WO1996037200A1 - Use of dha as a pharmaceutical composition - Google Patents

Use of dha as a pharmaceutical composition Download PDF

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Publication number
WO1996037200A1
WO1996037200A1 PCT/GB1996/001265 GB9601265W WO9637200A1 WO 1996037200 A1 WO1996037200 A1 WO 1996037200A1 GB 9601265 W GB9601265 W GB 9601265W WO 9637200 A1 WO9637200 A1 WO 9637200A1
Authority
WO
WIPO (PCT)
Prior art keywords
dha
administration
medicament
fatty acids
linolenic
Prior art date
Application number
PCT/GB1996/001265
Other languages
French (fr)
Inventor
Barbara Jacqueline Stordy
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 to DK96919911T priority Critical patent/DK0774962T3/en
Priority to US08/776,250 priority patent/US6150411A/en
Priority to JP8535515A priority patent/JPH10503531A/en
Priority to AU58277/96A priority patent/AU722474B2/en
Priority to EP96919911A priority patent/EP0774962B1/en
Priority to AT96919911T priority patent/ATE264676T1/en
Application filed by Scotia Holdings Plc filed Critical Scotia Holdings Plc
Priority to DE69632236T priority patent/DE69632236T2/en
Priority to KR1019970700488A priority patent/KR970704433A/en
Publication of WO1996037200A1 publication Critical patent/WO1996037200A1/en
Priority to FI970298A priority patent/FI970298A0/en
Priority to NO970317A priority patent/NO970317L/en
Priority to HK98113985A priority patent/HK1012575A1/en

Links

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
    • 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
    • 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
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents

Definitions

  • Dyslexia is a major problem of human development. It is a disorder manifest by difficulty in learning to read despite conventional instruction, adequate intelligence and socio-cultural opportunities, and arises from fundamental cognitive disabilities.
  • Dyslexia is four to five times commoner in boys than girls, commoner in children with atopic eczema and asthma than those without, and also commoner in offenders than the law abiding. It is associated with a loss of normal brain asymmetry which is demonstrable using modern brain scanning methods and also on functional tests. It is recognised to be a disorder with an organic basis.
  • DHA Docosahexaenoic
  • dark adaptation can be influenced by a number of known nutrients, including vitamins A and C, riboflavin, nicotinic acid, thiamin and zinc, all subjects were asked to keep a careful 7 day record of food eaten and the results analysed by the diet analysis program, COMPEAT 4. No differences between the control and dyslexia groups in any of these nutrients were detected.
  • Tests for influence of DHA on dark adaptation was therefore conducted. For a period of one month 5 dyslexics and 5 controls were given 4 capsules per day of a fish oil which contained 120 mg of DHA per capsule, with no vitamin A or vitamin D. Dark adaptation was then retested.
  • DHA had no effects on dark adaptation, although in one subject adaptation clearly improved.
  • DHA consistently and significantly improved dark adaptation (p ⁇ 0.041).
  • DHA supplements given to dyslexic children have been found to be associated with apparent improvements in reading ability and behaviour.
  • the invention lies in combating dyslexia or inadequate night vision or dark adaptation in dyslexics or normal individuals, by administering DHA or a precursor n-3 EFA, and particularly in:-
  • a method of treating the conditions by administering DHA or precursor to children and adults showing them.
  • the invention also lies in a method of preparation of a medicament, for use in combating dyslexia or inadequate night vision or dark adaptation as above, when DHA or precursor is used.
  • DHA is a key fatty acid in both the retina and the brain
  • n-6 fatty acids derived from linoleic acid (Figure 1) are also important in these tissues.
  • DHA and eicosapentaenoic acid (EPA) (which is usually associated with DHA in fish oils) can in some circumstances inhibit conversion of LA to gamma-linolenic acid (GLA)
  • GLA gamma-linolenic acid
  • DGLA dihomo-gamma-linolenic acid
  • AA arachidonic acid
  • SA stearidonic acid
  • the fatty acids may be delivered in any appropriate form which can raise the levels of DHA and/or the other fatty acids in the blood.
  • Appropriate forms are the free fatty acids; their salts, including lithium salts: esters; diesters of 1,3-propane diol and other diols; amides; alcohols; tri-, di- and monoglycerides; phospholipids such as phosphatidyl-choline or phosphatidyl-ethanolamine; or any other pharmaceutically acceptable combined form.
  • the fatty acids are not toxic and so they may be given in doses of from 1 mg to 100 g per day, preferably 20 mg to 10 g and very preferably 50 mg to 2g/day. They may be administered orally, enterally, parenterally or topically by any appropriate formulation including capsules, pastilles, tablets, powders, emulsions, suspensions, oils, creams, lotions, patches, liposomes, galactosomes or any other form known to those skilled in the art.
  • the ratio of DHA to n-6 acids, when present, in the formulations may range from 1:100 to 100:1, preferably 5: 1 to 1:5 and very preferably 3: 1 to 1:3.
  • soft gelatin capsules or hard gelatin capsules, or pastilles or tablets or other pharmaceutical or nutritional dosage forms containing 100 mg DHA and optionally 100 mg GLA, 100 mg AA and/or 100 mg EPA, for pre-emptive consumption by women in pregnancy or by infants, or for consumption by diagnosed dyslexic children or adults, to give a daily dose of DHA of 20 mg to 10 g.
  • Granules or powder for use as above made with gum acacia, gelatin, starch or other appropriate material containing by weight in each gram, 50 mg DHA, optionally with 50 mg of DGLA, 50 mg AA and/or 50 mg SA.

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  • Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Hospice & Palliative Care (AREA)
  • Psychiatry (AREA)
  • Ophthalmology & Optometry (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicines Containing Plant Substances (AREA)
  • Fats And Perfumes (AREA)
  • Coloring Foods And Improving Nutritive Qualities (AREA)
  • Cephalosporin Compounds (AREA)

Abstract

A method of combating dyslexia, or inadequate night vision or dark adaptation in dyslexics or normal persons, and a method of manufacture of a medicament for such purposes, characterised by administering/incorporating DHA as an active in effective amount, optionally in association with other n-3 essential fatty acids and n-6 essential fatty acids.

Description

USE OF DHA AS A PHARMACEUTICAL COMPOSITION
Background
Dyslexia is a major problem of human development. It is a disorder manifest by difficulty in learning to read despite conventional instruction, adequate intelligence and socio-cultural opportunities, and arises from fundamental cognitive disabilities.
Dyslexia is four to five times commoner in boys than girls, commoner in children with atopic eczema and asthma than those without, and also commoner in offenders than the law abiding. It is associated with a loss of normal brain asymmetry which is demonstrable using modern brain scanning methods and also on functional tests. It is recognised to be a disorder with an organic basis.
Current Work
Docosahexaenoic (DHA) is a major constituent of the retina, of nerve tissue and of the brain, and studies have now been done to look for abnormalities in dyslexic individuals in the intake of nutrients known to be important in brain function, particularly DHA. The first study looked at 33 dyslexic children and 48 controls and was directed to maternal diet during pregnancy. Mothers were given a comprehensive questionnaire, directed particularly at the levels of alpha-linolenic acid (ALA) in the diet and the ratio of ALA to linoleic acid (LA). (ALA is converted to DHA within the body and that conversion can be inhibited by a high intake of LA). The pathways of metabolism of LA and ALA are shown in Figure 1. The study showed that the mothers of dyslexic children were significantly more likely to have consumed a diet with a low ALA:LA ratio during pregnancy.
A second study focused specifically on the intakes of foods, in particular fish and meats, which contain DHA itself. This study demonstrated that mothers of dyslexic children consumed diets lower in DHA. It was therefore decided to investigate whether DHA supplementation might be beneficial in dyslexic individuals. A test capable of quickly demonstrating an effect was needed, and as DHA is known to be particularly important in the function of the retinal rods, required for vision in the dark, it was decided to test for reduced retinal DHA levels in dyslexia, as indicated by dark adaptation. Ten adults with dyslexia (4 females and 6 males) and ten control subjects (6 females and four males) were recruited. They were all young adults with age range of 18-26 years. Dark adaptation was tested using a standard instrument, the Friedman Visual Field Analyser, set for the dark adaptation function. One eye was occluded, bright light was shone in the other eye to bleach the retina and the room was darkened. Measurements of dark adaptation were made at one minute intervals by assessing the intensity of very brief flashes of light which could just be detected. Measurements were continued until no further adaptation was observed.
Because dark adaptation can be influenced by a number of known nutrients, including vitamins A and C, riboflavin, nicotinic acid, thiamin and zinc, all subjects were asked to keep a careful 7 day record of food eaten and the results analysed by the diet analysis program, COMPEAT 4. No differences between the control and dyslexia groups in any of these nutrients were detected.
The results for the two groups are presented in Figure 2 which shows the means and standard deviations. The dyslexics at every time point show poorer dark adaptation than the controls and the differences between the two groups are statistically significant (p<0.05).
Tests for influence of DHA on dark adaptation was therefore conducted. For a period of one month 5 dyslexics and 5 controls were given 4 capsules per day of a fish oil which contained 120 mg of DHA per capsule, with no vitamin A or vitamin D. Dark adaptation was then retested.
In four of the controls, DHA had no effects on dark adaptation, although in one subject adaptation clearly improved. In contrast, in the dyslexic subjects as shown in Figure 3, DHA consistently and significantly improved dark adaptation (p< 0.041). Subsequently, DHA supplements given to dyslexic children have been found to be associated with apparent improvements in reading ability and behaviour. These reports are currently anecdotal and subjective but more formal controlled studies are in preparation.
The Invention
The invention lies in combating dyslexia or inadequate night vision or dark adaptation in dyslexics or normal individuals, by administering DHA or a precursor n-3 EFA, and particularly in:-
1. A method of treating the conditions by administering DHA or precursor to children and adults showing them.
2. A method of preventing the conditions by administering DHA or precursor to women during pregnancy and to infants in the year after birth.
The invention also lies in a method of preparation of a medicament, for use in combating dyslexia or inadequate night vision or dark adaptation as above, when DHA or precursor is used.
Although DHA is a key fatty acid in both the retina and the brain, the n-6 fatty acids derived from linoleic acid (Figure 1) are also important in these tissues. Because DHA and eicosapentaenoic acid (EPA) (which is usually associated with DHA in fish oils) can in some circumstances inhibit conversion of LA to gamma-linolenic acid (GLA), it may be appropriate in some situations to provide, with the DHA, supplements of LA or preferably GLA, dihomo-gamma-linolenic acid (DGLA) or arachidonic acid (AA) to prevent depletion of these important fatty acids. It may also be appropriate to provide other n-3 essential fatty acids such as alpha-linolenic acid, stearidonic acid (SA) or EPA for their specific properties rather than as DHA precursors.
The fatty acids may be delivered in any appropriate form which can raise the levels of DHA and/or the other fatty acids in the blood. Appropriate forms are the free fatty acids; their salts, including lithium salts: esters; diesters of 1,3-propane diol and other diols; amides; alcohols; tri-, di- and monoglycerides; phospholipids such as phosphatidyl-choline or phosphatidyl-ethanolamine; or any other pharmaceutically acceptable combined form.
The fatty acids are not toxic and so they may be given in doses of from 1 mg to 100 g per day, preferably 20 mg to 10 g and very preferably 50 mg to 2g/day. They may be administered orally, enterally, parenterally or topically by any appropriate formulation including capsules, pastilles, tablets, powders, emulsions, suspensions, oils, creams, lotions, patches, liposomes, galactosomes or any other form known to those skilled in the art.
The use of DHA as such is preferred. The ratio of DHA to n-6 acids, when present, in the formulations may range from 1:100 to 100:1, preferably 5: 1 to 1:5 and very preferably 3: 1 to 1:3.
Examples
The following formulations and their use illustrate the invention, by way of example.
1. For use in combating dyslexia, soft gelatin capsules or hard gelatin capsules, or pastilles or tablets or other pharmaceutical or nutritional dosage forms containing 100 mg DHA and optionally 100 mg GLA, 100 mg AA and/or 100 mg EPA, for pre-emptive consumption by women in pregnancy or by infants, or for consumption by diagnosed dyslexic children or adults, to give a daily dose of DHA of 20 mg to 10 g.
2. Granules or powder for use as above, made with gum acacia, gelatin, starch or other appropriate material containing by weight in each gram, 50 mg DHA, optionally with 50 mg of DGLA, 50 mg AA and/or 50 mg SA.
3. Oils for use as above for use as salad oils or for incorporation into any appropriate food material containing 5% by weight DHA, optionally with 10% by weight GLA, 5% by weight AA and 5% by weight EPA. 4. Whips, foams, creams, mousses or other liquid or semi-liquid formulations for use as above as foods and containing 2% DHA and optionally 2% by weight GLA, 2% AA, 2% DGLA, 2% SA and 2% EPA.
5. Creams, ointments, lotions, shampoos, patches, sticks, pessaries, suppositories or any other dosage form for use as above for topical application in which the active material is an oil containing 3% DHA, optionally with 5% by weight DGLA, 2% AA and 3% EPA.
6-10. Formulations as in 1-5 but in which the active ingredients are DHA with any one (or more than one) of the n-6 EFAs selected from GLA, DGLA and AA, and/or any one (or more than one) of the n-3 EFAs selected from SA, 20:4n-3, DPA or EPA.
11-15. Formulations as in 1-5 but in which the active ingredients are DHA and either GLA or DGLA of the n-6 series and/or EPA of the n-3 series.
16-20. Formulations as in 1-5 but for use in improvement of dark adaptation and/or nocturnal vision generally in dyslexic or non-dyslexic individuals.

Claims

1. A method of combating dyslexia, or inadequate night vision or dark adaptation in dyslexics or normal persons, and a method of manufacture of a medicament for such purposes, characterised by administering/incorporating DHA as an active in effective amount.
2. A method according to Claim 1, administration being to children or adults showing one or more of the conditions.
3. A preventative method according to Claim 1, administration being to women during pregnancy or to infants in the year after birth.
4. A method according to any preceding claim wherein one or more n-6 EFAs drawn from the group consisting of linoleic, gamma-linolenic, dihomogamma-linolenic and arachidonic acids and/or one or more n-3 EFAs drawn from the group consisting of alpha-linolenic, stearidonic and eicosapentaenoic acids is used in addition to the DHA.
5. A method according to Claim 1, 2 or 3 wherein a precursor n-3 essential fatty acid is substituted for all or part of the DHA.
6. A method according to Claim 1, 2 or 3 wherein administration is of, or the medicament is suited to administration of, 1 mg to 100 g, preferably 20 mg to 10 g and very preferably 50 mg to 2 g per day of the DHA.
7. A method according to Claim 4 or 5 wherein administration is of, or the medicament is suited to administration of, amounts of fatty acids that in total are within the ranges in Claim 6.
8. A method according to Claim 4 wherein administration is of, or the medicament is suited to administration of, DHA and n-6 essential fatty acids in a weight ratio of 1: 100 to 100: 1, preferably 5: 1 to 1:5 and very preferably 3: 1 to 1:3.
9. A method according to any preceding claim wherein the DHA and/or other essential fatty acids are present as one or more of:- salts including lithium salts; esters; diesters of 1,3-propane diol and other diols; amides; fatty acid alcohols; mono-, di- or triglycerides; phosphatidyl-choline, phosphatidyl-ethanolamine or other phospholipid; or other pharmaceutically acceptable combined form.
PCT/GB1996/001265 1995-05-25 1996-05-24 Use of dha as a pharmaceutical composition WO1996037200A1 (en)

Priority Applications (11)

Application Number Priority Date Filing Date Title
US08/776,250 US6150411A (en) 1995-05-25 1996-05-24 Use of DHA as a pharmaceutical composition
JP8535515A JPH10503531A (en) 1995-05-25 1996-05-24 Use of DHA as a pharmaceutical composition
AU58277/96A AU722474B2 (en) 1995-05-25 1996-05-24 Use of DHA as a pharmaceutical composition
EP96919911A EP0774962B1 (en) 1995-05-25 1996-05-24 Use of dha in the treatment of dyslexia
AT96919911T ATE264676T1 (en) 1995-05-25 1996-05-24 USE OF DHA IN THE TREATMENT OF DYSLEXIA
DK96919911T DK0774962T3 (en) 1995-05-25 1996-05-24 Use of DHA in the treatment of dyslexia
DE69632236T DE69632236T2 (en) 1995-05-25 1996-05-24 USE OF DHA IN THE TREATMENT OF DYSLEXIA
KR1019970700488A KR970704433A (en) 1995-05-25 1996-05-24 Use of DHA as a pharmaceutical composition (Use of DHA as a pharmaceutical composition)
FI970298A FI970298A0 (en) 1995-05-25 1997-01-24 Use of DHA as a pharmaceutical composition
NO970317A NO970317L (en) 1995-05-25 1997-01-24 Use of DHA in a pharmaceutical composition
HK98113985A HK1012575A1 (en) 1995-05-25 1998-12-18 Use od dha in the treatment of dyslexia.

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB9510636.5 1995-05-25
GBGB9510636.5A GB9510636D0 (en) 1995-05-25 1995-05-25 Fatty acid treatment

Publications (1)

Publication Number Publication Date
WO1996037200A1 true WO1996037200A1 (en) 1996-11-28

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PCT/GB1996/001265 WO1996037200A1 (en) 1995-05-25 1996-05-24 Use of dha as a pharmaceutical composition

Country Status (17)

Country Link
US (1) US6150411A (en)
EP (1) EP0774962B1 (en)
JP (1) JPH10503531A (en)
KR (1) KR970704433A (en)
AT (1) ATE264676T1 (en)
AU (1) AU722474B2 (en)
CA (1) CA2195979A1 (en)
DE (1) DE69632236T2 (en)
DK (1) DK0774962T3 (en)
ES (1) ES2217317T3 (en)
FI (1) FI970298A0 (en)
GB (1) GB9510636D0 (en)
HK (1) HK1012575A1 (en)
NO (1) NO970317L (en)
PT (1) PT774962E (en)
WO (1) WO1996037200A1 (en)
ZA (1) ZA964215B (en)

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WO2001024645A1 (en) * 1999-10-07 2001-04-12 Societe Des Produits Nestle S.A. Nutritional composition
US6423325B1 (en) 1999-07-30 2002-07-23 Conopco, Inc. Skin care composition
EP1713463A2 (en) * 2004-01-19 2006-10-25 Martek Biosciences Corporation Reelin deficiency or dysfunction and methods related thereto
WO2010010365A1 (en) * 2008-07-24 2010-01-28 Pharma Marine As Polyunsaturated fatty acids for improving vision
US7687485B2 (en) 1999-09-30 2010-03-30 Drug Tech Corporation Formulation for menopausal women
US7935365B2 (en) 2003-10-22 2011-05-03 Enzymotec, Ltd. Glycerophospholipids for the improvement of cognitive functions
US7968112B2 (en) 2003-10-22 2011-06-28 Enzymotec Ltd. Lipids containing omega-3 and omega-6 fatty acids
US8052992B2 (en) 2003-10-22 2011-11-08 Enzymotec Ltd. Glycerophospholipids containing omega-3 and omega-6 fatty acids and their use in the treatment and improvement of cognitive functions
US8278351B2 (en) 2001-07-27 2012-10-02 Neptune Technologies & Bioressources, Inc. Natural marine source phospholipids comprising polyunsaturated fatty acids and their applications
US8586567B2 (en) 2009-10-29 2013-11-19 Acasti Pharma, Inc. Concentrated therapeutic phospholipid compositions
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US7998500B2 (en) 2005-08-04 2011-08-16 Vertical Pharmaceuticals, Inc. Nutritional supplement for women
US7901710B2 (en) 2005-08-04 2011-03-08 Vertical Pharmaceuticals, Inc. Nutritional supplement for use under physiologically stressful conditions
US8202546B2 (en) 2005-08-04 2012-06-19 Vertical Pharmaceuticals, Inc. Nutritional supplement for use under physiologically stressful conditions
US20070166411A1 (en) * 2005-12-16 2007-07-19 Bristol-Myers Squibb Company Nutritional supplement containing long-chain polyunsaturated fatty acids
US8343753B2 (en) * 2007-11-01 2013-01-01 Wake Forest University School Of Medicine Compositions, methods, and kits for polyunsaturated fatty acids from microalgae
US9119826B2 (en) 2011-02-16 2015-09-01 Pivotal Therapeutics, Inc. Omega 3 fatty acid for use as a prescription medical food and omega 3 fatty acid diagniostic assay for the dietary management of cardiovascular patients with cardiovascular disease (CVD) who are deficient in blood EPA and DHA levels
US8952000B2 (en) 2011-02-16 2015-02-10 Pivotal Therapeutics Inc. Cholesterol absorption inhibitor and omega 3 fatty acids for the reduction of cholesterol and for the prevention or reduction of cardiovascular, cardiac and vascular events
US8951514B2 (en) 2011-02-16 2015-02-10 Pivotal Therapeutics Inc. Statin and omega 3 fatty acids for reduction of apolipoprotein-B levels
US8715648B2 (en) 2011-02-16 2014-05-06 Pivotal Therapeutics Inc. Method for treating obesity with anti-obesity formulations and omega 3 fatty acids for the reduction of body weight in cardiovascular disease patients (CVD) and diabetics
US9216199B2 (en) 2013-12-05 2015-12-22 Buriva, LLC Nutritional supplement containing phospholipid-DHA derived from eggs
US9610302B2 (en) 2013-12-05 2017-04-04 Buriva, LLC. Composition containing phospholipid-DHA and B vitamins
US9233114B2 (en) 2013-12-05 2016-01-12 Buriva, LLC Dietary supplement containing phospholipid-DHA derived from eggs
US9549937B2 (en) 2013-12-05 2017-01-24 Burvia, LLC. Composition containing phospholipid-DHA and folate
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Cited By (24)

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WO2000021524A1 (en) * 1998-10-15 2000-04-20 Dsm N.V. Pufa supplements
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PT774962E (en) 2004-09-30
DE69632236T2 (en) 2005-04-14
EP0774962B1 (en) 2004-04-21
AU722474B2 (en) 2000-08-03
DE69632236D1 (en) 2004-05-27
NO970317L (en) 1997-01-24
FI970298A (en) 1997-01-24
ZA964215B (en) 1996-12-04
DK0774962T3 (en) 2004-08-09
HK1012575A1 (en) 1999-08-06
JPH10503531A (en) 1998-03-31
EP0774962A1 (en) 1997-05-28
KR970704433A (en) 1997-09-06
AU5827796A (en) 1996-12-11
US6150411A (en) 2000-11-21
GB9510636D0 (en) 1995-07-19
CA2195979A1 (en) 1996-11-28
ATE264676T1 (en) 2004-05-15
FI970298A0 (en) 1997-01-24
ES2217317T3 (en) 2004-11-01

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