WO2008153426A1 - Composition anti-inflammatoire et son utilisation - Google Patents

Composition anti-inflammatoire et son utilisation Download PDF

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Publication number
WO2008153426A1
WO2008153426A1 PCT/NZ2008/000146 NZ2008000146W WO2008153426A1 WO 2008153426 A1 WO2008153426 A1 WO 2008153426A1 NZ 2008000146 W NZ2008000146 W NZ 2008000146W WO 2008153426 A1 WO2008153426 A1 WO 2008153426A1
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Prior art keywords
oil
oils
composition
omega
marine
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PCT/NZ2008/000146
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English (en)
Inventor
Donald John Bell
Alan Groves
Lance Derek Searle
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Sealord Group Limited
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Publication of WO2008153426A1 publication Critical patent/WO2008153426A1/fr

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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
    • 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
    • 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]

Definitions

  • the present invention relates to anti-inflammatory compositions and uses thereof and in particular to compositions comprising a mixture of one or more marine oils with one or more omega 3 extracts of one or more marine oils and use of the compositions to treat or prevent inflammation or a condition selected from osteoarthritis, rheumatoid arthritis, an atopic condition, an allergy, arteriosclerosis, atherosclerosis, heart disease, high blood pressure, blood clots, hypotension, vasoconstriction, cancer, or depression.
  • Tissue extracts from the green shell mussel (GSM) Perna canaliculus are also reported to be useful as anti-inflammatory products. Individual subjects may respond differently to antiinflammatory agents (Noble et al, 2000). The availability of improved or alternative antiinflammatory agents is desirable for subjects suffering conditions associated with abnormal or undesirable inflammation. It would therefore be desirable to provide an improved or alternative anti-inflammatory composition.
  • GSM green shell mussel
  • the present invention relates to a composition
  • a composition comprising, consisting essentially of, or consisting of a mixture of (a) an omega 3 fatty acid extract of one or more marine oils, and (b) one or more marine oils.
  • the present invention relates to a method of treating or preventing inflammation or a condition selected from osteoarthritis, rheumatoid arthritis, an atopic condition, an allergy, arteriosclerosis, atherosclerosis, heart disease, high blood pressure, blood clots, hypotension, vasoconstriction, cancer, or depression, the method comprising separate, simultaneous, or sequential administration to a subject in need thereof of an effective amount of (a) an omega 3 fatty acid extract of one or more marine oils, and
  • the present invention relates to use of (a) an omega 3 fatty acid extract of one or more marine oils, and (b) one or more marine oils, to treat or prevent inflammation or a condition selected from osteoarthritis, rheumatoid arthritis, an atopic condition, an allergy, arteriosclerosis, atherosclerosis, heart disease, high blood pressure, blood clots, hypotension, vasoconstriction, cancer, or depression.
  • the medicament may be formulated for separate, simultaneous, or sequential administration of the extract and the one or more oils.
  • the present invention relates to a product containing
  • one or more marine oils as a combined preparation for separate, simultaneous, or sequential use to treat or prevent inflammation or a condition selected from osteoarthritis, rheumatoid arthritis, an atopic condition, an allergy, arteriosclerosis, atherosclerosis, heart disease, high blood pressure, blood clots, hypotension, vasoconstriction, cancer, or depression.
  • the mixture is a blend or admixture.
  • the one or more omega 3 fatty acid extracts is a mixture, blend or admixture of two or more omega 3 fatty acid extracts, or three or more omega 3 fatty acid extracts, or four or more omega 3 fatty acid extracts.
  • the omega 3 fatty acid extract comprises at least about 60, 65, 70, 75, 80, 85, 90, or 95% by weight omega 3 fatty acids or esters thereof.
  • the extract is prepared by supercritical fluid extraction of one or more marine oils, preferably supercritical CO 2 extraction of one or more marine oils.
  • the omega 3 fatty acid extract (also referred to as the omega 3 extract) comprises one or more fatty acids or one or more esters thereof or combinations thereof selected from ⁇ -linolenic acid (ALA) (18:3 (n-3); octadeca-9,12,15-trienoic acid), esters of ALA, stearidonic acid (SA) (18:4 (n-3); octadeca-6,9,12,15-tetraenoic acid), esters of SA, eicosatetraenoic acid (ETA) (20:4 (n-3); eicosa-8,ll,l4,17-tetraenoic acid), esters of ETA, eicosapentaenoic acid (EPA) (20:5 (n-3); eicosa-5,8,ll,14,17-pentaenoic acid), esters of EPA, docosapentaenoic acid (DPA) (22:5 (n-3); docosapentaeno
  • the fatty acids may be free fatty acids or esterified, preferably esterified.
  • Useful esterified fatty acids include methyl, ethyl, and propyl esters, and lipids (including glyceroHpids, glycerophospholipids, and phospholipids) or a combination of any two or more thereof.
  • the omega 3 fatty acid extract is an extract of one or more marine oils.
  • Preferred methods of extraction include solvent extraction, supercritical solvent extraction including supercritical CO 2 extraction, distillation, and chromatographic separation.
  • Preferred methods of solvent extraction include ethanol extraction.
  • the extract is prepared by solvent extraction, such as ethanol extraction, followed by distillation or supercritical extraction.
  • the extract is preparedly conversion of the marine oil, preferably a hoki oil, to ethyl esters followed by extraction of omega 3 fatty acids using supercritical CO 2 .
  • an additional extract from a plant oil, a marine oil, eggs, milk fat, or micro-algae, or a combination of any two or more thereof may also be added to the composition.
  • the marine oil selected from one or more marine mammal oils
  • the oil is a seal oil, or a squid oil, or a fish oil.
  • the cephalopod oil is an octopus oil (from cephalopods of the order Octopoda) or a squid oil (from cephalopods of the order Teuthida such as JLoligopki, Loligo bkekert, Nototodarus gotildi, and Nototodarus sloanii).
  • the fish oil is selected from alfonsino (a fish of the family Berycidae such as Betyx decadactylus), anchovy, barracouta (Thyrsites atun), barracuda (a fish of the genus
  • the oil is a winterised oil or a non-winterised oil or a combination thereof.
  • Preferred marine oils include hoki (Macrurotms novaei ⁇ elandiae) oil and winterised hoki oil.
  • the oil is winterised oil that has been chilled to at least about 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15°C and any solids removed by, for example, filtration or decanting.
  • the oil is a food grade oil.
  • the oil has been deodorised, preferably steam deodorised.
  • the oil is a cold-pressed oil or a neutralised oil or a cold-pressed neutralised oil.
  • the omega 3 extract comprises at least about 25, 30, 35, 40, 45, 50,
  • omega 3 fatty acids or esters thereof may be selected between any of these foregoing values (for example, about 25 to 50, 30 to 50,
  • omega 3 extract comprises at least about 25% by weight .omega 3 fatty acids or esters thereof.
  • the composition comprises or the medicament comprises at least about 0.1, 0.2, 0.5, 1, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 99, 99.5, 99.8 or 99.9% by weight of one or more omega 3 extracts and useful ranges may be selected between any of these foregoing values (for example, about 0.1 to 50, 0.2 to 50, 0.5 to 50, 1 to 50, 5 to 50, 10 to 50, 15 to 50, 20 to 50, 25 to 50, 30 to 50, 35 to 50, 40 to 50, 45 to 50, 0.1 to 60, 0.2 to 60, 0.5 to 60, 1 to 60, 5 to 60, 10 to 60, 15 to 60, 20 to 60, 25 to 60, 30 to 60, 35 to 60, 40 to 60, 45 to 60, 0.1 to 70, 0.2 to 70, 0.5 to 70, 1 to 70, 5 to 70, 10 to 70, 15 to 70, 20 to 70, 25 to 70, 30 to 70, 35 to 60, 40 to 60
  • composition or medicament comprises at least about 30 to 90% by weight of the one or more omega 3 extracts.
  • the composition comprises or the medicament comprises at least about 0.1, 0.2, 0.5, 1, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 99, 99.5, 99.8 or 99.9% by weight of one or more marine oils, and useful ranges may be selected between any of these foregoing values (for example, about 0.1 to 50, 0.2 to 50, 0.5 to 50, 1 to 50, 5 to 50, 10 to 50, 15 to 50, 20 to 50, 25 to 50, 30 to 50, 35 to 50, 40 to 50, 45 to 50, 0.1 to 60, 0.2 to 60, 0.5 to 60, 1 to 60, 5 to 60, 10 to 60, 15 to 60, 20 to 60, 25 to 60, 30 to 60, 35 to 60, 40 to 60, 45 to 60, 0.1 to 70, 0.2 to 70, 0.5 to 70, 1 to 70, 5 to 70, 10 to 70, 15 to 70, 20 to 70, 25 to 70, 30 to 70, 35 to 60, 40 to 60,
  • the ratio of the omega 3 extract to the oil in the composition is about 1:100 to about 100:1, about 1:10 to about 10:1, about 1:5 to about 5:1, about 1:2 to about 2:1, preferably about 2:3 or about 3:2.
  • the composition comprises at least about 0.001, 0.01, 0.05, 0.1,
  • 0.15, 0.2, 0.3, 0.4, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18 or 19 grams of the omega 3 extract and useful ranges may be selected between any of these foregoing values (for example, from about 0.01 to about 1 grams, about 0.01 to about 10 grams, about 0.01 to about 19 grams, from about 0.1 to about 1 grams, about 0.1 to about 10 grams, about 0.1 to about 19 grams, from about 1 to about 5 grams, about 1 to about 10 grams, about 1 to about 19 grams, about 5 to about 10 grams, and about 5 to about 19 grams).
  • the composition comprises at least about 0.001, 0.01, 0.05, 0.1, 0.15, 0.2, 0.3, 0.4, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18 or 19 grams of the oil and useful ranges may be selected between any of these foregoing values (for example, from about 0.01 to about 1 grams, about 0.01 to about 10 grams, about 0.01 to about 19 grams, from about 0.1 to about 1 grams, about 0.1 to about 10 grams, about 0.1 to about 19 grams, from about 1 to about 5 grams, about 1 to about 10 grams, about 1 to about 19 grams, about 5 to about 10 grams, and about 5 to about 19 grams).
  • the composition comprises, the medicament comprises, or the method comprises administration of about 5% to about 50% by weight omega 3 extract and about 50% to 90% by weight of one or more marine oils.
  • the marine oil is hoki oil.
  • the composition further comprises, consists essentially of or consists of about 0.1, 0.5, 1, 5, 10, 15, 20, 25, 30, 35, 40, 45 or 50% by weight another antiinflammatory agent and useful ranges may be selected between any of these foregoing values (for example, from about 0.1 to about 50%, from about 0.2 to about 50%, from about 0.5 to about 50%, from about 1 to about 50%, from about 5 to about 50%, from about 10 to about 50%, from about 15 to about 50%, from about 20 to about 50% J from about 25 to about 50%, from about 30 to about 50%, from about 35 to about 50%, from about 40 to about 50%, and from about 45 to about 50%).
  • another antiinflammatory agent and useful ranges may be selected between any of these foregoing values (for example, from about 0.1 to about 50%, from about 0.2 to about 50%, from about 0.5 to about 50%, from about 1 to about 50%, from about 5 to about 50%, from about 10 to about 50%, from about 15 to about 50%, from about 20 to about 50% J from about 25 to about 50%, from about 30 to about 50%, from
  • composition further comprises a pharmaceutically acceptable carrier.
  • the composition further comprises, the medicament further comprises, or the method further comprises administration of one or more agents selected from one or more antihistamines, one or more anti-inflammatories, one or more anti-rheumatics, one or more corticosteroids, one or more muscle relaxants, one or more greenshell mussel extracts, glucosamine or a salt thereof, vitamin E, and vitamin C, or a combination of any two or more thereof.
  • composition further comprises, the medicament further comprises, or the method further comprises administration of a greenshell mussel (GSM) extract (including whole-tissue extracts, gonad extracts, protein extracts, lipid extracts, or a combination of any two or more thereof, in liquid, dried, or powdered form), glucosamine (including salts thereof), or a combination of any two or more thereof.
  • GSM greenshell mussel
  • the composition further comprises, the medicament further comprises, or the method further comprises administration of one or more anti-inflammatory food components selected from vitamin E; vitamin C; greenshell mussel (GSM) extracts; LyprinolTM GSM extract; bromelain; a bioflavonoid mixture extracted from Pinus maritime (pine bark) such as PycnogenolTM; garlic; extracts of Ginkgo biloba leaves; Ephedra (ma-huang); a combination of three Chinese herbal extracts (Ling-Zhi (Ganoderma lucidum), Ku-Shen (Radix Sophora flavescentis) and Gan-Cao (Radix Glycyrrhiza uralensis)) known as ASHMI for "anti-asthma herbal medicine intervention"; Oxy 17TM available from Progressive Health Nutraceuticals, Inc.
  • GSM greenshell mussel
  • LyprinolTM GSM extract a bioflavonoid mixture extracted from Pinus maritime (pine bark) such
  • the composition further comprises a plant oil selected from coconut oil, corn oil, cottonseed oil, canola oil, rapeseed oil, olive oil, palm oil, peanut oil, ground nut oil, safflower oil, sesame, oil, soybean oil, sunflower oil, nut oil, hazelnut oil, almond oil, cashew oil, macadamia oil, pecan oil, pistachio oil, walnut oil, oils from melon and gourd seeds, bottle gourd oil, buffalo gourd oil, pumpkin seed oil, watermelon seed oil, acai oil, blackcurrant seed oil, borage seed oil, evening primrose oil, carob seed oil, amaranth oil, apricot oil, argan oil, artichoke oil, avocado oil, babassu oil, ben oil, borneo tallow nut oil, cohune oil, coriander seed oil, flax oil, flax seed oil, coriander seeds oil, grape seed oil, hemp oil, kapok seed oil,
  • a plant oil
  • the composition is in the form of a tablet, a caplet, a pill, a hard or soft capsule or a lozenge.
  • the composition is in the form of a cachet, a dispensable powder, granules, a suspension, an elixir, a liquid, or any other form that can be added to food or drink, including for example water or fruit juice.
  • the composition further comprises one or more constituents (such as antioxidants) which prevent or reduce degradation of the composition during storage or after administration.
  • the composition is or is formulated as a food, drink, food additive, drink additive, dietary supplement, nutritional product, medical food, nutraceutical, medicament or pharmaceutical.
  • the composition is formulated as a powder, liquid, food bar, spread, sauce, ointment, tablet or capsule.
  • the composition is formulated for oral, nasal or parenteral (including topical, subcutaneous, intramuscular and intravenous) administration.
  • the composition ' is formulated for ingestion, inhalation or topical application.
  • the composition is formulated for inhalation, preferably it is formulated as an inhalable powder, solution or aerosol.
  • the composition is formulated for topical application, preferably it is formulated as an ointment, cream or lotion.
  • the composition is formulated for separate, simultaneous or sequential administration of the extract and the oil. In one embodiment separate compositions are formulated for separate, simultaneous or sequential administration of the extract and the oil.
  • composition described above and an agent selected from therapeutic agents including but not limited to antihistamines, antiinflammatories, anti-rheumatics, corticosteroids, non-steroidal anti-inflammatory drugs (NSAIDs) including cyclooxygenase-2 selective inhibitors, and muscle relaxants, including a combination of any two or more thereof, are administered separately, simultaneously or sequentially.
  • the agent is selected from a greenshell mussel extract (including whole-tissue extracts, gonad extracts, protein extracts, and Hpid extracts, or a combination of any two or. more thereof), glucosamine (including salts thereof), anti-inflammatory food component (as described above), or a combination of any two or more thereof.
  • the inflammation is joint inflammation, muscle inflammation, tendon inflammation, ligament inflammation, joint damage, joint sprain or strain, muscle sprain, muscle strain, cartilage damage, osteoarthritis, or rheumatoid arthritis.
  • the condition is an atopic condition, an allergy, arteriosclerosis, atherosclerosis, heart disease, high blood pressure, blood clots, hypotension, vasoconstriction, cancer, or depression.
  • the inflammation is joint inflammation.
  • the inflammation is muscle inflammation, tendon inflammation, ligament inflammation, joint damage, joint sprain or strain, muscle sprain or strain, or cartilage damage.
  • the conditions is osteoarthritis or rheumatoid arthritis.
  • condition is an atopic condition.
  • condition is an allergy.
  • condition is arteriosclerosis, atherosclerosis, heart disease, high blood pressure, blood clots, hypotension, vasoconstriction, cancer, or depression.
  • the treatment is with steroid sparing effect.
  • Figure 1 is a graph showing the inhibition of neutrophil superoxide production by aspirin (in EtOH), hold oil, hoki omega 3 extract, and 33% w/w hoki omega 3 extract plus 67% w/w hoki oil (actual). Also shown is the expected result for 33% w/w hoki omega 3 extract plus 67% w/w hoki oil based on ' results for individual components. Test materials were assessed at concentrations of 100 ⁇ g/ml, 200 ⁇ g/ml, 400 ⁇ g/ml, and 800 ⁇ g/ml against a control assay with no test sample added. Statistical significance was assessed relative to control with an independent Student t-test. Aspirin (all concentrations), hoki oil plus hoki SFE (all concentrations): P ⁇ 0.01: Hoki oil (200 and 200 ug/ml), hoki SFE (200 ug/ml): P ⁇ 0.05.
  • compositions comprising a mixture of (a) one or more omega 3 fatty acid extracts of one or more marine oils, and (b) one or more marine oils have useful, preferably synergistic, activity to treat or prevent inflammation or a condition selected from osteoarthritis, rheumatoid arthritis, an atopic condition, an allergy, arteriosclerosis, atherosclerosis, heart disease, high blood pressure, blood clots, hypotension, vasoconstriction, cancer, or depression.
  • the present invention is based on the discovery that combinations of (1) an omega 3 fatty acid extract that comprises about 70% by weight omega 3 fatty acids; and (2) winterised hoki oil, have useful, preferably synergistic, antiinflammatory activity.
  • a preferred composition is 33% w/w hoki omega 3 extract plus 67% w/w hoki oil.
  • an "effective amount” is the amount required to confer therapeutic effect.
  • the interrelationship of dosages for animals and humans (based on milligrams per meter squared of body surface) is described by Freireich, et al. (1966).
  • Body surface area can be approximately determined from height and weight of the subject. See, e.g., Scientific Tables, Geigy
  • compositions of the invention that do not reduce the activity of the composition and is not toxic when administered in doses sufficient to deliver an effective amount of one or more active agents.
  • the formulations can be administered orally, nasally or parenterally (including topically, intramuscularly, inttaperitoneally, subcutaneously and intravenously).
  • steroids sparing is intended to mean that the dose of steroidal medication administered to a subject is able to be reduced to a level below that administered before the subject began taking a composition of the present invention or began using a method of the present invention.
  • the daily or weekly or monthly dose of steroids is able to be reduced by at least 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 6O 5 65, 70, 75, 80, 85, 90, 95 or 99%.
  • a "subject" in accordance with the invention is an animal, preferably a mammal, more preferably a mammalian companion animal or human.
  • Preferred companion animals include cats, dogs and horses.
  • compositions useful herein are superior, as measured by, for example, the extent of the effect in vitro or in vivo or both, compared to use of individual agents alone.
  • the effect of the combination of an omega 3 extract and an oil is synergistic if the effect is superior to the effect achievable with the extract alone or the oil alone.
  • the effect of the combination is synergistic if a beneficial effect is obtained in a group of patients that does not respond (or responds poorly) to an extract alone or an oil alone.
  • the effect of the combination is synergistic if one of the components is used at its conventional dose and the other component is used at a reduced dose and the effect, as measured by, for example, the extent of the effect in vitro or in vivo or both, is equivalent to or better than that achievable with conventional amounts of either one of the components of the combination treatment alone.
  • Related tetms such as "synergistic" are to be interpreted similarly.
  • treat and its derivatives should be interpreted in their broadest possible context. The term should not be taken to imply that a subject is treated until total recovery. Accordingly, “treat” broadly includes amelioration and/or prevention of the onset of the symptoms or severity of a particular condition.
  • Marine oils are known sources of omega 3 fatty acids.
  • the omega 3 fatty acids are oc- linolenic acid (ALA) (18:3 (n-3); octadeca-9,12,15-trienoic acid), stearidonic acid (SA) (18:4 (n-3); octadeca-6,9,12,15-tetraenoic acid), eicosatetraenoic acid (ETA) (20:4 (n-3); eicosa-8,11,14,17- tetraenoic acid), eicosapentaenoic acid (EPA) (20:5 (n-3); eicosa-5,8,ll,14,17-pentaenoic acid), docosapentaenoic acid (DPA) (22:5 (n-3); docosa-7,10,13,16,19-pentaenoic acid), and docosahexaenoic acid (DHA) (22:6 (n
  • Fatty acids useful herein include free fatty acids or esterified fatty acids or mixtures thereof.
  • Useful esterified fatty acids include methyl, ethyl, and propyl esters, and lipids (including glycerolipids, glycerophospholipids, and phospholipids).
  • the marine oil selected from one or more marine mammal oils (such as one or more seal oils from the families Odobenidae, Otariidae and Phocidae), one or more shellfish oils, one or more cephalopod oils (such as one or more whole cephalopod oils or one or more cephalopod offal oils or a combination thereof), and one or more fish oils, or a combination of any two or more thereof.
  • the oil is a seal oil, or a squid oil, or a fish oil.
  • the cephalopod oil is an octopus oil (order Octopoda) or a squid oil (order Teuthida).
  • the fish oil is selected from alfonsino (a fish of the family Berycidae such as Beryx decadactylus), anchovy, barracouta (Thyrsites atun), barracuda (a fish of the genus Sphjraend), baikal, bloater, cacha, cardinalfish (such as black cardinalfish), carp, cod (such as red cod and black cod), common mora (Mora mow, Ribaldo), dogfish (such as spiny dogfish Squahts acanthias), dory (such as John dory Zeusfaber or smooth oreo dory Pseitdocyttus maculatus), eel, elephant fish, eulachon, frost fish, gemfish, hake, herring, hilsa, hoki (Macruronus novae ⁇ elandiae), hilsa, jack fish (such as leatherjacket Oligoplites
  • the fish oil comprises an oil selected from one or more whole fish oils, one or more head oils, one or more offal oils, and one or more liver oils, or a combination of any two or more thereof.
  • the fatty acid profiles of some whole fish oils are provided in Table 1.
  • the ornega-3 fatty acid profiles of some whole fish oils are provided in Table 2.
  • the oil is a winterised oil.
  • Preferred marine oils include hoki
  • the oil is winterised oil that has been chilled to at least about 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15°C and any solids removed by, for example, filtration or decanting.
  • the oil is a food grade oil.
  • the oil has been deodorised, preferably steam deodorised.
  • the oil is a cold-pressed oil.
  • the oil is winterised oil.
  • Winterised oils are produced by cooling the oil to between 4 and 15°C and removing any solids.
  • the oil is chilled to at least about 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15°C and any solids removed.
  • Winterising can be a batch or continuous process.
  • the winterising process can be conducted by cooling oil in a heat exchanger, and decanting or filtering solids from the oil.
  • the oil temperature may be raised just before filtration to reduce viscosity and aid filtration.
  • an oil may be processed to deodorise (such as by steam deoderisation) it or to remove unwanted components.
  • oils may be a neutralised by treatment with an absorbent or treated by any conventional oil refining process.
  • Preferred oils are food grade oils such as cold-pressed oils or neutralised oils.
  • the oil is a hold oil.
  • Preferred hoki oils include but are not Limited to whole fish oils and oils prepared from part of the hoki including the head, offal, liver and any combination of any two or more thereof.
  • the vitamin E content of the oil of Table 1 is 9 mg/lOOg and the vitamin A content is 38 mg/100g.
  • Blank cells ate either less than 0.1 or not detected
  • Omega 3 fatty acids in free or esterif ⁇ ed from may be extracted from marine oils and then recombined with a whole or winterised marine oil.
  • a composition useful herein may also comprise one or more additional omega 3 fatty acid extracts of a plant oil, a marine oil, eggs, milk fat, micro-algae, or an micro-algal oil, or a combination of any two or more thereof.
  • Preferred methods of extraction include solvent extraction, supercritical solvent extraction including supercritical CO2 extraction, distillation, and chromatographic separation.
  • Preferred methods of solvent extraction include ethanol extraction.
  • the extract is prepared by solvent extraction, such as ethanol extraction, followed by distillation or supercritical extraction.
  • fatty acids present in the oil are converted to alkyl esters, preferably ethyl esters, and then subjected to distillation or supercritical extraction.
  • Useful esterified fatty acids include methyl, ethyl, and propyl esters.
  • Useful ester forms also include lipids (including glycerolipids, glycerophosphoHpids, and phospholipids). Methods of conversion of fatty acids in lipid form to alkyl esters are well known. •
  • the extract is prepared by conversion of the hoki oil to ethyl esters followed by extraction of omega 3 fatty acids using supercritical CO2.
  • the omega 3 fatty acid extract of a hoki oil is prepared by supercritical CO 2 extraction.
  • the fatty acid profile of a preferred fatty acid extract of hoki oil is shown in Table 3 below.
  • the extract is prepared by a method comprising
  • the condition is joint inflammation, muscle inflammation, tendon inflammation, ligament inflammation, joint damage, joint sprain or strain, muscle sprain, muscle strain, cartilage damage, osteoarthritis, rheumatoid arthritis, an atopic condition, an allergy, arteriosclerosis, atherosclerosis, heart disease, high blood pressure, blood clots, hypotension, vasoconstriction, cancer, or depression.
  • the condition is joint inflammation.
  • the condition is muscle inflammation, tendon inflammation, ligament inflammation, joint damage, joint sprain or strain, muscle sprain or strain, or cartilage damage.
  • the conditions is osteoarthritis or rheumatoid arthritis.
  • the condition is an atopic condition.
  • the condition is an allergy.
  • the condition is arteriosclerosis, atherosclerosis, heart disease, high blood pressure, blood clots, hypotension, vasoconstriction, cancer, or depression..
  • compositions, medicaments and methods of treatment or prevention described and useful herein may employ compositions as described below.
  • a composition useful herein may be formulated as a food, drink, food additive, drink additive, dietary supplement, nutritional product, medical food, nutraceutical, medicament or pharmaceutical.
  • a composition of the invention is formulated as a powder, liquid, food bar, spread, sauce, ointment, tablet or capsule. Appropriate formulations may be prepared by an art skilled worker with regard to that skill and the teaching of this specification.
  • compositions useful herein may be formulated to allow for administration to a subject by any chosen route, including but not limited to oral, nasal or parenteral (including topical, subcutaneous, intramuscular and intravenous) administration.
  • a pharmaceutical composition of the invention may be formulated with an appropriate pharmaceutically acceptable carrier (including excipients and diluents) selected with regard to the intended route of administration and standard pharmaceutical practice.
  • a composition of the invention can be administered orally as a powder, liquid, tablet or capsule, or topically as an ointment, cream or lotion.
  • Suitable formulations may contain additional agents as required, including emulsifying, antioxidant, flavouring or colouring agents, and may be adapted for immediate-, delayed-, modified-, sustained-, pulsed- or controlled-release.
  • compositions useful herein may be used alone or in combination with one or more other therapeutic agents.
  • the therapeutic agent may be a food, drink, food additive, drink additive, food component, drink component, dietary supplement, nutritional product, medical food, nutraceutical, medicament or pharmaceutical.
  • a composition of the invention and other therapeutic agent When used in combination with another therapeutic agent the administration of a composition of the invention and other therapeutic agent may be simultaneous or sequential.
  • Simultaneous administration includes the administration of a single dosage form that comprises all components and the administration of a composition of the invention and other therapeutic agent in separate dosage forms at substantially the same time.
  • Sequential administration includes the administration of a composition of the invention and other therapeutic agent according to different schedules, preferably so that there is an overlap in the periods during which the composition of the invention and other therapeutic agent are provided.
  • Suitable agents with which the compositions of the invention can be co-administered include antihistamines, anti-inflammatories, anti-rheumatics, corticosteroids, muscle relaxants, a greenshell mussel extract (selected from whole-tissue extracts, gonad extracts, protein extracts, and lipid extracts, or a combination of any two or more thereof), glucosamine (including salts thereof), including a combination of any two or more thereof, and other suitable agents known in the art.
  • a composition of the invention may further comprise or be administered with one or more anti-inflammatory food components including but not limited to choline, vitamin E; vitamin C; greenshell mussel (GSM) extracts; LyprinolTM GSM extract; bromelain; a bioflavonoid mixture extracted from Pinus maritime (pine bark) such as PycnogenolTM; garlic; extracts of Ginkgo biloba leaves; Ephedra (ma-huang); a combination of three Chinese herbal extracts (Ling-Zhi (Ganoderma lucidum), Ku-Shen (Radix Sophora flavescentis) and Gan-Cao (Radix Glycyrrhiza uralensis)) known as ASHMI for "anti-asthma herbal medicine intervention";
  • GSM greenshell mussel
  • LyprinolTM GSM extract a bioflavonoid mixture extracted from Pinus maritime (pine bark) such as PycnogenolTM
  • garlic extract
  • Useful greenshell mussel extracts include whole-tissue extracts, gonad extracts, protein extracts, and lipid extracts, or a combination of any two or more thereof, in liquid, dried, or powdered form, produced using known methods.
  • composition is a food, drink, food additive, drink additive, dietary supplement, nutritional product, medical food or nutraceutical.
  • a composition useful herein may further comprise a plant oil selected from coconut oil, corn oil, cottonseed oil, canola oil, rapeseed oil, olive oil, palm oil, peanut oil, ground nut oil, safflower oil, sesame oil, soybean oil, sunflower oil, nut oil, hazelnut oil, almond oil, cashew oil, macadamia oil, pecan oil, pistachio oil, walnut oil, oils from melon and gourd seeds, bottle gourd oil, buffalo gourd oil, pumpkin seed oil, watermelon seed oil, acai oil, blackcurrant seed oil, borage seed oil, evening primrose oil, carob seed oil, amaranth oil, apricot oil, argan oil, artichoke oil, avocado oil, babassu oil, ben oil, borneo tallow nut oil, cohune oil, coriander seed oil, flax oil, flax seed oil, coriander seeds oil, grape seed oil, hemp oil, kap
  • the dose of the composition administered, the period of administration, and the general administration regime may differ between subjects depending on such variables as the severity of symptoms of a subject, the type of disorder to be treated, the mode of administration chosen, and the age, sex and/or general health of a subject.
  • the inventors contemplate administration of from about 1 mg to about 1000 mg per kg body weight of a composition of the invention is administered per day, preferably about 50 to about 500 mg per kg per day.
  • the inventors contemplate administration of from about 0.05 mg to about 250 mg per kg body weight of a pharmaceutical composition according to the invention. It should be appreciated that administration may include a single daily dose or administration of a number of discrete divided doses as may be appropriate.
  • Hold oil was provided by Sealord Group Limited, New Zealand.
  • the oil was an unfractionated whole fish body oil of which at least 90% was from hoki (Macruronus novae2ealandiae). It contained 750ppm of mixed natural tocopherol antioxidant.
  • Docosahexaenoic acid PHA comprised 10-14% of total fatty acids (AOCS Official Method Ce lb-89) and eicosapentaenoic acid (EPA) comprised 5-8% of total fatty acids (AOCS Official Method Ce lb-89).
  • the total omega-3 fatty acid content was calculated to be 17-24%.
  • a lOOg sample comprised 17-21g saturated fatty acids, 38-42g monounsaturated fatty acids, and 19-23g polyunsaturated fatty acids (all by calculation).
  • a filtration step may be used after (1) to remove saturated fatty acid ethyl esters.
  • the present invention has utility in treating or preventing inflammatory conditions.
  • the described compositions and methods of the invention may be employed to treat or prevent one or more of the conditions discussed above.
  • Superoxide produced by activated neutrophils efficiently reduces the tetrazolium salt, WST-I to produce a soluble formazan: a simple colorimetric assay for measuring respiratory burst activation and for screening of anti-inflammatory agents. 2000 J Immunol. Meth. 238: 59-68.

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  • Health & Medical Sciences (AREA)
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  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Rheumatology (AREA)
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  • Pain & Pain Management (AREA)
  • Emergency Medicine (AREA)
  • Medicines Containing Plant Substances (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)

Abstract

L'invention porte sur des compositions comprenant un mélange d'un ou plusieurs extraits d'oméga 3 d'une ou plusieurs huiles marines et sur une ou plusieurs huiles marines et sur l'utilisation de la composition pour traiter ou prévenir une inflammation ou un trouble choisi parmi l'ostéoarthrite, la polyarthrite rhumatoïde, un trouble atopique, une allergie, l'artériosclérose, l'athérosclérose, une cardiopathie, une pression sanguine élevée, des caillots sanguins, l'hypotension, la vasoconstriction, le cancer ou la dépression.
PCT/NZ2008/000146 2007-06-15 2008-06-16 Composition anti-inflammatoire et son utilisation WO2008153426A1 (fr)

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WO2011143587A1 (fr) * 2010-05-13 2011-11-17 Nitromega Corp. Acides gras nitrés, neuroprotection et/ou inhibition du déclin cognitif
WO2011151632A1 (fr) * 2010-06-04 2011-12-08 Sana Pharma As Formulations alimentaires
NO20231264A1 (no) * 2009-09-14 2012-05-21 Chemoforma Ltd Fôrsammensetning
WO2012085366A1 (fr) * 2010-12-23 2012-06-28 Charabot Procede pour l'obtention d'un extrait odorant de fleurs et/ou feuilles fraiches par des solvants naturels
KR101316398B1 (ko) 2011-05-12 2013-10-08 영남대학교 산학협력단 장어 추출물을 유효성분으로 함유하는 염증성 질환 예방 또는 치료용 조성물
WO2014057296A1 (fr) * 2012-10-11 2014-04-17 Vélez-Rivera Héctor De Jes S Supplément nutritionnel pour des patients atteints de maladies rhumatismales
WO2015048590A1 (fr) * 2013-09-27 2015-04-02 Sher Justin Composition nutraceutique permettant l'inhibition de pde4, un meilleur métabolisme de la dopamine et une potentialisation à long terme
EP2787988A4 (fr) * 2011-12-08 2016-11-02 Metaproteomics Llc Compositions d'huile ajoutée et procédés pour une santé améliorée
WO2017015271A1 (fr) * 2015-07-20 2017-01-26 The Brigham And Women's Hospital, Inc. Éclaircissement de nouvelles résolvines de série 13 augmentant au moyen de l'atorvastatine et éliminant les infections
US11690878B2 (en) 2020-01-21 2023-07-04 Lintbells Limited Synergistic compositions

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Cited By (21)

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Publication number Priority date Publication date Assignee Title
WO2010114396A1 (fr) * 2009-03-31 2010-10-07 Bomac Research Limited Administration de médicament
NO341929B1 (no) * 2009-09-14 2018-02-19 Chemoforma Ltd Fôrsammensetning
NO347704B1 (no) * 2009-09-14 2024-02-26 Chemoforma Ltd Fôrsammensetning for fisk for anvendelse i å hindre eller redusere symptomer relatert til hjerte- og skjelettmuskelsykdom, HSMB.
NO20231264A1 (no) * 2009-09-14 2012-05-21 Chemoforma Ltd Fôrsammensetning
CN102843922A (zh) * 2010-05-13 2012-12-26 尼特罗米加公司 硝基脂肪酸–认知减退的神经保护和/或抑制
US8563609B2 (en) 2010-05-13 2013-10-22 Nitromega Corp. Nitro fatty acids - neuroprotection and/or inhibition of cognitive decline
WO2011143587A1 (fr) * 2010-05-13 2011-11-17 Nitromega Corp. Acides gras nitrés, neuroprotection et/ou inhibition du déclin cognitif
AT12966U1 (de) * 2010-06-04 2013-03-15 Sana Pharma As Nahrungsergänzungsformulierungen
WO2011151632A1 (fr) * 2010-06-04 2011-12-08 Sana Pharma As Formulations alimentaires
AU2011260037B2 (en) * 2010-06-04 2014-05-01 Sana Pharma As Dietary formulations
FR2969656A1 (fr) * 2010-12-23 2012-06-29 Charabot Procede pour l'obtention d'un extrait odorant de fleurs et/ou feuilles fraiches par des solvants naturels
WO2012085366A1 (fr) * 2010-12-23 2012-06-28 Charabot Procede pour l'obtention d'un extrait odorant de fleurs et/ou feuilles fraiches par des solvants naturels
US10577561B2 (en) 2010-12-23 2020-03-03 Charabot Process for obtaining a scented extract of fresh flowers and/or leaves using natural solvents
KR101316398B1 (ko) 2011-05-12 2013-10-08 영남대학교 산학협력단 장어 추출물을 유효성분으로 함유하는 염증성 질환 예방 또는 치료용 조성물
EP2787988A4 (fr) * 2011-12-08 2016-11-02 Metaproteomics Llc Compositions d'huile ajoutée et procédés pour une santé améliorée
WO2014057296A1 (fr) * 2012-10-11 2014-04-17 Vélez-Rivera Héctor De Jes S Supplément nutritionnel pour des patients atteints de maladies rhumatismales
US10058529B2 (en) 2013-09-27 2018-08-28 Justin SHER Nutraceutical composition for PDE4 inhibition, enhanced dopamine metabolism and long term potentiation
US9149457B2 (en) 2013-09-27 2015-10-06 Justin SHER Nutraceutical composition for PDE4 inhibition, enhanced dopamine metabolism and long term potentiation
WO2015048590A1 (fr) * 2013-09-27 2015-04-02 Sher Justin Composition nutraceutique permettant l'inhibition de pde4, un meilleur métabolisme de la dopamine et une potentialisation à long terme
WO2017015271A1 (fr) * 2015-07-20 2017-01-26 The Brigham And Women's Hospital, Inc. Éclaircissement de nouvelles résolvines de série 13 augmentant au moyen de l'atorvastatine et éliminant les infections
US11690878B2 (en) 2020-01-21 2023-07-04 Lintbells Limited Synergistic compositions

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