WO2010035013A1 - Huile de krill et comprimés d’huile de krill - Google Patents

Huile de krill et comprimés d’huile de krill Download PDF

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Publication number
WO2010035013A1
WO2010035013A1 PCT/GB2009/002311 GB2009002311W WO2010035013A1 WO 2010035013 A1 WO2010035013 A1 WO 2010035013A1 GB 2009002311 W GB2009002311 W GB 2009002311W WO 2010035013 A1 WO2010035013 A1 WO 2010035013A1
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WIPO (PCT)
Prior art keywords
krill oil
composition
carbohydrate
tablet
krill
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PCT/GB2009/002311
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English (en)
Inventor
Jo Klaveness
Original Assignee
Omegatri As
Campbell, Neil
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Filing date
Publication date
Application filed by Omegatri As, Campbell, Neil filed Critical Omegatri As
Publication of WO2010035013A1 publication Critical patent/WO2010035013A1/fr

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    • 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
    • A61K35/612—Crustaceans, e.g. crabs, lobsters, shrimps, krill or crayfish; Barnacles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system

Definitions

  • This invention relates to pharmaceutical and nutraceutical products in solid form, especially in the form of powder and tablets comprising krill oil and at least one carbohydrate optionally together with vitamins, minerals and/or pharmaceuticals, and the use of such tablets in the treatment or prophylaxis of disorders related to the cardiovascular system, skin and bone.
  • the invention concerns the use of tablets comprising high concentrations and high doses of omega- 3 phospholipids in form of krill oil in the treatment or prevention of hypertriglyceridemia and cardiac infarction.
  • Omega-3 and omega-6 fatty acids are fatty acids essential to human health but ones which cannot be manufactured by the body. For this reason, omega-3 fatty acids must be obtained from food sources and can be found in fish and certain plant oils. It is important to maintain an appropriate balance of omega-3 and omega-6 (another essential fatty acid) in the diet as these two substances work together to promote health. Omega-3 and omega-6 fatty acids play a crucial role in brain function as well as normal growth and development for example.
  • omega-6 fatty acid alpha-linolenic acid ALA
  • omega-3 fatty acids eicosapentaenoic acid EPA
  • DHA docosahexaenoic acid
  • omega-3 fatty acids help reduce inflammation whereas most omega-6 fatty acids tend to promote inflammation.
  • An inappropriate balance of these essential fatty acids contributes to the development of disease while a proper balance helps maintain and even improve health.
  • a healthy diet should consist of roughly one to four times more omega-6 fatty acids than omega-3 fatty acids.
  • the Mediterranean diet consists of a healthier balance between omega-3 and omega-6 fatty acids and many studies have shown that people who follow this diet are less likely to develop heart disease.
  • the Mediterranean diet does not include much meat (which is high in omega-6 fatty acids) and emphasizes foods rich in omega-3 fatty acids including whole grains, fresh fruits and vegetables, fish, olive oil, garlic, as well as moderate wine consumption.
  • omega-3 fatty acids or their derivatives have been made available to consumers as dietary supplements to try to restore the desired omega-3 to omega-6 balance. Omega-3 fatty acids or derivatives thereof are thus now taken routinely by many hundreds of thousands of individuals to prevent a variety of illnesses such as arthritis, cardiac infarction and stroke.
  • Omega-3 fatty acids are often provided to consumers in their naturally occurring triglyceride form.
  • the Omega-3 fatty acid triglyceride or the free fatty acid itself are generally sourced from natural oils such as marine oils. Since it is difficult to isolate the omega-3 acids in high purity from marine oils, omega-3 supplements often possess an unpleasant fishy after taste which the consumer dislikes. It is also a major problem for many individuals, such as the elderly and children, to swallow the gelatine capsules used today to contain the omega-3 material. Capsules are also expensive to produce.
  • omega-3 fatty acids might be in the form of esters (e.g. ethyl esters) and phospholipids.
  • Omega-3 comprising phospholipids is present in relative high concentrations in krill oil and the phospholipid form of omega-3 fatty acids is claimed to have higher bioavailability than other omega-3 fatty acid derivatives.
  • One such product comprising pure krill oil is capsules from Swanson Health products in US (Swanson EFAs comprising Antarctic pure Neptune Krill oil). Each capsule comprises of 500 mg krill oil.
  • Krill are small shrimp-like animals living in the sea in Antarctic and Arctic regions.
  • the total biomass of krill is huge, and over the last few years there has been an increasing interest in harvesting krill, especially from the Antarctic region.
  • Companies like Neptune Technologies and Aker Biomarine ASA in Oslo, Norway are companies focusing on krill harvesting, krill processing and marketing of krill based products.
  • krill There are several species of krill. The most popular species for use in krill products seems to be E. superba. The size and the composition of krill vary a lot from species to species. The composition of the krill also varies during the year.
  • the lipid composition of krill oil is very different from the lipid composition in fish oil.
  • Krill oil comprises of large quantities of phospholipids in addition to triglycerides and other lipophilic substances.
  • Krill oil typically comprise of 40-50% phospholipids, typically phosphatidylcholines and phosphatidylethanolamines.
  • Krill oil also contains astaxantin which is a natural antioxidant. Due to the content of astaxantin, the oil from krill is deep red in colour. The chemical composition of krill oil is thus more complex than fish oil.
  • WO2008050219 describes methods and equipment for extraction of lipid fractions from marine and aquatic animals.
  • US2006/0078625(Rockway) describes a composition including krill extracts and conjugated linoleic acid.
  • WO2008/006607 describes pharmaceutical and nutraceutical products comprising Vitamin K2 and krill oil.
  • WO2008/048107 (Aker Biomarine) describes floating trawl and methods for harvesting krill.
  • Capsule formulations are not mechanically resistant formulations and have the potential for leakage of krill oil from the capsule. This could result in discoloration of the environment (e.g. clothes, bags) due to the astaxantin present in the oil. Capsules are also a dosage form which many individuals are reluctant to swallow in view of their size and shape.
  • a further problem with capsule formulations of krill oil is their stability. Capsule formulations of krill oil have only limited stability, therefore. A further issue is that the amount of omega-3 which needs to be administered to achieve a clinical does is quite high. This means the capsules on the market are large making them even harder to swallow and also means that they contain high levels of krill oil and hence a strong, unpleasant fishy aftertaste. Alternatively, it means that the consumer has to take multiple smaller tablets which causes issues of repeated swallowing/after taste and expense.
  • krill oil in the form of complexes or mixtures with carbohydrates can be prepared as stable solid materials, e.g. in form of a powder. These solid materials, especially powders can easily be transformed into tablets with high concentration of krill oil in the tablet.
  • the present inventors have realised that ideal dosage forms for these compounds are tablets and these are readily swallowed and are cheap to manufacture.
  • tablets containing complexes or mixtures of krill oil with carbohydrates can be prepared by direct compression and moreover they can be prepared having a high concentration of the desired krill oil.
  • the invention provides a solid, preferably a powder, comprising krill oil and at least one carbohydrate.
  • a solid preferably a powder, comprising krill oil and at least one carbohydrate.
  • said solid is pharmaceutically or nutraceutically acceptable.
  • the invention provides a solid, preferably a powder, consisting of krill oil and at least one carbohydrate.
  • the invention provides a pharmaceutical or nutraceutical composition in the form of a tablet for oral administration comprising krill oil and at least one carbohydrate.
  • Said tablet is preferably formed from said pharmaceutically or nutraceutically acceptable powder.
  • the invention provides a pharmaceutical tablet as hereinbefore described for use in the treatment or prophylaxis of disorders related to the cardiovascular system, metabolic system, skin and bone.
  • the invention provides the use of krill oil and at least one carbohydrate in the manufacture of a medicament in the form of a solid, e.g. a powder or tablet, for use in the treatment or prophylaxis of disorders related to the cardiovascular system, metabolic system, skin and bone.
  • the invention provides a method of treatment or prophylaxis of disorders related to the cardiovascular system, metabolic system, skin and bone comprising administering to a patient a pharmaceutical tablet as hereinbefore described.
  • nutraceutical a composition comprising a food extract that provides medical or health benefits, including the prevention and treatment of disease.
  • the solid composition, especially powders and tablets of the invention comprise a mixture krill oil and at least one carbohydrate. That mixture is preferably in the form of a complex.
  • the term "complex" is used herein to designate that the krill oil, or at least some of the components in the krill oil, is associated with the carbohydrate through some form of intermolecular interaction involving non-covalent bonds. These bonds include relative weak bonds like hydrophobic interactions, ion-ion interactions, ion-dipole interactions, dipole-dipole interactions, hydrogen bonds or other weak chemical bonds. Without wishing to be limited by theory, it is the inventors opinion that these bonds are the basis for the observed transformation of the oil to a solid, in particular a dry powder. This unexpected observation forms part of the basis for this invention.
  • the krill oil used in the invention can be purchased from commercial sources such as Neptune Krill oil.
  • the krill oil of the invention preferably contains at least 20 wt%, e.g. at least 25 %, preferably at least 35 wt%, especially at least 40 wt% unsaturated fatty acid phospholipids, typically phosphatidylcholines and phosphatidylethanolamines.
  • the krill oil of the invention may contain at least 20 wt%, especially at least 25% omega-3 phospholipids.
  • the krill oil used in the invention may also contain astaxantin. It is within the scope of the invention for a mixture of different krill oils to be used.
  • the at least one carbohydrate used in the invention can be any carbohydrate including monosaccharides, disaccharides, oligosaccharides and polysaccharides and mixtures thereof.
  • the most preferred monosaccharide is lactose.
  • the most preferred disaccharide is sucrose.
  • the most preferred oligosaccharides are dextrins or cyclodextrins.
  • the most preferred polysaccharides are alginates, cellulose, starch, pectin, chitin and chitosan and derivatives of these compounds.
  • Lactose is available in different forms such as alpha-lactose, beta-lactose and spray dried lactose from various suppliers. All these lactose forms can be used in the present invention.
  • Cyclodextrins and derivatives of cyclodextrins are available. Cyclodextrins with different cavity size can optionally be substituted.
  • the preferred substituent include alkyl groups, hydroxyalkyl groups, acyl groups
  • cyclodextrins to be used together with krill oil to form powder or tablet of krill oil are alpha-cyclodextrin, beta-cyclodextrin and gamma- cyclodextrin, in particular unsubstituted alpha-, beta- or gamma-cyclodextrins and methyl or hydroxypropyl derivatives thereof.
  • the most highly preferred cyclodextrins are beta-cyclodextrin and hydroxypropyl-cyclodextrin.
  • cyclodextrins are used, it is believed that some of the compounds in the krill oil will form non covalent bonds to the inner part of the cyclodextrins.
  • the carbohydrate used is not a cyclodextrin.
  • the polysaccharides to be used to form krill oil powder can be charged or non-charged.
  • the molecular weight and the viscosity grade of the polysaccharide to be used according to the present invention can vary over a wide range.
  • the most preferred polysaccharides are alginates including salts and derivatives thereof, e.g. alginic acid, dextrins, cellulose specially including commercial grades of microcrystalline cellulose, methylcellulose, ethylcellulose, propylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, carboxymethylcellulose (e.g. its sodium salt), carboxymethylhydroxyethylcellulose, starch and alkylated starch, chitin and chitosan.
  • alginates including salts and derivatives thereof, e.g. alginic acid, dextrins, cellulose specially including commercial grades of microcrystalline cellulose, methylcellulose, ethylcellulose, propylcellulose, hydroxyethylcellulose,
  • the invention covers the use of calixarenes to form complexes with the fatty acid compounds.
  • Calixarenes are macrocyclic compounds capable of assuming a basket (or "calix") shaped conformation. They are formed from p-hydrocarbyl phenols and formaldehyde and the term applies to a variety of compounds derived by substitution of the hydrocarbon cyclo ⁇ oligo[(l,3-phenylene) methylene] ⁇ .
  • the invention provides a pharmaceutical or nutraceutical composition in the form of a solid, preferably powder or tablet for oral administration comprising krill oil and at least one calixarene, e.g. at least 10 wt% krill oil.
  • the pharmaceutical or nutraceutical solid, powder or tablet of the invention may comprise more than 10 wt%, e.g. more than 15 wt%, e.g. more than 20 wt%, especially more than 25 wt% of a complex or mixture comprising krill oil and at least one carbohydrate.
  • the solids, powders or tablets of the invention may contain at least 10 wt% krill oil e.g. at least 15 wt% or at least 20 wt% or at least 25 wt% krill oil.
  • the solids, powders or tablets of the invention may contain at least 10 wt% total oil content, e.g. at least 15 wt% or at least 20 wt% or at least 25 wt% krill oil
  • the weight ratio between krill oil (or oils total) and carbohydrate can vary over wide limits.
  • the weight ratio may be in the range of 1 : 10 to 10:1 (between the krill oil (or oils in total) and carbohydrate), such as 1 :5 to 5: 1 , preferably 1 :4 to 4: 1.
  • carbohyrate(s) is in excess.
  • the tablets of the invention preferably comprise krill oil/carbohydrate powder complex or mixture where the powder weight is more than 10% of the tablet weight , e.g. more than 20 %, preferably more than 30%, such as greater than 40%.
  • the complex can form more than 70% of the tablet weight, preferably more than 80% of the tablet weight most preferably more than 90% of the tablet weight.
  • the tablets of the invention preferably contain at least 100 mg, e.g. at least 125 mg, preferably at least 150 mg, such as at least 200 mg, e.g. at least 300 mg of krill oil or krill oil in combination with at least one other oil, preferably at least 400 mg, more preferably at least 500 mg, especially at least 600 mg.
  • the pharmaceutical or nutraceutical solid composition e.g. powder or tablet of the invention can contain other components in addition to krill oil and the at least one carbohydrate.
  • the composition of the invention can comprise at least one other oil, especially an oil containing omega-3 compounds, e.g. a marine oil such as a fish oil.
  • Crude marine oils contain a variety of fatty acids or derivatives thereof (e.g. esters thereof, in particular triglycerides) having differing carbon chain lengths and differing levels of unsaturation.
  • the crude marine oil used as an additional component in the powders and tablets of the invention can be derived from any marine source such as fish, especially seawater fish such as tuna, sardines, salmon, mackerel, herring, trout, halibut, cod, haddock, catfish, sole etc.
  • the use of oily fish is preferred.
  • the crude marine oil will derive from marine mammals such as seals, walrus or sea lions, preferably seals. Seal oil has been found to be especially rich in omega-3 compounds, e.g. of the order of 20-25 wt% and therefore forms an ideal additional oil for the powders and tablets of the invention. Seal oils are available from a variety of commercial sources.
  • a particularly preferred solid composition of the invention comprises a krill oil, another marine oil (e.g. a fish oil), and a cyclodextrin. It will be appreciated that the composition of the invention must still be in solid (ideally powder or tablet) form even when there is an additional oil present.
  • the pharmaceutical or nutraceutical tablet for oral administration preferably comprises more than 100 mg, e.g. at least 200 mg more preferably at least 300 mg, most preferably at least 400 mg of the mixture/complex of krill oil and at least one carbohydrate.
  • the solid composition e.g. powders and tablets of the invention comprising krill oil can be formulated together with one or more other active agents.
  • Active agents which could be combined with the complexes of the invention include pharmaceuticals, nutraceuticals, vitamins, minerals and other health supplementing compounds. Combination with drugs is highly preferable.
  • the most preferred drugs to be formulated together with fatty acid compounds in tablets according to the present invention are drugs for treatment and/or prophylaxis of diseases in the cardiovascular system, the metabolic system and in bone.
  • Typical such drugs include ACE-inhibitors, like for example enalapril, angiotensin II receptor antagonists like losartan, beta-blockers like propranolol, plasma cholesterol reducing compounds like statins, typically simvastatin or atorvastatin, and bisphosphonates like for example alendronate.
  • Other favourable drugs include glucosamine.
  • compositions of the invention also include simvastatin, atorvastatin, glucosamine, vitamins and/or minerals in particular calcium, e.g. in the form of calcium carbonate.
  • nutraceutical ingredients can be calcium, e.g. calcium carbonate, iron or other minerals, water-soluble vitamins like Vitamin B or Vitamin C, lipid-soluble vitamins like Vitamin A, D, K or E and ingredients present in the nature like for example herbs and extracts thereof. It is preferred if compositions of the invention are free of vitamin K, especially vitamin K2.
  • the invention provides a pharmaceutical tablet for oral administration comprising krill oil and at least one carbohydrate and at least one drug compound selected among drugs for treatment or prophylactic treatment of metabolic disorder.
  • Typical methods for preparation of the krill oil carbohydrate powder complex or mixture include for example, formation of the complex/mixture in water, in mixture of water and organic solvent(s) or water- free organic solvents at ambient temperatures.
  • Typical organic solvents include preferably methanol, ethanol and isopropanol but can also include acetone, DMSO, DMF and acetonitrile.
  • the ratio between carbohydrate and krill oil should preferably be so that the formed powder has good flowing and tabletting properties.
  • the powder complex or mixture with krill oil is isolated by filtration, evaporation, spray drying or freeze drying.
  • the krill oil is in the form of an oil when combined with the carbohydrate.
  • One preferred option is to use a solvent to prepare the powder. If a solvent is used the solvent is subsequently removed.
  • Preferred solvents are water and alcohols and mixtures of these solvents.
  • Preferred methods for removal of solvents when preparing the powder include freeze drying, evaporation and spray drying.
  • the mixture or complex of krill oil with carbohydrate is forms as a solid, preferably as a powder.
  • the material is a crystalline solid. It should not be an oily material. It will be appreciated that sometimes to achieve a powder a solid may need to be ground. In a further preferred embodiment therefore the mixture or complex of krill oil and at least one carbohydrate complex will be suitable for grinding to form a powder.
  • the invention therefore provides a process for converting a krill oil into a solid comprising contacting the krill oil with a carbohydrate to form a complex or mixture thereof and optionally drying to form a solid, preferably a powder.
  • Drying of the complex can be carried out by any known means.
  • the material can be vacuum dried or simply left to dry in ambient air. It could be gently heated to encourage drying.
  • Preferred drying methods include freeze drying and spray drying however. Spray drying techniques are disclosed in "Spray Drying Handbook", K. Masters, 5th edition, Longman Scientific Technical UK, 1991, the disclosure of which is hereby incorporated by reference at least for its teaching of spray drying methods.
  • krill oil comprises very many different phospholipids and other lipid compounds and hence there can be more than one complex formed.
  • the krill oil is in the form of a solid, especially a powder, especially a crystalline solid. This can be achieved through complex formation as described above or achieved by spray drying of a krill emulsion.
  • the tablets of the invention may be produced by compression or compaction of a formulation containing krill oil and certain excipients, typically selected to aid in the processing and to improve the properties of the tablet.
  • the tablets of the invention may be coated or uncoated and can be made from powdered, crystalline materials. Tablets may be plain, film or sugar coated, bisected, embossed, layered, or sustained release. Any film coating preferably comprise of a physiologically acceptable water-soluble organic polymer. They can be made in a variety of sizes, shapes and colours.
  • Excipients which may be present include diluents, binders, disintegrants, lubricants, glidants, anti-oxidants and in many cases, colorants.
  • the excipients used are classified according to the function they perform. For example, a glidant may be used to improve the flow of powder blend in the hopper and into the tablet die.
  • Lubricants are typically added to prevent the tableting materials from sticking to punches, minimize friction during tablet compression, and allow for removal of the compressed tablet from the die. Such lubricants are commonly included in the final tablet mix in amounts usually less than 1 % by weight. The most commonly used lubricants are magnesium stearate, stearic acid, hydrogenated oil, and sodium stearyl fumarate.
  • Tablets often contain diluents, such as lactose, which are added to increase the bulk weight of the blend resulting in a practical size for compression. This is often necessary where the dose of the drug is relatively small so the use of diluents is favoured in this invention where high doses of the fatty acid compounds are required.
  • Typical diluents include for example dicalcium phosphate, calcium sulphate, lactose, cellulose, kaolin, mannitol, sodium chloride, dry starch and other sugars.
  • the cellulose can preferably be microcrystalline cellulose (Avicel).
  • Binders are agents which impart cohesive qualities to the powdered material. Commonly used binders include starch, gelatin, sugars such as sucrose, glucose, dextrose, and lactose, natural and synthetic gums, carboxymethylcellulose, methylcellulose, polyvinylpyrrolidone, ethyl cellulose and waxes.
  • Disintegrants are often included to ensure that the tablet has an acceptable rate of disintegration.
  • Typical disintegrants include starch derivatives, crospovidone, croscaramelose and salts of carboxymethylcellulose.
  • Some binders, such as starch and cellulose, are also excellent disintegrants.
  • Krill oil contains astaxanthin, a natural antioxidant, so the use of additional anti-oxidants may not be required. It is possible however to add conventional antioxidants such as vitamin C, vitamin E and BHT to any tablet of the invention.
  • conventional antioxidants such as vitamin C, vitamin E and BHT
  • Other desirable characteristics of excipients include high compressibility to allow strong tablets to be made at low compression forces, good flow properties that can improve the flow of other excipients in the formula and cohesiveness (to prevent tablet from crumbling during processing, shipping and handling). The skilled man knows the type of excipients appropriate for tablet formulation. It is preferred if the total weight of excipients in a tablet of the invention is no more than 20 wt% of that tablet, preferably less than 15 wt% of the tablet, especially less than 10 wt% of the tablet.
  • the three processes for making compressed tablets are wet granulation, direct compression, and dry granulation (slugging or roller compaction). Whilst all three methods can be used to form the tablets of the invention, it is preferred if direct compression is employed.
  • the invention provides a process for the preparation of a tablet comprising krill oil and at least one carbohyrate comprising the direct compression of a mixture, preferably a complex thereof.
  • Dry granulation consists of blending, slugging the ingredients, dry screening, lubrication, and compression.
  • the wet granulation method is used to convert a powder mixture into granules having suitable flow and cohesive properties for tableting.
  • the procedure consists of mixing the powders in a suitable blender followed by adding the granulating solution under shear to the mixed powders to obtain a granulation.
  • the damp mass is then screened through a suitable screen and dried by tray drying or fluidized bed drying. Alternately, the wet mass may be dried and passed through a mill.
  • the overall process includes: weighing, dry powder blending, wet granulating, drying, milling, blending lubrication and compression.
  • Direct compression is a relatively quick process where the powdered materials are compressed directly without changing the physical and chemical properties of the drug.
  • the fatty acid compound, direct compression excipients and any other auxiliary substances, such as a glidant and lubricant are blended, e.g. in a twin shell blender or similar low shear apparatus before being compressed into tablets.
  • the advantages of direct compression include uniformity of blend, few manufacturing steps involved, (i.e. the overall process involves weighing of powders, blending and compression, hence less cost), elimination of heat and moisture, prime particle dissociation, and physical stability.
  • direct compression is usually limited to those situations where the drug or active ingredient has a crystalline structure and physical characteristics required to form pharmaceutically acceptable tablets. Since the fatty acid compounds of the invention typically present as oils, the use of direct compression to form oral dosage forms of fatty acid compounds is not reported. Moreover, since excipients need to be added to a direct compression formulation to allow the compression process to take place manufacturers are often limited to using the direct compression method in formulations containing a low dose of the active ingredient per compressed tablet as otherwise tablet sizes become to large for swallowing.
  • a solid dosage form containing a high dose drug i.e. where the drug itself comprises a substantial portion of the total compressed tablet weight
  • the drug itself has sufficient physical characteristics (e.g. cohesiveness) for the ingredients to be directly compressed.
  • the inventors have found that fatty acid mixtures and complexes of the invention possess the necessary physical characteristics.
  • the fatty acid compounds and complexes of the invention have unexpectedly good flow and compression characteristics.
  • the material optionally mixed with excipients as described above, for example microcrystalline cellulose and magnesium stearate, is free-flowing and sufficiently cohesive to act as a binder.
  • krill oil which can be presented in solid form as carbohydrate complexes or mixtures, especially solid forms comprising high amounts of krill oil, can be tabletted without prior granulation (i.e. by direct compression).
  • the most preferred method of production of tablets of the invention is therefore by direct compression.
  • the size of the tablets, according to the present invention can vary.
  • the tablet diameter can vary from 6 mm to 20 mm, preferably 8 to 14 mm.
  • the tablet weight can vary from 100 mg to 3 grams.
  • the most preferred tablets have tablet weights between 200 mg and 2 grams with a diameter from 8 to 12 mm.
  • the tablets are for oral administration either by direct swallowing thereof or by any other known means, e.g. chewable tablets, dissolution or suspension of the tablet in a drinkable liquid and so on.
  • tablets Whilst the tablets are primarily for use with human consumers, tablets might also be administered to animals, especially mammals, e.g. higher mammals.
  • fatty acid compounds of the invention have been confirmed in many studies.
  • Polyunsaturated fatty acids have been found to keep serum cholesterol levels low, stabilise irregular heartbeat, reduce blood pressure, improve autoimmune disease, improve depression disorders, treat psoriasis, treat rheumatoid arthritis, and to prevent colon cancer. They are generally applied in cardiovascular disorders and for the treatment of bone disorders.
  • the tablets of the invention are of particular interest in the treatment or prevention of hypertriglyceridemia and cardiac infarction.
  • Hypertriglyceridemia is a medical condition characterized by increased plasma concentration of triglycerides.
  • Beta-cyclodextrin 1500 1500 500 pale orange powder

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Abstract

La présente invention concerne une composition pharmaceutique ou nutraceutique sous forme solide, par exemple, sous forme de poudre ou de comprimés comportant de l’huile de krill et du glucide.
PCT/GB2009/002311 2008-09-26 2009-09-28 Huile de krill et comprimés d’huile de krill WO2010035013A1 (fr)

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GBGB0817701.6A GB0817701D0 (en) 2008-09-26 2008-09-26 Krill oil powder and krill oil tablets

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Cited By (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2012120378A1 (fr) * 2011-03-07 2012-09-13 Olympic Seafood As Compositions et procédés destinés à la supplémentation nutritionnelle
WO2012085671A3 (fr) * 2010-12-21 2013-04-11 Omegatri As Antioxydants dans la poudre et les comprimés à base d'huiles de poissons
US8609157B2 (en) 2009-10-30 2013-12-17 Tharos Ltd. Solvent-free process for obtaining phospholipids and neutral enriched krill oils
US20140271907A1 (en) * 2013-03-14 2014-09-18 Amarin Pharmaceuticals Ireland Limited Compositions comprising eicosapentaenoic acid and krill oil and methods of use thereof
JP2015159801A (ja) * 2014-02-28 2015-09-07 サンデン商事株式会社 γ−トコトリエノールにより酸化防止されたクリルオイルを含むサプリメント
CN105381471A (zh) * 2015-12-01 2016-03-09 桂龙药业(安徽)有限公司 磷虾油包合物及其制备方法及其应用
WO2016055860A1 (fr) * 2014-10-10 2016-04-14 Enzymotec Ltd. Préparations de lécithine marine à résistance accrue à l'oxydation
CN105995661A (zh) * 2016-05-25 2016-10-12 湖北楚米生物科技有限公司 一种南极磷虾油片及其制备工艺
CN107997155A (zh) * 2017-12-01 2018-05-08 北京斯利安药业有限公司 一种组合物、其应用和抗氧化、改善记忆力的产品
US10080803B2 (en) 2014-04-25 2018-09-25 Aker Biomarine Antartic As Emulsified krill phospholipid compositions
CN109259237A (zh) * 2018-10-22 2019-01-25 辽渔南极磷虾科技发展有限公司 一种高epa/dha型南极磷虾油磷脂丸及其制备方法
US10806742B2 (en) 2014-02-12 2020-10-20 Aker Biomarine Antarctic As Liquid phospholipid-containing compositions for the preparation of pharmaceuticals
US10960016B2 (en) 2014-02-12 2021-03-30 Aker Biomarine Antarctic As Capsules containing high doses of krill phospholipids
US11147841B2 (en) 2014-12-19 2021-10-19 Aker Biomarine Antarctic As Enhanced omega-3 formulations

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US9150815B2 (en) 2009-10-30 2015-10-06 Tharos Ltd. Solvent-free process for obtaining phospholipids and neutral enriched krill oils
US8609157B2 (en) 2009-10-30 2013-12-17 Tharos Ltd. Solvent-free process for obtaining phospholipids and neutral enriched krill oils
US8772516B2 (en) 2009-10-30 2014-07-08 Tharos. Ltd. Solvent-free process for obtaining phospholipids and neutral enriched krill oils
US8865236B2 (en) 2009-10-30 2014-10-21 Tharos Ltd. Solvent-Free Process for Obtaining Phospholipids and Neutral Enriched Krill Oils
US9011942B2 (en) 2009-10-30 2015-04-21 Tharos, Ltd. Solvent-free process for obtaining phospholipids and neutral enriched krill oils
WO2012085671A3 (fr) * 2010-12-21 2013-04-11 Omegatri As Antioxydants dans la poudre et les comprimés à base d'huiles de poissons
WO2012120378A1 (fr) * 2011-03-07 2012-09-13 Olympic Seafood As Compositions et procédés destinés à la supplémentation nutritionnelle
US20140271907A1 (en) * 2013-03-14 2014-09-18 Amarin Pharmaceuticals Ireland Limited Compositions comprising eicosapentaenoic acid and krill oil and methods of use thereof
US10806742B2 (en) 2014-02-12 2020-10-20 Aker Biomarine Antarctic As Liquid phospholipid-containing compositions for the preparation of pharmaceuticals
US10960016B2 (en) 2014-02-12 2021-03-30 Aker Biomarine Antarctic As Capsules containing high doses of krill phospholipids
JP2015159801A (ja) * 2014-02-28 2015-09-07 サンデン商事株式会社 γ−トコトリエノールにより酸化防止されたクリルオイルを含むサプリメント
US10080803B2 (en) 2014-04-25 2018-09-25 Aker Biomarine Antartic As Emulsified krill phospholipid compositions
WO2016055860A1 (fr) * 2014-10-10 2016-04-14 Enzymotec Ltd. Préparations de lécithine marine à résistance accrue à l'oxydation
CN107105695A (zh) * 2014-10-10 2017-08-29 恩兹莫特克有限公司 具有增强的抗氧化性的海洋卵磷脂制剂
US11147841B2 (en) 2014-12-19 2021-10-19 Aker Biomarine Antarctic As Enhanced omega-3 formulations
CN105381471A (zh) * 2015-12-01 2016-03-09 桂龙药业(安徽)有限公司 磷虾油包合物及其制备方法及其应用
CN105995661A (zh) * 2016-05-25 2016-10-12 湖北楚米生物科技有限公司 一种南极磷虾油片及其制备工艺
CN107997155A (zh) * 2017-12-01 2018-05-08 北京斯利安药业有限公司 一种组合物、其应用和抗氧化、改善记忆力的产品
CN109259237A (zh) * 2018-10-22 2019-01-25 辽渔南极磷虾科技发展有限公司 一种高epa/dha型南极磷虾油磷脂丸及其制备方法

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