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WO2001045726A2 - Utilisation de procyanidines dans la modulation de l'expression genetique des cytokines et de la secretion des proteines - Google Patents

Utilisation de procyanidines dans la modulation de l'expression genetique des cytokines et de la secretion des proteines Download PDF

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Publication number
WO2001045726A2
WO2001045726A2 PCT/US2000/035059 US0035059W WO0145726A2 WO 2001045726 A2 WO2001045726 A2 WO 2001045726A2 US 0035059 W US0035059 W US 0035059W WO 0145726 A2 WO0145726 A2 WO 0145726A2
Authority
WO
WIPO (PCT)
Prior art keywords
cocoa
procyanidin
oligomers
use according
ofthe
Prior art date
Application number
PCT/US2000/035059
Other languages
English (en)
Other versions
WO2001045726A3 (fr
Inventor
Harold H. Schmitz
Original Assignee
Mars, Incorporated
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Mars, Incorporated filed Critical Mars, Incorporated
Priority to AU22896/01A priority Critical patent/AU2289601A/en
Publication of WO2001045726A2 publication Critical patent/WO2001045726A2/fr
Publication of WO2001045726A3 publication Critical patent/WO2001045726A3/fr

Links

Classifications

    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23G—COCOA; COCOA PRODUCTS, e.g. CHOCOLATE; SUBSTITUTES FOR COCOA OR COCOA PRODUCTS; CONFECTIONERY; CHEWING GUM; ICE-CREAM; PREPARATION THEREOF
    • A23G1/00—Cocoa; Cocoa products, e.g. chocolate; Substitutes therefor
    • A23G1/30—Cocoa products, e.g. chocolate; Substitutes therefor
    • A23G1/32—Cocoa products, e.g. chocolate; Substitutes therefor characterised by the composition containing organic or inorganic compounds
    • A23G1/42—Cocoa products, e.g. chocolate; Substitutes therefor characterised by the composition containing organic or inorganic compounds containing microorganisms or enzymes; containing paramedical or dietetical agents, e.g. vitamins
    • A23G1/426—Cocoa products, e.g. chocolate; Substitutes therefor characterised by the composition containing organic or inorganic compounds containing microorganisms or enzymes; containing paramedical or dietetical agents, e.g. vitamins containing vitamins or antibiotics
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • 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
    • A23L33/105—Plant extracts, their artificial duplicates or their derivatives
    • 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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/06—Antiasthmatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders

Definitions

  • the methylated procyanidin monomer or oligomer is of formula (A') n wherein n is 1 to 18 and A' is a monomer unit of formula:
  • the procyanidin is reacted with diazomethane for twenty minutes at room temperature and left to react overnight in the freezer; the reaction is stopped by using acetic acid in methanol; the solvent is removed and the solids are dried under vacuum.
  • the reaction may be monitored using mass spectrometry.
  • a person of skill in the art can optimize the conditions to obtain the desired degree of methylation.
  • the procyanidin may be methylated at one or more hydroxyl groups, one or more carbon positions that are not sterically hindered, or both.
  • a methylated procyanidin tetramer prepared, for example, using a diazomethane may be methylated at 14-18 ofthe OH groups.
  • the invention relates to the use ofthe compound(s) described herein for the manufacture of a medicament, food or dietary supplement for treating a viral infection, or for reducing the symptoms of a viral infection, in a subject infected with a virus.
  • the subject is a mammal such as a human or a veterinary animal, which has been infected with a virus.
  • the invention relates to a method for treating a viral infection, or for reducing symptoms of a viral infection, in a mammal by administering to the mammal an effective amount ofthe compound(s) ofthe invention.
  • infections ofthe nasal tract caused by a rhinovirus or any serotype ofthe myxovirus are prevented or attenuated.
  • the cocoa polyphenols may be administered in dosages and to achieve body concentrations as described above for asthma applications.
  • Cytokines function as the messengers ofthe immune system: they assist in regulating the development and actions of immune effector cells, and also have effector functions of their own. For this reason the manipulation of cytokine levels can be seen as a potential source of disease therapy, particularly for conditions in which the pathology is caused largely by an inappropriate immune response. Furthermore, modulating cytokine levels could be developed into a prophylactic therapy for ill-health of all kinds: firstly by the enhancement of immune responses against external pathogens such as viruses and also cancer cells, and secondly by enhancing cytokines which have a stimulatory effect on the production of substances which are beneficial for the health, for example IL-1 and IL-2, which are both known to enhance NO levels in humans via the induction ofthe iNOS gene.
  • cocoa polyphenols may be used to treat, improve the immune response and/or alleviate the symptoms associated with inflammatory conditions such as allergy, rheumatoid arthritis, and asthma.
  • cytokine genes in response to a particular cocoa procyanidin application were measured using gene-specific semi-quantitative PCR. This method directly shows the effects that the cocoa procyanidins have on the synthesis of cytokine mRNA.
  • PCR is a well-controlled, simple, rapid, reproducible, and non-radioisotopic method for analysis of cytokine mRNA, it may not be sufficient to obtain a complete understanding ofthe cytokine expression and secretion. It is known that control of cytokine protein synthesis and secretion is extremely complex, and can be regulated at many different levels apart from the transcriptional level.
  • IL- l ⁇ protein is maintained in the cell cytosol in the form of pro-IL-l ⁇ , so stimulation of the cell may lead to cleavage of this protein and release ofthe mature cytokine without affecting transcription (Dinarello et al, "IL-1, IL-1 Receptors and IL-1 Receptor Antagonists", Intern Rev Immunol, 16:457-499, 1998). For this reason it was decided to perform assays for cytokine protein secretion, in parallel with the RT- PCR.
  • Example 9 describes the formulation of cocoa procyanidins tablets, for use in the pharmaceutical, diet supplement and food areas.
  • Example 10 describes the preparation ofthe cocoa procyanidins as capsules for similar applications.
  • Example 11 describes the preparation of Standard of Identity (SOI) and non-SOI chocolates containing the high cocoa polyphenol extract or cocoa solids obtained from methods described herein.
  • SOI Standard of Identity
  • KITS KITS
  • dNTP mix (10 mM of each of dATP, dCTP, dGTP, dTTP) (Pharmacia Biotech, Uppsala, Sweden), 0.5 ⁇ g oligo-dTs, and 200 U Superscript II (Gibco BRL).
  • PCR polymerase chain reaction

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Natural Medicines & Medicinal Plants (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Pulmonology (AREA)
  • Botany (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Polymers & Plastics (AREA)
  • Food Science & Technology (AREA)
  • Nutrition Science (AREA)
  • Mycology (AREA)
  • Microbiology (AREA)
  • Communicable Diseases (AREA)
  • Medical Informatics (AREA)
  • Biotechnology (AREA)
  • Alternative & Traditional Medicine (AREA)
  • Epidemiology (AREA)
  • Virology (AREA)
  • Inorganic Chemistry (AREA)
  • Oncology (AREA)
  • Immunology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines Containing Plant Substances (AREA)

Abstract

L'invention concerne des procyanidines du cacao et des extraits de cacao qui comprennent des monomères de procyanidine et leurs oligomères et qui sont utiles dans la modulation d'une réponse immunitaire et d'une réponse inflammatoire chez un mammifère. Les procyanidines du cacao et les extraits liquides ou séchés de cacao peuvent être ajoutés à de la nourriture, des suppléments nutritifs et des produits pharmaceutiques pour la modulation d'un produit génétique à base de cytokines et des taux de protéines afin d'obtenir des effets bénéfiques pour les sujets souffrant d'asthme ou d'infections ou exposés à des infections virales.
PCT/US2000/035059 1999-12-21 2000-12-21 Utilisation de procyanidines dans la modulation de l'expression genetique des cytokines et de la secretion des proteines WO2001045726A2 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU22896/01A AU2289601A (en) 1999-12-21 2000-12-21 The use of procyanidins in the modulation of cytokine gene expression and protein secretion

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US46875399A 1999-12-21 1999-12-21
US09/468,753 1999-12-21

Publications (2)

Publication Number Publication Date
WO2001045726A2 true WO2001045726A2 (fr) 2001-06-28
WO2001045726A3 WO2001045726A3 (fr) 2002-01-03

Family

ID=23861094

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2000/035059 WO2001045726A2 (fr) 1999-12-21 2000-12-21 Utilisation de procyanidines dans la modulation de l'expression genetique des cytokines et de la secretion des proteines

Country Status (2)

Country Link
AU (1) AU2289601A (fr)
WO (1) WO2001045726A2 (fr)

Cited By (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1314420A1 (fr) * 2001-11-23 2003-05-28 Cognis Iberia, S.L. Compositions contre le vieillissement
FR2838055A1 (fr) * 2002-04-05 2003-10-10 Cep Nouvelle utilisation d'un extrait de cacao et les compositions cosmetiques et/ou dermatologiques a cet effet
WO2004050614A3 (fr) * 2002-12-02 2004-07-29 Mars Inc Flavanols et procyanidines promoteurs de l'homeostasie
WO2006006172A3 (fr) * 2004-07-15 2006-05-04 Univ Ramot Utilisation d'agents anti-amyloides pour traiter et determiner des infections pathogenes
EP1913821A1 (fr) * 2006-10-20 2008-04-23 Kraft Foods R & D, Inc. Zweigniederlassung München Extraits de plantes riches en polyphénoliques
US7491699B2 (en) 2002-12-09 2009-02-17 Ramot At Tel Aviv University Ltd. Peptide nanostructures and methods of generating and using the same
US7504383B2 (en) 2003-01-07 2009-03-17 Ramot At Tel Aviv University Ltd. Peptide nanostructures encapsulating a foreign material and method of manufacturing same
US7732479B2 (en) 2004-08-19 2010-06-08 Tel Aviv University Future Technology Development L.P. Compositions for treating amyloid associated diseases
WO2012014165A1 (fr) * 2010-07-28 2012-02-02 Indus Biotech Private Limited Procédé de traitement d'une affection broncho-constrictrice
EP2170091A4 (fr) * 2007-06-21 2013-09-04 Mars Inc Produits comestibles ayant un contenu élevé en polyphénol de cacao et un arome amélioré et les extraits de cacao moulu utilisés dedans
US8563273B2 (en) 2002-09-06 2013-10-22 Tel Aviv University Future Technology Development L.P. Method of screening for compounds that disaggregate amyloid aggregates
TWI421072B (zh) * 2011-08-19 2014-01-01 Indus Biotech Private Ltd 控制支氣管收縮病狀之方法
US8697634B2 (en) 2002-01-31 2014-04-15 Tel Aviv University Future Technology Development L.P. Peptides and methods using same for diagnosis and treatment of amyloid-associated disease
US9096645B2 (en) 2010-11-15 2015-08-04 Ramot At Tel-Aviv University Ltd. Dipeptide analogs for treating conditions associated with amyloid fibril formation
US20150335695A1 (en) * 2014-05-25 2015-11-26 Tu Song-Anh Nguyen Therapeutic Nutritional Supplement to Alleviate Symptoms of COPD and Delay the Progression Thereof
WO2016046375A1 (fr) * 2014-09-25 2016-03-31 Institut National De La Sante Et De La Recherche Medicale (Inserm) Extrait de theobroma cacao pour son utilisation dans le traitement ou la prévention de troubles associés aux récepteurs tyrosine kinases
US10004828B2 (en) 2005-10-11 2018-06-26 Romat at Tel-Aviv University Ltd. Self-assembled Fmoc-ff hydrogels

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005031362A2 (fr) 2003-10-02 2005-04-07 Ramot At Tel Aviv University Ltd. Nouveaux agents antibacteriens et procedes permettant de les identifier et de les utiliser
EP1781310B1 (fr) 2004-08-02 2015-10-14 Ramot at Tel Aviv University Ltd. Articles de nanostructures a base de peptides et leur procede de formation

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5554645A (en) * 1994-10-03 1996-09-10 Mars, Incorporated Antineoplastic cocoa extracts and methods for making and using the same
US6015913A (en) * 1996-09-06 2000-01-18 Mars, Incorporated Method for producing fat and/or solids from cocoa beans

Cited By (28)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1314420A1 (fr) * 2001-11-23 2003-05-28 Cognis Iberia, S.L. Compositions contre le vieillissement
WO2003043595A1 (fr) * 2001-11-23 2003-05-30 Cognis Iberia, S.L. Agents anti-vieillissement
US8993510B2 (en) 2002-01-31 2015-03-31 Tel Aviv University Future Technology Development L.P. Peptides and methods using same for diagnosis and treatment of amyloid-associated disease
US8697634B2 (en) 2002-01-31 2014-04-15 Tel Aviv University Future Technology Development L.P. Peptides and methods using same for diagnosis and treatment of amyloid-associated disease
FR2838055A1 (fr) * 2002-04-05 2003-10-10 Cep Nouvelle utilisation d'un extrait de cacao et les compositions cosmetiques et/ou dermatologiques a cet effet
US8563273B2 (en) 2002-09-06 2013-10-22 Tel Aviv University Future Technology Development L.P. Method of screening for compounds that disaggregate amyloid aggregates
WO2004050614A3 (fr) * 2002-12-02 2004-07-29 Mars Inc Flavanols et procyanidines promoteurs de l'homeostasie
US7491699B2 (en) 2002-12-09 2009-02-17 Ramot At Tel Aviv University Ltd. Peptide nanostructures and methods of generating and using the same
US7504383B2 (en) 2003-01-07 2009-03-17 Ramot At Tel Aviv University Ltd. Peptide nanostructures encapsulating a foreign material and method of manufacturing same
WO2006006172A3 (fr) * 2004-07-15 2006-05-04 Univ Ramot Utilisation d'agents anti-amyloides pour traiter et determiner des infections pathogenes
US7732479B2 (en) 2004-08-19 2010-06-08 Tel Aviv University Future Technology Development L.P. Compositions for treating amyloid associated diseases
US10004828B2 (en) 2005-10-11 2018-06-26 Romat at Tel-Aviv University Ltd. Self-assembled Fmoc-ff hydrogels
EP1913821A1 (fr) * 2006-10-20 2008-04-23 Kraft Foods R & D, Inc. Zweigniederlassung München Extraits de plantes riches en polyphénoliques
US8906957B2 (en) 2006-10-20 2014-12-09 Kraft Foods R & D, Inc. Polyphenol-rich extract from plant material
US9114114B2 (en) 2007-06-21 2015-08-25 Mars, Inc. Edible products having a high cocoa polyphenol content and improved flavor and the milled cocoa extracts used therein
EP2170091A4 (fr) * 2007-06-21 2013-09-04 Mars Inc Produits comestibles ayant un contenu élevé en polyphénol de cacao et un arome amélioré et les extraits de cacao moulu utilisés dedans
US10155017B2 (en) 2007-06-21 2018-12-18 Mars, Inc. Edible products having a high cocoa polyphenol content and improved flavor and the milled cocoa extracts used therein
CN103025382A (zh) * 2010-07-28 2013-04-03 梧桐生物技术私人有限公司 处理支气管收缩病症的方法
AU2011284357B2 (en) * 2010-07-28 2013-09-26 Indus Biotech Private Limited A method of managing broncho-constrictive condition
KR101535959B1 (ko) * 2010-07-28 2015-07-10 인두스 바이오텍 프라이빗 리미티드 기관지 수축 질환의 관리 방법
CN103025382B (zh) * 2010-07-28 2016-04-20 梧桐生物技术私人有限公司 组合物在制备用于处理支气管收缩病症的药物中的应用
WO2012014165A1 (fr) * 2010-07-28 2012-02-02 Indus Biotech Private Limited Procédé de traitement d'une affection broncho-constrictrice
RU2532357C2 (ru) * 2010-07-28 2014-11-10 Индус Биотек Прайвит Лимитед Способ терапии бронхо-констриктивных состояний
US9096645B2 (en) 2010-11-15 2015-08-04 Ramot At Tel-Aviv University Ltd. Dipeptide analogs for treating conditions associated with amyloid fibril formation
US9630989B2 (en) 2010-11-15 2017-04-25 Ramot At Tel-Aviv University Ltd. Dipeptide analogs for treating conditions associated with amyloid fibril formation
TWI421072B (zh) * 2011-08-19 2014-01-01 Indus Biotech Private Ltd 控制支氣管收縮病狀之方法
US20150335695A1 (en) * 2014-05-25 2015-11-26 Tu Song-Anh Nguyen Therapeutic Nutritional Supplement to Alleviate Symptoms of COPD and Delay the Progression Thereof
WO2016046375A1 (fr) * 2014-09-25 2016-03-31 Institut National De La Sante Et De La Recherche Medicale (Inserm) Extrait de theobroma cacao pour son utilisation dans le traitement ou la prévention de troubles associés aux récepteurs tyrosine kinases

Also Published As

Publication number Publication date
WO2001045726A3 (fr) 2002-01-03
AU2289601A (en) 2001-07-03

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