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WO2003091237A1 - Procede de production de materiau riche en proanthocyanidine - Google Patents

Procede de production de materiau riche en proanthocyanidine Download PDF

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Publication number
WO2003091237A1
WO2003091237A1 PCT/JP2003/002001 JP0302001W WO03091237A1 WO 2003091237 A1 WO2003091237 A1 WO 2003091237A1 JP 0302001 W JP0302001 W JP 0302001W WO 03091237 A1 WO03091237 A1 WO 03091237A1
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WIPO (PCT)
Prior art keywords
proanthocyanidin
extract
opc
weight
extraction
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PCT/JP2003/002001
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English (en)
Japanese (ja)
Inventor
Isao Kouno
Takashi Tanaka
Gen-Ichiro Nonaka
Kinya Takagaki
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Toyo Shinyaku Co., Ltd.
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Filing date
Publication date
Application filed by Toyo Shinyaku Co., Ltd. filed Critical Toyo Shinyaku Co., Ltd.
Priority to AU2003211279A priority Critical patent/AU2003211279A1/en
Priority to JP2003587797A priority patent/JPWO2003091237A1/ja
Publication of WO2003091237A1 publication Critical patent/WO2003091237A1/fr

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
    • C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
    • C07D311/58—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4
    • C07D311/60—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4 with aryl radicals attached in position 2
    • C07D311/62—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4 with aryl radicals attached in position 2 with oxygen atoms directly attached in position 3, e.g. anthocyanidins
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline 
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/12—Antihypertensives

Definitions

  • the present invention relates to a method for efficiently producing a proanthocyanidin-containing substance containing a large amount of OPC having high physiological activity.
  • Proanthocyanidins are polymerized or condensed tannins present in various plants. They are formed by condensation or polymerization of flavan-1-ol or flavan-1,4-diol as a structural unit (hereinafter referred to as condensation polymerization). , Are the combined compounds. These are given their names because they produce anthocyanidins such as cyanidin, delphinidin, and pelargonidin by acid treatment.
  • proanthocyanidins having a low polymerization degree are suitably used.
  • a polycondensate having a degree of polymerization of 2 to 30 (2 to 30 mer) is preferable, a polycondensate having a degree of polymerization of 2 to 10 (2 to 10 mer) is more preferable, and a degree of polymerization of 2 to 30 is preferred.
  • Condensed polymers of (4) to (4 to 4) are more preferably used.
  • the condensed polymers of proanthocyanidins having a degree of polymerization of 2 to 4 and containing flavan-13-ol-Z or flavan-3,4-diol as a structural unit are referred to as OPCs.
  • OPCs organic e.g.
  • Proanthocyanidins a type of polyphenol, are potent antioxidants produced by plants and are concentrated in plant leaves, bark, fruit bark or seed parts.
  • Proanthocyanidins, especially OPC are specifically It is found in dough seeds, pine bark, peanut skin, ginkgo biloba, false acacia fruit, and lingonberry fruit. It is also known that cola nuts in West Africa, the roots of ratania in Peru, and green tea in Japan also contain OPC. OPC is a substance that cannot be produced in the human body.
  • OPC has the power of antioxidant action, the effect of suppressing bacterial growth in the oral cavity and reducing plaque (gum); the effect of restoring the elasticity of blood vessels; Prevents damage, prevents damaged fat from aggregating on the inner wall of blood vessels, and adhering cholesterol; regenerating vitamin E decomposed by active oxygen; as an enhancer of vitamin E It is known to have the effect of
  • tannin which is a polymer of flavan-3-ol and / or flavan-1,4-diol, and chitin, chitosan, and derivatives thereof are useful for staphylococcus aureus, salmonella, typhoid, cholera, and the like. Its antibacterial and bactericidal effects are remarkable. In particular, it has been reported that MRSA (methicillin-resistant staphylococci), which has been talked about because most antibiotics do not work, is also effective.
  • MRSA methicillin-resistant staphylococci
  • Proanthocyanidins are generally obtained by extraction from plants.
  • the solvent used for the extraction include water; organic solvents such as methanol, ethanol, acetone, hexane, and ethyl acetate; and mixtures thereof (Japanese Patent Application Laid-Open No. 11-801488).
  • simply extracting with a solvent results in low recovery and low purity of oral anthocyanidins. Therefore, in order to use it as a raw material for health foods, cosmetics, and pharmaceuticals, further concentration and purification processes are required to increase the purity, which requires a long time.
  • Japanese Patent Application Laid-open No. Hei 5-279694 and Japanese Patent Application Laid-Open No. Hei 6-56689 describe a method for recovering polyphenols containing proanthocyanidins.
  • polyphenols are adsorbed to chitin, and polyphenols are The chitin with adsorbed phenols is used as a polyphenol product.
  • the adsorbed polyphenols are polyphenols having a high degree of polymerization, and the content of the above-mentioned highly active dimer to tetramer OPC is extremely low, so that the physiological activity such as antioxidant action is low. Low.
  • the present inventors diligently studied a method for efficiently obtaining a proanthocyanidin-containing substance having a useful OPC content and having a useful physiological activity.
  • proanthocyanidins are extracted from the plant, and the resulting extract is brought into contact with a predetermined amount of chitin, chitosan, or a derivative thereof, and non-adsorbed substances are recovered, thereby achieving high bioactivity.
  • a proanthocyanidin-containing substance rich in OPC can be obtained efficiently.
  • the present inventors have found that a proanthocyanidin-containing material having a higher OPC content can be obtained by further treating the proanthocyanidin-containing material with a synthetic resin-based adsorbent, thereby completing the present invention.
  • the present invention provides a method for producing a proanthocyanidin-containing substance, the method comprising: (a) a step of extracting or squeezing from a plant by extraction or squeezing; and (b) the extract or squeezed juice.
  • the polyphenol content of the extract or juice And contacting it with 2 to 10 times the dry weight of chitin, chitosan, or a derivative thereof to recover non-adsorbed substances.
  • the extraction is a hot water extraction.
  • the method further includes the step of (c) contacting the non-adsorbed substance obtained in the step (b) with the synthetic resin-based adsorbent.
  • the present invention also provides a proanthocyanidin-containing substance containing an oligomeric proanthocyanidin and a catechin, wherein the proanthocyanidin-containing substance is contained in the proanthocyanidin-containing substance in terms of dry weight in terms of oligomeric proanthocyanin. It contains 30% by weight or more of nisin and 5 to 15% by weight of techin.
  • the plant used in the present invention is a plant containing proanthocyanidin, and its type is not particularly limited.
  • Bark of cedar, cypress, pine, etc. which contains a large amount of proanthocyanin; grape, blueberry, strawberry, apogado, fruit of Nisekasia, lingonberry, elderberry, peel or seed; barley; wheat; soybean; black soybean; cacao; red bean Conker shell; peanut shell; ginkgo biloba; tea leaves and tea extract; sorghum cane; apple fruit; kumazasa; fucoidan; yacon leaves; cola nuts (eg, West African cola nuts); ratania (eg, Peru) Ratania) root; and the like.
  • pine bark, grape seeds and pericarp, peanut thin skin, and the like are particularly preferably used.
  • proanthocyanidins are extracted from the plant, or juice is obtained from the plant.
  • the plant is preferably crushed to an appropriate size from the viewpoint of extraction efficiency to increase the surface area per volume.
  • the method of crushing is not particularly limited. For example, crushed material processed by cutter, slicer, etc .; mixer 1. A crushed product treated with a juicer, blender, or masco mouth whatsoever may be used.
  • the size of the crushed or crushed material is 0.1 to 0.1 cm, preferably 0.1 to 5 cm.
  • water or an organic solvent such as ethanol, methanol or ethyl acetate may be added at the time of crushing.
  • Water or an organic solvent is used as the extraction solvent.
  • the organic solvent include methanol, ethanol, 1-propanol, 2_propanol ⁇ ⁇ , 1-butanol, 2-butanol, acetone, hexane, cyclohexane, propylene glycolone, hydrous ethanolanol, hydrous propylene glycol, and ethynolemethinole.
  • a mixed solvent of water and an organic solvent is also preferably used. These organic solvents may be used alone or in combination. From the viewpoint of waste liquid treatment during production, water is preferably used.
  • the amount of the extraction solvent to be added to the plant can be set in consideration of the target proanthocyanidin concentration and the extraction efficiency.
  • the weight ratio of plant: water is 1: 5 to 1:50, preferably 1:10 to 1:20.
  • the amount of extraction solvent to be added may be adjusted in consideration of the amount used for crushing.
  • extraction is performed with hot water at 50 to 120 ° C, preferably 70 to 100 ° C. Hot water may be added to the plant, or water may be added to the plant and then heated.
  • the extraction time is generally 10 minutes to 24 hours, but can be appropriately determined depending on the extraction temperature.
  • an extraction method using an organic solvent extraction by warming or supercritical fluid extraction may be performed.
  • a method of adding a heated solvent to the body or a method of adding a solvent to the plant and heating is used.
  • a water-ethanol mixed solvent with a weight ratio of water to ethanol of 1: 1 is used as an extraction solvent in a 5-fold amount with respect to the crushed plant, and the mixture is refluxed at 70 to 75 ° C. While stirring for 3 hours.
  • the extraction temperature must be set to a value equal to or lower than the boiling point of the organic solvent.
  • the supercritical fluid extraction method is a method of extracting a target component using a supercritical fluid, which is a fluid that has exceeded the critical point (critical temperature, critical pressure) of the gas-liquid of a substance.
  • a supercritical fluid a fluid that has exceeded the critical point (critical temperature, critical pressure) of the gas-liquid of a substance.
  • the supercritical fluid carbon dioxide, ethylene, propane, nitrous oxide (laugh gas) and the like are used, and carbon dioxide is preferably used.
  • the supercritical fluid extraction method includes an extraction step of extracting a target component with a supercritical fluid and a separation step of separating the target component from a supercritical fluid. In the separation process, either extraction separation by pressure change, extraction separation by temperature change, or extraction separation using adsorbent / absorbent may be performed.
  • supercritical fluid extraction by an entrainer addition method may be performed.
  • ethanol, propanol, n-hexane, acetone, toluene, other aliphatic lower alcohols, aliphatic hydrocarbons, aromatic hydrocarbons, or ketones are added to a supercritical fluid.
  • the solubility of the target extract, such as OPCs and catechins (described below) in the extraction fluid is dramatically improved. It increases or increases the selectivity of the separation and allows for efficient extraction of proanthocyanidins.
  • any of a batch type, a semi-continuous type, and a continuous type may be used.
  • juice When juice is obtained from a plant, the plant is directly squeezed or, after being appropriately cut or crushed, squeezed.
  • This method uses plants with a high moisture content. It is suitably adopted when For example, in the case of grape berries, squeezing produces squeezed juice containing pulp anthocyanidins.
  • a crushed plant containing solids derived from the plant obtained by crushing the plant eg, the crushed grape fruit
  • the crushed plant containing the solid content of is also included in the juice.
  • extract the obtained extract or squeezed juice (hereinafter referred to as extract, etc.) and a predetermined amount of chitin, chitosan, or a derivative thereof (hereinafter, chitin, chitosan, and at least one of these derivatives) (Referred to as chitins).
  • this step is referred to as a contact step.
  • the chitin used in the contacting step may be in the form of a powder, or may be in the form of a fiber, fibril, film, porous body, microbead, or the like. Alternatively, it may be bonded to a carrier such as a resin.
  • the predetermined amount of chitin means 2 to 10 times, preferably 3 to 8 times, more preferably 4 to 7 times the amount of chitin by dry weight with respect to the polyphenol content in the extract and the like.
  • the weight excluding the weight of the carrier portion is defined as the weight of the chitin.
  • the polyphenol content in extracts and the like can be determined, for example, by fractionating a part (about 1 to 5 mL) of the extract, powdering by hot air drying, freeze drying, vacuum drying, and vacuum concentration. It can be calculated by measuring the weight of the powder of extract, etc. (hereinafter referred to as extract powder), and measuring the polyphenol content (%) in the extract powder by the Fo1 in method. it can.
  • the measurement of the polyphenol content (%) in the extract powder by the F o 1 in method is performed, for example, as follows. First, catechin is dissolved in purified water as a polyphenol standard substance, and a standard specimen is prepared stepwise within a range of 0.05 to 0.05% by weight / volume. Next, the extract powder is appropriately dissolved in purified water within the range of 0.01 to 0.05 weight / volume% to prepare a specimen.
  • Standard samples Each sample and 2.5 ml of Folin reagent (2.5 g of sodium tungstate, 0.5 g of phosphomolybdic acid, and 1.25 ml of an 85% by weight phosphoric acid solution in 10 O ml) Aqueous solution) and stirred for 3 minutes, then add 3 mL of 10% by volume sodium carbonate solution, and leave for 1 hour. After standing, collect the supernatant by centrifugation, and measure the absorbance of this supernatant at 70 nm. A calibration curve is created from the absorbances of the standard samples at each concentration, and the concentration of polyphenol contained in the sample is obtained using this calibration curve. The polyphenol content (%) in the extract powder can be calculated from the obtained polyphenol concentration and the sample concentration.
  • the contact may be performed by any method as long as the extract or the like contacts the chitin.
  • a chitin resin in which chitin is bound to a synthetic resin carrier is filled in a column, a column method in which an extract is passed, a chitin is added to the extract, etc., and after a certain time, the chitin is removed.
  • an organic solvent is contained in the extract or the like, it is necessary to dilute the extract or the like to such an extent that chitins do not dissolve in the organic solvent or to remove the organic solvent.
  • insolubles contained in the extract and the like in advance in consideration of clogging of the column and the like.
  • Methods for removing insolubles include methods commonly used by those skilled in the art, for example, filtration and centrifugation. Filtration is preferably used in terms of processing time. Filtration may preferably be performed at 50 to 100 ° C. The higher the temperature, the more proanthocyanidin can be recovered, and it is preferably carried out at 50 ° C or higher, more preferably at 70 ° C or higher. More proanthocyanidins can be recovered by washing the insolubles removed by filtration with hot water or a heated solvent at 70 ° C or more.
  • the resulting extract is taken into account in consideration of the efficiency of adsorption to chitins.
  • the extract is cooled to 4 to 30 ° C.
  • the cooling include natural cooling by standing to cool; forced cooling using water, ice, or a cooling device such as a freezer or a refrigerator.
  • the extract is passed through a column packed with chitins.
  • a proanthocyanin-containing substance is obtained from pine bark using chitin derived from Rikiji, the polyphenol content in the hot water extract of pine bark is measured, and then the content of the polyphenol is determined.
  • the pine bark extract is passed through a column packed with 2 to 10 times, more preferably 3 to 8 times, the amount of chitin by dry weight. Thereafter, the column is washed with about 2 to 3 times the volume of the column with water, and the resulting protean cyanidin-containing substance can be obtained by collecting the column passing liquid and the washing liquid.
  • the proanthocyanidin-containing substance also includes a concentrate, a diluent, a powder, and the like obtained by a method usually used by those skilled in the art.
  • the treatment with chitins may be performed, for example, by adding 2 to 10 times, preferably 3 to 8 times the dry weight of chitin relative to the dry weight of polyphenol in the hot water extract of pine bark. It is preferable to carry out the reaction for 1 to 3 hours with stirring.
  • the chitins are removed by filtration or centrifugation to obtain a broantocyanidin-containing substance.
  • proanthocyanidin-containing substance I a proanthocyanidin-containing substance having a high OPC content
  • proanthocyanidin-containing substance I a proanthocyanidin-containing substance having a high OPC content
  • Pro Ant Xia two gin inclusions I are dry weight in OPC (Origome Rick Pro Ant Xia two gin) 3 0-9 0 weight 0/0, and more preferably contains 4 0 wt% to 7 0% by weight.
  • the resulting pro Ant Xia two gin inclusions I is more preferably a catechin in terms of dry weight 5-1 5 wt%, more preferably 1 0-1 5 weight 0/0 can contain.
  • Catechins are poorly water-soluble by themselves, and their physiological activities OPC has the property of increasing the water solubility of catechins and, at the same time, activating the action of catechins when coexisting with catechins. Therefore, the proanthocyanidin-containing substance I containing OPC and catechins is particularly useful.
  • Catechins are a general term for polyhydroxyflavan-1-ol.
  • Examples of power techins include (+)-catechin, (1) i-epicatechin, (+)-gallocatechin, (1) i-epigallocatechin, epigallocatechin gallate, and epeki tekin gallate.
  • it includes afzelequin, which is derived from natural products, and 3- (galloyl) derivatives of (+)-forcechin or gallocatechin.
  • catechins include carcinogenesis inhibitory action, arteriosclerosis preventive action, fat metabolic disorder inhibitory action, blood pressure increase inhibitory action, platelet aggregation inhibitory action, antiallergic action, antiviral action, antibacterial action, caries prevention action, bad breath It has a protective effect, a normalizing effect on the intestinal flora, a scavenging effect of active oxygen and free radicals, an antioxidant effect, and an antidiabetic effect for suppressing an increase in blood sugar.
  • the resulting proanthocyanidin-containing substance I is further treated with a synthetic resin-based adsorbent to remove impurities such as saccharides and organic acids, and further purified. That is, the proanthocyanidin-containing substance I is brought into contact with a synthetic resin-based adsorbent, the proanthocyanidin is adsorbed on the synthetic resin-based adsorbent, and then eluted with a predetermined solvent, whereby the OPC content is reduced.
  • An extremely high proanthocyanidin content (hereinafter referred to as proanthocyanidin content II) can be obtained.
  • the synthetic resin-based adsorbent used for the above purification include an organic resin, an ion exchange resin, silica gel, and reversed-phase silica gel.
  • an aromatic resin such as a styrene-dibutylbenzene-based resin, an atalylic acid-based methacrylic resin, and an atarilonitrile-based aliphatic resin can be used.
  • it is an aromatic resin.
  • These resins are preferably porous.
  • Acrylic methacrylic resins include DIAION (registered trademark) HP 1MG and HP 2MG (all manufactured by Mitsubishi Chemical Corporation); As the aromatic resin, SP-900 (manufactured by Mitsubishi Chemical Corporation), Amberlite (registered trademark) XAD-2, XAD-4, XAD-16, XAD-2000 (all manufactured by Organo Corporation); hydrophobic Examples of the aromatic resin having a hydrophilic substituent include Diaion (registered trademark) SP-205, SP-206, SP-207, HP-1MG, EX-0021 (all manufactured by Mitsubishi Chemical Corporation), Amberley G (registered trademark) XAD-7, XAD-8 (all manufactured by Organo Co., Ltd.); Unsubstituted aromatic resins include DIAION (registered trademark) HP-10, HP-20, HP-2 1, HP-30, HP-40, HP-50 (or more, manufactured by Mitsubishi Chemical Corporation) Aromatic resins obtained by specially treating unsubstituted groups include SP-825,
  • any of a cation exchange resin and an anion exchange resin can be used.
  • Commercially available cation exchange resins include, for example, resins having a sulfonate group as a functional group, such as Amberlite (registered trademark) CG-4000, CG-5000, CG_6000, CG-8000, IR- 116, IR-118, IR-120B, IR-122, IR-124, XT-1007, XT-1009, XT-1002 (all manufactured by Olgano Corporation).
  • a weakly basic anion exchange resin for example, OPT I PORE—XUS 40285.00, OPT I PORE—XUS 40390.00 (both manufactured by Da Chemical Co., Ltd.), which are resins having a quaternary amine as a functional group.
  • the solvent to be dissolved when using the ion exchange resin is preferably water, and the column temperature is 50 to 120 ° (:, preferably, the column is under normal pressure or pressurized state.
  • the amount of the synthetic resin-based adsorbent may be appropriately set depending on the type of the solvent, the type of the synthetic resin-based adsorbent, and the like. For example, it is preferable to use 0.01 to 5 times the weight of the synthetic resin-based adsorbent with respect to the dry weight of the proanthocyanidin-containing substance I.
  • a synthetic resin-based adsorbent is packed in a column, and the proanthocyanidin-containing substance I is passed through the column. Pass water 5 to 10 times the weight of the synthetic resin adsorbent. Thereby, saccharides and organic acids as impurities are removed. Then elute proanthocyanidin with a suitable solvent.
  • the solvent include water, methanol, ethanol, ethyl acetate, chloroform, and a mixed solvent thereof.
  • a mixed solvent of water and ethanol is used.
  • the mixing ratio of water and ethanol depends on the synthetic resin adsorbent used. For example, in the case of Diaion HP-20, the ratio of water: ethanol is 1: 1 to 4: 1 by volume. In this way, a proanthocyanidin-containing substance II having an extremely high OPC content is obtained.
  • the proanthocyanidin-containing substance II obtained through the above purification step may contain 0 to 80% by weight or more, preferably 95% by weight or more in terms of dry weight.
  • This proanthocyanidin-containing substance II contains an extremely large amount of OPC, but hardly contains phytotechins.
  • a proanthocyanidin-containing substance containing 5 to 15% by weight of phytotechins Object I can also be.
  • it can be obtained by adding high-purity tetekins to proanthocyanin-containing substance II.
  • the proanthocyanidin-containing substance I or II produced by the above method can be concentrated to produce a food material.
  • concentration various methods such as membrane concentration, heat concentration, vacuum (reduced pressure) concentration, and freeze concentration are used.
  • these proanthocyanidin-containing substances I or II are sterilized and stored. Sterilization is performed by a method used by those skilled in the art, such as airflow sterilization, high-pressure sterilization, and heat sterilization.
  • proanthocyanidin-containing substances I or II may be concentrated, dried, or powdered after sterilization. Drying is performed by a method commonly used by those skilled in the art. Among them, freeze drying, vacuum drying, and spray drying are preferably used.
  • the proanthocyanidin-containing substance I or II thus obtained can be used as a raw material for foods, cosmetics, and pharmaceuticals.
  • proanthocyanidin-containing substance I or II can also be used as a drink, a gelled food or the like.
  • proanthocyanidin-containing substances are not only used for eating and drinking as they are, but also mixed with excipients, bulking agents, binders, thickeners, emulsifiers, flavors, food additives, seasonings, etc., depending on the application.
  • it can be formed into the form of granules, tablets, and the like. For example, it can be mixed with royal jelly, vitamins, protein, calcium, chitosan, lecithin, caffeine, etc., and taste can be adjusted with a sugar solution and a seasoning.
  • capsules such as hard capsules and soft capsules, pills, or tea bags. These may be eaten as they are, or may be dissolved in water, hot water, milk, or the like, depending on their shape or preference. In the case of tea bags, etc., the ingredients may be leached before drinking.
  • V / V represents (capacity / capacity), and (W / W) represents (weight / weight).
  • the dry powder of the proanthocyanidin-containing solution Ia obtained as described above is mixed with a component including OPC, a component including force techins, and other components including a polymer (hereinafter, referred to as other components). Then, they were separated as follows. First, 25 mL of Sefadex LH-20 (manufactured by Pharmacia Biotech Co., Ltd.) swollen with water was packed in a 15 ⁇ 30 OmL column, and washed with 25 mL of ethanol.
  • Sefadex LH-20 manufactured by Pharmacia Biotech Co., Ltd.
  • the TLC development conditions and detection method are as follows.
  • TLC Silica gel plate (Merck & CO., Inc.)
  • Detection reagents sulfuric acid and anisaldehyde sulphate
  • the elution fractions confirmed to contain OPC by TLC detection were combined to obtain an OPC fraction.
  • the fractions other than the OPC fraction were subjected to TLC using catechin as an index (R f value: 0.8), and separated into a fraction containing phytotechins and a fraction of other components.
  • the TLC development conditions and detection method were the same as described above.
  • the fraction containing phytotechins was further separated into catechins and components other than phytotechins as follows. First, the fraction containing force techins was freeze-dried, the obtained powder was dissolved in 3 mL of water, and this was swollen with water and 2 OmL of MCI gel (manufactured by Mitsubishi Chemical Corporation) was applied to 15X. The liquid was adsorbed by passing through a column packed in a 30 OmL column.
  • the OPC fraction, the hapticins fraction, the fractions other than the catechins, and the other component fractions obtained as described above were each powdered by freeze-drying, and the dry weight was measured.
  • the obtained OPC is a dry powder of the proanthocyanin-containing solution Ia 10
  • Omg was 30.2 mg. That is, the content of OPC in proanthocyanidin-containing liquid Ia is 30.2% by weight in terms of dry weight, and 347 mg of OPC should be contained in the total amount of oral anthocyanidin-containing liquid Ia. I was strong.
  • the resulting tetekins were 10.1 mg. That is, the content of catechins in the proanthocyanidin-containing solution Ia was 10.1% by weight in terms of dry weight, and the amount of catechins in the total amount of the proanthocyanidin-containing solution Ia was 1 16 It was found to contain mg. Note 99, OPC fraction, force catechins fraction, fraction of components other than the force text emissions such, and the sum of the fractions of the other components, the dry powder 10 Omg of Puroantoshi Anijin containing liquid I a. It was 2 mg, and almost all of it had been recovered.
  • Table 1 shows the dry weight of the proanthocyanidin-containing liquid Ia, and the contents and contents of OPC and kytechins in terms of dry weight. (Examples 2 and 3)
  • Example 1 was repeated except that the amount of chitin packed in the column was 2.5 g, equivalent to 5 times the dry weight of polyphenol in the extract, and 3.5 g, equivalent to 7 times the dry weight of the polyphenol in the extract.
  • 44 OmL of proanthocyanidin-containing solutions Ib and Ic were obtained.
  • the proanthocyanidin-containing solutions Ib and Ic were concentrated under reduced pressure at a volume of 22 OmL, and the weight of each of the obtained dry powders was measured. The entire amount of each proanthocyanidin-containing solution Ib and Ic was dried. It was converted to weight.
  • the dry weight of the proanthocyanidin-containing solution Ib was 1024 mg, and the dry weight of the proanthocyanidin-containing solution Ic was 632 mg.
  • the content and content of OPC and catechins in terms of dry weight were determined in the same manner as in Example 1. The results are shown in Table 1.
  • the total dry weight of the obtained fractions was 98.9 mg and 99.5 mg, respectively, for 10 Omg of dry powder of proanthocyanidin-containing solutions Ib and Ic, respectively. Had been recovered.
  • proanthocyanidin-containing solution Ib obtained in Example 2.
  • the proanthocyanidin-containing solution Ib was passed through a column filled with 5 g of an aromatic synthetic resin (Diaion HP-20: manufactured by Mitsubishi Chemical Corporation), and the proanthocyanidin was adsorbed on the column.
  • the column was washed with 2 OmL of purified water, and then the column was eluted with a 20 to 40% (V / V) mixed solvent of ethanol and water to obtain 40 mL of proanthocyanidin-containing solution IIb.
  • Example 1 Example 1 was repeated except that the amount of chitin packed in the column was 0.5 g, which was equivalent to 1 times the dry weight of polyphenol in the extract, and 6.5 g, which was equivalent to 13 times the dry weight of polyphenol in the extract.
  • 44 OmL of proanthocyanidin-containing solutions Id and Ie were obtained.
  • 22 OmL of each half of the proanthocyanidin-containing solutions Id and Ie were concentrated under reduced pressure, and the weight of each of the obtained dry powders was measured. The total amount of each of the oral anthocyanidin-containing solutions Id and Ie was determined. It was converted to dry weight.
  • the dry weight of the proanthocyanidin-containing solution Id was 2288 mg, and the dry weight of the proanthocyanidin-containing solution Ie was 472 mg.
  • the content and the content in terms of dry weight of the OPC and force techins were measured in the same manner as in Example 1. The results are shown in Table 1.
  • the total dry weight of the obtained fractions was 99.3 mg and 98.8 mg, respectively, for 10 Omg of dry powder of proanthocyanidin-containing solutions Id and Ie, respectively, and almost all of them were Had been recovered.
  • proanthocyanidin-containing solutions Ia to I obtained by treating with 3 to 7 times the amount of chitin relative to the polyphenol content in the extract. Contains 30% by weight or more of OPC on a dry weight basis. These O PC content corresponds to about 2 times the polyphenol contained in extracts powder (15.78 wt. / 0).
  • Particularly Puroantoshia - Gin containing liquid I b and I c are the OPC on a dry weight amount conversion also contains 40 weight 0/0 above.
  • proanthocyanidin-containing solutions Id and Ie obtained by treating with 1 or 13 times the amount of chitin relative to the dry weight of polyphenol in the extract OPC was calculated to be 17.2 in terms of dry weight. % And 10.5% by weight, which were lower than those treated with 3 to 7 times the amount of chitin. From these results, it is shown that by treating a plant extract or the like with a predetermined amount of chitin, a proanthocyanidin, particularly a brothocyanidin-containing substance containing a high proportion of OPC can be obtained. Furthermore, pro-Ant Xia two Jin-containing solution I to I c is, 10.
  • a force enemy emissions such in terms of dry weight from 1 to 14.8 wt 0/0 T while containing, Puroantoshia two Jin-containing solution I
  • the dtekines contained in d and Ie were 7.3% by weight and 3.8% by weight, respectively. This is because treatment of plant extracts and the like with a predetermined amount of chitin allows not only OPCs but also high-technologies to be more expensive.
  • Fig. 7 shows that a proanthocyanin-containing material can be obtained.
  • the proanthocyanin-containing solution I Ib contained 80% by weight or more of OPC in terms of dry weight.
  • the above extract powder was added to the remaining extract, adjusted to a total volume of 1.2 L with hot water, allowed to cool to 25 ° C, and chitin in a dry weight of about 7 times the polyphenol content. 10 g was added, and the mixture was stirred for 3 hours. After stirring, the mixture was filtered to obtain 1.2 L of a proanthocyanidin-containing solution If.
  • the proanthocyanidin-containing solution If was concentrated under reduced pressure to obtain 3.36 g of a dry powder of the proanthocyanidin-containing solution If. l
  • the OPC and catechin contents were measured in the same manner as in Example 1 using the dry powder of the proanthocyanidin-containing solution If of O Omg, and it was found that OPC was 40% by weight or more on a dry weight basis. It was found to contain 12.1% by weight of force techins.
  • 3.26 g of the proanthocyanidin-containing solution If dry powder was dissolved in 2 L of methanol and passed through a column packed with 50 g of Diaion HP 20 as in Example 1. The proanthocyanidins were adsorbed.
  • a proanthocyanidin-containing substance containing OPC having a high physiological activity in a high ratio can be easily obtained.
  • the proanthocyanidin-containing material having a high OPC content also contains phytotechins. Therefore, OPC has a synergistic effect of activating the action of catechins.
  • a proanthocyanidin-containing substance having an extremely high OPC content can be provided. Since the proanthocyanidin-containing substance having an extremely high OPC content contains almost no catechins, it can be used as a more purified OPC.
  • These proanthocyanidin-containing substances are effective in improving vascular enhancement, hypertension, coldness, etc., and are very useful as raw materials for producing foods, cosmetics, and pharmaceuticals.

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Abstract

L'invention concerne un matériau contenant de la proanthocyanidine, riche en proanthocyanidine oligomère (OPC) d'activité physiologique élevée, pouvant être obtenu par extraction de proanthocyanidine d'une plante, puis par mise en contact de l'extrait obtenu avec une quantité définie de chitine, de chitosan ou d'un dérivé de ces composés, et par récupération de matières non adsorbées. Un traitement subséquent de ce matériau contenant de la proanthocyanidine avec un adsorbant à base de résine synthétique permet d'obtenir un matériau contenant de la proanthocyanidine avec une teneur très élevée en OPC.
PCT/JP2003/002001 2002-04-24 2003-02-24 Procede de production de materiau riche en proanthocyanidine WO2003091237A1 (fr)

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EP1669338A4 (fr) * 2003-10-01 2008-04-16 Toyo Shinyaku Co Ltd Procede de production d'un produit a teneur elevee en proanthocyanidine
US8642088B2 (en) 2009-09-04 2014-02-04 Wisconsin Alumni Research Foundation Tannin-chitosan composites
US9114114B2 (en) 2007-06-21 2015-08-25 Mars, Inc. Edible products having a high cocoa polyphenol content and improved flavor and the milled cocoa extracts used therein
JP2015163644A (ja) * 2009-05-26 2015-09-10 株式会社アモーレパシフィックＡｍｏｒｅｐａｃｉｆｉｃ Ｃｏｒｐｏｒａｔｉｏｎ 豆抽出物を含有する血液循環改善及び血管健康増進用組成物
JPWO2014065369A1 (ja) * 2012-10-25 2016-09-08 日本製紙株式会社 茶葉抽出物
US10183007B2 (en) 2005-02-25 2019-01-22 Usien Pharmaceutical Co., Ltd. Method of producing proanthocyanidin oligomer
US12234578B2 (en) 2020-01-29 2025-02-25 Wisconsin Alumni Research Foundation Tannin composite fibers
US12303564B2 (en) 2021-11-09 2025-05-20 Wisconsin Alumni Research Foundation Composite chitosan-tannin-active agent compositions and methods of making and using same

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US7306815B2 (en) * 2000-08-31 2007-12-11 Phenolics, Llc Compositions enriched in phenolic compounds and methods for producing the same
WO2006061915A1 (fr) * 2004-12-09 2006-06-15 Toyo Shinyaku Co., Ltd. Préparation curative pour la peau
US7863466B2 (en) 2005-04-15 2011-01-04 Toyo Shinyaku Co., Ltd. Method of producing proanthocyanidin-containing material
JP4977024B2 (ja) * 2005-04-15 2012-07-18 株式会社東洋新薬 プロアントシアニジン含有物の製造方法

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Cited By (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1669338A4 (fr) * 2003-10-01 2008-04-16 Toyo Shinyaku Co Ltd Procede de production d'un produit a teneur elevee en proanthocyanidine
US10183007B2 (en) 2005-02-25 2019-01-22 Usien Pharmaceutical Co., Ltd. Method of producing proanthocyanidin oligomer
US9114114B2 (en) 2007-06-21 2015-08-25 Mars, Inc. Edible products having a high cocoa polyphenol content and improved flavor and the milled cocoa extracts used therein
US10155017B2 (en) 2007-06-21 2018-12-18 Mars, Inc. Edible products having a high cocoa polyphenol content and improved flavor and the milled cocoa extracts used therein
JP2015163644A (ja) * 2009-05-26 2015-09-10 株式会社アモーレパシフィックＡｍｏｒｅｐａｃｉｆｉｃ Ｃｏｒｐｏｒａｔｉｏｎ 豆抽出物を含有する血液循環改善及び血管健康増進用組成物
US11197903B2 (en) 2009-05-26 2021-12-14 Amorepacific Corporation Composition containing a bean extract for improving blood circulation and vascular health and method for improving blood circulation and vascular health
US8642088B2 (en) 2009-09-04 2014-02-04 Wisconsin Alumni Research Foundation Tannin-chitosan composites
US9545423B2 (en) 2009-09-04 2017-01-17 Wisconsin Alumni Research Foundation Tannin-chitosan composites
US10104888B2 (en) 2009-09-04 2018-10-23 Wisconsin Alumni Research Foundation Tannin-chitosan composites
JPWO2014065369A1 (ja) * 2012-10-25 2016-09-08 日本製紙株式会社 茶葉抽出物
US12234578B2 (en) 2020-01-29 2025-02-25 Wisconsin Alumni Research Foundation Tannin composite fibers
US12303564B2 (en) 2021-11-09 2025-05-20 Wisconsin Alumni Research Foundation Composite chitosan-tannin-active agent compositions and methods of making and using same

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AU2003211279A1 (en) 2003-11-10
AU2002311198A1 (en) 2003-11-10
WO2003090770A1 (fr) 2003-11-06
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JP3595816B2 (ja) 2004-12-02
JPWO2003090770A1 (ja) 2005-08-25

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