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WO2010084661A1 - Composition, aliment, substance alimentaire, préparation pharmaceutique, produit cosmétique et matière première contenant chacun un composé d'isothiocyanate - Google Patents

Composition, aliment, substance alimentaire, préparation pharmaceutique, produit cosmétique et matière première contenant chacun un composé d'isothiocyanate Download PDF

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Publication number
WO2010084661A1
WO2010084661A1 PCT/JP2009/069512 JP2009069512W WO2010084661A1 WO 2010084661 A1 WO2010084661 A1 WO 2010084661A1 JP 2009069512 W JP2009069512 W JP 2009069512W WO 2010084661 A1 WO2010084661 A1 WO 2010084661A1
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Prior art keywords
isothiocyanate
food
isothiocyanates
insulin
growth factor
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PCT/JP2009/069512
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English (en)
Japanese (ja)
Inventor
佳伸 市川
研二 岡嶋
直明 原田
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金印株式会社
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Priority claimed from JP2009012950A external-priority patent/JP2010001282A/ja
Application filed by 金印株式会社 filed Critical 金印株式会社
Publication of WO2010084661A1 publication Critical patent/WO2010084661A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/12—Ketones
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/191—Carboxylic acids, e.g. valproic acid having two or more hydroxy groups, e.g. gluconic acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/216—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acids having aromatic rings, e.g. benactizyne, clofibrate
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
    • A61K31/222—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin with compounds having aromatic groups, e.g. dipivefrine, ibopamine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/26—Cyanate or isocyanate esters; Thiocyanate or isothiocyanate esters
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline 
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline 
    • A61K31/353—3,4-Dihydrobenzopyrans, e.g. chroman, catechin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/73—Rosaceae (Rose family), e.g. strawberry, chokeberry, blackberry, pear or firethorn
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/14—Drugs for dermatological disorders for baldness or alopecia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A61P25/16—Anti-Parkinson drugs
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/24—Antidepressants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/12—Antihypertensives

Definitions

  • the present invention has an action to promote the production and release of calcitonin gene-related peptide (CGRP) and an action to promote the secretion of insulin-like growth factor-1 (IGF-1), and various diseases such as hypertension, obesity and other lifestyle-related diseases, and cognition
  • CGRP calcitonin gene-related peptide
  • IGF-1 insulin-like growth factor-1
  • the present invention relates to isothiocyanates-containing compositions, foods, food materials, medicines, and cosmetics for the purpose of prevention of diseases and depression, improvement of QOL, and beauty.
  • CGRP Calcitonin gene related peptide
  • CGRP suppresses vasodilation, osteoblast proliferation, osteoclast activation, appetite suppression, and HF k B activation, thereby suppressing TNF- ⁇ production and cancer cell apoptosis.
  • CGRP vascular endothelial cells
  • production of prostaglandins such as NO and PGI 2 is enhanced, but these substances exert a TNF- ⁇ production inhibitory action in addition to the blood flow increasing action .
  • CGRP is known to exert an important effect on the circulatory system, including systemic vasodilation, positive chronotropism and inotropic activity, extracorporeal excretion of NaCl, coronary vasodilation, and renal blood. It has a flow increase effect etc.
  • IGF-1 Insulin-like growth factor-1
  • IGF-1 is a peptide hormone with a molecular weight of about 7500, which has a structure and action very similar to insulin (see, for example, Non-Patent Document 5).
  • IGF-1 is known to actively maintain cells in a healthy state, such as promoting cell differentiation and promoting cell growth (see, for example, Non-Patent Documents 6, 7 and 8).
  • the object of the present invention is to provide a composition, food, food material, medicine and cosmetics exhibiting CGRP and IGF-1 secretion promoting action for the purpose of preventing various diseases mentioned above or improving QOL and beauty. is there.
  • isothiocyanates and at least one selected from the group consisting of isoflavones, raspberry ketones, capsiates, gluconic acid, chlorogenic acid, cocoa polyphenols, and hachicho-miso Contained in combination it is characterized in that it exhibits a production and release promoting action of calcitonin gene-related peptide (CGRP) or an insulin-like growth factor-1 (IGF-1) secretion promoting action.
  • CGRP calcitonin gene-related peptide
  • IGF-1 insulin-like growth factor-1
  • isothiocyanates and isoflavones isothiocyanates and isoflavones, raspberry ketone, capsiate, gluconic acid, chlorogenic acid, cocoa polyphenols, and Haccho miso from the group It is characterized in that it contains at least one selected in combination and exhibits a production and release promoting action of calcitonin gene-related peptide (CGRP) or an insulin-like growth factor-1 (IGF-1) secretion promoting action.
  • CGRP calcitonin gene-related peptide
  • IGF-1 insulin-like growth factor-1
  • the present invention contains isothiocyanates and at least one selected from the group consisting of isoflavones, raspberry ketones, capsiates, gluconic acid, chlorogenic acid, cocoa polyphenols, and haccho miso to produce calcitonin gene related peptide (CGRP) And, since it has been made to exhibit a release promoting action and a secretion promoting action of insulin-like growth factor-1 (IGF-1), effects such as prevention of various diseases, improvement of QOL, and beauty can be exhibited.
  • IGF-1 insulin-like growth factor-1
  • the composition of the present invention is a combination of isothiocyanates with at least one selected from the group consisting of isoflavones, raspberry ketones, capsiates, gluconic acid, chlorogenic acids, cocoa polyphenols, and haccho miso. And each of these components as an essential component.
  • the essential component refers to an optional component, and refers to a component which is necessarily contained in the constitution, and is not subject to quantitative restriction.
  • the isothiocyanates used in the present invention are 4-methylsulfinylbutyl isothiocyanate, 5-methylsulfinylpentyl isothiocyanate, 6-methylsulfinylhexyl isothiocyanate, 7-methylsulfinylheptyl isothiocyanate, 8-methylsulfinyloctyl isothiocyanate, Allyl isothiocyanate, secondary butyl isothiocyanate, 3-butenyl isothiocyanate, 4-pentenyl isothiocyanate, 5-hexenyl isothiocyanate, 5-methyl thiopentyl isothiocyanate, 6-methyl thiohexyl isothiocyanate, 7-methyl thioheptyl isothiocyanate , 8-Methylthiooctyl isothiocyanate, ⁇ -phenethyl isothiocyanate, benzyl
  • the isothiocyanates that can be used in the present invention are not limited to the above compounds, and all isothiocyanates can be used as a raw material.
  • the above-mentioned isothiocyanates are also effective in chemically synthesized ones, and the effect is not different depending on the synthesis method and the source material, and they do not affect the present invention at all.
  • the chemical synthesis of isothiocyanates is specifically described as follows. In principle, it follows the method of Kiaer et al. (Kiaer et al. Acta Chem. Scand, 11, 1298, 1957).
  • isothiocyanates can be obtained from cruciferous plants mainly from natural resources.
  • the method includes grinding or grating treatment, extraction treatment with a solvent, and drying treatment singly or in combination, the method is not limited at all in the present invention.
  • the raw materials containing the above-mentioned isothiocyanates include the following.
  • Batissidae (Bataceae), Brassicaceae (Brassicaceae), Breschnadidae (Bretschneideraceae), Citrusaceae (Capparaceae), Papaya (Caricaceae), Euphorbiaceae (Euphorbiaceae), Gyrostemonidae (Gyrostemonaceae), Limnantes ( Limnanthaceae), Wasabinaceae (Moringaceae), Pentadipiprandaceae (Pentadiplandraceae), Phytolaccidae (Phytolaccaceae), Tobellanaceae (Pittosporaceae), Prunellanaceae (Resedaceae), Salvadoriaceae (Salvadoraceae), Touariaceae (Tovar) plants of the family Luceidae (Tropaeolaceae), for example, Batis maritima (Japanese name unknown), wasabi (Wasabia), Bat
  • Incana Japanese name unknown
  • Shinobumokusou Reseda alba
  • Salvadora persica Japanese name unknown
  • Tovaria pendula Japanese name unknown
  • Kumquat deer Kumquat deer
  • the isothiocyanates which can be used in the present invention are not limited to those obtained from the above-mentioned plant species, and all natural resources containing isothiocyanates can be used as a raw material.
  • the origin of isoflavones used in the present invention is not particularly limited, and examples thereof include soybean seeds, soya root and foods using them.
  • soybean hypocotyl is advantageous because it contains a large amount of isoflavone. It is also possible to use foods such as natto.
  • isoflavones daidzein, genistein, glycitein, soy in, genistin, glycitin, 6 ′ ′-O-malonyl soyin, 6 ′ ′-O-malonylgenistin, 6 ′ ′-O-malonylglycitin, 6 ′ ′-O-acetyl soy
  • the above-ment daidzein, genistein
  • soy and soy foods soy hypocotyls, extracts of soda rootstock and purified products thereof because high concentrations of isoflavones are used.
  • the solvent for extracting isoflavones is not particularly limited, but it is preferable to use water or an alcohol such as ethanol.
  • a synthetic adsorbent, ion exchange resin, ultrafiltration or the like it is not particularly limited.
  • the extract or purified liquid may be used as it is, or a concentrate obtained by concentrating them or a powder obtained by drying the extract or purified liquid may be used.
  • the raspberry ketone used in the present invention is not particularly limited, but it is desirable to use raspberry-derived raspberry ketone from the viewpoint of easy collection and safety.
  • the capsiate used in the present invention is not particularly limited, but it is desirable to use the variety "CH-19 sweet" selected and bred from pepper, from the viewpoint of easy collection and safety.
  • the above raspberry ketone and capsiate may be used as they are by grinding raspberry or the above-mentioned specific pepper variety as it is, but since raspberry ketone or capsiate having a high concentration is used, the extract or its purified product may be used. It is also possible to use.
  • the solvent for extracting raspberry ketone and capsiate is not particularly limited, but it is preferable to use water or an alcohol such as ethanol.
  • the extract or purified liquid may be used as it is, or a concentrate obtained by concentrating them or a powder obtained by drying the extract or purified liquid may be used.
  • capsiate used in the present invention capsaicin may be used, or peppers of generally grown varieties or extracts thereof may be used. Stimulative, long-term, it is difficult for all people to use on a daily basis. Therefore, it is desirable to use capsiate which is considered to be less irritating.
  • gluconic acid used in the present invention is not particularly limited, it is desirable to use gluconic acid derived from honey or royal jelly from the viewpoint of easy intake and safety.
  • miso and vinegar may be used.
  • the chlorogenic acid used in the present invention is not particularly limited, but it is desirable to use coffee bean-derived chlorogenic acid from the viewpoint of easy collection and safety.
  • the above gluconic acid and chlorogenic acid can be used by grinding honey and royal jelly or coffee beans as it is, but using gluconic acid and chlorogenic acid with high concentration, their extracts and their purification It is also possible to use a thing.
  • the solvent for extracting gluconic acid and chlorogenic acid is not particularly limited, but it is preferable to use water or an alcohol such as ethanol.
  • purification can use synthetic adsorbent, ion exchange resin, ultrafiltration etc., it is not specifically limited.
  • the extract or purified liquid may be used as it is, or a concentrate obtained by concentrating them or a powder obtained by drying the extract or purified liquid may be used.
  • gluconic acid used in the present invention it is also possible to use calcium gluconate, potassium gluconate, copper gluconate, sodium gluconate, magnesium gluconate, manganese gluconate and the like as gluconate.
  • the cocoa polyphenols used in the present invention can also be taken from foods that use cocoa, such as chocolate and cocoa.
  • cocoa polyphenol in order to use a high concentration cocoa polyphenol, it is also possible to use its extract and its refinement
  • the solvent for extracting cocoa polyphenol is not particularly limited, but it is preferable to use water or an alcohol such as ethanol.
  • purification can use synthetic adsorbent, ion exchange resin, ultrafiltration etc., it is not specifically limited.
  • the extract or purified liquid may be used as it is, or a concentrate obtained by concentrating them or a powder obtained by drying the extract or purified liquid may be used.
  • Hatcho miso used in the present invention is mainly made in Okazaki City, Aichi Prefecture. The soybean miso is characterized by being aged for 2 years or more.
  • an extract of Haccho Miso may be used.
  • the solvent to be extracted is not particularly limited, but it is preferable to use water or an alcohol such as ethanol.
  • purification can use synthetic adsorbent, ion exchange resin, ultrafiltration etc., it is not specifically limited.
  • the extract or purified liquid may be used as it is, or a concentrate obtained by concentrating them or a powder obtained by drying the extract or purified liquid may be used.
  • composition of the present invention comprises, as essential components, isoflavone, raspberry ketone, capsiate, gluconic acid, chlorogenic acid, cocoa polyphenol, and at least one of hachicho-miso and the isothiocyanates obtained as described above.
  • a mixture of these may be used directly as it is, but generally, a solution or dispersion of these in a suitable liquid carrier or a mixture in a suitable powder carrier is used.
  • the content for the above-mentioned isothiocyanates to become an active ingredient is usually preferably in the range of 0.0001 to 0.5% by weight (hereinafter abbreviated as "%") in the liquid form, and it is preferable In the case of 0.001 to 20% in the case of granules, it is preferable that the range of 0.001 to 10% is in the case of granules.
  • the content of isoflavone as an active ingredient is generally preferably 0.001 to 0.5% by weight (hereinafter abbreviated as "%") in the liquid preparation, and 0. The range of 01 to 80% is preferable, and in the case of granules, the range of 0.01 to 40% is preferable.
  • the content for the raspberry ketone to be an active ingredient is usually preferably in the range of 0.05 to 20% in the solution, and preferably in the range of 0.05 to 100% in the case of powders. In the case of granules, it is preferably in the range of 0.05 to 100%.
  • the content for the above-mentioned capsiate to become an active ingredient is usually suitably in the range of 0.0001 to 0.05% in the liquid preparation and in the range of 0.0001 to 5% in the dust preparation. In the case of granules, it is preferable to be in the range of 0.0001 to 5%.
  • the content for the above-mentioned gluconic acid to become an active ingredient is usually suitably in the range of 0.05 to 10% in the liquid preparation, and in the range of 0.05 to 20% in the powder preparation In the case of granules, the preferred range is 0.05 to 10%.
  • the content for the chlorogenic acid to be an active ingredient is generally preferably in the range of 0.05 to 20% in the liquid preparation and in the range of 0.05 to 10% in the dust In the case of granules, the preferred range is 0.05 to 10%.
  • the content for the above-mentioned cocoa polyphenol to become an active ingredient is usually suitably in the range of 0.5 to 20% in the liquid preparation and in the range of 0.5 to 10% in the case of powders.
  • the content for the above-mentioned Haccho miso to become an active ingredient is usually suitable in the range of 10 to 100% in the liquid preparation, and preferably in the range of 20 to 50% in the powder preparation, In the case of granules, it is preferable that it is in the range of 20 to 50%.
  • isoflavone, raspberry ketone, capsiate, gluconic acid, chlorogenic acid, cocoa polyphenol, and Haccho miso can be used in combination within the above range.
  • the edible composition of the present invention is expected to have the same action and effect as the above-mentioned action and effect seen when administered to humans not only in humans but also in animals such as pets and livestock.
  • the dose differs depending on the difference between the organisms to be administered and which one of the various effects described above is to be obtained. It is set appropriately. For example, for an adult, the mixture of the above isoflavones etc.
  • compositions of the present invention can be taken alone, but can also be used by being added to various food products or medicines. Specifically, liquid foods such as soft drinks, tea beverages, drinks, alcoholic beverages, solid foods such as fruits, breads, noodles, seasonings, etc., pharmaceuticals such as powders, granules, capsules and tablets Add to quasi-drugs etc.
  • the composition of the present invention can also obtain the same effect as taking it orally or applying it by sniffing the isothiocyanate contained or exposing it to volatilized isothiocyanates. . Specifically, it can be used by blending it into an aroma oil, a fragrance, daily necessities for perfume, cosmetics, perfumes, fibers or resins, etc. and volatilizing the components.
  • the concentration when exposed to volatilized isothiocyanate, the concentration is not limited, but it is desirable that the concentration is within the range that can be recognized by human being without causing irritation or discomfort. There is no particular relationship between the concentration and the effect.
  • Test Example 1 Changes in IGF-1 and CGRP Concentrations in Mice by Administration of Isothiocyanates
  • a standard diet was prepared for C57BL / 6 mice (male, 5 mice in each group) of 6-8 weeks divided into 16 groups.
  • a test product was administered. After administration for 4 weeks, various organs collected under anesthesia were immersed in 1 N acetic acid solution, homogenized, and centrifuged to measure IGF-1 concentration in the supernatant. Blood was also collected to measure plasma IGF-1 and CGRP concentrations. The concentrations of IGF-1 and CGRP in mouse brain and plasma are shown in Table 1.
  • 6-MSITC 6-methylsulfinyl hexyl isothiocyanate
  • the above 16 groups are administered 6-MSITC (MS), isoflavone (IS), 6-MSITC + isoflavone (MS + IS) administered, raspberry ketone (RA) administered, 6-MSITC Raspberry ketone (MS + RA) administration group, capsiate (CE) administration group, 6-MSITC + capsiate (MS + CE) administration group, gluconic acid (GA) administration group, 6-MSITC + gluconic acid (MS + GA) administration group, chlorogenic acid (CA) administration group 6-MSITC + chlorogenic acid (MS + CA) administration group, cocoa polyphenol (CP) administration group, 6-MSITC + cocoa polyphenol (MS + CP) administration group, Haccho miso (HM) administration group, 6-MSITC + Haccho miso (MS + HM) administration group Any of non-administration group (standard diet
  • each group is added to the standard diet, and in the MS administration group, 6-MSITC is administered at 0.1 mg / kg / day.
  • the IS administration group 50 mg / kg / day of isoflavone was administered.
  • the RA administration group 400 mg / kg / day of raspberry ketone was administered.
  • the CE administration group administration of 0.1 mg / kg of capsiate.
  • gluconic acid was administered at 1 mg / kg / day.
  • chlorogenic acid was administered at 1 mg / kg / day.
  • CP administration group 50 mg / kg / day of cocoa polyphenol was administered.
  • Haccho Miso was administered at 600 mg / kg / day.
  • mice The effect of improving learning function by isothiocyanates For the mice divided into 16 groups (5 mice in each group), in addition to the standard diet for 4 weeks a test product is administered, and then the Morris water maze test is carried out for 5 days And assessed the impact on the learning function.
  • the above 16 groups are administered 6-MSITC (MS), isoflavone (IS), 6-MSITC + isoflavone (MS + IS) administered, raspberry ketone (RA) administered, 6-MSITC Raspberry ketone (MS + RA) administration group, capsiate (CE) administration group, 6-MSITC + capsiate (MS + CE) administration group, gluconic acid (GA) administration group, 6-MSITC + gluconic acid (MS + GA) administration group, chlorogenic acid (CA) administration group 6-MSITC + chlorogenic acid (MS + CA) administration group, cocoa polyphenol (CP) administration group, 6-MSITC + cocoa polyphenol (MS + CP) administration group, Haccho miso (HM) administration group, 6-MSITC + Haccho miso (MS + HM) administration group Any of the non-administration group (standard diet only, control group) Or to belong.
  • each group is added to the standard diet, and in the MS administration group, 6-MSITC is administered at 0.1 mg / kg / day.
  • the IS administration group 50 mg / kg / day of isoflavone was administered.
  • the RA administration group 400 mg / kg / day of raspberry ketone was administered.
  • the CE administration group 0.1 mg / kg of capsiate was administered.
  • the GA administration group gluconic acid was administered at 1 mg / kg / day.
  • chlorogenic acid was administered at 1 mg / kg / day.
  • cocoa polyphenol 50 mg / kg / day was administered.
  • Haccho Miso was administered at 600 mg / kg / day.
  • Test Example 3 Test of nerve regeneration effect in mouse brain by 6-MSITC administration After Example 2, the brains of mice used in the experiment were collected, and the influence on nerve regeneration was evaluated. At that time, newborn neurons were detected by using 5-bromo-2-deoxyuridine (Brdu) and Brdu antibodies. Histological evaluation was performed by measuring left and right hippocampal neuronal layer length and neuronal cell number and calculating the number per unit length (mm). As a result, the number of neoplastic cells was significantly increased in the MS administration group as compared to the control group. In addition, in the group administered in combination with MS and other test substances, the tendency to increase was more remarkable.
  • Prdu 5-bromo-2-deoxyuridine
  • Example 4 Evaluation of antidepressant action by 6-MSITC administration As in Example 2, divided into 16 groups, the effect on the antidepressant action in mice receiving the standard diet and each test sample was examined by tail suspension test . Male mice weighing 20-25 g and 8 weeks old were used. The tail of the mouse was pinched and hung upside down with a wooden clip fixed at a height of 35 cm from the floor on a stand 60 cm high. The mouse is active at first, but gives up gradually to move. The antidepressant effect of the administered ingredients was evaluated as shortening of the non-moving time (inactive time) within 6 minutes after the start of suspension. As a result, in the MS administration group, the inactive time was significantly reduced by 30% as compared with the control group.
  • Test Example 5 Test of action to promote calcitonin gene related peptide production by 6-MSITC in ovariectomized rats and effect on osteoporosis 80 SD female rats (5 rats per group, divided into 17 groups) Twenty groups of 21 groups were given an ovariectomized rat on day 10 after excision and a standard diet [Ca-deficient diet (Ca: 0.004%, P: 0.3%)] etc. I kept it for 28 days. Thereafter, they were fasted overnight (18 hours), and rats in all groups were sacrificed and femurs were removed therefrom.
  • the 16 groups from which the ovaries were removed were, for example, the 6-MSITC (MS) administration group, the isoflavone (IS) administration group, 6-MSITC + isoflavone (MS + IS IS Administration group, raspberry ketone (RA) administration group, 6-MSITC + raspberry ketone (MS + RA) administration group, capsiate (CE) administration group, 6-MSITC + capsiate (MS + CE) administration group, gluconic acid (GA) administration group, 6-MSITC + glucone Acid (MS + GA) administration group, chlorogenic acid (CA) administration group, 6-MSITC + chlorogenic acid (MS + CA) administration group, cocoa polyphenol (CP) administration group, 6-MSITC + cocoa polyphenol (MS + CP) administration group, Haccho miso (HM) Administration group, 6-MSITC + Haccho miso (MS + HM) administration , It belongs to one of the non-administered group (standard diet only.
  • Control group That is, each group is added to the standard diet, and in the MS administration group, 6-MSITC is administered at 0.1 mg / kg / day.
  • IS administration group 50 mg / kg / day of isoflavone was administered.
  • RA administration group raspberry ketone 400 mg / kg / day was administered.
  • CE administration group 0.1 mg / kg of capsiate was administered.
  • GA administration group gluconic acid was administered at 1 mg / kg / day.
  • CA administration group chlorogenic acid 1 mg / kg / day was administered.
  • CP administration group 50 mg / kg / day of cocoa polyphenol was administered.
  • HM Haccho Miso was administered at 600 mg / kg / day. Furthermore, the combination of MS + IS, MS + RA, MS + CE, MS + GA, MS + CA, MS + CP, and MS + HM was performed using these combinations. Then, based on the femur removed from the 17 groups described above, that is, the normal group (without ovariectomy) and the control group (ovariectomy) and 15 test groups (administration of ovariectomy + 6-MSITC etc.) The weight was measured and the volume was measured by a pycnometer to calculate bone density. In addition, measurement of calcitonin gene related peptide concentration (CGRP) in bone tissue was also performed. These results are shown together in Table 3 below.
  • CGRP calcitonin gene related peptide concentration
  • 6-MSITC intake of 6-MSITC has an effect on hypertension since it promotes production and release of calcitonin gene-related peptide. Furthermore, it has been confirmed that the action is enhanced by the combination of 6-MSITC with at least one of isoflavone, raspberry ketone, capsiate, gluconic acid, chlorogenic acid, cocoa polyphenol and Haccho miso.
  • the animals were fed with a feed adjusted to have an intake of capsiate (CE) of 1 mg / kg body weight / day.
  • CE capsiate
  • the animals were fed with a feed adjusted to have an intake of gluconic acid (GA) of 4 mg / kg body weight / day.
  • the animals were fed with a feed adjusted to have an intake of chlorogenic acid (CA) of 3 mg / kg body weight / day.
  • CA chlorogenic acid
  • the animals were fed with a feed adjusted to have an intake of cocoa polyphenol (CP) of 200 mg / kg body weight / day.
  • CP cocoa polyphenol
  • the animals were reared with a feed adjusted to have an intake of 600 mg / kg body weight / day of Haccho Miso (HM).
  • At least one of isoflavone, raspberry ketone, capsiate, gluconic acid, chlorogenic acid, cocoa polyphenols, and haccho miso and 6-MSITC are simultaneously measured as a result of measuring the amount of calcitonin gene-related peptide and insulin-like growth factor in hair follicles. It was found that the given group was significantly more than the other groups.
  • gluconic acid 100 mg was ingested daily by administration of a tablet containing gluconic acid (GA).
  • 100 mg of chlorogenic acid was ingested daily by administration of a tablet containing chlorogenic acid (CA).
  • CA chlorogenic acid
  • CP cocoa polyphenol
  • HM Hachidamei
  • Groups 3, 5, 7, 9, 11, 13, 15 were also ingested with these combinations as shown in Table 5.
  • Group 16 was ingested a simulated tablet. This was done for six months.
  • the number of hair loss collected during the above test was measured to evaluate the hair loss improving effect.
  • the measurement method of the above-mentioned hair loss performed four days continuous hair washing, collected the hair loss of the last three days with the fine nonwoven fabric of mesh, counted the number, and was performed. And the judgment of the said evaluation was shown as follows from the change of the number of hair loss in each time with respect to sampling before. +++: The number of hair loss has been reduced by 30 or more, and a remarkable effect was observed. ++: The number of hair loss has been reduced by more than 20, and a considerable effect was observed. +: The number of hair loss was reduced by 10 or more, and a slight effect was observed.
  • ⁇ Decrease or decrease in the number of hair loss was less than 10, and almost no effect was observed. From the results in Table 5 above, when 6-MSITC is ingested alone or in combination with at least one of isoflavone, raspberry ketone, capsiate, gluconic acid, chlorogenic acid, cocoa polyphenols, and Haccho miso together with 6-MSITC, a simulated tablet is obtained. Hair loss was improved compared to the group who received Also, in the group in which 6-MSITC and isoflavone or royal jelly were simultaneously ingested, a remarkable improvement effect on hair loss was observed.
  • Test of hair growth effect on humans by applying lotion containing isothiocyanates The subject was a volunteer male (30 to 50 years old) having hair loss and thin hair trouble, and was divided into a total of 9 groups of 5 persons. .
  • groups 1 to 8 1 ml of a lotion containing 0.01% of 6-MSITC is applied to the scalp once a day, and in group 2, isoflavone is taken as a 50 mg tablet daily, and in group 3 raspberry ketone is daily It was ingested in a 600 mg tablet.
  • capsiate was ingested in 2 mg tablets per day, and in group 5 gluconic acid was ingested in 100 mg tablets per day.
  • group 6 chlorogenic acid was ingested in 100 mg tablets per day, and in group 7, cocoa polyphenol was ingested in 600 mg tablets per day.
  • group 8 Hachcho miso was ingested in a daily dose of 5000 mg tablets, and group 9 was similarly applied with a lotion containing no 6-MSITC as a control group, and ingested simulated tablets. This was done for six months. Next, the number of hair loss collected during the above test (before the start of application of the lotion, after 3 months of application and after 6 months of application) was measured to evaluate the hair loss improving effect.
  • the measurement method of the above-mentioned hair loss performed four days continuous hair washing, collected the hair loss of the last three days with the fine nonwoven fabric of mesh, counted the number, and was performed. And judgment of the above-mentioned evaluation was displayed as follows from change of the number of hair loss in each time to before the start of application of a lotion. +++: The number of hair loss decreased by 30 or more, and a remarkable effect was recognized. ++: The number of hair loss decreased by 20 or more, and a considerable effect was recognized. +: The number of hair loss decreased by 10 or more, and a slight effect was recognized. ⁇ : The decrease in the number of hair loss is less than or increased by 10, and it can not be said to be effective. The results are shown in Table 7 below.
  • the composition of the present invention comprises, as essential components, at least one of isoflavone, raspberry ketone, capsiate, gluconic acid, chlorogenic acid, cocoa polyphenols, and hacho-miso and 6-MSITC, and is derived from insulin-like growth factor-I.

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Abstract

La présente invention concerne une composition présentant une activité favorisant la production et la libération d'un peptide associé au gène de la calcitonine (CGRP) et une activité favorisant la sécrétion du facteur de croissance de type insulinique 1 (IGF-1). La composition peut contribuer à la prévention de diverses maladies, l'amélioration du QRL, l'augmentation d'une belle apparence et analogues. La composition comprend une combinaison d'un composé d'isothiocyanate et d'au moins une substance choisie dans un groupe constitué d'isoflavone, de cétone de framboise, de capsiate, d'acide gluconique, d'acide chlorogénique, de polyphénol de cacao et de Haccho miso (une sorte de pâte de soja fermentée).
PCT/JP2009/069512 2009-01-23 2009-11-11 Composition, aliment, substance alimentaire, préparation pharmaceutique, produit cosmétique et matière première contenant chacun un composé d'isothiocyanate WO2010084661A1 (fr)

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Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2015036370A (ja) * 2013-08-13 2015-02-23 晨星興産株式会社 サツマイモポリフェノール抽出液を用いた毛生え組成物
WO2018066707A1 (fr) * 2016-10-07 2018-04-12 株式会社 Ｐａｌ Inhibiteur de vieillissement, inhibiteur de calcification de tissu mou et inhibiteur de destruction de tissu pulmonaire
CN107929474A (zh) * 2017-12-15 2018-04-20 苏州科技城医院 一种治疗抑郁症的药物组合物
CN108601753A (zh) * 2015-12-01 2018-09-28 宝洁公司 抑制胆碱向三甲胺(tma)的转化的方法
US11246844B2 (en) 2016-06-29 2022-02-15 The Procter & Gamble Company Methods for inhibiting conversion of choline to trimethylamine (TMA)

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JP2009126826A (ja) * 2007-11-22 2009-06-11 Atsuo Sekiyama 抗ストレス剤
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JPH03153614A (ja) * 1989-11-09 1991-07-01 Minato Sangyo Kk 育毛剤
JP2003113117A (ja) * 2001-07-31 2003-04-18 Daicho Kikaku:Kk 抗うつ剤、抗更年期障害剤、抗老人性痴呆症剤、抗アルツハイマー剤
JP2005536449A (ja) * 2001-12-18 2005-12-02 ブラシカ・ファウンデーション・ケモプロテクション・リサーチ，インコーポレイテッド グルタチオンおよび第２相解毒酵素による酸化ストレス障害の予防および治療
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Cited By (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2015036370A (ja) * 2013-08-13 2015-02-23 晨星興産株式会社 サツマイモポリフェノール抽出液を用いた毛生え組成物
CN108601753A (zh) * 2015-12-01 2018-09-28 宝洁公司 抑制胆碱向三甲胺(tma)的转化的方法
CN108601754A (zh) * 2015-12-01 2018-09-28 宝洁公司 抑制肉毒碱向三甲胺（tma）转化的方法
US10780072B2 (en) 2015-12-01 2020-09-22 The Procter & Gamble Company Methods for inhibiting conversion of choline to trimethylamine (TMA)
US10786479B2 (en) 2015-12-01 2020-09-29 The Procter & Gamble Company Methods for inhibiting conversion of carnitine to trimethylamine (TMA)
US11246844B2 (en) 2016-06-29 2022-02-15 The Procter & Gamble Company Methods for inhibiting conversion of choline to trimethylamine (TMA)
WO2018066707A1 (fr) * 2016-10-07 2018-04-12 株式会社 Ｐａｌ Inhibiteur de vieillissement, inhibiteur de calcification de tissu mou et inhibiteur de destruction de tissu pulmonaire
JPWO2018066707A1 (ja) * 2016-10-07 2019-09-05 株式会社Ｐａｌ 老化抑制剤、軟部組織の石灰化抑制剤、及び肺組織破壊抑制剤
JP7068704B2 (ja) 2016-10-07 2022-05-17 株式会社Pal 老化抑制剤、軟部組織の石灰化抑制剤、及び肺組織破壊抑制剤
CN107929474A (zh) * 2017-12-15 2018-04-20 苏州科技城医院 一种治疗抑郁症的药物组合物

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