WO2008153426A1

WO2008153426A1 - Anti-inflammatory composition and use thereof

Info

Publication number: WO2008153426A1
Application number: PCT/NZ2008/000146
Authority: WO
Inventors: Donald John Bell; Alan Groves; Lance Derek Searle
Original assignee: Sealord Group Limited
Priority date: 2007-06-15
Filing date: 2008-06-16
Publication date: 2008-12-18

Abstract

Compositions comprising a mixture of one or more omega 3 extracts of one or more marine oils and one or more marine oils and use of the composition 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.

Description

ANTI-INFLAMMATORY COMPOSITION AND USE THEREOF

FIELD OF THE INVENTION

[0001] 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..

BACKGROUND

[0002] Conditions associated with abnormal or undesirable inflammation such as soft tissue injuries and rheumatoid arthritis can be difficult to manage (Scott et al, 1998). Marine oils high in EPA (eicosapentaenoic acid; 20:5 (n-3); eicosa-5,8,ll,14,17-pentaenoic acid) and DHA (docosahexaenoic acid; 22:6 (n-3); docosa-4,7,10,13,16,19-hexaenoic acid) are reported to be useful as anti-inflammatory products including for the treatment of rheumatoid arthritis and related conditions (Cleland et al, 2003; Cleland and James, 2006) with steroid-sparing effects (Galarraga et al, 2008). 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.

SUMMARY OF THE INVENTION

[0003] Accordingly, in one aspect the present invention relates to 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.

[0004] In another aspect 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

(b) one or more oils more marine oils.

[0005] In another aspect 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. In one embodiment where the use is in the manufacture of a medicament, the medicament may be formulated for separate, simultaneous, or sequential administration of the extract and the one or more oils.

[0006] In another aspect the present invention relates to a product containing

(a) an omega 3 fatty acid extract of one or more marine oils, and

(b) 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.

[0007] The following embodiments may relate to any of the above aspects.

[0008] In one embodiment the mixture is a blend or admixture. In one embodiment 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. In one embodiment 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. In one embodiment the extract is prepared by supercritical fluid extraction of one or more marine oils, preferably supercritical CO₂ extraction of one or more marine oils.

[0009] In one embodiment 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 α-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); docosa-7,10,13,16,19-pentaenoic acid), esters of DPA, and docosahexaenoic acid (DHA) (22:6 (n-3); docosa-4,7,10,13,16,19-hexaenoic acid), esters of DHA, of a combination of any two or more thereof. 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.

[0010] 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 CO₂ extraction, distillation, and chromatographic separation. Preferred methods of solvent extraction include ethanol extraction. In one embodiment the extract is prepared by solvent extraction, such as ethanol extraction, followed by distillation or supercritical extraction. In one preferred embodiment 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 CO₂. In alternative embodiments, 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.

[0011] In one embodiment the marine oil selected from one or more marine mammal oils

(such as one or more oils from seals of the families Odobenidae, Otariidae or 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. In various embodiments the oil is a seal oil, or a squid oil, or a fish oil.

[0012] In one embodiment 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).

[0013] In one embodiment 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

Sphyraenά), baikal, bloater, cacha, cardinalfish (such as black cardinalfish), carp, cod (such as red cod and black cod), common mora (Mora moro, Ribaldo), dogfish (such as spiny dogfish Sqitalus acanthias), dory (such as John dory Zeusfaber or smooth oreo dory Pseudocyttus maculatus), eel, elephant fish, eulachon, frost fish, gemfϊsh, hake, herring, hilsa, hold (Macnironus novae^elandiae), jack fish (such as leather) acket Oligoplites saums), katla, kahawai (a fish of the family Arripidae such as Arripis xylabion or Λrήpis trutta.), kipper, ling (including burbot Lota lota, blue ling Molva dypterygia, cobia Rachycentron canadum, common ling Molva molva, pink cusk-eel Genyptβrus blacodes and red hake Urophyάs chuss), mackerel (such as blue mackerel Scomber australasiais and Jack mackerel Trachurns symmetric ), morwong (such as tarakihi Nemadactylus macropterus), tαullet (a fish of the family Mugilidae, such as grey mullet Mugil cephalus) orange roughy, pangas, pilchard, rig, salmon, sardine, sea perch, shark (such as school shark Gakorhimis gakns and pale ghost shark Hydrolagus bemisi), sprat, stargazer (a fish of the family Uranoscopidae), swordfish, trevally, trout, tuna (including species of the genera Tlmnnus and other fish in the family Scombridae commonly known as 'tuna', such as slender tuna A-llothunnusfallai), wharehou (such as common wharehou Se no Ie Ua brama, white warehou Seriolella caenika and silver warehou Seriolella punctata), whitebait, and whiting (such as southern blue whiting Microtnesistius australis) oils, or a combination of any two or more thereof. In various embodiments 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.

[0014] In one embodiment the oil is a winterised oil or a non-winterised oil or a combination thereof. Preferred marine oils include hoki (Macrurotms novaeiξelandiae) oil and winterised hoki oil. In one embodiment 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. In one embodiment the oil is a food grade oil. In another embodiment the oil has been deodorised, preferably steam deodorised. In yet another embodiment the oil is a cold-pressed oil or a neutralised oil or a cold-pressed neutralised oil.

[0015] In one embodiment the omega 3 extract comprises at least about 25, 30, 35, 40, 45, 50,

55, 60, 65, 70, 75, 80, 85, 90, or 95% by weight omega 3 fatty acids or esters thereof, and useful ranges may be selected between any of these foregoing values (for example, about 25 to 50, 30 to 50,

35 to 50, 40 to 50, 25 to 60, 30 to 60, 35 to 60, 40 to 60, 45 to 60, 50 to 60, 25 to 70, 30 to 70, 35 to 70, 40 to 70, 45 to 70, 50 to 70, 55 to 70, 60 to 70, 25 to 80, 30 to 80, 35 to 80, 40 to 80, 45 to 80, 50 to 80, 55 to 80, 60 to 80, 65 to 80, 70 to 80, 25 to 90, 30 to 90, 35 to 90, 40 to 90, 45 to 90, 50 to 90,

55 to 90, 60 to 90, 65 to 90, 70 to 90, 75 to 90, 80 to 90, 25 to 95, 30 to 95, 35 to 95, 40 to 95, 45 to 95, 50 to 95, 55 to 95, 60 to 95, 65 to 95, 70 to 95, 75 to 95 and 80 to 95%). In one preferred embodiment the omega 3 extract comprises at least about 25% by weight .omega 3 fatty acids or esters thereof.

[0016] In one embodiment 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 70, 40 to 70, 45 to 70, 0.1 to 80, 0.2 to 80, 0.5 to 80, 1 to 80, 5 to 80, 10 to 80, 15 to 80, 20 to

80, 25 to 80, 30 to 80, 35 to 80, 40 to 80, 45 to 80, 0.1 to 90, 0.2 to 90, 0.5 to 90, 1 to 90, 5 to 90, 10 to 90, 15 to 9O₃ 20 to 90, 25 to 90, 30 to 90, 35 to 90, 40 to 90, 45 to 90, 0.1 to 99, 0.2 to 99, 0.5 to 99, 1 to 99, 5 to 99, 10 to 99, 15 to 99, 20 to 99, 25 to 99, 30 to 99, 35 to 99, 40 to 99 and 45 to 99%). Preferably the composition or medicament comprises at least about 30 to 90% by weight of the one or more omega 3 extracts.

[0017] In one embodiment 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 70, 40 to 70, 45 to 70, 0.1 to 80, 0.2 to 80, 0.5 to 80, 1 to 80, 5 to 80, 10 to 80, 15 to 80, 20 to 80, 25 to 80, 30 to^'80, 35 to 80, 40 to 80, 45 to 80, 0.1 to 90, 0.2 to 90, 0.5 to 90, 1 to 90, 5 to 90, 10 to 90, 15 to 90, 20 to 90, 25 to 90, 30 to 90, 35 to 90, 40 to 90, 45 to 90, 0.1 to 99, 0.2 to 99, 0.5 to 99, 1 to 99, 5 to 99, 10 to 99, 15 to 99, 20 to 99, 25 to 99, 30 to 99, 35 to 99, 40 to 99 and 45 to 99%).

[0018] In one embodiment 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.

[0019] In one embodiment 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).

[0020] In one embodiment 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).

[0021] In one embodiment 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. In one embodiment the marine oil is hoki oil.

[0022] In one embodiment 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%).

[0023] In one embodiment the composition further comprises a pharmaceutically acceptable carrier. In one embodiment 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.

[0024] In one embodiment the 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.

[0025] In one embodiment 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 Pycnogenol™; 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 17™ available from Progressive Health Nutraceuticals, Inc. (USA); extracts from the mushrooms Cordyceps sinensis, Ganoderma lucidium (Reishi), and Tremella fuciformis (Silver- Ear); perilla leaf extract; rosmarinic acid; flavonoids (such as luteolin, fisetin and apigenin); simple sugars (such as L-fucose and N-acetylneuraminic acid); methylsulfonylmethane; soy protein or genistein or both; quercetin;, spkulina; forskolin; and mixtures of any two or more thereof.

[0026] In one embodiment 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, kiwi fruit oil, lallemantia oil, meadowfoam seed oil, linseed oil, mustard oil, okra seed oil, perilla seed oil, pequi oil, pine nut oil, poppyseed oil, prune kernel oil, quinoa oil, ramtil oil, rice bran oil, tea oil, and wheat germ oil, or a combination of any two or more thereof. Preferred plant oils are those high in omega 3 fatty acids.

[0027] In one embodiment the composition is in the form of a tablet, a caplet, a pill, a hard or soft capsule or a lozenge. In one embodiment 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. In one embodiment the composition further comprises one or more constituents (such as antioxidants) which prevent or reduce degradation of the composition during storage or after administration.

[0028] In one embodiment the composition is or is formulated as a food, drink, food additive, drink additive, dietary supplement, nutritional product, medical food, nutraceutical, medicament or pharmaceutical. Preferably, the composition is formulated as a powder, liquid, food bar, spread, sauce, ointment, tablet or capsule.

[0029] In one embodiment the composition is formulated for oral, nasal or parenteral (including topical, subcutaneous, intramuscular and intravenous) administration. In one embodiment the composition^' is formulated for ingestion, inhalation or topical application. Where the composition is formulated for inhalation, preferably it is formulated as an inhalable powder, solution or aerosol. Where the composition is formulated for topical application, preferably it is formulated as an ointment, cream or lotion. [0030] In one embodiment 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. In one embodiment the 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. In one embodiment 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.

[0031] In one embodiment 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. In one embodiment the condition is an atopic condition, an allergy, arteriosclerosis, atherosclerosis, heart disease, high blood pressure, blood clots, hypotension, vasoconstriction, cancer, or depression. In one preferred embodiment the inflammation is joint inflammation. In another preferred embodiment the inflammation is muscle inflammation, tendon inflammation, ligament inflammation, joint damage, joint sprain or strain, muscle sprain or strain, or cartilage damage. In another preferred embodiment the conditions is osteoarthritis or rheumatoid arthritis. In another preferred embodiment the condition is an atopic condition. In another preferred embodiment the condition is an allergy. In yet another preferred embodiment the condition is arteriosclerosis, atherosclerosis, heart disease, high blood pressure, blood clots, hypotension, vasoconstriction, cancer, or depression. In various embodiments, the treatment is with steroid sparing effect.

[0032] In this specification where reference has been made to patent specifications, other external documents, or other sources of information, this is generally for the purpose of providing a context for discussing the features of the invention. Unless specifically stated otherwise, reference to such external documents is not to be construed as an admission that such documents, or such sources of information, in any jurisdiction, are prior art, or form part of the common general knowledge in the art.

[0033] It is intended that reference to a range of numbers disclosed herein (for example, 1 to 10) also incorporates reference to all rational numbers within that range (for example, 1, 1.1, 2, 3, 3.9, 4, 5, 6, 6.5, 7, 8, 9 and 10) and also any range of rational numbers within that range (for example, 2 to 8, 1.5 to 5.5 and 3.1 to 4.7) and, therefore, all sub-ranges of all ranges expressly disclosed herein are hereby expressly disclosed. These are only examples of what is specifically intended and all possible combinations of numerical values between the lowest value and the highest value enumerated are to be considered to be expressly stated in this application in a similar manner.

BRIEF DESCRIPTION OF THE DRAWINGS

[0034] 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 μg/ml, 200 μg/ml, 400 μg/ml, and 800 μg/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.

DETAILED DESCRIPTION OF THE INVENTION

[0035] The present invention is based on the discovery that 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.. In particular, 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.

1. Definitions

[0036] The term "comprising" as used in this specification means "consisting at least in part of. When interpreting statements in this specification which include that term, the features, prefaced by that term in each statement or claim, all need to be present but other features can also be present. The related terms "comprises" and "comprised" are to be interpreted similarly.

[0037] 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

Pharmaceuticals, Aϊdley, New York, 1970, 537. Effective doses also vary, as recognized by those skilled in the art, dependent on route of administration, carrier usage, and the like.

[0038] The term "pharmaceutically acceptable carrier" is intended to refer to a carrier including but not limited to an excipient, diluent or auxiliary that can be administered to a subject as a component of a composition of the invention that does 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).

[0039] The term "steroid 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. Preferably 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, 6O₅ 65, 70, 75, 80, 85, 90, 95 or 99%.

[0040] 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.

[0041] The term "synergy" as used in this specification means the effects of 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. For example, 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. Further, 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. In addition, 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.

[0042] The term "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.

2. Marine oils

[0043] 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-3); docosa-4,7,10,13,16,19-hexaenoic acid). These fatty acids are present in different amounts and proportions in different oils. 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).

[0044] In one embodiment 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. In various embodiments the oil is a seal oil, or a squid oil, or a fish oil. In one embodiment the cephalopod oil is an octopus oil (order Octopoda) or a squid oil (order Teuthida).

[0045] In one embodiment 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 saunis), katla, kahawai (a fish of the family Arripidae such as A.rήpis xylabion oiA.mpis truttaϊ), kipper, ling (including burbot Lota lota, blue ling Molva dypterygia, cobia Raώycentron canadum, common ling Molva molva, pink cusk-eel Genyptertis blacodes and red hake Orophyάs ώuss), mackerel (such as blue mackerel Scomber australasicus and Jack mackerel Traώurus symmetricus), morwong (such as tarakrhi Nemadactylus macroptetns), mullet (a fish of the family Mugilidae, such as grey mullet Mugil cephalus) orange roughy, pangas, pilchard, rig, black cod, salmon, sardine, sea perch, shark (such as school shark Gahorhinus galeus and pale ghost shark Hydrolagm bemisi), sprat, stargazer (a fish of the family Uranoscopidae), swordfish, trevally, trout, tuna

(including species of the genera TImnnus and other fish in the family Scombridae commonly known as 'tuna', such as slender tuna Allothunmis fallaϊ), wharehou (such as common wharehou Serioklla bra?)ia, white warehou Serioklla caerulea and silver warehou Serioklla punctata), whitebait, and whiting (such as southern blue whiting Micromesistius australis) and swordfish oils, or a combination of any two or more thereof. In various embodiments 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.

[0046] In one embodiment the oil is a winterised oil. Preferred marine oils include hoki

(Macruronus nopaezζe/andiae) oil and winterised hold oil. In one embodiment 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. In one embodiment the oil is a food grade oil. In another embodiment the oil has been deodorised, preferably steam deodorised. In yet another embodiment the oil is a cold-pressed oil.

[0047] In one embodiment the oil is winterised oil. Winterised oils are produced by cooling the oil to between 4 and 15°C and removing any solids. In one embodiment 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. With or without winterising, an oil may be processed to deodorise (such as by steam deoderisation) it or to remove unwanted components. For example, 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.

[0048] In one embodiment 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. U(

Blank cells ate either less than 0.1 or not detected

(1) Hold oil based on average of 5 year data

(2) O'Conner C J et al. Handbook of Australasian Edible Oils. Editor: CJ O'Conner (2007)

(3) Cod liver oil data from National Food Institute, Denmark, www.foodcomp.dk

(4) Tuna oil data from Sinclair et al. Allergie et immunologie VoI XXXII Nό7 (2000) pp261 - 271

Table 2 - Omega-3 fatty acid profile of some whole oils

3. Omega 3 fatty acid extracts of marine oils

[0049] Omega 3 fatty acids in free or esterifϊed from may be extracted from marine oils and then recombined with a whole or winterised marine oil. In some embodiments 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. In one embodiment the extract is prepared by solvent extraction, such as ethanol extraction, followed by distillation or supercritical extraction. In another embodiment, 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. ^•

[0050] In one preferred embodiment the extract is prepared by conversion of the hoki oil to ethyl esters followed by extraction of omega 3 fatty acids using supercritical CO2.

[0051] Methods of supercritical extraction of fish oil components including ethyl esters have been reported by Staby, A.and Mollerup, J. (Separation of constituents of fish oil using supercritical fluids : a review of experimental solubility, extraction, and chromatographic data, Fluid phase equilib., 1993, 91(2):349-386) and Perretti, G., et al (Supercritical carbon dioxide fractionation of fish oil fatty acid ethyl esters, J. Supercritical Fluids, 2007, 40(3):349-353), both incorporated herein by reference.

[0052] In one embodiment the omega 3 fatty acid extract of a hoki oil is prepared by supercritical CO₂ extraction. The fatty acid profile of a preferred fatty acid extract of hoki oil is shown in Table 3 below. In. a preferred embodiment the extract is prepared by a method comprising

(a) providing a hoki oil comprising omega 3 fatty acids,

(b) converting the omega 3 fatty acids to alkyl esters,

(c) contacting the hoki oil with supercritical CO₂ to produce a first phase containing the omega 3 alkyl esters and a second phase, and

(d) separating first phase from the second phase.

Table 3 - Fatt acid profile of a preferred hoki oil extract

4. Methods of treatment or prevention

[0053] The combinations of an omega 3 extract and an oil as described herein are useful to treat or prevent a variety of conditions.

[0054] In one embodiment 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. In one embodiment the condition is joint inflammation. In one embodiment the condition is muscle inflammation, tendon inflammation, ligament inflammation, joint damage, joint sprain or strain, muscle sprain or strain, or cartilage damage. In another embodiment the conditions is osteoarthritis or rheumatoid arthritis. In another embodiment the condition is an atopic condition. In another embodiment the condition is an allergy. In another embodiment the condition is arteriosclerosis, atherosclerosis, heart disease, high blood pressure, blood clots, hypotension, vasoconstriction, cancer, or depression..

[0055] Compositions, medicaments and methods of treatment or prevention described and useful herein may employ compositions as described below.

5. Compositions useful according to the invention

[0056] 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. Preferably, 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.

[0057]. The 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.

[0058] Thus, 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. For example, 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.

[0059] The 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.

[0060] 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.

[0061] 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.

[0062] In one embodiment 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 Pycnogenol™; 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 17™ available from Progressive Health Nutraceuticals, Inc. (USA); extracts from the mushrooms Cordyceps sinensis, Ganoderma lucidium (Reishi), and Tremella fuciformis (Silver-Ear); perilla leaf extract; rosmarinic acid; flavonoids (such as luteolin, fisetin andapigenin); simple sugars

(such as L-fucose and N-acetylneuraminic acid); methylsulfonylmethane; soy protein or genistein or both; quercetin; spirulina; forskolin; and mixtures thereof. 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.

Preferably the composition is a food, drink, food additive, drink additive, dietary supplement, nutritional product, medical food or nutraceutical.

[0063] In one embodiment 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, kapok seed oil, kiwi fruit oil, lallemantia oil, meadowfoam seed oil, linseed oil, mustard oil, okra seed oil, perilla seed oil, pequi oil, pine nut oil, poppyseed oil, prune kernel oil, quinoa oil, ramtil oil, rice bran oil, tea oil, and wheat germ oil, or a combination of any two or more thereof. Preferred plant oils are those high in omega

3 fatty acids.

[0064] As will be appreciated, 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. However, by way of general example, 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. In one embodiment, 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.

[0065] Various aspects of the invention will now be illustrated in non-limiting ways by reference to the following examples.

EXAMPLES

[0066] 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).

EXAMPLE 1 - Production of winterised Hoki oil

[0067] A sample of the oil was winterized by cooling to 10⁰C in a refrigerator and the liquid phase decanted from the solid phase.

EXAMPLE 2 - Production of an omega 3 Hoki oil extract using supet critical CO2

[0068] A sample of the oil was subjected to supercritical CO2 extraction after first converting fatty acids to ethyl esters. Omega 3 fatty acids were concentrated from about 20% w/w in the native oil to about 70% w/w in the omega 3 extract. The process involved:

(1) mixing the oil into a hot aqueous ethanolic solution containing urea to form ethyl esters, and (2) extraction of omega 3 fatty acids in supercritical CO₂.

[0069] In some embodiments, a filtration step may be used after (1) to remove saturated fatty acid ethyl esters.

EXAMPLE 3 - Assessment of an anti-inflammatory combination

[0070] The winterized oil, omega 3 extract, and omega 3 extract in the native oil were tested in triplicate according to the method of Tan and Berridge(2000). Aspirin in ethanol was used as a positive control. Control and test materials were formulated to the concentrations identified above in the Figure descriptions using 20% ethanol. The results are shown in Figure 1 as described above. The effects of a combination of the 33% w/w hoki omega 3 extract plus 67% w/w hoki oil (actual) were greater than the effects seen for either the extract or oil alone. 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. The expected result indicates the degree of improved effect seen with the combination of the extract and the oil.

INDUSTRIAL APPLICATION

[0071] 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.

[0072] Those persons skilled in the art will understand that the above description is provided by way of illustration only and that the invention is not limited thereto.

REFERENCES

Cleland LG, James MJ- Marine oils for antiinflammatory effect — time to take stock. J Rheumatol. 2006 Feb;33(2):207-9.

Cleland LG, James MJ, Proudman SM. The role of fish oils in the treatment of rheumatoid arthritis. Drugs. 2003 63(9):845-53. Galarraga B, Ho M, Youssef HM, Hill A, McMahon H, HaU C, Ogston S, NuId G, Belch JJ. Cod liver oil (n-3 fatty acids) as an non-steroidal anti-inflammatory drug sparing agent in rheumatoid arthritis. Rheumatology. 2008 47(5):665-9.

Noble SL, King DS, Olutade JI. Cyclooxygenase-2 enzyme inhibitors: place in therapy. Am Fam Physician. 2000 61(12):3669-76. Scott DL, Shipley M, Dawson A, Edwards S, Symmons DP, Woolf AD. The clinical management of rheumatoid arthritis and osteoarthritis: strategies for improving clinical effectiveness. BrJ Rheumatol. 1998 37(5):546-54

Tan AS, Berridge MV. 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.

Claims

WHAT WE CLAIM IS:

1. A composition 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.

2. A composition of claim 1 wherein 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.

3. A composition of claim 1 or 2 wherein the omega 3 fatty acid extract is prepared by supercritical fluid extraction of one or more marine oils.

4. A composition of claim 1 or 2 wherein the omega 3 fatty acid extract is prepared by supercritical CO₂ extraction of one or more marine oils.

5. A composition of any one of claims 1 to 4 wherein the omega 3 fatty acid extract comprises one or more fatty acids or one or more esters thereof or combinations thereof selected from the group comprising eicosatetraenoic acid (ETA), esters of ETA, eicosapentaenoic acid (EPA), esters of EPA, docosapentaenoic acid (DPA), esters of DPA, docosahexaenoic acid (DHA), and esters of DHA, or a combination of any two or more thereof.

6. A composition of claim 5 wherein the esters are methyl, ethyl or propyl esters, or a combination of any two or more thereof.

7. A composition of any one of claims 1 to 6 wherein the marine oil is selected from the group comprising one or more marine mammal oils, one or more shellfish oils, one or more cephalopod oils, one or more fish oils, or a combination of any two or more thereof.

8. A composition of claim 7 wherein the marine mammal oil comprises one or more seal oils.

9. A composition of claim 7 wherein the cephalopod oil comprises one or more squid oils.

10. A composition of claim 7 wherein the fish oil comprises one or more oils selected from the group comprising anchovy, baikal, bloater, cacha, carp, dogfish, dory, eel, eulachon, herring, hoki, hilsa, jack fish, katla, kipper, mackerel, orange roughy, pangas, pilchard, cod, salmon, sardine, shark, sprat, trout, tuna, wharehou, whitebait, whiting, and swordfish oil, or a combination of any two or more thereof.

11. A composition of any one of claims 1 to 6 wherein the marine oil comprises one or more hold oils.

12. A composition of any one of claims 7 to 11 wherein the fish oil or hoki oil comprises one or more oils selected from the group comprising one or more whole fish oils, one or more head oils, one or more offal oils, and one or more Ever oils, or a combination of any two or more thereof.

13. A composition of any one of claims 7 to 12 wherein the marine oil, fish oil or hoki oil comprises one or more winterised oils, one or more non-winterised oils, or a combination thereof.

14. A composition of any one of claims 1 to 13 wherein the composition further comprises one or more plant oils or one or more marine oils or a combination thereof.

15. A composition of any one of claims 1 to 14 wherein the composition further comprises one or more seal oils, one or more shellfish oils, one or more fish oils, or a combination of any two or more thereof.

16. A composition of any one of claims 1 to 15 wherein the composition comprises at least about 30 to 90% by weight of the one or more omega 3 extracts.

17. A composition of any one of claims 1 to 16 wherein the composition further comprises one or more additional agents selected from one or more antihistamines, one or more anti-inflammatory agents, one or more anti-rheumatics, one or more corticosteroids, one or more muscle relaxants, one o£ more greenshell mussel extracts, glucosamine or a salt thereof, vitamin E, vitamin C, or a combination of any two or more thereof.

18. A composition of any one of claims 1 to 17 wherein the composition further comprises a pharmaceutically acceptable carrier.

19. 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) one or more omega 3 fatty acid extracts of one ot mote marine oils, and (b) one or more marine oils.

20. A method of claim 19 comprising administration of a composition of any one of claims 1 to 18.

21. Use of (a) one or more omega 3 fatty acid extracts 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.

22. Use of a composition of any one of claims 1 to 18 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.

23. A method or use of any one of claims 19 to 22 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, with steroid sparing effect.

24. A method or use of any one of claims 19 to 23 wherein the inflammation is joint inflammation, muscle inflammation, tendon inflammation, ligament inflammation, or inflammation associated with joint damage, joint sprain, joint strain, muscle sprain, muscle strain, cartilage damage, osteoarthritis, oϊ rheumatoid arthritis.