JP2012224602A - Age formation inhibitor - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an AGE formation inhibitor that further effectively inhibits AGE formation and has improved safety to a living body.SOLUTION: This AGE formation inhibitor includes fucoxanthin as an active ingredient.

Description

The present invention relates to a novel AGE production inhibitor. The present invention is widely used for pharmaceuticals, foods, external preparations for skin, and the like.

  Although there are still many unclear points regarding the process of producing AGE (Advanced Glycation End-product), it is considered that non-enzymatic saccharification reaction is the main component. That is, in AGE, an amino group present in a protein in an initial reaction and an aldehyde group of a reducing sugar such as glucose react non-enzymatically (Glycation), and an Amadori transfer product is formed via a Schiff base, It is considered that this is formed in a late reaction through a long and complicated cleavage or condensation.

Diabetic complications include retinopathy, nephropathy, neuropathy, ischemic heart disease, cerebrovascular disorder, etc. One of the causes of these diseases is that AGEs generated in hyperglycemic organisms are involved It has been confirmed (see Non-Patent Document 1, for example). Diabetic nephropathy is a microangiopathy of the kidney caused by diabetes, and glomerular basement membrane thickening and mesangial region expansion are the basic pathological changes. In recent years, with the increase of diabetic patients, diabetic nephropathy causes end-stage renal failure, and an increasing number of patients reach dialysis treatment. AGEs that can be achieved by maintaining a hyperglycemic state include 1) increased vascular permeability; 2) promoted protein and lipoprotein deposition; 3) inactivated nitric oxide (NO); 4) promoted extracellular matrix production; It is thought that it is involved in nephropathy onset (for example, refer nonpatent literature 2).

For the purpose of preventing and improving diabetic complications, various AGE production inhibitors for the purpose of inhibiting the production of such AGE are known.

As such an AGE production inhibitor, for example, a novel AGE production-inhibiting composition that inhibits the production of AGE as a cause causing diabetic complications such as nephropathy and retinopathy (see, for example, Patent Document 1), And an agent that inhibits AGE formation (see, for example, Patent Document 2). However, pharmaceuticals such as AGE production inhibitors are still in the development stage, and conventionally, such synthetic compounds often have unexpected side effects, preventing diseases through diet rather than treatment with synthetic pharmaceuticals. Research on ingredients or food ingredients with functions that can be suppressed, ameliorated and treated has gained attention.

On the other hand, a final glycation product (AGE) production inhibiting composition (for example, see Patent Documents 3 to 5) characterized by containing an extract of a plant as a food under such a background is also disclosed.

However, the inhibitory activity of AGE-inhibiting active ingredients present in such plant extracts is generally very low compared to synthetic compounds, and the amount of active ingredient present in the extracts is generally very low.

In order to prevent or treat diabetic complications, it is necessary to continue for a long period of time. Therefore, there is a demand for an AGE production inhibitor that can achieve both effective suppression of AGE generation and avoidance of side effects. .

Higashi, Tee. (Higasi, T) et al., BIO Clinica, 1997, Vol. 12, No. 2, p. 19-21 Bubba, tee. (Baba, T) et al., BIO Clinica, 1997, Vol. 12, No. 2, p. 39-48 Japanese Patent Laid-Open No. 10-324629 JP 2005-170935 A JP 2006-28090 A JP 2005-343842 A JP 2005-320262 A

  In recent years, apart from diabetes, it has become clear that AGE is closely related to skin aging. AGE increases with aging, but when a Maillard reaction occurs in the collagen part of the skin protein, the amino group of the lysine residue or the guanidyl group of the arginine residue and the carbonyl group of the sugar in the protein are non-enzymatic. AGE is generated and the collagen parts are cross-linked. When a cross-linked structure is formed, the molecule becomes hard, and the original elasticity of the skin is lost. Moreover, the cross-linked product is judged as a foreign substance, and the secretion amount of degrading enzymes (collagenase, elastase) increases. As a result, the firmness and elasticity of the skin is lost, the skin becomes brittle, and wrinkles, sagging and dullness are generated.

In this way, AGE generation mechanism has attracted attention not only from the viewpoint of triggering diabetic complications but also from the viewpoint of anti-aging.

  An object of the present invention is to provide an AGE production inhibitor that effectively inhibits AGE production and has improved safety for living bodies. With the goal.

In order to solve the above problems, the technical features of the present invention are as follows.
1. An AGE production inhibitor containing fucoxanthin as an active ingredient.

It is a graph which shows the AGE production inhibitory effect of a fucoxanthin (Example).

上記フコキサンチンを得る方法は特に限定されないが、天然物から抽出することが好ましい。より安定なフコキサンチンを得ることができるからである。
また、天然物からフコキサンチンを得る場合、その原料は特に限定されないが、例えば、海藻類、褐藻類等が挙げられる。尚、これらは、何れか一方のみを用いても良いし、両方を併用しても良い。 The present invention is described in detail below.
The present invention is characterized by containing fucoxanthin as an active ingredient.
Fucoxanthin is a known substance whose chemical formula is known as follows, and a substance with high purity has an orange columnar crystal structure.

The method for obtaining the fucoxanthin is not particularly limited, but it is preferably extracted from a natural product. This is because more stable fucoxanthin can be obtained.
Moreover, when obtaining fucoxanthin from a natural product, the raw material is not specifically limited, For example, seaweed, brown algae, etc. are mentioned. Note that only one of these may be used, or both may be used in combination.

The “seaweed” is not particularly limited, but for example, it is preferable to use kombu, wakame, arame, hondawala, akamoku, hijiki and the like. This is because they contain a relatively large amount of fucoxanthin, and are abundant as resources and industrially contribute as raw materials. These may be used alone or in combination of two or more.
Examples of the “brown algae” include, for example, Laminariaceae, Chlamaceae, etc. (Laminariales), Hibamatae, Sargasaceae, etc. (Chordaceae), brown algae belonging to the order of the order of the order of the family Chronariae (Spermatochnaceae) and the like are more preferred, but not limited thereto. These may be used alone or in combination of two or more.
In addition, as for the said sea algae and brown algae, both of these extracts may be used and any one extract may be used.

  Although the extraction method which obtains fucoxanthin from the said seaweed and brown algae is not specifically limited, For example, polar solvent extraction, supercritical extraction, etc. are mentioned. Only one of these may be performed, or both of them may be performed. Moreover, this extraction may be performed only once each method, or may be performed twice or more.

  Here, when extracting by polar solvent extraction, the polar solvent to be used is not particularly limited. For example, water, methanol, ethanol, isopropanol, acetone, 1,3-butylene glycol, ethylene glycol, propylene glycol, glycerin, acetic acid, Examples include ethyl acetate, ether, hexane and the like. Of these, water, methanol, and ethanol are preferred. It is because an active ingredient can be extracted efficiently. These may be used alone or in combination of two or more.

  When water is used as the extraction solvent, the extraction temperature is 20 to 100 ° C, preferably about 40 to 70 ° C. This is because if the extraction temperature is too low, it is difficult to extract active ingredients. The kind of water for extraction is not particularly limited, and tap water, distilled water, mineral water, alkaline ionized water and the like can be used.

  When ethanol or hydrous ethanol is used as the extraction solvent, the ethanol concentration is preferably 30 wt% or more, preferably 50 wt% or more (including 100 wt%). This is because when the amount is less than 30 wt%, the extraction amount of the active ingredient tends to decrease. The extraction temperature is 0 to 95 ° C, preferably about 20 to 80 ° C. In addition, the water-containing ethanol extraction may be repeated at various concentrations in order to improve the content of the active ingredient.

  In addition, when extracting with a polar solvent, the extraction method is not particularly limited, and for example, any method such as continuous extraction, immersion extraction, countercurrent extraction, etc. can be adopted, and any device can be used at room temperature or under reflux heating. Can be used. In addition, when extracting by the method mentioned above, only one of these may be performed and these methods may be combined. These extractions may be performed only once or may be performed twice or more.

As a specific method, an extraction raw material is put into a treatment tank filled with an extraction solvent, and an active ingredient is eluted while stirring. For example, when water, water-containing ethanol, or ethanol is used as the extraction solvent, the polar solvent is used in an amount of about 5 to 100 times (weight ratio) of the extraction raw material, and the extraction is performed for about 1 minute to 150 hours. The active ingredient is eluted in the solvent, and then filtered to remove the extraction residue to obtain an extract. Thereafter, the extract is subjected to treatments such as dilution, concentration, drying, and purification according to a conventional method to obtain an extract containing a high concentration of fucoxanthin.
Examples of the purification method include activated carbon treatment, resin adsorption treatment, ion exchange resin, liquid-liquid countercurrent distribution, and the like.

  Furthermore, when performing extraction by supercritical extraction, the supercritical fluid used at this time is not particularly limited, and examples thereof include carbon dioxide and nitrogen. In addition, these may use only 1 type and may use 2 or more types together. Of these, carbon dioxide is particularly preferred. It is because an active ingredient can be extracted more easily. The extraction method at this time may be performed by a known method. Thereafter, the extract is subjected to treatments such as dilution, concentration, drying, and purification according to a conventional method to obtain an extract containing a high concentration of fucoxanthin.

Since the AGE production inhibitor of the present invention effectively inhibits AGE production, it can effectively prevent diabetic complications such as nephropathy and retinopathy.
Further, by further suppressing AGE production, particularly by inhibiting AGE production in fibroblasts, cross-linking of collagen parts in the skin can be improved, and skin hardening can be prevented.

The AGE production inhibitor of the present invention can be used as a material for various foods and drinks. Examples of food and drink include edible oils (salad oil, confectionery (gum, candy, caramel, chocolate, cookies, snacks, jelly, gummi, tablet confectionery, etc.), noodles (soba, udon, ramen, etc.), dairy products (milk , Ice cream, yogurt, etc.), seasonings (miso, soy sauce, etc.), soups, beverages (juice, coffee, tea, tea, carbonated drinks, sports drinks, etc.) and health foods (tablets, Capsules, etc.), nutritional supplements (nutrient drinks, etc.) The AGE production inhibitor of the present invention may be appropriately blended with these foods and drinks.

These foods and drinks can be blended with various ingredients depending on the type, for example, glucose, fructose, sucrose, maltose, sorbitol, stevioside, corn syrup, lactose, citric acid, tartaric acid, malic acid, succinic acid. Acid, lactic acid, L-ascorbic acid, dl-α-tocopherol, sodium erythorbate, glycerin, propylene glycol, glycerin fatty acid ester, polyglycerin fatty acid ester, sucrose fatty acid ester, sorbitan fatty acid ester, propylene glycol fatty acid ester, gum arabic, Food materials such as carrageenan, casein, gelatin, pectin, agar, vitamin Bs, nicotinic acid amide, calcium pantothenate, amino acids, calcium salts, pigments, fragrances and preservatives can be used. Further, the present AGE production inhibitor having a health maintenance function includes other antioxidants and health food materials such as reduced ascorbic acid (vitamin C), vitamin E, reduced glutatin, tocotrienol, vitamin A derivatives. Lycopene, β-cryptoxanthin, astaxanthin, zeaxanthin, fucoxanthin, uric acid, ubiquinone, coenzyme Q10, folic acid, garlic extract, allicin, sesamin, lignans, catechin, isoflavone, chalcone, tannins, flavonoids, coumarins, isocoumarins , Blueberry extract, health food material) (Vitamin) A, V. B1, V. B2, V.B. B6, V.I. B12, V.I. C, V.D. D, V.D. E, V.E. P, choline, niacin, pantothenic acid, calcium folate, EPA, oligosaccharide, dietary fiber, squalene, soy lecithin, taurine, donariella, protein, octacosanol, DHA, egg yolk lecithin, linoleic acid, lactoferrin, magnesium, zinc, chromium, selenium , Potassium, heme iron, oyster meat extract, chitosan, chitin oligosaccharide, collagen, chondroitin, elastin, turmeric, licorice, kokushi, keihi, hawthorn, ginger, ganoderma, swordfish extract, suppon, licorice, kokushi, keihi, seiyou, Hawthorn, ginger, ganoderma, plantain, chamomile, chamomile, dandelion, hibiscus, honey, boren, royal jelly, lime, lavender, rosehip, rosemary, sage, bifidobacteria, faecalis Lacris, wheat germ oil, sesame oil, perilla oil, soybean oil, medium chain fatty acid, agaricus, ginkgo biloba extract, chondroitin, brown rice germ extract, litchi, onion, DHA, EPA, DPA, strawberry tea, cordyceps, garlic, bee, Papaya, Puaru, Propolis, Meguri Tree, Yabushitake, Royal Jelly, Saw Palmetto, Hyaluronic Acid, Gabba, Harpseal Oil, Shark Cartilage, Glucosamine, Lecithin, Phosphatidylserine, Padlock Carrot, Mulberry Leaf, Soybean Extract, Echinacea, Ekokogi , Barley extract, olive leaf, olive fruit, Gymnema, banaba, Salacia, Garcinia, chitosan, St. John's wort, jujube, carrot, passionflower, broccoli, placenta, pearl barley, grape seed, peanut seed coat, bilberry, buoy Cook Cohosh, Maria Thistle, Laurel, Sage, Rosemary, Luffa, Black Vinegar, Goya, Maca, Safflower, Flax, Oolong Tea, Flower Thorn, Caffeine, Capsaicin, Xylooligosaccharide, Glucosamine, Buckwheat, Citrus, Dietary Fiber, Protein, Prunes , Spirulina, Barley Young Leaves, Nucleic Acid, Yeast, Shiitake Mushroom, Plum Meat, Amino Acid, Deep Sea Mushroom Extract, Noni, Oyster Meat, Suppon, Champignon, Plantain, Acerola, Pineapple, Banana, Peach, Apricot, Melon, Strawberry, Raspberry, Orange , Fucoidan, Meshima Cobb, Cranberry, Zinc, Iron, Silk Peptide, Glycine, Niacin, Chest Tree, Ceramide, L-Cysteine, Red Wine Juice, Millet, Horsetail, Biotin, Centella Asiatica, Hascup, Pycnogenol, Fuqui, Ruba Bulb, clove, puer, citric acid, brewer's yeast, merirot, black zinger, ginger, gadget, nattokinase, benichouji, tocotrienol, lactoferrin, buckwheat, cocoa, dokudami, kiwi, hihatu, lotus leaf, paffia, star fruit, etc. Can be blended.

As a specific production method, fucoxanthin is spray-dried or freeze-dried together with powdered cellulose, and this can be easily contained in foods and drinks (instant foods, etc.) by making powders, granules, tablets or solutions.
In addition, fucoxanthin can be dissolved in, for example, fats and oils, ethanol, glycerin, or a mixture thereof to form a liquid and added to a beverage or added to a solid food. If necessary, it can be mixed with a binder such as gum arabic or dextrin to form a powder or granules and added to a beverage or a solid food.

As the addition amount when applying the AGE production inhibitor of the present invention to foods and drinks, since the main purpose is disease prevention and health maintenance, the content of active ingredients in the foods and drinks is 1 to 20 wt% or less in total. Preferably there is.

The AGE production inhibitor of the present invention may be used as a raw material for medicines (including pharmaceuticals and quasi drugs). It can be produced by appropriately blending the AGE production inhibitor of the present invention with a raw material for a pharmaceutical preparation. Examples of the pharmaceutical raw material that can be blended in the AGE production inhibitor of the present invention include, for example, excipients (glucose, lactose, sucrose, sodium chloride, starch, calcium carbonate, kaolin, crystalline cellulose, cocoa butter, hydrogenated vegetable oil, kaolin, and talc. Etc.), binder (distilled water, physiological saline, ethanol water, simple syrup, glucose solution, starch solution, gelatin solution, carboxymethylcellulose, potassium phosphate, polyvinylpyrrolidone, etc.), disintegrant (sodium alginate, agar, hydrogen carbonate) Sodium, calcium carbonate, sodium lauryl sulfate, stearic acid monoglyceride, starch, lactose, gum arabic powder, gelatin, ethanol, etc.), disintegration inhibitors (sucrose, stearin, cocoa butter, hydrogenated oil, etc.), absorption enhancers (fourth) Quaternary ammonium base, sodium lauryl sulfate ), Adsorbent (glycerin, starch, lactose, kaolin, bentonite, silicic acid, etc.), lubricants (purified talc, stearates, polyethylene glycol, and the like) and the like.

The administration method of the AGE production inhibitor according to the present invention can be generally administered orally in the form of tablets, pills, soft / hard capsules, fine granules, powders, granules, liquids, etc. It may be administered parenterally. When administered as a parenteral agent, it can be applied in the form of a solution, or in the form of a haptic agent, lotion agent, ointment, tincture, cream, etc. with the addition of a dispersant, suspension, stabilizer, etc. can do.

The dose may vary depending on the administration method, medical condition, age of the patient, etc., but for adults, it can be generally administered as 1 to 1000 mg as an active ingredient per day, and for children it is usually about 0.5 to 500 mg.
The mixing ratio of the AGE production inhibitor can be appropriately changed depending on the dosage form, but is usually about 0.3 to 15.0 wt% when administered orally or by mucosal absorption, and when administered parenterally. , About 0.01 to 10 wt%. In addition, since the dose varies depending on various conditions, a dose smaller than the above dose may be sufficient, or it may be necessary to administer beyond the range.

Examples of the form of external skin material to which the AGE production inhibitor of the present invention can be blended include, for example, emulsion, soap, facial cleanser, bath preparation, cream, emulsion, lotion, eau de cologne, shaving cream, shaving lotion, Cosmetic oil, suntan / sunscreen lotion, powder, foundation, perfume, pack, nail cream, enamel, enamel remover, eyebrow, blusher, eye cream, eye shadow, mascara, eyeliner, lipstick, lip balm, shampoo, rinse , Treatments, hair dyes, dispersions, cleaning agents and the like.
Examples of the form of a pharmaceutical or quasi-drug that can contain the AGE production inhibitor of the present invention include ointments, creams, and liquids for external use.

In addition to the AGE production inhibitor according to the present invention, the external preparation for skin of the above form includes ingredients, oils, and high-grade ingredients blended in skin external preparations such as cosmetics and quasi-drugs as long as the AGE production inhibitory effect is not impaired Alcohols, fatty acids, ultraviolet absorbers, powders, pigments, surfactants, polyhydric alcohols / sugars, polymers, physiologically active ingredients, solvents, antioxidants, fragrances, preservatives, and the like can be blended.
Examples are listed below, but the present invention is not limited to these examples.
(1) Examples of oil components Ester-based oil phase components: glyceryl tri-2-ethylhexanoate, cetyl 2-ethylhexanoate, isopropyl myristate, butyl myristate, isopropyl palmitate, ethyl stearate, octyl palmitate, isostearic acid Isocetyl, butyl stearate, butyl myristate, ethyl linoleate, isopropyl linoleate, ethyl oleate, isocetyl myristate, isostearyl myristate, isostearyl palmitate, octyldodecyl myristate, isocetyl isostearate, diethyl sebacate, adipine Diisopropyl acid, isoaralkyl neopentanoate, glyceryl tri (capryl / capric acid), trimethylolpropane tri-2-ethylhexanoate, triisostearic acid tri Tyrololpropane, pentaerythritol tetra-2-ethylhexanoate, cetyl caprylate, decyl laurate, hexyl laurate, decyl myristate, myristyl myristate, cetyl myristate, stearyl stearate, decyl oleate, cetyl ricinoleate, lauric acid Isostearyl, isotridecyl myristate, isocetyl myristate, isostearyl myristate, isocetyl palmitate, isostearyl palmitate, octyl stearate, isocetyl stearate, isodecyl oleate, octyldodecyl linoleate, octyldodecyl isoleate, isopropyl isostearate , Cetostearyl 2-ethylhexanoate, stearyl 2-ethylhexanoate, hexyl isostearate, diocta Ethylene glycol acid, ethylene glycol dioleate, propylene glycol dicaprate, propylene glycol di (capryl / capric acid), propylene glycol dicaprylate, neopentyl glycol dicaprate, neopentyl glycol dioctanoate, glyceryl tricaprylate, glyceryl triundecylate, tri Glyceryl isopalmitate, glyceryl triisostearate, octyldodecyl neopentanoate, isostearyl octoate, octyl isononanoate, hexyldecyl neodecanoate, octyldodecyl neodecanoate, isocetyl isostearate, isostearyl isostearate, octyldecyl isostearate, polyglycerin Oleic acid ester, polyglycerol isostearic acid ester, charcoal Dipropyl acid, dialkyl carbonate (C12-18), triisocetyl citrate, triisoaralkyl citrate, triisooctyl citrate, lauryl lactate, myristyl lactate, cetyl lactate, octyldecyl lactate, triethyl citrate, acetyl triethyl citrate, citrate Acetyl tributyl acid, trioctyl citrate, diisostearyl malate, 2-ethylhexyl hydroxystearate, di2-ethylhexyl succinate, diisobutyl adipate, diisopropyl sebacate, dioctyl sebacate, cholesteryl stearate, cholesteryl isostearate, hydroxystearic acid Cholesteryl acid, cholesteryl oleate, dihydrocholesteryl oleate, phytosteryl isostearate, phytosteryl oleate, 12-sulfate Aroyl hydroxystearic acid isocetyl, 12-stearoyl-hydroxystearic acid stearyl 12-stearoyl-hydroxystearic acid isostearate, and the like.
Hydrocarbon oil phase components: squalane, liquid paraffin, α-olefin oligomer, isoparaffin, ceresin, paraffin, liquid isoparaffin, polybutene, microcrystalline wax, petrolatum and the like.
Animal and vegetable oils and their hydrogenated oils, and naturally occurring waxes: beef tallow, hydrogenated beef tallow, lard, hydrogenated tallow, horse oil, hydrogenated horse oil, mink oil, orange luffy oil, fish oil, hydrogenated fish oil, egg yolk oil and other animal oils and Its hardened oil, avocado oil, almond oil, olive oil, cacao butter, apricot oil, kukui nut oil, sesame oil, wheat germ oil, rice germ oil, rice bran oil, safflower oil, shea butter, soybean oil, evening primrose oil, perilla oil, Tea seed oil, camellia oil, corn oil, rapeseed oil, hardened rapeseed oil, palm kernel oil, hardened palm kernel oil, palm oil, hardened palm oil, peanut oil, hardened peanut oil, castor oil, hardened castor oil, sunflower oil, Vegetable oil such as grape seed oil, jojoba oil, hardened jojoba oil, macadamia nut oil, medhome oil, cottonseed oil, hardened cottonseed oil, coconut oil, hardened coconut oil and its hardened oil, beeswax, Acid number beeswax, lanolin, reduced lanolin, hydrogenated lanolin, liquid lanolin, carnauba wax and montan wax.
Silicone oil phase components: dimethylpolysiloxane, methylphenylpolysiloxane, methylcyclopolysiloxane, octamethylpolysiloxane, decamethylpolysiloxane, dodecamethylcyclosiloxane, methylhydrogenpolysiloxane, polyether-modified organopolysiloxane, dimethyl Siloxane / methylcetyloxysiloxane copolymer, dimethylsiloxane / methylstearoxysiloxane copolymer, alkyl-modified organopolysiloxane, terminal-modified organopolysiloxane, amino-modified silicone oil, amino-modified organopolysiloxane, dimethiconol, silicone gel, acrylic Examples include silicone, trimethylsiloxysilicic acid, and silicone RTV rubber.
Fluorine oil phase components: perfluoropolyether, fluorine-modified organopolysiloxane, fluorinated pitch, fluorocarbon, fluoroalcohol, fluoroalkyl / polyoxyalkylene co-modified organopolysiloxane, and the like.
(2) Examples of higher alcohols include lauryl alcohol, myristyl alcohol, cetyl alcohol, stearyl alcohol, isostearyl alcohol, oleyl alcohol, behenyl alcohol, 2-ethylhexanol, hexadecyl alcohol, octyldodecanol and the like.
(3) Examples of fatty acids Caprylic acid, capric acid, undecylenic acid, lauric acid, myristic acid, palmitic acid, palmitoleic acid, stearic acid, isostearic acid, oleic acid, linoleic acid, linolenic acid, arachidic acid, arachidonic acid, behenic acid , Erucic acid, 2-ethylhexanoic acid and the like.
(4) Examples of UV absorbers Paraaminobenzoic acid, amyl paraaminobenzoate, ethyldihydroxypropyl paraaminobenzoate, glyceryl paraaminobenzoate, ethyl paraaminobenzoate, octyl paraaminobenzoate, octyldimethyl paraaminobenzoate, ethylene glycol salicylate, salicylic acid Octyl, triethanolamine salicylate, phenyl salicylate, butylphenyl salicylate, benzyl salicylate, homomenthyl salicylate, benzyl cinnamate, octyl paramethoxycinnamate, 2-ethylhexyl paramethoxycinnamate, mono 2-diparamethoxycinnamate Glyceryl ethylhexanoate, isopropyl paramethoxycinnamate, diethanolamine salt of paramethoxyhydrocinnamate, diisopropyl diisopropylke Cinnamic acid ester mixture, urocanic acid, ethyl urocanate, hydroxymethoxybenzophenone, hydroxymethoxybenzophenonesulfonic acid and its salt, dihydroxymethoxybenzophenone, dihydroxymethoxybenzophenone sodium disulfonate, dihydroxybenzophenone, dihydroxydimethoxybenzophenone, hydroxyoctoxybenzophenone, Tetrahydroxybenzophenone, butylmethoxydibenzoylmethane, 2,4,6-trianilino-p- (carbo-2-ethylhexyl-1-oxy) -1,3,5-triazine, 2- (2-hydroxy-5-methyl) Phenyl) benzotriazole, methyl-O-aminobenzoate, 2-ethylhexyl-2-cyano-3,3-diphenyl acrylate, phenol Rubenzimidazole sulfate, 3- (4-methylbenzylidene) camphor, isopropyldibenzoylmethane, 4- (3,4-dimethoxyphenylmethylene) -2,5-dioxo-1-imidazolidinepropionate 2-ethylhexyl, and the like, and These polymer derivatives, silane derivatives and the like can be mentioned.
(5) Examples of powders and pigments: Red No. 104, Red No. 201, Yellow No. 4, Blue No. 1, Black No. 401 and other dyes, Yellow No. 4 AL lake, Yellow No. 203 BA lake and other lake dyes, Nylon powder , Silk powder, urethane powder, Teflon (registered trademark) powder, silicone powder, polymethyl methacrylate powder, cellulose powder, starch, silicone elastomer spherical powder, polyethylene powder, yellow iron oxide, red iron oxide, black Colored pigments such as iron oxide, chromium oxide, carbon black, ultramarine and bitumen, white pigments such as zinc oxide, titanium oxide and cerium oxide, extender pigments such as talc, mica, sericite, kaolin and barium sulfate plate, titanium mica Pearl pigments such as barium sulfate, calcium carbonate, magnesium carbonate, aluminum silicate, silica Metal salts such as magnesium, inorganic powders such as silica and alumina, metal soap such as aluminum stearate, magnesium stearate, zinc palmitate, zinc myristate, magnesium myristate, zinc laurate, zinc undecylenate, bentonite, smectite And boron nitride. There are no particular restrictions on the shape of these powders (spherical, rod-like, needle-like, plate-like, irregular shape, flake-like, spindle-like, etc.) and particle diameter. These powders are conventionally known surface treatments such as fluorine compound treatment, silicone treatment, silicone resin treatment, pendant treatment, silane coupling agent treatment, titanium coupling agent treatment, oil agent treatment, N-acylated lysine treatment, The surface treatment may or may not be performed in advance by polyacrylic acid treatment, metal soap treatment, amino acid treatment, lecithin treatment, inorganic compound treatment, plasma treatment, mechanochemical treatment or the like.
(6) Examples of surfactants Anionic surfactants: fatty acid soap, α-acyl sulfonate, alkyl sulfonate, alkyl allyl sulfonate, alkyl naphthalene sulfonate, alkyl sulfate, POE alkyl ether sulfate Salt, alkylamide sulfate, alkyl phosphate, POE alkyl phosphate, alkylamide phosphate, alkyloyl alkyl taurate, N-acyl amino acid salt, POE alkyl ether carboxylate, alkyl sulfosuccinate, alkyl sulfo Examples thereof include sodium acetate, acylated hydrolyzed collagen peptide salt, and perfluoroalkyl phosphate.
Cationic surfactant: alkyltrimethylammonium chloride, stearyltrimethylammonium chloride, stearyltrimethylammonium bromide, cetostearyltrimethylammonium chloride, distearyldimethylammonium chloride, stearyldimethylbenzylammonium chloride, behenyltrimethylammonium bromide, benzalkonium chloride , Behenic acid amidopropyldimethylhydroxypropylammonium chloride, stearic acid diethylaminoethylamide, stearic acid dimethylaminopropylamide, lanolin derivative quaternary ammonium salts, and the like.
Amphoteric surfactants: carboxybetaine type, amide betaine type, sulfobetaine type, hydroxysulfobetaine type, amide sulfobetaine type, phosphobetaine type, aminocarboxylate type, imidazoline derivative type, amidoamine type and the like.
Nonionic surfactant: propylene glycol fatty acid ester, glycerin fatty acid ester, polyglycerin fatty acid ester, sorbitan fatty acid ester, POE sorbitan fatty acid ester, POE sorbit fatty acid ester, POE glycerin fatty acid ester, POE alkyl ether, POE fatty acid ester, POE cured castor Oil, POE castor oil, POE / POP copolymer, POE / POP alkyl ether, polyether-modified silicone lauric acid alkanolamide, alkylamine oxide, hydrogenated soybean phospholipid and the like.
Natural surfactant: lecithin, saponin, sugar surfactant and the like.
(7) Examples of polyhydric alcohols and sugars Ethylene glycol, diethylene glycol, polyethylene glycol, propylene glycol, dipropylene glycol, polypropylene glycol, glycerin, diglycerin, polyglycerin, 3-methyl-1,3-butanediol, 1, 3 -Butylene glycol, sorbitol, mannitol, raffinose, erythritol, glucose, sucrose, fructose, xylitol, lactose, maltose, maltitol, trehalose, alkylated trehalose, mixed isomerized sugar, sulfated trehalose, pullulan and the like. These chemically modified compounds can also be used.
(8) Examples of polymers Acrylic ester / methacrylic acid ester copolymer (plus size, manufactured by Kyoyo Chemical), vinyl acetate / crotonic acid copolymer (resin 28-1310, manufactured by NSC), vinyl acetate / croton Acid / vinyl neodecanate copolymer (28-2930, manufactured by NSC), methyl vinyl ether maleic acid half ester (Gantrez ES, manufactured by ISP), T-butyl acrylate / ethyl acrylate / methacrylic acid copolymer (rubymer) , Manufactured by BASF), vinylpyrrolidone / vinyl acetate / vinyl propionate copolymer (rubiscol VAP, manufactured by BASF), vinyl acetate / crotonic acid copolymer (ruby set CA, manufactured by BASF), vinyl acetate / croton Acid / vinyl pyrrolidone copolymer (ruby set CAP, BA F), vinyl pyrrolidone / acrylate copolymer (Rubiflex, BASF), acrylate / acrylamide copolymer (Ultrahold, BASF), vinyl acetate / butyl maleate / isobornyl acrylate copolymer Anionic polymer compounds such as coalescence (Advantage, made by ISP), carboxyvinyl polymer (Carbopol, made by BFGoodrich), acrylic acid / alkyl methacrylate copolymer (Pemulene, made by BFGoodrich), and dialkylaminoethyl methacrylate Amphoteric products such as amphoteric products of polymers (Yuka Former, manufactured by Mitsubishi Chemical), octyl acrylate acrylate / hydroxypropyl acrylate / butylaminoethyl methacrylate copolymer (AMPHOMER, manufactured by NSC), etc. Molecular compounds, cationic polymer compounds such as quaternized vinylpyrrolidone / dimethylaminoethyl methacrylate (GAFQUAT, manufactured by ISP), methylvinylimidazolium chloride / vinylpyrrolidone copolymer (ruby coat, manufactured by BASF), polyvinylpyrrolidone (Lubicol K, manufactured by BASF), vinylpyrrolidone / vinyl acetate copolymer (Rubicol VA, manufactured by BASF), vinylpyrrolidone / dimethylaminoethyl methacrylate copolymer (copolymer 937, manufactured by ISP), vinyl caprolactam / Nonionic polymer compounds such as vinylpyrrolidone / dimethylaminoethyl methacrylate copolymer (copolymer VC713, manufactured by ISP) and the like. Cellulose or derivatives thereof, keratin and collagen or derivatives thereof, calcium alginate, pullulan, agar, gelatin, tamarind seed polysaccharide, xanthan gum, carrageenan, high methoxyl pectin, low methoxyl pectin, guar gum, gum arabic, crystalline cellulose, arabino Naturally derived polymer compounds such as galactan, gum karaya, gum tragacanth, alginic acid, albumin, casein, curdlan, gellan gum and dextran can also be suitably used.
(9) Examples of physiologically active ingredients Examples of physiologically active ingredients include substances that impart some physiological activity to the skin when applied to the skin. For example, whitening ingredients, anti-inflammatory agents, anti-aging agents, UV protection agents, slimming agents, tanning agents, antioxidants, hair growth agents, hair restorers, moisturizers, blood circulation promoters, antibacterial agents, bactericides, desiccants, A cooling sensation agent, a warming sensation agent, vitamins, an amino acid, a wound healing promoter, an irritation relaxation agent, an analgesic agent, a cell activator, an enzyme component, etc. are mentioned. Examples of these suitable ingredients include, for example, ashitaba extract, avocado extract, amateur extract, altea extract, arnica extract, aloe extract, apricot extract, apricot kernel extract, ginkgo biloba extract, fennel extract, turmeric extract, oolong tea extract, ages Extract, Echinacea leaf extract, Ogon extract, Oat extract, Oen extract, Barley extract, Hypericum extract, Oyster extract, Dutch mustard extract, Orange extract, Seawater dried product, Seaweed extract, Hydrolyzed elastin, Hydrolyzed wheat powder, Hydrolyzed silk , Chamomile extract, carrot extract, cormorant extract, licorice extract, calcade extract, oyster extract, kiwi extract, kina extract, cucumber extract, guanosine, gardenia extract, kumazasa Kiss, Clara extract, Walnut extract, Grapefruit extract, Clematis extract, Chlorella extract, Mulberry extract, Gentian extract, Black tea extract, Yeast extract, Burdock extract, Rice bran ferment extract, Rice germ oil, Comfrey extract, Collagen, Cowberry extract, Saisin extract , Psycho extract, Saitai extract, Salvia extract, Soybean extract, Sasa extract, Hawthorn extract, Salamander extract, Shiitake extract, Giant extract, Shikon extract, Perilla extract, Linden extract, Shimotake extract, Japanese peony extract, Ginger root extract, Birch extract, Japanese cedar Extract, Kizuta extract, Hawthorn extract, Elderberry extract, Achillea millefolium extract, Pepper extract, Sage extract, Zenia A extract, sensu extract, assembly extract, soybean extract, thymus extract, thyme extract, tea extract, clove extract, chigaya extract, chimpi extract, toki extract, toukisenka extract, tonin extract, spruce extract, dokudami extract, tomato extract, natto extract, carrot extract, Garlic extract, Novara extract, Hibiscus extract, Bacmond extract, Parsley extract, Honey, Camelis extract, Parietalia extract, Butterberry extract, Bisabolol, Biwa extract, Japanese dandelion extract, Fukinoto extract, Bukcho extract, Butcher bloom extract, Grape extract, Propolis, Loofah extract, safflower extract, peppermint extract, bodaiju extract, button extract, hop extract, pine extract, Maroni Eki , Mizuba pepper extract, Mukuroji extract, Melissa extract, Peach extract, Cornflower extract, Eucalyptus extract, Yukinoshita extract, Yokuinin extract, Mugwort extract, Lavender extract, Apple extract, Lettuce extract, Lemon extract, Astragalus extract, Rose extract, Rosemary extract, Roman chamomile extract, royal jelly extract, strawberry extract, hihatsu extract, lotus leaf extract, paffia extract, star fruit extract and the like.
Biopolymers such as deoxyribonucleic acid, mucopolysaccharide, sodium hyaluronate, sodium chondroitin sulfate, collagen, elastin, chitin, chitosan, hydrolyzed eggshell membranes, amino acids, hydrolyzed peptides, sodium lactate, urea, sodium pyrrolidonecarboxylate , Moisturizing ingredients such as betaine, whey, trimethylglycine, oily ingredients such as sphingolipid, ceramide, phytosphingosine, cholesterol, cholesterol derivatives, phospholipids, ε-aminocaproic acid, glycyrrhizic acid, β-glycyrrhetinic acid, lysozyme chloride, guaiazrene Anti-inflammatory agents such as hydrocortisone, vitamin A, vitamin B2, vitamin B6, vitamin C, vitamin D, vitamin E, calcium pantothenate, biotin, nicotinamide, vitamin Vitamins such as C-ester, active ingredients such as allantoin, diisopropylamine dichloroacetate, 4-aminomethylcyclohexanecarboxylic acid, antioxidants such as tocopherol, carotenoid, flavonoid, tannin, lignan, saponin, α-hydroxy acid, β -Cell activators such as hydroxy acids, blood circulation promoters such as γ-oryzanol and vitamin E derivatives, wound healing agents such as retinol and retinol derivatives, arbutin, kojic acid, placenta extract, sulfur, ellagic acid, linoleic acid, tranexamic acid , Whitening agents such as glutathione, cephalanthin, licorice extract, red pepper tincture, hinokitiol, garlic iodide extract, pyridoxine hydrochloride, DL-α-tocopherol, DL-α-tocopherol acetate, nicotinic acid, nicotinic acid derivatives , Calcium pantothenate, D-pantothenyl alcohol, acetyl pantothenyl ethyl ether, biotin, allantoin, isopropylmethylphenol, estradiol, ethinylestradiol, capronium chloride, benzalkonium chloride, diphenhydramine hydrochloride, takanal, camphor, salicylic acid, vanillylamide nonyl , Nonanoic acid vanillylamide, piroctone olamine, glyceryl pentatecanate, L-menthol, mononitroguaiacol, resorcin, γ-aminobutyric acid, benzethonium chloride, mexiletine hydrochloride, auxin, female hormone, cantharis tincture, cyclosporine, zinc pyrithione, hydrocol Thizone, minoxidil, polyoxyethylene sorbitan monostearate, peppermint oil, Sasanishikie Hair tonic, such as the scan and the like.
(10) Examples of antioxidants: sodium bisulfite, sodium sulfite, erythorbic acid, sodium erythorbate, dilauryl thiodipropionate, tocopherol, tolylbiguanide, nordihydroguaiaretic acid, parahydroxyanisole, butylhydroxyanisole, dibutylhydroxy Examples include toluene, ascorbyl stearate, ascorbyl palmitate, octyl gallate, propyl gallate, carotenoids, flavonoids, tannins, lignans, saponins, plant extracts that have an antioxidant effect such as apple extract and clove extract.
(11) Examples of solvents Purified water, ethanol, lower alcohol, ethers, LPG, fluorocarbon, N-methylpyrrolidone, fluoroalcohol, volatile straight-chain silicone, next-generation chlorofluorocarbon and the like.

Example: Preparation of fucoxanthin The thawed raw kombu was crushed and extracted with ethanol at 40 ° C for 1 hour. Thereafter, the mixture was filtered, and the filtrate was further concentrated with an evaporator. Thereafter, desalting and dechlorination steps were performed to obtain the residue. Further, the residue was separated on a silica gel column and eluted with ethanol to obtain an eluate, and then the eluate was concentrated with an evaporator to obtain a crude fucoxanthin fraction. This crude fucoxanthin fraction was purified by HPLC (conditions: column: ODS, 20 mm id ′ 250 mm, mobile phase: acetonitrile / methanol / water (60:25:15)) to obtain a fucoxanthin fraction. Further, as a result of comparing this fraction with ¹³ C and ¹ H NMR spectra and the spectrum of a standard product, it was confirmed that this fraction had a fucoxanthin content of 92.0%.

Test example: Evaluation of AGE production inhibitory action Method: D-glucose (10%) and bovine serum albumin (fraction 5, 1%)
Containing phosphate buffer (pH:
7.4, 900 mL) was added to the sample solution (100 mL) and allowed to stand at 60 ° C. for 3 days. The reaction solution was diluted with purified water so that the fluorescence intensity was around 500, and the fluorescence intensity (measurement wavelength: 370 nm, excitation wavelength: 440 nm) was measured. Fucoxanthin was dissolved in DMSO and then diluted with a phosphate buffer so that the DMSO concentration would be 10%.

Results and Evaluation of Examples Fucoxanthin showed inhibitory activity against AGE production at concentrations of 30, 100 mg / mL.

The compounding example of the AGE production inhibitor (fucoxanthin) by this invention is shown.
Formulation Example 1: Chewing gum
53.0wt% sugar
Gum base 20.0
Glucose 10.0
Minamata 16.0
Fragrance 0.5
AGE production inhibitor 0.5
100.0 wt%

Formulation Example 2: Gummy
Reduced water tank 40.0wt%
Granulated sugar 20.0
Buto sugar 20.0
Gelatin 4.7
Water 9.68
Yuzu fruit juice 4.0
Yuzu Flavor 0.6
Dye 0.02
AGE production inhibitor 1.0
100.0 wt%

Formulation Example 3: Candy
50.0 wt% sugar
Minamata 33.0
Water 14.4
Organic acid 2.0
Fragrance 0.2
AGE production inhibitor 0.4
100.0 wt%

Formulation Example 4: Yogurt (hard / soft)
Milk 41.5wt%
Nonfat dry milk 5.8
Sugar 8.0
Agar 0.15
Gelatin 0.1
Lactic acid bacteria 0.005
AGE production inhibitor 0.4
Perfume
Water residue
100.0 wt%

Formulation Example 5: Soft drink
Fructose glucose liquid sugar 30.0wt%
Emulsifier 0.5
AGE production inhibitor 0.3
Perfume
Purified water residue
100.0 wt%

Formulation Example 6: Tablets
76.4 wt% sugar
Glucose 19.0
Sucrose fatty acid ester 0.2
AGE production inhibitor 0.5
Purified water 3.9
100.0 wt%

Formulation Example 7: Soft capsule
Brown rice germ oil 47.0wt%
Yuzu seed oil 40.0
Emulsifier 12.0
AGE production inhibitor 1.0
100.0 wt%

Formulation Example 8: Tablet
Lactose 54.0wt%
Crystalline cellulose 30.0
Starch degradation product 10.0
Glycerin fatty acid ester 5.0
AGE production inhibitor 1.0
100.0 wt%

Formulation Example 9: Cosmetic cream
Squalane 20.0wt%
Beeswax 5.0
Refined jojoba oil 5.0
Glycerin 5.0
Glycerol monostearate 2.0
Polyoxyethylene (20) sorbitan
Monostearate 2.0
AGE production inhibitor 2.0
Preservative appropriate amount
Perfume
Purified water residue
100.0 wt%

Formulation Example 10: lotion
Ethanol 5.0wt%
Glycerin 2.0
1,3-butylene glycol 2.0
Polyethylene oleyl ether 0.5
Sodium citrate 0.1
Citric acid 0.1
AGE production inhibitor 0.1
Purified water residue
100.0 wt%

Formulation Example 11: Body gel
Macadamia nut oil 2.0wt%
Octyldodecyl myristate 10.0
Methylphenylpolysiloxane 5.0
Behenyl alcohol 3.0
Stearic acid 3.0
Batyl alcohol 1.0
Glyceryl monostearate 1.0
Tetraoleic acid polyoxyethylene sorbit
2.0
Hydrogenated soybean phospholipid 1.0
Ceramide 0.1
Retinol palmitate 0.1
Preservative appropriate amount
Camellia extract 1.0
AGE production inhibitor 1.0
1,3-butylene glycol 5.0
Purified water residue
100.0 wt%

Formulation Example 12: Emulsion
Squalane 4.0wt%
Vaseline 2.5
Cetanol 2.0
Glycerin 2.0
Lipophilic glyceryl monostearate
1.0
Stearic acid 1.0
L-Arginine 1.0
AGE production inhibitor 0.5
Potassium hydroxide 0.1
Fragrance
Purified water residue
100.0 wt%

Formulation Example 13: Bath agent (liquid)
Propylene glycol 50.0wt%
Ethanol 20.0
Sodium sulfate 5.0
AGE production inhibitor 0.5
Lanolin 0.5
Avocado oil 0.5
Dye 1.5
Fragrance 22.0
100.0 wt%

  As described above, the present invention can suppress the production of AGE, thereby effectively preventing diabetes and further effectively suppressing the aging of the skin.

Claims (1)

An AGE production inhibitor containing fucoxanthin as an active ingredient.

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