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US20070149617A1 - Use of an omega-3 lipid-based emulsion following ischemic injury to provide protection and recovery in human organs - Google Patents

Use of an omega-3 lipid-based emulsion following ischemic injury to provide protection and recovery in human organs Download PDF

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US20070149617A1
US20070149617A1 US11/558,568 US55856806A US2007149617A1 US 20070149617 A1 US20070149617 A1 US 20070149617A1 US 55856806 A US55856806 A US 55856806A US 2007149617 A1 US2007149617 A1 US 2007149617A1
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omega
lipid
oil
based emulsion
hypoxic
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Richard Deckelbaum
Susan Vannucci
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Columbia University in the City of New York
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Assigned to TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK, THE reassignment TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK, THE ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: DECKELBAUM, RICHARD J., VANNUCCI, SUSAN J.
Publication of US20070149617A1 publication Critical patent/US20070149617A1/en
Priority to US13/336,290 priority patent/US9084801B2/en
Priority to US14/738,822 priority patent/US20150272921A1/en
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    • 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
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
    • A61K31/23—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin of acids having a carboxyl group bound to a chain of seven or more carbon atoms
    • A61K31/232—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin of acids having a carboxyl group bound to a chain of seven or more carbon atoms having three or more double bonds, e.g. etretinate
    • 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
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/56—Materials from animals other than mammals
    • A61K35/60—Fish, e.g. seahorses; Fish eggs
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/10—Dispersions; Emulsions
    • A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
    • 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
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • 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

Definitions

  • Cerebral hypoxia-ischemia is a major cause of morbidity and mortality through all stages of the life cycle, including for infants born prematurely, for children in intensive care units, and for elderly with cerebral vascular accidents. Infants and children who survive hypoxic-ischemic encephalopathy demonstrate lifelong neurologic handicaps, including cerebral palsy, mental retardation, epilepsy, and learning disabilities. Vannucci, R. C. (2000). “Hypoxic-ischemic encephalopathy,” American Journal of Perinatology 17(3): 113-120.
  • Lipid emulsions are commonly used in pediatric intensive care and are an important source of calories in these critically-ill children.
  • Most commercially available emulsions are formed from soybean oil, which have high concentrations of omega-6 (n-6) fatty acids.
  • Lipid emulsions rich in omega-3 (n-3) fatty acids such as ⁇ -linolenic acid, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), are derived from fish oils, and are not yet widely available for clinical use.
  • omega-3 oils have been shown to have beneficial effects in neurologic diseases such as epilepsy, depression, and behavioral disorders.
  • the present invention provides a method of limiting neurological damage resulting from hypoxic-ischemia comprising, administering an omega-3 lipid-based emulsion after a cerebral hypoxic-ischemia insult wherein the omega-3 lipid-based emulsion comprises omega-3 oil effective to confer protection against neurological damage.
  • the present invention also provides a method of limiting cell death resulting from hypoxic-ischemia comprising, administering an omega-3 lipid-based emulsion after a cerebral hypoxic-ischemia insult wherein the omega-3 lipid-based emulsion comprises omega-3 oil effective to confer protection to limit cell death.
  • Administration of the omega-3 lipid-based emulsion may be either enteral or parenteral. Methods of the present invention also provide further comprise administering a conventional stroke treatment or preventative medication.
  • Omega-3 lipid-based emulsions of the present invention comprise at least 10%, preferably at least 20%, omega-3 oil, by weight.
  • the omega-3 oil comprises at least 10%, preferably at least 20%, omega-3 triglyceride and/or omega-3 diglyceride and the fatty acids of the omega 3-triglyceride and/or omega-3 diglyceride comprise at least 40% EPA and/or DHA.
  • Omega-3 lipid-based emulsions may be administered at any effective dose, such as a dose of 0.05 g/kg to 4 g/kg, and may be administered any time after a hypoxic-ischemic insult, such as 20 minutes to six hours after the ischemic insult or 0-12 hours after the ischemic insult. Additional later administrations are also contemplated, for example an additional later administration is provided 1-24 hours after the insult.
  • the methods of the present invention are useful when ischemia has occurred in the organs selected from the group consisting of brain, lung, heart, kidney and large or small intestine.
  • the present invention also provides an omega-3 lipid-based emulsion suitable for enteral or parenteral administration, wherein said emusion confers a protective benefit on cells against cell death following a hypoxic-ischemic insult, said emulsion comprising at least 20% omega-3 oil, by weight, and wherein the omega-3 oil comprises at least 20% omega-3 triglycerides and/or diglycerides, and wherein fatty acids of the omega-3 triglyceride and/or diglycerides comprise at least 40% EPA and/or DHA.
  • the present invention also provides the use of an omega-3 lipid-based emulsion as described herein to make a medicament to limit neurological damage and/or cell death resulting from hypoxic-ischemia.
  • FIG. 1 provides the results of an experiment where rats were given an omega-3 lipid-based emulsion as a neuroprotective both prior and after 60 minutes of hypoxic-ischemia.
  • FIG. 2 provides the results of an experiment where rats were given an omega-3 lipid-based emulsion as a neuroprotective both prior and after 65 minutes of hypoxic-ischemia.
  • FIG. 3 shows the neuroprotective effect of omega-3 triglycerides just before hypoxic/ischemic insult on the size of brain infarcts as determined by TTC staining.
  • FIG. 4 shows the results of four separate experiments where rats were given an omega-3 lipid-based emulsion after 60 minutes of hypoxic-ischemia. Note that 40% of the treated animals had no brain damage and another 40% had less damage than the mean of control animals as assessed by TTC staining.
  • omega-3 lipid-based emulsion is an oil-in-water emulsion comprising at least about 10% omega-3 oil (and up to 100% omega-3 oil).
  • omega-3 lipid-based emulsion comprises at least 20% omega-3 oil.
  • omega-3 oils means any omega-3 fatty acid, including free omega-3 fatty acids and omega-3 triglycerides and omega-3 diglycerides.
  • omega-3 fatty acid means a polyunsaturated fatty acid wherein one of the carbon-carbon double bonds is between the third and fourth carbon atoms from the distal end of the hydrocarbon side chain of the fatty acid.
  • examples of “omega-3 fatty acid” include ⁇ -linolenic acid (18:3n-3; ⁇ -ALA; ⁇ 3,6,9 ), eicosapentaenoic acid (20:5n-3; EPA; ⁇ 5,8,11,14,17 ), docosahexaenoic acid (22:6n-3; DHA) and docosapentaenoic acid (22:5n-3; DPA; ⁇ 7,10,13,16,19 ), wherein EPA and DHA are most preferred.
  • Omega-3 fatty acids having at least 20 carbon atoms are herein called “long chain omega-3 fatty acids.”
  • omega-3 triglyceride or “omega-3 diglyceride” refers to a triglyceride or a diglyceride, respectively, comprising at least one omega-3 fatty acid esterified with a glycerol moiety.
  • omega-3 tri/diglyceride means that omega-3 fatty acid comprises an omega-3 triglyceride and/or a diglyceride or any combination thereof.
  • cerebral hypoxia-ischemia of sufficient duration to deplete high energy reserves in neural cells initiates a cascade of events over the hours to days of reperfusion that culminates in extensive death, both necrotic and apoptotic. These events include the generation of reactive oxygen species and oxidative damage to cells, release of inflammatory mediators and initiation of prolonged inflammatory reactions, and ongoing apoptosis that can continue for weeks to months. This applies to ischemic injury to organs in young, adult and elderly humans.
  • neuronal loss following hypoxia/ischemia is believed to result, at least in part, from elevated glutamate release and excitoxicity.
  • Excess glutamate activation of N-methyl-D-aspartic acid (NMDA) receptors induces pro-apoptotic pathways and inhibits anti-apoptotic signaling pathways.
  • Omega-3 fatty acids can modify a number of signaling pathways to effect transcriptional regulation.
  • omega-3 fatty acids protect neurons by modulating signaling pathways that counter the effects of hyper stimulated NMDA receptors, protection against free radical generation and consequent oxidative damage, and thereby prevent/reduce post-ischemic inflammation and release of inflammatory mediators.
  • the present invention provides methods of limiting or preventing cell death and cell/tissue damage resulting from hypoxic-ischemia. “Limiting” as used herein includes decreasing and/or preventing.
  • the methods of present invention comprise administering an omega-3 lipid-based emulsion of the present invention after an hypoxic-ischemia insult.
  • the present invention also provides, in those cases where the hypoxic-ischemic insult can be predicted, methods of limiting or preventing cell death and cell/tissue damage comprising administering an omega-3 lipid-based emulsion of the present invention before the hypoxic-ischemia insult.
  • the present invention limits neural cell death and/or limits neurological damage. Since the basic mechanisms of cell death following ischemia after an hypoxic-ischemic insult are similar in most bodily organs, the present invention also provides limiting cell death in other organs such as the heart, large and small intestines, kidney and lung following an hypoxic-ischemia insult. For example, after a colonic ischemic event due to acute mesenteric artery ischemia, chronic mesenteric artery ischemia or ischemia due to mesenteric venous thrombosis, the present invention provides a method of limiting intestinal cell death. Similar prevention of cell death would apply to myocardial infarction.
  • omega-6 fatty acids such as omega-6 linoleic acids are far less effective in neuroprotection and cardiac protection when provided before an ischemic event.
  • the studies involved the administration of Intralipid®, a soy oil based emulsion containing 55% of its fatty acids as omega-6 linoleic acid, with a very low content of EPA and DHA ( ⁇ 2%).
  • Intralipid® a soy oil based emulsion containing 55% of its fatty acids as omega-6 linoleic acid
  • DHA very low content of EPA and DHA
  • the methods of the present invention comprise administering an omega-3 lipid-based emulsion comprising at least 10%, preferably at least 20% (up to 100%) by weight of omega-3 oil.
  • the omega-3 oil comprises at least 10%, preferably at least 20% (up to 100%) omega-3 tri/diglycerides.
  • the fatty acids in the omega-3 tri/diglycerides preferably comprise at least 40% (up to 100%) EPA and/or DHA.
  • Sources of omega-3 fatty acids may be from any suitable source such as from fish oils, other oils or may even be synthesized. Although EPA and DHA are preferred omega-3 fatty acids, other omega-3 fatty acids may be used.
  • Methods of the present invention preferably comprise administering omega-3 lipid-based emulsions of the present invention either enterally (for example, orogastric or nasogastric) or parenterally (for example, subcutaneous, intravenous, intramuscular, intraperitoneal). Most preferably the emulsion is administered intravenously.
  • Omega-3 lipid-based emulsions of the present invention are preferably provided at a dose capable of providing a protective benefit.
  • a suitable effective and tolerable dose for a human would be about 0.05 g/kg to about 4.0 g/kg. Higher doses may be given as necessary.
  • Omega-3 lipid-based emulsions of the present invention are preferably administered parenterally and/or enterally after the ischemic insult (or in some embodiments, before the insult when it can be predicted).
  • the emulsion may be administered to prevent/reduce tissue damage after cerebral hypoxia or stroke as well as hypoxic-ischemic insults in other organs such as heart, kidney, lung, etc.
  • an omega-3 lipid-based emulsion is administered as soon as possible after the insult (or before in cases where the insult can be predicted) to provide a greater limitation of cell death.
  • an omega-3 lipid-based emulsion is administered from 0-12 hours after the insult. Ideally the administration occurs anywhere from 20 minutes to 6 hours after the insult.
  • the emulsion is administered 0-2 hours after the insult.
  • the present invention also provides for multiple administrations of the omega-3 lipid-based emulsion.
  • the emulsion may be first administered within 20 minutes of the insult, followed by a second administration 1-24 hours after the insult.
  • the present invention also contemplates multiple administration(s) of omega-3 lipid-based emulsions following the insult.
  • methods of limiting or preventing cell death and cell/tissue damage resulting from hypoxic-ischemia further comprise administering an omega-3 lipid-based emulsion of the present in conjunction with standard available therapies (such as surgery and angioplasty) and/or medications given to prevent or treat hypoxia-ischemia.
  • therapies such as surgery and angioplasty
  • the following drugs are often administered to prevent or treat strokes: antiplatelet medications such as aspirin, clopidogrel, dipyridamole, ticlopidine; anticoagulants such as heparin and warfarin; and thrombolytic agents such as tissue plasminogen activator.
  • Omega-3 lipid-based emulsions may be oil-in-water (o/w) emulsions in which the outer continuous phase consists of distilled water purified or sterilized for parenteral purposes.
  • oil-in-water emulsions may be obtained by standard methods, i.e. by mixing the oil components followed by emulsification and sterilization.
  • the pH value of the lipid emulsion may be adjusted to a physiologically acceptable value, preferably to a pH of from about 6.0 to about 9.0, more preferably from about 6.5 to about 8.5.
  • Auxiliary agents and additives may be added to the oil mixture prior to emulsification or prior to sterilization.
  • Omega-3 lipid-based emulsions according to the invention can be prepared by known standard procedures with inertization. Typically, first the lipids, emulsifier and other auxiliary agents and additives are mixed and then filled up with water with dispersing. The water may optionally contain additional water-soluble components (e.g. glycerol). Preferably omega-3 lipid-based emulsions of the present invention contain lipid particles having a diameter of about 100-400 nanometer, with an average size of 300 nanometers.
  • Omega-3 lipid-based emulsions of the present invention comprise at least 10%, preferably at least 20% (up to 100%) by weight of omega-3 oil.
  • the omega-3 oil comprises at least 10%, preferably at least 20% (up to 100%) omega-3 tri/diglyceride.
  • Fatty acids in the omega-3 tri/diglyceride preferably comprise at least 40% (up to 100%) EPA and/or DHA.
  • the omega-3 lipid-based emulsion preferably comprises 10% to 100% omega-3 tri/diglyceride.
  • omega-3 tri/diglyceride contains at least 40% (up to 100%) of their fatty acids as EPA and/or DHA.
  • omega-3 emulsions of the present invention are sterile and have a particle size that is preferably between 100-400 nanometer mean diameter, with an average size of 300 nm.
  • omega-3 lipid-based emulsion (0.25 cc)(a 20% long chain omega-3 triglyceride-based formula having >45% of total omega-3 fatty acid as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)) via orogastric feeding tube, and six control rats were given 0.25 cc water, both enterally.
  • the 20% omega-3 lipid-based emulsion was made placing 20 gm of omega-3 triglyceride in 100 ml of water, and emulsifying with 1.2 gm of egg yolk lecithin.
  • Rats were allowed to recover for 2 hours, then they underwent hypoxia-ischemia for 60 minutes of 8% oxygen at a constant temperature.
  • the six pre-treated rats were given another dose of 50 mg omega-3 lipid-based emulsion immediately after the hypoxia-ischemia and control rats were given another 0.25 cc water. All rats were euthanized at 72 hours of reperfusion.
  • the brains were removed and cut into 2 mm sections and stained with 2,3,5,Triphenyl-2H-tetrazolium chloride (TTC).
  • TTC 2,3,5,Triphenyl-2H-tetrazolium chloride
  • the six pre-treated rats were given another dose of 50 mg omega-3 lipid-based emulsion immediately after the hypoxia-ischemia and control rats were given another 0.25 cc water. All rats were euthanized at 72 hours of reperfusion.
  • the brains were removed and cut into 2 mm sections and stained with 2,3,5,Triphenyl-2H-tetrazolium chloride (TTC). The sections were scored as follows:
  • Four of the six control rats survived with a mean score of 2.75+/ ⁇ 0.50, while five of the six treated rats survived with a mean score of 1.70+/ 0.76 (p ⁇ 0.05). See FIG. 2 .
  • the rats were euthanized and their brains removed, cut into 2 mm sections and stained with 2,3,5triphenyl-2H-tetrazolium chloride (TTC).
  • TTC 2,3,5triphenyl-2H-tetrazolium chloride
  • the damage in each animal was then given a score from 0 (no damage) to 4 (>60% ipsilateral hemisphere infarcted).
  • rat pups Postnatal day 19-21 rat pups were subjected to unilateral carotid artery ligation and 60 minutes of hypoxic ischemia, according to the previously described protocol.
  • rats were treated by parenteral injection of omega-3 lipid-based emulsion (100 mg) immediately after the insult, and again at four hours after the insult.
  • the emulsion was as described above in Example 1. Brain damage was evaluated by TTC staining at 72 hours of reperfusion. In each instance, administration of the omega-3 lipid-based oil emulsion provided greater than 50% protection, i.e. reduction of tissue damage.
  • FIG. 4 shows the results of these experiments.
  • FIG. 4 represents at total of 14 control subjects (saline-treated) and 21 treated subjects (omega-3 lipid-based emulsion treated). Mean damage scores were: 1.93 ⁇ 0.22 (SEM), control, 0.78 ⁇ 0.16 emulsion-treated; p ⁇ 0.0001 by two-tailed test.
  • the data in FIG. 4 is presented as a scatter plot.
  • 40% of the treated animals were 100% protected (no damage at all, compared to 1/14 untreated; 40% suffered only mild damage, compared to 1/14 mildly damaged untreated animals.
  • Fatty acyl composition analyses of brain lipids (by gas liquid chromatography) after hypoxia/ischemia show no relative differences between infarcted brain versus non infarcted brain indicating that effects of acute administration of n-3 emulsions are not dependent on fatty acid compositional changes in brain membranes.
  • absolute concentrations of all fatty acids fell to similar degrees by about 15% (ug fatty acid per gram wet brain) indicating brain edema. This decrease did not occur with administration of n-3 emulsions indicating that these n-3 fatty acids prevented the brain edema as well as infarction.
  • ROS reactive oxygen species
  • Sections of the brain are stained (including both involved and non-involved hemispheres) with antibodies recognizing activated proteins known to participate in neuronal apoptosis (caspase 3, Jun N-terminal kinases), neuronal survival (activated Akt, phosphorylated BAD, FKHR) or to mediate the effects of NMDA-R signaling (CAM KII, and protein kinase C isoforms, in particular PKC ⁇ and PKC ⁇ ). Sections are co-stained with antibodies recognizing neuronal specific proteins (Tau), astrocytes (GFAP) or microglia.
  • activated proteins known to participate in neuronal apoptosis caspase 3, Jun N-terminal kinases
  • neuronal survival activated Akt, phosphorylated BAD, FKHR
  • CAM KII protein kinase C isoforms, in particular PKC ⁇ and PKC ⁇
  • Sections are co-stained with antibodies recognizing neuronal specific

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US13/336,290 US9084801B2 (en) 2005-11-14 2011-12-23 Use of an omega-3 lipid-based emulsion following ischemic injury to provide protection and recovery in human organs
US14/738,822 US20150272921A1 (en) 2005-11-14 2015-06-12 Use of an Omega-3 Lipid-Based Emulsion Following Ischemic Injury to Provide Protection and Recovery in Human Organs

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20100196461A1 (en) * 2009-01-30 2010-08-05 Simpkins Cuthbert O Resuscitation fluid
US20110086914A1 (en) * 2009-10-13 2011-04-14 Bailes Julian E Methods for Treating Traumatic Brain Injury
US20110200645A1 (en) * 2010-02-18 2011-08-18 Martek Biosciences Corporation DHA Free Fatty Acid Emulsions
US20110206741A1 (en) * 2010-02-18 2011-08-25 Martek Biosciences Corporation DHA Triglyceride Emulsions
US8343753B2 (en) 2007-11-01 2013-01-01 Wake Forest University School Of Medicine Compositions, methods, and kits for polyunsaturated fatty acids from microalgae
WO2014072311A1 (fr) 2012-11-07 2014-05-15 Centre Hospitalier Universitaire Vaudois Médicament comprenant au moins un acide gras polyinsaturé oméga-3
US8906855B2 (en) 2007-12-22 2014-12-09 Vivacelle Bio, Inc. Methods and compositions for treating conditions related to lack of blood supply, shock and neuronal injuries
US9387162B2 (en) 2007-12-22 2016-07-12 Vivacelle Bio, Inc. Methods and compositions for treating conditions related to lack of blood supply, shock, and neuronal injuries
CN111182902A (zh) * 2017-09-01 2020-05-19 黄玲惠 用于治疗缺血的黏性组合物
EP4255459A4 (fr) * 2020-12-07 2024-10-30 The Trustees Of Columbia University In The City Of New York Compositions et procédés de neuroprotection dans l'encéphalopathie hypoxique-ischémique néonatale

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* Cited by examiner, † Cited by third party
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US20100197785A1 (en) * 2007-07-25 2010-08-05 Epax As Omega-3 fatty acid fortified composition
WO2013044176A2 (fr) * 2011-09-23 2013-03-28 University Of Southern California Méthodes et compositions pour le traitement de l'accident ischémique cérébral
EP2958559A4 (fr) * 2013-02-20 2016-07-20 Univ Columbia Utilisation d'une émulsion à base de lipides oméga-3 pour protéger les organes humains d'un accident ischémique
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JP2020503320A (ja) * 2017-01-08 2020-01-30 レスキュー・ファーマ・インコーポレイテッドＲｅｓｑ Ｐｈａｒｍａ， Ｉｎｃ． 術中低血圧に関連する損傷を減らす方法
EP3802762B1 (fr) 2018-06-05 2023-12-13 DSM IP Assets B.V. Procédé de production de diglycérides

Citations (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5160759A (en) * 1989-06-07 1992-11-03 Kao Corporation Edible oil-in-water emulsion
US5214062A (en) * 1992-04-08 1993-05-25 Clintec Nutrition Co. Method and composition for treating immune disorders, inflammation and chronic infections
US5700837A (en) * 1994-04-21 1997-12-23 Nestec Ltd. Method and composition for normalizing injury response
US6020020A (en) * 1995-11-24 2000-02-01 Loders-Croklaan B.V. Composition based on fish oil
US6306908B1 (en) * 1997-02-21 2001-10-23 Abbott Laboratories Methods for reducing the incidence of necrotizing enterocolitis
US6448292B2 (en) * 2000-03-21 2002-09-10 Kao Corporation Oil composition
US20030144356A1 (en) * 2000-05-25 2003-07-31 Goodale David Buell Formulation
US20030149118A1 (en) * 2000-09-29 2003-08-07 Kraft Foods Holdings, Inc. Method and composition which inhibits the oxidation of omega-3 and omega-6 polyunsaturated lipids
US20030175403A1 (en) * 2002-03-14 2003-09-18 Gurin Michael H. Potentiated bioactive additives and method of use
US20070281993A1 (en) * 2004-03-04 2007-12-06 Geila Rozen Structured Triglycerides And Emulsions Comprising Same

Family Cites Families (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1988005261A1 (fr) 1987-01-16 1988-07-28 Tops Systems, Inc. Systeme de perfusion totale pour organes
US4895876A (en) 1987-03-20 1990-01-23 Air Products And Chemicals, Inc. Concentrated stable fluorochemical aqueous emulsions containing triglycerides
US6444432B1 (en) 1997-06-13 2002-09-03 Alan M. Kleinfeld Method of detection of cardiac ischemia using fatty acid binding protein
US6153653A (en) * 1997-11-26 2000-11-28 Protarga, Inc. Choline compositions and uses thereof
EP1075252A2 (fr) * 1998-05-07 2001-02-14 ELAN CORPORATION, Plc Systemes d'apport de medicament de preconcentre de microemulsion et d'emulsion depourvues de solvant/cosolvant
EP1279400A1 (fr) * 2001-07-25 2003-01-29 Target Hit sa Modification de la teneur en acides gras de membranes cellulaires d'organes et de tissus
GB0210212D0 (en) * 2002-05-03 2002-06-12 Univ Southampton Effects of dietary N-3 and N-6 pufa intake on atheromatous plaque stability
NZ539624A (en) * 2002-09-27 2008-08-29 Martek Biosciences Corp Prophylactic docosahexaenoic acid therapy for patients with subclinical inflammation
EP1660069A4 (fr) * 2003-08-05 2009-03-18 Univ Louisiana State Protections de neuroprotectine contre l'apoptose cellulaire, les degats d'une attaque d'apoplexie, la maladie d'alzheimer et la degeneration retinienne
WO2008036353A2 (fr) 2006-09-19 2008-03-27 The Trustees Of Columbia University In The City Of New York Émulsions de diglycérides oméga-3
US9034389B2 (en) 2009-03-11 2015-05-19 Stable Solutions Llc Omega-3 enriched fish oil-in-water parenteral nutrition emulsions
US20110206741A1 (en) 2010-02-18 2011-08-25 Martek Biosciences Corporation DHA Triglyceride Emulsions

Patent Citations (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5160759A (en) * 1989-06-07 1992-11-03 Kao Corporation Edible oil-in-water emulsion
US5214062A (en) * 1992-04-08 1993-05-25 Clintec Nutrition Co. Method and composition for treating immune disorders, inflammation and chronic infections
US5700837A (en) * 1994-04-21 1997-12-23 Nestec Ltd. Method and composition for normalizing injury response
US6020020A (en) * 1995-11-24 2000-02-01 Loders-Croklaan B.V. Composition based on fish oil
US6306908B1 (en) * 1997-02-21 2001-10-23 Abbott Laboratories Methods for reducing the incidence of necrotizing enterocolitis
US6448292B2 (en) * 2000-03-21 2002-09-10 Kao Corporation Oil composition
US20030144356A1 (en) * 2000-05-25 2003-07-31 Goodale David Buell Formulation
US20030149118A1 (en) * 2000-09-29 2003-08-07 Kraft Foods Holdings, Inc. Method and composition which inhibits the oxidation of omega-3 and omega-6 polyunsaturated lipids
US20030175403A1 (en) * 2002-03-14 2003-09-18 Gurin Michael H. Potentiated bioactive additives and method of use
US20070281993A1 (en) * 2004-03-04 2007-12-06 Geila Rozen Structured Triglycerides And Emulsions Comprising Same

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
Billman, George, Prevention of Ischemia-induced Ventricular Fibrillation by [omega]3 fatty acids, 1994, Proc. Natl. Acad. Sci. USA, Vol 91, pages 4427-4430. *
Billman, George, The Effects of Omega-3 Fatty Acids on Ventricular Fibrillation Induced by Myocardial Ischemia, 1994, American Heart Association, Preceedings from the Scientific Conference on Omega-3 Fatty Acids in Nutrition, Vascular Biology, and Medicine (Houston, Texas), April 17-19, 1994, pages 159-165. *

Cited By (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8343753B2 (en) 2007-11-01 2013-01-01 Wake Forest University School Of Medicine Compositions, methods, and kits for polyunsaturated fatty acids from microalgae
US9622968B2 (en) 2007-12-22 2017-04-18 Vivacelle Bio, Inc. Methods and compositions for treating conditions related to lack of blood supply, shock and neuronal injuries
US8906855B2 (en) 2007-12-22 2014-12-09 Vivacelle Bio, Inc. Methods and compositions for treating conditions related to lack of blood supply, shock and neuronal injuries
US9387162B2 (en) 2007-12-22 2016-07-12 Vivacelle Bio, Inc. Methods and compositions for treating conditions related to lack of blood supply, shock, and neuronal injuries
US9439855B2 (en) 2007-12-22 2016-09-13 Vivacelle Bio, Inc. Methods and compositions for treating conditions related to lack of blood supply, shock and neuronal injuries
US20100196461A1 (en) * 2009-01-30 2010-08-05 Simpkins Cuthbert O Resuscitation fluid
US20110086914A1 (en) * 2009-10-13 2011-04-14 Bailes Julian E Methods for Treating Traumatic Brain Injury
US20110206741A1 (en) * 2010-02-18 2011-08-25 Martek Biosciences Corporation DHA Triglyceride Emulsions
US20110200645A1 (en) * 2010-02-18 2011-08-18 Martek Biosciences Corporation DHA Free Fatty Acid Emulsions
WO2014072311A1 (fr) 2012-11-07 2014-05-15 Centre Hospitalier Universitaire Vaudois Médicament comprenant au moins un acide gras polyinsaturé oméga-3
CN111182902A (zh) * 2017-09-01 2020-05-19 黄玲惠 用于治疗缺血的黏性组合物
JP2020536850A (ja) * 2017-09-01 2020-12-17 エクセル メッド、エルエルシー 虚血を処置するための粘稠性組成物
CN116999555A (zh) * 2017-09-01 2023-11-07 黄玲惠 用于治疗缺血的黏性组合物
JP7710660B2 (ja) 2017-09-01 2025-07-22 エクセル メッド、エルエルシー 虚血を処置するための粘稠性組成物
EP4255459A4 (fr) * 2020-12-07 2024-10-30 The Trustees Of Columbia University In The City Of New York Compositions et procédés de neuroprotection dans l'encéphalopathie hypoxique-ischémique néonatale

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