WO2006067864A1 - Proanthocyanidin-containing composition - Google Patents

Proanthocyanidin-containing composition Download PDF

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Publication number
WO2006067864A1
WO2006067864A1 PCT/JP2004/019788 JP2004019788W WO2006067864A1 WO 2006067864 A1 WO2006067864 A1 WO 2006067864A1 JP 2004019788 W JP2004019788 W JP 2004019788W WO 2006067864 A1 WO2006067864 A1 WO 2006067864A1
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WIPO (PCT)
Prior art keywords
proanthocyanidins
group
catechins
weight
extract
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PCT/JP2004/019788
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French (fr)
Japanese (ja)
Inventor
Kinya Takagaki
Takeshi Mitsui
Original Assignee
Toyo Shinyaku Co., Ltd.
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Priority to PCT/JP2004/019788 priority Critical patent/WO2006067864A1/en
Publication of WO2006067864A1 publication Critical patent/WO2006067864A1/en

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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/335Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35Heterocyclic 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
    • A61K31/352Heterocyclic 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 
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/335Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35Heterocyclic 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
    • A61K31/352Heterocyclic 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 
    • A61K31/3533,4-Dihydrobenzopyrans, e.g. chroman, catechin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00Drugs for disorders of the metabolism
    • A61P3/06Antihyperlipidemics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00Drugs for disorders of the metabolism
    • A61P3/08Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics

Definitions

  • the present invention relates to a composition for enhancing the bioactive action of proanthocyanidins.
  • Proanthocyanidins are condensed or polymerized tannins (hereinafter referred to as polycondensation) present in various plants, and are a group of compounds obtained by polycondensation using flavan 1-ol or flavan 1,3-diol as a constituent unit. is there. These are given their names because they produce anthocyanidins such as cyanidin, delphinidin, and pelargonidin by acid treatment.
  • oligomeric proanthocyanidin hereinafter referred to as OPC.
  • Proanthocyanidins are a kind of polyphenols and have a strong antioxidant action (Japanese Patent Laid-Open No. Sho 61-16982), and further improve blood lipids; antihypertensive effects; Effect of suppressing blood sugar level rise; Effect of restoring blood vessel elasticity
  • Anti-vascular effect It is known to have an effect of increasing the utilization efficiency of vitamin C; and an effect of improving blood fluidity.
  • An object of the present invention is to provide a novel composition that can further enhance various physiologically active actions of proanthocyanidins.
  • composition of the present invention is characterized by containing proanthocyanidins and catechins having a 3,4,5-trihydroxyphenyl group.
  • composition of the present invention contains proanthocyanidins and catechins having a 3,4,5-trihydroxyphenyl group.
  • the 3, 4, 5_trihydroxyphenino group is a galloyl group.
  • compositions containing the above-mentioned proanthocyanidins and trihydroxenyl group-containing power textiles to improve the blood lipids and lipid metabolism of proanthocyanidins It can remarkably enhance physiological activities such as blood glucose level rise inhibitory effect, antihypertensive effect, blood flow improving effect, and skin beautifying effect. These effects are excellent effects that cannot be obtained by single administration of catechins having a proanthocyanidin and a trihydroxyphenyl group, respectively.
  • the composition of the present invention can be effectively used for foods, pharmaceuticals, quasi drugs, cosmetics and the like. Brief Description of Drawings
  • Figure 1 shows a rat with a pine bark extract and a category with trihydroxyphenyl groups. Feeds containing quinine, pine bark extract and catechin not containing trihydroxyphenyl group, and feed containing only pine bark extract 2 It is a graph which shows transition of the blood pressure increase rate.
  • composition of the present invention contains proanthocyanidins and catechins having a 3, 4, 5_trihydroxyphenyl group, and optionally contains other components.
  • proanthocyanidins and catechins having a 3, 4, 5_trihydroxyphenyl group and optionally contains other components.
  • each component will be described.
  • proanthocyanidins used in the present invention those containing a large amount of a condensation polymer having a low degree of polymerization are suitable.
  • a condensation polymer having a low degree of polymerization a condensation polymer having a degree of polymerization of 2 to 30 (a 2 to 30 mer) is preferable, and a condensation polymer having a degree of polymerization of 2 to 10 (a 2 to 10 mer).
  • a condensation polymer having a degree of polymerization of 2 to 4 (2 to 4 mer: OPC) is more preferred.
  • OPC is a particularly powerful antioxidant.
  • Proanthocyanidins are concentrated in plant leaves, bark, fruit peels or seeds.
  • Proanthocyanidins are specifically the bark of plants such as pine, straw, and yamatake; grapes, blueberries, strawberries, avocados, false acacia, berries or seeds of barley; wheat; soybeans; black It is contained in soybeans, cacao, red beans, tochi nut shells, peanut skins, ichiyo leaves, etc. Also, West African cola nuts, Peruvian Latania roots. Japanese green tea is known to contain OPC. OPC is a substance that cannot be produced in the human body.
  • proanthocyanidins with a high OPC content or proanthocyanidins with a high OPc content are used.
  • proanthocyanidins with a high degree of polymerization are used.
  • excellent lipid metabolism improvement effect, antihypertensive effect, blood glucose level rise suppression effect, etc. are obtained.
  • materials such as the bark of the above-mentioned plant, pulverized fruits or seeds, or extracts thereof can be used.
  • an extract derived from a plant because it contains abundant proanthocyanidins, and it is particularly preferable to use an extract derived from pine bark.
  • pine bark is rich in OPC, so it is preferably used as a raw material for proanthocyanidins.
  • the extract is preferably one from which impurities have been removed.
  • pine bark rich in OPC as a raw material plant will be described as a method for preparing an extract containing puffer anthocyanidin as a main component.
  • Pinus martima Pinus martima, larch, black pine, waka pine, Japanese pine, pine pine, Korean pine, high pine, Ryuyuki pine, Utsushima pine, Daiyu pine, white pine, Quebec in Canada
  • An extract of a bark of a plant belonging to the order of pine is preferably used. Above all, the bark extract of French coastal pine (Pinus Martima) is preferred.
  • French coastal pine is a marine pine that grows on the Atlantic coast of southern France.
  • This French coastal pine bark contains proanthocyanidins, organic acids, and other physiologically active ingredients.
  • Proanthocyanidins which are the main ingredients, have strong antioxidative effects to remove active oxygen. It is known that there is.
  • the pine bark extract is obtained by extracting the above pine bark with water or an organic solvent. When water is used, it is preferable to use warm water or hot water. To improve the extraction efficiency, salt such as sodium chloride is added to these waters. And are preferred.
  • organic solvent used for extraction organic solvents that are acceptable for the production of foods or pharmaceuticals are used.
  • water and organic solvents may be used alone or in combination.
  • water, hot water, ethanol, water-containing ethanol, and water-containing propylene glycol are preferable, and water, hot water, ethanol, and water-containing ethanol are more preferable from the viewpoint of safety when used in foods and pharmaceuticals.
  • the method for extracting proanthocyanidins from pine bark is not particularly limited. For example, by extracting 1 to 50 parts by weight of hot water of 50 to 120 ° C., preferably 70 to 100 ° C. with respect to 1 part by weight of pine bark dry, A pine bark extract having a high bioactivity and high water solubility can be obtained. A warm extraction method, a supercritical fluid extraction method, or the like may be used.
  • supercritical fluid extraction may be performed by an entrainer addition method.
  • ethanol, propanol, n-hexane, acetone, toluene, other aliphatic lower alcohols, aliphatic hydrocarbons, aromatic hydrocarbons, or ketones are added to a supercritical fluid.
  • it is a method for enhancing the selectivity of separation, and a method for efficiently obtaining a pine bark extract.
  • pine bark extracts For extraction from pine bark, you can combine several extraction methods. It is possible to obtain pine bark extracts with various compositions by combining multiple extraction methods. It becomes ability.
  • the pine bark extract obtained by the above extraction may be purified for the purpose of increasing the content of proanthocyanidins.
  • a solvent such as ethyl acetate is usually used, but from the viewpoint of safety as a food or pharmaceutical, a method that does not use a solvent, such as ultrafiltration or Diaion HP-2O, Sephadex It is preferable to purify by a column method or a batch method using an adsorbent carrier such as LH 20 or chitin.
  • the pine bark extract containing proanthocyanidin as a main component is specifically prepared by the following method, but this is an example and is not limited to this method.
  • the washing step is repeated twice, in which the precipitate is added again to 1 L of chloroform and precipitated.
  • this method for example, about 5 g of pine bark extract containing 20% by weight or more of OPC and 5% by weight or more of strong techins can be obtained.
  • Extracts derived from raw material plants such as the above pine husks contain 40% by weight or more of pro It is preferable to contain anthocyanidin. Further, the extract derived from the raw material plant preferably contains 20% by weight or more of OPC, more preferably 30% by weight or more. As described above, a pine bark extract is preferably used as a raw material containing proanthocyanidins in a high proportion.
  • OPC is an antioxidant, it has the effect of reducing the risk rate of adult diseases such as cancer, heart disease, and cerebral thrombosis, and has the effect of improving the allergy in nature such as arthritis, atopic dermatitis, and hay fever.
  • it suppresses bacterial growth in the oral cavity and reduces plaque (dental glands); restores the elasticity of blood vessels; prevents lipoproteins in the blood from being damaged by active oxygen; It also has the effect of preventing cholesterol from adhering to the inner wall of blood vessels and adhering cholesterol; the effect of regenerating vitamin E decomposed by active oxygen; and the effect of enhancing vitamin E.
  • composition of the present invention contains catechins having a 3,4,5-trihydroxyphenyl group (hereinafter sometimes referred to as THP catechins).
  • Catechin is a generic name for polyhydroxyflavan 1-ol, (+) — force techin (referred to as catechin in a narrow sense), gallocatechin, afuzerekin, (+) 3-galloyl derivative of The 3-galloyl derivative of yopi gallocatechin is common.
  • THP catechins examples include (+)-gallocatechin, (1) one-epigalocatechin, force-techin gallate, epicatechin gallate, gallocatechin gallate, and epigallocatechin gallate.
  • catechins in which the trihydroxyphenyl group is a galloyl group are preferred.
  • Such catechins having a galloyl group include force techin gallate, epicatechin gallate, gallocatechin gallate, and epigallocatechin gallate.
  • THP catechins are contained in plants such as camellias (for example, tea leaves such as green tea, black tea, and ulong tea) and mao. These plants or their meals or extracts may be used as THP catechins. Preferably, it is a camellia plant, or a pulverized product thereof or an extract thereof.
  • green tea leaves contain about 10-15% catechins, of which about 80% or more are THP catechins and about 50% or more are TH P catechins. Since it is a catechin having one galloyl group, it is preferable.
  • THP catechins together with proanthocyanidins, can remarkably enhance various bioactive effects of proanthocyanidins.
  • THP catechins are materials that efficiently enhance the multiple bioactive effects of proanthocyanidins.
  • catechins having a galloyl group not only have high antioxidant activity, but also have excellent effects such as an inhibitory effect on blood glucose level increase, antihypertensive effect, anti-lipaemia, and the like, so proanthocyanidins It is possible to remarkably enhance various physiologically active actions possessed by.
  • THP catechins are other anti-carcinogenic effects, arteriosclerosis-preventing effects, fat-metabolism-suppressing effects, blood pressure rise-inhibiting effects, platelet aggregation-inhibiting effects, anti-allergic effects, anti-viral effects, anti-bacterial effects, caries-preventing effects, bad breath It is known to have an inhibitory action, an intestinal microbiota normalizing action, an active oxygen and free radical scavenging action, and an antioxidant action.
  • composition of the present invention contains the above-mentioned proanthocyanidins and THP catechins, and may contain various components as necessary.
  • normal food and medicine Ingredients that can be added as excipients (excipients, extenders, binders, thickeners, emulsifiers, colorants, fragrances, nutritional ingredients, food additives, etc.); and usually as external preparations for skin of cosmetics, quasi drugs Ingredients used (whitening agent, moisturizer, antioxidant, UV absorber, UV scattering agent, antiseptic, fragrance, gelling agent, polymer, oil component, surfactant, thickener, alcohol, Powder components, colorants, aqueous components, various skin nutrients, etc.).
  • Nutritional components include, for example, ascorbic acid, tocopherol, riboflavin, vitamins such as 3 -carotene, folic acid, and piotin; minerals such as calcium, magnesium, selenium, iron; included in taurine, garlic, etc.
  • Flavanoids such as hesperidin and quercetin; Flavonoids; Dietary fibers such as indigestible dextrin, alginic acid, chitin, chitosan and guagam; Proteins such as soy protein and collagen; Peptides; Amino acids; Milk Animal fats such as fat, lard, beef tallow and fish oil; vegetable oils such as soybean oil and rapeseed oil; fruits such as orange, lemon, grapefruit and strawberry and their juices; royal jelly and propolis.
  • food-added calories include honey, reduced maltose, lactose, sugar alcohol, liquid sugar, and seasonings.
  • the composition of the present invention contains proanthocyanidins and THP strength textiles and, if necessary, other ingredients.
  • proanthocyanidins and THP catechins may be any of isolated compounds, food materials containing them, and extracts of the food materials.
  • a plant extract containing THP strength is added to a plant extract containing proanthocyanidins.
  • it contains proanthocyanidins such as pine bark and cinnamon bark, and most of the catechins contained are trihydroxide.
  • a plant extract containing THP catechins is added to a plant extract that is a catechin that does not have a siphenyl group.
  • the plant extract contains both proanthocyanidins and THP catechins
  • add necessary ingredients for example, pine bark extract containing a large amount of proanthocyanidins
  • the amount ratio of each component in the composition can be adjusted as appropriate.
  • the content ratio of proanthocyanidins and THP catechins in the composition of the present invention is arbitrary.
  • the above-mentioned THP strength techins are 1 part by weight to 5000 parts by weight, more preferably 3 parts by weight to 2000 parts by weight, still more preferably 10 parts by weight to 1000 parts by weight, Most preferably, it can be contained in a proportion of 50 to 500 parts by weight.
  • proanthocyanidin in the composition of this invention is preferably contained so that the daily intake per adult is 1 to 1000 mg, more preferably 2 to 500 mg as proanthocyanidins.
  • transdermal administration since it is a topical administration, it is preferable to have a predetermined concentration.
  • proanthocyanidins are preferably contained in the composition in an amount of preferably 0.0001% to 20% by weight. More preferably, it may be contained in a proportion of 0.0001% to 10% by weight, more preferably 0.001% to 10% by weight, and most preferably 0.01% to 10% by weight.
  • THP catechins are preferably 0. 00001 wt% to 20 wt%, more preferably 0.001 wt% to 20 wt%, more preferably 0.001 wt% to 20 wt%, most preferably 0.01 wt% to 20 wt% May be contained.
  • the composition of the present invention can be prepared in various forms depending on the purpose, for example, as a food, a pharmaceutical, a quasi-drug, or a cosmetic.
  • composition of the present invention when the composition of the present invention is orally ingested (administered) as food, pharmaceuticals, quasi drugs, etc., there is no particular limitation on the form.
  • capsules such as hard capsules and soft capsules, tablets, pills, powder (powder), granules, tea bags, bowl-like viscous liquids, liquids, pastes, etc. are used in a form commonly used by those skilled in the art. .
  • these may be taken as they are, or may be taken by dissolving in water, hot water, milk, etc., or may be taken after leaching the ingredients.
  • composition of the present invention is applied to the skin as a quasi-drug, cosmetic, etc.
  • these forms are not particularly limited, such as ointments, creams, emulsions, lotions, packs, poultices, bath preparations, etc. Any form can be used as long as it is conventionally used for an external preparation for skin.
  • pine husk extract containing 40% by weight of proanthocyanidins as a material containing proanthocyanidins (containing 20% by weight of OPC in the material) (trade name: Flavandinol, Toyo Shinyaku Co., Ltd.) ) was used.
  • the THP catechins, catechin 8 0 weight 0/0 containing green tea-derived extract (trade name, containing these forces catechins having Garoi Le group 6 0 wt% or more: Porifuenon 7 0 S, Tokyo Food Techno Co., Ltd.) and an extract derived from green tea containing 93% by weight of Epigalocatechin Gallate (trade names: Theavigo, Roche “Vitamin” Japan Co., Ltd.) were used.
  • polyphenone 70 S contains 48% by weight or more of THP-powered tekins, Referred to as the “tea catechin 48", “Teabiko” is, the THP force catechins from that it contains 93 by weight 0/0 or more, Les as “tea catechin 93", to Ukoto.
  • Catechin (Sigma Aldrich Japan) was used as a catechin having no trihydroxyphenyl group.
  • a solid feed was prepared in the same manner as in Example 1 except that tea catechin 93 was used instead of tea catechin 48 (referred to as feed 2). (Comparative Example 1)
  • a solid feed was prepared in the same manner as in Example 1 except that catechin was used instead of tea catechin 48 (referred to as feed 3).
  • a solid feed was prepared in the same manner as in Example 1 except that tea catechin 48 was not mixed (referred to as feed 4). (Comparative Example 3)
  • a solid feed was prepared in the same manner as in Example 1 except that the pine bark extract was not mixed (referred to as feed 5).
  • Three-week-old male guinea pigs (Japan SLC Co., Ltd.) were given a commercial solid feed (RC4, Oriental Yeast Co., Ltd.) for one week to acclimate.
  • the guinea pigs were divided into groups of 7 by a total randomization method. Each group of guinea pigs was allowed free intake of the above feeds 1-5 for 28 days. Furthermore, as a control group, a group that freely ingested purified feed was established. After the intake period, the total cholesterol level, LDL cholesterol level, HDL cholesterol level, and triglyceride level in the blood of each group of guinea pigs were measured. The results are shown in Table 1. The measurement method is as follows.
  • Total cholesterol (mgZd L) was measured by enzymatic method using “Serotech” TCHO-L (manufactured by Serotech Co., Ltd.).
  • LDL cholesterol (mgZd L) was measured by an enzyme method using Cholestest LDL (Daiichi Chemical Co., Ltd.).
  • HDL cholesterol (mg / d L) was measured by enzymatic method using Choleest HDL (Daiichi Chemical Co., Ltd.).
  • Triglyceride (mgZd L) was measured by an enzymatic method using “Cellotech” TG-L (manufactured by Seguchi Tech Co., Ltd.). table 1
  • a solid feed was prepared in the same manner as in Example 4 except that catechin was used instead of tea catechin 48 (referred to as feed 7).
  • a solid feed was prepared in the same manner as in Example 4 except that tea catechin 48 was not mixed (referred to as feed 8).
  • the composition containing pine bark extract and THP catechins has an effect of improving blood lipids and suppressing an increase in blood glucose level. Is considered to be obtained.
  • SHR and other disease model joint study group Four-week-old male SHR rats (SHR and other disease model joint study group) were acclimated with a basic diet and water for one week. The rats were divided into 7 groups, so that the average fit of each group was almost uniform. The rats in each group were allowed to freely take the above diets 6-8 for 28 days. In addition, a group with free intake of basic feed was established as a control group. During the intake period, all groups received free drinking water containing 1% by weight of NaC1.
  • Pine bark extract, tea catechin 93, and excipients are mixed in the proportions (weight%) shown in Table 3 to produce tablets (about 200 mg per tablet). Yes.
  • the balance is purified water
  • the group to which the skin lotion (lotion 1) containing the pine bark extract of the example and the THP catechins was applied was either one of the pine bark extract of the comparative example and the THP strength techin. It can be seen that skin wrinkles, spots, and kusumi are improved compared to the group to which the skin lotion containing only the skin lotion (skin lotions 2 and 3) is applied. This indicates that the pine peel extract and trihydroxif 2 It shows that a composition containing a catechin having a ru group has a beautifying effect.
  • composition of the present invention can be administered orally (taken) or transdermally (applied) to improve the lipid metabolism of proanthocyanidins, improve blood lipids, suppress blood glucose elevation, and antihypertensive.
  • Physiologically active effects such as blood flow improvement effect and skin beautifying effect can be remarkably enhanced. These effects are excellent effects that cannot be obtained when proanthocyanidins and THP strength techins are administered alone.
  • the composition of the present invention can be used for foods, pharmaceuticals, quasi drugs, cosmetics and the like.

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Abstract

A composition comprising a proanthocyanidin and a catechin having a trihydroxyphenyl. This composition realizes striking enhancement of the various physiological activities of proanthocyanidin.

Description

プロアントシァニジン含有組成物  Proanthocyanidin-containing composition
技術分野 Technical field
本発明は、 プロアントシァ-ジンの生理活性作用を増強するための組成物 に関する。  The present invention relates to a composition for enhancing the bioactive action of proanthocyanidins.
明 田  Akita
背景技術 Background art
プロアントシァニジンは、 各種植物中に存在する縮合または重合 (以下、 縮重合という) したタンニンであり、 フラバン一 3—オールまたはフラバン 一 3, 4—ジオールを構成単位として縮重合した化合物群である。 これらは、 酸処理によりシァニジン、 デルフィ二ジン、 ペラルゴ二ジンなどのアントシ ァニジンを生成することから、 その名称が与えられている。 プロアントシァ 二ジンの中でも、 特に重合度が 2〜4の縮重合体をオリゴメリック ·プロア ン卜シァニジン (oligomeric proanthocyanidin;以下、 OPCとレヽう) と いう。  Proanthocyanidins are condensed or polymerized tannins (hereinafter referred to as polycondensation) present in various plants, and are a group of compounds obtained by polycondensation using flavan 1-ol or flavan 1,3-diol as a constituent unit. is there. These are given their names because they produce anthocyanidins such as cyanidin, delphinidin, and pelargonidin by acid treatment. Among proanthocyanidins, a polycondensation polymer having a degree of polymerization of 2 to 4 is called oligomeric proanthocyanidin (hereinafter referred to as OPC).
プロアントシァニジンは、 ポリフエノール類の一種で、 強力な抗酸化作用 を有し(特開昭 6 1— 1 6 982号公報)、 さらに、 血中脂質を改善する効 果;抗高血圧効果;血糖値上昇抑制効果;血管の弾力性を回復させる効果 Proanthocyanidins are a kind of polyphenols and have a strong antioxidant action (Japanese Patent Laid-Open No. Sho 61-16982), and further improve blood lipids; antihypertensive effects; Effect of suppressing blood sugar level rise; Effect of restoring blood vessel elasticity
(血管保護効果) ; ビタミン Cの利用効率を高める効果;血液の流動性を改 善する効果などを有することが知られている。 (Anti-vascular effect); It is known to have an effect of increasing the utilization efficiency of vitamin C; and an effect of improving blood fluidity.
近年、 このようなプロアントシァニジンの種々の生理活性作用を有効利用 するために、 他の成分との組み合わせが検討され、 プロアントシァニジンの 生理活性作用の増強や他の疾病疾患に対する相乗的な効果が見出されている (特開 2003— 146 8 98号公報、 特開 2003— 9 596 5号公報、 特開 2002— 275076号公報、 特許第 2503107号明細書、 特開 平 5— 1 12441号公報、 特開平 1 1— 80009号公報および特開 20 02— 238497号公報) 。 し力 し、 このような作用のみならず、 プロア ントシァニジンが有する種々の生理活性作用をより高めることの可能な手段 が求められている。 In recent years, in order to effectively utilize various bioactive effects of such proanthocyanidins, combinations with other components have been studied, and the bioactive actions of proanthocyanidins are enhanced and synergistic with other diseases and diseases. Have been found (Japanese Patent Laid-Open No. 2003-146 8 98, Japanese Patent Laid-Open No. 2003-9596 5, JP-A-2002-275076, JP-A-2503107, JP-A-5-112441, JP-A-11-80009 and JP-A-2002-238497). However, there is a need for means capable of enhancing not only such actions but also various physiologically active actions of proanthocyanidins.
発明の開示 Disclosure of the invention
本発明は、 プロアントシァニジンが有する種々の生理活性作用をより高め ることができる新規な組成物を提供することを目的とする。  An object of the present invention is to provide a novel composition that can further enhance various physiologically active actions of proanthocyanidins.
本発明の組成物は、 プロアントシァニジンと 3, 4, 5—トリヒ ドロキシ フエ二ル基を有するカテキン類とを含有することを特徴とする。  The composition of the present invention is characterized by containing proanthocyanidins and catechins having a 3,4,5-trihydroxyphenyl group.
本発明の組成物は、 プロアントシァニジンと 3, 4, 5—トリヒ ドロキシ フェ二ル基を有するカテキン類とを含有する。  The composition of the present invention contains proanthocyanidins and catechins having a 3,4,5-trihydroxyphenyl group.
好ましい実施態様においては、 上記 3, 4, 5 _トリヒ ドロキシフエ二ノレ 基は、 ガロイル基である。  In a preferred embodiment, the 3, 4, 5_trihydroxyphenino group is a galloyl group.
上記のプロアントシァニジンと トリヒ ドロキシフエ二ル基を有する力テキ ン類とを含有する組成物を経口投与あるいは経皮投与することにより、 プロ アントシァニジンが有する血中の脂質改善効果、 脂質代謝改善効果、 血糖値 上昇抑制効果、 抗高血圧効果、 血流改善効果、 美肌効果などの生理活性を顕 著に増強することができる。 これらの効果は、 プロアントシァニジンおよび トリヒ ドロキシフエ二ル基を有するカテキン類それぞれ単独投与では得られ ない優れた効果である。 本発明の組成物は、 食品、 医薬品、 医薬部外品、 ィ匕 粧品などに効果的に利用され得る。 図面の簡単な説明  Oral or transdermal administration of a composition containing the above-mentioned proanthocyanidins and trihydroxenyl group-containing power textiles to improve the blood lipids and lipid metabolism of proanthocyanidins It can remarkably enhance physiological activities such as blood glucose level rise inhibitory effect, antihypertensive effect, blood flow improving effect, and skin beautifying effect. These effects are excellent effects that cannot be obtained by single administration of catechins having a proanthocyanidin and a trihydroxyphenyl group, respectively. The composition of the present invention can be effectively used for foods, pharmaceuticals, quasi drugs, cosmetics and the like. Brief Description of Drawings
図 1は、 ラットに松樹皮抽出物と トリヒ ドロキシフエ二ル基を有するカテ キン類とを含有する飼料、 松樹皮抽出物と トリヒ ドロキシフエ二ル基を有し ないカテキンを含有する飼料、 および松樹皮抽出物のみを含有する飼料をそ れぞれ 2 8日間摂取させた場合の、 血圧上昇率の推移を示すグラフである。 発明を実施するための最良の形態 Figure 1 shows a rat with a pine bark extract and a category with trihydroxyphenyl groups. Feeds containing quinine, pine bark extract and catechin not containing trihydroxyphenyl group, and feed containing only pine bark extract 2 It is a graph which shows transition of the blood pressure increase rate. BEST MODE FOR CARRYING OUT THE INVENTION
以下、 本発明の組成物について説明する。 なお、 以下に説明する構成は、 本発明を限定するものでなく、 本発明の趣旨の範囲内で種々改変することが できることは当業者に明らかである。  Hereinafter, the composition of the present invention will be described. The configurations described below are not intended to limit the present invention, and it will be apparent to those skilled in the art that various modifications can be made within the spirit of the present invention.
本発明の組成物は、 プロアントシァニジンと 3 , 4, 5 _トリヒ ドロキシ フヱ二ル基を有するカテキン類とを含有し、 必要に応じて、 その他の成分を 含有する。 以下、 各成分について説明する。  The composition of the present invention contains proanthocyanidins and catechins having a 3, 4, 5_trihydroxyphenyl group, and optionally contains other components. Hereinafter, each component will be described.
(プロアントシァニジン) (Proanthocyanidins)
本発明に用いられるプロアントシァニジンとしては、 重合度の低い縮重合 体が多く含まれるものが好適である。 重合度の低い縮重合体としては、 重合 度が 2〜 3 0の縮重合体 ( 2〜 3 0量体) が好ましく、 重合度が 2〜 1 0の 縮重合体 (2〜1 0量体) がより好ましく、 重合度が 2〜4の縮重合体 (2 〜4量体: O P C ) がさらに好ましい。 O P Cは、 特に強力な抗酸化物質で ある。 プロアントシァニジンは、 植物の葉、 樹皮、 果物の皮もしくは種の部 分に集中的に含まれている。 プロアントシァニジン、 特に O P Cは、 具体的 には、 松、 樫、 山挑などの植物の樹皮;ブドウ、 ブルーベリー、 イチゴ、 ァ ボガド、 ニセアカシア、 コケモモの果実もしくは種子;大麦;小麦;大豆; 黒大豆;カカオ;小豆; トチの実の殻; ピーナッツの薄皮;ィチヨゥ葉など に含まれている。 また、 西アフリカのコーラナッツ、 ペルーのラタニアの根. 日本の緑茶にも、 O P Cが含まれることが知られている。 O P Cは、 ヒ トの 体内では、 生成することのできない物質である。 特に、 O P C含有量が高いプロアントシァニジンまたは O P c含有量が高 いプロアントシァニジンを含む抽出物を用いると、 重合度の高いプロアント シァニジン (O P C含有量が少ないもの) を用いた場合と対比して、 優れた 脂質代謝改善効果、 抗高血圧効果、 血糖値上昇抑制効果などが得られる。 本発明の組成物に用いられるプロアントシァニジンとしては、 上記植物の 樹皮、 果実もしくは種子の粉砕物、 またはこれらの抽出物のような材料を使 用することができる。 これらの中で、 プロアントシァニジンを豊富に含有す る点で、 植物由来の抽出物を用いることが好ましく、 特に、 松樹皮由来の抽 出物を用いることが好ましい。 上記プロアントシァニジンを含む植物のうち、 松樹皮が O P Cを豊富に含むため、 プロアントシァニジンの原料として好ま しく用いられる。 上記抽出物は、 さらに、 夾雑物を除去したものが好ましい。 以下、 O P Cを豊富に含む松樹皮を原料植物として用いた例に挙げて、 プ 口アントシァニジンを主成分とする抽出物の調製方法を説明する。 As the proanthocyanidins used in the present invention, those containing a large amount of a condensation polymer having a low degree of polymerization are suitable. As the condensation polymer having a low degree of polymerization, a condensation polymer having a degree of polymerization of 2 to 30 (a 2 to 30 mer) is preferable, and a condensation polymer having a degree of polymerization of 2 to 10 (a 2 to 10 mer). ) Is more preferred, and a condensation polymer having a degree of polymerization of 2 to 4 (2 to 4 mer: OPC) is more preferred. OPC is a particularly powerful antioxidant. Proanthocyanidins are concentrated in plant leaves, bark, fruit peels or seeds. Proanthocyanidins, especially OPCs, are specifically the bark of plants such as pine, straw, and yamatake; grapes, blueberries, strawberries, avocados, false acacia, berries or seeds of barley; wheat; soybeans; black It is contained in soybeans, cacao, red beans, tochi nut shells, peanut skins, ichiyo leaves, etc. Also, West African cola nuts, Peruvian Latania roots. Japanese green tea is known to contain OPC. OPC is a substance that cannot be produced in the human body. In particular, when an extract containing proanthocyanidins with a high OPC content or proanthocyanidins with a high OPc content is used, proanthocyanidins with a high degree of polymerization (those with a low OPC content) are used. In contrast, excellent lipid metabolism improvement effect, antihypertensive effect, blood glucose level rise suppression effect, etc. are obtained. As the proanthocyanidins used in the composition of the present invention, materials such as the bark of the above-mentioned plant, pulverized fruits or seeds, or extracts thereof can be used. Among these, it is preferable to use an extract derived from a plant because it contains abundant proanthocyanidins, and it is particularly preferable to use an extract derived from pine bark. Among the plants containing proanthocyanidins, pine bark is rich in OPC, so it is preferably used as a raw material for proanthocyanidins. The extract is preferably one from which impurities have been removed. Hereinafter, an example of using pine bark rich in OPC as a raw material plant will be described as a method for preparing an extract containing puffer anthocyanidin as a main component.
松榭皮抽出物としては、 フランス海岸松 (Pinus Martima) 、 カラマツ、 クロマツ、 ァカマツ、 ヒメコマツ、 ゴヨウマツ、 チョウセンマツ、 ハイマツ、 リュウキユウマツ、 ゥックシマツ、 ダイォゥマツ、 シロマツ、 カナダのケべ ック地方のァネダなどのマツ目に属する植物の樹皮の抽出物が好ましく用い られる。 中でも、 フランス海岸松 (Pinus Martima) の樹皮抽出物が好まし い。  Pinus martima, larch, black pine, waka pine, Japanese pine, pine pine, Korean pine, high pine, Ryuyuki pine, Utsushima pine, Daiyu pine, white pine, Quebec in Canada An extract of a bark of a plant belonging to the order of pine is preferably used. Above all, the bark extract of French coastal pine (Pinus Martima) is preferred.
フランス海岸松は、 南仏の大西洋沿岸の一部に生育している海洋性松をい う。 このフランス海岸松の樹皮は、 プロアントシァニジン、 有機酸、 ならび にその他の生理活性成分などを含有し、 その主要成分であるプロアントシァ 二ジンに、 活性酸素を除去する強レ、抗酸化作用があることが知られている。 松樹皮抽出物は、 上記の松榭皮を水または有機溶媒で抽出して得られる。 水を用いる場合には、 温水または熱水を用いることが好ましい。 これらの水 には、 抽出効率を向上させる点から、 塩化ナトリウムなどの塩を添加するこ とが好ましい。 抽出に用いる有機溶媒としては、 食品あるいは薬剤の製造に 許容される有機溶媒が用いられ、 例えば、 メタノール、 エタノール、 1ープ ロパノール、 2—プロパノーノレ、 1ーブタノール、 2—ブタノール、 ァセト ン、 へキサン、 シクロへキサン、 プロピレングリコーノレ、 含水エタノール、 含水プロピレングリコール、 メチルェチルケトン、 グリセリン、 酢酸メチル、 酢酸ェチル、 ジェチルエーテル、 ジクロロメタン、 食用油脂、 1 , 1 , 1 , 2—テトラフルォロェタン、 および 1 , 1 , 2—トリクロロェテンが挙げら れる。 これらの水および有機溶媒は単独で用いてもよいし、 組合わせて用い てもよレ、。 特に、 水、 熱水、 エタノール、 含水エタノール、 および含水プロ ピレンダリコールが好ましく、 食品、 医薬品に用いるときの安全性の観点か ら、 水、 熱水、 エタノール、 および含水エタノールがより好ましい。 French coastal pine is a marine pine that grows on the Atlantic coast of southern France. This French coastal pine bark contains proanthocyanidins, organic acids, and other physiologically active ingredients. Proanthocyanidins, which are the main ingredients, have strong antioxidative effects to remove active oxygen. It is known that there is. The pine bark extract is obtained by extracting the above pine bark with water or an organic solvent. When water is used, it is preferable to use warm water or hot water. To improve the extraction efficiency, salt such as sodium chloride is added to these waters. And are preferred. As the organic solvent used for extraction, organic solvents that are acceptable for the production of foods or pharmaceuticals are used. For example, methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, 2-butanol, acetone, hexane , Cyclohexane, propylene glycol, water-containing ethanol, water-containing propylene glycol, methyl ethyl ketone, glycerin, methyl acetate, ethyl acetate, jetyl ether, dichloromethane, edible fats and oils, 1, 1, 1, 2-tetrafluoro And 1,1,1,2-trichloroethene. These water and organic solvents may be used alone or in combination. In particular, water, hot water, ethanol, water-containing ethanol, and water-containing propylene glycol are preferable, and water, hot water, ethanol, and water-containing ethanol are more preferable from the viewpoint of safety when used in foods and pharmaceuticals.
松樹皮からプロアントシァニジンを抽出する方法は、 特に限定されない。 例えば、 松樹皮の乾燥重量 1重量部に対して、 5 0〜 1 2 0 °C、 好ましくは 7 0〜 1 0 0 °Cの熱水を 1 〜 5 0重量部加えて抽出することによって、 生理 活性作用が高く、 水溶解性の高い松樹皮抽出物を得ることができる。 加温抽 出法、 超臨界流体抽出法などを用いてもよい。  The method for extracting proanthocyanidins from pine bark is not particularly limited. For example, by extracting 1 to 50 parts by weight of hot water of 50 to 120 ° C., preferably 70 to 100 ° C. with respect to 1 part by weight of pine bark dry, A pine bark extract having a high bioactivity and high water solubility can be obtained. A warm extraction method, a supercritical fluid extraction method, or the like may be used.
また、 ェントレーナー添加法による超臨界流体抽出を行ってもよい。 この 方法は、 超臨界流体に、 例えば、 エタノール、 プロパノール、 n—へキサン、 アセトン、 トルエン、 その他の脂肪族低級アルコール類、 脂肪族炭化水素類、 芳香族炭化水素類、 またはケトン類を 2〜 2 O WZV%程度添加し、 得られ た抽出流体で超臨界流体抽出を行うことによって、 O P C、 カテキン類 (後 述) などの目的とする抽出物の抽出溶媒に対する溶解度を飛躍的に上昇させ る、 あるいは分離の選択性を増強させる方法であり、 効率的に松樹皮抽出物 を得る方法である。  Alternatively, supercritical fluid extraction may be performed by an entrainer addition method. In this method, for example, ethanol, propanol, n-hexane, acetone, toluene, other aliphatic lower alcohols, aliphatic hydrocarbons, aromatic hydrocarbons, or ketones are added to a supercritical fluid. Add about 2 O WZV% and perform supercritical fluid extraction with the resulting extraction fluid to dramatically increase the solubility of the target extract, such as OPC and catechins (described later), in the extraction solvent. Alternatively, it is a method for enhancing the selectivity of separation, and a method for efficiently obtaining a pine bark extract.
松樹皮からの抽出は、 複数の抽出方法を組み合わせてもよレ、。 複数の抽出 方法を組み合わせることにより、 種々の組成の松樹皮抽出物を得ることが可 能となる。 For extraction from pine bark, you can combine several extraction methods. It is possible to obtain pine bark extracts with various compositions by combining multiple extraction methods. It becomes ability.
上記抽出により得られた松樹皮抽出物は、 プロアントシァニジン含有量を 増加させる目的で精製してもよい。 精製には、 通常、 酢酸ェチルなどの溶媒 が用いられるが、 食品、 医薬品としての安全性の面から、 溶媒を使用しない 方法、 例えば、 限外濾過、 あるいはダイヤイオン H P— 2 0、 セフアデック ス一 L H 2 0、 キチンなどの吸着性担体を用いたカラム法またはバッチ法に より精製することが好ましい。  The pine bark extract obtained by the above extraction may be purified for the purpose of increasing the content of proanthocyanidins. For purification, a solvent such as ethyl acetate is usually used, but from the viewpoint of safety as a food or pharmaceutical, a method that does not use a solvent, such as ultrafiltration or Diaion HP-2O, Sephadex It is preferable to purify by a column method or a batch method using an adsorbent carrier such as LH 20 or chitin.
本発明において、 プロアントシァニジンを主成分として含む松樹皮抽出物 は、 具体的には、 以下のような方法によりに調製されるが、 これは例示であ り、 この方法に限定されない。  In the present invention, the pine bark extract containing proanthocyanidin as a main component is specifically prepared by the following method, but this is an example and is not limited to this method.
フランス海岸松の樹皮 1 k gを、 塩化ナトリゥムの飽和溶液 3 Lに入れ、 1 0 0 °Cにて 3 0分間抽出し、 抽出液を得る (抽出工程) 。 その後、 抽出液 を濾過し、 得られる不溶物を塩化ナトリゥムの飽和溶液 5 0 O m Lで洗浄し、 洗浄液を得る (洗浄工程) 。 この抽出液と洗浄液を合わせて、 松樹皮の粗抽 出液を得る。  1 kg of French coastal pine bark is placed in 3 L of saturated sodium chloride solution and extracted at 100 ° C for 30 minutes to obtain an extract (extraction process). Thereafter, the extract is filtered, and the resulting insoluble matter is washed with 50 O mL of a saturated solution of sodium chloride to obtain a washing solution (washing step). The extract and washing solution are combined to obtain a crude extract of pine bark.
次いで、 この粗抽出液に酢酸ェチル 2 5 O m Lを添加して分液し、 酢酸ェ チル層を回収する工程を 5回行う。 回収した酢酸ェチル溶液を合わせて、 無 水硫酸ナトリウム 2 0 0 gに直接添加して脱水する。 その後、 この酢酸ェチ ル溶液を濾過し、 濾液を元の 5分の 1量になるまで減圧濃縮する。 濃縮され た酢酸ェチル溶液を 2 Lのクロ口ホルムに注ぎ、 攪拌して得られる沈殿物を 濾過により回収する。 その後、 この沈殿物を酢酸ェチル 1 0 O m Lに溶解し た後、 再度 1 Lのクロ口ホルムに添加して沈殿させる操作を 2回繰り返す洗 浄工程を行う。 この方法により、 例えば、 O P Cを 2 0重量%以上含み、 力 つ力テキン類を 5重量%以上含有する、 約 5 gの松樹皮抽出物を得ることが できる。  Next, 25 mL of ethyl acetate is added to the crude extract and the phases are separated to recover the ethyl acetate layer 5 times. Combine the recovered ethyl acetate solution and add directly to 200 g of anhydrous sodium sulfate for dehydration. Then, the ethyl acetate solution is filtered, and the filtrate is concentrated under reduced pressure until the original volume is reduced to one-fifth. The concentrated ethyl acetate solution is poured into 2 L of chloroform and the precipitate obtained by stirring is collected by filtration. Then, after the precipitate is dissolved in 10 mL of ethyl acetate, the washing step is repeated twice, in which the precipitate is added again to 1 L of chloroform and precipitated. According to this method, for example, about 5 g of pine bark extract containing 20% by weight or more of OPC and 5% by weight or more of strong techins can be obtained.
上記松榭皮のような原料植物に由来する抽出物は、 4 0重量%以上のプロ アントシァニジンを含有することが好ましい。 さらに、 この原料植物由来の 抽出物中に O P Cを 2 0重量%以上含有することが好ましく、 3 0重量%以 上含有することがより好ましい。 このようにプロアントシァニジンを高い割 合で含有する原料として、 上述のように松樹皮抽出物が好ましく用いられる。 Extracts derived from raw material plants such as the above pine husks contain 40% by weight or more of pro It is preferable to contain anthocyanidin. Further, the extract derived from the raw material plant preferably contains 20% by weight or more of OPC, more preferably 30% by weight or more. As described above, a pine bark extract is preferably used as a raw material containing proanthocyanidins in a high proportion.
O P Cは、 抗酸化物質であるため、 ガン ·心臓病 ·脳血栓などの成人病の 危険率を低下する効果、 関節炎 ·ァトピー性皮膚炎 ·花粉症などのァレルギ 一体質の改善効果などを有する。 さらに、 口腔内のバクテリア増殖を抑制し てプラーク (歯こう) を減少させる効果;血管の弾力性を回復させる効果; 血液中でのリポタンパク質が活性酸素によりダメージを受けるのを防止して、 損傷したリポタンパク質が血管の内壁に凝集し、 コレステロールが付着する ことを防止する効果;活性酸素によって分解されたビタミン Eを再生させる 効果; ビタミン Eの増強剤としての効果なども有する。  Since OPC is an antioxidant, it has the effect of reducing the risk rate of adult diseases such as cancer, heart disease, and cerebral thrombosis, and has the effect of improving the allergy in nature such as arthritis, atopic dermatitis, and hay fever. In addition, it suppresses bacterial growth in the oral cavity and reduces plaque (dental glands); restores the elasticity of blood vessels; prevents lipoproteins in the blood from being damaged by active oxygen; It also has the effect of preventing cholesterol from adhering to the inner wall of blood vessels and adhering cholesterol; the effect of regenerating vitamin E decomposed by active oxygen; and the effect of enhancing vitamin E.
( 3, 4, 5—トリヒ ドロキシフエ二ル基を有するカテキン類) (Catechin having 3, 4, 5-trihydroxyphenyl group)
本発明の組成物は、 3 , 4 , 5—トリヒ ドロキシフエ二ル基を有するカテ キン類 (以下、 T H Pカテキン類という場合がある) を含有する。 カテキン 類とは、 ポリヒ ドロキシフラバン一 3—オールの総称であり、 (+ ) —力テ キン (狭義のカテキンといわれる) 、 ガロカテキン、 ァフゼレキン、 (+ ) 一力テキンの 3—ガロイル誘導体、 およぴガロカテキンの 3—ガロイル誘導 体などが一般的である。  The composition of the present invention contains catechins having a 3,4,5-trihydroxyphenyl group (hereinafter sometimes referred to as THP catechins). Catechin is a generic name for polyhydroxyflavan 1-ol, (+) — force techin (referred to as catechin in a narrow sense), gallocatechin, afuzerekin, (+) 3-galloyl derivative of The 3-galloyl derivative of yopi gallocatechin is common.
T H Pカテキン類としては、 (+ ) —ガロカテキン、 (一) 一ェピガロカ テキン、 力テキンガレート、 ェピカテキンガレート、 ガロカテキンガレート、 ェピガロカテキンガレートなどが挙げられる。 これらの T H Pカテキン類の 中でも、 トリヒ ドロキシフエニル基がガロイル基であるカテキン類が好まし い。 このようなガロイル基を有するカテキン類としては、 力テキンガレート、 ェピカテキンガレート、 ガロカテキンガレート、 ェピガロカテキンガレート などが挙げられる。 Examples of THP catechins include (+)-gallocatechin, (1) one-epigalocatechin, force-techin gallate, epicatechin gallate, gallocatechin gallate, and epigallocatechin gallate. Of these THP catechins, catechins in which the trihydroxyphenyl group is a galloyl group are preferred. Such catechins having a galloyl group include force techin gallate, epicatechin gallate, gallocatechin gallate, and epigallocatechin gallate. Etc.
THPカテキン類は、 例えば、 ツバキ科の植物 (例えば、 緑茶、 紅茶、 ゥ 一ロン茶などの茶葉) 、 麻黄などの植物体に含有される。 これらの植物ある いはその粉碎物または抽出物を THPカテキン類として用いてもよい。 好ま しくはツバキ科の植物、 あるいはその粉砕物またはその抽出物である。 例え ば、 緑茶の葉には、 約 10〜1 5%のカテキンが含有されており、 このカテ キンのうち、 約 80%以上が THPカテキン類であり、 約 50%以上が TH Pカテキン類の 1つであるガロイル基を有するカテキン類であるため、 好適 である。  THP catechins are contained in plants such as camellias (for example, tea leaves such as green tea, black tea, and ulong tea) and mao. These plants or their meals or extracts may be used as THP catechins. Preferably, it is a camellia plant, or a pulverized product thereof or an extract thereof. For example, green tea leaves contain about 10-15% catechins, of which about 80% or more are THP catechins and about 50% or more are TH P catechins. Since it is a catechin having one galloyl group, it is preferable.
THPカテキン類は、 プロアントシァニジンと相俟って、 プロアントシァ 二ジンが有する種々の生理活性作用を顕著に増強することができる。 このよ うに、 THPカテキン類が、 プロアントシァニジンの複数の生理活性作用を 効率よく増強する材料であることは、 発明者らにより初めて見出された。 特 に、 ガロイル基を有するカテキン類は、 高い抗酸化活性だけでなく、 血糖値 上昇抑制作用、 抗高血圧作用、 抗髙脂血症等にも優れた効果を有することか ら、 プロアントシァニジンが有する種々の生理活性作用をさらに顕著に増強 することができる。  THP catechins, together with proanthocyanidins, can remarkably enhance various bioactive effects of proanthocyanidins. Thus, the inventors found for the first time that THP catechins are materials that efficiently enhance the multiple bioactive effects of proanthocyanidins. In particular, catechins having a galloyl group not only have high antioxidant activity, but also have excellent effects such as an inhibitory effect on blood glucose level increase, antihypertensive effect, anti-lipaemia, and the like, so proanthocyanidins It is possible to remarkably enhance various physiologically active actions possessed by.
THPカテキン類は、 その他、 発癌抑制作用、 動脈硬化予防作用、 脂肪代 謝異常の抑制作用、 血圧上昇抑制作用、 血小板凝集抑制作用、 抗アレルギー 作用、 抗ウィルス作用、 抗菌作用、 虫歯予防作用、 口臭防止作用、 腸内細菌 叢正常化作用、 活性酸素やフリーラジカルの消去作用、 抗酸化作用などがあ ることが知られている。  THP catechins are other anti-carcinogenic effects, arteriosclerosis-preventing effects, fat-metabolism-suppressing effects, blood pressure rise-inhibiting effects, platelet aggregation-inhibiting effects, anti-allergic effects, anti-viral effects, anti-bacterial effects, caries-preventing effects, bad breath It is known to have an inhibitory action, an intestinal microbiota normalizing action, an active oxygen and free radical scavenging action, and an antioxidant action.
(その他の成分) (Other ingredients)
本発明の組成物は、 上記プロアントシァニジンと THPカテキン類とを含 み、 必要に応じて、 種々の成分を含有し得る。 例えば、 通常の食品や医薬品 として添加し得る成分 (賦形剤、 増量剤、 結合剤、 増粘剤、 乳化剤、 着色料、 香料、 栄養成分、 食品添加物など) ;および化粧品、 医薬部外品などの皮膚 外用剤として通常用いられる成分 (美白剤、 保湿剤、 酸化防止剤、 紫外線吸 収剤、 紫外線散乱剤、 防腐剤、 香料、 ゲル化剤、 高分子ポリマー、 油性成分、 界面活性剤、 増粘剤、 アルコール類、 粉末成分、 色剤、 水性成分、 各種皮膚 栄養剤など) が挙げられる。 The composition of the present invention contains the above-mentioned proanthocyanidins and THP catechins, and may contain various components as necessary. For example, normal food and medicine Ingredients that can be added as excipients (excipients, extenders, binders, thickeners, emulsifiers, colorants, fragrances, nutritional ingredients, food additives, etc.); and usually as external preparations for skin of cosmetics, quasi drugs Ingredients used (whitening agent, moisturizer, antioxidant, UV absorber, UV scattering agent, antiseptic, fragrance, gelling agent, polymer, oil component, surfactant, thickener, alcohol, Powder components, colorants, aqueous components, various skin nutrients, etc.).
栄養成分としては、 例えば、 ァスコルビン酸、 トコフエロール、 リボフラ ビン、 ]3 -カロテン、 葉酸、 ピオチンなどのビタミン類; カルシウム、 マグ ネシゥム、 セレン、 鉄などのミネラル類; タウリン、 ニンニクなどに含まれ る含硫化合物;ヘスペリジン、 ケルセチンなどのフラバノィ ド類ゃフラボノ イ ド類;難消化性デキストリン、 アルギン酸、 キチン、 キトサン、 グァーガ ムなどの食物繊維;大豆蛋白、 コラーゲンなどのタンパク質;ペプチド;ァ ミノ酸;乳脂肪、 ラード、 牛脂、 魚油などの動物性油脂;大豆油、 菜種油な どの植物性油脂;オレンジ、 レモン、 グレープフルーツ、 いちごなどの果実 およびその果汁; ローヤルゼリー、 プロポリスなどが挙げられる。 食品添カロ 物としては、 はちみつ、 還元麦芽糖、 乳糖、 糖アルコール、 液糖、 調味料な どが挙げられる。  Nutritional components include, for example, ascorbic acid, tocopherol, riboflavin, vitamins such as 3 -carotene, folic acid, and piotin; minerals such as calcium, magnesium, selenium, iron; included in taurine, garlic, etc. Sulfur compounds; Flavanoids such as hesperidin and quercetin; Flavonoids; Dietary fibers such as indigestible dextrin, alginic acid, chitin, chitosan and guagam; Proteins such as soy protein and collagen; Peptides; Amino acids; Milk Animal fats such as fat, lard, beef tallow and fish oil; vegetable oils such as soybean oil and rapeseed oil; fruits such as orange, lemon, grapefruit and strawberry and their juices; royal jelly and propolis. Examples of food-added calories include honey, reduced maltose, lactose, sugar alcohol, liquid sugar, and seasonings.
(プロアントシァニジン含有組成物) (Proanthocyanidin-containing composition)
本発明の組成物は、 上述のように、 プロアントシァニジンと T H P力テキ ン類とを含有し、 必要に応じて、 その他の成分を含有する。 プロアントシァ 二ジンおよび T H Pカテキン類は、 上述のように、 単離された化合物、 それ らを含む食品材料、 およびその食品材料の抽出物のいずれでもよい。 例えば、 プロアントシァニジンを含有する植物抽出物に T H P力テキン類を含有する 植物抽出物を加える。 具体的には、 松樹皮、 桂皮などのようにプロアントシ ァニジンを含有し、 さらに含有されるカテキン類のほとんどがトリヒ ドロキ シフエ二ル基を有しないカテキン類である植物の抽出物に、 THPカテキン 類を含む植物抽出物を加える。 植物抽出物が、 プロアントシァニジンおよび THPカテキン類の両者を含む場合は、 目的に応じて、 必要とされる成分 (例えば、 プロアントシァニジンを多量に含有する松樹皮抽出物) を加える ことによって、 組成物中の各成分の量比が適宜調整され得る。 As described above, the composition of the present invention contains proanthocyanidins and THP strength textiles and, if necessary, other ingredients. As described above, proanthocyanidins and THP catechins may be any of isolated compounds, food materials containing them, and extracts of the food materials. For example, a plant extract containing THP strength is added to a plant extract containing proanthocyanidins. Specifically, it contains proanthocyanidins such as pine bark and cinnamon bark, and most of the catechins contained are trihydroxide. A plant extract containing THP catechins is added to a plant extract that is a catechin that does not have a siphenyl group. If the plant extract contains both proanthocyanidins and THP catechins, add necessary ingredients (for example, pine bark extract containing a large amount of proanthocyanidins) depending on the purpose. The amount ratio of each component in the composition can be adjusted as appropriate.
本発明の組成物中のプロアントシァニジンと THPカテキン類との含有割 合は、 任意である。 好ましくは、 プロアントシァニジン 100重量部に対し て、 上記 THP力テキン類を 1重量部〜 5000重量部、 より好ましくは 3 重量部〜 2000重量部、 さらに好ましくは 10重量部〜 1000重量部、 最も好ましくは 50重量部〜 500重量部の割合で含有し得る。  The content ratio of proanthocyanidins and THP catechins in the composition of the present invention is arbitrary. Preferably, with respect to 100 parts by weight of proanthocyanidins, the above-mentioned THP strength techins are 1 part by weight to 5000 parts by weight, more preferably 3 parts by weight to 2000 parts by weight, still more preferably 10 parts by weight to 1000 parts by weight, Most preferably, it can be contained in a proportion of 50 to 500 parts by weight.
本発明の組成物中のプロアントシァニジンの含有量に特に制限はない。 好 ましくは、 成人 1日あたりの摂取量が、 プロアントシァニジンとして 1〜1 000mg、 より好ましくは 2〜500mgとなるように含有することが好 ましい。 経皮投与の場合は、 局所的な投与となるため、 所定濃度であること が好ましく、 具体的には、 プロアントシァニジンが、 組成物中に、 好ましく は 0. 00001重量%〜20重量%、 より好ましくは 0. 0001重量% 〜10重量%、 さらに好ましくは 0. 001重量%〜10重量%、 最も好ま しくは 0. 01重量%〜 10重量%の割合で含有され得る。  There is no restriction | limiting in particular in content of proanthocyanidin in the composition of this invention. Preferably, it is preferably contained so that the daily intake per adult is 1 to 1000 mg, more preferably 2 to 500 mg as proanthocyanidins. In the case of transdermal administration, since it is a topical administration, it is preferable to have a predetermined concentration. Specifically, proanthocyanidins are preferably contained in the composition in an amount of preferably 0.0001% to 20% by weight. More preferably, it may be contained in a proportion of 0.0001% to 10% by weight, more preferably 0.001% to 10% by weight, and most preferably 0.01% to 10% by weight.
本発明の組成物中の THPカテキン類の含有量に特に制限はない。 好まし くは成人 1 日あたりの摂取量が、 10mg〜: I 0000mg、 より好ましく は 20mg〜500 Omgとなるように含有することが好ましい。 経皮投与 の場合は、 プロアントシァニジンと同様に局所的な投与となるため、 所定濃 度であることが好ましく、 具体的には、 THPカテキン類が、 組成物中に、 好ましくは 0. 00001重量%〜20重量%、 より好ましくは 0. 000 1重量%〜20重量%、 さらに好ましくは 0. 001重量%〜20重量%、 最も好ましくは 0. 01重量%〜20重量%の割合で含有され得る。 本発明の組成物は、 目的に応じて、 例えば、 食品、 医薬品、 医薬部外品、 化粧品などとして、 各種の形態に調製することができる。 There is no restriction | limiting in particular in content of THP catechin in the composition of this invention. It is preferable that the daily intake for adults is 10 mg to: I 0000 mg, more preferably 20 mg to 500 Omg. In the case of transdermal administration, as with proanthocyanidins, since it is a topical administration, it is preferable to have a predetermined concentration.Specifically, THP catechins are preferably 0. 00001 wt% to 20 wt%, more preferably 0.001 wt% to 20 wt%, more preferably 0.001 wt% to 20 wt%, most preferably 0.01 wt% to 20 wt% May be contained. The composition of the present invention can be prepared in various forms depending on the purpose, for example, as a food, a pharmaceutical, a quasi-drug, or a cosmetic.
上述の用途のうち、 本発明の組成物を食品、 医薬品、 医薬部外品などとし て経口摂取 (投与) する場合、 その形態に特に制限はない。 例えば、 ハード カプセル、 ソフトカプセルなどのカプセル剤、 錠剤、 丸剤、 粉末 (散剤) 、 顆粒、 ティーバッグ、 飴状の粘稠な液体、 液体、 ペーストなどの当業者が通 常用いる形態で利用される。 これらは、 形状または好みに応じて、 そのまま 摂取してもよく、 あるいは水、 湯、 牛乳などに溶いて飲んでもよく、 成分を 浸出させたものを摂取してもよい。  Among the above-mentioned uses, when the composition of the present invention is orally ingested (administered) as food, pharmaceuticals, quasi drugs, etc., there is no particular limitation on the form. For example, capsules such as hard capsules and soft capsules, tablets, pills, powder (powder), granules, tea bags, bowl-like viscous liquids, liquids, pastes, etc. are used in a form commonly used by those skilled in the art. . Depending on the shape or preference, these may be taken as they are, or may be taken by dissolving in water, hot water, milk, etc., or may be taken after leaching the ingredients.
本発明の組成物を医薬部外品、 化粧品などとして皮膚に塗布する場合にも、 これらの形態に特に制限はなく、 軟膏剤、 クリーム剤、 乳液、 ローション、 パック、 湿布剤、 浴用剤などの従来皮膚外用剤に用いられる形態であればい ずれでもよい。 実施例  Even when the composition of the present invention is applied to the skin as a quasi-drug, cosmetic, etc., these forms are not particularly limited, such as ointments, creams, emulsions, lotions, packs, poultices, bath preparations, etc. Any form can be used as long as it is conventionally used for an external preparation for skin. Example
以下に実施例を挙げて本発明を説明するが、 本発明がこの実施例により制 限されないことはいうまでもない。  Hereinafter, the present invention will be described with reference to examples, but it goes without saying that the present invention is not limited to the examples.
本実施例においては、 プロアントシァニジンを含む材料としてプロアント シァニジンを 4 0重量% (O P Cとして材料中 2 0重量%含有) 含有する松 榭皮抽出物 (商品名 : フラバンジ ノール、 東洋新薬株式会社) を用いた。 T H Pカテキン類としては、 カテキンを 8 0重量0 /0含有し、 このうちガロイ ル基を有する力テキン類を 6 0重量%以上含有する緑茶由来の抽出物 (商品 名 :ポリフエノン 7 0 S、 東京フードテクノ株式会社) およびェピガロカテ キンガレートを 9 3重量%含有する緑茶由来の抽出物 (商品名 :テアビゴ、 ロシュ ' ビタミン 'ジャパン株式会社) を用いた。 ここで、 上記 「ポリフエ ノン 7 0 S」 を、 T H P力テキン類を 4 8重量%以上含有することから、 「茶カテキン 48」 といい、 「テアビコ」 は、 THP力テキン類を 93重 量0 /0以上含有することから、 「茶カテキン 93」 とレ、うことにする。 トリヒ ドロキシフエ二ル基を有しないカテキン類としてカテキン (シグマ アルド リツチ ジャパン) を用いた。 In this example, pine husk extract containing 40% by weight of proanthocyanidins as a material containing proanthocyanidins (containing 20% by weight of OPC in the material) (trade name: Flavandinol, Toyo Shinyaku Co., Ltd.) ) Was used. The THP catechins, catechin 8 0 weight 0/0 containing green tea-derived extract (trade name, containing these forces catechins having Garoi Le group 6 0 wt% or more: Porifuenon 7 0 S, Tokyo Food Techno Co., Ltd.) and an extract derived from green tea containing 93% by weight of Epigalocatechin Gallate (trade names: Theavigo, Roche “Vitamin” Japan Co., Ltd.) were used. Here, since the above-mentioned “polyphenone 70 S” contains 48% by weight or more of THP-powered tekins, Referred to as the "tea catechin 48", "Teabiko" is, the THP force catechins from that it contains 93 by weight 0/0 or more, Les as "tea catechin 93", to Ukoto. Catechin (Sigma Aldrich Japan) was used as a catechin having no trihydroxyphenyl group.
(実施例 1 ) (Example 1)
次の材料を混合し、 精製飼料を調製した: コーンスターチ 29. 49重 量0 /0、 ミルクカゼイン 20重量%、 アルフアルファミール 10重量0 /0、 - ポテトスターチ 10重量0 /0、 セルロースパウダー 10重量0 /0、 シユークロー ス 10重量0 /0、 大豆油 6重量0 /0、 ミネラル混合物 (Α Ι Ν— 76) 3. 5重 量0 /0、 ビタミン混合物 (Α Ι Ν— 76) 1重量0 /0、 およびァスコルビン酸 0. 01重量%。 松榭皮抽出物が全体の 1. 0重量%および茶カテキン 48が全 体の 0. 5重量%となるように、 これらを精製飼料に混合し、 成形して固形 飼料を調製した (飼料 1とする) 。 By mixing the following materials were prepared purified diet: corn starch 29.49 by weight 0/0, milk casein 20 wt%, Alf alpha meal 10 weight 0/0, - potato starch 10 weight 0/0, cellulose powder 10 weight 0/0, Shiyukuro scan 10 weight 0/0, soybean 6 wt 0/0, mineral mixture (Α Ι Ν- 76) 3. 5 by weight 0/0, vitamin mixture (Α Ι Ν- 76) 1 wt 0/0, and Asukorubin acid 0.01 wt%. These were mixed with refined feed so that the pine peel extract was 1.0% by weight and tea catechin 48 was 0.5% by weight. And).
(実施例 2) (Example 2)
茶カテキン 48の代わりに、 茶カテキン 93を用いたこと以外は、 実施例 1と同様にして、 固形飼料を調製した (飼料 2とする) 。 (比較例 1 )  A solid feed was prepared in the same manner as in Example 1 except that tea catechin 93 was used instead of tea catechin 48 (referred to as feed 2). (Comparative Example 1)
茶カテキン 48の代わりに、 カテキンを用いたこと以外は、 実施例 1と同 様にして、 固形飼料を調製した (飼料 3とする) 。  A solid feed was prepared in the same manner as in Example 1 except that catechin was used instead of tea catechin 48 (referred to as feed 3).
(比較例 2) (Comparative Example 2)
茶カテキン 48を混合しなかったこと以外は、 実施例 1と同様にして、 固 形飼料を調製した (飼料 4とする) 。 (比較例 3) A solid feed was prepared in the same manner as in Example 1 except that tea catechin 48 was not mixed (referred to as feed 4). (Comparative Example 3)
松樹皮抽出物を混合しなかったこと以外は、 実施例 1と同様にして、 固形 飼料を調製した (飼料 5とする) 。  A solid feed was prepared in the same manner as in Example 1 except that the pine bark extract was not mixed (referred to as feed 5).
(実施例 3 :血中の脂質改善効果および脂質代 改善効果) (Example 3: Blood lipid improving effect and lipid cost improving effect)
3週齢の雄性モルモッ ト (日本エスエルシー株式会社) に市販の固形飼料 (RC4、 オリエンタル酵母株式会社) を一週間与えて馴化させた。 このモ ルモットを総無作為化法により一群 7匹ずつわけた。 各群のモルモットに上 記飼料 1〜 5をそれぞれ 28日間自由摂取させた。 さらに、 対照群として精 製飼料を自由摂取した群を設けた。 摂取期間終了後、 各群のモルモッ トの血 中の総コレステロ一ノレ値、 LDLコレステロール値、 HDLコレステロール 値、 およびトリグリセリ ドの濃度を測定した。 結果を表 1に示す。 なお、 測 定方法は以下のとおりである。  Three-week-old male guinea pigs (Japan SLC Co., Ltd.) were given a commercial solid feed (RC4, Oriental Yeast Co., Ltd.) for one week to acclimate. The guinea pigs were divided into groups of 7 by a total randomization method. Each group of guinea pigs was allowed free intake of the above feeds 1-5 for 28 days. Furthermore, as a control group, a group that freely ingested purified feed was established. After the intake period, the total cholesterol level, LDL cholesterol level, HDL cholesterol level, and triglyceride level in the blood of each group of guinea pigs were measured. The results are shown in Table 1. The measurement method is as follows.
総コレステロール (mgZd L) は、 「セロテック」 TCHO— L (株式 会社セロテック製) を用いて、 酵素法により測定した。  Total cholesterol (mgZd L) was measured by enzymatic method using “Serotech” TCHO-L (manufactured by Serotech Co., Ltd.).
LDLコレステロール (mgZd L) は、 コレステスト LDL (第一化学 薬品株式会社製) を用いて、 酵素法により測定した。  LDL cholesterol (mgZd L) was measured by an enzyme method using Cholestest LDL (Daiichi Chemical Co., Ltd.).
HDLコレステロール (mg/d L) は、 コレステス ト HDL (第一化学 薬品株式会社製) を用いて、 酵素法により測定した。  HDL cholesterol (mg / d L) was measured by enzymatic method using Choleest HDL (Daiichi Chemical Co., Ltd.).
トリグリセリ ド (mgZd L) は、 「セロテック」 TG—L (株式会社セ 口テック製) を用いて、 酵素法により測定した。 表 1 Triglyceride (mgZd L) was measured by an enzymatic method using “Cellotech” TG-L (manufactured by Seguchi Tech Co., Ltd.). table 1
Figure imgf000015_0001
Figure imgf000015_0001
平均値土標準偏差  Average soil standard deviation
表 1の結果から、 実施例の松樹皮抽出物と ΤΗΡカテキン類とを含有する 飼料 (飼料 1および 2) を摂取した群は、 比較例の松樹皮抽出物とトリヒ ド ロキシフエニル基 (ΤΗΡ基) を有しないカテキンを含む飼料 (飼料 3) 、 あるいは松樹皮抽出物および T HPカテキン類のいずれか一方のみを含む飼 料 (飼料 4および 5) を摂取した群に比べて、 血中総コレステロール、 およ びトリグリセリ ドの含有量が低いことがわかる。 さらに、 コレステロールの うち、 善玉といわれる HDLコレステロールの血中濃度が高いことがわかる。 これらのことは、 プロアントシァニジンと THPカテキン類とを含有する組 成物が、 それぞれ単独で摂取した場合には得られない優れた血中脂質改善効 果および脂質代謝改善効果を有することを示す。 From the results in Table 1, the group that ingested the feed (feeds 1 and 2) containing the pine bark extract of the example and the coconut catechins showed that the pine bark extract of the comparative example and the trihydroxyphenyl group (ΤΗΡ group) Compared with the group ingesting feed containing catechins without feed (feed 3), or feed containing only one of pine bark extract and THP catechins (feeds 4 and 5), It can also be seen that the triglyceride content is low. Furthermore, it can be seen that among cholesterol, the blood concentration of HDL cholesterol, which is said to be good, is high. These facts indicate that the composition containing proanthocyanidins and THP catechins has excellent blood lipid improvement effects and lipid metabolism improvement effects that cannot be obtained when taken alone. Show.
(実施例 4) (Example 4)
松樹皮抽出物が全体の 0. 5重量%および茶カテキン 48が全体の 0. 5 重量%となるように、 基本飼料 (MF飼料、 オリエンタル酵母株式会社) に 混合し、 成形して固形飼料を調製した (飼料 6とする) 。 (比較例 4 ) Mix with basic feed (MF feed, Oriental Yeast Co., Ltd.) so that pine bark extract is 0.5% by weight and tea catechin 48 is 0.5% by weight. Prepared (referred to as feed 6). (Comparative Example 4)
茶カテキン 4 8の代わりに、 カテキンを用いたこと以外は、 実施例 4と同 様にして、 固形飼料を調製した (飼料 7とする) 。  A solid feed was prepared in the same manner as in Example 4 except that catechin was used instead of tea catechin 48 (referred to as feed 7).
(比較例 5 ) (Comparative Example 5)
茶カテキン 4 8を混合しなかったこと以外は、 実施例 4と同様にして、 固 形飼料を調製した (飼料 8とする) 。  A solid feed was prepared in the same manner as in Example 4 except that tea catechin 48 was not mixed (referred to as feed 8).
(実施例 5 :血糖値上昇抑制効果) (Example 5: blood glucose level increase suppressing effect)
1群 5匹の 4週齢の S D系ラット (日本エスエルシー株式会社) に上記飼 料 6〜 8をそれぞれ 2週間自由摂取させた。 さらに、 対照群として基本飼料 を自由摂取した群を設けた。 摂取期間終了後、 1 2時間絶食した。 その後、 各群のラットそれぞれに、 グルコースが 2 5 O m g / 1 0 0 g体重となるよ うに、 2 0重量%グルコース溶液を強制経口投与することによりグルコース 負荷試験を行った。 負荷試験直前の血糖値と負荷試験後 6 0分経過後の血糖 値を測定し、 血糖値上昇抑制効果を評価した。 結果を表 2に示す。 表 2  One group of 5 4-week-old SD rats (Japan SLC Co., Ltd.) were allowed to freely take the above feeds 6 to 8 for 2 weeks each. In addition, a group that freely ingested basic feed was established as a control group. After the intake period, I fasted for 12 hours. Thereafter, a glucose tolerance test was performed by forcibly administering a 20 wt% glucose solution to each group of rats so that the glucose was 25 O mg / 100 g body weight. The blood glucose level immediately before the load test and the blood glucose level 60 minutes after the load test were measured to evaluate the effect of suppressing the increase in blood glucose level. The results are shown in Table 2. Table 2
血糖値 (mg dL) Blood glucose level (mg dL)
ゲルコ-ス負荷試験前 ク'ルコ-ス負荷試験後 負荷試験前後の差 Before the gel course load test After the course test Before and after the load test
A B B-A 飼料 6 実施例 4 148 182 34 飼料 7 比較例 4 152 201 49 飼料 8 比較例 5 153 198 45 基本飼料 対照例 154 217 63 表 2の結果から、 実施例の松樹皮抽出物と THPカテキン類とを含有する 飼料 (飼料 6) を摂取した群は、 比較例の松樹皮抽出物と トリヒ ドロキシフ ェニル基 (THP.基) を有しないカテキンを含む飼料 (飼料 7) 、 あるいは 松樹皮抽出物のみを含む飼料 (飼料 8) を摂取した群に比べて、 血糖値の上 昇が抑制されていることがわかる。 AB BA feed 6 Example 4 148 182 34 Feed 7 Comparative example 4 152 201 49 Feed 8 Comparative example 5 153 198 45 Basic feed Control example 154 217 63 From the results shown in Table 2, the group that ingested the feed (feed 6) containing the pine bark extract of the example and the THP catechins had the pine bark extract of the comparative example and the trihydroxyphenyl group (THP. Group). It can be seen that the increase in blood glucose level is suppressed as compared with the group ingesting the feed containing catechin not contained (Feed 7) or the feed containing only the pine bark extract (Feed 8).
上記表 1および表 2の結果から、 松樹皮抽出物と T H Pカテキン類とを含 有する組成物は、 血中脂質改善効果および血糖値上昇抑制効果を有するため、 ダイエツトに対しても高レ、効果が得られるものと考えられる。  From the results in Table 1 and Table 2 above, the composition containing pine bark extract and THP catechins has an effect of improving blood lipids and suppressing an increase in blood glucose level. Is considered to be obtained.
(実施例 6 :抗高血圧効果) (Example 6: Antihypertensive effect)
4週齢の雄性の SHRラット (SHR等疾患モデル共同研究会) に基本飼 料と水とを 1週間与えて馴化させた。 このラットを各群の体重の平均 fitがほ ぼ均一となるように、 一群 7匹ずつわけた。 各群のラットに上記飼料 6〜 8 をそれぞれ 28日間自由摂取させた。 さらに、 対照群として基本飼料を自由 摂取した群を設けた。 なお、 摂取期間中、 Na C 1を 1重量%含有する飲水 を全群に自由摂取させた。  Four-week-old male SHR rats (SHR and other disease model joint study group) were acclimated with a basic diet and water for one week. The rats were divided into 7 groups, so that the average fit of each group was almost uniform. The rats in each group were allowed to freely take the above diets 6-8 for 28 days. In addition, a group with free intake of basic feed was established as a control group. During the intake period, all groups received free drinking water containing 1% by weight of NaC1.
飼料給餌開始日を 0日目として、 7、 14、 21、 および 28日目に、 各 群のラットの収縮期血圧を非観血式自動血圧計 (B P— 98A : ソフ ト口 ン) を用いて測定した。 給餌開始日の収縮期血圧に対する各給餌日数経過後 の収縮期血圧の上昇率を以下の式からそれぞれ算出した。 収縮期血圧の上昇 率の推移を図 1に示す。 収縮期血圧増加率 () = (給麵経過後の収縮期血圧) χΊ 00 Using the non-invasive automatic sphygmomanometer (BP-98A: soft mouth), the systolic blood pressure of the rats in each group was measured on days 7, 14, 21, and 28, starting on the day of feeding. Measured. The rate of increase in systolic blood pressure after the lapse of each feeding day relative to the systolic blood pressure on the feeding start day was calculated from the following equations. Figure 1 shows the change in the rate of increase in systolic blood pressure. Increase rate of systolic blood pressure ( % ) = (systolic blood pressure after feeding) χΊ 00
(給餌開始曰の収縮期血圧) 図 1の結果から、 実施例の松樹皮抽出物と ΤΗΡカテキン類とを含有する 飼料 (飼料 6) を摂取した群は、 比較例の松樹皮抽出物と トリヒ ドロキシフ ェニル基 (THP基) を有しないカテキンを含む飼料 (飼料 7) 、 あるいは 松樹皮抽出物のみを含む飼料 (飼料 8) を摂取した群に比べて、 血圧の上昇 を抑制していることがわかる。 このことは、 松樹皮抽出物と THPカテキン 類とを含有する糸且成物が、 高血圧症の予防 ·治療剤として有効であることを 示す。 (Systolic blood pressure of the feeding start cocoon) From the results of Fig. 1, the group ingested the diet (feed 6) containing the pine bark extract of the example and the coconut catechins, the pine bark extract of the comparative example and the chicken Droxif It can be seen that the increase in blood pressure was suppressed compared to the group that ingested the feed containing catechins that do not have an enyl group (THP group) (Feed 7) or the feed containing only pine bark extract (Feed 8). . This indicates that the yarn and composition containing pine bark extract and THP catechins is effective as a prophylactic / therapeutic agent for hypertension.
(実施例 7) (Example 7)
松樹皮抽出物、 茶カテキン 93、 および賦形剤を表 3に記載の割合 (重 量%) にて混合して錠剤 (1錠当たり、 約 200mg) を製造し、 これを食 ロロ 1とレブし。  Pine bark extract, tea catechin 93, and excipients are mixed in the proportions (weight%) shown in Table 3 to produce tablets (about 200 mg per tablet). Yes.
(比較例 6および 7) (Comparative Examples 6 and 7)
実施例 7と同様にして、 表 3に記載の成分を混合して錠剤 (1錠当たり、 約 200mg) をそれぞれ製造し、 これらを食品 2および 3とした。 表 3  In the same manner as in Example 7, the ingredients listed in Table 3 were mixed to produce tablets (about 200 mg per tablet). Table 3
Figure imgf000018_0001
Figure imgf000018_0001
単位は重量%  Unit is% by weight
* 1 THPカテキン類 93重量%以上含有  * 1 Contains 93% by weight or more of THP catechins
* 2···ΤΗΡカテキン類含有せず (実施例 8 :血流改善効果) * 2 ······· Does not contain catechins (Example 8: Blood flow improvement effect)
22〜63歳までの健常男女 24名 (男性 12名、 女性 12名) を被験者 とし、 性別を均等にする以外はランダムに 3群にわけた。 各群 8名の被験者 について、 まず、 食品摂取前に血流量を測定した。 次いで、 被験者に上記食 品 1〜3 (1錠当たり約 20 Omg) を 1日あたり 2錠の割合で水 10 Om Lと共に摂取させた。 この摂取を 28日間にわたって行い、 摂取期間終了後、 再度血流量を測定した。 血流量は、 右手の人差し指の皮下の部位を血流計 Twenty-four healthy men and women aged between 22 and 63 years old (12 men and 12 women) were the subjects, and they were randomly divided into three groups, except for equal gender. For 8 subjects in each group, blood flow was first measured before food intake. The subjects then took the above foods 1-3 (approximately 20 Omg per tablet) at a rate of 2 tablets per day with 10 OmL of water. This ingestion was carried out for 28 days, and after the ingestion period, blood flow was measured again. The blood flow is measured on the subcutaneous part of the index finger of the right hand.
(レーザー血流画像化装置 P IM II ; Swe d e n P e rm i e d社) を用いて測定した。 なお、 測定前の 3時間は飲食を避け、 安静にしてもらつ た。 結果を表 4に示す。 表 4の値は、 平均値士標準誤差であり、 数値が大き いほど、 血流量が多いことを示す。 表 4 (Laser blood flow imaging device PIM II; Swedish company). In addition, I avoided eating and drinking for 3 hours before the measurement and asked me to rest. The results are shown in Table 4. The values in Table 4 are average standard error. The larger the value, the greater the blood flow. Table 4
Figure imgf000019_0001
Figure imgf000019_0001
平均値土標準偏差  Average soil standard deviation
表 4の結果から、 実施例の松榭皮抽出物と ΤΗΡカテキン類とを含有する 食品 (食品 1) を摂取した群は、 比較例の松樹皮抽出物と トリヒ ドロキシフ ェニル基 (ΤΗΡ基) を有しないカテキンを含む食品 (食品 2) 、 あるいは 松樹皮抽出物のみを含む食品 (食品 3) を摂取した群に比べて、 血流量が大 きく増加していることがわかる。 このことは、 松樹皮抽出物と ΤΗΡ力テキ ン類とを含有する組成物が、 末梢組織における血流改善効果を有することを 示す , From the results in Table 4, the group that ingested the food (food 1) containing the pine husk extract of the example and the potato catechins had the pine bark extract of the comparative example and the trihydroxyphenyl group (ΤΗΡ). It can be seen that the blood flow is greatly increased compared to the group that ingested the food containing catechin (food 2) or the food containing only pine bark extract (food 3). This indicates that the composition containing pine bark extract and repulsive textiles has an effect of improving blood flow in peripheral tissues. ,
(実施例 9 ) (Example 9)
松榭皮抽出物、 茶カテキン 4 8、 アルコール、 グリセリン、 および 1, 3 ーブチレングリコールを表 5に記載の割合 (重量%) にて精製水に溶解させ、 化粧水を調製した。 これを化粧水 1とした。  Pine lotion extract, tea catechin 48, alcohol, glycerin, and 1,3-butylene glycol were dissolved in purified water in the proportions (% by weight) shown in Table 5 to prepare a lotion. This was named lotion 1.
(比較例 8および 9 ) (Comparative Examples 8 and 9)
実施例 9と同様にして、 表 5に記載の成分を混合して精製水に溶解させ、 化粧水を調製した。 これらを化粧水 2および 3とした。 表 5  In the same manner as in Example 9, the ingredients listed in Table 5 were mixed and dissolved in purified water to prepare a skin lotion. These were designated as lotions 2 and 3. Table 5
Figure imgf000020_0001
Figure imgf000020_0001
単位は重量%  Unit is% by weight
残部は精製水  The balance is purified water
* 1 " 'THPカテキン類 48重量%以上含有  * 1 "'THP catechins more than 48% by weight
(実施例 1 0 :美肌効果) (Example 10: Skin beautifying effect)
肌の荒れ (シミ、 シヮ、 およびクスミ) について悩みを持つ 1 8名の女性 を被験者としてランダムに 3群にわけた。 各群の被験者の肌の荒れについて 気になる個所に、 上記化粧水 1〜3 ( 2 m L ) を就寝前に 1日 1回の頻度で 塗布した。 この塗布を 2 8日間にわたって行った。 塗布期間終了後にシミ、 シヮ、 およびクスミについて改善効果があつたかどうかを自己評価してもら い、 各項目について明らかに改善効果があった人数をカウントした。 結果を 表 6に示す, 表 6 Randomly divided into 8 groups of 18 women who were worried about rough skin (stains, wrinkles, and kusumi). The above-mentioned lotion 1 to 3 (2 mL) was applied once a day before going to bed at a place where the skin of the subjects in each group was concerned. This application was performed for 28 days. At the end of the application period, we asked the self-assessment of whether there was an improvement effect on stains, stains, and kusumi, and counted the number of people who clearly had an improvement effect on each item. The result Table 6 shows, Table 6
Figure imgf000021_0001
Figure imgf000021_0001
表 6の結果から、 実施例の松樹皮抽出物と T H Pカテキン類とを含有する 化粧水 (化粧水 1 ) を塗布した群は、 比較例の松樹皮抽出物および T H P力 テキン類のいずれか一方のみを含有する化粧水 (化粧水 2および 3 ) を塗布 した群に比べて、 シヮ、 シミ、 およびクスミが改善されていることがわかる, このことは、 松榭皮抽出物と トリヒ ドロキシフヱ二ル基を有するカテキン類 とを含有する組成物が、 美肌効果を有することを示す。 産業上の利用可能性 From the results shown in Table 6, the group to which the skin lotion (lotion 1) containing the pine bark extract of the example and the THP catechins was applied was either one of the pine bark extract of the comparative example and the THP strength techin. It can be seen that skin wrinkles, spots, and kusumi are improved compared to the group to which the skin lotion containing only the skin lotion (skin lotions 2 and 3) is applied. This indicates that the pine peel extract and trihydroxif 2 It shows that a composition containing a catechin having a ru group has a beautifying effect. Industrial applicability
本発明の組成物は、 経口投与 (摂取) あるいは経皮投与 (塗布) すること により、 プロアントシァニジンが有する脂質代謝改善効果、 血中の脂質改善 効果、 血糖値上昇抑制効果、 抗高血圧効果、 血流改善効果、 美肌効果などの 生理活性作用を顕著に増強することができる。 これらの効果は、 プロアント シァニジンおよび T H P力テキン類をそれぞれ単独で投与した場合には得ら れない優れた効果である。 本発明の組成物は、 食品、 医薬品、 医薬部外品、 化粧品などに利用し得る。  The composition of the present invention can be administered orally (taken) or transdermally (applied) to improve the lipid metabolism of proanthocyanidins, improve blood lipids, suppress blood glucose elevation, and antihypertensive. Physiologically active effects such as blood flow improvement effect and skin beautifying effect can be remarkably enhanced. These effects are excellent effects that cannot be obtained when proanthocyanidins and THP strength techins are administered alone. The composition of the present invention can be used for foods, pharmaceuticals, quasi drugs, cosmetics and the like.

Claims

請求の範囲 The scope of the claims
1. プロアントシァニジンと 3, 4, 5—トリヒ ドロキシフエ二ル基を有す るカテキン類とを含有する、 組成物。 1. A composition containing proanthocyanidins and catechins having a 3, 4, 5-trihydroxyphenyl group.
2. 前記 3, 4, 5—トリヒ ドロキシフエニル基が、 ガロイル基である、 請 求項 1に記載の組成物。 2. The composition according to claim 1, wherein the 3,4,5-trihydroxyphenyl group is a galloyl group.
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Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2002275076A (en) * 2001-03-15 2002-09-25 Toyo Shinyaku:Kk Inhibitor of elevation of glycemia and healthy food
JP2003095965A (en) * 2001-09-27 2003-04-03 Toyo Shinyaku:Kk Hypertension-preventing and treating medicine
JP2003095964A (en) * 2001-09-21 2003-04-03 Toyo Shinyaku:Kk Anti-stress medicine
JP2003146898A (en) * 2001-11-09 2003-05-21 Toyo Shinyaku:Kk Hyperlipemia-improving agent
JP2003238428A (en) * 2002-02-18 2003-08-27 Toyo Shinyaku:Kk Cold-constitution curing agent and health food
WO2003090673A2 (en) * 2002-04-22 2003-11-06 Rtc Research & Development, Llc. Compositions and methods for promoting weight loss, thermogenesis, appetite suppression, lean muscle mass, increasing metabolism and boosting energy levels, and use as a dietary supplement in mammals
JP2004346132A (en) * 2003-05-20 2004-12-09 Toyo Shinyaku:Kk Flavan compound-containing composition

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2002275076A (en) * 2001-03-15 2002-09-25 Toyo Shinyaku:Kk Inhibitor of elevation of glycemia and healthy food
JP2003095964A (en) * 2001-09-21 2003-04-03 Toyo Shinyaku:Kk Anti-stress medicine
JP2003095965A (en) * 2001-09-27 2003-04-03 Toyo Shinyaku:Kk Hypertension-preventing and treating medicine
JP2003146898A (en) * 2001-11-09 2003-05-21 Toyo Shinyaku:Kk Hyperlipemia-improving agent
JP2003238428A (en) * 2002-02-18 2003-08-27 Toyo Shinyaku:Kk Cold-constitution curing agent and health food
WO2003090673A2 (en) * 2002-04-22 2003-11-06 Rtc Research & Development, Llc. Compositions and methods for promoting weight loss, thermogenesis, appetite suppression, lean muscle mass, increasing metabolism and boosting energy levels, and use as a dietary supplement in mammals
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