WO2011093290A1 - Agent anti-inflammatoire - Google Patents

Agent anti-inflammatoire Download PDF

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Publication number
WO2011093290A1
WO2011093290A1 PCT/JP2011/051384 JP2011051384W WO2011093290A1 WO 2011093290 A1 WO2011093290 A1 WO 2011093290A1 JP 2011051384 W JP2011051384 W JP 2011051384W WO 2011093290 A1 WO2011093290 A1 WO 2011093290A1
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Prior art keywords
inflammatory agent
inflammatory
solvent
green
light
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PCT/JP2011/051384
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English (en)
Japanese (ja)
Inventor
伸二郎 今井
啓子 田中
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株式会社日清製粉グループ本社
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Priority to JP2011551859A priority Critical patent/JP5602164B2/ja
Publication of WO2011093290A1 publication Critical patent/WO2011093290A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
    • A—HUMAN NECESSITIES
    • A21—BAKING; EDIBLE DOUGHS
    • A21D—TREATMENT, e.g. PRESERVATION, OF FLOUR OR DOUGH, e.g. BY ADDITION OF MATERIALS; BAKING; BAKERY PRODUCTS; PRESERVATION THEREOF
    • A21D2/00—Treatment of flour or dough by adding materials thereto before or during baking
    • A21D2/08—Treatment of flour or dough by adding materials thereto before or during baking by adding organic substances
    • A21D2/36—Vegetable material
    • A21D2/38—Seed germs; Germinated cereals; Extracts thereof
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23D—EDIBLE OILS OR FATS, e.g. MARGARINES, SHORTENINGS, COOKING OILS
    • A23D7/00—Edible oil or fat compositions containing an aqueous phase, e.g. margarines
    • A23D7/005—Edible oil or fat compositions containing an aqueous phase, e.g. margarines characterised by ingredients other than fatty acid triglycerides
    • A23D7/0053—Compositions other than spreads
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23G—COCOA; COCOA PRODUCTS, e.g. CHOCOLATE; SUBSTITUTES FOR COCOA OR COCOA PRODUCTS; CONFECTIONERY; CHEWING GUM; ICE-CREAM; PREPARATION THEREOF
    • A23G3/00—Sweetmeats; Confectionery; Marzipan; Coated or filled products
    • A23G3/34—Sweetmeats, confectionery or marzipan; Processes for the preparation thereof
    • A23G3/36—Sweetmeats, confectionery or marzipan; Processes for the preparation thereof characterised by the composition containing organic or inorganic compounds
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K10/00—Animal feeding-stuffs
    • A23K10/30—Animal feeding-stuffs from material of plant origin, e.g. roots, seeds or hay; from material of fungal origin, e.g. mushrooms
    • 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
    • A23L2/00—Non-alcoholic beverages; Dry compositions or concentrates therefor; Their preparation
    • A23L2/02—Non-alcoholic beverages; Dry compositions or concentrates therefor; Their preparation containing fruit or vegetable juices
    • 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
    • A23L23/00—Soups; Sauces; Preparation or treatment thereof
    • 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
    • A23L27/00—Spices; Flavouring agents or condiments; Artificial sweetening agents; Table salts; Dietetic salt substitutes; Preparation or treatment thereof
    • A23L27/60—Salad dressings; Mayonnaise; Ketchup
    • 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
    • A23L33/105—Plant extracts, their artificial duplicates or their derivatives
    • 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
    • A23L7/00—Cereal-derived products; Malt products; Preparation or treatment thereof
    • A23L7/10—Cereal-derived products
    • A23L7/196—Products in which the original granular shape is maintained, e.g. parboiled rice
    • A23L7/1965—Cooked; Precooked; Fried or pre-fried in a non-aqueous liquid frying medium, e.g. oil
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
    • A61K41/10—Inactivation or decontamination of a medicinal preparation prior to administration to an animal or a person
    • A61K41/17—Inactivation or decontamination of a medicinal preparation prior to administration to an animal or a person by ultraviolet [UV] or infrared [IR] light, X-rays or gamma rays
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Definitions

  • the present invention relates to an anti-inflammatory agent, food and drink containing the same, and a method for producing the anti-inflammatory agent.
  • Anti-inflammatory agents treat inflammatory diseases such as gastritis and ulcerative colitis, arthritis such as rheumatoid arthritis and degenerative osteoarthritis, and inflammatory symptoms such as hay fever, allergic rhinitis, allergic conjunctivitis and atopic dermatitis Useful for.
  • inflammatory diseases such as gastritis and ulcerative colitis, arthritis such as rheumatoid arthritis and degenerative osteoarthritis
  • inflammatory symptoms such as hay fever, allergic rhinitis, allergic conjunctivitis and atopic dermatitis Useful for.
  • steroidal anti-inflammatory agents, non-steroidal anti-inflammatory agents, immunosuppressive agents and the like have been known so far. However, since all have strong side effects, there is a problem that careful administration under the guidance and management of a doctor is required.
  • an anti-inflammatory agent that can be taken on a daily basis and that can effectively relieve inflammatory diseases and symptoms.
  • Patent Document 1 discloses an antiallergic composition that improves inflammatory symptoms in an atopic dermatitis model animal containing stachyose as an active ingredient, and describes that stachyose can be extracted from soybean seeds.
  • the amount of stachyose contained in soybean seeds is extremely small, and a sufficient amount cannot be obtained only by performing a normal extraction operation. Therefore, in order to concentrate to a concentration of 98% or more where the effect is recognized, it is necessary to perform a complicated purification step such as chromatography, and as a result, there is a problem that it is too costly.
  • stachyose is indigestible, and there is a problem that diarrhea and the like may occur when ingested at a high concentration.
  • the problem of the present invention is that it can be ingested safely, inexpensively and simply on a daily basis, has a remarkable inflammation-suppressing action, and is effective in preventing and / or improving various inflammatory diseases and inflammatory symptoms. Is to develop and provide natural materials.
  • IL-2 extremely strong interleukin 2
  • the present invention relates to the following matters.
  • An anti-inflammatory agent comprising a photoactivation treatment substance derived from a solvent extract of green soybean seeds.
  • the light irradiation treatment is a treatment of irradiating light so that a product of illuminance (kilolux: klx) and irradiation time (hr) is 40 klx ⁇ hr or more.
  • polar solvent is one or more selected from water, lower alcohol, chloroform or dimethyl sulfoxide.
  • Anti-inflammatory food, beverage, feed and cosmetic containing the anti-inflammatory agent according to any one of (1) to (7).
  • a method for producing an anti-inflammatory agent comprising: (a) a step of extracting a solvent extractant from green soybean seeds; and (b) a step of photoactivating the solvent extract.
  • Inflammatory agents can be provided.
  • the IL-2 production inhibitory effect by the anti-inflammatory agent derived from the solvent extract of various soybean seeds is shown.
  • the relationship between irradiation time and IL-2 production suppression effect is shown.
  • 3 is a graph showing the effect of anti-inflammatory agents on improving skin inflammation in mice. The actual improvement effect of the skin inflammation of the mouse
  • the first aspect of the present invention is an anti-inflammatory agent.
  • the anti-inflammatory agent of the present invention comprises a photoactive treatment substance derived from a solvent extractant of green soybean seed as an active ingredient.
  • the anti-inflammatory agent of the present invention will be specifically described.
  • anti-inflammatory agent refers to a substance having an anti-inflammatory action.
  • Anti-inflammatory means prevention, treatment, reduction or alleviation of various adverse effects caused by production of IL-2 (interleukin 2), which is a kind of cytokine. IL-2 is produced by T cells and NK cells (natural killer cells), and functions to proliferate and activate T cells, B cells, and NK cells, enhance antibody production in B cells, and enhance cytotoxic activity. It has been known.
  • Various adverse effects caused by the production of IL-2 means, for example, local or systemic inflammatory symptoms caused by inflammatory cells activated by IL-2 and various two effects induced by them. Refers to the following symptoms.
  • inflammatory diseases such as gastritis and ulcerative colitis, arthritis such as rheumatoid arthritis and degenerative osteoarthritis, and various allergic properties such as hay fever, allergic rhinitis, allergic conjunctivitis and atopic dermatitis Applicable to inflammatory diseases.
  • the allergic inflammatory disease here does not include a disease caused by an IgE-mediated type I allergic reaction, which is also called an immediate allergic reaction.
  • papules and pigmentation are included in one of “various adverse effects caused by IL-2 production”, but not pruritus.
  • green soybean is a general term for soybean (GlycineGmax) varieties in which seed seed coats and / or embryos in a fully ripe state exhibit a green color.
  • GlycineGmax soybean (GlycineGmax) varieties in which seed seed coats and / or embryos in a fully ripe state exhibit a green color.
  • green soybeans are varieties that have green seed coats and embryos, such as Akita Midori, green varieties that have seed coats that are green, such as kurakake, and green varieties that have green seeds, or large-sleeve shakes. Varieties in which only the seed coat exhibits a green color are known, but the green soybean of the present invention may be any variety as long as at least the embryo exhibits a green color. Preferably, the seed coat and embryo have a green color. In addition, even if it is green soybean, the color of “umbilical” varies depending on the variety, such as yellow, green, dark brown, and black, but is not particularly limited.
  • the “completely ripe state” refers to a state in which a seed is sufficiently matured to have a germination ability. Therefore, even if it is soybeans other than green soybeans, soybean seeds in an immature state generally referred to as green soybeans exhibit a green color, but varieties that exhibit a green color only in such an immature state are those of the present invention. Not applicable to green soybeans.
  • green refers to a color recognized by the human eye based on reflected light having a wavelength of 490 nm to 570 nm. Therefore, as long as it is within the wavelength range, the density is not limited, and includes, for example, light green, yellow green, green, and blue green.
  • the “seed” includes a seed coat and / or an embryo, and the embryo includes a cotyledon and a hypocotyl.
  • the “solvent extract of green soybean seed” refers to a solution (extract) after eluting the components contained in the seed of green soybean into the solvent, and a dried product (whether powder or solid). ), The redissolved solution of the dried product or a combination thereof.
  • the solvent is not particularly limited, but is preferably a polar solvent, and for example, water, lower alcohol, chloroform, dimethyl sulfoxide (DMSO) or a combination thereof is more preferable. Among these, water, ethanol or a combination thereof is particularly preferable because it is not harmful or extremely low even when administered to animals including humans.
  • the solvent extract of green soybean seed before the photoactive treatment contains a precursor of the photoactive treatment substance.
  • the “photoactivation treatment substance” is an active ingredient of the anti-inflammatory agent of the present invention and has an IL-2 production inhibitory effect.
  • the photoactivation treatment substance can be obtained by subjecting the green soybean seed solvent extract to light irradiation treatment, more specifically, a precursor of the photoactivation treatment substance contained in the extract. In order to obtain the precursor of the photoactive treatment substance, it is not always necessary to purify the solvent extract, and it may be a crude state in which other components are mixed.
  • photoactivation treatment refers to a treatment for converting a precursor of a photoactivation treatment substance into a photoactivation treatment substance by irradiating light to a solvent extract of green soybean seeds.
  • the “light” here includes not only visible rays but also invisible rays such as infrared rays and ultraviolet rays. Specifically, it refers to light having a wavelength of, for example, 200 nm to 800 nm, preferably 280 to 700 nm, more preferably 360 to 650 nm.
  • a specific treatment method is not particularly limited as long as the precursor of the photoactivation treatment substance can be irradiated with light.
  • the irradiation is performed so that the product of the illuminance (kilolux: klx) and the irradiation time (hr) for the solvent extract of green soybean seeds is 40 klx ⁇ hr or more.
  • the solvent extract of green soybean seeds is a dried product (including powders and solids) of the extract, it is preferably dissolved again in the solvent before the photoactivation treatment. It is because light can be sufficiently distributed throughout the solvent extract of green soybean seeds when irradiated with light in the liquid state.
  • the anti-inflammatory agent of the present invention may be constituted by a solvent extract of green soybean seed subjected to photoactivation treatment alone or in combination with one or more other substances having an anti-inflammatory action.
  • the dose or intake thereof may be such that the photoactivated substance is in the range of 0.01 to 100 g per day for an adult on a dry mass basis.
  • the photoactivated substance is in the range of 0.01 to 100 g per day for an adult on a dry mass basis.
  • 1 solvent extract is used.
  • 0.05 g to 500 g per day may be administered or ingested.
  • the typical daily intake of the photoactivated treatment substance is 0.1 to 50 g.
  • the treatment substance is highly safe derived from soybean seeds, its intake Can be further increased.
  • the daily intake may be taken once, but may be administered or taken in several divided doses.
  • the anti-inflammatory agent of the present invention can be used as a pharmaceutical composition.
  • the dosage form includes, for example, oral preparations such as tablets, capsules, granules, powders, syrups, dry syrups, liquids and suspensions, enterals such as inhalants and suppositories. Examples include preparations, ointments, creams, gels, external preparations for skin such as patches, drops, injections and the like. Of these, oral agents are preferable because they can be used easily.
  • Such dosage forms can be used for solvent extracts of green soybean seeds containing photoactivatable substances, such as conventional carriers such as excipients, disintegrants, binders, lubricants, surfactants, Molecules, sweeteners, flavoring agents, acidulants and the like can be blended according to the dosage form and can be produced according to conventional methods.
  • conventional carriers such as excipients, disintegrants, binders, lubricants, surfactants, Molecules, sweeteners, flavoring agents, acidulants and the like
  • the surface may be coated by a known method.
  • Liquid preparations such as liquids and suspensions may be dissolved or suspended in a suitable solvent such as water or ethanol.
  • the content of the photoactivation treatment substance in the solvent extract of green soybean seed in the pharmaceutical composition varies depending on the dosage form, but is usually 0.001 to 99% by mass, preferably 0.01 to 80% by mass based on the dry mass. It is desirable that the daily dose can be controlled so that the above-mentioned daily intake for adults can be taken.
  • the production amount of IL-2 can be suppressed by using it alone or together with other anti-inflammatory agents, so that inflammatory cells and immune cells can be suppressed. It becomes possible to reduce the function of the. Therefore, prevention and prevention of inflammatory diseases such as gastritis and ulcerative colitis, arthritis such as rheumatoid arthritis and degenerative osteoarthritis, hay fever, allergic rhinitis, allergic conjunctivitis and atopic dermatitis It is useful for improving, promoting health, or promoting nutritional tonic.
  • inflammatory diseases such as gastritis and ulcerative colitis, arthritis such as rheumatoid arthritis and degenerative osteoarthritis, hay fever, allergic rhinitis, allergic conjunctivitis and atopic dermatitis
  • the anti-inflammatory agent of the present invention also has an effect as an immunosuppressive agent because it has a potent IL-2 production inhibitory action, as shown in the Examples described later. Therefore, for example, it is also useful for preventing side effects during / after organ transplantation.
  • the anti-inflammatory agent of the present invention is made from green soybean seeds used as food, it is highly safe and has a good flavor. Daily continuous administration of the period is possible. Furthermore, long-term continuous intake is easy as various pharmaceutical, food and feed forms.
  • the active ingredient of the anti-inflammatory agent of the present invention can be produced by a simple operation of activating the solvent extract of green soybean seeds with light, and is highly economical because it is highly effective.
  • the second aspect of the present invention is an anti-inflammatory food and drink, feed and cosmetic.
  • the anti-inflammatory food, beverage, feed and cosmetic of the present invention are characterized by containing one or more anti-inflammatory agents of the first aspect.
  • each composition will be described.
  • the food and drink for anti-inflammatory and feed of the present invention are food and drink and feed containing the anti-inflammatory agent of the present invention as an active ingredient.
  • the form is not particularly limited, and other than the health food, functional food, food for specified health use, feed such as livestock, racehorse or appreciation animal, pet food, etc. All foods and drinks or feeds that can contain inflammatory agents are included. More specifically, these can be in various preparation forms such as liquid foods such as tablets, chewable tablets, powders, capsules, granules, drinks, and enteral nutrients.
  • a food and drink product in the form of a preparation can be produced by the same method as that for the pharmaceutical composition.
  • food and beverage products include green tea, oolong tea, tea and other tea drinks, soft drinks, jelly drinks, sports drinks, milk drinks, carbonated drinks, fruit juice drinks, lactic acid bacteria drinks, fermented milk drinks, powdered drinks, cocoa drinks, purified water, etc.
  • Beverages, butter, jam, sprinkles, margarine spreads, mayonnaise, shortening, custard cream, dressings, breads, cooked rice, noodles, pasta, miso soup, tofu, milk, yogurt, soup or sauces, confectionery (e.g. (Biscuits, cookies, chocolate, candy, cake, ice cream, chewing gum, tablets) and the like.
  • the feed of the present invention can be used in almost the same composition and form as the food and drink of the present invention, the description relating to the food and drink in this specification can be applied to the feed as well.
  • the food further includes other food materials used in the production of food, various nutrients, various vitamins, minerals, amino acids, various fats and oils, various additives (for example, taste ingredients, sweeteners, acidulants such as organic acids, interfaces, etc.
  • Activators, pH adjusters, stabilizers, antioxidants, dyes, flavors can be blended and manufactured according to conventional methods.
  • the foodstuff which concerns on this invention can also be manufactured by mix
  • the content of the photoactivation treatment substance derived from the solvent extract of green soybean seed in food varies depending on the form of the food, but is usually 0.001 to 80% by mass, preferably 0.01 to 50% by mass based on the dry mass. %, More preferably in the range of 1 to 50% by weight.
  • the daily intake may be taken once, but it may be taken in several divided doses. It is preferable to use a shape that allows the daily intake to be managed so that the daily intake per adult can be eaten and consumed.
  • the anti-inflammatory agent of the present invention can also be used as cosmetics.
  • the photoactivatable substance derived from the solvent extract of green soybean seeds may be used as it is as a cosmetic, or it may be formulated by a general-purpose method and used in emulsions, cosmetics, creams, lotions. , Essence, packs and sheets, foundation, funny, blusher, lipstick, eye shadow, eyeliner, mascara, facial cleanser, skin cleanser, gel, gel, skin cleanser, body shampoo, shampoo, rinse, etc.
  • Cosmetics include, in addition to the photo-activated treatment substance derived from the solvent extract of green soybean seeds, known excipients and fragrances depending on the desired dosage form, fats and oils, surfactants, preservatives, metals Conventional methods including sequestering agents, water-soluble polymers, thickeners, pigments and other powder components, UV protection agents, humectants, antioxidants, pH regulators, detergents, desiccants, emulsifiers, etc. Can be manufactured according to.
  • the content of the photoactivation treatment substance derived from the solvent extract of green soybean seed in the cosmetic is not particularly limited, but is usually in the range of 0.001 to 80% by mass, preferably 0.01 to 50% by mass based on the dry mass. Is within.
  • foods, feeds and cosmetics containing the anti-inflammatory agent of the present invention include, for example, conjugated linoleic acid, taurine, glutathione, carnitine, creatine, coenzyme Q, glucuronic acid, glucuronolactone, pepper extract, Ginger extract, cacao extract, guarana extract, garcinia extract, theanine, ⁇ -aminobutyric acid, capsaicin, capsiate, various organic acids, flavonoids, polyphenols, catechins, xanthine derivatives, resistant oligosaccharides such as fructo-oligosaccharides, polyvinyl Pyrrolidone or the like may be blended.
  • the amount of these additives is appropriately determined according to the form of the composition, the type of additive, and the amount of intake to be desired, but is 0.01 to 70% by mass in the agent, food, feed and cosmetics of the present invention. Within the range, preferably within the range of 0.1 to 50% by mass.
  • the food, feed or cosmetic of the present invention contains the anti-inflammatory agent of the present invention of the above aspect as an active ingredient, the same effects as the anti-inflammatory agent can be obtained when applied continuously. That is, the production amount of IL-2 can be suppressed, and the functions of inflammatory cells and immune cells can be reduced. Therefore, prevention and prevention of inflammatory diseases such as gastritis and ulcerative colitis, arthritis such as rheumatoid arthritis and degenerative osteoarthritis, hay fever, allergic rhinitis, allergic conjunctivitis and atopic dermatitis It is useful for improving, promoting health, or promoting nutritional tonic.
  • inflammatory diseases such as gastritis and ulcerative colitis, arthritis such as rheumatoid arthritis and degenerative osteoarthritis, hay fever, allergic rhinitis, allergic conjunctivitis and atopic dermatitis
  • the anti-inflammatory agent of the present invention is also useful as an immunosuppressant, and is useful, for example, for preventing side effects during / after organ transplantation.
  • the agent of the present invention is made from green soybean seeds used as food, it is highly safe and has a good flavor, so it can be taken orally as it is or applied as a cosmetic. It is possible, and it can be easily taken for a long time as a form of food or feed.
  • a third aspect of the present invention is a method for producing an anti-inflammatory agent.
  • the manufacturing method of the present invention includes (1) an extraction process, and (2) a photoactivation process process. Hereinafter, each step will be described in detail.
  • Extraction process is a process of extracting a solvent extract from green soybean seeds.
  • One or more varieties can be used for green soybean seeds.
  • seeds other than green soybeans for example, yellow soybeans and black soybeans
  • the state of green soybean seed used in this process is not particularly limited. For example, immature one (so-called green soybean state), mature one (including dried and undried state), germinated one (including after rooting and before cotyledon opening) or a combination thereof Can be used. Moreover, you may use only an embryo other than all the seeds. The use of all seeds is preferred. Further, the shape of the green soybean seed used in this step is not limited to the state of the seed taken out from the cocoon or a fragment of the seed, but is preferably crushed, squeezed and extracted juice or those It is a combination. This is because more of the precursor of the photoactivation treatment substance contained in the green soybean seed is subjected to the photoactivation treatment.
  • the solvent that can be used in this step is not particularly limited, but water or an organic solvent is preferable.
  • water include pure water, distilled water, tap water, acid water, alkaline water, and neutral water.
  • organic solvents include alcohols that are liquid at room temperature, such as lower alcohols such as methanol, ethanol, n-propanol, isopropanol, and n-butanol, and polyhydric alcohols such as 1,3-butylene glycol, propylene glycol, and glycerin.
  • Ethers such as diethyl ether and propyl ether; esters such as butyl acetate and ethyl acetate; polar organic solvents such as chloroform and DMSO are preferred.
  • the said solvent may be used independently and may be used in combination of 2 or more type.
  • the water-containing organic solvent mentioned later is mentioned.
  • the content of the aqueous component in the water-containing organic solvent is usually 80% by volume or less, preferably 65% by volume or less, more preferably 50% by volume or less.
  • green soybean seeds and solvent are placed in the extraction tank.
  • Green soybean seeds may be put in a tank containing a solvent, or a solvent may be added to a tank containing green soybean seeds. Or you may put them in an extraction tank simultaneously. Alternatively, either one or both of the green soybean seed and the solvent can be put in the extraction tank first, and the rest can be added during the present step.
  • the extraction method is not particularly limited, and examples thereof include a known method such as a method in which green soybean seeds are immersed in an extraction solvent, stirred or refluxed, or a supercritical fluid extraction method.
  • green soybean seeds are added to a solvent at room temperature or warmed under reduced pressure, normal pressure or increased pressure, and extracted with immersion or stirring, and extracted with reflux in the solvent. Etc.
  • the extraction temperature is from 5 ° C. to the boiling point of the solvent or less.
  • the extraction time is appropriately about 30 minutes to 72 hours, although it varies depending on the type of solvent used, extraction conditions, and the content of aqueous components in the case of a water-containing organic solvent.
  • the extraction operation can also be performed by a supercritical fluid extraction method using carbon dioxide or the like.
  • the mixture containing the extract and the residue is subjected to filtration or centrifugation as necessary to obtain an extract from which the solid component as a residue has been removed.
  • the removed solid component can be subjected to an extraction operation again using the same type of solvent or a different type of solvent, and this operation may be repeated several times.
  • the extract thus obtained can be used as it is as a solvent extract of green soybean seeds for the photoactivation treatment step described later. Furthermore, if necessary, it can be dried and powdered by a method such as freeze drying or spray drying.
  • the dried and pulverized solvent extract is convenient in terms of storage or transportation when time is required before being subjected to the photoactivation process or when the photoactivation process is performed at a different location from the extraction process.
  • any specific drying method may be used as long as the solvent extract of green soybean seeds is not denatured or thermally decomposed. Examples of such methods include filtration, centrifugation, centrifugal filtration, spray drying, spray cool, drum drying, vacuum drying, freeze drying, and the like, and these methods can be used alone or in combination.
  • Photoactivation treatment step This step is a step of subjecting the green soybean seed solvent extract obtained in the extraction step to a photoactivation treatment.
  • the solvent extract of green soybean seeds in this step is the same as that of the extract of the soybean soybean seeds, in a state where the extract is dried and solidified or pulverized, or after being once powdered or solid. It can be provided in a liquid state redissolved, resuspended or redispersed in a solvent. Preferably, it is provided in any of the above liquid states. This is because, in the liquid state, it can be arranged so that the precursor of the photoactivation processing substance contained in the extract is uniformly exposed to light. If the solvent extract of green soybean seed once powdered or solidified is made into a liquid state again, the solvent extract can be used if the volume of the solvent used for redissolution is less than the volume of the extract after the extraction step. This is convenient because the amount of the precursor of the photoactivation treatment substance in the composition can be concentrated.
  • the light source used for the photoactivation treatment is not particularly limited as long as it can emit light having a wavelength of 200 to 800 nm, preferably 280 to 700 nm, more preferably 360 to 650 nm.
  • fluorescent lamps including black lights
  • mercury lamps including HID lamps
  • LEDs light emitting diodes
  • incandescent bulbs and combinations thereof can be used. Since the strength of the anti-inflammatory action obtained by the present invention varies depending on the illuminance and irradiation time of the photoactivation treatment, it is preferable to adjust the illuminance and irradiation time of the irradiated light.
  • the adjusting means include a method in which a product obtained by multiplying the illuminance and the irradiation time with respect to the solvent extract of green soybean seeds becomes a certain value or more.
  • the product of illuminance (klx) and irradiation time (hr) is adjusted to be 40 klx ⁇ hr or more, preferably 80 klx ⁇ hr or more, more preferably 150 klx ⁇ hr or more.
  • an anti-inflammatory agent having a high anti-inflammatory effect can be produced easily and relatively inexpensively from green soybean seeds.
  • Example 1 Preparation of solvent extract in various soybean seeds and production of anti-inflammatory agent of the present invention> (1) Manufacture of anti-inflammatory agent derived from ethanol extract of various soybean seeds First, 1.4 g of pulverized soybean seeds shown in Table 1 were degreased. In order to prepare a solvent extract, 5 times the amount of ethanol was added, and the mixture was extracted by shaking at room temperature for 2 hours, and then filtered to remove insolubles, and the ethanol extract was recovered. Ethanol was distilled off to obtain about 20 to 40 mg of solvent extract from each soybean seed.
  • soybean seed solvent extract containing the photoactivation treatment substance those derived from green soybean seeds were used as anti-inflammatory agent test sample 1, and other soybean (black soybean, yellow soybean, other colored soybeans) seeds The derived one was used as Comparative Sample 1 in Example 2 below.
  • Example 2 Verification of IL-2 production inhibitory action by anti-inflammatory agent of the present invention in vitro (1)> Jurkat cells used a working stock that had been stored frozen. This stock cell was used within the range where the passage number did not exceed 10. As a medium, RPMI1640 was used as a basal medium, and 10% of fetal bovine serum inactivated by heating at 56 ° C. for 30 minutes was added thereto. Cultivation was performed in a carbon dioxide incubator under 100% wet conditions at a carbon dioxide gas concentration of 37%. For the test, a culture in a semi-confluent state was used.
  • DuoSet ELISA Development System human IL-2 (R & D Systems) was used for ELISA.
  • an unstimulated example an example in which neither PMA, A23187, nor a test sample was added was set, and an example in which only a test sample was not added was set as a stimulated example.
  • the anti-inflammatory agent derived from the solvent extract of green soybean seeds has a stronger IL-2 production inhibitory effect on Jurkat cells than the solvent extracts of other soybean seeds. Became clear.
  • Example 3 Verification of IL-2 production inhibitory action by anti-inflammatory agent of the present invention (2)>
  • the photoactivation treatment was performed on the test sample 2 prepared in (2) of Example 1 while changing the light irradiation conditions.
  • Five plates were prepared by dispensing 100 ⁇ L of DMSO sample solution into each well of a 24-well culture plate (BD Falcon). Each plate was placed at a certain distance (Table 2) from the fluorescent lamp stand, and was allowed to stand for 36 hours and irradiated with light. Table 2 shows the relationship between distance and illuminance.
  • Illuminance was measured by placing an illuminometer (illuminance data logger: PHR-51, T & T) at the plate installation position. Samples were taken out from some wells of each plate after 3, 6, 12, 24, and 36 hours during the photoactivation treatment, and IL-2 production inhibitory action was measured in the same manner as in Example 2.
  • the vertical axis of the figure shows the relative value (%) when the IL-2 production rate in the sample in the non-photoactivated state is defined as 100.
  • the IL-2 production inhibitory effect after 24 and 36 hours could not be measured, and in the sample at a distance of 57 cm, the IL-2 production inhibitory effect after 3 hours could not be measured.
  • Example 4 Evaluation of anti-inflammatory agent of the present invention using inflammation model animal> The effect of the anti-inflammatory agent of the present invention on dermatitis caused by repeated application of antigen to NC / Nga mice, which are atopic dermatitis models, was examined.
  • mice (NC / Nga, rabbit, 6 weeks old; manufactured by Japan SLC) were used after acclimation.
  • AIN-76 refined feed was raised and grouped into 3 groups (control group, water extraction group and ethanol extraction group) shown in Table 3 for every 8 animals, and each test feed shown in the same table was fed after grouping.
  • the antigen solution Biosta AD (containing a protein derived from Dermatophagoides farinae; manufactured by Biosta Co., Ltd.) was used, and the application of the antigen solution was started from the start date of feeding the test feed, and then applied every 7 days.
  • the anti-inflammatory agent of the present invention was administered in a mixed diet. After 4, 5, and 6 weeks from the start of application (after application of 5, 6, and 7 times, respectively), the skin inflammation symptoms of each animal were scored according to Table 4.
  • FIG. 3 The score result is shown in FIG. 3, and a rear view (shaved) 6 weeks after the start of application in the mice of the subject group, (hot) water extraction group and ethanol extraction group used in this example is shown in FIG.
  • the back surface is inflamed extensively (arrow in the figure).
  • such inflammation is not observed in the water extraction group and the ethanol extraction group. From this result, it was clarified that the water extraction group and the ethanol extraction group in which the anti-inflammatory agent of the present invention was mixed with food can significantly suppress the onset of skin inflammation as compared with the control group.
  • Example 5 Production of tablets> 85 g of the anti-inflammatory agent obtained in the same manner as in Example 1 (3), 10 g of crystalline cellulose (Asahi Kasei) and 4 g of polyvinyl pyrrolidone (BASF) are mixed, and 30 mL of ethanol is added thereto, followed by a wet method. Granules were produced according to After the granules were dried, 1.2 g of magnesium stearate was added to obtain granules for tableting, and tableting was performed using a tableting machine to produce 100 tablets each having 1 g.
  • crystalline cellulose Asahi Kasei
  • BASF polyvinyl pyrrolidone
  • Example 6 Production of granules> 100 g of the anti-inflammatory agent obtained in the same manner as in Example 1 (3), 100 g of lactose (DMV) and 40 g of crystalline cellulose (Asahi Kasei) were mixed, and 130 mL of ethanol was added to the kneader, and the usual method Kneaded for 5 minutes. After kneading, the mixture was sieved with 10 mesh and dried at 50 ° C. in a dryer. After drying, the size was adjusted to obtain 240 g of a granule.
  • Example 7 Production of syrup> Boil 400 g of purified water, stir it, add 750 g of white sugar and 100 g of the treated substance obtained in the same manner as in Example 1 (4), dissolve, wipe with heat, and add purified water to this. In addition, a syrup was prepared with a total volume of 1000 mL.
  • Example 8 Production of liquid food> To 700 g of pure water at about 65 ° C., 40 g of sodium caseinate (DMV), 160 g of maltodextrin (Sanwa starch) and 50 g of the anti-inflammatory agent obtained in the same manner as in Example 1 (4) were added and dissolved. Vitamin mix and each component mixture of trace minerals were added. The obtained mixed solution was put into a homomixer and roughly emulsified at about 8,000 rpm for 15 minutes. The obtained emulsion is cooled to about 20 ° C., and after adding a fragrance, the final mess up is performed. Sterilization was performed to obtain a liquid food.
  • DMV sodium caseinate
  • 160 g of maltodextrin Sanwa starch
  • 50 g of the anti-inflammatory agent obtained in the same manner as in Example 1 (4) were added and dissolved. Vitamin mix and each component mixture of trace minerals were added. The obtained mixed solution was put into a homomixer and roughly emulsified at about 8,000 rpm
  • Example 9 Production of bread> 160g of flour (strong flour) and 2g of dry yeast were mixed. Separately, 5 g of the anti-inflammatory agent obtained in the same manner as in Example 1 (3), 25 g of sugar, 3 g of salt, and 6 g of skim milk powder were dissolved in 70 g of hot water, and 1 egg was added and mixed well. Add this to the above mixture of flour and dry yeast, knead well by hand, add about 40 g of butter and knead well to make 20 roll bread dough, then ferment these bread dough, Egg rolls were applied and baked in an oven at 180 ° C. for about 15 minutes to prepare a roll.
  • Example 10 Production of confectionery> Margarine and sugar were mixed and stirred well using a mixer to prepare whipped. Half of this was added to make a cream. An anti-inflammatory agent obtained in the same manner as in Example 1 (3) was added thereto, and lightly mixed to prepare a dough. The dough was shaped and baked in an oven at 150 ° C. for 25 minutes to make a confectionery.
  • Example 11 Production of confectionery> The whole egg was loosened with a whisk, and 90g sugar sweetener was added and mixed well. To this, 10 g of an anti-inflammatory agent obtained in the same manner as in Example 1 (4), 40 g of wheat flour and baking powder were added, mixed with stirring, butter and rum were further added and mixed well to prepare a dough. The dough was put into a mold and baked in an oven at 170 ° C. for 15 minutes to prepare a confectionery.
  • Example 12 Production of retort rice> 2.5 g of anti-inflammatory agent obtained in the same manner as in Example 1 (4) was added to a general amount of water using 2 rice and cooked, and this was filled in a retort pack according to a conventional method. Then, it sealed, performing nitrogen substitution, and sterilized for 15 minutes at 121 degreeC, and obtained the retort rice.
  • Example 13 Production of sauce for pasta> One serving (150 g) of meat sauce for pasta was put in a pan, and 1 g of the anti-inflammatory agent obtained in the same manner as in Example 1 (3) was added thereto and heated and mixed. After filling this pouch with a pouch, the pouch was sealed with nitrogen substitution and sterilized at 121 ° C. for 15 minutes to obtain a meat sauce for pasta.
  • Example 14 Production of vegetable juice> An anti-inflammatory agent obtained in the same manner as in Example 1 (3) was added to and mixed with a commercially available vegetable juice so as to be 5% by mass to prepare a vegetable juice.
  • Example 15 Production of consomme soup> Put each slice of onion 100g, carrot 100g, long onion 100g, celery 50g, and tomato 100g into a pan, add 500g minced beef meat, 2 egg whites, 1kg beef bouillon, cook on fire when boiling Weakly, boil for 1 hour on low heat while removing ax and fat floating on the surface, add 50 g of anti-inflammatory agent obtained in the same manner as in Example 1 (3), boil for another 30 minutes, and rub with cloth Got a consomme soup.
  • Example 16 Production of ointment> A liquid.
  • Polyoxyethylene hydrogenated castor oil 60 2% by mass ⁇
  • Polyethylene glycol monostearate 1% by mass ⁇ Butyl paraoxybenzoate: 0.1% by mass C liquid.
  • -Purified water Appropriate amount up to 100% by mass Mix B solution while heating and dissolving at 70 ° C to make oil phase. Liquid A was mixed while being heated and dissolved at 70 ° C., and the oil phase of liquid B was added to the mixture for emulsification, followed by cooling while adding liquid C and mixing well to obtain an ointment.

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Abstract

Une matière naturelle est développée, laquelle peut continuer à être couramment consommée d'une façon sûre, à bon marché et pratique, qui a un effet prononcé de suppression de l'inflammation, et qui est efficace dans la prévention et/ou l'amélioration de diverses maladies inflammatoires et de divers états inflammatoires. Il a été découvert qu'une matière activée par la lumière, issue d'un extrait par solvant de graines de soja sauvage possède un effet suppresseur de la production d'interleukine-2 qui est extrêmement puissant. Sur la base desdites découvertes, l'invention propose un agent anti-inflammatoire comprenant ladite matière activée par la lumière.
PCT/JP2011/051384 2010-01-26 2011-01-26 Agent anti-inflammatoire WO2011093290A1 (fr)

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Citations (4)

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JP2004535458A (ja) * 2001-07-02 2004-11-25 ピュアセル・テクノロジーズ・インコーポレーテッド 炎症過程の調節に有用なチラコイドを含む組成物
JP2005002112A (ja) * 2003-06-05 2005-01-06 L'oreal Sa 皮膚の内在性カロテノイドの分解を阻止するための青色光遮蔽剤の使用；新規なアミノアリールビニル−ｓ−トリアジン化合物及びその用途
JP2007320902A (ja) * 2006-05-31 2007-12-13 Utsunomiya Univ クロロフィル・ナノ粒子及びの製造方法
JP2010053125A (ja) * 2008-07-28 2010-03-11 Nisshin Pharma Inc 抗アレルギー剤

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JP2004535458A (ja) * 2001-07-02 2004-11-25 ピュアセル・テクノロジーズ・インコーポレーテッド 炎症過程の調節に有用なチラコイドを含む組成物
JP2005002112A (ja) * 2003-06-05 2005-01-06 L'oreal Sa 皮膚の内在性カロテノイドの分解を阻止するための青色光遮蔽剤の使用；新規なアミノアリールビニル−ｓ−トリアジン化合物及びその用途
JP2007320902A (ja) * 2006-05-31 2007-12-13 Utsunomiya Univ クロロフィル・ナノ粒子及びの製造方法
JP2010053125A (ja) * 2008-07-28 2010-03-11 Nisshin Pharma Inc 抗アレルギー剤

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