WO2014203362A1 - Ginsenoside composition - Google Patents

Ginsenoside composition Download PDF

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Publication number
WO2014203362A1
WO2014203362A1 PCT/JP2013/066895 JP2013066895W WO2014203362A1 WO 2014203362 A1 WO2014203362 A1 WO 2014203362A1 JP 2013066895 W JP2013066895 W JP 2013066895W WO 2014203362 A1 WO2014203362 A1 WO 2014203362A1
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Prior art keywords
ppt
ginsenoside
components
composition
ginseng
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PCT/JP2013/066895
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French (fr)
Japanese (ja)
Inventor
金 昌樹
慶光 金
昌康 長谷川
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金氏高麗人参株式会社
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Priority to PCT/JP2013/066895 priority Critical patent/WO2014203362A1/en
Priority to JP2015513908A priority patent/JPWO2014203362A1/en
Publication of WO2014203362A1 publication Critical patent/WO2014203362A1/en

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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A61K47/40Cyclodextrins; Derivatives thereof
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23LFOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/105Plant extracts, their artificial duplicates or their derivatives
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/56Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/575Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/70Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7028Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
    • A61K31/7034Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
    • A61K31/704Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/63Steroids; Derivatives thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/72Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
    • A61K8/73Polysaccharides
    • A61K8/738Cyclodextrins
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/20Pills, tablets, discs, rods
    • A61K9/2004Excipients; Inactive ingredients
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • A61P17/16Emollients or protectives, e.g. against radiation
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q5/00Preparations for care of the hair
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23VINDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00Food compositions, function of food ingredients or processes for food or foodstuffs
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/40Chemical, physico-chemical or functional or structural properties of particular ingredients
    • A61K2800/56Compounds, absorbed onto or entrapped into a solid carrier, e.g. encapsulated perfumes, inclusion compounds, sustained release forms
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/80Process related aspects concerning the preparation of the cosmetic composition or the storage or application thereof
    • A61K2800/92Oral administration

Definitions

  • the present invention is suitable for use in oral compositions (foods, nutritional supplements, health foods, functional foods, pharmaceuticals, etc.) and body-related parenteral compositions (cosmetics, hair restorers, bathing agents, etc.).
  • the present invention relates to a ginsenoside composition derived from useful ginseng.
  • CY is a diol-based ginsenoside commonly called “compound Y (compound Y)”, and its chemical name is “20-O- [ ⁇ -L-arabinopyranosyl (1 ⁇ 6) - ⁇ -D-glucopyranosyl] -20 (S) protopanaxadiol” It is.
  • CK is a diol-based ginsenoside commonly called “compound K (compound K)”, and its chemical name is “20-O- ⁇ -D-Glucopyranosyl-20 (S) -protopanaxadiol” And “20 (S) -protopanaxadiol-20-O- ⁇ -D-glucopyranoside” Also called. “CK” may also be referred to as “ginsenoside M1” or simply “M1”.
  • PPT Proteinaxatriol
  • M4 “PPT” is also referred to as “genuine saponigen” or “genuine aglycone”.
  • PPT is “20-O- ⁇ -D-glucopyranosyl-20 (S) prototopanaxatriol” commonly called “F1” which is a triol-based ginsenoside or “6-O- ⁇ ” commonly called Rh1.
  • -D-glucopyranosyl-20 (S) protopanaxatriol ” corresponds to a glucoside group removed.
  • Ginsenoside is roughly classified into a diol type, a triol type, and an oleanoic type. Among them, an important one is a diol type and a triol type. The former diol system is said to act on the calming of the central nerve, and the latter triol system is said to act on the excitation of the central nerve.
  • ginseng contains a lot of ginsenoside Rb1, a diol major ginsenoside, and ginsenoside Re, a triol major ginsenoside. Hard to be absorbed.
  • these major ginsenosides the sugar chains of major ginsenosides are degraded by ⁇ -glucosidase secreted by intestinal bacteria to become minor saponins (minor ginsenosides), which facilitates absorption into the body.
  • diol minor ginsenosides but ginsenoside CY and CK, which the present inventors have focused on, are also included in the category (diol type).
  • triol minor ginsenosides but protopanaxatriol (PPT), which is ginsenoside which the present inventors have focused on, is also included in the category (triol series).
  • ginsenoside CK ginsenoside CY, protopanaxatriol
  • raw ginseng eg ginseng
  • dried ginseng red ginseng steamed with ginseng and dried.
  • PPT PPT
  • these CK, CY, and PPT are produced only when carbohydrates are decomposed by human intestinal microorganisms.
  • the intestinal environment of humans varies, and it is said that there are not a few people who cannot decompose the sugar chain of ginsenoside, for example, 1 in 4 people.
  • Ginsenoside CY is a raw material for the above CK and is also a pharmacologically active ginsenoside. Triol ginsenoside has been reported to have anti-inflammatory and anti-allergic effects. However, most of them are reports on F1 and Rh1 (parts are different but both are PPTs with a glucoside group), and there are few references on PPT.
  • Patent Document 1 JP-A-9-176017 (Patent Document 1) discloses an anticancer drug containing Mc, CK, PPT, or CY as an active ingredient. However, this document has no description or suggestion of using any two or more of them together. In addition, there is no description or suggestion about how to use other than anticancer drugs. Note that the chemical name of “Mc” in Patent Document 1 is “20-O- [ ⁇ -L-arabinofuranosyl (1 ⁇ 6) - ⁇ -D-glucopyranosyl] -20 (S) proto”.
  • Patent Document 2 Claim 2 of Japanese Patent Application Laid-Open No. 2003-212776 (Patent No. 4549625) (Patent Document 2) shows finely-emulsified particles comprising a mixture of Compound K (ie CK), F1 and Compound Y (ie CY). . However, there is no description about PPT.
  • Patent Document 3 JP-T-2004-519224 (Patent No. 495547)
  • Patent Document 3 discloses a ginsenoside glucosidase in which the substrates are protopanaxadiol ginsenoside and protopanaxatriol ginsenoside, and the reaction product is CK, aglycone, or the like. It is shown.
  • Patent Document 4 Japanese Patent Application Laid-Open No. 2004-49154 (Patent No. 3678362) (Patent Document 4) describes fermented carrots obtained by fermenting ginseng with a specific strain, and “M1 (that is, CK)” and “ A method for producing fermented ginseng containing "M4 (ie PPT)" is shown. However, there is no description about CY.
  • Patent Document 5 Japanese Patent Laid-Open No. 10-99094 discloses a prototype in which Prevotella sp. S-1 strain is cultured in a medium supplemented with ginseng saponin to produce and accumulate Compound K (ie CK) and Compound Y (ie CY). A method for producing panaxadiol saponin metabolites is shown.
  • Patent Document 6 JP 2008-155998 discloses an anxiolytic antidepressant containing ginseng extract as an active ingredient, and the contents of M1 (CK) and M4 (PPT) There is also a description that the ratio (M1 / M4) is 1 or more (claim 6).
  • the use of this activator is a pharmaceutical composition, a food composition or a feed composition (Claim 7).
  • Patent Document 7 JP 2008-155999 discloses a GABAergic neuron activator containing ginseng extract as an active ingredient, and contains M1 (for CK) and M4 (for PPT). There is also a description that the quantity ratio (M1 / M4) is 1 or more (claim 6). The use of this activator is a pharmaceutical composition, a food composition or a feed composition (Claim 7).
  • Patent Document 8 Japanese Patent Application Laid-Open No. 2010-132625 discloses an antidiabetic agent having a content ratio (M1 / M4) of M1 (for CK) and M4 (for PPT) of 1 or more ( Claim 7).
  • Patent Documents 1 to 8 The ginsenoside components described in Patent Documents 1 to 8 described above are compared with the essential ginsenoside 3 components of the present invention as shown in the following Table 1 ( ⁇ is described and ⁇ is not described). As shown in Table 1, these Patent Documents 1 to 8 do not describe compositions containing all of the essential three components of the present invention (three components of CY, CK and PPT).
  • Patent Document 1 (Patent Document 1) -1- According to the claim of Patent Document 1, paragraphs 0003 to 0005, formulation example 1 of paragraph 0009, formulation example 2 of paragraph 0010, table 1 according to example 1, table 2 and table 3 according to example 2, and example 3
  • Patent Document 1 relates to an anticancer agent, and there is no description about the purpose or use other than the anticancer agent.
  • Patent Document 2 discloses that “CY (Compound Y)” and “CK (Compound K)” are used together, and further, these two components and “g-PPT” in which the 20 (S) site is an O-Glu group There is a description about the combined use. However, there is no description about using a substance containing three components “CY (Compound Y)”, “CK (Compound K)” and “PPT”.
  • Patent Document 3 Tables 1 to 6, Tables 8 to 9, and Table 12 of Patent Document 3 describe that reaction products containing CK, F2, aglycone, and the like can be obtained by enzymatic hydrolysis, as in the present invention. There is no description about obtaining what contains the three components “CY, CK and PPT”. Incidentally, F2 is a precursor of “CK”.
  • Patent Documents 4 to 8 show ginsenoside compositions containing “CY and CK” or ginsenoside compositions containing “CK and PPT”.
  • CY, CK and PPT There is no mention of obtaining one containing three components.
  • CY + CK and CK + PPT or the combined use of “CY + PPT” (that is, depending on the two-component composition of the composition located on the outer side of the triangle chart of the present invention, )
  • the effects as excellent as those of the present invention cannot be expected.
  • the ginsenoside composition of the present invention comprises:
  • compound Y which is ginsenoside
  • compound K as “CK”
  • PPT protopanaxatriol
  • it must contain three components of CY, CK and PPT as essential components.
  • the three vertices of the triangular chart are A, B, and C.
  • the scale of 0 ⁇ 1 of CY is attached to the A ⁇ B side
  • the scale of 0 ⁇ 1 of CK is attached to the B ⁇ C side
  • C ⁇ A.
  • the main use of the above ginsenoside composition is an oral composition or a body-related parenteral composition.
  • the three components consisting of CY, CK and PPT in the above ginsenoside composition are preferably in a state of being included in cyclodextrin.
  • the ginsenoside composition of the present invention is characterized by comprising three components of CY, CK and PPT as essential components and containing these components in a specific ratio.
  • CY is a diol minor ginsenoside
  • CK is a diol minor ginsenoside
  • PPT is a triol minor ginsenoside.
  • PPT corresponds to that in which the glucoside group is removed from F1 or Rh1, but even if F1 or Rh1, which is a PPT with a glucoside group, is used instead of PPT in the above three components, it is as much as the composition of the present invention. We cannot expect an excellent effect.
  • the composition containing the above-mentioned three components can obtain a desired proportion of the three-component composition at once by performing the first-stage and second-stage enzyme reactions using a glycolytic enzyme.
  • it is also easy to adjust a desired three-component composition by appropriately blending a three-component composition obtained under different conditions or one containing one or two components.
  • the ginsenoside composition of the present invention when compound CY is abbreviated as “CY”, compound CK is abbreviated as “CK”, and protopanaxatriol is abbreviated as “PPT”, contains these three components as essential components. To do.
  • the three vertices of the triangular chart are A, B, and C
  • the A ⁇ B side is marked with a CY 0 ⁇ 1 scale
  • the B ⁇ C side is marked with a CK 0 ⁇ 1 scale
  • the above three components CY, CK, PPT The weight ratio of each component to the total weight is P1 (0.75, 0.2, 0.05), P2 (0.1, 0.85, 0.05), P3 (0.1, 0.2, 0.7) It is essential to be within the area surrounded by the three points. (The weight ratio of the above three components means that it is in a triangular region surrounded by a thick line in the triangular charts of FIGS. 1 and 2 in the examples described later.)
  • composition of CY, CK, PPT is on the A ⁇ B side, B ⁇ C side or C ⁇ A side of the above triangular chart, that is, when only two components are common to the composition of the present invention. Is not as effective as the composition of the present invention.
  • composition of CY, CK, and PPT is at the three apexes of the above triangular chart, that is, when only one component is common to the composition of the present invention, it is further inferior to the case where only the above two components are common. Only the effect is played.
  • composition of CY, CK, and PPT is inside the region surrounded by the three sides in the above triangular diagram, but is outside the triangular region surrounded by the thick line in the triangular diagram, that region The effects are clearly inferior to those in the case.
  • a delicate balance between the diol-based minor ginsenoside and the triol-based minor ginsenoside acts to maximize the efficacy of the composition.
  • each component of CY, CK, and PPT in the above composition varies depending on the dosage form (liquid / emulsion, tablet / granule / powder) of the composition, and is not generally determined. As described above, it is preferably 5 ppm or more, more preferably 10 ppm or more, and particularly preferably 20 ppm or more.
  • ginseng particularly American ginseng and ginseng (especially ginseng) containing a large amount of ginsenoside.
  • the following two-step reaction with ⁇ -glucosidase was attempted using the extract as a raw material.
  • a first-stage enzymatic reaction is carried out to produce ginsenoside F2 by allowing ⁇ -glucosidase to act on ginsenoside Rb1 or Rd.
  • the enzyme in the reaction solution containing F2 is deactivated, and then a second reaction of the reaction of producing ginsenoside CK (compound CK) by acting with a different ⁇ -glucosidase is performed.
  • a composition containing three, two or one of CY, CK and PPT is suitable.
  • a composition containing the three components in a desired ratio may be prepared, or the ratio between the three components may be finely adjusted.
  • composition containing three components of CY, CK and PPT in the present invention is preferably in a state of being included in cyclodextrin (especially ⁇ -cyclodextrin). The reason is as follows.
  • -2- CY, CK, and PPT are all poorly soluble in water and easily soluble in alcohols. Therefore, a powdery composition having a high content of CY, CK, and PPT has a property that it exists in a lump even when added to an aqueous liquid and is difficult to disperse. Therefore, even if a powder containing a high content of CY, CK, and PPT is ingested, it is difficult to disperse as a lump in the intestine, so that it is difficult to absorb the living body in such a dispersed state.
  • compositions of the present invention are oral compositions (general foods, processed foods, health foods, nutritional supplements, functional foods, and other foods; health maintenance (prevention), health deterioration prevention (progression) Suppression) or pharmaceuticals for treatment) and body related parenteral compositions (cosmetics, hair restorers, baths, etc.).
  • Example 1 [Production of composition comprising ginsenoside CY, CK and PPT] -1- Ginseng was dried into a powder, and 10 times the weight of 60-80% ethanol solution was added to the powder, and the extract was extracted by heating at 70-80 ° C. -2- A sugar-degrading enzyme ( ⁇ -glucosidase) for food processing was added to the extract, and the first stage enzyme reaction was performed at 40 to 60 ° C. for 2 to 4 days. -3- After completion of the first stage reaction, the enzyme reaction solution was heated to inactivate the enzyme. Subsequently, centrifugation was performed and the supernatant was collected.
  • ⁇ -glucosidase ⁇ -glucosidase
  • each ginsenoside (CY, CK, PPT) in the sample is calculated by comparing the peak area of each ginsenoside (CY, CK, PPT) standard product with the peak area of each ginsenoside (CY, CK, PPT) in the sample solution. did.
  • a moisturizing effect evaluation test was conducted by 100 female panelists aged 35 to 70 who had dry skin and rough skin. 100 panelists were divided into 20 groups of 5 people, and the same number of creams as the group number was used. Specifically, the cream was applied to the site where rough skin was caused after 2 to 4 times of water work a day. We had you evaluate.
  • the moisturizing effect of each cream was determined as follows based on the total value of the “average improvement in skin roughness” score and the “moist feeling” score of the group average. ⁇ The effect is large when the total value is "8.0 or more" ( ⁇ ) ⁇ The effect is medium ( ⁇ ) when the total value is less than 8.0 and 7.0 or more ⁇ Slightly less effective when total value is less than 7.0 and greater than 6.0 ( ⁇ ) ⁇ If the total value is less than 6.0 and 4.0 or more, the effect is small ( ⁇ ) ⁇ No effect when total value is less than 4.0 ( ⁇ )
  • (Cream composition) A cream was prepared according to the following formulation. • 25.0% by weight squalane • 6.0% by weight beeswax • 5.0% by weight glycerin • 5.0% by weight glycerin monostearate • 2.0% by weight polyoxyethylene sorbitan monostearate 5.0% by weight of ethanol-Ginsenoside composition in the amount shown in Table 1-Appropriate amount of preservative-Appropriate amount of fragrance-Residual purified water
  • a triangular area (vertices P1, P2, and P3) surrounded by a thick line including the experiment numbers MK-1 to MK-9 with the effect ⁇ is a particularly preferable area.
  • the unit of “upper part: content of three components” is “ppm” (“mg / kg”, that is, the number of mg of each component per 1 kg of cream).
  • Example 2 [Evaluation test of cold amelioration effect by tablet intake] A ginsenoside composition containing 15 different concentrations of ginsenoside CY, CK, and PPT was prepared. That is, 15 ginsenoside compositions were prepared by using a red ginseng concentrated extract as a raw material and changing the amount of addition of several types of ⁇ -glucosidase, or changing pH, temperature, reaction time, and the like. Each of the compositions was pulverized once, and then ⁇ -CD ( ⁇ -cyclodextrin) and water were added, and 15 kinds of ginsenoside CY, CK and PPT coexisting powders were obtained by inclusion by a conventional method. Using them, 15 types of tablets were prepared. The ginsenoside content is shown in Table 2. The tablet has a disk shape, and the composition of the tablet is 94% of ginsenoside-containing powder and 6% by weight of excipient sucrose fatty acid ester. One tablet is 300 mg.
  • a clinical trial for cold syndrome was conducted with a total of 75 subjects, 30 men and 45 women aged 50-70 years with cold syndrome. Two men and three women were randomly grouped into 15 groups. Three tablets of the same number as the group number were taken daily for 1 month. All subjects checked their subjective symptoms for coldness before ingestion and one month after ingestion. In the subjective symptom chart, the state of coldness is divided into seven stages as follows (however, the present state is applied to the winter season).
  • ⁇ State 1 Because the limbs cool down and wake up for small nights, you can't sleep well without putting an electric blanket or red bean.
  • ⁇ State 2 The limbs get cold, but not enough to put an electric blanket or red bean into the nodding. 3: It is more difficult to leave the place where there is sunlight, heating, kotatsu, and stove ⁇ State 4: I don't care much about heating, but I am wearing thick ⁇ State 5: When I move my body slightly thinking that my limbs will cool down It ’s getting warmer ⁇ State 6: Do n’t worry about cold hands and feet ⁇ State 7: Body is warm and warm
  • the improvement score of each group was calculated by summing the points of improvement effect of each group of five people. At this time, if the total score is 13 or more, the effect is large ( ⁇ ) ⁇ Effective 12-10 ( ⁇ ) ⁇ 9-8 are slightly smaller in effect ( ⁇ ) ⁇ 7 ⁇ 4 is less effective ( ⁇ ) ⁇ Almost no effect or no effect for 3 or less ( ⁇ ) It was determined.
  • Ginsenoside powder prepared from ginseng CY 290 mg / g, CK 350 mg / g, and PPT 120 mg / g was added 1.5 times by weight of ⁇ -cyclodextrin and 4 times by weight of water. Homogenization was performed while cooling at 000 rpm for 10 minutes. Thereafter, concentration and drying were performed, and the dried solid was pulverized to obtain a powder in which ginsenoside CY, CK and PPT were included. Next, prepare two beakers with 200 ml of water, add ginsenoside powder before inclusion to one, add the encapsulated powder to the other, and stir both. However, the latter dispersed immediately and became dissolved.
  • the ginsenoside composition of the present invention includes oral compositions (food, nutritional supplements, health foods, functional foods, pharmaceuticals, etc.), body-related parenteral compositions (cosmetics, hair restorers, bathing agents, etc.) ).

Abstract

The purpose of the present invention is to provide a ginsenoside composition derived from ginseng that is useful for compositions for oral administration and compositions for parenteral administration relating to body. The ginsenoside composition contains CY, CK and PPT as three essential components, each of said CY, CK and PPT being a ginsenoside compound, wherein, when the three angles of a triangular figure are denoted by A, B and C and the scales CY 0→1, CK 0→1 and PPT 0→1 are mounted respectively to the sides A→B, B→C and C→A [wherein each of these scales is to be read in the inward direction of an extension line running outside the triangular figure], the ratios by weight of the individual three components CY, CK and PPT to the total weight thereof are located within an area surrounded by specific three points (i.e., P1, P2 and P3).

Description

ジンセノサイド組成物Ginsenoside composition
 本発明は、経口用の組成物(食品、栄養補助食品、健康食品、機能性食品、医薬品など)、身体関連の非経口用の組成物(化粧料、育毛剤、入浴剤など)の用途に有用な薬用人参由来のジンセノサイド組成物に関するものである。 The present invention is suitable for use in oral compositions (foods, nutritional supplements, health foods, functional foods, pharmaceuticals, etc.) and body-related parenteral compositions (cosmetics, hair restorers, bathing agents, etc.). The present invention relates to a ginsenoside composition derived from useful ginseng.
[用語の説明と略称]
 本発明の組成物を構成する3つの成分のそれぞれは、いずれも正式な化学名があるが、煩雑である上に紛らわしいので、本発明を説明するにあたっては慣用的な略称である「CY」、「CK」、「PPT」の用語を使うことにする。
[Terminology and abbreviations]
Each of the three components constituting the composition of the present invention has a formal chemical name, but it is cumbersome and confusing. Therefore, in describing the present invention, “CY”, which is a common abbreviation, The terms “CK” and “PPT” will be used.
(CYについて)
 「CY」は、「コンパウンドY(化合物Y)」と通称されるジオール系のジンセノサイドであって、その化学名は、
 「20-O-[α-L-アラビノピラノシル(1→6)-β-D-グルコピラノシル]-20(S)プロトパナキサジオール」
である。
(About CY)
“CY” is a diol-based ginsenoside commonly called “compound Y (compound Y)”, and its chemical name is
“20-O- [α-L-arabinopyranosyl (1 → 6) -β-D-glucopyranosyl] -20 (S) protopanaxadiol”
It is.
(CKについて)
 「CK」は、「コンパウンドK(化合物K)」と通称されるジオール系のジンセノサイドであって、その化学名は、
 「20-O-β-D-グルコピラノシル-20(S)-プロトパナキサジオール」
であり、
 「20(S)-プロトパナキサジオール-20-O-β-D-グルコピラノサイド」
とも称される。
 「CK」は、「ジンセノサイドM1」または単に「M1」と称されることもある。
(About CK)
“CK” is a diol-based ginsenoside commonly called “compound K (compound K)”, and its chemical name is
“20-O-β-D-Glucopyranosyl-20 (S) -protopanaxadiol”
And
“20 (S) -protopanaxadiol-20-O-β-D-glucopyranoside”
Also called.
“CK” may also be referred to as “ginsenoside M1” or simply “M1”.
(PPTについて)
 「プロトパナキサトリオール」は、本明細書においては「PPT」と称することにする。「PPT」は、「M4」とも通称される。
 「PPT」は、「真正サポニゲン」または「真正アグリコン」とも称される。
 「PPT」は、トリオール系のジンセノサイドである「F1」と通称される「20-O-β-D-グルコピラノシル-20(S)プロトパナキサトリオール」またはRh1と通称される「6-O-β-D-グルコピラノシル-20(S)プロトパナキサトリオール」からグルコシド基が外れたものに相当する。
(About PPT)
“Protopanaxatriol” will be referred to herein as “PPT”. “PPT” is also commonly referred to as “M4”.
“PPT” is also referred to as “genuine saponigen” or “genuine aglycone”.
“PPT” is “20-O-β-D-glucopyranosyl-20 (S) prototopanaxatriol” commonly called “F1” which is a triol-based ginsenoside or “6-O-β” commonly called Rh1. -D-glucopyranosyl-20 (S) protopanaxatriol ”corresponds to a glucoside group removed.
(英文表記と片仮名表記について)
 なお、英文表記の「ginsenoside」の部分は、「ジンセノサイド」や「ジンセノシド」や「ギンセノシド」などと片仮名表記される。
 英文表記の「panaxa」の部分は、「パナキサ」や「パナクサ」と片仮名表記される。(ただし、特表2010-520894においては、英文表記が「panxa」とされており、「パンキサ」と片仮名表記されている。)
 本発明の出願に先立つ従来技術の検索(特許電子図書館のデータベースを利用)にあたっては、それらの同義語にも配慮して検索を行っている。
(About English and Katakana)
In English, “ginsenoside” is written in katakana as “ginsenoside”, “ginsenoside”, “ginsenoside”, or the like.
The part of “panaxa” in English is written as “Panaxa” or “Panaxa” in katakana. (However, in the special table 2010-520894, the English notation is “panxa” and “Punka” is indicated by Katakana.)
Prior art searches prior to the filing of the present invention (using a database of a patent electronic library) are conducted in consideration of their synonyms.
[各種のジンセノサイドについて]
-1-
 薬用人参の有用成分であるサポニンは、ジンセノサイドと称される。現在においては、40種類以上のジンセノサイドが知られている。
 ジンセノサイドは、ジオール系とトリオール系とオレアノイック系とに大別されるが、その中でも重要なものがジオール系とトリオール系である。前者のジオール系は中枢神経の沈静化に作用し、後者のトリオール系は中枢神経の興奮化に作用すると言われている。
[About various ginsenosides]
-1-
Saponin, which is a useful ingredient of ginseng, is called ginsenoside. At present, more than 40 types of ginsenosides are known.
Ginsenoside is roughly classified into a diol type, a triol type, and an oleanoic type. Among them, an important one is a diol type and a triol type. The former diol system is said to act on the calming of the central nerve, and the latter triol system is said to act on the excitation of the central nerve.
-2-
 生の薬用人参(たとえば高麗人参)にはジオール系のメイジャージンセノサイドであるジンセノサイドRb1やトリオール系のメイジャージンセノサイドであるジンセノサイドReが多く含まれているが、それらのメイジャージンセノサイドを摂取しても人の体内に吸収されにくい。
 これらのメイジャージンセノサイドについては、腸内細菌が分泌するβ-グルコシダーゼによりメイジャージンセノサイドの糖鎖が分解されてマイナーサポニン(マイナージンセノサイド)になることにより、体内への吸収が容易になってくる。
 ジオール系マイナージンセノサイドには多種のものがあるが、本発明者らが着目しているジンセノサイドCYやCKもその範疇(ジオール系)に含まれる。
 トリオール系マイナージンセノサイドにも多種のものがあるが、本発明者らが着目しているジンセノサイドであるプロトパナキサトリオール(PPT)もその範疇(トリオール系)に含まれる。
-2-
Raw ginseng (for example, ginseng) contains a lot of ginsenoside Rb1, a diol major ginsenoside, and ginsenoside Re, a triol major ginsenoside. Hard to be absorbed.
As for these major ginsenosides, the sugar chains of major ginsenosides are degraded by β-glucosidase secreted by intestinal bacteria to become minor saponins (minor ginsenosides), which facilitates absorption into the body.
There are various types of diol minor ginsenosides, but ginsenoside CY and CK, which the present inventors have focused on, are also included in the category (diol type).
There are various types of triol minor ginsenosides, but protopanaxatriol (PPT), which is ginsenoside which the present inventors have focused on, is also included in the category (triol series).
-3-
 さて、生の薬用人参(たとえば高麗人参)、それを乾燥した白参、生の高麗人参を蒸気で蒸して乾燥させた紅参などには、上述のジンセノサイドCK、ジンセノサイドCY、プロトパナキサトリオール(PPT)は、いずれも含まれていない。
 これらのCK、CY、PPTは、上述のように、人の腸内微生物により糖質が分解されてはじめて生成するものである。
 しかしながら、人の腸内環境は様々であって、ジンセノサイドの糖鎖を分解できない人も、たとえば4人に1人というように、決して少なくはないと言われている。
-3-
For example, ginsenoside CK, ginsenoside CY, protopanaxatriol (see above) may be used for raw ginseng (eg ginseng), dried ginseng, red ginseng steamed with ginseng and dried. PPT) is not included.
As described above, these CK, CY, and PPT are produced only when carbohydrates are decomposed by human intestinal microorganisms.
However, the intestinal environment of humans varies, and it is said that there are not a few people who cannot decompose the sugar chain of ginsenoside, for example, 1 in 4 people.
-4-
 ジンセノサイドCKについては、現在までに、多くの研究者によって、抗癌活性、皮膚への効果、血流の改善、抗炎症作用、糖尿病の改善、抗ストレス作用、抗うつ作用、肝臓保護効果などが報告されている。
 ジンセノサイドCYは、上記のCKの原料となるほか、それ自体も薬理活性のあるジンセノサイドでもある。
 トリオール系ジンセノサイドについては、その抗炎症作用や抗アレルギー作用などが報告されている。ただし、多くはF1やRh1(部位は異なるが、いずれもグルコシド基付きのPPTである)についての報告であり、PPTについては文献が少ない。
-4-
About ginsenoside CK, to date, many researchers have demonstrated anticancer activity, effects on the skin, improvement of blood flow, anti-inflammatory action, improvement of diabetes, anti-stress action, antidepressant action, liver protection effect, etc. It has been reported.
Ginsenoside CY is a raw material for the above CK and is also a pharmacologically active ginsenoside.
Triol ginsenoside has been reported to have anti-inflammatory and anti-allergic effects. However, most of them are reports on F1 and Rh1 (parts are different but both are PPTs with a glucoside group), and there are few references on PPT.
[特許文献1~8について]
(特許文献1)
 特開平9-176017(特許文献1)にはMcまたはCKまたはPPTまたはCYを有効成分として含有する制癌剤が示されている。
 ただし、この文献には、それらのうちの任意の2者またはそれ以上を併用することについては何の記載も示唆もない。また、制癌剤以外の使い方についても何の記載も示唆もない。
 念のため注記すると、この特許文献1における「Mc」の化学名は「20-O-[α-L-アラビノフラノシル(1→6)-β-D-グルコピラノシル]-20(S)プロトパナキサジオール」であって、「CY」の化学名である「20-O-[α-L-アラビノピラノシル(1→6)-β-D-グルコピラノシル]-20(S)プロトパナキサジオール」とは別物質である。(Mcの「フラノシル」は5員環、CYのピラノシルは6員環。)
[Regarding Patent Documents 1 to 8]
(Patent Document 1)
JP-A-9-176017 (Patent Document 1) discloses an anticancer drug containing Mc, CK, PPT, or CY as an active ingredient.
However, this document has no description or suggestion of using any two or more of them together. In addition, there is no description or suggestion about how to use other than anticancer drugs.
Note that the chemical name of “Mc” in Patent Document 1 is “20-O- [α-L-arabinofuranosyl (1 → 6) -β-D-glucopyranosyl] -20 (S) proto”. “20-O- [α-L-arabinopyranosyl (1 → 6) -β-D-glucopyranosyl] -20 (S) protopanaki”, which is the chemical name of “PANAXAdiol” Sadiol "is a different substance. (Mc's “furanosyl” is a 5-membered ring, and CY's pyranosyl is a 6-membered ring.)
(特許文献2)
 特開2003-212776(特許第4549625号)(特許文献2)の請求項2には、化合物K(つまりCK)、F1および化合物Y(つまりCY)の混合物からなる微細乳化粒子が示されている。ただし、PPTについては記載がない。
(Patent Document 2)
Claim 2 of Japanese Patent Application Laid-Open No. 2003-212776 (Patent No. 4549625) (Patent Document 2) shows finely-emulsified particles comprising a mixture of Compound K (ie CK), F1 and Compound Y (ie CY). . However, there is no description about PPT.
(特許文献3)
 特表2004-519224(特許第4953547号)(特許文献3)には、基質がプロトパナキサジオール系ジンセノサイドおよびプロトパナキサトリオール系ジンセノサイドであり、反応生成物がCKやアグリコンなどであるジンセノサイドグルコシダーゼが示されている。
(Patent Document 3)
JP-T-2004-519224 (Patent No. 495547) (Patent Document 3) discloses a ginsenoside glucosidase in which the substrates are protopanaxadiol ginsenoside and protopanaxatriol ginsenoside, and the reaction product is CK, aglycone, or the like. It is shown.
(特許文献4)
 特開2004-49154(特許第3678362号)(特許文献4)には、人参を特定の菌株により発酵して得られる発酵人参であって、当該発酵人参中に「M1(つまりCK)」並びに「M4(つまりPPT)」を含有する発酵人参の製造法が示されている。ただし、CYについては記載がない。
(Patent Document 4)
Japanese Patent Application Laid-Open No. 2004-49154 (Patent No. 3678362) (Patent Document 4) describes fermented carrots obtained by fermenting ginseng with a specific strain, and “M1 (that is, CK)” and “ A method for producing fermented ginseng containing "M4 (ie PPT)" is shown. However, there is no description about CY.
(特許文献5)
 特開平10-99094(特許文献5)には、プレボテラ属S-1菌株を、薬用人参サポニンを添加した培地に培養し、化合物K(つまりCK)および化合物Y(つまりCY)を生成蓄積させるプロトパナキサジオールサポニン代謝産物の製造法が示されている。
(Patent Document 5)
Japanese Patent Laid-Open No. 10-99094 (Patent Document 5) discloses a prototype in which Prevotella sp. S-1 strain is cultured in a medium supplemented with ginseng saponin to produce and accumulate Compound K (ie CK) and Compound Y (ie CY). A method for producing panaxadiol saponin metabolites is shown.
(特許文献6)
 特表2008-155998(特許文献6)には、朝鮮人参エキスを有効成分として含有する抗不安抗うつ剤が示されており、M1(CKのこと)とM4(PPTのこと)との含有量比(M1/M4)が1以上であることについても記載がある(請求項6)。この賦活剤の用途は、医薬組成物、食品組成物または飼料組成物である(請求項7)。
(Patent Document 6)
JP 2008-155998 (Patent Document 6) discloses an anxiolytic antidepressant containing ginseng extract as an active ingredient, and the contents of M1 (CK) and M4 (PPT) There is also a description that the ratio (M1 / M4) is 1 or more (claim 6). The use of this activator is a pharmaceutical composition, a food composition or a feed composition (Claim 7).
(特許文献7)
 特表2008-155999(特許文献7)には、朝鮮人参エキスを有効成分として含有するGABA作動性ニューロン賦活剤が示されており、M1(CKのこと)とM4(PPTのこと)との含有量比(M1/M4)が1以上であることについても記載がある(請求項6)。この賦活剤の用途は、医薬組成物、食品組成物または飼料組成物である(請求項7)。
(Patent Document 7)
JP 2008-155999 (Patent Document 7) discloses a GABAergic neuron activator containing ginseng extract as an active ingredient, and contains M1 (for CK) and M4 (for PPT). There is also a description that the quantity ratio (M1 / M4) is 1 or more (claim 6). The use of this activator is a pharmaceutical composition, a food composition or a feed composition (Claim 7).
(特許文献8)
 特開2010-132625(特許文献8)には、M1(CKのこと)とM4(PPTのこと)との含有量比(M1/M4)が1以上である抗糖尿病剤が示されている(請求項7)。
(Patent Document 8)
Japanese Patent Application Laid-Open No. 2010-132625 (Patent Document 8) discloses an antidiabetic agent having a content ratio (M1 / M4) of M1 (for CK) and M4 (for PPT) of 1 or more ( Claim 7).
特開平9-176017JP 9-176017 A 特開2003-212776(特許第4549625号)JP 2003-212776 (Patent No. 4549625) 特表2004-519224(特許第4953547号)Special Table 2004-519224 (Patent No. 495547) 特開2004-49154(特許第3678362号)JP 2004-49154 (Patent No. 3678362) 特開平10-99094JP-A-10-99094 特表2008-155998Special table 2008-155998 特表2008-155999Special table 2008-155999 特開2010-132625JP 2010-132625 A
(特許文献1~8に記載の事項)
 上記の特許文献1~8に記載のジンセノサイド成分を、本発明の必須のジンセノサイド3成分と対比してみると、次の表1のようになる(○は記載あり、×は記載なし)。
 表1のように、これらの特許文献1~8には、本発明の必須の3成分(CYとCKとPPTとの3成分)の全てを含有する組成物については記載がない。
(Matters described in Patent Documents 1 to 8)
The ginsenoside components described in Patent Documents 1 to 8 described above are compared with the essential ginsenoside 3 components of the present invention as shown in the following Table 1 (◯ is described and × is not described).
As shown in Table 1, these Patent Documents 1 to 8 do not describe compositions containing all of the essential three components of the present invention (three components of CY, CK and PPT).
Figure JPOXMLDOC01-appb-T000001
 
Figure JPOXMLDOC01-appb-T000001
 
(特許文献1)
-1-
 特許文献1の請求項、段落0003~0005、段落0009の製剤例1、段落0010の製剤例2、実施例1にかかる表1、実施例2にかかる表2と表3、実施例3にかかる表4の直後の箇所、段落0014の発明の効果の箇所には、「ジンセノシドMc」または「化合物K」または「化合物Y」または「PPT」の個々を有効成分として含有する制癌剤が示されている。
(Patent Document 1)
-1-
According to the claim of Patent Document 1, paragraphs 0003 to 0005, formulation example 1 of paragraph 0009, formulation example 2 of paragraph 0010, table 1 according to example 1, table 2 and table 3 according to example 2, and example 3 The part immediately after Table 4, the part of the effect of the invention of paragraph 0014, shows an anticancer agent containing each of “Ginsenoside Mc” or “Compound K” or “Compound Y” or “PPT” as an active ingredient. .
-2-
 しかしながら、特許文献1の表1、表2、表3、表4のように、細胞障害活性試験、増殖阻害試験、遊走阻害試験、基底膜浸潤抑制試験は全て上記4つのジンセノサイド成分のうち「個々のジンセノサイド成分」について行っており、これら4つの成分のうちの2成分以上を併用した試験は行っていない。
 また、特許文献1の発明は制癌剤に関するものであって、制癌剤以外の目的ないし用途については記載がない。
-2-
However, as shown in Table 1, Table 2, Table 3, and Table 4 of Patent Document 1, the cytotoxic activity test, the growth inhibition test, the migration inhibition test, and the basement membrane invasion suppression test are all “individual” among the above four ginsenoside components. Of ginsenoside component ", and a test using two or more of these four components in combination has not been conducted.
Further, the invention of Patent Document 1 relates to an anticancer agent, and there is no description about the purpose or use other than the anticancer agent.
(特許文献2)
 特許文献2には、「CY(化合物Y)」と「CK(化合物K)」との併用、さらにはこれらの2成分と20(S)部位がO-Glu基である「g-PPT」との併用については記載がある。しかしながら、「CY(化合物Y)」と「CK(化合物K)」と「PPT」との3成分を含むものを使用することについては何の記載もない。
(Patent Document 2)
Patent Document 2 discloses that “CY (Compound Y)” and “CK (Compound K)” are used together, and further, these two components and “g-PPT” in which the 20 (S) site is an O-Glu group There is a description about the combined use. However, there is no description about using a substance containing three components “CY (Compound Y)”, “CK (Compound K)” and “PPT”.
(特許文献3)
 特許文献3の表1~6、表8~9、表12には、酵素による加水分解によりCK、F2,アグリコンなどを含む反応生成物が得られることにつき記載があるが、本発明のように「CY,CKおよびPPT」の3成分を含むものを得ることについては何の記載もない。ちなみに、F2は「CK」の前駆物質である。
(Patent Document 3)
Tables 1 to 6, Tables 8 to 9, and Table 12 of Patent Document 3 describe that reaction products containing CK, F2, aglycone, and the like can be obtained by enzymatic hydrolysis, as in the present invention. There is no description about obtaining what contains the three components “CY, CK and PPT”. Incidentally, F2 is a precursor of “CK”.
(特許文献4~8)
 特許文献4~8には、「CYおよびCK」を含むジンセノサイド組成物、あるいは「CKおよびPPT」を含むジンセノサイド組成物が示されているが、本発明のように「CY,CKおよびPPT」の3成分を含むものを得ることについては何の記載もない。
 そして、「CY+CK」の併用や「CK+PPT」の併用によっては、あるいは「CY+PPT」の併用によっては、(すなわち、本発明の三角図表の外側の辺上に位置する組成の2成分組成物によっては、)本発明の場合ほどのすぐれた作用効果は到底期待しえない。
(Patent Documents 4 to 8)
Patent Documents 4 to 8 show ginsenoside compositions containing “CY and CK” or ginsenoside compositions containing “CK and PPT”. However, as in the present invention, “CY, CK and PPT” There is no mention of obtaining one containing three components.
And depending on the combined use of “CY + CK” and “CK + PPT” or the combined use of “CY + PPT” (that is, depending on the two-component composition of the composition located on the outer side of the triangle chart of the present invention, ) The effects as excellent as those of the present invention cannot be expected.
 本発明のジンセノサイド組成物は、
 いずれもジンセノサイドであるコンパウンドYを「CY」、コンパウンドKを「CK」、プロトパナキサトリオールを「PPT」と略記するとき、CY、CKおよびPPTの3成分を必須成分として含有するものであること、および、
 三角図表の3頂点をA,B,Cとし、A→B辺にはCYの0→1の目盛りを付し、B→C辺にはCKの0→1の目盛りを付し、C→A辺にはPPTの0→1の目盛りを付し、かつこれらの目盛りは三角図表の外側に張り出した延長線の内向き方向に読むものとするとき、前記の3成分CY、CK、PPTの合計重量に対する各成分の重量割合が、
 P1(0.75,0.2,0.05),
 P2(0.1,0.85,0.05),
 P3(0.1,0.2,0.7)
の3点で囲まれた範囲内にあること、
を特徴とするものである。
The ginsenoside composition of the present invention comprises:
In any case, when compound Y, which is ginsenoside, is abbreviated as “CY”, compound K as “CK”, and protopanaxatriol as “PPT”, it must contain three components of CY, CK and PPT as essential components. ,and,
The three vertices of the triangular chart are A, B, and C. The scale of 0 → 1 of CY is attached to the A → B side, the scale of 0 → 1 of CK is attached to the B → C side, and C → A. When the side is marked with a PPT scale of 0 → 1, and these scales are read in the direction of the inward extension of the triangle, the total weight of the three components CY, CK and PPT The weight ratio of each component is
P1 (0.75, 0.2, 0.05),
P2 (0.1, 0.85, 0.05),
P3 (0.1, 0.2, 0.7)
Within the range surrounded by the three points
It is characterized by.
 上記のジンセノサイド組成物の主たる用途は、経口用の組成物または身体関連の非経口用の組成物である。 The main use of the above ginsenoside composition is an oral composition or a body-related parenteral composition.
 上記のジンセノサイド組成物におけるCY、CKおよびPPTからなる3成分は、シクロデキストリンに包接された状態にあることが好ましい。 The three components consisting of CY, CK and PPT in the above ginsenoside composition are preferably in a state of being included in cyclodextrin.
-1-
 本発明のジンセノサイド組成物は、CY、CKおよびPPTの3成分を必須成分としかつそれらの成分を特定の割合で含有することを特徴とするものである。
 ここで、CYはジオール系のマイナージンセノサイド、CKもジオール系のマイナージンセノサイド、PPTはトリオール系のマイナージンセノサイドである。
 なお、PPTはF1またはRh1からグルコシド基が外れたものに相当するが、上記3成分中のPPTに代えてグルコシド基付きのPPTであるF1やRh1を用いても、本発明の組成物ほどのすぐれた作用効果は期待しえない。
-1-
The ginsenoside composition of the present invention is characterized by comprising three components of CY, CK and PPT as essential components and containing these components in a specific ratio.
Here, CY is a diol minor ginsenoside, CK is a diol minor ginsenoside, and PPT is a triol minor ginsenoside.
In addition, PPT corresponds to that in which the glucoside group is removed from F1 or Rh1, but even if F1 or Rh1, which is a PPT with a glucoside group, is used instead of PPT in the above three components, it is as much as the composition of the present invention. We cannot expect an excellent effect.
-2-
 上記の3成分からなる組成物を用いてたとえば化粧用クリームを調製して使用したときには、その3成分のうちのいずれか1成分あるいは任意の組み合わせの2成分から調製したクリームに比し、顕著にすぐれた作用効果(一例をあげれば後述の実施例の箇所で述べるような保湿効果)が奏される。
-2-
When, for example, a cosmetic cream is prepared and used using the above-mentioned three-component composition, it is significantly different from a cream prepared from any one of the three components or any combination of two components. An excellent operational effect (a moisturizing effect as described in the section of an example described later) is achieved.
-3-
 また、上記の3成分からなる組成物を用いてたとえば錠剤やエキスを調製して摂取したときは、その3成分のうちのいずれか1成分あるいは任意の組み合わせの2成分から調製した錠剤を摂取した場合に比し、顕著にすぐれた作用効果(一例をあげれば後述の実施例の箇所で述べるような冷え症改善効果)が奏される。
-3-
In addition, when a tablet or extract is prepared and ingested using the above three-component composition, for example, a tablet prepared from any one of these three components or any combination of two components is ingested. Compared to the case, the effect is significantly superior (an example is a cooling effect improving effect as described in the examples described later).
-4-
 さらに、上記の3成分を含む組成物は、糖分解酵素を用いて1段階目と2段階目の酵素反応を行うことにより、一挙に所望の割合の3成分組成物を取得することができる。
 この場合、別の条件で取得した3成分組成物や1~2成分を含むものを適宜配合して、所期の3成分組成に調整することも容易である。
-4-
Furthermore, the composition containing the above-mentioned three components can obtain a desired proportion of the three-component composition at once by performing the first-stage and second-stage enzyme reactions using a glycolytic enzyme.
In this case, it is also easy to adjust a desired three-component composition by appropriately blending a three-component composition obtained under different conditions or one containing one or two components.
クリームによる保湿効果を示した三角図表である。It is a triangle chart which showed the moisturizing effect by cream. 冷え症改善効果を示した三角図表である。It is a triangular chart which showed the cold improvement effect.
 以下、本発明を詳細に説明する。 Hereinafter, the present invention will be described in detail.
(本発明の組成物を構成する3成分とそれらの割合)
-1-
 本発明のジンセノサイド組成物は、コンパウンドCYを「CY」、コンパウンドCKを「CK」、プロトパナキサトリオールを「PPT」と略記するとき、これらの3成分を必須成分として含有することを必須要件とするものである。
(Three components constituting the composition of the present invention and their ratio)
-1-
The ginsenoside composition of the present invention, when compound CY is abbreviated as “CY”, compound CK is abbreviated as “CK”, and protopanaxatriol is abbreviated as “PPT”, contains these three components as essential components. To do.
-2-
 加えて、三角図表の3頂点をA,B,Cとし、A→B辺にはCYの0→1の目盛りを付し、B→C辺にはCKの0→1の目盛りを付し、C→A辺にはPPTの0→1の目盛りを付し、かつこれらの目盛りは三角図表の外側に張り出した延長線の内向き方向に読むものとするとき、前記の3成分CY、CK、PPTの合計重量に対する各成分の重量割合が、
 P1(0.75,0.2,0.05),
 P2(0.1,0.85,0.05),
 P3(0.1,0.2,0.7)
の3点で囲まれた領域内にあることを必須要件とするものである。
 (上記の3成分の重量割合は、後述の実施例における図1、図2の三角図表の太線で囲まれた三角形の領域内にあることを意味している。)
-2-
In addition, the three vertices of the triangular chart are A, B, and C, the A → B side is marked with a CY 0 → 1 scale, the B → C side is marked with a CK 0 → 1 scale, When the C → A side is marked with PPT 0 → 1 scales and these scales are read in the direction of the extension line extending outward from the triangular chart, the above three components CY, CK, PPT The weight ratio of each component to the total weight is
P1 (0.75, 0.2, 0.05),
P2 (0.1, 0.85, 0.05),
P3 (0.1, 0.2, 0.7)
It is essential to be within the area surrounded by the three points.
(The weight ratio of the above three components means that it is in a triangular region surrounded by a thick line in the triangular charts of FIGS. 1 and 2 in the examples described later.)
-3-
 なお、CY、CK、PPTの組成が、上記の三角図表のA→B辺、B→C辺またはC→A辺上にあるとき、すなわち本発明の組成とは2成分のみが共通する場合には、本発明の組成物ほどのすぐれた作用効果は奏されない。
 CY、CK、PPTの組成が上記の三角図表の3つの頂点にあるとき、すなわち本発明の組成とは1成分のみが共通する場合には、上述の2成分のみが共通する場合よりもさらに劣る効果しか奏されない。
 そして、CY、CK、PPTの組成が上記の三角図表における3辺で囲まれた領域の内部にあっても、その三角図表の太線で囲まれた三角形の領域の外側にある場合は、その領域内にある場合に比しては作用効果が明らかに劣る。
 3成分が上記の領域内にあるときに、ジオール系のマイナージンセノサイドとトリオール系のマイナージンセノサイドとの微妙なバランスが作用して、該組成物の効能が最大限に発揮されるものと考えられる。
-3-
When the composition of CY, CK, PPT is on the A → B side, B → C side or C → A side of the above triangular chart, that is, when only two components are common to the composition of the present invention. Is not as effective as the composition of the present invention.
When the composition of CY, CK, and PPT is at the three apexes of the above triangular chart, that is, when only one component is common to the composition of the present invention, it is further inferior to the case where only the above two components are common. Only the effect is played.
If the composition of CY, CK, and PPT is inside the region surrounded by the three sides in the above triangular diagram, but is outside the triangular region surrounded by the thick line in the triangular diagram, that region The effects are clearly inferior to those in the case.
When the three components are in the above range, a delicate balance between the diol-based minor ginsenoside and the triol-based minor ginsenoside acts to maximize the efficacy of the composition.
-4-
 上記の組成物におけるCY、CK、PPTの各成分の量は、その組成物の剤形(液剤・乳剤か、錠剤・顆粒剤・散剤か)によっても異なるので一概には決められないが、1ppm以上、望ましくは5ppm以上、さらには10ppm以上、殊に20ppm以上であることが好ましい。
-4-
The amount of each component of CY, CK, and PPT in the above composition varies depending on the dosage form (liquid / emulsion, tablet / granule / powder) of the composition, and is not generally determined. As described above, it is preferably 5 ppm or more, more preferably 10 ppm or more, and particularly preferably 20 ppm or more.
(CY、CK、PPTの3成分を含む組成物の取得)
-1-
 ジンセノサイドCK、CY、PPTのそれぞれの製造法については、研究論文や特許文献などにおいて、薬用人参エキスの発酵処理や、エキス中のジンセノサイド類のβ-グルコシダーゼによる酵素反応などによる製造法が報告されている。
 しかしながら、いずれの製造法にあっても生成量はわずかであって、実用化は難しいものばかりである。
 しかも、CK、CY、PPTの3成分が共存しているという報告は(ましてそれらの3成分が上記三角図表の太線で囲まれた三角形の領域内に存在しているという報告は)、皆無であると思われる。
(Acquisition of a composition containing three components of CY, CK and PPT)
-1-
Regarding the production methods of ginsenoside CK, CY, and PPT, research methods and patent literature reported on the production method of ginseng extract by fermentation and enzymatic reaction of β-glucosidase of ginsenosides in the extract. Yes.
However, in any of the production methods, the amount of production is very small, and practical application is difficult.
In addition, there is no report that the three components of CK, CY, and PPT coexist (no report that these three components are present in the triangular area surrounded by the thick line in the above triangle diagram). It appears to be.
-2-
 しかるに、本発明者らは、ジンセノサイドCY、CKおよびPPTを同時にかつ高濃度に製造する方法につき鋭意検討した結果、薬用人参、殊にジンセノサイドを多く含むアメリカ人参や高麗人参(特に高麗紅参)のエキスを原料として、β-グルコシダーゼによる次の2段階反応を試みた。
 (1)ジンセノサイドRb1やRdにβ-グルコシダーゼを作用させてジンセノサイドF2を作る1段階目の酵素反応を行う。
 (2)ついで、そのF2を含む反応液中の酵素を失活させてから、異なるβ-グルコシダーゼで作用させてジンセノサイドCK(コンパウンドCK)を作る反応の2段階目の反応を行う。
-2-
However, as a result of intensive studies on a method for simultaneously producing ginsenoside CY, CK and PPT at high concentrations, the present inventors have found that ginseng, particularly American ginseng and ginseng (especially ginseng) containing a large amount of ginsenoside. The following two-step reaction with β-glucosidase was attempted using the extract as a raw material.
(1) A first-stage enzymatic reaction is carried out to produce ginsenoside F2 by allowing β-glucosidase to act on ginsenoside Rb1 or Rd.
(2) Next, the enzyme in the reaction solution containing F2 is deactivated, and then a second reaction of the reaction of producing ginsenoside CK (compound CK) by acting with a different β-glucosidase is performed.
-3-
 この2段階目の反応後の反応液中に生じた沈殿物にはCKおよびCYが高濃度に存在している上、PPTも高濃度に生成しているので、適当な操作によりCY、CKおよびPPTを高濃度に含む目的物を得ることができるのである。
-3-
In the precipitate generated in the reaction solution after the second stage reaction, CK and CY are present in high concentration, and PPT is also formed in high concentration. An object containing a high concentration of PPT can be obtained.
-4-
 なお、上記のようにCY、CKおよびPPTを所望の割合で含む組成物を一挙に得る方法に代えて、CY、CKおよびPPTのうちの3者または2者または1者を含む組成物を適当な割合で混合することにより、3成分を所望の割合で含む組成物を調合したり、3成分間の割合を微調整したりしても差し支えない。
-4-
In place of the method for obtaining a composition containing CY, CK and PPT in a desired ratio at a time as described above, a composition containing three, two or one of CY, CK and PPT is suitable. By mixing at a proper ratio, a composition containing the three components in a desired ratio may be prepared, or the ratio between the three components may be finely adjusted.
(シクロデキストリンによる包接化)
-1-
 本発明におけるCY、CKおよびPPTの3成分を含む組成物は、シクロデキストリン(殊にγ-シクロデキストリン)に包接された状態にあることが好ましい。その理由は次の如くである。
(Inclusion with cyclodextrin)
-1-
The composition containing three components of CY, CK and PPT in the present invention is preferably in a state of being included in cyclodextrin (especially γ-cyclodextrin). The reason is as follows.
-2-
 CY、CK、PPTはいずれも水に難溶で、アルコール類には易溶である。そのため、CY、CK、PPTが高含有量の粉末状の組成物は、水系の液体に添加しても塊りになって存在し、分散しにくいという性質がある。
 そのため、CY、CKおよびPPTが高含量の粉末を摂取しても、腸内で塊りとなって分散しがたいので、そのような分散状態では生体への吸収は困難になる。
-2-
CY, CK, and PPT are all poorly soluble in water and easily soluble in alcohols. Therefore, a powdery composition having a high content of CY, CK, and PPT has a property that it exists in a lump even when added to an aqueous liquid and is difficult to disperse.
Therefore, even if a powder containing a high content of CY, CK, and PPT is ingested, it is difficult to disperse as a lump in the intestine, so that it is difficult to absorb the living body in such a dispersed state.
-3-
 しかるに、CY、CK、PPTを含有する組成物をシクロデキストリンで包接すると、水系でも塊りにならずにミクロに分散し、分子レベルでこれらの成分が生体に吸収されるようになるのである。
 CY、CK、PPTの3成分の組成物のシクロデキストリンよる包接化は、今まで知られていなかったものと考えられる。
-3-
However, when a composition containing CY, CK, and PPT is included in cyclodextrin, it does not become agglomerated even in an aqueous system and is dispersed microscopically, and these components are absorbed by the living body at the molecular level. .
The inclusion of CY, CK, and PPT in a three-component composition with cyclodextrin is considered to be unknown until now.
-4-
 一般にシクロデキストリンよるジンセノサイドの包接化については知られているが、CY、CK、PPTの3成分を含有する組成物自体についての検討が従来はなされていなかったので、その3成分組成物とシクロデキストリンとの関係についての検討については考慮外にあったものと思われる。
-4-
In general, the inclusion of ginsenoside by cyclodextrin is known, but no investigation has been made on the composition itself containing the three components of CY, CK, and PPT. The study on the relationship with dextrin seems to have been out of consideration.
(用途)
 本発明の組成物の用途の代表例は、経口用の組成物(一般食品、加工食品、健康食品、栄養補助食品、機能性食品などの食品類;健康維持(予防)、健康悪化防止(進行抑制)あるいは治療のための医薬類)および身体関連の非経口用の組成物(化粧料、育毛剤、入浴剤など)である。
(Use)
Typical examples of the use of the composition of the present invention are oral compositions (general foods, processed foods, health foods, nutritional supplements, functional foods, and other foods; health maintenance (prevention), health deterioration prevention (progression) Suppression) or pharmaceuticals for treatment) and body related parenteral compositions (cosmetics, hair restorers, baths, etc.).
 次に実施例をあげて本発明をさらに説明する。 Next, the present invention will be further described with reference to examples.
[実施例1]
[ジンセノサイドCY、CKおよびPPTからなる組成物の製造]
-1-
 薬用人参を乾燥粉末化し、その粉末に10倍重量の60~80%エタノール溶液を加え、70~80℃で加熱することにより、エキスを抽出した。
-2-
 抽出エキスに食品加工用の糖分解酵素(β-グルコシダーゼ)を加え、40~60℃で2~4日間、1段階目の酵素反応を行った。
-3-
 1段階目の反応終了後、酵素反応液を加熱して酵素を失活させた。ついで、遠心操作を行い、上清を回収した。
-4-
 回収した上清に食品加工用の糖分解酵素(β-グルコシダーゼ)を加え、40~60℃で2~4日間、2段階目の酵素反応を行った。
-5-
 2段階目の反応終了後、酵素反応液中に生じた沈殿物を遠心操作によって回収し、エタノールに溶解した。さらに、そのエタノール溶液において生じた沈殿物を遠心操作によって除去し、ジンセノサイドCY、CKおよびPPTを高含有量含むエキスを得た。
-6-
 このエキスからジンセノサイドCY、CKおよびPPTを高含有量含む粉末にする場合は、さらに濃縮・乾燥操作を行い、溶媒のエタノールを留去した後、乾固した固形物を粉末化すればよい。
[Example 1]
[Production of composition comprising ginsenoside CY, CK and PPT]
-1-
Ginseng was dried into a powder, and 10 times the weight of 60-80% ethanol solution was added to the powder, and the extract was extracted by heating at 70-80 ° C.
-2-
A sugar-degrading enzyme (β-glucosidase) for food processing was added to the extract, and the first stage enzyme reaction was performed at 40 to 60 ° C. for 2 to 4 days.
-3-
After completion of the first stage reaction, the enzyme reaction solution was heated to inactivate the enzyme. Subsequently, centrifugation was performed and the supernatant was collected.
-4-
A glycolytic enzyme (β-glucosidase) for food processing was added to the collected supernatant, and the second stage enzyme reaction was performed at 40 to 60 ° C. for 2 to 4 days.
-5
After completion of the second stage reaction, the precipitate produced in the enzyme reaction solution was collected by centrifugation and dissolved in ethanol. Furthermore, the precipitate produced in the ethanol solution was removed by centrifugation to obtain an extract containing a high content of ginsenoside CY, CK and PPT.
-6-
In order to obtain a powder containing a high content of ginsenosides CY, CK and PPT from this extract, further concentration and drying operations are carried out to distill off ethanol as a solvent, and then the dried solid matter may be powdered.
[ジンセノサイドCY、CKおよびPPTの分析法]
-1-
 試料粉末1gを正確に量り、日本薬局方「ニンジン」「コウジン」に記載された方法でジンセノサイド成分を抽出した。さらにC18簡易カラムを用いてジンセノサイド成分を粗精製した後、メンブランフィルターによってろ過し、これを試料溶液とした。
 次に、C18カラムを用いた高速液体クロマトグラフィー(HPLC)により試料溶液を分析、定量した。
-2-
 HPLCにおいては、アセトニトリル濃度が40~55%の移動相で分離を行った。各ジンセノサイド(CY、CKおよびPPT)標準品のピーク面積と試料溶液の各ジンセノサイド(CY、CK、PPT)のピーク面積の比較により、試料中の各ジンセノサイド(CY、CK、PPT)含有量を算出した。
[Analytical method of ginsenoside CY, CK and PPT]
-1-
1 g of sample powder was accurately weighed, and ginsenoside components were extracted by the methods described in Japanese Pharmacopoeia “Carrot” and “Koujin”. Furthermore, after roughly purifying the ginsenoside component using a C18 simple column, it was filtered through a membrane filter to obtain a sample solution.
Next, the sample solution was analyzed and quantified by high performance liquid chromatography (HPLC) using a C18 column.
-2-
In HPLC, separation was performed with a mobile phase having an acetonitrile concentration of 40 to 55%. The content of each ginsenoside (CY, CK, PPT) in the sample is calculated by comparing the peak area of each ginsenoside (CY, CK, PPT) standard product with the peak area of each ginsenoside (CY, CK, PPT) in the sample solution. did.
[ジンセノサイドCY、CKおよびPPTのγ-CDへの包接化]
-1-
 ジンセノサイドCY、CKおよびPPTの高含有粉末にγ-CD(γ-シクロデキストリン)を加えた。このとき、ジンセノサイドCY、CKおよびPPTとγ-CDの重量比が1:1~1:2となるようにした。さらに、ジンセノサイド高含有粉末の4~5倍重量の水を加えた。
-2-
 混合した試料をホモジナイズした。ホモジナイズ操作は、ホモジナイザーを使用して、10,000回転/分で10分間、冷却を間にはさんで2回行った。
-3-
 ホモジナイズ操作後の溶液を回収し、濃縮・乾燥操作を行い、乾固した固形物を粉末化して、γ-CDに包接されたCK、CYおよびPPTの組成物の粉末を得た。
[Inclusion of ginsenoside CY, CK and PPT into γ-CD]
-1-
Γ-CD (γ-cyclodextrin) was added to a powder with high content of ginsenoside CY, CK and PPT. At this time, the weight ratio of ginsenoside CY, CK, PPT and γ-CD was set to 1: 1 to 1: 2. Further, 4 to 5 times the weight of water of the high ginsenoside powder was added.
-2-
The mixed sample was homogenized. The homogenization operation was performed twice using a homogenizer at 10,000 rpm for 10 minutes, with cooling in between.
-3-
The solution after the homogenization operation was collected, concentrated and dried, and the dried solid was pulverized to obtain a powder of a composition of CK, CY and PPT encapsulated in γ-CD.
[クリームによる保湿効果の評価試験]
 上記で得たジンセノサイド組成物を用い、下記の表1の組成の化粧クリーム20種類を調製した。
 種々の濃度のジンセノサイドCY、CKおよびPPTを含有するジンセノサイド組成物20種類の調製は、原料を紅参濃縮エキスとし、数種類のβ-グルコシダーゼを用いてそれらの添加量を変化させた場合や、pH、温度、反応時間なども変化させて、20種類のジンセノサイド組成物を調製した。
[Evaluation test of moisturizing effect by cream]
Using the ginsenoside composition obtained above, 20 types of cosmetic creams having the compositions shown in Table 1 below were prepared.
Preparation of 20 types of ginsenoside compositions containing various concentrations of ginsenoside CY, CK, and PPT is possible when the raw material is red ginseng concentrate extract and the amount of addition is changed using several types of β-glucosidase, Twenty kinds of ginsenoside compositions were prepared by changing the temperature and reaction time.
 乾燥肌で肌荒れのある35歳から70歳までの女性パネラー100名による保湿効果評価試験を行った。
 パネラー100名を5名づつの20グループに分け、グループ番号と同じ番号のクリームを使用してもらった。具体的には、1日2~4回の水仕事後に肌荒れを起こしている部位にクリームを塗布してもらい、1カ月後に肌荒れ改善の程度としっとり感の程度について、以下の5段階で全員に評価してもらった。
A moisturizing effect evaluation test was conducted by 100 female panelists aged 35 to 70 who had dry skin and rough skin.
100 panelists were divided into 20 groups of 5 people, and the same number of creams as the group number was used. Specifically, the cream was applied to the site where rough skin was caused after 2 to 4 times of water work a day. We had you evaluate.
(肌荒れ改善)
 1点…使用前よりも悪化
 2点…使用前とほとんど同じ
 3点…使用前に比べやや改善
 4点…使用前に比べ改善
 5点…使用前に比べかなり改善
(Improves rough skin)
1 point: worse than before use 2 points: almost the same as before use 3 points: slightly improved compared to before use 4 points: improved compared to before use 5 points: considerably improved compared to before use
(しっとり感)
 1点…使用前よりも悪化
 2点…使用前とほとんど同じ
 3点…使用前に比べややしっとりしている
 4点…使用前に比べしっとりしている
 5点…使用前に比べかなりしっとりしている
(Moist feeling)
1 point: worse than before 2 points: almost the same as before 3 points: slightly moist compared to before use 4 points: moist compared to before use 5 points: considerably moist than before use Have
(保湿効果の判定)
 なお、各クリームの保湿効果は、グループ平均の「肌荒れ改善」の点数と「しっとり感」の点数とを合計した値につき、次のように判定した。
 ・合計値が「8.0以上の場合」を効果が大(●)
 ・合計値が「8.0未満で7.0以上の場合」を効果が中(○)
 ・合計値が「7.0未満で6.0以上の場合」を効果がやや小(□)
 ・合計値が「6.0未満で4.0以上の場合」を効果が小(△)
 ・合計値が「4.0未満の場合」を効果なし(×)
(Determination of moisturizing effect)
In addition, the moisturizing effect of each cream was determined as follows based on the total value of the “average improvement in skin roughness” score and the “moist feeling” score of the group average.
・ The effect is large when the total value is "8.0 or more" (●)
・ The effect is medium (○) when the total value is less than 8.0 and 7.0 or more
・ Slightly less effective when total value is less than 7.0 and greater than 6.0 (□)
・ If the total value is less than 6.0 and 4.0 or more, the effect is small (△)
・ No effect when total value is less than 4.0 (×)
(クリームの組成)
 次の処方にてクリームを調製した。
 ・25.0重量%のスクワラン
 ・ 6.0重量%のミツロウ
 ・ 5.0重量%のグリセリン
 ・ 5.0重量%のグリセリンモノステアレート
 ・ 2.0重量%のポリオキシエチレンソルビタンモノステアレート
 ・ 5.0重量%のエタノール
 ・ 表1に示す配合量のジンセノサイド組成物
 ・ 適量の防腐剤
 ・ 適量の香料
 ・ 残余の精製水
(Cream composition)
A cream was prepared according to the following formulation.
• 25.0% by weight squalane • 6.0% by weight beeswax • 5.0% by weight glycerin • 5.0% by weight glycerin monostearate • 2.0% by weight polyoxyethylene sorbitan monostearate 5.0% by weight of ethanol-Ginsenoside composition in the amount shown in Table 1-Appropriate amount of preservative-Appropriate amount of fragrance-Residual purified water
(結果)
 結果を表2~表3および図1に示す。
 なお、表にまとめたときにわかりやすいように、グループの番号とクリームの番号は、効果が●、○、□、△、×のグループに分けて、付け直しを行ってある。(○評価は、該当する例がなかった。)
 表2~表3の実験番号の欄の「MK-」は「moisture keeping(保湿)の略号であり、その「MK-」の右側の「1~20」の数字は、付け直し後のグループ番号である。
 図1においては、実験番号のうちの「MK-」を省略して、「1~20」の数字のみを三角図表内に記入してある。なお、効果が●の実験番号MK-1からMK-9を含む太線で囲んだ三角形の領域(頂点はP1,P2,P3)は、特に好ましい領域である。
 表2、3中の「上段:3成分の含有量」の単位は「ppm」(「mg/kg」、つまりクリーム1kg当りの各成分のmg数)である。
(result)
The results are shown in Tables 2 to 3 and FIG.
In order to make it easier to understand when compiled in the table, the group numbers and cream numbers have been re-assigned into groups with effects of ●, ○, □, Δ, and ×. (The evaluation was not applicable)
“MK-” in the column of the experiment number in Tables 2 to 3 is an abbreviation for “moisture keeping”, and the numbers “1 to 20” on the right side of “MK-” are the group numbers after re-attachment. It is.
In FIG. 1, “MK-” in the experiment number is omitted, and only the numbers “1 to 20” are entered in the triangle chart. A triangular area (vertices P1, P2, and P3) surrounded by a thick line including the experiment numbers MK-1 to MK-9 with the effect ● is a particularly preferable area.
In Tables 2 and 3, the unit of “upper part: content of three components” is “ppm” (“mg / kg”, that is, the number of mg of each component per 1 kg of cream).
Figure JPOXMLDOC01-appb-T000002
 
Figure JPOXMLDOC01-appb-T000002
 
Figure JPOXMLDOC01-appb-T000003
 
Figure JPOXMLDOC01-appb-T000003
 
[実施例2]
[錠剤摂取による冷え症改善効果の評価試験]
 15種類の濃度のジンセノサイドCY、CK、PPTを含有するジンセノサイド組成物を作製した。
 すなわち、原料を紅参濃縮エキスとし、数種類のβ-グルコシダーゼを用いてその添加量を変化させた場合や、pH、温度、反応時間なども変化させて、15種類のジンセノサイド組成物を調製した。
 その各組成物を一旦粉末化し、次にγ-CD(γ-シクロデキストリン)と水とを加えて定法により包接化した15種類のジンセノサイドCY、CK、PPT共存粉末を得た。
 それらを用いて15種類の錠剤を作製した。ジンセノサイド含有量は表2に示す。
 錠剤の形状は円盤形とし、錠剤の組成は、ジンセノサイド含有粉末が94%、賦形剤のショ糖脂肪酸エステルが6重量%である。1錠は300mgである。
[Example 2]
[Evaluation test of cold amelioration effect by tablet intake]
A ginsenoside composition containing 15 different concentrations of ginsenoside CY, CK, and PPT was prepared.
That is, 15 ginsenoside compositions were prepared by using a red ginseng concentrated extract as a raw material and changing the amount of addition of several types of β-glucosidase, or changing pH, temperature, reaction time, and the like.
Each of the compositions was pulverized once, and then γ-CD (γ-cyclodextrin) and water were added, and 15 kinds of ginsenoside CY, CK and PPT coexisting powders were obtained by inclusion by a conventional method.
Using them, 15 types of tablets were prepared. The ginsenoside content is shown in Table 2.
The tablet has a disk shape, and the composition of the tablet is 94% of ginsenoside-containing powder and 6% by weight of excipient sucrose fatty acid ester. One tablet is 300 mg.
 冷え症を持つ50~70歳の男性30名と女性45名の計75名を被験者として、冷え症に対する臨床試験を行った。
 無作為に男性2名と女性3名を1グループとし、15グループにグループ分けした。
 グループ番号と同じ番号の錠剤を毎日3粒、1ケ月間継続摂取した。摂取前と摂取1ケ月後に、被験者全員が冷え症に対する自覚症状をチェックした。自覚症状表には、冷え症の状態が次のように7段階に分かれている(但し、今の状態を冬季にあてはめる)。
A clinical trial for cold syndrome was conducted with a total of 75 subjects, 30 men and 45 women aged 50-70 years with cold syndrome.
Two men and three women were randomly grouped into 15 groups.
Three tablets of the same number as the group number were taken daily for 1 month. All subjects checked their subjective symptoms for coldness before ingestion and one month after ingestion. In the subjective symptom chart, the state of coldness is divided into seven stages as follows (however, the present state is applied to the winter season).
・状態1:手足が冷えて夜小用に起きるので、電気毛布やあんかを入れないとよく眠れない
・状態2:手足が冷えるが、夜具に電気毛布やあんかを入れるほどではない
・状態3:日当たりや、暖房、コタツ、ストーブのあるところを離れにくいほうである
・状態4:暖房はそれほど気にしないが厚着をしている
・状態5:手足が冷えると思って身体を少し動かすと暖かくなってくる
・状態6:手足の冷えなど気にならない
・状態7:身体がポカポカして手足も暖かい
・ State 1: Because the limbs cool down and wake up for small nights, you can't sleep well without putting an electric blanket or red bean. ・ State 2: The limbs get cold, but not enough to put an electric blanket or red bean into the nodding. 3: It is more difficult to leave the place where there is sunlight, heating, kotatsu, and stove ・ State 4: I don't care much about heating, but I am wearing thick ・ State 5: When I move my body slightly thinking that my limbs will cool down It ’s getting warmer ・ State 6: Do n’t worry about cold hands and feet ・ State 7: Body is warm and warm
 被験者全員が摂取前と摂取1ケ月後の状態について上記に当てはまる状態の数字を記入してもらい、数字が上昇するかどうかで冷え症に対する改善効果を評価した。
・数字が3段階以上上昇した場合、著効とし3点をつける
・数字が2段階上昇した場合、有効とし2点をつける
・数字が1段階上昇した場合、やや有効とし1点をつける
・数字に変化なしまたは下降した場合、無効とし0点とする
All the subjects were asked to fill in the numbers corresponding to the above for the state before ingestion and one month after ingestion, and the improvement effect on coldness was evaluated by whether the number increased.
・ If the number rises by 3 or more levels, it will be marked as 3 points. ・ If the number rises by 2 levels, it will be marked as 2 points. ・ If the number rises by 1 level, it will be scored as slightly valid. If there is no change or descends, it becomes invalid and 0 points
 各グループ5名の改善効果の点数を合計して、各グループの改善度を求めた。
 このときには、合計の点数が
 ・13以上を効果が大(●)
 ・12~10を効果が中(○)
 ・ 9~ 8を効果がやや小(□)
 ・ 7~ 4を効果が小(△)
 ・ 3以下を効果ほぼなしまたは効果なし(×)
と判定した。
The improvement score of each group was calculated by summing the points of improvement effect of each group of five people.
At this time, if the total score is 13 or more, the effect is large (●)
・ Effective 12-10 (○)
・ 9-8 are slightly smaller in effect (□)
・ 7 ~ 4 is less effective (△)
・ Almost no effect or no effect for 3 or less (×)
It was determined.
 結果を表4および図2に示す。
 表4の実験番号の欄の「OS-」は「oversensitiveness to cold(冷え症)の略号であり、その「OS-」の右側の「1~15」の数字はグループ番号である。
 なお、上述のように錠剤1錠は300mgであるので、たとえばOS-01の「CY+CK+PPT=30mg/粒」は、錠剤1kg当りでは10万mg(10万ppm)に相当する。
The results are shown in Table 4 and FIG.
“OS-” in the column of the experiment number in Table 4 is an abbreviation for “oversensitivity to cold”, and the numbers “1 to 15” on the right side of “OS-” are group numbers.
As described above, since one tablet is 300 mg, for example, “CY + CK + PPT = 30 mg / grain” of OS-01 corresponds to 100,000 mg (100,000 ppm) per 1 kg of tablet.
Figure JPOXMLDOC01-appb-T000004
 
Figure JPOXMLDOC01-appb-T000004
 
[実施例3]
[γ-シクロデキストリンによる包接化の効果]
 高麗紅参のエキスから調製したジンセノサイドCY290mg/g、CK350mg/g、PPT120mg/gを含有するジンセノサイド粉末にγ-シクロデキストリンを1.5倍重量加え、さらに4倍重量の水を加えて、10,000回転/分にて10分間、冷却しながらホモジナイズした。
 その後、濃縮・乾燥を行い、乾固した固形物を粉末化して、ジンセノサイドCY、CKおよびPPTが包接された粉末を得た。
 次に200mlの水を入れたビーカーを2個用意し、一方には包接前のジンセノサイド粉末を添加し、もう一方には包接された粉末を添加して両方とも攪拌したところ、前者は塊りとなって分散しなかったが、後者はすぐに分散し、溶解状態となった。
[Example 3]
[Effect of inclusion by γ-cyclodextrin]
Ginsenoside powder prepared from ginseng CY 290 mg / g, CK 350 mg / g, and PPT 120 mg / g was added 1.5 times by weight of γ-cyclodextrin and 4 times by weight of water. Homogenization was performed while cooling at 000 rpm for 10 minutes.
Thereafter, concentration and drying were performed, and the dried solid was pulverized to obtain a powder in which ginsenoside CY, CK and PPT were included.
Next, prepare two beakers with 200 ml of water, add ginsenoside powder before inclusion to one, add the encapsulated powder to the other, and stir both. However, the latter dispersed immediately and became dissolved.
 本発明のジンセノサイド組成物は、経口用の組成物(食品、栄養補助食品、健康食品、機能性食品、医薬品など)、身体関連の非経口用の組成物(化粧料、育毛剤、入浴剤など)などの用途に有用である。
 
The ginsenoside composition of the present invention includes oral compositions (food, nutritional supplements, health foods, functional foods, pharmaceuticals, etc.), body-related parenteral compositions (cosmetics, hair restorers, bathing agents, etc.) ).

Claims (3)

  1.  いずれもジンセノサイドであるコンパウンドYを「CY」、コンパウンドKを「CK」、プロトパナキサトリオールを「PPT」と略記するとき、CY、CKおよびPPTの3成分を必須成分として含有するものであること、および、
     三角図表の3頂点をA,B,Cとし、A→B辺にはCYの0→1の目盛りを付し、B→C辺にはCKの0→1の目盛りを付し、C→A辺にはPPTの0→1の目盛りを付し、かつこれらの目盛りは三角図表の外側に張り出した延長線の内向き方向に読むものとするとき、前記の3成分CY、CK、PPTの合計重量に対する各成分の重量割合が、
     P1(0.75,0.2,0.05),
     P2(0.1,0.85,0.05),
     P3(0.1,0.2,0.7)
    の3点で囲まれた領域内にあること、
    を特徴とするジンセノサイド組成物。
    In any case, when compound Y, which is ginsenoside, is abbreviated as “CY”, compound K as “CK”, and protopanaxatriol as “PPT”, it must contain three components of CY, CK and PPT as essential components. ,and,
    The three vertices of the triangular chart are A, B, and C. The scale of 0 → 1 of CY is attached to the A → B side, the scale of 0 → 1 of CK is attached to the B → C side, and C → A. When the side is marked with a PPT scale of 0 → 1, and these scales are read in the direction of the inward extension of the triangle, the total weight of the three components CY, CK and PPT The weight ratio of each component is
    P1 (0.75, 0.2, 0.05),
    P2 (0.1, 0.85, 0.05),
    P3 (0.1, 0.2, 0.7)
    In the area surrounded by the three points
    A ginsenoside composition characterized by the above.
  2.  経口用の組成物または身体関連の非経口用の組成物であることを特徴とする請求項1記載のジンセノサイド組成物。 The ginsenoside composition according to claim 1, which is an oral composition or a body-related parenteral composition.
  3.  CY、CKおよびPPTからなる3成分がシクロデキストリンに包接された状態にあることを特徴とする請求項1記載のジンセノサイド組成物。
     
    The ginsenoside composition according to claim 1, wherein the three components comprising CY, CK and PPT are in a state of being included in cyclodextrin.
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KR20210112738A (en) * 2020-03-06 2021-09-15 성균관대학교산학협력단 Cosmetic composition for skin moisturizing comprising protopanaxatriol as an active ingredient
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