WO1998048788A1 - Traitement de la depression et de l'anxiete au moyen d'acide docosahexaenoique ou d'antioxydants naturels - Google Patents

Traitement de la depression et de l'anxiete au moyen d'acide docosahexaenoique ou d'antioxydants naturels Download PDF

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Publication number
WO1998048788A1
WO1998048788A1 PCT/GB1998/001260 GB9801260W WO9848788A1 WO 1998048788 A1 WO1998048788 A1 WO 1998048788A1 GB 9801260 W GB9801260 W GB 9801260W WO 9848788 A1 WO9848788 A1 WO 9848788A1
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WO
WIPO (PCT)
Prior art keywords
depression
day
dha
anxiety
acid
Prior art date
Application number
PCT/GB1998/001260
Other languages
English (en)
Inventor
David Frederick Horrobin
Original Assignee
Scotia Holdings Plc
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
Priority claimed from GBGB9708700.1A external-priority patent/GB9708700D0/en
Priority claimed from GBGB9708703.5A external-priority patent/GB9708703D0/en
Application filed by Scotia Holdings Plc filed Critical Scotia Holdings Plc
Priority to AU72225/98A priority Critical patent/AU7222598A/en
Publication of WO1998048788A1 publication Critical patent/WO1998048788A1/fr

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Classifications

    • 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
    • A61K31/20—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
    • A61K31/202—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids having three or more double bonds, e.g. linolenic

Definitions

  • the invention relates to treatment of depression and anxiety.
  • n-3 essential fatty acids are important structural elements of the brain. They are required for normal function of all nerve cells.
  • the n-6 EFAs are also important components of nerve cell membranes. The two types of EFA are metabolised by the pathways shown in Table 1.
  • AdrA Adrenic acid
  • the acids which in nature are of the all - cis configuration, are systematically named as derivatives of the corresponding octadecanoic, eicosanoic or docosanoic acids, e.g. LA z,z-octadeca - 9,12 - dienoic acid or DHA z,z,z,z,z,z - docosa- 4,7J0J3J6J9 - hexaenoic acid, but numerical designations based on the number of carbon atoms, the number of centres of unsaturation and the number of carbon atoms from the end of the chain to where the unsaturation begins, such as, correspondingly, 18:2 n-6 or 22:6 n-3, are convenient.
  • Initials e.g. EPA, and shortened forms of the name e.g. eicosapentaenoic acid, are used as trivial names in some instances.
  • a deficiency of a substances does not necessarily mean that the substance can be used in therapy.
  • the patients were treated with capsules of DHA in triglyceride form and each dose was given for a period of eight weeks.
  • a dose of 250mg DHA/day the patients experienced no improvement in depression score.
  • two patients experienced a moderate but not complete improvement, but the third experienced no change
  • the third patient experienced a modest improvement and in the two patients who had improved on 500mg./day there was near complete resolution of symptoms.
  • the two patients who had recovered remained completely recovered. The third patient improved further but without complete resolution.
  • n-3 EFAs in blood are caused by increased exposure to oxidants such as cigarette smoke or car exhaust fumes or by inadequate intakes of the many different nutritional factors which contribute to the total antioxidant activity of the body, given that n-3 EFAs are highly susceptible to oxidation.
  • the antioxidant systems of the body are very complex and require the close interaction of many different compounds. Just as providing large amounts of one B vitamin could not compensate for the deficiencies of other B vitamins, so supplying one component of the antioxidant system cannot compensate for others which may be missing. Most clinical trials of antioxidants have made the mistake of giving large amounts of one or other antioxidant without attempting to provide a balanced intake of all the likely antioxidants and related co-factors. The applicants have therefore carried out a study in which those antioxidants and related co-factors most likely to be deficient in normal people were provided and compared with placebo for their effects on depression.
  • the materials which were provided were ascorbic acid (lOOmg), pyridoxine hydrochloride (25mg), beta-carotene (3mg), vitamin E (lOOmg), zinc (4mg), nicotinamide (lOmg) and selenium (450 microg).
  • the figures in brackets represent the amounts provided each day.
  • Placebo capsules contained coconut oil.
  • HAD Anxiety and Depression
  • the invention lies in use of DHA in a method of making a medicament for treating depression, anxiety, "feeling down” or “feeling blue”, by the administration of DHA at 350 to 3g or more (up to lOg) per day, preferably 500 mg to 2g per day, and in such treatment itself.
  • fatty acids of the n-3 series such as alpha-linolenic acid (ALA), stearidonic acid (SA), eicosapentaenoic acid (EPA) and docosapentaenoic acid (DPA n-3) may optionally be added, as may fatty acids of the n-6 series such as linoleic acid (LA), gamma-linolenic acid (GLA), dihomogamma linolenic acid (DGLA) and arachidonic acid (AA), at 250 mg to 2000mg/day. Since patients with depression frequently fail to eat properly, the DHA may also optionally be provided with supplements of essential minerals and vitamins. In addition, because EFAs like DHA are easily oxidised, there are advantages in combining it with physiologically effective lipophilic antioxidant compounds such as vitamin E, alpha- lipoic acid and beta-carotene.
  • ALA alpha-linolenic acid
  • SA stearidonic acid
  • EPA eico
  • the DHA may be administered in any form which is able to raise the levels of DHA in the blood.
  • the oral route is likely to be the one preferred, but topical or parenteral routes are also possible.
  • Appropriate forms of DHA are triglycerides, diglycerides. mono-glycerides, free fatty acid, ethyl or other appropriate esters including derivatives of 1, 2- or 1, 3 -propane diol or of geminal one-carbon diols, anhydrides, amides, cholesterol esters, phospholipids of any type or any other appropriate derivatives.
  • the invention lies in the antioxidant mix discussed earlier, both as such and when used in preparation of a medicament for the treatment of anxiety, depression, "feeling down” or “feeling blue". Depression may be in terms of "the blues", unhappiness or feeling low, or any other manifestation of depressed mood, and the invention extends to the treatment itself.
  • the actives are as set out below in Table 3.
  • the figures represent the daily dose to be administered.
  • the daily dose may be provided in a single capsule, tablet or other solid or liquid dosage form known to those skilled in the art, or may be provided in divided doses to make up the full daily dose.
  • the ingredients may be provided in any form assimilable after oral administration.
  • Vitamin C ascorbic acid 50mg/day lOg/day
  • Vitamin B6 (pyridoxine or other forms) 15mg/day lOOmg/day
  • Zinc (as sulphate, gluconate or other forms) 2mg/day 50mg/day
  • Vitamin E 50mg/day lOOOmg/day Selenium (as selenite, selenate, conjugates such as selenomethionine, or other forms) 1 OOmicrog/day 1000 microg/day
  • Each of the above compounds may be presented in any appropriate biologically available form.
  • the above are necessary actives in the formulation.
  • To them may be added optionally other nutrients but in particular n-3 essential fatty acids such as alpha- linolenic acid (ALA), stearidonic acid (SA), eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA n-3) and docosahexaenoic acid (DHA).
  • fatty acids may be provided in any appropriate form as discussed earlier herein, in a dose ranging from 1 Omg to 1 Og per day.
  • Folic acid may also be a valuable nutrient in anxiety and depression and so it too may be added to the formulation in dose ranging from 10 to 1000 microg/day.
  • lipophilic antioxidants such as vitamin E, beta-carotene or alpha-lipoic acid.
  • antioxidant formulations as such or for use against depression or anxiety are:

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

Préparation d'un médicament contre la dépression ou l'anxiété au moyen de compositions d'antioxydants naturels ou de compositions d'acides gras essentiels (acide docosahexaenoïque, DHA) associées éventuellement, soit à des agents nutritifs essentiels, soit à des antioxydants naturels.
PCT/GB1998/001260 1997-04-29 1998-04-23 Traitement de la depression et de l'anxiete au moyen d'acide docosahexaenoique ou d'antioxydants naturels WO1998048788A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU72225/98A AU7222598A (en) 1997-04-29 1998-04-23 Treatment of depression and anxiety using docosahexaenoic acid or natural antioxidants

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
GBGB9708700.1A GB9708700D0 (en) 1997-04-29 1997-04-29 Treatment of depression
GB9708700.1 1997-04-29
GBGB9708703.5A GB9708703D0 (en) 1997-04-29 1997-04-29 Treatment of depression and anxiety
GB9708703.5 1997-04-29

Publications (1)

Publication Number Publication Date
WO1998048788A1 true WO1998048788A1 (fr) 1998-11-05

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/GB1998/001260 WO1998048788A1 (fr) 1997-04-29 1998-04-23 Traitement de la depression et de l'anxiete au moyen d'acide docosahexaenoique ou d'antioxydants naturels

Country Status (2)

Country Link
AU (1) AU7222598A (fr)
WO (1) WO1998048788A1 (fr)

Cited By (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000041484A2 (fr) * 1999-01-14 2000-07-20 Institut De Recherche Biologique S.A. Nouvelle utilisation de phospholipides d'origine vegetale et animale en therapeutique nutritionnelle
WO2000044360A2 (fr) * 1999-01-27 2000-08-03 Laxdale Limited Medicaments pour le traitement de troubles psychiatriques et cerebraux
WO2000051684A2 (fr) * 1999-03-03 2000-09-08 Scarista Limited Regulateurs de transacylase independante de la coenzyme a comme medicaments psychotropes
NL1019368C2 (nl) * 2001-11-14 2003-05-20 Nutricia Nv Preparaat voor het verbeteren van receptorwerking.
WO2005034846A2 (fr) 2003-09-11 2005-04-21 Michigan State University Compositions de withanamide and withanolide et procede d'utilisation de celles-ci
US6919330B2 (en) * 2002-02-07 2005-07-19 Laxdale Limited Formulations of drugs
EP1713463A2 (fr) * 2004-01-19 2006-10-25 Martek Biosciences Corporation Dysfonctionnement ou d ficit de reelin et techniques associ es
EP1765319A1 (fr) * 2004-04-16 2007-03-28 Solvay Pharmaceuticals GmbH Acides gras essentiels pour la prévention et/ou le traitment des dépressions chez des patients présentant des maladies coronaires du coeur
US7208180B2 (en) * 2000-05-08 2007-04-24 N.V. Nutricia Method and preparation for the preventing and/or treating vascular disorders and secondary disorders associated therewith
WO2008028633A1 (fr) * 2006-09-08 2008-03-13 Dsm Ip Assets B.V. Composition de soin de la peau
WO2009099886A1 (fr) * 2008-01-31 2009-08-13 Monsanto Technology Llc Procédé d’amélioration de dépôt de déhydroépiandrostérone (dha) et fonction et/ou développement associés
US8377912B2 (en) 2000-05-08 2013-02-19 N. V. Nutricia Preparation for the prevention and/or treatment of vascular disorders
EP3139741A4 (fr) * 2014-05-08 2017-11-29 DSM IP Assets B.V. Procédés et compositions comprenant de l'acide 10-hydroxy-2-décénoïque
WO2019238998A1 (fr) * 2018-06-13 2019-12-19 Servicio Andaluz De Salud Utilisation d'antioxydants pour le traitement de la dépression chez des patients adultes

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EP0347056A1 (fr) * 1988-06-10 1989-12-20 Scotia Holdings Plc Compositions d'acides gras essentiels
EP0440341A1 (fr) * 1990-01-18 1991-08-07 Scotia Holdings Plc Compositions d'acides gras essentiels et thérapie
WO1996034846A1 (fr) * 1995-05-01 1996-11-07 Scotia Holdings Plc Derives de 1,3-propanediol utilises comme composes bioactifs
FR2749133A1 (fr) * 1996-06-04 1997-12-05 Pierre Moreau Obtention d'oeufs specifiquement enrichis en acide cervonique (acide docosahexaenoique ou dha). applications alimentaires, therapeutiques et industrielles de ces oeufs et de leurs extraits lipidiques

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EP0440341A1 (fr) * 1990-01-18 1991-08-07 Scotia Holdings Plc Compositions d'acides gras essentiels et thérapie
WO1996034846A1 (fr) * 1995-05-01 1996-11-07 Scotia Holdings Plc Derives de 1,3-propanediol utilises comme composes bioactifs
WO1996034855A1 (fr) * 1995-05-01 1996-11-07 Scotia Holdings Plc Esters d'acides gras utilises comme composes bioactifs
FR2749133A1 (fr) * 1996-06-04 1997-12-05 Pierre Moreau Obtention d'oeufs specifiquement enrichis en acide cervonique (acide docosahexaenoique ou dha). applications alimentaires, therapeutiques et industrielles de ces oeufs et de leurs extraits lipidiques

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HIBBELN J.R. ET AL: "Dietary polyunsaturated fatty acids and depression: when cholesterol does not satisfy", AM. J. CLIN. NUTR. (UNITED STATES), vol. 62, no. 1, 1995, pages 1 - 9, XP002071081 *
IRMISCH G. ET AL: "Changes of the concentration of certain biochemical parameters in depressive patients depending on the severity of illness", PHARMACOPSYCHIATRY, vol. 30, no. 5, September 1997 (1997-09-01), pages 184, XP002071082 *
KOUDELOVÁ J. ET AL: "The natural antioxidant capacity in patients with major depression", HOMEOSTASIS IN HELATH AND DISEASE (CZECH REPUBLIC), vol. 38, no. 1, January 1997 (1997-01-01), pages 2 - 3, XP002079305 *
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Cited By (35)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2788437A1 (fr) * 1999-01-14 2000-07-21 Inst Rech Biolog Sa Nouvelle utilisation de phospholipides d'origine vegetale et animale en therapeutique nutritionnelle
WO2000041484A3 (fr) * 1999-01-14 2001-05-17 Inst Rech Biolog Sa Nouvelle utilisation de phospholipides d'origine vegetale et animale en therapeutique nutritionnelle
WO2000041484A2 (fr) * 1999-01-14 2000-07-20 Institut De Recherche Biologique S.A. Nouvelle utilisation de phospholipides d'origine vegetale et animale en therapeutique nutritionnelle
WO2000044360A2 (fr) * 1999-01-27 2000-08-03 Laxdale Limited Medicaments pour le traitement de troubles psychiatriques et cerebraux
WO2000044360A3 (fr) * 1999-01-27 2000-11-30 Laxdale Ltd Medicaments pour le traitement de troubles psychiatriques et cerebraux
WO2000051684A2 (fr) * 1999-03-03 2000-09-08 Scarista Limited Regulateurs de transacylase independante de la coenzyme a comme medicaments psychotropes
WO2000051684A3 (fr) * 1999-03-03 2001-01-04 Scarista Ltd Regulateurs de transacylase independante de la coenzyme a comme medicaments psychotropes
US7208180B2 (en) * 2000-05-08 2007-04-24 N.V. Nutricia Method and preparation for the preventing and/or treating vascular disorders and secondary disorders associated therewith
US8865687B2 (en) 2000-05-08 2014-10-21 N.V. Nutricia Preparation for the prevention and/or treatment of vascular disorders
US8377912B2 (en) 2000-05-08 2013-02-19 N. V. Nutricia Preparation for the prevention and/or treatment of vascular disorders
EP2340826A3 (fr) * 2001-11-14 2012-09-12 N.V. Nutricia Procédé et préparation permettant de prévenir et/ou de traiter les troubles neurologiques ou neuro-dégénératifs
US9504712B2 (en) 2001-11-14 2016-11-29 N.V. Nutricia Preparation for improving the action of receptors
US9844525B2 (en) 2001-11-14 2017-12-19 N.V. Nutricia Preparation for improving the action of receptors
NL1019368C2 (nl) * 2001-11-14 2003-05-20 Nutricia Nv Preparaat voor het verbeteren van receptorwerking.
WO2003041701A3 (fr) * 2001-11-14 2004-03-18 Nutricia Nv Preparation permettant d'ameliorer l'action de recepteurs
US8362078B2 (en) 2001-11-14 2013-01-29 N.V. Nutricia Method for reducing the severity of neurological disorders
EP2340827A3 (fr) * 2001-11-14 2012-11-14 N.V. Nutricia Procédé et préparation empêchant et/ou traitant les troubles neurologiques ou neuro-dégénératifs à l'aide d'une combinaison de médicaments
EP2340825A3 (fr) * 2001-11-14 2011-09-07 N.V. Nutricia Procédé et préparation empêchant et/ou traitant les troubles neurologiques ou neuro-dégénératifs à l'aide d'un précurseur de neurotransmetteur
US7384981B2 (en) 2001-11-14 2008-06-10 N.V. Nutricia Preparation for improving the action of receptors
EP2363125A1 (fr) * 2001-11-14 2011-09-07 N.V. Nutricia Préparation pour améliorer l'activité des récepteurs
US7888391B2 (en) 2001-11-14 2011-02-15 N.V. Nutricia Method for reducing the severity of neurological disorders
US6919330B2 (en) * 2002-02-07 2005-07-19 Laxdale Limited Formulations of drugs
WO2005034846A2 (fr) 2003-09-11 2005-04-21 Michigan State University Compositions de withanamide and withanolide et procede d'utilisation de celles-ci
US7282593B2 (en) 2003-09-11 2007-10-16 Board Of Trustees Of Michigan State University Withanamide and withanolide compositions and method of use thereof
JP2007524674A (ja) * 2004-01-19 2007-08-30 マーテック・バイオサイエンシーズ・コーポレーション リーリン欠損症または機能障害およびそれに関連する方法
EP1713463A4 (fr) * 2004-01-19 2009-03-18 Martek Biosciences Corp Dysfonctionnement ou d ficit de reelin et techniques associ es
EP1713463A2 (fr) * 2004-01-19 2006-10-25 Martek Biosciences Corporation Dysfonctionnement ou d ficit de reelin et techniques associ es
JP2007532605A (ja) * 2004-04-16 2007-11-15 ゾルファイ　ファーマスーティカルズ　ゲゼルシャフト　ミット　ベシュレンクテル　ハフツング 冠性心疾患または冠状動脈疾患を持つ患者の鬱病の予防および／または治療における必須脂肪酸
EP1765319A1 (fr) * 2004-04-16 2007-03-28 Solvay Pharmaceuticals GmbH Acides gras essentiels pour la prévention et/ou le traitment des dépressions chez des patients présentant des maladies coronaires du coeur
WO2008028633A1 (fr) * 2006-09-08 2008-03-13 Dsm Ip Assets B.V. Composition de soin de la peau
WO2009099886A1 (fr) * 2008-01-31 2009-08-13 Monsanto Technology Llc Procédé d’amélioration de dépôt de déhydroépiandrostérone (dha) et fonction et/ou développement associés
EP3139741A4 (fr) * 2014-05-08 2017-11-29 DSM IP Assets B.V. Procédés et compositions comprenant de l'acide 10-hydroxy-2-décénoïque
US10004711B2 (en) 2014-05-08 2018-06-26 Dsm Ip Assets B.V. Methods and compositions comprising 10-hydroxy-2-decenoic acid
TWI743022B (zh) * 2014-05-08 2021-10-21 荷蘭商帝斯曼知識產權資產管理有限公司 包含10-羥基-2-癸烯酸之方法及組成物
WO2019238998A1 (fr) * 2018-06-13 2019-12-19 Servicio Andaluz De Salud Utilisation d'antioxydants pour le traitement de la dépression chez des patients adultes

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