WO2000073254A1 - Concentration et purification d'esters d'acides gras polyinsatures par couplage distillation transesterification enzymatique - Google Patents

Concentration et purification d'esters d'acides gras polyinsatures par couplage distillation transesterification enzymatique Download PDF

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WO2000073254A1
WO2000073254A1 PCT/CA2000/000643 CA0000643W WO0073254A1 WO 2000073254 A1 WO2000073254 A1 WO 2000073254A1 CA 0000643 W CA0000643 W CA 0000643W WO 0073254 A1 WO0073254 A1 WO 0073254A1
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process according
esters
alcohol
fatty acid
fatty acids
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PCT/CA2000/000643
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English (en)
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François Le Goffic
Anh Dung Nguyen
Chiraz Khayat-Frydman
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Jfs Envirohealth Ltd.
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Priority to JP2000621321A priority Critical patent/JP2003500082A/ja
Priority to AU53774/00A priority patent/AU5377400A/en
Priority to EP00938359A priority patent/EP1100764A1/fr
Publication of WO2000073254A1 publication Critical patent/WO2000073254A1/fr

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    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
    • C12P7/00—Preparation of oxygen-containing organic compounds
    • C12P7/64—Fats; Fatty oils; Ester-type waxes; Higher fatty acids, i.e. having at least seven carbon atoms in an unbroken chain bound to a carboxyl group; Oxidised oils or fats
    • C12P7/6436—Fatty acid esters
    • C12P7/6445—Glycerides
    • C12P7/6458—Glycerides by transesterification, e.g. interesterification, ester interchange, alcoholysis or acidolysis
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
    • C12P7/00—Preparation of oxygen-containing organic compounds
    • C12P7/64—Fats; Fatty oils; Ester-type waxes; Higher fatty acids, i.e. having at least seven carbon atoms in an unbroken chain bound to a carboxyl group; Oxidised oils or fats
    • C12P7/6436—Fatty acid esters
    • C12P7/6445—Glycerides
    • C12P7/6472—Glycerides containing polyunsaturated fatty acid [PUFA] residues, i.e. having two or more double bonds in their backbone
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C67/00—Preparation of carboxylic acid esters
    • C07C67/03—Preparation of carboxylic acid esters by reacting an ester group with a hydroxy group
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C67/00—Preparation of carboxylic acid esters
    • C07C67/48—Separation; Purification; Stabilisation; Use of additives
    • C07C67/52—Separation; Purification; Stabilisation; Use of additives by change in the physical state, e.g. crystallisation
    • C07C67/54—Separation; Purification; Stabilisation; Use of additives by change in the physical state, e.g. crystallisation by distillation
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
    • C12P7/00—Preparation of oxygen-containing organic compounds
    • C12P7/64—Fats; Fatty oils; Ester-type waxes; Higher fatty acids, i.e. having at least seven carbon atoms in an unbroken chain bound to a carboxyl group; Oxidised oils or fats
    • C12P7/6436—Fatty acid esters
    • C12P7/6445—Glycerides
    • C12P7/6454—Glycerides by esterification

Definitions

  • the present invention relates to a process for producing highly concentrated preparations of polyunsaturated fatty acids and their esters from oils from various sources, especially fish oils, vegetable oils and microalgae oils.
  • the process uses a combination of molecular distillation and selective enzymatic transesterification catalysed by upases which desirably can be immobilized.
  • fatty acids mostly encountered, usually as their triglyceride esters but not exclusively, in fish oils and vegetable oils are oleic acid (C18:l), palmitoleic acid (C16:l), palmitic acid (C16:0) and gadolenic acid (C20:l), but other fatty acids possessing from 14 to 24 carbon atoms in their structure, with or without double bounds, can also be found.
  • Polyunsaturated fatty acids possessing 3 double bonds or more are components of high economic value and have many applications in the pharmaceutical, nutrient and cosmetic fields.
  • Two well-known families are the so-called ⁇ 3 and ⁇ 6 families, which include a single double bond located three and six carbon atoms respectively from the terminal methyl group.
  • the two most important members of the ⁇ 3 family are eicosapentaenoic acid (EPA, C20:5) and docosahexenoic acid (DHA, C22:6) which play an important role in human physiology. They participate in the construction of cellular membranes and, as precursors of prostaglandins, in the formation of PGI3 and TxA3, which are extremely important factors for platelet aggregation prevention. Furthermore, DHA is the most important component of brain lipids and is believed to have a role in synaptic membrane functioning.
  • the principal members of the ⁇ family are ⁇ -linolenic (GLA, C18:3) acid and arachidonic acid (AA, C20:4). The former is an essential fatty acid and used for certain therapeutic purposes such as the treatment of multiple sclerosis. The latter participates in prostaglandin metabolism and possesses specific functions in brain and retina.
  • Fish oils are important sources for EPA and DHA.
  • the weight percentages of EPA+DHA of the total fatty acids range from 7% (in Pacific herring oil) to 28% (in Pacific squid oil) .
  • the most common source for EPA and DHA is sardine oil with a combined concentration of about 25%, comprising 18% EPA and 7% DHA.
  • Other possible sources are salmon oil (19% EPA and DHA), menhaden oil (24%), cod liver oil (24%), and mackerel oil (15%) .
  • the ratio of EPA to DHA in fish oils is usually about 2:1, but tuna oil contains about 5% EPA and about 18% DHA.
  • EPA and DHA are also found in lipids produced by marine microalgae such as Monodus subterraneus UTEX 151 (34.2% EPA), Chlorella minutissima UTEX 2341 (31.3% EPA), Crypthecodinium cohnii UTEX L1649 (19.9% DHA) or Amphidini um carterae UTEX LB 1002 (17% DHA) .
  • soybean and canola oils provide ⁇ linolenic acid (precursor of EPA and DHA) at 8-10% of the total fatty acids.
  • the major sources for ⁇ -linolenic acid are borage, evening primrose and black current oils. The first is more important with 20% to 23% of ⁇ -linolenic acid, while the second contains only about 10% of ⁇ -linolenic acid and the last 14% to 20%.
  • the composition of the reaction medium can be carefully controlled to purify selectively polyunsaturated fatty acids by the urea adduct formation method (Han, Daeseok; Shin, Hyun-Kyung; Yoon, Suk Hoo, ACS Symp. Ser. 1997, 674 (Flavor and Lipid Chemistry of Seafoods) ) .
  • EPA and DHA have also been purified through silver salt complexation (EP 454 430, and EP 303 668), by chromatography (Robles Medina, .; Gimenez Gimenez,A.; Garcia Camacho, F.; Sanchez Perez, J.A.; Molina Grima, E . ; Contreras Gomez, A.; J.Am.Oil Chem. Soc. 1995 72(5) 575-83). These processes result in the preparation of highly purified polyunsaturated fatty acids, but only in very small quantities.
  • the silver ion, Ag + can be immobilized on a clay mineral (Yamaguchi, Michihiro; Tanaka, Isao; Ohtsu, Yutaka; Yukagaku 1991 40(10), 959-64), which makes the method more practical.
  • a clay mineral Yamauchi, Michihiro; Tanaka, Isao; Ohtsu, Yutaka; Yukagaku 1991 40(10), 959-64
  • a very promising method currently used to obtain concentrates of polyunsaturated fatty acids is molecular distillation. This method makes use of high vacuum conditions to distil the thermolabile polyunsaturated fatty acids. This process, in some cases, results in very high concentrates of polyunsaturated fatty acids.
  • a British patent (GB 2 218 984) has claimed the process to be appropriate for industrial production of EPA and DHA. However multiple distillations are necessary to obtain a high concentration of polyunsaturated fatty acids and the distillation temperature used is very low (from 50 to 85°C) .
  • Using a low temperature has an advantage of not altering the nature of the easily oxidized polyunsaturated fatty acids, but causes a major problem in industrial production since the throughput is proportional to the difference between the vapour pressure of the products to be distilled and the operating pressure, and the former is a function of temperature.
  • molecular distillation Although very powerful, the concept of molecular distillation is close to that of batch distillation and thus has limitations. In particular, if the composition of the raw material is complex, molecular distillation does not allow an effective purification and for instance is inappropriate for the production of DHA free from EPA and vice versa. The same problem is encountered for the production of ⁇ -linolenic acid free from linoleic and oleic acids.
  • Another way to obtain polyunsaturated fatty acids in high concentration is selective hydrolysis or selective synthesis using specific enzymes.
  • Different upases known to have a selectivity for saturated fatty acids over polyunsaturated fatty acids are used.
  • the most common way is to hydrolyse oils containing polyunsaturated fatty acid triglycerides followed by washing or extraction (JP 05095792, JP 03108489, and JP 07203979) .
  • This invention seeks to provide an efficient economical process for the concentration and the purification of polyunsaturated fatty acids as onoesters of lower alcohols.
  • the raw material for the process is either fish oil containing different concentrations of eicosapentaenoic acid (EPA C20:5) and docosahexaenoic acid (DHA C22:6), or vegetable oils like borage, evening primrose or black current oils, containing different concentrations of ⁇ -linolenic acid (GLA C18:3), or oils isolated from microalgae or other micro-organisms which contain fatty acids like DHA or arachidonic acid (AA C20:4).
  • these desired acids are usually present in the natural oil as the triglyceride ester.
  • the fatty acid triglyceride ester is first transesterified chemically.
  • the esters are either submitted to fractionation concentration (EPA-DHA) prior to enzymatic transesterification catalysed by an appropriate enzyme, or directly enzymatically transesterified.
  • the course of the reaction is followed by gas chromatography. It is stopped by the removal of the enzyme by filtration or centrifugation.
  • the transesterified oil product is submitted, generally, to two molecular or so-called short path distillations.
  • the excess of transesterification alcohol is removed as distillate, and the oil is also deodorized.
  • a distillate is produced comprising the unsaturated fatty acid ester of interest as a generally clear, odorless compound.
  • the residue of this distillation can also be used as a potential wax base, or split into its component fatty acids, or fatty acid esters of lower alcohols, which can also be purified by short path distillation.
  • this invention comprises a multistep process which can be summarised as follows.
  • Step 1 Oils containing polyunsaturated fatty acid triglycerides, such as sardine oil, borage oil and the like as described above, are first transesterified for three hours, with a primary lower alkyl alcohol at room temperature, using an alkali metal alcoholate of the same lower alkyl alcohol as catalyst. The esters obtained are separated from the glycerol formed during the reaction by decantation. The excess alcohol is removed under vacuum (15 bars) . The mixture is then treated according to its composition and to the polyunsaturated acids to be purified, using the following procedure.
  • Step 2 The mixture of ethyl esters is subjected to a preliminary optional short path distillation at 160-190°C and a pressure of 10 "3 bar to remove impurities, which constitute the distillation residue.
  • the distillate comprises the desired fatty acid ethyl esters.
  • Step 3 The distillate from step 2, or the esters mixture from step 1 if step 2 is omitted, is subjected to short path distillation at 130-160°C and a pressure of 10 "3 mbar to separate the mixture into two ester fractions.
  • the distillate is rich in esters of fatty acids possessing 18 carbons or less, and the distilland is rich in esters of fatty acids possessing 20 carbons or more.
  • Step 4 The purified ethyl esters from Step 3 are transesterified with a mono- or poly-alkoxy alcohol using a reaction specific lipase, in the presence of sufficient water for the lipase enzyme to catalyse the transesterification reaction, to provide a mixture of fatty acid ethyl esters rich in polyunsaturated fatty acids and fatty acid alkoxyalkyl esters rich in saturated and monounsaturated fatty acids .
  • Step 5 The unreacted alcohol remaining after the transesterification reaction in Step 4 is removed by short path distillation at 60-90°C under a pressure of 10 "3 mbar, or by washing with water followed by a suitable drying procedure.
  • Step 6 The esters mixture from Step 5 is subjected to a final short path distillation at 100-180°C to separate the fatty acid ethyl esters distillate from fatty acid alkoxy alkyl esters (distilland) .
  • steps 1 and 2 are not used in the purification of ⁇ -linolenic acid from borage oil as the principal constituents of this oil are linolenic, linoleic and oleic acids, which cannot be separated efficiently by distillation.
  • Step 4 is omitted whenever a too high molecular weight alcohol such as polyethylene glycol methyl ether 350 is used.
  • the primary lower alkyl alcohol preferably contains up to 7 carbon atoms, or can be benzyl alcohol. More preferably, the lower alkyl alcohol is ethyl alcohol.
  • step 4 the amount of enzyme used is preferably from about 0.5% to about 5.0% by weight of the fatty acid esters present in the oil, and the amount of water present is from 1% to 10% by weight of the enzyme.
  • the lipase enzyme is chosen from the group consisting of: Lipozyme IM from a Mucor miehei strain; Lipase D from a Rhizopus delemar strain; and Esterase 30000 from a Mucor miehei strain.
  • the transesterification in step 4 is carried out at a temperature of 50 - 70°C, and a pressure of from about 0.1 - 20 mbars. More preferably, the transesterification in step 4 is carried out at a temperature of 60 - 70°C, and a pressure of about 15 mbars.
  • the present invention provides a process to obtain polyunsaturated fatty acids on a large scale. It can be applied to different kinds of oils by coupling short path distillation and selective enzymatic transesterification.
  • the two techniques can be used in a modular way in order to obtain products with a desirable composition. The combination makes it possible for the following to be obtained:
  • thermolabile polyunsaturated fatty acid esters In any of the purification steps, whenever the product is subject to heating, for either a distillation step or in the enzymatic reaction, it is always under vacuum. This minimises any oxidation and the degradation of the thermolabile polyunsaturated fatty acid esters.
  • the polyunsaturated fatty acids are purified as ethyl esters, whose vapour pressure is higher than that of the corresponding free acids. This makes it possible to obtain a high throughput in the short path distillation steps at 130- Steps 1 and 2 are used principally for the purification of EPA and DHA.
  • the ethyl esters of these fatty acids have a much lower rate of distillation than that of lower fatty acids (C18, C16 and lower).
  • a preliminary distillation makes it possible to obtain products containing up to 33% EPA and 22% DHA, and eliminates a high proportion of the lower fatty acids which are also present.
  • the quantity of products to be treated enzymatically is therefore much smaller than the original material, usually from about 10% to about 20% of the starting material, according to its composition.
  • the key step of the whole procedure is the transesterification of the fatty acid ethyl esters with a mono - or polyalkoxy alcohol, such as 2- (2-butoxyethoxy) ethanol and polyethylene glycol methyl ether 350, using a reaction specific lipase such as Lipozyme IM (Novo) under a vacuum of 10-20 mbars, and at appropriate temperature, such as 60-70°C for Lipozyme) .
  • the reaction equilibrium is displaced by removing under vacuum the ethanol formed during the reaction.
  • the rate at which the enzyme catalyses the transesterification reaction depends on the degree of unsaturation of the fatty acid in the ethyl ester; the reaction generally becomes slower as the degree of unsaturation increases.
  • the fatty acid ethyl esters rich in polyunsaturated fatty acids are then separated from the products of the enzymatic reaction comprising the fatty acid alkoxyalkyl esters rich in saturated and monounsaturated fatty acids by a second short path distillation at 100-180°C under a pressure of 10 "3 mbars.
  • the fatty acid ethyl esters rich in polyunsaturated fatty acids are recovered in the distillate while the fatty acid alkoxyalkyl esters rich in saturated and monounsaturated fatty acids, whose vapour pressure is practically nil, are recovered as the distilland.
  • This short path distillation step is also used to remove the excess of alcohol if it has a zero vapour pressure, as in the case of polyethylene glycol.
  • the distillate product obtained is highly rich in polyunsaturated fatty acid ethyl esters, and can contain more than 80% in most cases and can reach 90% or more.
  • alkoxy alcohol is crucial for the purification.
  • the alkoxy alcohol esters formed by the enzymatic reaction cannot be distilled in the range of temperature used for the distillation of fatty acid ethyl esters and thus the two ester types can be separated very efficiently by short path distillation.
  • the enzyme selectivity is much higher with an alkoxy alcohol than with an aliphatic alcohol.
  • oleyl alcohol for example, the enzymatic transesterification by Lipozyme IM is practically the same for all the fatty acids while with polyethylene glycol methyl ether 350, the reaction rate for saturated and monounsaturated fatty acids esters is at least 12 times greater than that for EPA (C20:5) ester and DHA ester.
  • This characteristic allows not only the enrichment of polyunsaturated fatty acids but also the separation of DHA from EPA.
  • the mixture of fatty acid ethyl esters enriched in EPA and DHA is subject to a transesterification with polyethylene glycol methyl ether by Lipozyme IM to convert EPA into its ester with polyethylene glycol methyl ether, which is then separated from DHA ethyl ester by short path distillation.
  • EPA is recovered in its free form after a saponification or hydrolysis, or as an ester of a lower alcohol by a suitable transesterification reaction.
  • ⁇ -linolenic acid which is one of the polyunsaturated fatty acids in borage and evening primrose oils, can also be isolated by the above procedure.
  • 2- (2-butoxyethoxy) ethanol seems to be the best alcohol for the purification of ⁇ -linolenic acid ester, as ⁇ -linolenate ethyl ester with a concentration of up to 90% can be obtained at a yield of up to about 96%.
  • the product is then submitted to short path distillation at 160 °C under a pressure of 10 3 mbars, and about 9.5 kg of clear, limpid ethyl esters is obtained as the distillate, containing 18% EPA and 7% DHA as their ethyl esters.
  • the ethyl esters mixture is then submitted to short path distillation at 150 °C under a pressure of 10 ⁇ 3 mbars.
  • the distilland representing 15 to 30% of the throughput is recovered.
  • This product contains at least 28% to 40% EPA, and 20% to 35% DHA, as the ethyl esters. With more careful control, the process can produce 33% EPA and 22% DHA, as the ethyl esters.
  • distilland from this first distillation is distilled again at 100-120°C and gives rise to an odourless distillate. Both distillations are carried out a pressure of 10 "3 mbars. Analysis by gas chromatography reveals that a concentration of AA ethyl ester higher than 95% can be reached.
  • fatty acid ethyl esters containing 23% ⁇ -linolenic acid from borage oil
  • borage oil 100 parts by weight of fatty acid ethyl esters containing 23% ⁇ -linolenic acid (from borage oil) is transesterified with 600 to 800 parts by weight of 2- (2-butoxy ethoxy) ethanol and 6 to 10 parts of Lipozyme IM or lipase D from Rhizopus delemar or esterase 30000 from Mucor mihei strains, in one presence of sufficient water for the enzymatic reaction to proceed, under a vacuum of 9 to 15 mbars and at a temperature of 50-60°C. The reaction is stopped by removing the enzyme by filtration. The resulting oil is submitted to two short path distillations. In the first one, performed between 50°C and 60°C, excess alcohol is removed as distillate.
  • distilland residue thus obtained is subjected to a second distillation at 100-120°C. Both distillations are carried out at a pressure of 10 "3 mbar.
  • the distillate is recovered and analysed by gas chromatography. A clear odourless oil is obtained, which contains no less than 50% ⁇ -linolenic acid ethyl ester. This concentration can reach 90%.
  • a mixture of fatty acid ethyl esters from evening primrose oil is treated under the same conditions as in Example 4. After a few hours (between 2 and 4), the reaction is stopped and the oil treated as in Example .
  • the product comprises a ⁇ -linolenic acid ethyl ester concentrate containing between 25% and 40%. This concentration can be dramatically increased when longer reaction times are applied.

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Abstract

L'invention se rapporte à un procédé de production de préparations fortement concentrées d'acides gras polyinsaturés et de leurs esters à partir d'huiles, notamment d'huiles de poisson, dans lesquelles ils sont présents principalement sous forme de leurs esters triglycérides. Ce procédé met en oeuvre la combinaison d'une transestérification des triglycérides avec un alcool d'alkyle inférieur ou un alcool de benzyle, d'une distillation moléculaire et d'une transestérification enzymatique sélective avec un alcoxy-alcool, catalysée par des lipases qui peuvent être immobilisées si nécessaire. Ce procédé permet la séparation du mélange d'acides habituellement rencontré dans les huiles, ainsi que l'extraction à rendement élevé des acides désirés. Les acides qu'il est typiquement possible d'extraire au moyen de ce procédé sont l'acide eicosapentanoïque (EPA, C20:5) et l'acide docosahexanoïque (DHA, C22:6).
PCT/CA2000/000643 1999-05-31 2000-05-31 Concentration et purification d'esters d'acides gras polyinsatures par couplage distillation transesterification enzymatique WO2000073254A1 (fr)

Priority Applications (3)

Application Number Priority Date Filing Date Title
JP2000621321A JP2003500082A (ja) 1999-05-31 2000-05-31 蒸留−酵素的エステル交換の組合せによるポリ不飽和脂肪酸エステルの濃縮及び精製
AU53774/00A AU5377400A (en) 1999-05-31 2000-05-31 Concentration and purification of polyunsaturated fatty acid esters by distillation-enzymatic transesterification coupling
EP00938359A EP1100764A1 (fr) 1999-05-31 2000-05-31 Concentration et purification d'esters d'acides gras polyinsatures par couplage distillation transesterification enzymatique

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CA2,273,570 1999-05-31
CA002273570A CA2273570A1 (fr) 1999-05-31 1999-05-31 Concentration et purification d'ester d'acides gras polyinsatures par distillation-transesterification enzymatique

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WO2004043894A1 (fr) * 2002-11-14 2004-05-27 Pronova Biocare As Esterification de petrole marin catalysee par des lipases
WO2007149577A2 (fr) * 2006-06-23 2007-12-27 The Procter & Gamble Company Acides gras oméga 3 concentrés et sans odeur
EP1978101A1 (fr) 2007-04-02 2008-10-08 Cognis IP Management GmbH Procédé d'enrichissement en acides gras polyinsaturés
EP1978102A1 (fr) 2007-04-02 2008-10-08 Cognis IP Management GmbH Un mélange comprenant des glycérides d'acides gras
WO2009006317A1 (fr) 2007-06-29 2009-01-08 Martek Biosciences Corporation Production et purification d'esters d'acides gras polyinsaturés
WO2009020406A1 (fr) * 2007-08-07 2009-02-12 Granate Seed Limited Procédés de préparation de substances lipidiques, substances lipidiques ainsi produites et leurs utilisations
WO2009154369A2 (fr) * 2008-06-20 2009-12-23 에이케이바이오텍 주식회사 Procédé de purification à haut degré de pureté d'acides gras oméga-3 hautement insaturés
US7666666B2 (en) * 2004-09-20 2010-02-23 Sunho Biodiesel Corporation Fuel production
US7678930B2 (en) 2002-07-11 2010-03-16 Pronova Biopharma Norge As Process for decreasing the amount of cholesterol in a marine oil using a volatile working fluid
US7718698B2 (en) 2002-07-11 2010-05-18 Pronova Biopharma Norge As Process for decreasing environmental pollutants in an oil or a fat
WO2011072346A1 (fr) * 2009-12-17 2011-06-23 Npc Indústrias Químicas Ltda. Procédé de modification d'huiles végétales et plastifiant primaire pour polymères vinyliques
WO2012130961A1 (fr) * 2011-03-30 2012-10-04 Novozymes A/S Procédé d'estérification
US8420349B2 (en) 2007-07-12 2013-04-16 Ocean Nutrition Canada Limited Enzymatic modification of oil
FR2994696A1 (fr) * 2012-05-29 2014-02-28 Roquette Freres Procede continu d'enrichissement en esters ethyliques de dha d'une huile produite par des microalgues
US8951761B2 (en) 2005-06-16 2015-02-10 Dsm Nutritional Products Ag Immobilized enzymes and methods of using thereof
US20150057353A1 (en) * 2006-07-05 2015-02-26 Photonz Corporation Limited production of ultrapure EPA and polar lipids form largely heterotrophic culture
EP2172558A4 (fr) * 2007-07-30 2015-05-27 Nippon Suisan Kaisha Ltd Procédé de fabrication d'une huile enrichie en epa et d'une huile enrichie en dha
US9079847B2 (en) 2010-01-27 2015-07-14 Basf Pharma (Callanish) Limited Process for preparing and purifying fatty acids
CN107043794A (zh) * 2017-06-12 2017-08-15 浙江工业大学 一种酶催化红花油醇解制备脂肪酸乙酯的方法
US10041097B2 (en) 2003-12-30 2018-08-07 Dsm Ip Assets B.V. Deaeration process
US10119098B2 (en) 2005-05-23 2018-11-06 Epax Norway As Concentration of fatty acid alkyl esters by enzymatic reactions with glycerol
US10240172B2 (en) * 2013-08-30 2019-03-26 Bizen Chemical Co., Ltd. Method for producing high purity omega-3 fatty acid ethyl ester
WO2021191385A1 (fr) * 2020-03-27 2021-09-30 Polaris Procede de fractionnement d'acides gras a deux carbones de difference par distillation moleculaire
EP3890719A4 (fr) * 2018-12-06 2022-08-24 Epax Norway AS Compositions d'acides gras à très longue chaîne
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