, polypropylene glycol, tetraethylene glycol, diglycerin, polyethylene glycol, triglycerin, tetraglycerin, polyglycerin, etc.); divalent alcohol ethers (eg, ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, ethylene glycol mono) Butyl ether, ethylene glycol monophenyl ether, ethylene glycol monohexyl ether, ethylene glycol mono 2-methylhexyl ether, ethylene glycol isoamyl ether, ethylene glycol benzyl ether, ethylene glycol isopropyl ether, ethylene glycol dimethyl ether, ethylene glycol diethyl ether, ethylene glycol di Butyl ether, Pyrene glycol monomethyl ether, propylene glycol monoethyl ether, propylene glycol monobutyl ether, propylene glycol isopropyl ether, etc.); polyhydric alcohol polymer alkyl ethers (for example, diethylene glycol monomethyl ether, diethylene glycol monoethyl ether, diethylene glycol monobutyl ether, diethylene glycol dimethyl ether, Diethylene glycol diethyl ether, diethylene glycol butyl ether, diethylene glycol methyl ethyl ether, triethylene glycol monomethyl ether, triethylene glycol monoethyl ether, dipropylene glycol methyl ether, dipropylene glycol ethyl ether, dipropylene glycol Butyl ether, etc.); dihydric alcohol ether esters (for example, ethylene glycol monomethyl ether acetate, ethylene glycol monoethyl ether acetate, ethylene glycol monobutyl ether acetate, ethylene glycol monophenyl ether acetate, diethylene glycol monoethyl ether acetate, diethylene glycol monobutyl ether acetate, propylene) Glycol monomethyl ether acetate, propylene glycol monoethyl ether acetate, propylene glycol monopropyl ether acetate, propylene glycol monophenyl ether acetate, etc.); glycerin monoalkyl ether (for example, chimyl alcohol, ceralkyl alcohol, batyl alcohol, etc.); Cole (eg, sorbitol, maltitol, maltotriose, mannitol, sucrose, erythritol, glucose, fructose, amylolytic sugar, maltose, xylitol, amylolytic sugar reducing alcohol, etc.); glycolide; tetrahydrofurfuryl alcohol; POE -Tetrahydrofurfuryl alcohol; POP-butyl ether; POP / POE-butyl ether; Tripolyoxypropylene glycerin ether; POP-glycerin ether; POP-glycerin ether phosphate; POP / POE-pentane erythritol ether, polyglycerin and the like.

  Examples of higher alcohols include linear alcohols (eg, lauryl alcohol, cetyl alcohol, stearyl alcohol, behenyl alcohol, myristyl alcohol, oleyl alcohol, cetostearyl alcohol); branched chain alcohols (eg, monostearyl glycerin ether (batyl alcohol) ), 2-decyltetradecinol, lanolin alcohol, cholesterol, phytosterol, hexyldodecanol, isostearyl alcohol, octyldodecanol and the like.

Examples of monosaccharides include tricarbon sugars (eg, D-glyceryl aldehyde, dihydroxyacetone, etc.); tetracarbon sugars (eg, D-erythrose, D-erythrulose, D-treose, erythritol, etc.); pentose sugars (eg, L-arabinose, D-xylose, L-lyxose, D-arabinose, D-ribose, D-ribulose, D-xylulose, L-xylulose, etc .; hexose (eg, D-glucose, D-talose, D) -Bucicose, D-galactose, D-fructose, L-galactose, L-mannose, D-tagatose, etc.); pentose sugar (eg, aldheptose, heproose, etc.); octose sugar (eg, octulose, etc.); For example, 2-deoxy-D-ribose, 6-deoxy-L-galactose, 6-deoxy-L Mannose, etc.]; amino sugars (eg, D-glucosamine, D-galactosamine, sialic acid, aminouronic acid, muramic acid, etc.); uronic acids (eg, D-glucuronic acid, D-mannuronic acid, L-guluronic acid, D- Galacturonic acid, L-iduronic acid, etc.).
Examples of the oligosaccharide include sucrose, umbelliferose, lactose, planteose, isolicnose, α, α-trehalose, raffinose, lycnose, umbilicin, stachyose verbus course, and the like.

Examples of the polysaccharide include cellulose, quince seed, chondroitin sulfate, starch, galactan, dermatan sulfate, glycogen, gum arabic, heparan sulfate, hyaluronic acid, tragacanth gum, keratan sulfate, chondroitin, xanthan gum, mucoitin sulfate, guar gum, dextran, kerato sulfate. , Locust bingham, succinoglucan, caronic acid and the like.
Examples of amino acids include neutral amino acids (eg, threonine, cysteine, etc.); basic amino acids (eg, hydroxylysine, etc.) and the like. Examples of the amino acid derivative include acyl sarcosine sodium (lauroyl sarcosine sodium), acyl glutamate, acyl β-alanine sodium, glutathione, and pyrrolidone carboxylic acid.

  Examples of the organic amine include monoethanolamine, diethanolamine, triethanolamine, morpholine, triisopropanolamine, 2-amino-2-methyl-1,3-propanediol, 2-amino-2-methyl-1-propanol, and the like. Is mentioned.

  Examples of the polymer emulsion include an acrylic resin emulsion, a polyethyl acrylate emulsion, an acrylic resin liquid, a polyacryl alkyl ester emulsion, a polyvinyl acetate resin emulsion, and a natural rubber latex.

  Examples of the pH adjusting agent include buffers such as lactic acid-sodium lactate, citric acid-sodium citrate, and succinic acid-sodium succinate.

  Examples of vitamins include vitamin A, B1, B2, B6, C, E and derivatives thereof, pantothenic acid and derivatives thereof, biotin and the like.

Examples of the antioxidant include vitamin E and derivatives thereof (dl-α (β, γ) -tocopherol, dl-α-tocopherol acetate, nicotinic acid-dl-α-tocopherol, linoleic acid-dl-α-tocopherol, Tocopherols such as dl-α-tocopherol succinate and derivatives thereof, ubiquinones, etc., vitamin A and derivatives thereof (retinol palmitate, retinol acetate such as retinol and derivatives thereof, retinal such as dehydroretinal and derivatives thereof), carotenoids (Carotene, lycopene, astaxanthin, etc.), vitamin B and its derivatives (thiamine hydrochloride, thiamine sulfate, riboflavin, riboflavin acetate, pyridoxine hydrochloride, pyridoxine dioctanoate, flavin adenine dinucleotide, cyanocobalamin, Acids, nicotinic acid amides, nicotinic acids such as benzyl nicotinate, cholines, etc.), vitamin C and derivatives thereof (L-ascorbic acid alkyl esters such as L-ascorbyl dipalmitate and L-ascorbyl tetraisopalmitate, L- Ascorbic acid phosphate, L-ascorbic acid sulfate, etc.), vitamin D and its derivatives (ergocalciferol, cholecalciferol, dihydroxystannal etc.), rutin and its derivatives, thiotaurine, taurine, hydroquinone and its derivatives, histidine Catechins and derivatives thereof, grabrizine, glabrene, liquiritin, isoliquiritin and licorice extract containing these, glutathione and derivatives thereof, dibutylhydroxytoluene, butylhydroxyanisole , Gallic acid and its derivatives, cholesterol and its derivatives, superoxide dismutase, mannitol, cucumber extract, quette extract, gentian (gentian) extract, genus shochu extract, hawthorn extract, peonies extract, ginkgo biloba extract, koganebana (Ougon) extract, carrot extract, maika (maikai, hermanus) extract, sunpens (kawara ketsumei) extract, tormentilla extract, parsley extract, grape extract, button (button pi) extract, mokka (bokeh) extract , Melissa extract, Yashajitsu (Yasha) extract, Yukinoshita extract, Rosemary (mannenrou) extract, lettuce extract, tea extract (Oolong tea, black tea, green tea, etc.), microbial fermentation metabolites, seaweed extract, Ganoderma extract, eggshell membrane extract, fetus Extracts include swingle extract or the like. (In parentheses, plant aliases and herbal medicine names are listed.)
Examples of the antioxidant assistant include phosphoric acid, citric acid, ascorbic acid, maleic acid, malonic acid, succinic acid, fumaric acid, kephalin, hexametaphosphate, phytic acid, and ethylenediaminetetraacetic acid.

  Examples of humectants include polyethylene glycol, propylene glycol, glycerin, 1,3-butylene glycol, xylitol, sorbitol, maltitol, chondroitin sulfate, hyaluronic acid, mucoitin sulfate, caronic acid, atelocollagen, cholesteryl-12-hydroxystearate, and lactic acid. Examples thereof include sodium, bile salt, dl-pyrrolidone carboxylate, short-chain soluble collagen, diglycerin (EO) PO adduct, Izayoi rose extract, yarrow extract, and mellote extract.

As a whitening agent, vitamin C and its derivatives (L-ascorbic acid alkyl esters such as L-ascorbyl dipalmitate, L-ascorbyl tetraisopalmitate, L-ascorbic acid phosphate, L-ascorbic acid sulfate, etc.) , Placenta extract, grabrizine, glabrene, liquiritin, isoliquiritin and licorice extract, pearl barley (yokuinin) extract, koganebana (ogon) extract, seaweed extract (comb, macombu, wakame, hijiki, hibamata, sujime Brown algae such as tiger beetle, tsunoarame, honda lawa, giant kelp; clover, tsunomatsu, sugi nori, usubanori, asakusanori, matsunori, tosaka pine, funori, ogonori, caimenso, igisori, egori Algae: Chlorella, Aonori, Donariella, Chlorococcus, Anaaaosa, Kawanoori, Marimo, Shiogusa, Casanori, Futojuzumo, Tamajuzumo, Aeguro, Aomidoro, etc .; Cyanobacteria such as Spirulina, etc.) Bikakuren extract, grape extract , Wheat extract, tomato extract, carotenoids (carotene, lycopene, astaxanthin, etc.), agarose, oligosaccharides, neoagarobiose, hydroquinone and its derivatives, cysteine and its derivatives, asparagus extract, ibukitorano extract, Neurose extract, Ezocogi extract, Pea extract, Chamomile extract, Caquette extract, Orange extract, Raspberry extract, Kiwi extract, Clara extract, Coffee extract, Gogo Oil, Sesame oil, Sesame extract, Rice extract, Rice extract, Saisin extract, Hawthorn extract, Kawaraketsumei (Sampens) extract, Peonies extract, Shirayuri extract, Mulberry (Sohakuhi) extract, Toki extract , Beech extract, beech sprout extract, black currant extract, hop extract, maika (maikai, hamanasu) extract, bokeh (mokka) extract, yukinoshita extract, tea extract (Oolong tea, black tea, green tea, etc. ), Ganoderma extract, microbial fermentation metabolite, soybean extract, molasses extract, Rakan fruit extract and the like. (In parentheses, plant aliases and herbal medicine names are listed.)
Anti-inflammatory agents include glycyrrhizic acid and its derivatives, glycyrrhetinic acid and its derivatives, vitamin B and its derivatives (thiamine hydrochloride, thiamine sulfate, riboflavin, riboflavin acetate, pyridoxine hydrochloride, pyridoxine dioctanoate, flavin adenine dinucleotide , Nicotinic acid such as cyanocobalamin, folic acid, nicotinic acid amide, benzyl nicotinate, choline, tranexamic acid, thiotaurine, hypotaurine, aloe extract, ashitaba extract, altea extract, arnica extract, sulfur and its derivatives, nettle Extract, Paramecium extract, Turmeric extract, Yellowfin extract, Hypericum extract, Chamomile extract, Comfrey extract, Honeysuckle extract, Cucumber Song extract, Salvia (sage) extract, Walnut extract (Juyu) extract, Perilla extract, Birch extract, Elderberry extract, Grape extract, Mulberry extract, Eucalyptus extract, Artemisia extract, Astragalus extract Examples include extracts, chondroitin sulfate and derivatives thereof, zinc oxide, etc. (In parentheses, plant aliases, herbal medicine names, etc. are described.)
Examples of the antibacterial agent include methyl paraben, ethyl paraben, butyl paraben, phenoxyethanol and the like.

Examples of cell activators include carotenoids (such as carotene, lycopene, astaxanthin), vitamin A and derivatives thereof (retinol such as retinol palmitate and retinol acetate; and retinals such as dehydroretinal and derivatives thereof), vitamin C and its derivatives. Derivatives (L-ascorbic acid alkyl esters such as L-ascorbyl dipalmitate and L-ascorbyl tetraisopalmitate, L-ascorbic acid phosphate, L-ascorbic acid sulfate, etc.), vitamin B and its derivatives (thiamine hydrochloride) Salt, thiamine sulfate, riboflavin, riboflavin acetate, pyridoxine hydrochloride, pyridoxine dioctanoate, flavin adenine dinucleotide, cyanocobalamin, folic acid, nicotinamide and benzyl nicotinate (Tinic acids, choline, etc.), ribonucleic acid and salts thereof, deoxyribonucleic acid and salts thereof, α- and γ-linolenic acid, xanthine and derivatives thereof (caffeine, etc.), amino acids and derivatives thereof (serine, glutamic acid, theanine, hydroxy) Proline, pyrrolidone carboxylic acid, etc.), docosahexaenoic acid and its derivatives, eicosapentaenoic acid and its derivatives, citric acid, lactic acid, malic acid, succinic acid, almond extract, asparagus extract, apricot extract, ginkgo biloba extract , Kihada extract, barley extract, kiwi extract, cucumber extract, shiitake extract, cedar extract, assembly extract, soybean extract, jujube extract, clover extract , Pepper extract, red pepper extract, tomato extract, Garlic extract, carrot extract, hinokitiol, beech extract, grape seed oil, beech extract, beech bud extract, peach extract, eucalyptus extract, lily extract, lettuce extract, lemon extract, rosemary (Mannenrou) extract, malt root extract, animal-derived extract (mollusk and other mollusc extracts, shell extract, shellfish extract, fish extract, chicken crown extract, royal jelly, silk protein and its degradation product, placenta Extract, serum deproteinized extract, lactoferrin or degradation product thereof), yeast extract, microbial fermentation metabolite (derived from lactic acid bacteria, bifidobacteria, etc.), ganoderma extract and the like. (In parentheses, plant aliases and herbal medicine names are listed.)
Examples of peripheral vascular blood flow promoters include vitamin E and its derivatives, assembly extract, garlic extract, ginger extract, red pepper extract, rosemary extract and the like.

  The Maillard reaction inhibitor of the present invention and one or more components described above can be combined to provide a multifunctional cosmetic.

  When blending the Maillard reaction inhibitor of the present invention in cosmetics or quasi-drugs, the blended amount of the cell extract of the genus Murasaki plant or its processed product is solid to the total amount of cosmetics or quasi-drugs. In terms of conversion, it is usually 0.001 to 10% by weight, preferably 0.01 to 5% by weight, and the blending amount of caffeic acid polymer is usually 0.0001 to 5% with respect to the total amount of cosmetics or quasi drugs. % By weight, preferably 0.001 to 2% by weight.

Hereinafter, although a reference example and an example are given and the present invention is explained in detail, the present invention is not limited to these examples.
[Reference Example 1] Preparation of Murasaki cultured cell extract from cultured cells derived from Lithospermum erythrorhizon Murasaki's sterilized sterilized with 2% antiformin solution or 70% ethanol solution in advance on Linsmeier Skoog (LS) agar solid medium A cotyledon tissue piece was placed and statically cultured in a dark place at 25 ° C. to obtain purple callus. By repeating the passage, the M-18TOM strain in which the content of p-O-β-D-glucosylbenzoic acid (PHBOG) was maintained high was obtained from a number of flasks. Next, 1 g of callus of M-18TOM strain (fresh weight) was transferred to a liquid culture medium of LS (containing 1 μM indoleacetic acid and 10 μM kinetin as plant hormones and 30 g / l sucrose as a carbon source) in an Erlenmeyer flask containing 20 ml. Rotating culture (amplitude 25 mm, 100 rpm) on a shaker and subcultured every 14 days to increase the growth rate of callus. In a subculture process by liquid culture, when cultivated experimentally in a liquid medium of M-9, there are a flask containing cultured cells that produce shikonin and a flask containing cultured cells that are not produced. The 18TOM strain and the cultured cells that were not produced were designated as the WM18 strain. Furthermore, while subcultured the M-18TOM strain, a cultured cell line that did not produce shikonin was isolated, and the newly obtained strain that did not produce shikonin was named TomK2.

The TomK2 strain cultured cells thus obtained were transferred to a culture tank containing 150 l of an M-9 liquid medium and cultured with aeration and stirring at 25 ° C. for 21 days. After completion of the culture, the cultured cells and the culture solution were separated by filtration, and the obtained cultured cells were dried by ventilation at 60 ° C. Add 100 liters of 80 vol% ethyl alcohol solution to 100 g of dried Lithospermum erythrorhizon cultured cells (TomK2 strain), extract at room temperature for 3 days, filter, and evaporate the solvent under reduced pressure to remove murasaki cultured cell extract. Got.
Reference Example 2 Obtaining Caffeic Acid Polymer Murasaki cultured cell extract is subjected to low pressure column chromatography (column: φ45 × 500 mm, filler: Wakosil 25C18 (15-30 μm), solvent: 30% methanol aqueous solution to 100% methanol linear gradient. ), The peak portion corresponding to each caffeic acid polymer compound (rosmarinic acid, lysospermic acid, lysospermic acid B, epilabdocin) is fractionated, and the solvent of each fraction is distilled off under reduced pressure. A caffeic acid polymer was obtained.
[Example 1]
Using the fluorescence intensity derived from AGEs as an index, the inhibitory effect of the Maillard reaction was evaluated. 25 μg / mL Murasaki cultured cell extract dissolved in type I collagen, 200 mM glucose, 15 mM sodium azide, 5% DMSO with a final concentration of 0.9 mg / mL was mixed, and the mixture was kept at 37 ° C. and 100% humidity in a light-shielding tube. Incubated. The solution was stirred once every two days, and the fluorescence intensity observed after 3 weeks was measured ex. 335 nm, em. Measured at 420 nm, the change was compared. The results are shown in Table 1.
[Example 2]
The test substance was carried out in the same manner as in Example 1 except that 100 nM epilabdocin, lysospermic acid B, lysospermic acid, rosmarinic acid or caffeic acid was used. The results are shown in Table 1.
[Comparative Example 1]
The procedure was the same as that described in Example 1, except that 100 μM or 100 nM aminoguanidine was used instead of the Murasaki cultured cell extract. The results are shown in Table 1.
[Comparative Example 2]
The procedure was the same as that described in Example 1 except that no Murasaki cultured cell extract was added. The results are shown in Table 1.

Inhibition of fluorescence intensity derived from 70% AGEs was observed with the addition of 100 μM aminoguanidine used as a positive target, and 70% inhibition was also observed with the addition of 25 μg / mL Murasaki cultured cell extract and 100 nM epilabdocin. Epilabdocin showed the same inhibitory effect at 1/1000 concentration as compared to aminoguanidine. Aminoguanidine was not inhibited at 100 nM concentration.
[Example 3]
The Maillard reaction inhibitory effect was evaluated using the production amount of 3-deoxyglucosone known as an intermediate product in the Maillard reaction with collagen and glucose as an index. 3-Deoxyglucosone contained in the sample incubated in the same manner as in Example 1 was converted to 2,3-diaminonaphthalene and quantified by HPLC using 2,3-butanedione as an internal standard under the following conditions. The results are shown in Table 2.
HPLC condition column: COSMOSIL 5PE-MS (4.6 × 250 mm, manufactured by Nacalai Tesque)
Measurement wavelength: 268 nm
Moving bed: 50 mM phosphoric acid: acetonitrile: methanol = 6: 2: 2
Flow rate: 1.0 mL / min [Example 4]
The test was carried out in the same manner as in Example 3 except that the test substance was 100 μM or 100 nM epilabdocin, lysospermic acid B, lysospermic acid, rosmarinic acid or caffeic acid. The results are shown in Table 2.
[Comparative Example 3]
The same procedure as described in Example 3 was performed except that 100 μM or 100 nM aminoguanidine was used instead of the Murasaki cultured cell extract. The results are shown in Table 2.
[Comparative Example 4]
The procedure was the same as that described in Example 3 except that no Murasaki cultured cell extract was added. The results are shown in Table 2.

Murasaki cultured cell extract and caffeic acid polymer showed a strong 3-deoxyglucosone production inhibitory effect equal to or better than aminoguanidine.
[Example 5]
The Maillard reaction inhibitory effect was evaluated using the production amount of 3-deoxyglucosone in Maillard reaction with bovine serum albumin (BSA, Sigma-Aldrich) and glucose as an index. The same procedure as in Example 3 was performed except that BSA having a final concentration of 50 mg / mL was used instead of type I collagen as a protein substrate in the method of Example 1. The results are shown in Table 3.
[Example 6]
The test was carried out in the same manner as in Example 5 except that the test substance was 100 μM or 100 nM epilabdocin, lysospermic acid B, lysospermic acid, rosmarinic acid or caffeic acid. The results are shown in Table 3.
[Comparative Example 5]
The same procedure as described in Example 5 was performed except that 100 μM or 100 nM aminoguanidine was used instead of the Murasaki cultured cell extract. The results are shown in Table 3.
[Comparative Example 6]
The procedure was the same as that described in Example 5 except that no Murasaki cultured cell extract was added. The results are shown in Table 3.

Murasaki cultured cell extract and caffeic acid polymer showed a strong 3-deoxyglucosone production inhibitory effect equal to or better than aminoguanidine.
[Example 7]
Normally, collagen fibers are recognized to produce α1 fibers by treatment with collagenase collagenase. However, when the Maillard reaction proceeds and the collagen fibers are denatured, the production of α1 fibers is suppressed because it becomes difficult to receive the action of collagenase. From this, the denaturation of collagen fibers by Maillard reaction was evaluated by measuring the production of α1 fibers observed after collagenase treatment. That is, 50 μl of a sample after 9 weeks incubated in the same manner as in Example 1, 16.09 units of collagenase (type IV,
from clostridium histolyticum, 715 unit / mg solid (manufactured by Sigma-aldrich), 0.1 mol / l CaCl ₂ in 50 mM Tris-HCl buffer solution (ph 7.5, 4 ° C.), and incubated at 37 ° C. for 1 hour 24 μl of the supernatant obtained by centrifugation at 8000 × g for 10 minutes was subjected to 10% SDS-polyacrylamide gel electrophoresis. The detected α1 fiber band was taken into a PC with a scanner (EPSON ES-2200) and quantified by a quantitative image analysis method (L Process V2.0 and Image Gauge V4.0, FUJI PHOTOFILM Co, Ltd.). The results are shown in Table 4.
[Example 8]
The test substance was carried out in the same manner as in Example 7 except that 100 μM or 100 nM of epilabdocin, lysospermic acid B, lysospermic acid, rosmarinic acid or caffeic acid was used. The results are shown in Table 4.
[Comparative Example 7]
The same procedure as described in Example 7 was performed except that 100 μM or 100 nM aminoguanidine was used instead of the Murasaki cultured cell extract. The results are shown in Table 4.
[Comparative Example 8]
The procedure was the same as that described in Example 7 except that no Murasaki cultured cell extract was added. The results are shown in Table 4.

  Murasaki extract cell extract, epilabdocin, lysospermic acid B, lysospermic acid at 100 nM concentration, rosmarinic acid at 100 μM concentration has higher α1 fiber band strength compared to no addition, and collagen fiber denaturation is suppressed It was. In particular, Murasaki cultured cell extract and epilabdocin showed a very high α1 fiber band strength compared to aminoguanidine.

Hereinafter, formulation examples (weight basis) of various dosage forms and anti-aging cosmetics containing Maillard reaction inhibitor according to the present invention will be described as production examples.
[Production Example 1] Lotion (Ingredient) (%)
(1) Glycerin: 10.0
(2) 1,3-butylene glycol: 6.0
(3) Murasaki cultured cell extract * 1: 1.0
(4) Citric acid: 0.1
(5) Sodium citrate: 0.3
(6) Purified water: remaining amount (7) polyoxyethylene (60EO) hydrogenated castor oil: 0.5
(8) Ethyl alcohol: 8.0
(9) Preservative: Appropriate amount (10) Fragrance: Appropriate amount * 1 Produced in Reference Example 1 (Production method)
A. Components (1) to (6) are mixed and dissolved.
B. Components (7) to (10) are mixed and dissolved.
C. A and B were mixed and uniformed to obtain a skin lotion.
[Production Example 2] Emulsion (component) (%)
(1) Sorbitan monostearate: 0.3
(2) Polyoxyethylene sorbitan monooleate (20.E.O.): 0.1
(3) Lipophilic glyceryl monostearate: 0.2
(4) Stearic acid: 0.5
(5) Cetanol: 0.5
(6) Squalane: 3.0
(7) Liquid paraffin: 4.0
(8) Glyceryl tri-2-ethylhexanoate: 2.0
(9) Methyl polysiloxane: 1.0
(10) Hydrogenated soybean phospholipid: 0.1
(11) Nicotinic acid dl-α-tocopherol: 0.05
(12) Preservative: Appropriate amount (13) Carboxyvinyl polymer aqueous solution (10%): 1.0
(14) Sodium hydroxide: 0.05
(15) Glycerin: 5.0
(16) 1,3-butylene glycol: 7.0
(17) Purified water: remaining amount (18) ethyl alcohol: 5.0
(19) Murasaki cultured cell extract: 0.1
(20) L-oxyproline: 0.2
(21) Hemp cellulose powder: 3.0
(22) Fragrance: appropriate amount (production method)
A. Ingredients (13) to (17) are heated and mixed and maintained at 70 ° C.
B. Ingredients (1) to (12) are heated and mixed and maintained at 70 ° C.
C. Add B to A, mix and uniformly emulsify.
D. After cooling C, (18) to (22) were added and mixed uniformly to obtain an emulsion.
[Production Example 3] Ointment (component) (%)
(1) Stearic acid: 18.0
(2) Cetanol: 4.0
(3) dl-α-tocopherol: 0.2
(4) Preservative: appropriate amount (5) Triethanolamine: 2.0
(6) Glycerin: 5.0
(7) Purified water: remaining amount (8) Murasaki cultured cell extract: 1.0
(9) Dipotassium glycyrrhizinate: 0.5
(10) Yeast extract: 0.5
(Manufacturing method)
A. A part of components (5), (6) and (7) is heat mixed and kept at 75 ° C.
B. Ingredients (1) to (4) are heated and mixed and maintained at 75 ° C.
C. Gradually add A to B.
D. (8)-(10) which melt | dissolved with the remainder of (7) was added, cooling C, and ointment was obtained.

[Production Example 4] Pack (component) (%)
(1) Polyvinyl alcohol: 15.0
(2) Silicic anhydride: 0.5
(3) Polyethylene glycol: 0.5
(4) Polyoxypropylene methyl glucoside: 5.0
(5) Glycerin: 5.0
(6) Purified water: remaining amount (7) ethyl alcohol: 20.0
(8) Preservative: appropriate amount (9) Murasaki cultured cell extract: 0.3
(10) Fragrance: appropriate amount (production method)
A. Components (1) to (6) are mixed, heated to 70 ° C., and stirred.
B. Mix components (7) and (8).
C. The above B was added to the previous A, mixed and then cooled to uniformly disperse (9) and (10) to obtain a pack.
[Production Example 5] Sunscreen emulsion (component) (%)
(1) Polyoxyalkylene-modified organopolysiloxane: 1.0
(2) Dimethylpolysiloxane: 5.0
(3) Octamethylcyclotetrasiloxane: 20.0
(4) Isotridecyl isononanoate: 5.0
(5) Paramethoxycinnamic acid-2-ethylhexyl: 5.0
(6) Preservative: appropriate amount (7) perfume: appropriate amount (8) fine particle titanium oxide: 10.0
(9) Particle zinc oxide: 10.0
(10) Zirconium oxide: 5.0
(11) Polystyrene powder: 3.0
(12) Trimethylsiloxysilicic acid: 0.5
(13) Dipropylene glycol: 3.0
(14) Ethyl alcohol: 10.0
(15) Purified water: Remaining amount (16) Salt: 0.2
(17) Murasaki cultured cell extract: 2.0
(18) Seaweed extract: 3.0
(Manufacturing method)
A. Components (1) to (12) are mixed and dispersed.
B. Components (13) to (16) are mixed and dispersed.
C. Add B to A and emulsify uniformly.
D. Components (17) and (18) were added to C to obtain a sunscreen emulsion.

[Production Example 6] Body soap (component) (%)
(1) Potassium laurate: 15.0
(2) Potassium myristate: 5.0
(3) Propylene glycol: 5.0
(4) Murasaki cultured cell extract: 2.0
(5) t-cinnamic acid: 0.01
(6) p-coumaric acid: 0.01
(7) Ferulic acid: 0.03
(8) Polyethylene powder: 0.5
(9) Amino acid: 0.5
(10) Hydroxypropyl chitosan solution: 0.5
(11) Preservative: Appropriate amount (12) pH adjuster: Appropriate amount (13) Fragrance: Appropriate amount (14) Purified water: Remaining amount [Production Example 7] Beverage (component) (%)
(1) Glucose liquid sugar: 30.0
(2) Grapefruit juice: 45.0
(3) Tangerine juice: 5.0
(4) Epilabdocin: 0.01
(5) Fructose: 4.0
(6) Fragrance: Appropriate amount (7) Acidulant: Appropriate amount [Production Example 8] Sausage (component) (%)
(1) Minced meat: 80.0
(2) Egg: 10.0
(3) Spices: 2.0
(4) Seasoning: 2.0
(5) Epirabidosine: 0.01
(6) Capsicum extract: 4.0
(7) p-hydroxybenzoic acid: 0.01

Claims (7)

  Maillard reaction inhibitor containing cultured cell extract of Murasaki genus plant or processed product thereof as an active ingredient.   Maillard reaction inhibitor containing a caffeic acid polymer as an active ingredient.   The Maillard reaction inhibition according to claim 2, wherein the caffeic acid polymer is one or more selected from rosmarinic acid or a salt thereof, lysospermic acid or a salt thereof, lysospermic acid B or a salt thereof, and epilabdocin or a salt thereof. Agent.   A skin external preparation comprising the Maillard reaction inhibitor according to any one of claims 1 to 3 as an active ingredient. Maillard reaction inhibitor composition containing the following components (A) and (B).
(A) One or more medicinal components selected from the group consisting of a cell extract extracted from a plant of the genus Murasaki, a processed product thereof, or a caffeic acid polymer, and (B) a whitening agent, an antioxidant, and an anti-inflammatory agent One or more medicinal components selected from the group consisting of an antibacterial agent, a cell activator, a moisturizer, and a peripheral blood flow promoter.   A prophylactic and therapeutic agent for diabetic complications, comprising one or more selected from the Maillard reaction inhibitor according to any one of claims 1 to 3.   Food / beverage products containing 1 type, or 2 or more types chosen from the Maillard reaction inhibitor in any one of Claims 1-3.