WO2016027837A1 - 経口美容剤 - Google Patents

経口美容剤 Download PDF

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Publication number
WO2016027837A1
WO2016027837A1 PCT/JP2015/073272 JP2015073272W WO2016027837A1 WO 2016027837 A1 WO2016027837 A1 WO 2016027837A1 JP 2015073272 W JP2015073272 W JP 2015073272W WO 2016027837 A1 WO2016027837 A1 WO 2016027837A1
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WIPO (PCT)
Prior art keywords
hesperidin
glycosyl
hesperetin
glycosyl hesperetin
reducing agent
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PCT/JP2015/073272
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English (en)
French (fr)
Japanese (ja)
Inventor
伸 遠藤
三幸 神戸
浩一 西
晶 川島
亜希子 安田
仁志 三皷
利夫 有安
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株式会社林原
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Priority to JP2016544235A priority Critical patent/JP6678928B2/ja
Priority to KR1020177007095A priority patent/KR102554508B1/ko
Publication of WO2016027837A1 publication Critical patent/WO2016027837A1/ja

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    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/125—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives containing carbohydrate syrups; containing sugars; containing sugar alcohols; containing starch hydrolysates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/08—Solutions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/60—Sugars; Derivatives thereof
    • A61K8/602—Glycosides, e.g. rutin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/10—Dispersions; Emulsions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2200/00—Function of food ingredients
    • A23V2200/30—Foods, ingredients or supplements having a functional effect on health
    • A23V2200/318—Foods, ingredients or supplements having a functional effect on health having an effect on skin health and hair or coat

Definitions

  • the present invention relates to an oral beauty agent, and more particularly, to an oral beauty agent for improving yellowing, texture, and skin quality of skin.
  • beauty foods are similar to ordinary foods and beverages in that they are taken orally, they are usually common in that specific nutrients and functional ingredients are enhanced to achieve the desired purpose. It is different from food and drink. In addition, beauty foods are not intended to have immediate effects like drugs or to treat specific diseases, and it is difficult to ingest sufficient amounts of ordinary foods and beverages. It differs from pharmaceuticals in that it is intended to supplement specific nutrients and functional ingredients that are useful for beauty. Examples of beauty foods include oral compositions containing nutrients and functional ingredients useful for beauty such as chondroitin sulfate, coenzyme Q10, hyaluronic acid, and glucosamine, as described in Patent Documents 1 and 2. .
  • Patent Document 3 discloses a melanin-lowering agent and a skin lightness-lowering inhibitor containing ⁇ -glycosyl hesperidin, which are used as foods and drinks or oral preparations, but they reduce the amount of melanin in the skin.
  • the skin yellowness is an index completely different from the skin lightness (for example, Non-Patent Document 1). 2), texture, and means for improving skin quality and means for improving inconvenience when orally ingesting ⁇ -glycosyl hesperidin are not disclosed.
  • Patent Document 4 discloses means for improving skin color using ⁇ -glycosyl hesperidin, which is based on an external preparation for skin containing ⁇ -glycosyl hesperidin. External preparations are clearly different from cosmetic foods that are orally ingested in the form of administration or usage.
  • Non-Patent Document 1 Yoko Yashiki, “Fragrance JOURNAL”, Vol. 40, No. 4, pp. 80-82, 2012
  • Non-Patent Document 2 Yuji Kajita, “Color Material”, Vol. 76, No. 2, pp. 78-83, 2003
  • an object of the present invention is to provide an oral beauty agent that can effectively improve the yellowish dullness, texture, and skin quality of the skin.
  • the oral beauty agent according to the present invention is not only a beauty food to be taken orally, but also in the form of a health food, nutritional functional food, health functional food, food for specified health, etc. for the purpose of improving beauty. Is included.
  • the present inventors have made extensive research efforts, and as a result, when a human being continuously orally ingests glycosyl hesperetin on a daily basis, the skin yellowing, texture, and skin quality are effective.
  • the present invention was completed by newly finding that it can be improved and establishing its application.
  • the present invention solves the above-mentioned problems by providing an oral cosmetic agent for improving yellowness, texture, and skin quality containing glycosyl hesperetin as an active ingredient.
  • glycosyl hesperetin as used in the present specification means all compounds in which saccharides are bound to hesperetin, that is, all compounds having a hesperetin skeleton, and specific examples thereof include hesperidin and the rhamnose group constituting hesperidin's rutinose. 7-O- ⁇ -glucosyl hesperetin having a structure, and ⁇ -glycosyl hesperidin in which a saccharide (eg, a saccharide such as D-glucose, D-fructose, or D-galactose) is ⁇ -linked in an equimolar amount or more to hesperidin It is done.
  • a saccharide eg, a saccharide such as D-glucose, D-fructose, or D-galactose
  • hesperidin also called vitamin P
  • vitamin P has a structure in which rutinose composed of rhamnose and glucose is bound to hesperetin.
  • the compound is represented by the structural formula shown in the following chemical formula 1 and is often contained in citrus peels and the like. It is a component.
  • 7-O- ⁇ -glucosyl hesperetin is a compound represented by the structural formula shown in the following chemical formula 2, and has a feature of being highly water-soluble compared to hesperidin.
  • 7-O- ⁇ -glucosyl hesperetin is produced by, for example, causing ⁇ -L-rhamnosidase (EC 3.2.1.40) to act on a solution containing ⁇ -glucosyl hesperidin and hesperidin as disclosed in Patent Document 1. Can be manufactured.
  • ⁇ -glycosyl hesperidin is a compound in which saccharide (eg, saccharides such as D-glucose, D-fructose, or D-galactose) is ⁇ -linked to hesperidin in an equimolar amount or more.
  • saccharide eg, saccharides such as D-glucose, D-fructose, or D-galactose
  • a typical example of ⁇ -glycosyl hesperidin is ⁇ -glucosyl hesperidin represented by the structural formula shown in the following chemical formula 3 in which one glucose ⁇ -links to glucose in the rutinose structure of hesperidin (also known as enzyme-treated hesperidin, glycosylated hesperidin). , Water-soluble hesperidin, or sugar transfer vitamin P).
  • the trade name “Hayashibara Hesperidin (registered trademark) S” is commercially available.
  • glycosyl hesperetin itself is a safe and highly versatile compound that has been widely used as a material for various foods, cosmetics, pharmaceuticals, quasi drugs, and the like.
  • ⁇ -glycosyl hesperidin is more water-soluble than hesperidin and 7-O- ⁇ -glucosyl hesperetin, and is easy to handle. In vivo, it is the same as hesperidin and 7-O- ⁇ -glucosyl hesperetin. It is hydrolyzed to hesperetin under the action of in vivo enzymes, and exhibits the physiological activity inherent in hesperetin.
  • the oral cosmetic preparation of the present invention is an oral cosmetic preparation containing glycosyl hesperetin as an active ingredient, and can be ingested safely and easily by humans on a daily basis, and can be taken orally without discomfort, and is industrially inexpensive. Can be provided. According to such an oral beauty agent of the present invention, yellowish dullness, texture, and skin quality can be effectively improved.
  • the oral beauty agent of the present invention is a so-called working woman who applies to women in their 40s and older who are concerned about yellowing of skin, roughness of skin, and deterioration of skin quality. When it does, it has the outstanding characteristic that a desired effect is exhibited more notably than other subjects.
  • glycosyl hesperetin contained in the oral cosmetic agent of the present invention as an active ingredient means that human beings can be taken orally on a daily basis safely and easily without discomfort, and can be provided industrially at low cost. As long as the intended effects of the present invention can be achieved, the origin, production method, purity and the like can be used without particular limitation.
  • glycosyl hesperetin referred to in the present specification means a general compound in which a saccharide is bound to hesperetin, as described above, and more specifically, hesperidin that generates hesperetin by the action of an in vivo enzyme. , 7-O- ⁇ -glucosyl hesperetin, and ⁇ -glycosyl hesperidin.
  • glycosyl hesperetins if humans can safely and easily, and miscellaneous taste, coloring, odor and the like are significantly or significantly reduced, can be taken orally without discomfort, and can be provided industrially at low cost, Whether it is a commercially available product or a conventionally known production method, it can be used more suitably in the present invention. Since the present invention is not an invention relating to a method for producing glycosyl hesperetin itself, the details of the production method are omitted in the present specification, but the outline thereof is as follows.
  • glycosyl hesperetins used in the present invention hesperidin is industrially extracted from citrus fruits, pericarp, seeds, immature fruits, etc., which are hesperidin-containing plants, and appropriately extracted with a solvent such as water or alcohol. The desired amount can be produced.
  • ⁇ -glycosyl hesperidin is a glycosyltransferase in a solution containing hesperidin and an ⁇ -glucosyl sugar compound as disclosed in, for example, JP-A No. 11-346792.
  • ⁇ -glycosyl hesperidin which is collected, and the desired amount can be industrially produced at low cost.
  • 7-O- ⁇ -glucosyl hesperetin is obtained by combining ⁇ -glycosyl hesperidin and hesperidin obtained by the action of glycosyltransferase.
  • ⁇ -L-rhamnosidase act on the contained enzyme reaction solution to produce 7-O- ⁇ -glucosyl hesperetin and collecting this, the desired amount can be industrially produced at low cost.
  • glycosyl hesperetin used in the present invention among the commercially available products and glycosyl hesperetins obtained by a conventionally known production method, a high-purity product with less impurities is preferably used.
  • glycosyl hesperetin-containing composition which contains a physiologically acceptable ionic compound, which is produced in a secondary manner in the form of a so-called so-called glycosyl hesperetin.
  • glycosyl hesperetin is mainly used as a contaminant, an unreacted raw material derived from the manufacturing raw material, or a physiologically produced physiologically secondary product in the manufacturing process.
  • a glycosyl hesperetin-containing composition comprising an acceptable ionic compound is simply referred to as glycosyl hesperetin.
  • the glycosyl hesperetin used in the present invention includes high-purity glycosyl hesperetin obtained through a crystallization step.
  • the present inventors have proposed a conventional method for reducing the content of concomitant substances contained in conventional glycosyl hesperidin for the purpose of eliminating miscellaneous taste, coloring, etc., which were disadvantages of the conventionally known glycosyl hesperetin.
  • Glycosyl hesperetin with reduced odor hereinafter referred to as “miscellaneous taste, etc.” in some cases
  • miscellaneous taste and coloration by improving a part thereof
  • the manufacturing method was established and disclosed in Japanese Patent Application No. 2014-41066 and International Patent Application No. PCT / JP2015 / 056230 pamphlet. Glycosyl hesperetin with reduced miscellaneous taste, etc.
  • glycosyl hesperetin with reduced miscellaneous taste and the like can be advantageously used as the most suitable glycosyl hesperetin for carrying out the present invention.
  • glycosyl hesperetin with reduced miscellaneous taste and its physical properties
  • Glycosyl hesperetin with reduced miscellaneous tastes is obtained by (a) preparing an aqueous solution containing hesperidin and a partial degradation product of starch, and (b) glycosyl containing ⁇ -glucosyl hesperidin by allowing a glycosyltransferase to act on the obtained aqueous solution.
  • a production method comprising a step of producing a hesperetin-containing composition and (c) a step of collecting the produced glycosyl hesperetin-containing composition, wherein one or two or more of the steps (a) to (c) above are performed as a reducing agent.
  • glycosyl hesperetin prepared through the reducing agent treatment step may be referred to as “reducing agent-treated product”), enzyme reaction ( (Transglycosylation reaction, etc.), reducing agent treatment, and purification method will be sequentially described.
  • hesperidin which is a raw material for producing a reducing agent-treated product
  • any of the conventional hesperidins used in the production of glycosyl hesperetin can be used.
  • Squeezed liquid, or a partially purified product thereof may be used in appropriate combination of one or more.
  • hesperidin-containing plant examples include citrus fruits belonging to the genus Citrus mandarin, such as mandarin oranges, oranges, perfumed citrus fruits, miscellaneous citrus fruits, tangoles, tanzeros, buntans, and kumquats.
  • Citrus mandarin such as mandarin oranges, oranges, perfumed citrus fruits, miscellaneous citrus fruits, tangoles, tanzeros, buntans, and kumquats.
  • hesperidin-containing site examples include citrus fruits, pericarps, seeds, and immature fruits.
  • any glycosyltransferase can be used as long as it can transfer to hesperidin to produce ⁇ -glycosyl hesperidin as glycosyl hesperetin when a glycosyltransferase described below is allowed to act.
  • Dextrin, cyclodextrin, malto-oligosaccharide and other starch partial decomposition products, and one or more starch partial decomposition products selected from liquefied starch, gelatinized starch and the like are appropriately selected.
  • the amount of the partially decomposed starch used in the enzyme reaction described later is usually about 0.1 to about 150 times, preferably about 1 to about 100 times, more preferably, relative to the mass of the raw material hesperidin. Is used in an amount selected from the range of about 2 to about 50 times.
  • the sugar derived from the partial starch degradation product is transferred to hesperidin, and ⁇ -glycosyl hesperidin is efficiently produced.
  • excess unreacted hesperidin remains in the enzymatic reaction system as much as possible. It is desirable to use an amount of starch partial degradation product.
  • the reason for this is that, in the purification step described later, the partially decomposed starch and saccharides derived therefrom can be separated from ⁇ -glycosyl hesperidin relatively easily, whereas hesperidin behaves together with ⁇ -glycosyl hesperidin, This is because it is difficult to separate from ⁇ -glycosyl hesperidin, so that if the remaining amount of unreacted hesperidin is extremely low, the resulting glycosyl hesperetin has a disadvantage that the water solubility of the resulting glycosyl hesperetin is low.
  • the enzyme reaction referred to in the present specification means an enzyme reaction in which ⁇ -glycosyl hesperidin is produced by allowing glycosyltransferase to act on hesperidin as a raw material for production and a partially degraded starch.
  • glycosyltransferase used in the enzyme reaction, ⁇ -glucosidase (EC 3.2.1.20), cyclomaltodextrin glucanotransferase (EC 2.4.1.19, hereinafter referred to as “CGTase”). ), ⁇ -amylase (EC 3.2.1.1) and the like.
  • Examples of the ⁇ -glucosidase include enzymes derived from animal and plant tissues such as pig liver and buckwheat seeds, or Aspergillus genus such as Mucor, Penicillium, and Aspergillus niger.
  • CGTase examples include those derived from mold cultures belonging to the above, or those obtained by culturing microorganisms such as yeast belonging to the genus Saccharomyces in a nutrient medium, such as Bacillus genus. , Geobacillus genus, Klebsiella genus, Paenibacillus genus, Thermococcus genus, Sir Ana erotic Citrobacter (Thermoanaerobacter) genus Brevibacterium (Brevibacterium) genus Pyrococcus (Pyrococcus) genus Brevibacillus (Brevibacillus) genus, and it can be exemplified those Saccharomyces (Saccharomyces) genus from.
  • microorganisms such as yeast belonging to the genus Saccharomyces in a nutrient medium, such as Bacillus genus. , Geobacillus genus, Klebsiella genus
  • ⁇ -amylase one or two or more kinds derived from bacteria belonging to the genus Aspergillus such as bacteria belonging to the genus Geobacillus or Aspergillus niger are appropriately combined. Can be used.
  • These glycosyltransferases can be either natural or genetically modified as long as the object of the present invention can be achieved, and if there are commercially available products, they can also be used as appropriate. Moreover, it is not always necessary to purify and use any of the above-mentioned glycosyltransferases. Usually, even a crude enzyme can be used as long as the object of the present invention can be achieved.
  • the production rate of ⁇ -glycosyl hesperidin can be increased by adopting a partially degraded starch suitable for the glycosyltransferase.
  • malto-oligosaccharides such as maltose, maltotriose, maltotetraose, or dextrose equivalent (DE) from about 10 to about 70 starch partial degradation products, when CGTase is used, From ⁇ -, ⁇ -, or ⁇ -cyclodextrin or starch paste of DE1 or less to a starch partial degradation product of DE about 60, and further, when ⁇ -amylase is used, from starch paste of DE1 or less to DE A partially decomposed starch such as 30 dextrins is preferably used.
  • DE dextrose equivalent
  • a solution containing hesperidin as high as possible is desirable, for example, a suspension containing hesperidin in a suspended state, dissolved in a solvent such as water at a high temperature of room temperature or higher, or A solution containing a high concentration of hesperidin dissolved in an alkali side pH exceeding 7.0 with an alkali agent is preferably used.
  • alkaline agent examples include one or two or more strong alkaline aqueous solutions of about 0.1 to about 1.0 N sodium hydroxide aqueous solution, potassium hydroxide aqueous solution, sodium carbonate aqueous solution, calcium hydroxide aqueous solution, aqueous ammonia and the like. Can be used as appropriate.
  • the concentration of hesperidin when hesperidin is used in the form of a solution using an alkaline agent is usually about 0.005 w / v% or more, preferably about 0.05 to about 10 w / v%, more preferably about 0.5. To about 10 w / v%, more preferably about 1 to about 10 w / v%.
  • hesperidin when hesperidin is used in a suspended form without using an alkaline agent, hesperidin is suspended in a solvent such as water to form a suspended hesperidin, and the concentration of hesperidin is usually about 0.1 to about 2 w / v%, more preferably about 0.2 to about 2 w / v%, more preferably about 0.3 to about 2 w / v%.
  • the temperature and time when glycosyltransferase is allowed to act on hesperidin and starch partial degradation products are the concentrations of hesperidin and starch partial degradation products used in the enzymatic reaction, the type of glycosyltransferase, the optimum temperature, the optimum pH, or the action.
  • about 50 to about 100.degree. C. preferably about 60 to about 90.degree. C., more preferably about 70 to about 90.degree. C., and about 5 to about 100 hours.
  • it is in the range of about 10 to about 80 hours, more preferably about 20 to about 70 hours.
  • the pH and temperature when glycosyltransferase is allowed to act on an alkaline solution containing a high concentration of hesperidin depends on the type of glycosyltransferase, the optimum pH, the optimum temperature, the amount of action, and the concentration of hesperidin. As high as possible at which the glycosyltransferase can act, as high as possible, specifically about pH 7.5 to about 10, preferably about pH 8 to about 10, and about 40 to about 80 ° C. More preferably, the temperature is in the range of about 50 to about 80 ° C. Since hesperidin in the alkaline solution is liable to decompose, it is desirable to keep hesperidin as light-shielded and anaerobic as possible in order to prevent this.
  • the pH at which glycosyltransferase acts on suspended hesperidin varies depending on the type of glycosyltransferase, the optimum temperature, the optimum pH, or the amount of action, and the concentration of suspended hesperidin.
  • the pH is in the range of about 4 to about 7, preferably about 4.5 to about 6.5.
  • hesperidin-rich solution in order to increase the solubility of hesperidin before the enzyme reaction and facilitate the transglycosylation reaction to hesperidin, it is highly compatible with water in a hesperidin-rich solution, particularly in a hesperidin-rich aqueous solution.
  • An appropriate amount of an organic solvent such as methanol, ethanol, n-propanol, iso-propanol, n-butanol, acetol, acetone, and other lower alcohols, lower ketones, and the like may be optionally present together.
  • the amount of enzyme and reaction time are closely related, and usually from an economic viewpoint, about 5 to about 150 hours, preferably about 10 to about 100 hours, more preferably about 20 to about 80 hours.
  • the amount of the enzyme that completes the enzymatic reaction may be appropriately set according to the type of glycosyltransferase used. In addition, it is optional to repeat the reaction in batch mode using the immobilized glycosyltransferase or to perform the reaction in a continuous mode.
  • the enzyme reaction solution containing ⁇ -glycosyl hesperidin and hesperidin obtained after the glycosyltransferase reaction is used as it is or after purification with a porous synthetic adsorption resin, if necessary, and then glucoamylase (EC 3.2.1). .3), or by partial hydrolysis with an amylase such as ⁇ -amylase (EC 3.2.1.2) to reduce the number of ⁇ -D-glucosyl groups of ⁇ -glycosyl hesperidin.
  • glucoamylase is allowed to act, a polymer higher than ⁇ -maltosyl hesperidin can be hydrolyzed to produce glucose and to produce and accumulate ⁇ -glucosyl hesperidin.
  • ⁇ -amylase when allowed to act, a polymer higher than ⁇ -maltotriosyl hesperidin is hydrolyzed to generate maltose, and a mixture containing ⁇ -glucosyl hesperidin and ⁇ -maltosyl hesperidin is generated. Can be accumulated.
  • glucoamylase and ⁇ -L-rhamnosidase have a close relationship between the amount of the enzyme and the enzyme reaction time.
  • about 5 to about 150 hours preferably The amount of the enzyme that completes the enzyme reaction in about 10 to about 100 hours, more preferably in about 20 to about 80 hours, may be appropriately set according to the type of enzyme. It is also possible to carry out the reaction repeatedly in batch mode using immobilized ⁇ -L-rhamnosidase, or to perform reaction in a continuous mode without interruption.
  • the reducing agent treatment referred to in the specification of the present application means that a specific reducing agent is used, and the miscellaneous taste and coloring of glycosyl hesperetin (hereinafter sometimes abbreviated as “miscellaneous taste / coloring”), and further the odor is significant or It means a treatment for remarkably reducing, and (a) a step of preparing an aqueous solution containing hesperidin and a partial degradation product of starch, and (a) a glycosyltransferase acting on the resulting aqueous solution -Used in one or more of the steps of producing a glycosyl hesperetin-containing composition containing glucosyl hesperidin and (c) collecting the produced glycosyl hesperetin-containing composition, or (a) to (c) It means that the predetermined amount is added to the starting material before one or more steps and / or the resulting product after the steps.
  • the reducing agent used in the method for producing glycosyl hesperetin with reduced miscellaneous taste is not particularly limited as long as the intended purpose of the present invention can be achieved, and general-purpose inorganic and organic reducing agents in the field. Any of the agents can be used. However, since the glycosyl hesperetin or high-purity glycosyl hesperetin used in the present invention including the reducing agent-treated product is mainly assumed to be applied to humans, it is highly safe, stable and easy to handle. It is desirable to use an excellent reducing agent.
  • the former reducing agent can significantly reduce the miscellaneous taste of glycosyl hesperetin prepared without the treatment of the reducing agent, and the coloring and off-flavor can be further reduced. Since a significantly reduced high-quality glycosyl hesperetin can be provided, it can be more suitably used in the present invention. Although the reason is not clear, it is presumed as follows.
  • the organic reducing agent when used for the purpose of the present invention, has a lower effect of reducing the taste / coloration compared to the inorganic reducing agent, or the organic reducing agent is an organic substance, so If the degradation product or modification product of the organic reducing agent remains without being completely removed in the purification process of the reducing agent-treated product, they may remain in the final product glycosyl hesperetin. This may be due to the negative impact on quality.
  • sulfites (Also referred to as sulfites) is a reducing agent that can be more suitably used in the present invention because it is excellent in terms of safety, stability, and handleability.
  • inorganic reducing agents such as sodium sulfite, potassium sulfite, sodium hydrogen sulfite, sodium hyposulfite, potassium hyposulfite, sodium pyrosulfite, potassium pyrosulfite, sodium metasulfite, potassium metasulfite, sodium metabisulfite, and meta Sulphites such as potassium bisulfite can be most suitably used in the present invention.
  • the reducing agent is applied to one step in the production process of glycosyl hesperetin with reduced miscellaneous taste or the like, or the starting material before and / or the resultant product after that step.
  • the appropriate amount is appropriately subdivided into the starting material before and / or the resulting material before the process, the intended object of the present invention can be efficiently achieved with a smaller amount of reducing agent. Can do.
  • the total amount of the reducing agent added in each of the steps (a) to (c), after the (a) enzyme reaction (when other enzymes other than glycosyltransferase are used, all of them are used). Is usually 0.001% or more, preferably 0.01 to 3%, more preferably 0.01 to 1%, based on the mass of the enzyme reaction solution obtained after More preferably, an amount selected from a range corresponding to 0.01 to 0.5% is used.
  • the reducing agent is added before the step (c)
  • usually the remaining reducing agent is substantially removed in the purification step, thereby reducing the miscellaneous taste obtained as the final product. Is not substantially detected in the treated glycosylhesperetin.
  • the amount of the reducing agent added in all the steps is generally 0.001% or more, preferably 0.01% or more, more preferably, in total, with respect to the mass of the enzyme reaction solution obtained after the enzyme reaction. Is added once or multiple times so as to be in the range of 0.01 to 1%.
  • the temperature at the time of addition is usually the temperature employed in the steps (a) to (c), but it can also be set to a temperature higher than that temperature. Specifically, a temperature of room temperature or higher, preferably 50 ° C. or higher, more preferably 70 ° C. or higher, more preferably 80 ° C. or higher, and more preferably 90 to 120 ° C. can be exemplified.
  • the enzyme reaction solution thus obtained can be directly used as glycosyl hesperetin with reduced miscellaneous taste and the like suitably used in the present invention.
  • the enzyme reaction solution is appropriately combined with one or more means such as a separation method, a filtration method, a purification method using a porous synthetic resin, a concentration method, a spraying method, a drying method and the like known in the art.
  • the product is treated with a reducing agent such as liquid, solid or powder.
  • the porous synthetic resin means a synthetic resin such as a porous, wide adsorption surface area and nonionic styrene-divinylbenzene polymer, phenol-formalin resin, acrylate resin, methacrylate resin, for example.
  • Amberlite XAD-1 Amberlite XAD-2, Amberlite XAD-4, Amberlite XAD-7, Amberlite XAD-8, Amberlite XAD-11, And resins such as Amberlite XAD-12; trade names manufactured by Mitsubishi Chemical Corporation: Diaion HP-10, Diaion HP-20, Diaion HP-30, Diaion HP-40, Diaion HP-50, Diamond Ion HP-2MG, Sepa beads SP70, Sepa beads SP 07, Sepabeads SP700, resins such as Sepabeads SP800; and IMACTI Ltd. trade name: Imakuti Syn-42, can be exemplified resins such Imakuti Syn-44, and Imakuti Syn-46.
  • glycosyl hesperetin is adsorbed on the porous synthetic adsorbent, while remaining starch partially decomposes. Substances and water-soluble saccharides flow out of the column without being adsorbed.
  • the glycosyl hesperetins hesperidin, 7-O- ⁇ -glucosyl hesperetin, and ⁇ -glycosyl hesperidin usually behave together and cannot be separated individually by the porous synthetic adsorbent.
  • glycosyl hesperetin-containing eluate thus obtained is subjected to a distillation treatment to distill off the organic solvent, and then concentrated to a desired concentration to obtain a glycosyl hesperetin with reduced hesperidin content and reduced miscellaneous taste. can get.
  • the elution operation of glycosyl hesperetin with the organic solvent also serves as a regeneration operation of the porous synthetic adsorbent, which has the advantage of enabling the porous synthetic adsorbent to be used repeatedly.
  • glycosyl hesperetin with reduced liquid miscellaneous taste and the like is optionally dried and powdered by a known drying method to obtain a powdery glycosyl hesperetin that is preferably used in the present invention.
  • the characteristic miscellaneous taste that was a disadvantage of glycosyl hesperetin prepared without the reducing agent treatment step (hereinafter sometimes referred to as “reducing agent non-treated product”) is significantly reduced,
  • a reducing agent-treated product in which coloring and odor are effectively reduced can be produced.
  • the taste / coloring or odor peculiar to the non-reducing agent-treated product does not substantially change only by applying the purification method. That is, for example, the purification method using the porous synthetic adsorbent, which is widely used in the manufacturing process of non-reducing agent treated products, is not only a partially decomposed product of starch and water-soluble saccharides but also impurities such as water-soluble salts.
  • glycosyl hesperetin preferably used in the present invention in particular, a reducing agent-treated product has a significantly reduced miscellaneous taste, low electrical conductivity, and a reduced content of ionic compounds involved in electrical conductivity.
  • the ionic compound include nariltin, diosmine, neoponcillin, which is originally contained in hesperidin as a raw material, or a compound such as glucosylnariltin and glucosylneoponcillin, which are enzyme reaction products, and their degradation.
  • a compound closely related to the degradation product thereof, or a furfural as an index in the present invention which is considered to be derived from a raw material for producing glycosyl hesperetin or produced as a secondary product in the production process.
  • compounds that liberate metal cations such as calcium, potassium, magnesium, and sodium in a solution state.
  • the components such as nariltin, diosmin, neoponcillin, glucosylnariltin, glucosylneoponcillin are usually contained in a small amount in the reducing agent-treated product suitably used in the present invention.
  • the mechanism by which reducing taste is used to obtain miscellaneous taste and coloration, especially glycosyl hesperetin with significantly reduced miscellaneous taste is not clear, but if estimated, It is as follows.
  • the causative agent of the taste shown in the above (1) and (2) is modified by a reducing agent, and is easily separated from glycosyl hesperetin in a purification step using a porous synthetic adsorbent and the like. A significantly reduced reducing agent-treated product is obtained.
  • examples of the glycosyl hesperetin preferably used in the present invention include those in which the glycosyl hesperetin-containing product and a reducing agent are contacted to significantly reduce the miscellaneous taste of the glycosyl hesperetin-containing product.
  • Such a glycosyl hesperetin-containing product is also included in the reducing agent-treated product referred to in the present specification.
  • the miscellaneous taste of the glycosyl hesperetin-containing product can be significantly reduced, and coloring and odor can be effectively reduced significantly.
  • the contact between the glycosyl hesperetin-containing product and the reducing agent is preferably carried out in a solution state or a suspended state using an appropriate solvent such as water, rather than in a solid state.
  • an appropriate solvent such as water
  • examples of the glycosyl hesperetin-containing product with which the reducing agent is contacted include glycosyl hesperetin containing one or more selected from hesperidin, ⁇ -glycosyl hesperidin, and 7-O- ⁇ -glucosyl hesperetin.
  • the glycosyl hesperetin-containing material is usually 70% by mass or more and less than 100% by mass (hereinafter, unless otherwise specified, “% by mass” is abbreviated as “%”) per dry solid. More preferable examples include glycosyl hesperetin containing 80% or more and less than 100%, and more preferably 90% or more and less than 100%.
  • the reducing agent to be used can be the same as that used for producing a reducing agent-treated product.
  • the amount of the reducing agent used is usually 0.00001% or more, preferably 0.0001 to 0.5%, more preferably 0.001 to 0.4 per dry solid of glycosyl hesperetin. %, More preferably in the range of 0.001 to 0.3%, mixing them uniformly and bringing the glycosyl hesperetin and the reducing agent into contact with each other to prepare without the above reducing agent treatment Even if it is a non-reducing agent treated product, the peculiar taste and the like can be significantly or remarkably reduced.
  • liquid reducing agent-treated product is concentrated by a known concentration method to obtain a syrup-like or paste-like reducing agent-treated product, which is further dried by a known drying method to form a solid, granular, or powder. It is also optional to use a reducing agent-treated product.
  • the reducing agent-treated product in which the peculiar taste and the like, which was a drawback of the non-reducing agent-treated product is significantly or significantly reduced. Can be obtained.
  • the reducing agent-treated product obtained by the above production method is substantially free of furfural and is a kind of phenol ether, 4-vinylanisole (also called 4-methoxystyrene) (hereinafter referred to as “4-VA”). "Abbreviated as”.)
  • 4-VA 4-methoxystyrene
  • glycosyl hesperetins used in the present invention not only the miscellaneous taste is significantly reduced but also the coloring and odor are significantly reduced. In the present invention, it is most preferably used.
  • the phrase “substantially free of furfural” refers to glycosyl hesperetin having a significantly lower level of furfural content than conventional products.
  • GC / MS analysis method an analysis method using a gas chromatograph mass (GC / MS) analyzer shown in “(1) Furfural content” in Experiment 2 described later (hereinafter abbreviated as “GC / MS analysis method”).
  • ppb gas chromatograph mass
  • it means less than 20 ppb, more preferably less than 15 ppb, particularly preferably less than 10 ppb.
  • glycosyl hesperetins of the present invention those in which the furfural content is reduced to below the detection limit of the GC / MS analysis method are significantly reduced in miscellaneous taste and markedly colored compared to the conventional product. It is a reduced, very high quality glycosyl hesperetin.
  • the glycosyl hesperetin used in the present invention is blended in a composition for oral use by humans, it is not always necessary to have the highest purity. Therefore, the furfural content is below the detection limit. There is not necessarily a need to be reduced to a level, or a need to be free of furfural.
  • the glycosyl hesperetin used in the present invention is not required to substantially contain furfural, and the amount of the glycosyl hesperetin is significantly smaller than the conventional product or less than the detection limit as long as the intended purpose of the present invention can be achieved.
  • Furfural may be contained.
  • the glycosyl hesperetin used in the present invention is more preferably one that does not substantially contain the above-mentioned furfural.
  • the furfural content is less than about 320 ppb, preferably about Those having a molecular weight of less than 310 ppb can exhibit an action for improving or reducing yellowing of skin, so that these glycosyl hesperetins can also be used in the present invention.
  • the 4-VA is a component presumed to be produced due to the production raw material of glycosyl hesperetin, and the content in the resulting glycosyl hesperetin is usually less than 30 ppb per dry solid, and 4-VA The content is usually in parallel with the furfural content when the furfural content is less than 200 ppb. It should be noted that “substantially free of 4-VA” means that the 4-VA content is significantly higher than that of other glycosyl hesperetin-containing compositions such as non-reducing agent treated products other than the reducing agent treated product, as in the case of furfural. Means being at a low level.
  • the 4-VA content in the reducing agent-treated product was measured by an analytical method using a GC / MS analyzer shown in “(2) 4-VA content” in Experiment 2 described later.
  • a GC / MS analyzer shown in “(2) 4-VA content” in Experiment 2 described later.
  • less than 30 ppb preferably less than 15 ppb, more preferably less than 10 ppb, even more preferably less than 5 ppb, even more preferably less than 3 ppb, even more preferably less than 2 ppb per dry solid It is.
  • the reducing agent-treated product has an excellent feature in which coloring (hereinafter, sometimes referred to as “coloring degree”) is significantly reduced as compared with the non-reducing agent-treated product.
  • coloring degree of glycosyl hesperetin is measured by the method shown in “(3) Color tone and coloring degree” of Experiment 2 described later, and the outline thereof is as follows. That is, after an aqueous solution containing a predetermined concentration of glycosyl hesperetin is heat-treated in a sealed container, the color of the treatment liquid is visually observed, and the absorbance at a wavelength of 420 nm (OD 420 nm ) and the absorbance at a wavelength of 720 nm (OD) are measured by a spectrophotometer.
  • the difference in absorbance at both wavelengths (OD 420 nm -OD 720 nm ) is determined, and the measured value is taken as the coloring degree.
  • the difference in absorbance is less than 0.24, preferably 0.20 or less, more preferably 0.17 or less, still more preferably more than 0 and less than 0. What is 15 or less can be illustrated.
  • heating the aqueous solution of glycosyl hesperetin is based on the fact that coloring due to heating of glycosyl hesperetin is due to the disadvantage that the degree of coloration of the non-reducing agent-treated product increases remarkably. It was set for the purpose of evaluation.
  • the reducing agent-treated product is a glycosyl hesperetin-containing composition containing glycosyl hesperetin and a physiologically acceptable ionic compound, which is a 1 w / v% aqueous solution, heated at 100 ° C. for 30 minutes in a sealed container,
  • the electrical conductivity at 20 ° C. is less than 10 ⁇ S / cm, preferably less than 8 ⁇ S / cm, more preferably less than 6 ⁇ S / cm, and even more preferably more than 0 ⁇ S / cm and more than 4.5 ⁇ S / cm.
  • a glycosyl hesperetin-containing composition that is less than
  • the physiologically acceptable ionic compound referred to in the present specification is essentially contained in a reducing agent-untreated product and a reducing agent-treated product, which is orally ingested by humans, apart from the amount of the physiologically acceptable ionic compound.
  • a reducing agent-untreated product and a reducing agent-treated product, which is orally ingested by humans, apart from the amount of the physiologically acceptable ionic compound.
  • safe physiologically acceptable ionic compounds that are either inherently contained in the raw material of manufacture or produced as a secondary product during the manufacturing process and are safe for ingestion by humans.
  • Physiologically acceptable ionic compound are either inherently contained in the raw material of manufacture or produced as a secondary product during the manufacturing process and are safe for ingestion by humans.
  • glycosyl hesperetin-containing composition for example, naryltin, diosmine, neoponcillin, or glucosylnariltin which is an enzyme reaction product, which is inherently included in the hesperidin raw material, It means a decomposition product such as glucosyl neoponcilin and a compound closely related to the decomposition product, and releases metal ions such as calcium, potassium, magnesium and sodium which are cationic metal elements in a solution state. Compound etc. are mentioned.
  • the reducing agent-treated product obtained by the production method is a composition mainly composed of one or more glycosyl hesperetins selected from hesperidin, ⁇ -glycosyl hesperidin, and 7-O- ⁇ -glucosyl hesperetin.
  • the total glycosyl hesperetin content per dry solid of the composition is usually 90% or more and less than 100%, preferably 93% or more and less than 100%, more preferably 95% or more. It is less than 100%, more preferably 97% or more and less than 100%, and still more preferably 98% or more and less than 100%.
  • the ⁇ -glycosyl hesperidin content referred to in the present specification refers to a composition containing ⁇ -glycosyl hesperidin as a sample, which is diluted or dissolved to 0.1% (w / v) with purified water, and a 0.45 ⁇ m membrane.
  • the sample was subjected to high performance liquid chromatography (HPLC) analysis under the following conditions, using the reagent hesperidin (sales by Wako Pure Chemical Industries, Ltd.) as a standard substance, and the peak area appearing in the chromatogram at UV 280 nm Calculated on the basis of the molecular weight of each component such as hesperidin, ⁇ -glycosyl hesperidin ( ⁇ -glucosyl hesperidin, etc.), and the content of each component in a composition converted to the amount of anhydrous substance.
  • HPLC high performance liquid chromatography
  • HPLC device “LC-20AD” (manufactured by Shimadzu Corporation)
  • Degasser “DGU-20A3” (manufactured by Shimadzu Corporation)
  • Sample injection amount 10 ⁇ 1
  • Eluent water / acetonitrile / acetic acid (80/20 / 0.01 (volume ratio))
  • Flow velocity 0.7 m1 / min
  • Temperature 40 ° C
  • Detection UV detector “SPD-20A” (manufactured by Shimadzu Corporation)
  • Data processor “Chromatopack C-R7A” (manufactured by Shimadzu Corporation)
  • Hesperidin content Analyzed by HPLC, and calculated based on the ratio of the peak area to the peak area of the reagent hesperidin (sold by Wako Pure Chemical Industries, Ltd.) as a standard substance with a predetermined concentration.
  • ⁇ -glucosyl hesperidin content analyzed by HPLC, the ratio of the peak area to the peak area of the reagent hesperidin (sales of Wako Pure Chemical Industries, Ltd.) as a standard substance of a predetermined concentration, ⁇ -glycosyl hesperidin and Calculated based on the molecular weight ratio of hesperidin.
  • glycosyl hesperetin content Analyzed by HPLC, the ratio of the peak area to the peak area of the reagent hesperidin (sold by Wako Pure Chemical Industries, Ltd.) as a standard substance of a predetermined concentration, and other glycosyl hesperetin Calculated based on the molecular weight ratio with hesperidin.
  • glycosyl hesperetin in which ⁇ -glycosyl hesperidin is ⁇ -glucosyl hesperidin, is the intended effect in the present invention, that is, the effect of improving yellowing of skin and texture, And the effect of improving the skin quality such as dryness of the skin, erythema, irritation, and pruritus is more preferable.
  • the preferred content of ⁇ -glucosyl hesperidin in the glycosyl hesperetin is usually 60 to 90%, preferably 70 to 90%, more preferably 75 to 90%, based on the dry solids of the composition. Yes, they are preferable because the above-described effects are more prominent.
  • a 1 w / v% aqueous solution was prepared, heated in a sealed container at 100 ° C. for 30 minutes, adjusted to room temperature, put into a cell having a width of 1 cm, and a spectrophotometer the less the difference in absorbance at both wavelengths when measuring the absorbance at a wavelength of 420 nm (OD 420 nm) and wavelength 720nm (OD 720nm) (OD 420nm -OD 720nm) is 0.24, preferably 0.20 or less, more preferably Is 0.17 or less, and more preferably 0 or more and 0.15 or less, the intended effects in the present invention, that is, the skin yellowing and texture-improving action, and skin dryness, erythema, It is preferable because the effect of improving the skin quality such as irritation and pruritus is exhibited more remarkably. Further, it is also superior in that miscellaneous taste / coloring and odor are significantly or
  • the calcium, potassium, magnesium, and sodium contents per dry solid of the reducing agent-treated product as measured by high frequency inductively coupled plasma emission spectrometry are the following numerical values.
  • the reducing agent-treated product has a significantly different taste, is significantly reduced in coloring and odor, and is excellent in thermal stability. For example, it can be treated at a high temperature of 80 to 100 ° C. Even if it is heated for 30 minutes or more, or the step of containing the reducing agent-treated product or the oral cosmetic containing the same is stored at room temperature or slightly above room temperature for several tens of minutes to several months. In addition, miscellaneous taste / coloration due to the reducing agent-treated product, and further, odor is maintained without change compared to immediately after production, or their increase is effectively suppressed. Furthermore, the reducing agent-treated product has an advantage of good acid resistance and heat resistance.
  • the glycosyl hesperetin used in the present invention is a compound having a hesperetin skeleton, whether treated with a reducing agent or not treated with a reducing agent.
  • ⁇ -glycosyl hesperidin such as ⁇ -glucosyl hesperidin
  • Flavonoids such as nariltin, diosmine, neoponcillin, glucosylnariltin, and (4) trace components such as salts are considered to be produced as secondary products.
  • the glycosyl hesperetin may contain hesperetin as long as the intended effects of the present invention are not hindered.
  • the glycosyl hesperetin used in the present invention includes hesperetin whose dispersibility in a solvent such as water is improved by a known physical or chemical method or the like within a range in which the intended effect of the present invention is not hindered. It is also possible to mix appropriately.
  • the upper limit of the purity of glycosyl hesperetin used in the present invention that is, the content of glycosyl hesperetin per dry solid is usually 99% that can be provided industrially in relatively large quantities, inexpensively and easily, and 98% for providing cheaply. In order to provide it at a lower cost, the content may be as low as 97% or less.
  • the lower limit of the glycosyl hesperetin content is usually 90% or more, preferably 93% or more, more preferably 95% or more, and more preferably 97% by mass or more.
  • the glycosyl hesperetin used in the present invention when the glycosyl hesperetin is ⁇ -glycosyl hesperidin such as ⁇ -glucosyl hesperidin, the ⁇ -glycosyl hesperidin content per dry solid is 50% or more and less than 100%.
  • the glycosyl hesperetin is ⁇ -glycosyl hesperidin such as ⁇ -glucosyl hesperidin
  • the ⁇ -glycosyl hesperidin content per dry solid is 50% or more and less than 100%.
  • the upper limit of the ⁇ -glucosyl hesperidin content in glycosyl hesperetin used in the present invention is usually relatively large, inexpensive and easily provided industrially when the oral beauty solvent according to the present invention is provided at a lower cost. It may be as low as 90% or less, 85% or less for lower cost, and 80% or less for lower cost.
  • the lower limit of the ⁇ -glucosyl hesperidin content is usually preferably 60% or more, 65% or more, or 70% or more for the same reason as the glycosyl hesperetin content.
  • the oral beauty agent of the present invention contains various glycosyl hesperetins such as non-reducing agent-treated products and / or reducing agent-treated products as active ingredients.
  • glycosyl hesperetins such as non-reducing agent-treated products and / or reducing agent-treated products as active ingredients.
  • Glycosyl hesperetin is a so-called beauty to improve skin yellowing, texture, and skin quality that has recently attracted attention because it can effectively improve skin quality such as dryness, erythema, irritation, and pruritus.
  • glycosyl hesperetin As food, health food, nutritional functional food, functional health food, food for specified health use, and for other beauty food, health food, nutritional functional food, health functional food, food for specified health use, or food and drink It can be advantageously blended appropriately.
  • polyphenols such as resveratrol, quercetin, chlorogenic acid, anthocyanin, curcumin, kaempferol, flavonoids; artichoke leaf extract, tomorrow leaf extract, strawberry seed extract, ginkgo leaf extract Plant extracts such as Wenzhou mandarin orange extract, cassis extract, kiwi seed extract, cranberry extract, acerola extract, amla extract and aronia extract; carotenoids such as astaxanthin and ⁇ -carotene; and plant extracts or compounds having a saccharification reaction inhibitory action When used in combination with one or more ingredients, the effect of improving the yellowing, texture, and skin quality of the skin produced by glycosyl hesperetin
  • Examples of the plant extract or compound having an inhibitory action on saccharification reaction include Ibright, Aomi, Akigumi, Agrimony, Agni fruit, Akebi, Acai fruit, Ashwagandha, Asunaro, Acacia catechu, Abemaki, Achacha, Anise, American witch hazel, Aristine, Ikariso , Itadori, Ginkgo biloba, Strawberry, Itohayuri, Itofonori, Inubiwa, Ipe bark, Itohamomiji, Iwatoyuri, Fennel, Witch hazel, Wintergreen, Turmeric, Ume, Vulture, Epimedium brevicornum, Ages, Echinacea ezoe Elder, Elba Mate, Ogashi, Ogaku, Ouren, Milk Thistle, Oats, Obatanekibana, Okajiki, Otome Yuri, Onita Tiger lily, oregano, orange, pumpkin seeds, bonito bark, coconut
  • Extracts of seaweed such as hanafunori, fukurofunori, mafunori; extracts of raw coffee beans, sweet potato shochu, agaricus mycelium; and equol, isoflavone, 1,4-anthraquinone, 1-amino-2-hydroxy Methyl anthraquinone, 4-aminophenol, 1,3,5-trihydroxybenzene, kojic acid, 3,4-dihydroxyphenylacetic acid, caffeic acid, ifenprodil, 6-hydroxy-2,5,7,8-tetramethylchroman -2-carboxylic acid, 6-hydroxyindole, 7-hydroxy-4,6-dimethylphthalide ⁇ -lipoic acid, 4-hydroxychalcone, pearl protein hydrolyzate, aminoguanidine, erythrosine sodium, ergothioneine, resveratrol, hydroxystilbenes such as 3,3 ′, 5,5′-tetrahydroxystilbene, oxindole, Car
  • the plant extract or compound having a saccharification reaction inhibitory action more preferably used in the present invention includes Ashwagandha, Asunaro, Acacia catechu, Ginkgo biloba, Wintergreen, Aubergine, Orange, Pumpkin seeds, Katsuaba bark, Kusunohagasiwa , Glucosylrutin, Cowberry, Perilla, Buckwheat leaf, Davila rugosa, Dokudami, Himewabamiso, Safflower ragwort, Matatabi, Ryukyuchiku, Ryukyu strawberry, Apple immature fruit, Persimmon leaf, Licorice leaf, Moon peach leaf, Butterberry leaf extract And equol, isoflavone, ifenprodil, pearl protein hydrolyzate, catechol, caffeic acid, and purnin.
  • Oral cosmetics of the present invention include troches, liver oil drops, complex vitamins, mouth fresheners, mouth-flavored tablets, oral / tube feeding, oral medicines, various solids, granules, powders, suspensions, pastes It is also optional to use it in various compositions in the form of jelly, jelly or liquid.
  • glycosyl hesperetin in the oral cosmetic of the present invention can be adjusted as appropriate depending on the intake frequency of the oral cosmetic and the state of the skin.
  • glycosyl hesperetin selected from one or more selected from hesperidin, ⁇ -glycosyl hesperidin, and 7-O- ⁇ -glucosyl hesperetin is all regarded as hesperidin.
  • converted to hesperidin When converted to mass (hereinafter referred to simply as “converted to hesperidin” in the present specification), they are more than 10% and less than 100%, preferably more than 15% and less than 100%, more preferably , More than 20% and less than 100%, more preferably more than 30% and less than 100%.
  • the ingestion frequency, ingestion amount, and ingestion period of the oral beauty agent of the present invention are selected from hesperidin, ⁇ -glycosyl hesperidin, and one or more glycosyl hesperetins selected from 7-O- ⁇ -glucosyl hesperetin.
  • Glycosyl hesperetin is a solid, granular, powder, suspension, paste, etc., such as the aforementioned lozenges, liver oil drops, complex vitamins, mouth fresheners, mouth-flavored tablets, oral / tube feeding, oral medicines, etc.
  • a method of blending into various compositions in a jelly-like or liquid form for example, mixing, kneading, mixing, adding, dissolving, dipping, penetrating, spraying, applying, spraying in the process until the composition is completed.
  • One or more known methods such as injection can be used as appropriate.
  • the oral cosmetic agent of the present invention thus obtained can be used not only in itself but also in various compositions containing the same even when kept or stored at room temperature or slightly above room temperature for several tens of minutes to several months. In addition to the miscellaneous taste and coloration caused by the oral cosmetic agent, the odor is not at all or is remarkably reduced to such an extent that it cannot be perceived.
  • the oral beauty agent of the present invention also functions as a highly safe natural antioxidant, stabilizer, quality improver, vitamin P enhancer, etc., and is used as a food, drink, beauty food, health food, and nutritionally functional food. It is also optional to use it in various compositions such as health functional foods, foods for specified health use, feeds and feeds.
  • Example 1 Oral intake test>
  • Outline For the purpose of investigating the effects of glycosyl hesperetin on the skin, using the powdered glycosyl hesperetin-containing composition obtained in Example 1 described later and prepared without using a predetermined reducing agent, Oral study with 42 working women aged 35 to 55 who have chronic fatigue symptoms known to adversely affect their condition and are concerned about their skin condition such as rough skin
  • An intake test was conducted. That is, the subject is orally ingested with a predetermined test sample for a predetermined period, and the instrument is measured for yellowish dullness on the subject's skin (face), and the skin surface texture is visually determined by a doctor. As for, a visual judgment and an inquiry by a doctor were performed, and the influence of the test sample on the skin was evaluated.
  • test sample A a capsule tablet type test sample containing glycosyl hesperetin
  • test sample B a capsule tablet type test sample
  • Test procedure 21 subjects were randomly divided into 21 groups, group A and group B, test sample A as a test sample in group A, and test sample B in group B 2 once a day. Each tablet was ingested orally for 12 weeks. Although the time to ingest the test sample was not specified, each instructed to take it at the same time zone as much as possible.
  • the color difference of each subject's cheeks was measured using a color difference meter and evaluated for yellowing of the skin (see “A” below). The texture of the skin surface of the subject's face (see “I” below) was evaluated, and further, the skin quality was evaluated by visual judgment and interview by a doctor (see “C” below).
  • each said evaluation was implemented also before the oral intake start (0W) of the test sample, and 6 weeks (6W) after the oral intake start.
  • data analysis in group B was performed based on subject data of 20 subjects.
  • the a * value represents the degree of redness of the skin
  • the “b * value” represents the degree of yellowness of the skin.
  • Skin dullness which is a superordinate concept of skin yellowishness, occurs on the entire face or around the eyes and cheeks, and the redness of the skin decreases, yellowing increases, and the glossiness and transparency of the skin decreases. Is a technical term that refers to a state where the brightness decreases due to shadows due to unevenness on the skin surface, etc. It is said that the main cause is yellowing (yellowing).
  • the L * value and the b * value is an index of skin brightness
  • the b * value is an index of yellowness
  • they are independent numerical values that are not linked to each other. It is.
  • the degree of skin pigmentation (melanin) can be well divided using the angle when the L * value and the b * value are plotted on a plane as an index.
  • the b * value is influenced by factors other than melanin
  • the L * value and b * value, including the a * value are numerical values for describing the color, and are specific to melanin.
  • glycosyl hesperetin when glycosyl hesperetin is orally ingested by humans, it is thought that glycosyl hesperetin produces hesperetin under the action of in vivo enzymes, and this hesperetin is thought to exert an action to improve or reduce yellowing of skin.
  • Glycosyl hesperetin such as hesperidin, 7-O- ⁇ -glucosyl hesperidin, and ⁇ -glycosyl hesperidin, or compositions containing the same are orally ingested by humans, it is judged to have an effect of improving or reducing yellowing of skin.
  • glycosyl hesperetin has the effect of effectively improving all of the skin quality such as dryness of the skin, erythema, irritation, and pruritus as well as effectively improving the yellowing and texture of the skin. It is judged.
  • a reducing agent treatment was used instead of the glycosyl hesperetin blended in the test sample A used in this test.
  • the reducing agent-treated product is significantly or significantly reduced or significantly improved in taste, color, odor, etc., compared to the non-reducing agent-treated product. Therefore, it has the advantage that it can be taken orally without discomfort. That is, the taste of the reducing agent-treated product is significantly reduced as compared with the test sample A used in this test, that is, glycosyl hesperetin (non-reducing agent-treated product) prepared without using a predetermined reducing agent.
  • the coloring and the unpleasant odor are remarkably reduced, for example, oral cosmetics containing reducing agent-treated products shown in Examples 2 to 8 described later as active ingredients are continuously administered to humans on a daily basis. Therefore, the product treated with the reducing agent is the most suitable glycosyl for carrying out the present invention. Hesperetin.
  • Example 2 Physical properties of glycosyl hesperetin> As glycosyl hesperetin, four powdered glycosyl hesperetins (test samples) prepared in the same manner as those described in Examples 2, 4, 5 and 6 except that no reducing agent was used in the methods described later. 1 to 4) and the method of Example 2, except that 0.1, 0.09, 0.07, or 0.04% by mass of sodium pyrosulfite was used as the reducing agent. Four types of powdered glycosyl hesperetin (test samples 5 to 8) prepared in the above were used.
  • Test sample 1 was prepared without using a predetermined reducing agent, and the contents of ⁇ -glucosyl hesperidin, hesperidin, and other components were almost the same as those of powdered glycosyl hesperetin obtained in Example 1. This is equivalent to the powdered glycosyl hesperetin obtained in Example 1.
  • GC / MS analysis conditions > GC / MS analyzer: “Claras 680 GC” and “Claras SQ8T” (both manufactured by PerkinElmer) Column: VF-WAXms [30 m (column length) ⁇ 0.25 mm (inner diameter), film thickness 0.25 ⁇ m] (manufactured by AGILENT J & W) Detector: Mass spectrometer Carrier: Helium gas Linear velocity: 35 cm / sec Temperature rising condition: Hold at 40 ° C. for 3 minutes, increase temperature from 40 ° C. to 80 ° C. at a rate of 5 ° C./min, and then to 80 ° C. to 200 ° C.
  • the temperature is raised at a rate of 10 ° C./minute, held at 200 ° C. for 7 minutes, heated from 200 ° C. to 220 ° C. at a rate of 10 ° C./minute, and further held at 220 ° C. for 8 minutes.
  • Surrogate substance Cyclohexanol Internal standard substance: Henicosan Extraction solvent: Diethyl ether
  • the 4-VA content was measured using the following reagents, procedures, and apparatus. In addition, the measurement was performed according to “Notice of Benzene in Soft Drinks” issued on July 28, 2006, by the Food Safety Foundation No. 0728008, the Ministry of Health, Labor and Welfare, Ministry of Health, Labor and Welfare of the Ministry of Health, Labor and Welfare.
  • standard solution A 0.0005 mass% 4-VA solution
  • standard solution B A mass% 4-VA solution
  • each of these test samples 1 to 8 was dissolved in pure water so as to be a 1 w / v% aqueous solution, heated at 100 ° C. for 30 minutes in a sealed container, and then obtained test
  • the aqueous solutions of Samples 1 to 8 were each cooled to 20 ° C., and the electric conductivity at 20 ° C. was measured with an electric conductivity meter (trade name “CM-50AT”, manufactured by Toa DKK Corporation).
  • the content of the cationic metal element was determined by the following method as a simple method. That is, for each of the test samples 1 to 8, about 0.5 g is precisely weighed in a 50 mL container (trade name “Falcon Tube”, manufactured by Nippon Becton Dickinson Co., Ltd.), heated and dissolved in 20 mL of ultrapure water, and precisely Add 0.54 mL of 60w / w% nitric acid aqueous solution for analysis, heat at 70 ° C. for 14 hours, cool to room temperature, make the total volume to 50 mL with ultrapure water, and use the metal elements under the following analyzer and measurement conditions The content was determined. As a control, only ultrapure water was used.
  • Inductively coupled plasma emission spectrometer “CIROS-120” (Spectro) ⁇ Plasma power: 1,400W Plasma gas (Ar): 13.0 L / min Auxiliary gas (Ar): 1.0 L / min Nebulizer gas (Ar): 1.0 L / min Pump operation: 1.0 mL / min Calculation method of metal element content (ppm): ⁇ (measured value of test sample)-(measured value of control) ⁇ x dilution factor
  • test samples 1 to 4 were all over 300 ppb, whereas all of test samples 5 to 8 were about 10 ppb. Further, the 4-VA contents of test samples 1 to 4 were all over 40 ppb, whereas the test samples 5 to 8 were all about 2 ppb or less.
  • the aqueous solutions of the test samples 1 to 4 (reducing agent non-treated product) was light yellow
  • the aqueous solutions of the test samples 5 to 8 (reducing agent-treated product) was clearly lighter than the test samples 1 to 4.
  • the degree of coloration by the spectrophotometer was 0.24 or more for all of the aqueous solutions of the test samples 1 to 4, whereas the aqueous solutions of the test samples 5 to 8 were all 0.20 or less. It was low.
  • the coloring degree of the test samples 5 to 8 showed a lower value as the amount of the reducing agent used was larger.
  • the electrical conductivity of the aqueous solutions of test samples 1 to 4 was about 11 to about 12 ⁇ S / cm and over 10 ⁇ S / cm, whereas the aqueous solutions of test samples 5 to 8 were About 3 to about 7 ⁇ S / cm and less than 10 ⁇ S / cm.
  • test samples 5 to 8 As apparent from Table 2, the contents of metal elements (calcium, potassium, magnesium, and sodium) in test samples 5 to 8 are clearly lower than those of test samples 1 to 4, and the results are shown in FIG. It was in good agreement with the measurement results.
  • the reducing agent-treated product has a significantly reduced furfural content, and the 4-VA content, coloring degree, electrical conductivity, and metal element content are also significantly reduced. It has been found.
  • sample A glycosyl hesperetin
  • sample B non-reducing agent-treated product And glycosyl hesperetin
  • Coloring determination test 9 healthy males and females (2 females, 7 males) aged 28 to 57 years old were used as panels, and test samples 9 to 11 and Sample B (hereinafter referred to as “control”) were used.
  • An evaluation test for coloring was performed. That is, each of the test samples 9 to 11 and the control were dissolved in distilled water at room temperature so as to be a 1 w / w% aqueous solution, and they were visually observed by each panelist, and each panelist compared with the control for each test sample. When it was evaluated that “coloring was reduced”, it was determined as “determination A1”, and when it was evaluated “not colored”, it was determined as “determination B1”.
  • the furfural content and the 4-VA content can be used as indicators for distinguishing glycosyl hesperetin in which the miscellaneous taste is significantly reduced and the coloring is significantly reduced. That is, if the furfural content is 200 ppb or less and the 4-VA content is 30 ppb or less, glycosylation with significantly reduced miscellaneous taste and remarkably reduced coloring as compared with the non-reducing agent-treated product. Hesperetin can be obtained.
  • Table 2 in the above-described Experiment 2 and Table 3 below summarizes the relationship between the miscellaneous taste of powdered glycosyl hesperetin shown in Examples 1 to 8 described later, the furfural content and the 4-VA content.
  • Table 4 the furfural content of test samples 5 to 8 which are reducing agent-treated products and powdered glycosyl hesperetins of Examples 2 to 8 (hereinafter collectively referred to as “reducing agent-treated samples”) is 191 ppb or less.
  • the 4-VA content was 28.7 ppb or less, and the miscellaneous taste peculiar to the non-reducing agent-treated product was significantly reduced.
  • the furfural content of the powdered glycosyl hesperetin (hereinafter collectively referred to as “reducing agent non-treated sample”) of the test samples 1 to 5 which are non-reducing agent treated products is 308 ppb or more, and the 4-VA content is It was 40.0 ppb or more, and had a miscellaneous taste peculiar to the non-reducing agent-treated product.
  • the glycosyl hesperetin treated with the reducing agent is significantly reduced in taste, and the coloring and odor are also significantly reduced compared to the glycosyl hesperetin not treated with the reducing agent. It has been found that human beings can be taken orally on a daily basis safely and easily, and without discomfort.
  • ⁇ Experiment 4 Sensory test> (1) Preparation of test sample Of test samples 5 to 8 which are reducing agent-treated products used in Experiment 2, the values of furfural content, coloring degree, electrical conductivity, and metal element content are intermediate. Among the test sample 6 shown and the test samples 1 to 4 which are non-reducing agent-treated products, the test sample 1 having the lowest values of furfural content, coloring degree, electrical conductivity, and metal element content, The sensory test shown in the following (2) was conducted using 8 healthy men and women of 28 to 59 years old (2 women and 6 men) as a panel.
  • test sample 1 a reducing agent non-treated product
  • test sample 6 a reducing agent treated product
  • RO water water that has passed through a reverse osmosis membrane
  • test samples 1 and 6 were stored in a sealed container until they were subjected to the following test.
  • each of the non-heated test samples 1 and 6 was sealed in a container, heated in a boiling water bath for 30 minutes, and cooled to room temperature to be heated test samples 1 and 6.
  • each panelist adjusted the room temperature to the non-heated test samples 1 and 6 (each 10 mL) and the heated test samples 1 and 6 (each 10 mL) obtained in (1). Each was evaluated for a) coloring and (b) odor. Thereafter, each panelist was asked to boil their mouth with white hot water before tasting each test sample, and then (c) bitterness (including astringency, gummy, astringent taste), (d) aftertaste, and (e) Each person was evaluated about the odor at the time of tasting. Evaluation criteria are as shown in Table 5 below.
  • the non-heated test sample 6 is used as a control
  • the heated test sample 1 is used as a control
  • Each panelist was evaluated. The results are shown in Table 6 and Table 7, respectively.
  • the evaluation results shown in Tables 6 and 7 include (a) coloring, (b) odor, ( ⁇ ) for the ⁇ -glucosyl hesperidin-containing composition (heated / unheated test sample 1) as a non-reducing agent-treated product.
  • the evaluation results of c) bitterness, (d) aftertaste, and (e) odor are not shown, the evaluation results shown in Tables 5 and 6 are based on glycosyl hesperetin, which is a non-reducing agent-treated product. Since the evaluation results of the reducing agent-treated product glycosyl hesperetin are as follows, the evaluation result of the reducing agent-treated product itself is an intermediate value for each evaluation item in terms of the score (five-level evaluation) shown in the evaluation criteria. “3”.
  • the non-heated test sample 6, that is, the reducing agent-treated product that has not been heat-treated is (a) colored, (b) odor, (c) bitterness, (d)
  • the number of panels evaluated as the highest “1” in the five-level evaluation was 4 out of 8, 4 people, 3 people, 0 people, 3 people, and 4 people, respectively ( 14 people in total).
  • the heated test sample 6 shown in the evaluation results of Table 6, that is, the heat-treated reducing agent-treated product is (a) colored, (b) odor, (c) bitter, (d) aftertaste, and (e) odor.
  • the number of panels evaluated as the highest “1” in the 5-level evaluation was 4 out of 8, 4, 5, 4, and 4 (total of 24), respectively.
  • This result shows that the product treated with the reducing agent is a high-quality glycosyl hesperetin in which not only the bitterness and coloring inherent in the product not treated with the reducing agent but also the odor is effectively reduced.
  • the non-heated test sample 6 (glycosyl hesperetin-containing composition that has not been heat-treated) has (a) coloring, (b) odor, (c) bitterness, (d) odor, the number of panels evaluated as “5”, which is the lowest in the 5-level evaluation, and “4”, which is one level higher than the minimum level, was 0 (total 0). It was.
  • the heated test sample 6 (heat-treated glycosyl hesperetin-containing composition) was (a) colored, (b) odor, (c) bitter, (d) aftertaste, and ( e) Regarding the odor evaluation items, the number of panels evaluated as “5”, which is the lowest in the 5-level evaluation, and “4”, which is one level higher than the lowest level, was 0 (total 0).
  • This result indicates that the product treated with the reducing agent is a high-quality glycosyl hesperetin-containing composition in which not only the taste and color but also the odor is effectively reduced compared to the product not treated with the reducing agent.
  • the reducing agent-treated product is (a) colored, (b) odor, (c) bitterness peculiar to the reducing agent non-treated product regardless of heating / non-heating. It was found that all the evaluation items of (d) aftertaste and (e) odor are remarkably excellent, and the difference in superiority and inferiority appears as a more remarkable difference when heated. *
  • test samples 5, 7, and 8 shown in “(1) Preparation of test sample” in Experiment 3 were also subjected to “(2) Sensory test” in this experiment 4, and were almost equivalent to the test sample 6. Results were obtained. *
  • the reducing agent-treated product has significantly reduced bitterness and aftertaste, i.e., miscellaneous taste, which is unique to the non-reducing agent-treated product, and significantly reduces coloring and odor compared to the non-reducing agent-treated product. Turned out to be. *
  • the reducing agent-treated product has significantly reduced bitterness and aftertaste, i.e., miscellaneous taste, which is characteristic of the non-reducing agent-treated product glycosyl hesperetin, and the coloring and odor are remarkable Has been found to be reduced.
  • ⁇ Oral beauty agent> As a raw material, 7 parts by mass of dextrin (DE20) is used for 1 part by mass of hesperidin in the same manner as described in Example A-2 of JP-A No. 11-346792, and derived from Bacillus stearothermophilus. Add 20 units of cyclomaltodextrin / glucanotransferase (produced by Hayashibara Co., Ltd.) per gram of dextrin, maintain at pH 6.0 and 75 ° C., and react for 24 hours to obtain a syrup-like glycosyl hesperetin-containing composition.
  • DE20 dextrin
  • glucanotransferase produced by Hayashibara Co., Ltd.
  • the furfural content of this product was 310 ppb, the 4-VA content was 40.0 ppb, the coloring degree was 0.24, and the electric conductivity was about 11 ⁇ S / cm.
  • the product contained about 3 ppm, about 0.2 ppm, about 0.4 ppm, and about 1 ppm of calcium, potassium, magnesium, and sodium, respectively, per dry solid.
  • DE20 dextrin
  • the resulting enzyme reaction solution is heated to inactivate the remaining enzyme, filtered, and the filtrate is applied to a column packed with a porous synthetic adsorbent, trade name “Diaion HP-10” (Mitsubishi Chemical Corporation).
  • the liquid was passed at a space velocity (SV) of 2.
  • SV space velocity
  • ⁇ -glucosyl hesperidin and unreacted hesperidin in the solution adsorbed to the porous synthetic adsorbent, and D-glucose, salts and the like flowed out without being adsorbed.
  • purified water is passed through the column, the column is washed, and further passed while increasing the concentration of the aqueous ethanol solution stepwise.
  • the fraction containing ⁇ -glucosyl hesperidin is collected, concentrated under reduced pressure, powdered, A pale yellow powdered glycosyl hesperetin-containing composition was obtained in a yield of about 70% based on the mass of raw material hesperidin per dry solid.
  • the powdered glycosyl hesperetin-containing composition obtained in this example contained 80.0% by mass of ⁇ -glucosyl hesperidin, 12.3% by mass of hesperidin, and 7.7% by mass of other components.
  • This product had a furfural content of 12 ppb, a 4-VA content of 2 ppb, a coloring degree of 0.19, and an electric conductivity of about 6 ⁇ S / cm.
  • the product contained about 0.4 ppm, about 0.05 ppm, about 0.1 ppm, and about 0.1 ppm of calcium, potassium, magnesium, and sodium, respectively, per dry solid.
  • this product is significantly reduced in taste and color and significantly reduced odor compared to the powdered glycosyl hesperetin-containing composition obtained in Example 1 produced without using a predetermined reducing agent.
  • a predetermined reducing agent Even when heated for 30 minutes at a relatively high temperature of 90 to 100 ° C., not only the taste and color, but also the odor was effectively reduced.
  • the oral beauty agent of this example is an oral beauty agent that has excellent storage stability and can be taken orally by a human on a daily basis safely and easily without discomfort, and has an action to improve yellowing and texture of skin, and It has excellent advantages that can effectively improve skin quality such as dry skin, erythema, irritation, and pruritus.
  • the solution was dissolved with stirring for 30 minutes, neutralized with 0.01 N hydrochloric acid solution, and then immediately Geobacillus stearothermophilus Tc-91 strain (National Institute of Advanced Industrial Science and Technology, Patent Biodeposition Center) No. FERM BP-11273) -derived CGTase was added at 20 units per gram of dextrin, maintained at pH 6.0, 75 ° C., and allowed to react for 24 hours with stirring.
  • the resulting enzyme reaction solution is heated to inactivate the remaining enzyme, filtered, and the filtrate is applied to a column packed with a porous synthetic adsorbent, trade name “Diaion HP-10” (Mitsubishi Chemical Corporation).
  • the solution was passed through SV2.
  • ⁇ -glucosyl hesperidin and unreacted hesperidin in the solution were adsorbed on the porous synthetic adsorbent, and saccharides, salts and the like flowed out without being adsorbed.
  • purified water is passed through the column, the column is washed, and further passed while increasing the concentration of the aqueous ethanol solution stepwise.
  • the fraction containing ⁇ -glucosyl hesperidin is collected, concentrated under reduced pressure, powdered, A pale yellow powdered glycosyl hesperetin-containing composition was obtained in a yield of about 68% based on the mass of raw material hesperidin per dry solid.
  • the powdered glycosyl hesperetin-containing composition obtained in this example contained 79.0% by mass of ⁇ -glucosyl hesperidin, 14.0% by mass of hesperidin, and 7.0% by mass of other components.
  • the furfural content of this product was 11 ppb, the 4-VA content was 1.5 ppb, the coloring degree was 0.14, and the electrical conductivity was about 4 ⁇ S / cm. Moreover, this product contained about 0.4 ppm, about 0.06 ppm, about 0.1 ppm, and about 0.1 ppm of calcium, potassium, magnesium, and sodium, respectively, per dry solid.
  • this product Compared with the powdered glycosyl hesperetin-containing composition obtained in Example 1 produced without using a predetermined reducing agent, this product has significantly reduced miscellaneous taste and coloring and significantly reduced odor. In addition, even when heated for 30 minutes at a relatively high temperature of 90 to 100 ° C., not only miscellaneous taste and coloring, but also the odor was effectively reduced.
  • the oral beauty agent of this example is an oral beauty agent that has excellent storage stability and can be taken orally by a human on a daily basis safely and easily without discomfort, and has an action to improve yellowing and texture of skin, and It has excellent advantages that can effectively improve skin quality such as dry skin, erythema, irritation, and pruritus.
  • FERM BP-11273 was added per gram of dextrin and maintained at pH 6.0 and 75 ° C. and reacted for 24 hours, about 72% of hesperidin was found to be It was converted to ⁇ -glycosyl hesperidin.
  • the resulting enzyme reaction solution is heated to inactivate the remaining enzyme, filtered, and the filtrate is applied to a column packed with a porous synthetic adsorbent, trade name “Diaion HP-20” (sold by Mitsubishi Chemical Corporation). The solution was passed through SV2.
  • ⁇ -glycosyl hesperidin and unreacted hesperidin in the solution were adsorbed on the porous synthetic adsorbent, and D-glucose, salts and the like flowed out without being adsorbed.
  • purified water is passed through the column, the column is washed, and further passed while gradually increasing the concentration of the aqueous ethanol solution.
  • the fraction containing ⁇ -glycosyl hesperidin is collected, concentrated under reduced pressure, and powdered.
  • a pale yellow powdery ⁇ -glycosyl hesperidin-containing composition was obtained in a yield of about 71% based on the mass of raw material hesperidin per dry solid.
  • the powdered glycosyl hesperetin-containing composition obtained in this example contained 76.0% by mass of ⁇ -glycosyl hesperidin, 18.5% by mass of hesperidin, and 5.5% by mass of other components.
  • the furfural content of this product was 10 ppb, the 4-VA content was 3.0 ppb, the coloring degree was 0.17, and the electric conductivity was about 4 ⁇ S / cm. Further, this product contained about 0.3 ppm, about 0.04 ppm, about 0.1 ppm and about 0.05 ppm of calcium, potassium, magnesium and sodium, respectively, per dry solid.
  • this product is significantly reduced in taste and color and significantly reduced odor compared to the powdered glycosyl hesperetin-containing composition obtained in Example 1 produced without using a predetermined reducing agent.
  • this product even when heated for 30 minutes at a relatively high temperature of 90 to 100 ° C., it has excellent characteristics in which odor is effectively reduced as well as miscellaneous taste and coloring.
  • the oral beauty agent of this example is an oral beauty agent that has excellent storage stability and can be taken orally by a human on a daily basis safely and easily without discomfort, and has an action to improve yellowing and texture of skin, and It has excellent advantages that can effectively improve skin quality such as dry skin, erythema, irritation, and pruritus.
  • glucoamylase was added thereto.
  • Glucoteam manufactured by Nagase ChemteX Corporation
  • the resulting enzyme reaction solution was heated to inactivate the remaining enzyme.
  • hesperidinase trade name “Soluble Hesperidinase ⁇ Tanabe> No.
  • ⁇ -glucosyl hesperidin, 7-O- ⁇ -glucosyl hesperetin, and unreacted hesperidin in the solution were adsorbed to the porous synthetic adsorbent, and D-glucose, salts, and the like flowed out without being adsorbed.
  • purified water is passed through the column, the column is washed, and further passed while increasing the concentration of the aqueous ethanol solution stepwise.
  • the ⁇ -glucosyl hesperidin fraction is collected, concentrated under reduced pressure, powdered, and lightly added.
  • a yellow powdered glycosyl hesperetin-containing composition was obtained in a yield of about 70% based on the mass of raw material hesperidin per dry solid.
  • the powdered glycosyl hesperetin-containing composition obtained in this example is composed of 81.9% by weight of ⁇ -glucosyl hesperidin, 0.5% by weight of hesperidin, 8.9% by weight of 7-O- ⁇ -glucosyl hesperetin, and others. Of 8.7% by mass.
  • the furfural content of this product was 9 ppb, the 4-VA content was 2.0 ppb, the coloring degree was 0.16, and the electric conductivity was about 4 ⁇ S / cm.
  • the product contained about 0.3 ppm, about 0.03 ppm, about 0.05 ppm, and about 0.05 ppm of calcium, potassium, magnesium, and sodium, respectively, per dry solid.
  • this product Compared with the powdered glycosyl hesperetin-containing composition obtained in Example 1 produced without using a predetermined reducing agent, this product has significantly reduced miscellaneous taste and coloring and significantly reduced odor. In addition, even when heated for 30 minutes at a relatively high temperature of 90 to 100 ° C., it has excellent characteristics in which odor is effectively reduced as well as miscellaneous taste and coloring.
  • the oral beauty agent of this example is an oral beauty agent that has excellent storage stability and can be taken orally by a human on a daily basis safely and easily without discomfort, and has an action to improve yellowing and texture of skin, and It has excellent advantages that can effectively improve skin quality such as dry skin, erythema, irritation, and pruritus.
  • ⁇ Oral beauty agent 50 parts by mass of hesperidin and 1 part by mass of sodium hyposulfite were dissolved in 0.9 part by mass of a 0.25N aqueous sodium hydroxide solution at 80 ° C., 150 parts by mass of DE8 dextrin was added and dissolved, and the pH was adjusted to 9.0. After the adjustment, CGTase derived from Geobacillus stearothermophilus Tc-91 strain (Independent Administrative Institution, National Institute of Advanced Industrial Science and Technology, Patent Biological Depositary Accession No. FERM BP-11273) was added at 15 units per 1 part by mass of dextrin. The solution was adjusted to pH 8.3 while heating up to 0 ° C. and reacted for 6 hours.
  • glucoamylase (trade name “Glucoteam”, manufactured by Nagase ChemteX Corporation) was added, and the mixture was further reacted at 55 ° C. for 24 hours.
  • the resulting enzyme reaction solution is heated to inactivate the enzyme and applied to a column packed with a medium polarity porous adsorption resin (trade name “Amberlite XAD-7”, manufactured by Rohm & Haas).
  • the column was washed with water, and the resin adsorbing component was eluted with an 80 v / v% aqueous ethanol solution. After removing ethanol in the eluate, freeze-drying, ⁇ -glucosyl hesperidin 82.0 wt%, 7-O- ⁇ -glucosyl hesperetin 8.0 wt%, hesperidin 1.0 wt%, and other A powdery glycosyl hesperetin-containing composition containing 9.0% by weight of the component was obtained.
  • This product had a furfural content of 10 ppb, a 4-VA content of 1.5 ppb, a coloring degree of 0.15, and an electric conductivity of less than 10 ⁇ S / cm. Moreover, this product contained about 0.4 ppm, about 0.04 ppm, about 0.1 ppm and about 0.2 ppm of calcium, potassium, magnesium and sodium, respectively, per dry solid.
  • this product Compared with the powdered glycosyl hesperetin-containing composition obtained in Example 1 produced without using a predetermined reducing agent, this product has significantly reduced miscellaneous taste and coloring and significantly reduced odor. In addition, even when heated for 30 minutes at a relatively high temperature of 90 to 100 ° C., it has excellent characteristics in which odor is effectively reduced as well as miscellaneous taste and coloring.
  • the oral beauty agent of this example is an oral beauty agent that has excellent storage stability and can be taken orally by a human on a daily basis safely and easily without discomfort, and has an action to improve yellowing and texture of skin, and It has excellent advantages that can effectively improve skin quality such as dry skin, erythema, irritation, and pruritus.
  • This product had a furfural content of 180 ppb, a 4-VA content of 20.0 ppb, a coloring degree of 0.23, and an electric conductivity of less than 10 ⁇ S / cm. Moreover, this product contained about 0.5 ppm, about 0.08 ppm, about 0.1 ppm, and about 0.3 ppm of calcium, potassium, magnesium, and sodium, respectively, per dry solid.
  • this product is inferior to the powdered glycosyl hesperetin-containing composition obtained in Examples 2 to 5, the miscellaneous taste is significantly reduced and the coloring and odor are remarkable as compared with the non-reducing agent-treated product.
  • the taste and taste are significantly reduced as compared to the non-reducing agent-treated product. Also have excellent properties that are effectively reduced significantly.
  • oral beauty agent This product or beauty food containing this, health food, nutritional functional food, health functional food, or food for specified health use (collectively referred to as “oral beauty agent”), and the temperature Even when kept or stored for several tens of minutes to several months at a temperature below or below that range, excellent effects are exhibited in which odor is effectively reduced as well as miscellaneous taste and coloring derived from this product .
  • the oral beauty agent is an oral beauty agent that has excellent storage stability and can be taken orally by humans on a daily basis safely and easily without discomfort. Skin quality such as dryness, erythema, irritation, and pruritus can be effectively improved.
  • ⁇ Oral beauty agent> In the same manner as in Example 7 except that potassium metasulfite was replaced with sodium hydrogen sulfite, a light yellow powdered glycosyl hesperetin-containing composition was obtained at a yield of about 65% based on the mass of raw material hesperidin per dry solid. Got in.
  • the powdered glycosyl hesperetin-containing composition obtained in this example contained 77.2% ⁇ -glucosyl hesperidin, 16.5% hesperidin, and 6.3% other components.
  • This product had a furfural content of 191 ppb, a 4-VA content of 28.7 ppb, a coloration degree of 0.23, and an electrical conductivity of less than 10 ⁇ S / cm. Moreover, this product contained about 0.5 ppm, about 0.07 ppm, about 0.09 ppm, and about 0.4 ppm of calcium, potassium, magnesium, and sodium, respectively, per dry solid.
  • this product is inferior to the physical properties of the powdered glycosyl hesperetin-containing compositions obtained in Examples 2 to 6, this product has significantly reduced miscellaneous taste compared to the non-reducing agent-treated product.
  • coloring and odor are remarkably reduced, and after heating for 30 minutes at a relatively high temperature of 90 to 100 ° C., the miscellaneous taste is significantly reduced as compared with the non-reducing agent-treated product.
  • it has excellent characteristics that coloring and odor are also effectively reduced remarkably.
  • the product is processed into beauty foods, health foods, functional nutritional foods, functional health foods, or foods for specified health use (hereinafter collectively referred to as “oral beauty agents”) containing the product, and the temperature range. Even when kept or stored for several tens of minutes to several months at a temperature lower than that, excellent effects are exhibited in which the odor is effectively reduced as well as the miscellaneous taste and coloring derived from this product.
  • the oral beauty agent is an oral beauty agent that has excellent storage stability and can be taken orally by humans on a daily basis safely and easily without discomfort. Skin quality such as dryness, erythema, irritation, and pruritus can be effectively improved.
  • ⁇ Oral beauty agent 10 parts by mass of calcium acetate monohydrate, 50 parts by mass of L-magnesium lactate trihydrate, 57 parts by mass of maltose, 150 parts by mass of the powdered glycosyl hesperetin-containing composition obtained in Example 1, and ⁇ -containing 20% eicosapentaenoic acid 12 parts by mass of cyclodextrin inclusion compound is uniformly mixed and granulated by a granulating machine, and then encapsulated in a gelatin capsule according to a conventional method to contain 300 mg of contents per capsule.
  • this product is effective in improving the yellowness and texture of skin by daily daily oral intake of 1 to 10 capsules by humans, as well as dryness of the skin, erythema and irritation. And skin quality such as pruritus can be effectively improved.
  • ⁇ Oral beauty agent 10 parts by weight of any of the glycosyl hesperetin-containing compositions obtained in Examples 2 to 8, 0.003 parts by weight of sucralose, 2-glucoside ascorbic acid (trade name “ASCOFRESH” (registered trademark), sold by Hayashibara Co., Ltd.) 0.01 parts by mass and 20 parts by mass of dextrin were mixed with stirring, and 0.5 g each was housed in a stick-shaped light-shielding / moisture-proof packaging container to obtain 7 types of powdered oral cosmetics of the present invention.
  • This product is substantially free of miscellaneous taste, coloring and odor, and can be taken orally by humans easily and continuously on a daily basis without discomfort.
  • this product is added to various beverages such as water, tea, tea, coffee, and other foods and drinks, orally and continuously ingested by humans on a daily basis, It can improve dullness and texture, and can effectively improve skin quality such as dryness, erythema, irritation and pruritus.
  • This product is substantially free of miscellaneous taste, coloration, and off-flavor, and can be taken orally by humans easily and continuously on a daily basis.
  • This product is effective in improving skin yellowing and texture by daily oral ingestion of about 30 to 100 mL per day by humans, as well as skin dryness, erythema, irritation and itching. Can effectively improve the skin quality.
  • This product is substantially free from miscellaneous taste, coloring, and off-flavor, and can be used as it is or by adding about 1 to 5 mL to drinks such as green tea, tea, coffee, cocoa, and soft drinks.
  • drinks such as green tea, tea, coffee, cocoa, and soft drinks.
  • skin quality such as dryness of the skin, erythema, irritation and pruritus.
  • ⁇ Oral beauty agent> From 1 part by weight of the powdered glycosyl hesperetin-containing composition obtained in Example 1 produced without using a predetermined reducing agent, from sodium sulfite, sodium hyposulfite, potassium pyrosulfite, sodium pyrosulfite, and sulfur dioxide One or two or more selected reducing agents are added in a total amount of 0.0005 parts by mass, uniformly dissolved in 50 parts by mass of purified water, microfiltered, filled into sterile containers, and multiple types of liquid oral cosmetics. An agent was obtained.
  • This product is stable in storage, with no substantial taste / coloring or odor increase or change due to the product even after storage for several tens of minutes to several months in a room temperature or relatively high temperature environment. And excellent thermal stability.
  • This product is substantially free from miscellaneous taste, coloring, and off-flavor, and can be used as it is or by adding about 1 to 5 mL to drinks such as green tea, tea, coffee, cocoa, and soft drinks.
  • drinks such as green tea, tea, coffee, cocoa, and soft drinks.
  • skin quality such as dryness of the skin, erythema, irritation and pruritus.
  • glycosyl hesperetin used in the oral cosmetic preparation of the present invention in particular, when glycosyl hesperetin prepared using a predetermined reducing agent is used, it is less complex than glycosyl hesperetin prepared without using a predetermined reducing agent.
  • the symbol “ ⁇ ” represents the ⁇ -glucosyl hesperidin-containing composition administration group
  • the symbol “ ⁇ ” represents the control group
  • the symbols “#”, “##”, and “###” are the numerical values of the ⁇ -glucosyl hesperidin-containing composition administration group and the control group, respectively, and the corresponding ⁇ -glucosyl hesperidin.
  • P (risk rate) in the statistical hypothesis test is significantly different between the values of the containing composition administration group and the control group at p ⁇ 0.1, p ⁇ 0.05, and p ⁇ 0.01. Show.

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EP3135682A4 (en) * 2014-03-03 2017-08-16 Hayashibara Co., Ltd. Glucosyl hesperidin, method for manufacturing same, and application for same
JP2022058792A (ja) * 2016-05-16 2022-04-12 グローバル バイオライフ インコーポレーテッド 炎症関連疾患及び障害を治療するための求電子的に強化されたフェノール化合物

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EP3135682A4 (en) * 2014-03-03 2017-08-16 Hayashibara Co., Ltd. Glucosyl hesperidin, method for manufacturing same, and application for same
US10703773B2 (en) 2014-03-03 2020-07-07 Hayashibara Co. Ltd. Glycosyl hesperetin and process for producing the same and uses thereof
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JP7376624B2 (ja) 2016-05-16 2023-11-08 グローバル バイオライフ インコーポレーテッド 炎症関連疾患及び障害を治療するための求電子的に強化されたフェノール化合物

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