JP2017079675A - Advanced glycation end product production inhibitor, and food, beverage and cosmetics comprising the same - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a novel pharmacological use of proteoglycan.SOLUTION: An advanced glycation end product production inhibitor has proteoglycan derived from aquatic organism cartilage of 0.004 mass% or more and 0.1 mass% or less, and Japanese cherry flower extract of 0.02 mass% or more and 0.5 mass% or less.SELECTED DRAWING: None

Description

  The present invention relates to a glycated end product production inhibitor containing proteoglycan derived from cartilage of aquatic organisms and cherry blossom extract, and foods, beverages and cosmetics containing the same.

  Proteoglycan is one of the complex carbohydrates, consisting of a core protein and glycosaminoglycan (acid mucopolysaccharide) that binds to it, and is present in the skin, cartilage, bone, blood vessel wall, etc. as the main components of the extracellular matrix. In recent years, a technique for separating and purifying proteoglycan from salmon cartilage safely and at low cost has been established, and a large amount of proteoglycan can be supplied. Therefore, research and development of proteoglycan has been energetically performed.

  Patent Document 1 (Japanese Patent Application Laid-Open No. 2007-131548) discloses a cell in which proteoglycan is one of a subset of helper T cells such as a TNF-α production inhibitory action, an IFN-γ production inhibitory action, and an IL-10 production promoting action. It has been reported to have various effects on molecules related to Th1 cells that control sexual immunity.

  Patent Document 2 (Japanese Patent Application Laid-Open No. 2010-254653) reports that proteoglycan has an action of suppressing differentiation induction of Th17 cells, which is one of a subset of helper T cells different from Th1 cells.

JP 2007-131548 A JP 2010-254653 A

However, the full pharmacological action of proteoglycans is still unclear.
Therefore, an object of the present invention is to provide a novel pharmacological use of proteoglycan.

  The present invention relates to terminal saccharification comprising proteoglycan derived from cartilage of aquatic organisms in an amount of 0.004% by mass to 0.1% by mass and cherry blossom extract in an amount of 0.02% by mass to 0.5% by mass. It is a product production inhibitor.

  In the terminal glycation product production inhibitor of the present invention, the mass ratio of the proteoglycan and the cherry blossom extract in the terminal glycation product production inhibitor is preferably in the range of 5: 1 to 1:25.

  This invention is a foodstuff, a drink, or cosmetics containing the said advanced saccharification product production inhibitor.

  ADVANTAGE OF THE INVENTION According to this invention, the terminal glycation product production inhibitor as a novel pharmacological use of proteoglycan can be provided.

It is a graph which shows the relationship between the density | concentration of a proteoglycan and a cherry tree flower extract, and the production amount of a terminal glycation product.

[Terminal saccharification product production inhibitor]
(Inhibition of glycated end product production)
Advanced glycation end-product (AGE) is a substance produced by non-enzymatic reaction of protein and saccharide. In vivo, lysine residues or arginine residues of proteins react with reducing sugars to form Amadori transfer products, which are thought to lead to AGE through complex reaction pathways such as oxidation, dehydration, and condensation. Yes. AGE accumulation in vivo is considered to be strongly involved in the development of lifestyle-related diseases such as diabetic complications, arteriosclerosis and osteoporosis as well as aging of skin and blood vessels. The present inventors have found that when proteoglycan derived from cartilage of aquatic organisms and cherry blossom extract are used in combination, an excellent terminal glycation product production suppression (hereinafter also referred to as AGE production suppression) action can be obtained.

  In one embodiment of the present invention, the terminal glycation product production inhibitor contains proteoglycan derived from cartilage of aquatic organisms and cherry blossom extract.

(Proteoglycan)
As the proteoglycan, one purified from cartilage of aquatic organisms such as salmon, shark, cow and whale can be used. Among them, it is preferable to use proteoglycan derived from salmon nasal cartilage from the viewpoint of availability of raw materials and ease of extraction operation.

  The purification method of proteoglycan is not particularly limited, and a known method can be used. For example, a method using acetic acid described in JP-A-2002-69097 can be suitably employed. In this method, for example, after elution of crude proteoglycan from minced salmon nasal cartilage using acetic acid as an elution solvent, the resulting eluate is filtered and centrifuged, and salt-saturated ethanol is added to the supernatant. And dissolving the semi-solid precipitate containing the crude proteoglycan obtained by centrifuging in acetic acid, followed by dialysis. According to this method, for example, proteoglycan having a molecular weight of about 100 to 400 kDa can be obtained from salmon nasal cartilage.

  As a method for purifying proteoglycan, the method described in JP-A-2008-11296 can also be suitably employed. In this method, for example, from frozen aquatic animal tissue, the temperature and pH of water used for extraction are appropriately set to separate lipids and precipitates, and the precipitates are recovered, and the precipitates are dried into a fine powder. Thereafter, a step of removing lipid remaining in the precipitate using an organic solvent such as ethanol is included. According to this method, a proteoglycan suitable for uses such as foods, beverages, and cosmetics can be obtained without accompanying the degradation of proteoglycans in the tissue and with less off-flavors.

  The proteoglycan is not necessarily highly purified, and may include a mixed composition of a plurality of proteoglycans having different molecular weights and other components that do not adversely affect the action of the proteoglycan.

  The proteoglycan content in the terminal glycation product production inhibitor is 0.004% by mass or more and 0.1% by mass or less. According to this, an excellent AGE production inhibitory action can be obtained. In addition, the content of proteoglycan can be appropriately selected depending on the formulation form, and is preferably 0.01% by mass or more and 0.1% by mass or less, for example, 0.02% by mass or more and 0.1% by mass or less. Is more preferable, and 0.04 mass% or more and 0.1 mass% or less is still more preferable.

(Sakura Flower Extract)
Cherry blossom extract is an extract of cherry blossoms. Sakura (cherry blossoms, buds) is a generic name of plants belonging to the family Rosaceae, excluding plums, peaches and apricots, and generally refers to those belonging to the subgenus Subgen. Cerasus.

  The cherry seeds used in the present invention are not particularly limited, and for example, cherry trees belonging to groups such as Yamazakura group, Edhigan group, Bean cherry group, Chojizakura group, Miyazakura group, Shinamizakura group and the like can be used. It should be noted that other species can be used without being limited to these groups.

  The cherry blossom extract includes caffeoyl glucose represented by the following formula (1), quercetin glucoside represented by the following formula (2), coumaroyl glucose represented by the following formula (3), and cinna represented by the following formula (4). Moyl glucose, kaempferol glucoside represented by the following formula (5), quercetin malonyl glucose represented by the following formula (6), kaempferol malonyl glucose represented by the following formula (7), and the like are included.

  When extracting the cherry blossom extract with a polar solvent, 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, ethyl acetate, ether, hexane, or the like can be used. 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 preferable because if the extraction temperature is too low, it is difficult to extract the active ingredient, and if the extraction temperature is too high, the cyanide contained in the cherry tends to remain, and the active ingredient tends to be decomposed. Absent. 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 hydrous alcohol is used as the extraction solvent, the alcohol concentration is 20% by weight or more, preferably 25 to 50% by weight. It is because it is difficult to obtain a high extraction amount of an active ingredient when it is less than 20% by weight. When the alcohol concentration is 30% by weight or more, the extraction temperature is 0 to 95 ° C, preferably about 0 to 50 ° C. In addition, the water-containing ethanol extraction may be repeated at various concentrations in order to improve the content of the active ingredient.

  When extracting the cherry blossom extract 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 it can be arbitrarily selected from room temperature to under reflux heating. Can be used. When performing extraction by the above-described method, only one of them may be performed, or these methods may be combined. Moreover, 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 or a hydrous alcohol is used as the extraction solvent, the extraction is performed for about 1 minute to 150 hours using a polar solvent of about 3 to 100 times (weight ratio) of the extraction raw material. The active ingredient is eluted in the solvent, and then filtered to remove the extraction residue to obtain an extract. Thereafter, a cherry blossom extract can be obtained by subjecting the extract to treatments such as dilution, concentration, drying, and purification according to a conventional method.

  Examples of the method for purifying the cherry blossom extract include activated carbon treatment, resin adsorption treatment, silica gel treatment, ion exchange resin, liquid-liquid countercurrent distribution, and membrane separation.

  When extracting a cherry blossom extract by supercritical extraction, a supercritical fluid is not specifically limited, For example, a carbon dioxide, nitrogen, etc. can be used. 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, a cherry blossom extract can be obtained by subjecting the extract to treatments such as dilution, concentration, drying, and purification according to a conventional method.

  The content of the cherry blossom extract in the terminal saccharification product production inhibitor is 0.02% by mass or more and 0.5% by mass or less. According to this, an excellent AGE production inhibitory action can be obtained. The content of the cherry blossom extract can be appropriately selected according to the formulation form, and is preferably 0.04% by mass to 0.5% by mass, for example, 0.1% by mass to 0.5% by mass. % Or less is more preferable, and 0.2 mass% or more and 0.5 mass% or less is further more preferable.

  In the glycation end product production inhibitor, the mass ratio of proteoglycan and cherry blossom extract is preferably in the range of 5: 1 to 1:25, more preferably in the range of 5: 1 to 1: 5, from the viewpoint of the AGE production inhibitory action. The range of 1: 1 to 1: 5 is more preferable.

(Administration method and formulation)
Examples of the method for administering the terminal glycation product production inhibitor include oral administration and transdermal administration. What is necessary is just to formulate in the dosage form suitable for each administration method in the case of administration.

  Examples of the dosage form include tablets, capsules, granules, powders, fine granules, pills, troches, sublingual tablets, ointments, emulsions, suspensions, syrups and the like. The preparation of these preparations includes non-toxic excipients, binders, lubricants, disintegrants, preservatives, isotonic agents, stabilizers, dispersants, antioxidants, colorants, flavoring agents, buffering agents. It can carry out by a method known per se using additives such as. Non-toxic additives include, for example, starch, gelatin, glucose, lactose, fructose, maltose, magnesium carbonate, talc, magnesium stearate, methylcellulose, carboxymethylcellulose, gum arabic, polyethylene glycol, propylene glycol, petrolatum, glycerin, ethanol Syrup, sodium chloride, sodium sulfite, sodium phosphate, citric acid, polyvinylpyrrolidone, water and the like. In addition, in order to reinforce or enhance the usefulness of the present invention, other drugs may be contained in the preparation.

  The dose of the terminal glycation product production inhibitor can be widely adjusted depending on the gender, age, weight, etc. of the subject of administration, and the severity of symptoms, but generally 0.2 mg / Kg or more and 20 mg / Kg or less per day It can be. The above dose may be administered once or divided into several times a day.

[Food, beverages, cosmetics]
The terminal saccharification product production inhibitor of the present invention is processed as it is or processed into food, nutritional functional food, food for specified health use, nutritional supplement, nutrient, beverage, animal medicine, feed, cosmetics, quasi-drug, pharmaceutical It can be used as a therapeutic or prophylactic agent.

  When used in foods, a terminal glycation product production inhibitor can be used by adding to general so-called foods. Examples of foods include dairy products such as cheese, prepared milk powder, ice cream and yogurt, chocolate, cookies, biscuits, candy, Japanese sweets, rice cakes, cakes, pie, puddings, and other flour products such as bread and noodles. , Rice products such as cooked rice, cooked rice, soy sauce, miso, mayonnaise, dressings and other seasonings. The food may be a processed fishery product, a processed agricultural product, or a processed livestock product. These foods may be in oral administration forms such as capsules (microcapsules, hard capsules, soft capsules), tablets, powders, chewable tablets, pills, syrups and beverages.

  When used in beverages, a terminal saccharification product production inhibitor can be used by adding to general so-called beverages. Examples of the beverage include tea, coffee, milk, milk beverage, fruit juice beverage, juice, lactic acid beverage, soft drink, nutrition drink, and beauty drink.

  When used in cosmetics, a terminal saccharification product production inhibitor can be used by adding to general so-called cosmetics. Cosmetics refer to things that are applied to the body by rubbing, spraying, etc. to keep the skin or hair healthy, or to cleanse, beautify, enhance appeal and change the appearance of the body. Cosmetics are classified into basic cosmetics, cosmetics for makeup, cosmetics for hair, and the like according to their uses. In the present specification, “cosmetics” includes those classified as quasi-drugs as defined in the Pharmaceutical Affairs Law, such as medicinal cosmetics. Cosmetics include, for example, cold creams, vanishing creams, mixed creams that are oily, massage creams, emollient creams, hizenic creams, creams for eyes and fingers, lip creams, shaving creams, after-shave creams, and the like; Moisturizing lotion, astringent lotion, acidic lotion, alkaline lotion, carmine lotion, after shave lotion and other lotions; latex such as emulsions containing polymer; beauty and beauty oils; body scrubs; packs and Peelable pack; foundation cream, vanishing type foundation, fountain, water fountain, kneading punishment, oily foundation including stick type, emulsion type cream foundation that is oil-in-water or water-in-oil type , Powdery foundation, liquid foundation, lipstick, blusher, brushing powder, eyeliner, eyeshadow, mascara, eyebrow, functional lipstick, lip liner pencil, lip gloss, lip balm, nail enamel, base coat, top coat, remover , Shampoos, conditioning shampoos, rinses, hair treatments, integrated rinse shampoos, hair restorers, hair nourishing agents, hair mousses and hair foams, hair sprays, hair mists, hair gels, set lotions, hair Liquid, scalp treatment, hair cream, hair oil, hair coating lotion, hair gloss spray, hair blow, pomade, tic Hair products including hair waxes, hair dyes, hair bleach, etc .; and bath and facial soaps, body cleansers, bath agents, bubble baths, deodorants, antiperspirants, slimming, fragrances, perfumes, perfumes , Eau de toilette, eau de cologne and other body care products.

  The present invention will be described more specifically with reference to examples. However, the present invention is not limited to these examples.

[Example 1]
In Example 1, the inhibitory action of proteoglycan and cherry blossom extract on production of advanced glycation end products was examined.

(experimental method)
Phosphate buffered saline (pH 7.) containing 7.2% by mass of D-glucose and bovine serum albumin (trade name “Fraction 5” manufactured by Wako Pure Chemical Industries, Ltd.) at a concentration of 1.6% by mass. 4) was prepared. Using the phosphate buffered saline, proteoglycan (trade name “Proteoglycan” manufactured by Kakuhiro Co., Ltd., derived from salmon nasal cartilage) and cherry blossom extract (trade name “Sakura Flower Extract” manufactured by Oriza Oil Chemical Co., Ltd.) 100 μL each of the solutions containing each of the above concentrations at the concentrations shown in Table 1 were prepared (Samples 1 to 3).

  The solutions of Sample 1 to Sample 3 were dispensed into 96-well plates and allowed to stand at 60 ° C. for 5 days. The fluorescence intensity (excitation wavelength: 370 nm, measurement wavelength: 440 nm) of the solution was measured using a fluorescence microplate reader, and used as an index of AGE production. The AGE production amount in the addition group (sample 1 to sample 3) was shown as a percentage with respect to the proteoglycan and cherry blossom extract non-addition group.

(result)
The results are shown in FIG. In FIG. 1, each value is shown as an average value and standard error of three cases. Asterisks represent significant differences according to Dunnett's multiple comparison test **: p <0.01, *: p <0.05. Moreover, proteoglycan was described as PG.

  When the AGE production amount of Sample 1 to Sample 3 was compared, the AGE production amount in a solution (sample 3) in which 1.0 mg / mL of proteoglycan was mixed with 5.0 mg / mL of cherry blossom extract was the lowest value. . In addition, the mixed solution (sample 3) significantly suppressed AGE production compared to the solution of proteoglycan alone (sample 1) and cherry blossom extract alone (sample 2). That is, the solution of Sample 3 showed the highest ability to suppress AGE production.

  The embodiments and examples disclosed herein are illustrative in all respects and should not be construed as being restrictive. The scope of the present invention is shown not by the above-described embodiment but by the scope of claims, and is intended to include meanings equivalent to the scope of claims and all modifications within the scope.

  The glycated end product production inhibitor of the present invention is a food, a nutritional functional food, a food for specified health use, a nutritional supplement, a nutrient, a beverage, an animal drug, a feed, a cosmetic, a quasi-drug, a pharmaceutical, a therapeutic drug or a preventive drug. Can be used for etc.

Claims (3)

  A glycated end product production inhibitor containing 0.004% by mass to 0.1% by mass of proteoglycan derived from aquatic organism cartilage and 0.02% by mass to 0.5% by mass of cherry blossom extract. . The mass ratio of the proteoglycan in the terminal glycation product production inhibitor and the cherry blossom extract is in the range of 5: 1 to 1:25.
The terminal glycation product production inhibitor according to claim 1.   A food, beverage or cosmetic comprising the terminal glycation product production inhibitor according to claim 1 or 2.

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