WO2014129238A1 - Composition d'activation de trpa1 - Google Patents

Composition d'activation de trpa1 Download PDF

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Publication number
WO2014129238A1
WO2014129238A1 PCT/JP2014/050763 JP2014050763W WO2014129238A1 WO 2014129238 A1 WO2014129238 A1 WO 2014129238A1 JP 2014050763 W JP2014050763 W JP 2014050763W WO 2014129238 A1 WO2014129238 A1 WO 2014129238A1
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WO
WIPO (PCT)
Prior art keywords
trans
trpa1
unsaturated aldehyde
double bond
carbon atoms
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PCT/JP2014/050763
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English (en)
Japanese (ja)
Inventor
徹 比良
原　博
千草 西山
貴稔 山下
今義　潤
Original Assignee
株式会社Ｊ－オイルミルズ
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Publication of WO2014129238A1 publication Critical patent/WO2014129238A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • 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
    • A61K31/11—Aldehydes
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/10—Laxatives
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/04—Anorexiants; Antiobesity agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/06—Antihyperlipidemics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q7/00—Preparations for affecting hair growth
    • A61Q7/02—Preparations for inhibiting or slowing hair growth
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/74—Biological properties of particular ingredients
    • A61K2800/78—Enzyme modulators, e.g. Enzyme agonists

Definitions

  • the present invention relates to a TRPA1 activation composition, and more particularly to a TRPA1 activation composition containing acrylic acid and / or a specific unsaturated aldehyde as an active ingredient.
  • TRPA1 When TRPA1 is activated by administering or applying the above TRPA1 activating component to mammals including humans, a cool feeling or a spicy feeling is aroused.
  • TRPA1 When TRPA1 is activated by a cooling sensation of 17 ° C. or less, body heat production is promoted and heat dissipation is suppressed, thereby suppressing a decrease in body temperature.
  • the suppression of the decrease in body temperature in a cold environment can also occur by the stimulation of carbonated water (Non-patent Document 3).
  • CCK has a physiological function of directly acting on the center to suppress appetite and induce a feeling of fullness.
  • TRPA1 activation induces appetite suppression and satiety through CCK secretion induction. If appetite suppression and satiety are obtained, body fat accumulation and obesity are suppressed, resulting in hyperlipidemia, hypercholesterolemia, hypertriglyceridemia, hypertension, arteriosclerosis, ischemic heart disease, stroke, Risk factors for diseases such as obstructive arteriosclerosis can be reduced. Therefore, the composition of the present invention is expected to be used as a body fat accumulation inhibitor, an adipocyte differentiation inducer, an appetite suppressant, an anti-obesity agent and the like.
  • Non-Patent Document 5 TRPA1 mRNA was detected in the murine and human duodenal mucosa, and in the mouse enteric nerve-derived cell line STC-1 (intestinal mouse neuroendocrine STC-1 cells). Stimulation of the STC-1 cell line with AITC increased intracellular calcium ions and significantly stimulated CCK secretion. AITC-induced CCK secretion was completely blocked by deficiency of extracellular calcium ions and ruthenium red (TRPA1 antagonist). From the findings of Non-Patent Document 5, the CCK secretion activity of a candidate substance that activates TRPA1 in the presence of a TRPA1 inhibitor, or the CCK secretion activity of the candidate substance in the presence or absence of extracellular calcium ions is examined. Thus, the TRPA1 activity ability of the candidate substance can be investigated.
  • Unsaturated aldehydes according to the present invention can be found in the TRPA1 inhibitor test using the STC-1 cell line and in the extracellular calcium ion depletion test, AITC, which is a TRPA1 activating component. Exhibited exactly the same behavior. Therefore, it can be said that the composition containing an unsaturated aldehyde according to the present invention as an active ingredient has TRPA1 activation ability.
  • unsaturated fatty acids and saturated or unsaturated hydrocarbons other than saturated aldehydes, saturated or unsaturated alcohols, saturated fatty acids or acrylic acid have inferior TRPA1 activation ability that can be evaluated by CCK secretion promoting activity.
  • Examples of such unsaturated aldehydes include trans, trans-2,4-hexadienal, trans, trans-2,4-heptadienal, trans, trans-2,4-nonadienal, trans, trans-2,4 -Decadienal, trans, trans-2,4-dodecadienal, 2-butenal, trans-2-heptenal, trans-2-octenal, trans-2-nonenal, trans-4-decenal, cis-4-decenal, etc. .
  • the composition of the present invention essentially contains the unsaturated aldehyde having a double bond at the 2-position.
  • unsaturated aldehydes include trans, trans-2,4-hexadienal, trans, trans-2,4-heptadienal, trans, trans-2,4-nonadienal, trans, trans-2,4 -Decadienal, trans, trans-2,4-dodecadienal, 2-butenal (crotonaldehyde), trans-2-heptenal, trans-2-octenal, trans-2-nonenal and the like.
  • the composition of the present invention essentially comprises the unsaturated aldehyde having two double bonds and the unsaturated aldehyde having one double bond, or the unsaturated aldehyde having two double bonds. It is preferable to include. It was found that a combination of two or more unsaturated aldehydes synergistically promotes TRPA1 activation ability.
  • the unsaturated aldehyde having one double bond preferably has 8 or less carbon atoms, and more preferably trans-2-octenal.
  • the unsaturated aldehyde having two double bonds is preferably trans, trans-2,4-hexadienal, trans, trans-2,4-heptadienal, trans, trans-2,4-decadienal. In addition, when the unsaturated aldehyde having two double bonds is essential, it is preferable that trans, trans-2,4-heptadienal is essential.
  • the composition of the present invention like the conventional TRPA1 activating component, arouses coolness and spiciness, suppresses body temperature decrease (especially, suppression in a cold environment), and induces differentiation of adipocytes in animals including humans. , Reduction of hair growth, constipation-type irritable bowel syndrome, prevention or treatment of flaccid constipation and functional gastrointestinal disorders, accelerated recovery of skin barrier function, delayed excretion of stomach contents, decreased food intake (appetite), hunger Effects such as a reduction in sensation and an increase in satiety are expected. Therefore, specific uses of the composition of the present invention are effective for beverages that can provide a cool feeling and spicy feeling, appetite suppression, bulimia prevention / improvement, obesity prevention / improvement, and body fat accumulation suppression. Addition to food and drink, etc. is mentioned.
  • the CCK producing cell line STC-1 derived from mouse small intestine was cultured in a Dulbecco's modified Eagle's medium containing 10% fetal calf serum in a 48-well plate at 37 ° C., 5% CO 2. In the presence, the cells were cultured for 2-3 days until they became subconfluent. After washing the wells with HEPES buffer, 100 ⁇ L of an evaluation solution containing 100 ⁇ M of a test substance was added and incubated at 37 ° C. for 60 minutes.
  • Intracellular calcium concentration measurement method The intracellular calcium ion concentration kinetics of the CCK producing cell line STC-1 was monitored using the fluorescent probe Fura 2-AM.
  • This probe is an aceoxymethyl (AM) body having a BAPTA structure exhibiting a calcium ion-selective complex-forming behavior and having increased liposolubility so as to be taken into cells.
  • the acetoxymethyl group is hydrolyzed by esterase in the cell, and Fura-2 is dispersed into the cell.
  • STC-1 cells were cultured on cover slips for 2 days.
  • 2 ⁇ M Fura-2-AM intracellular calcium ion indicator, obtained from Life Technologies Japan
  • HEPES buffer containing 0.005% Pluronic F-127 (surfactant, obtained from Life Technologies Japan Ltd.) It dissolved so that it might become.
  • the cover slip in which the cells were cultured in the above solution was exposed and kept at a temperature of 37 ° C. for 20 minutes to incorporate Fura-2-AM into the cells.
  • the cover slip was fixed to a folder and immersed in a cuvette containing HEPES buffer.
  • FIG. 1A shows a sample containing an unsaturated aldehyde (Examples 1 to 3) according to the present invention in the presence or absence of extracellular calcium ions in the presence or absence of extracellular calcium ions. It is a graph which shows the change of the amount of CCK secretion at the time of processing a cell with a solution. From the figure, trans, trans-2,4-hexadienal (Example 1), trans, trans-2,4 decadienal (Example 2), and t-2-octenal (Example 3) In the presence of ions, CCK secretion induction was significantly higher compared to the negative control (0.1% EtOH). However, CCK secretion activity was suppressed in the system in the absence of calcium.
  • the unsaturated aldehyde according to the present invention is extracellular calcium ion-dependent and TRPA1-dependent, in other words, has the ability to activate TRPA1.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Engineering & Computer Science (AREA)
  • Medicinal Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Epidemiology (AREA)
  • Dermatology (AREA)
  • Obesity (AREA)
  • Hematology (AREA)
  • Diabetes (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Child & Adolescent Psychology (AREA)
  • Vascular Medicine (AREA)
  • Emergency Medicine (AREA)
  • Birds (AREA)
  • Urology & Nephrology (AREA)
  • Mycology (AREA)
  • Nutrition Science (AREA)
  • Food Science & Technology (AREA)
  • Polymers & Plastics (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Seasonings (AREA)
  • Cosmetics (AREA)
  • Coloring Foods And Improving Nutritive Qualities (AREA)

Abstract

L'invention a pour objet un nouveau composant activateur de TRPA1 et l'utilisation du composant activateur de TRPA1. La composition d'activation de TRPA1 de la présente invention contient, comme principes actifs, un acide acrylique et/ou un aldéhyde insaturé qui a 4-12 atomes de carbone et une chaîne principale qui a une double liaison au moins en position 2 ou en position 4. A cet égard, dans les cas où une double liaison n'est qu'en position 2, la chaîne principale a 4-9 atomes de carbone, alors que dans les cas où une double liaison n'est qu'en position 4, la chaîne principale a 9-12 atomes de carbone. La présente invention porte également sur un aliment fonctionnel et sur un produit pharmaceutique, chacun de ceux-ci contenant cette composition.
PCT/JP2014/050763 2013-02-20 2014-01-17 Composition d'activation de trpa1 WO2014129238A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2013-030850 2013-02-20
JP2013030850A JP6077331B2 (ja) 2013-02-20 2013-02-20 Ｔｒｐａ１活性化組成物

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WO2014129238A1 true WO2014129238A1 (fr) 2014-08-28

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Publication number Priority date Publication date Assignee Title
US20190142629A1 (en) * 2016-04-28 2019-05-16 Sharp Kabushiki Kaisha Cooling pack and therapeutic tool used in cooling therapy
JP7366545B2 (ja) * 2019-01-04 2023-10-23 ハウス食品グループ本社株式会社 食欲不振改善用組成物
US20240041733A1 (en) * 2020-12-22 2024-02-08 Kinjirushi Co., Ltd. Dental care composition and method of promoting calcification in living body tissue
WO2023090313A1 (fr) 2021-11-16 2023-05-25 京都府公立大学法人 Composition pour augmenter la quantité d'aliments ingérés et/ou améliorer l'anorexie, et composition pour activer une ankyrine 1 à potentiel de récepteur transitoire

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2004018431A (ja) * 2002-06-14 2004-01-22 Kiyomitsu Kawasaki 口腔用香料組成物および該香料組成物を含有する口腔組成物
JP2007325561A (ja) * 2006-06-09 2007-12-20 National Agriculture & Food Research Organization 草食家畜の食欲を促進させる匂い混合物及び草食家畜の食欲促進方法
US20090264376A1 (en) * 2008-04-21 2009-10-22 Conopco, Inc., D/B/A Unilever Hoodia plant extract with improved flavor
JP2012034662A (ja) * 2010-08-11 2012-02-23 T Hasegawa Co Ltd 魚節香味改善剤
US20130315843A1 (en) * 2012-05-25 2013-11-28 The Procter & Gamble Company Composition for reduction of trpa1 and trpv1 sensations

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2004018431A (ja) * 2002-06-14 2004-01-22 Kiyomitsu Kawasaki 口腔用香料組成物および該香料組成物を含有する口腔組成物
JP2007325561A (ja) * 2006-06-09 2007-12-20 National Agriculture & Food Research Organization 草食家畜の食欲を促進させる匂い混合物及び草食家畜の食欲促進方法
US20090264376A1 (en) * 2008-04-21 2009-10-22 Conopco, Inc., D/B/A Unilever Hoodia plant extract with improved flavor
JP2012034662A (ja) * 2010-08-11 2012-02-23 T Hasegawa Co Ltd 魚節香味改善剤
US20130315843A1 (en) * 2012-05-25 2013-11-28 The Procter & Gamble Company Composition for reduction of trpa1 and trpv1 sensations

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
LAURA,S. ET AL.: "TRPA1 is activated by direct addition of cysteine residues to the N- hydroxysuccinyl esters of acrylic and cinnamic acids", PHARMACOLOGICAL RESEARCH, vol. 63, 2011, pages 30 - 36, XP028151220, DOI: doi:10.1016/j.phrs.2010.11.004 *
LINDSEY,M. ET AL.: "Noxious compounds activate TRPA1 ion channels through covalent modification of cysteines", NATURE, vol. 445, 2007, pages 541 - 545, XP009149873, DOI: doi:10.1038/nature05544 *
MARCELLO,T. ET AL.: "4-Hydroxynonenal, an endogenous aldehyde, causes pain and neurogenic inflammation through activation of the irritant receptor TRPA1", PNAS, vol. 104, no. 33, 2007, pages 13519 - 13524 *
UTAKO YANO: "Umeboshi no Tokuchoko Seibun ni Tsuite", KORYO, vol. 253, 2012, pages 37 - 43 *

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JP2015231953A (ja) 2015-12-24

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