WO1998016215A1 - Utilisation d'acides gras essentiels pour le traitement et la prevention de dommages par rayonnement aux erythrocytes - Google Patents

Utilisation d'acides gras essentiels pour le traitement et la prevention de dommages par rayonnement aux erythrocytes Download PDF

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Publication number
WO1998016215A1
WO1998016215A1 PCT/GB1997/002441 GB9702441W WO9816215A1 WO 1998016215 A1 WO1998016215 A1 WO 1998016215A1 GB 9702441 W GB9702441 W GB 9702441W WO 9816215 A1 WO9816215 A1 WO 9816215A1
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WO
WIPO (PCT)
Prior art keywords
fatty acids
acid
essential fatty
treatment
radiotherapy
Prior art date
Application number
PCT/GB1997/002441
Other languages
English (en)
Inventor
David Frederick Horrobin
Catherine Ann Scott
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
Application filed by Scotia Holdings Plc filed Critical Scotia Holdings Plc
Priority to AU41305/97A priority Critical patent/AU4130597A/en
Publication of WO1998016215A1 publication Critical patent/WO1998016215A1/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
    • 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

Definitions

  • the invention relates to fatty acid treatment
  • LA Linoleic acid
  • ALA ⁇ -hnolenic acid
  • GLA Stearidonic acid
  • Adrenic acid Adrenic acid
  • DHA Docosahexaenoic acid
  • Initials, e.g. EPA, and shortened forms of the name e.g. eicosapentaenoic acid are used as trivial names in some instances.
  • Radiotherapy As one of the commonest methods of treating cancer. It is effective in many patients. The main problem is the damage that the radiation does to normal tissues. This causes adverse effects in itself and also limits the dose of radiation which can be administered, often leading, as regards the effect on the cancer, to a sub-therapeutic treatment.
  • red cell membranes have a diameter greater than the diameter of most of the capillaries in the body.
  • the red cells In order to pass through the capillaries quickly to deliver oxygen to the tissues, the red cells must be fluid and flexible so that they can squeeze through. If the red cells become stiffer because of loss of unsaturated fatty acids, they will pass through the capillaries more slowly or not at all, thus reducing the rate of delivery of oxygen to the tissues. This is undesirable in principle but in the context of radiotherapy may have particular adverse consequences.
  • the efficiency of cancer cell killing by radiotherapy depends on a good oxygen supply to the tissues. The more oxygen there is, the more effectively will the cancer cells be destroyed, but damaged red cells will not deliver it effectively. Further, cancers often have precarious blood supply leading to resistance to radiation. Stiff red cells will exaggerate the problem by reducing further the supply of oxygen.
  • a second problem relates to the fatigue which is characteristic of patients undergoing radiotherapy and which has never been fully explained. Stiff red cells and a reduction in the oxygen supply to the tissues are important contributors to this fatigue.
  • the invention provides a method of countering red cell damage due to radiotherapy by the administration of essential fatty acids and, correspondingly, the use of essential fatty acids for the preparation of medicaments for the prevention and treatment of red cell damage due to radiotherapy.
  • the invention provides a method of countering post- radiotherapy fatigue by the administration of such acids.
  • This aspect likewise, embraces the use of the essential fatty acids for the preparation of a medicament for the prevention of treatment of post-radiotherapy fatigue.
  • the invention provides a method of countering hypoxia in radiotherapy by the administration of the acids.
  • This aspect again, embraces the use of the acids for the preparation of a medicament for the prevention or treatment of tissue hypoxia in radiotherapy.
  • EFAs in the cell membranes are those beyond the first delta-6-desaturase rate-limiting step in both series, that is gamma-linolenic acid and its metabolites in the n-6 series and stearidonic acid and its metabolites in the n-3 series.
  • n-6 or n-3 fatty acids alone may confer some benefit
  • optimum results are achieved with n-6 and n-3 EFAs together because both are required for normal membrane structure.
  • Particularly appropriate n-6 EFAS are GLA, DGLA and AA
  • particularly effective n-3 EFAs are SA, EPA, DPA and DHA.
  • the parent EFAs, linoleic and alpha-linolenic acid may be used optionally if desired.
  • the fatty acids may be administered in any form which allows their incorporation into the blood after administration by oral, enteral, parenteral, topical or any other appropriate route.
  • useful forms include the free fatty acids, salts including lithium salts, glycerides including mono di and triglycerides, amides, adducts with amines including meglumine, ascorbic acid and niacin derivatives, mono and diesters of the diols of our previous patent applications WO 96/34836 (PCT GB 96/01053) and WO 96/34855 (PCT GB 96/01052), cholesterol esters and phospholipids.
  • the doses of the acid(s) may range from 1 mg to 100 g per day, preferably 1 mg to 20 g and very preferably 50 mg to 5g, suitably delivered in dosage unit forms or as preparations containing 0.1 to 10% by weight of the fatty acids.
  • a foodstuff such as a granule, cream, gel, pastille, flake, powder or other form known to those skilled in the art containing 0.1 to 10% of GLA by weight used as last.
  • a group of 404 women undergoing radiotherapy after surgery for breast cancer was entered into a study in which members of the group were randomised to receive a sunflower oil placebo, containing the parent n-6 unsaturated fatty acid, linoleic acid, or active treatment with the highly unsaturated fatty acids of cell membranes or their immediate precusors.
  • fatty acids are dihomogammalinolenic acid (DGLA, 20:3 n-4) and arachidonic acid (AA, 20:4 n-6) of the n-6 series and eicosapentaenoic acid (EPA, 20:5 n-3), docosapentaenoic acid (DPA, 22:6 n-3) and docosahexaenoic acid (DHA, 22-6 n-3) of the n-3 series.
  • AA and DGLA for example can be formed from linoleic acid but the first step in this pathway, the conversion of linoleic acid to gamma-linolenic acid (GLA, 18:3 n-6) is very slow.
  • GLA gamma-linolenic acid
  • the placebo provided 3000 mg of linoleic acid per day whereas active treatment provided GLA (480 mg per day), EPA (96 mg/day) and DHA (64 mg/day).
  • active treatment provided GLA (480 mg per day), EPA (96 mg/day) and DHA (64 mg/day).
  • GLA 480 mg per day
  • EPA 96 mg/day
  • DHA 64 mg/day
  • Patients were subjected to conventional radiotherapy regimes, usually lasting 6-8 weeks and blood samples were taken at baseline and at 12 weeks when all radiotherapy was completed. Red cell fatty acid composition was measured in both samples. The results were striking.
  • the placebo as shown in table 2
  • the five key fatty acids fell by 20-30% during radiotherapy, leading to a substantial increase in red cell stiffness.
  • the reductions for all five were much less in the active treated group,
  • the co-administration of GLA, EPA and DHA substantially reduce the red cell damage.
  • Table 2 Percentage changes from baseline for the key highly unsaturated fatty acids of red cell membranes, p values are for differences between the change in the active group and the change in the placebo group (Student's test).

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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

L'invention concerne l'utilisation d'au moins un acide gras essentiel du typen-6 et/ou d'au moins un acide gras essentiel du type n-3 dans la préparation d'un médicament administré pour protéger les globules rouges et/ou éviter l'hypoxie durant une radiothérapie et/ou pour lutter contre la fatigue consécutive à ces thérapies.
PCT/GB1997/002441 1996-10-14 1997-09-11 Utilisation d'acides gras essentiels pour le traitement et la prevention de dommages par rayonnement aux erythrocytes WO1998016215A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU41305/97A AU4130597A (en) 1996-10-14 1997-09-11 Use of essential fatty acids for the treatment and prevention of radiation damage to erythrocytes

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB9621373.1 1996-10-14
GBGB9621373.1A GB9621373D0 (en) 1996-10-14 1996-10-14 Fatty acid treatment

Publications (1)

Publication Number Publication Date
WO1998016215A1 true WO1998016215A1 (fr) 1998-04-23

Family

ID=10801378

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/GB1997/002441 WO1998016215A1 (fr) 1996-10-14 1997-09-11 Utilisation d'acides gras essentiels pour le traitement et la prevention de dommages par rayonnement aux erythrocytes

Country Status (4)

Country Link
AU (1) AU4130597A (fr)
GB (1) GB9621373D0 (fr)
WO (1) WO1998016215A1 (fr)
ZA (1) ZA978226B (fr)

Cited By (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1220669A1 (fr) * 1999-10-13 2002-07-10 Marco A. Chacon Intervention therapeutique visant a reproduire l'effet d'une restriction calorique
US20060052446A1 (en) * 2000-08-23 2006-03-09 Chilton Floyd H Fatty acid-containing compositions and methods for the treatment of cytokine mediated disorders
US8092839B2 (en) 2004-12-13 2012-01-10 Swing Aerobics Licensing, Inc. Medicament for treatment of cancer and other diseases
WO2012010406A1 (fr) 2010-07-22 2012-01-26 Unilever Plc Combinaisons de rhamnolipides et d'enzymes pour nettoyage amélioré
US8293790B2 (en) 2011-10-19 2012-10-23 Dignity Sciences Limited Pharmaceutical compositions comprising DGLA and benzoyl peroxide and methods of use thereof
US8431165B2 (en) 2004-12-13 2013-04-30 Swing Aerobics Licensing, Inc. Medicament for treatment of cancer and other diseases
US8536223B2 (en) 2009-04-29 2013-09-17 Dignity Sciences Limited Use of PUFAs for treating skin inflammation
US10105333B2 (en) 2014-06-04 2018-10-23 Ds Biopharma Limited Pharmaceutical compositions comprising DGLA and use of same
CN108741081A (zh) * 2018-06-29 2018-11-06 许昌元化生物科技有限公司 一种含有亚麻酸的复合微粉及其制备方法
US12076304B2 (en) 2020-04-03 2024-09-03 Afimmune Limited Compositions comprising 15-HEPE and methods of treating or preventing hematologic disorders, and/or related diseases

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS58180423A (ja) * 1982-04-16 1983-10-21 Nippon Suisan Kaisha Ltd 末梢血流障害治療剤
EP0416855A2 (fr) * 1989-09-07 1991-03-13 Scotia Holdings Plc Acides gras pour le traitement et la prévention du dommage de la peau causé par la radiothérapie
EP0609064A1 (fr) * 1993-01-26 1994-08-03 Scotia Holdings Plc Utilisation des acides gras pour le traitement du dommage interne causé par le rayonnement

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS58180423A (ja) * 1982-04-16 1983-10-21 Nippon Suisan Kaisha Ltd 末梢血流障害治療剤
EP0416855A2 (fr) * 1989-09-07 1991-03-13 Scotia Holdings Plc Acides gras pour le traitement et la prévention du dommage de la peau causé par la radiothérapie
EP0609064A1 (fr) * 1993-01-26 1994-08-03 Scotia Holdings Plc Utilisation des acides gras pour le traitement du dommage interne causé par le rayonnement

Non-Patent Citations (6)

* Cited by examiner, † Cited by third party
Title
BARONZIO, G. ET AL: "Omega-3 fatty acids can improve radioresponse modifying tumor interstitial pressure, blood rheology and membrane peroxidability", ANTICANCER RESEARCH, vol. 14, no. 3, 1994, pages 1145 - 1154, XP002058619 *
DATABASE WPI Week 8348, Derwent World Patents Index; AN 83-829927, XP002058624 *
DATABASE WPI Week 9615, Derwent World Patents Index; AN 96-150112, XP002058623 *
HORROBIN, D.F.: "Is the main problem in free adical damage caused by radiation, oxygen and other toxins the loss of membrane essential fatty acids rather than the accumulation of toxic materials?", MEDICAL HYPOTHESES, vol. 35, no. 1, May 1991 (1991-05-01), pages 23 - 26, XP002058621 *
RYBCZYNSKA, M.: "The evaluation of erythrocyte membrane response to combined treatment of radiation and nitroimidazoles", INTERNATIONAL JOURNAL OF RADIATION BIOLOGY, vol. 58, no. 2, 1990, pages 313 - 323, XP002058620 *
YONEI, S. ET AL: "Studies on the mechanism of radiation induced structural disorganization of human erythrocyte membranes", INTERNATIONAL JOURNAL OF RADIATION BIOLOGY, vol. 46, no. 4, 1984, pages 463 - 71, XP002058622 *

Cited By (23)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1220669A4 (fr) * 1999-10-13 2004-12-08 Marco A Chacon Intervention therapeutique visant a reproduire l'effet d'une restriction calorique
US7414077B2 (en) * 1999-10-13 2008-08-19 Marco Chacon Therapeutic intervention to mimic the effect of caloric restriction
EP1220669A1 (fr) * 1999-10-13 2002-07-10 Marco A. Chacon Intervention therapeutique visant a reproduire l'effet d'une restriction calorique
US20060052446A1 (en) * 2000-08-23 2006-03-09 Chilton Floyd H Fatty acid-containing compositions and methods for the treatment of cytokine mediated disorders
US8431165B2 (en) 2004-12-13 2013-04-30 Swing Aerobics Licensing, Inc. Medicament for treatment of cancer and other diseases
US8092839B2 (en) 2004-12-13 2012-01-10 Swing Aerobics Licensing, Inc. Medicament for treatment of cancer and other diseases
US10918614B2 (en) 2009-04-29 2021-02-16 Ds Biopharma Limited Topical compositions comprising polyunsaturated fatty acids
US10328046B2 (en) 2009-04-29 2019-06-25 Ds Biopharma Limited Topical compositions comprising polyunsaturated fatty acids
US8536223B2 (en) 2009-04-29 2013-09-17 Dignity Sciences Limited Use of PUFAs for treating skin inflammation
US8729126B2 (en) 2009-04-29 2014-05-20 Dignity Sciences Limited Use of pufas for treating skin inflammation
US9216151B2 (en) 2009-04-29 2015-12-22 Dignity Sciences Limited. Use of PUFAS for treating skin inflammation
US9421163B2 (en) 2009-04-29 2016-08-23 Dignity Sciences Limited Topical compositions comprising polyunsaturated fatty acids
US9439850B2 (en) 2009-04-29 2016-09-13 Dignity Sciences Limited Use of pufas for treating skin inflammation
US9889106B2 (en) 2009-04-29 2018-02-13 Ds Biopharma Limited Topical compositions comprising polyunsaturated fatty acids
WO2012010406A1 (fr) 2010-07-22 2012-01-26 Unilever Plc Combinaisons de rhamnolipides et d'enzymes pour nettoyage amélioré
US9056086B2 (en) 2011-10-19 2015-06-16 Dignity Sciences Limited Pharmaceutical compositions comprising DGLA, 15-HEPE, and/or 15-HETrE and methods of use thereof
US8293790B2 (en) 2011-10-19 2012-10-23 Dignity Sciences Limited Pharmaceutical compositions comprising DGLA and benzoyl peroxide and methods of use thereof
US10105333B2 (en) 2014-06-04 2018-10-23 Ds Biopharma Limited Pharmaceutical compositions comprising DGLA and use of same
US10537543B2 (en) 2014-06-04 2020-01-21 Ds Biopharma Limited Pharmaceutical compositions comprising DGLA and use of same
US10849870B2 (en) 2014-06-04 2020-12-01 Ds Biopharma Limited Pharmaceutical compositions comprising DGLA and use of same
US11478442B2 (en) 2014-06-04 2022-10-25 Ds Biopharma Limited Pharmaceutical compositions comprising DGLA and use of same
CN108741081A (zh) * 2018-06-29 2018-11-06 许昌元化生物科技有限公司 一种含有亚麻酸的复合微粉及其制备方法
US12076304B2 (en) 2020-04-03 2024-09-03 Afimmune Limited Compositions comprising 15-HEPE and methods of treating or preventing hematologic disorders, and/or related diseases

Also Published As

Publication number Publication date
ZA978226B (en) 1998-05-11
GB9621373D0 (en) 1996-12-04
AU4130597A (en) 1998-05-11

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