EP1319057B1 - Method for producing starting materials for obtaining conjugated linoleic acid - Google Patents
Method for producing starting materials for obtaining conjugated linoleic acid Download PDFInfo
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- EP1319057B1 EP1319057B1 EP01972028A EP01972028A EP1319057B1 EP 1319057 B1 EP1319057 B1 EP 1319057B1 EP 01972028 A EP01972028 A EP 01972028A EP 01972028 A EP01972028 A EP 01972028A EP 1319057 B1 EP1319057 B1 EP 1319057B1
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- Prior art keywords
- linoleic acid
- reaction
- ethanol
- transesterification
- conjugated linoleic
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Classifications
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- C—CHEMISTRY; METALLURGY
- C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
- C11C—FATTY ACIDS FROM FATS, OILS OR WAXES; CANDLES; FATS, OILS OR FATTY ACIDS BY CHEMICAL MODIFICATION OF FATS, OILS, OR FATTY ACIDS OBTAINED THEREFROM
- C11C3/00—Fats, oils, or fatty acids by chemical modification of fats, oils, or fatty acids obtained therefrom
- C11C3/04—Fats, oils, or fatty acids by chemical modification of fats, oils, or fatty acids obtained therefrom by esterification of fats or fatty oils
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- C—CHEMISTRY; METALLURGY
- C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
- C11B—PRODUCING, e.g. BY PRESSING RAW MATERIALS OR BY EXTRACTION FROM WASTE MATERIALS, REFINING OR PRESERVING FATS, FATTY SUBSTANCES, e.g. LANOLIN, FATTY OILS OR WAXES; ESSENTIAL OILS; PERFUMES
- C11B3/00—Refining fats or fatty oils
- C11B3/12—Refining fats or fatty oils by distillation
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- C—CHEMISTRY; METALLURGY
- C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
- C11C—FATTY ACIDS FROM FATS, OILS OR WAXES; CANDLES; FATS, OILS OR FATTY ACIDS BY CHEMICAL MODIFICATION OF FATS, OILS, OR FATTY ACIDS OBTAINED THEREFROM
- C11C3/00—Fats, oils, or fatty acids by chemical modification of fats, oils, or fatty acids obtained therefrom
- C11C3/04—Fats, oils, or fatty acids by chemical modification of fats, oils, or fatty acids obtained therefrom by esterification of fats or fatty oils
- C11C3/10—Ester interchange
Definitions
- the invention is in the field of dietary supplements and concerns a process for producing raw materials for the production of conjugated linoleic acid.
- the polyunsaturated ⁇ -3 and ⁇ -6 fatty acids such as ⁇ -linolenic acid, linoleic acid count to the essential for mammals and humans fatty acids.
- ⁇ -linolenic acid linoleic acid
- linoleic acid There are other isomeric octadecadienoic acids in nature. Draw these by conjugated double bonds at the C atoms 9 and 11, 10 and 12 as well as 11 and 13 off.
- conjugated linoleic acids abbreviation: CLA - conjugated linoleic acid
- CLA CLA-like lipid peroxidation
- Shultz et al. reported the inhibitory effect on the in vitro growth of human cancer cells. Carcinogenesis 8, 1881-1887 (1987) and Cancer Lett. 63, 125-133 (1992).
- CLA has a high antioxidant effect, which, for example, the lipid peroxidation can be inhibited. Atherosclerosis 108, 19-25 (1994).
- conjugated linoleic acid in animal feed and in this context also in the human diet is z. B. from WO 96/06605 known.
- EP 0579 901 B reports on the use of conjugated linoleic acid for preventing weight loss or a reduction in weight gain or of annorexia caused by immune stimulation in humans or animals.
- WO 94/16690 is concerned with improving the efficiency of food utilization in animals by administering an effective amount of conjugated linoleic acid.
- CLA is obtained by a so-called conjugation of linoleic acid-containing precursors, i.e. Products containing a carboxylic acid function with 18-carbon atoms and 2 9- and 12-position double bonds, both in the cis configuration.
- linoleic acid-containing precursors i.e. Products containing a carboxylic acid function with 18-carbon atoms and 2 9- and 12-position double bonds, both in the cis configuration.
- there Care must be taken during the conjugation reaction that only the two main CLA isomers (9cis, 11trans and 10trans, 12cis) arise, whose effect in the above described literature is described.
- a mixture of isomers, such as CLA which is known for technical purposes is used, so in the paint production such.
- Edenor®UKD 6010 Manufacturer: Cognis, Dusseldorf
- the pure CLA is often obtained by saponification of linoleic acid-containing oils [WO 96/06605, EP 0902082 A1]. Disadvantage of these methods is the high proportion of undesired isomers. These can in turn be separated by enzymatic esterification, as described in WO 97/18320 . In order to better control the content of isomers, it is also possible to use the corresponding esters as precursors.
- the state of the art here is the production of the corresponding esters by esterification of the fatty acids with methanol or ethanol. It is described in the literature that suitable starting materials for gentle conjugation are in particular the methyl and ethyl esters of linoleic acid [WO 99/47135] .
- a linoleic triglyceride e.g. Sunflower oil, preferably safflower oil, preferably refined safflower oil transesterified with ethanol.
- a linoleic triglyceride e.g. Sunflower oil, preferably safflower oil, preferably refined safflower oil transesterified with ethanol.
- esterification with linoleic acid is surprising to observe that almost no unwanted pre-conjugations and isomerizations occur.
- the transesterification takes place under mild conditions, without the use of inert gas or ethylene or propylene glycol instead.
- the fatty acid glycerides to be used according to the invention as starting materials can be the usual natural vegetable or animal fats or oils. These include For example, linola oil, sunflower oil and particularly preferably safflower oil.
- the main ingredients These fats and oils are glycerides of various types of fatty acids that considerable amounts of impurities such as aldehyde compounds, phospholipid compounds and contain free fatty acids. These materials can be direct or be used after prior purification.
- the reaction is preferably carried out at a temperature in the Range of 80 to 120 ° C, preferably 85 to 100 ° C, particularly preferably 88 to 95 ° C. carried out.
- the glycerol accumulating during the reaction is passed through a coalescence separator withdrawn continuously and about two thirds of the total amount of catalyst are added continuously during the reaction.
- Suitable as catalysts alkali and / or alkaline earth metal alkoxides or hydroxides, especially sodium methoxide and / or sodium glycerate, and more preferably sodium ethylate.
- the Reaction proceeds over 4 to 7 hours, preferably 5 to 6 hours.
- the transesterification the reaction mixture is neutralized with citric acid.
- the process is particularly preferred for the preparation of a safflorethyl ester with a low content on undesired isomers.
- the distillation of the transesterified reaction mixture is used to separate off any resulting Glycerides, free glycerin and soaps.
- the reaction product gets as well a more appealing color.
- the content of palmitic acid and the content of linoleic acid be increased.
- a vacuum of 100 to 300 mbar distilled off the excess ethanol.
- free glycerol is separated via the separator.
- the temperature to 150 to 200 ° C, preferably 160 raised to 180 ° C. 5 to 10% flow are taken and the product up on Distilled 5 to 10% residue.
- a fractional distillation can be used.
- a batch distillation from a reactor with attached Carry out column which causes the C16 content in the feed distillate increases, or to carry out the distillation in two stages, whereby about 5 to 10% by volume of the forerun from the fractionation column decreases and the main run over the top of the column distilled.
- the content of C16 in the main run can be decrease from an initial value of 6.5 to 0.7% by weight while at the same time the amount of C18: 2 increases from 75.5 to 81.4 wt .-%.
- CLA Conjugated linoleic acid
- conjugated linoleic acid are preferably the main isomers 9cis, 11trans octadecadienoic acid and 10trans, 12cis and also any isomer mixtures, as they usually occur in the production of conjugated linoleic acid.
- the raw materials produced by the process according to the invention should already have a high Contain proportion of preferred isomers.
- the process of the invention is used to produce raw materials for recovery of conjugated linoleic acid (CLA).
- CLA conjugated linoleic acid
- the low proportion of unwanted isomers in Crude product saves further steps for isomer separation and purification during production the CLA.
- the CLA produced from the raw materials can be used in all those areas which are already known from the literature for conjugated linoleic acid, for example in foods, preferably so-called "functional foods” and in pharmaceuticals, hereby in particular as a supportive agent in the treatment of tumors or for treatment of persons suffering from catabolic states.
- Example 1 (transesterification).
- the experimental setup for the transesterification consisted of a 2 l reactor (double jacket) with reflux condenser, coalescence separator in the recycle loop and vacuum pump.
- As starting materials 1500 g of safflower oil, 240 g of ethanol, 47 g of sodium ethylate in the form of a 20 wt .-% ethanolic solution (sometimes added later during the reaction) and citric acid, also used in a 20 wt .-% ethanolic solution).
- the reaction was carried out at ambient pressure. To this was added the linoleic oil, heated to 60 ° C and added to ethanol and about one-third of the amount of Na-ethylate.
- the reactor contents were heated to about 90 ° C reaction temperature and the reaction was operated under reflux. Under running circulation pump (circulation rate 8 l / h), the resulting glycerol phase was withdrawn during the reaction and continuously every 30 min. about 4 g of catalyst solution added. The reaction time was 5.5 h. The reaction mixture was then neutralized with citric acid. For the separation of glycerides, free glycerol and soaps, a distillation was connected. At 100-300 mbar vacuum, the excess ethanol was removed. In addition, by separating out through the separator additional free glycerol, which was obtained by the ethanol distillation, separated.
- the bottom temperature was then raised to 160-180 ° C at a vacuum of 1-3 mbar, taken 5-10% forerun and then the main run distilled to 5-10% residue.
- the determination of the isomers and fatty acid fractions was carried out by a chromatographic method.
- a 120m long silica column 120m * 0.25mm Permabond® FFAP - 0.25 ⁇ m, reference: Macherey Nagel) was used with hydrogen as carrier gas.
- composition of the product is shown in Table 1: Composition of feed oil and distillate fraction (data as% by weight) isomer use oil distillate fraction C 16: 0 6.01 0.99 C 18: 0 2.80 3.10 C18: 1 c9 13.25 14.31 C 18: 2 c9, c12 74.74 76.69
- Comparative Example C1 esterification
- the experimental set-up for the esterification consisted of a heatable 2 l reactor with attached distillate cooler and trap, bottom temperature measurement and control via heater mushroom, immersion tube for N 2 entry, glass frit and Dosimat for ethanol addition and a vacuum pump.
- 1000 g of sunflower oil fatty acid (Edenor® Sb, Cognis GmbH Germany) 1000 g of ethanol (continuously added), 2.5 g of p-toluenesulfonic acid and sodium hydroxide in the form of a 6 wt .-% aqueous solution used.
- the reaction was operated at ambient pressure.
- composition of the product is shown in Table 2: Composition of feed oil and distillate fraction (data as% by weight) isomer use oil distillate fraction C18: 1 t9 ⁇ 0.05 0.49 C18: 1 t10 nb 0.31 C18: 1 t11 nb 0.40 c18: 1 c11 0.74 0.78 C18: 2 t9, t12 0.06 1.54 C18: 2 c9, t12 0.66 1.04
- Table 3 shows a comparison of the isomers and CLA from the reaction product of the transesterification and the esterification taking into account the different oleic / linoleic acid ratio in the raw materials used: Comparison transesterification / esterification Safflorethyl ester by transesterification (according to the invention) Safflower ethyl ester by esterification (comparative example) C 16/0 7.20 7.08 C 16/1 0.05 0.16 C 18/0 2.60 2.47 C 18 / 19t nn 0.53 C18 / 1 10t nn 0.41 C18 / 1 11t nn 0.46 C 18/1 9c 11,99 10.08 C 18/1 11c 0.60 0.95 C 18/2 9t, 12t 0.03 1.77 C 18/2 9c, 12t 1.49 1.30 C 18/2 9t, 12c nn 0.56 C 18/2 9c, 12c 75.03 73.12 Unidentified or larger C 18 1.01 1.21 Total
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Abstract
Description
Die Erfindung befindet sich auf dem Gebiet der Nahrungsergänzungsmittel und betrifft ein Verfahren zur Herstellung von Rohstoffen für die Gewinnung von konjugierter Linolsäure.The invention is in the field of dietary supplements and concerns a process for producing raw materials for the production of conjugated linoleic acid.
Die mehrfach ungesättigten ω-3 und ω-6 Fettsäuren wie α-Linolensäure, Linolsäure zählen zu den für die Säugetiere und den Menschen essentiellen Fettsäuren. Neben der Linolsäure existieren in der Natur noch andere isomere Octadecadiensäuren. Diese zeichnen sich durch konjugierte Doppelbindungen an den C-Atomen 9 und 11, 10 und 12 sowie 11 und 13 aus. Diese isomeren Octadecadiensäuren werden in der wissenschaftlichen Literatur unter dem Begriff konjugierte Linolsäuren (Abkürzung: CLA - conjugated linoleic acid) zusammengefaßt und haben in letzter Zeit zunehmend Beachtung gefunden. NUTRITION, VOL: 19/NR. 6 1995.The polyunsaturated ω-3 and ω-6 fatty acids such as α-linolenic acid, linoleic acid count to the essential for mammals and humans fatty acids. In addition to linoleic acid There are other isomeric octadecadienoic acids in nature. Draw these by conjugated double bonds at the C atoms 9 and 11, 10 and 12 as well as 11 and 13 off. These isomeric octadecadienoic acids are used in scientific Literature under the term conjugated linoleic acids (abbreviation: CLA - conjugated linoleic acid) and have recently received increasing attention. NUTRITION, VOL: 19 / NR. 6 1995.
Über die Bedeutung der CLA auf den Organismus haben verschiedenen Arbeitsgruppen
berichtet neuerdings wurde von Shultz et al. über die hemmende Wirkung auf das in
vitro-Wachstum von menschlichen Krebszellen berichtet. Carcinogenesis 8, 1881-1887
(1987) und Cancer Lett. 63, 125-133 (1992).
Daneben weist CLA eine hohe antioxidative Wirkung auf, womit beispielsweise die Lipidperoxidation
gehemmt werden kann. Atherosclerosis 108, 19-25 (1994).The importance of CLA on the organism has been reported by several working groups. Shultz et al. reported the inhibitory effect on the in vitro growth of human cancer cells. Carcinogenesis 8, 1881-1887 (1987) and Cancer Lett. 63, 125-133 (1992).
In addition, CLA has a high antioxidant effect, which, for example, the lipid peroxidation can be inhibited. Atherosclerosis 108, 19-25 (1994).
Der Einsatz von konjugierter Linolsäure in der Tierfütterung und in diesem Zusammenhang auch in der menschlichen Ernährung ist z. B. aus der WO 96/06605 bekannt. In der EP 0579 901 B wird über den Einsatz von konjugierter Linolsäure zur Vermeidung eines Gewichtsverlustes bzw. einer Verringerung der Gewichtszunahme oder von Annorexia die durch Immunstimulation verursacht wurde bei Menschen oder Tieren berichtet. Die WO 94/16690 beschäftigt sich mit der Effizienzverbesserung der Nahrungsverwertung bei Tieren, indem eine wirksame Menge von konjugierter Linolsäure verabreicht wird. The use of conjugated linoleic acid in animal feed and in this context also in the human diet is z. B. from WO 96/06605 known. EP 0579 901 B reports on the use of conjugated linoleic acid for preventing weight loss or a reduction in weight gain or of annorexia caused by immune stimulation in humans or animals. WO 94/16690 is concerned with improving the efficiency of food utilization in animals by administering an effective amount of conjugated linoleic acid.
CLA wird durch eine sogenannte Konjugierung von linolsäurehaltigen Vorprodukten erhalten, d.h. Produkten enthaltend eine Carbonsäurefunktion mit 18-C-Atomen und 2 Doppelbindungen in 9- und 12-Position, die beide in der cis-Konfiguration vorliegen. Dabei ist während der Konjugierungsreaktion darauf zu achten, daß nur die beiden CLA-Hauptisomere (9cis,11trans und 10trans,12cis) entstehen, deren Wirkung in der oben genannten Literatur beschrieben ist. Ein Isomerengemisch, wie es CLA darstellt, die für technische Zwecke eingesetzt wird, so in der Lackherstellung wie z.B. Edenor®UKD 6010 (Hersteller: Cognis, Düsseldorf), ist unerwünscht.CLA is obtained by a so-called conjugation of linoleic acid-containing precursors, i.e. Products containing a carboxylic acid function with 18-carbon atoms and 2 9- and 12-position double bonds, both in the cis configuration. there Care must be taken during the conjugation reaction that only the two main CLA isomers (9cis, 11trans and 10trans, 12cis) arise, whose effect in the above described literature is described. A mixture of isomers, such as CLA, which is known for technical purposes is used, so in the paint production such. Edenor®UKD 6010 (Manufacturer: Cognis, Dusseldorf), is undesirable.
Die reine CLA wird vielfach durch Verseifung linolsäurehaltiger Öle gewonnen [WO 96/06605, EP 0902082 A1]. Nachteil dieser Verfahren ist der hohe Anteil unerwünschter Isomere. Diese können wiederum durch enzymatische Veresterung getrennt werden, wie in der WO 97/18320 beschrieben. Um den Gehalt an Isomeren besser zu steuern, kann auch über die entsprechenden Ester als Vorprodukte gegangen werden. Stand der Technik ist hier die Herstellung der entsprechenden Ester durch Veresterung der Fettsäuren mit Methanol oder Ethanol. In der Literatur ist beschrieben, dass als Ausgangsstoffe für eine schonende Konjugierung insbesondere die Methyl- und Ethylester von Linolsäure geeignet sind [WO 99/47135]. Einen Hinweis auf die besondere Eignung einer der Methoden zur Herstellung von Methyl- oder Ethyllinoleat mit möglichst hoher Reinheit bezüglich der 9cis,12cis-Konfiguration ist nicht bekannt. In der WO 99/47135 wird ein Verfahren zur Herstellung konjugierter Linolsäure beschrieben, indem eine Veresterung oder Umesterung unter nicht-wässrigen Bedingungen stattfindet, in der der erhaltene Alkylester nachfolgend in einem weiteren Schritt isomerisiert wird.The pure CLA is often obtained by saponification of linoleic acid-containing oils [WO 96/06605, EP 0902082 A1]. Disadvantage of these methods is the high proportion of undesired isomers. These can in turn be separated by enzymatic esterification, as described in WO 97/18320 . In order to better control the content of isomers, it is also possible to use the corresponding esters as precursors. The state of the art here is the production of the corresponding esters by esterification of the fatty acids with methanol or ethanol. It is described in the literature that suitable starting materials for gentle conjugation are in particular the methyl and ethyl esters of linoleic acid [WO 99/47135] . An indication of the particular suitability of one of the methods for the preparation of methyl or ethyl linoleate with the highest possible purity with respect to the 9cis, 12cis configuration is not known. In WO 99/47135 a process for the preparation of conjugated linoleic acid is described by esterification or transesterification taking place under non-aqueous conditions in which the resulting alkyl ester is subsequently isomerized in a further step.
Ein weiteres Problem bei der Herstellung von CLA bzw. CLA-Vorstufen besteht darin, dass die erforderliche Absenkung des C16-Gehaltes bei gleichzeitiger Anreicherung des C18:2-Anteils bislang ohne fraktionierte Destillation in einer Kolonne für die Gesamtmenge des Rohesters nicht zu bewerkstelligen ist. Statt dessen wird nur ein Teil des Reaktorinhaltes gegen Ende der Hauptlauf-Destillation fraktioniert, was dazu führt, dass die Ausbeuten nicht zufriedenstellend sind.Another problem in the production of CLA or CLA precursors is that that the required lowering of the C16 content with simultaneous accumulation of the C18: 2 fraction so far without fractional distillation in a column for the total amount of the raw ester can not be accomplished. Instead, only a part of the reactor contents fractionated towards the end of the mainstream distillation, which leads to the Yields are not satisfactory.
Die Aufgabe der vorliegenden Erfindung bestand darin, Rohstoffe für die Herstellung von
konjugierter Linolsäure (CLA), wie z.B. Methyl- oder Ethyllinoleat aus linolsäurereichen
Vorprodukten herzustellen, mit den Maßgaben, dass
Gegenstand der Erfindung ist ein Verfahren zur Herstellung von Rohstoffen für die Gewinnung
von konjugierter Linolsäure, welches sich dadurch auszeichnet, dass man
Dazu wird ein linolreiches Triglycerid, z.B. Sonnenblumenöl, vorzugsweise Saffloröl, vorzugsweise raffiniertes Saffloröl, mit Ethanol umgeestert. Gegenüber einer Veresterung mit Linolsäure ist überraschend zu beobachten, dass fast keine unerwünschten Vor-Konjugierungen und Isomerisierungen auftreten. Die Umesterung findet unter schonenden Bedingungen, ohne Einsatz von Inertgas oder Ethylen- oder Propylenglycol statt.For this, a linoleic triglyceride, e.g. Sunflower oil, preferably safflower oil, preferably refined safflower oil transesterified with ethanol. Across from esterification with linoleic acid is surprising to observe that almost no unwanted pre-conjugations and isomerizations occur. The transesterification takes place under mild conditions, without the use of inert gas or ethylene or propylene glycol instead.
Die erfindungsgemäß als Ausgangsmaterialien einzusetzenden Fettsäureglyceride können die üblichen natürlichen pflanzlichen oder tierischen Fette oder Öle sein. Hierzu gehören beispielsweise Linolaöl, Sonnenblumenöl und besonders bevorzugt Saffloröl. Die Hauptbestandteile dieser Fette und Öle sind Glyceride verschiedener Arten von Fettsäuren, die beträchtliche Mengen an Verunreinigungen wie etwa Aldehydverbindungen, Phospholipidverbindungen und freie Fettsäuren enthalten. Diese Materialien können direkt oder nach vorheriger Aufreinigung eingesetzt werden. Es handelt sich um Fettsäuremischungen, die mindestens 60, bevorzugt über 70 besonders bevorzugt mehr als 75 Gew.-% konjugierte Linolsäure enthalten. Die Umsetzung findet ohne Einsatz von Inertgas unter kontrollierten Bedingungen statt. Die Reaktion wird bevorzugt bei einer Temperatur im Bereich von 80 bis 120 °C, vorzugsweise 85 bis 100°C, besonders bevorzugt 88 bis 95°C durchgeführt. Das während der Reaktion anfallende Glycerin wird über einen Koaleszenzabscheider kontinuierlich abgezogen und ungefähr zwei Drittel der gesamten Katalysatormenge werden während der Reaktion kontinuierlich zugefügt. Als Katalysatoren eignen sich Alkali- und/oder Erdalkalimetallalkoholate oder -hydroxide, insbesondere Natriummethanolat und /oder Natriumglycerat und besonders bevorzugt Natriumethylat. Die Reaktion läuft über 4 bis 7 Stunden, vorzugsweise 5 bis 6 Stunden ab. Im letzten Schritt der Umesterung wird das Reaktionsgemisch mit Citronensäure neutralisiert. Unter Berücksichtigung der bevorzugt eingesetzten Reaktionsprodukte dient das Verfahren besonders bevorzugt zur Herstellung eines Safflorethyl-esters mit einem geringen Gehalt an unerwünschten Isomeren.The fatty acid glycerides to be used according to the invention as starting materials can be the usual natural vegetable or animal fats or oils. These include For example, linola oil, sunflower oil and particularly preferably safflower oil. The main ingredients These fats and oils are glycerides of various types of fatty acids that considerable amounts of impurities such as aldehyde compounds, phospholipid compounds and contain free fatty acids. These materials can be direct or be used after prior purification. These are fatty acid mixtures, the at least 60, preferably more than 70, more preferably more than 75 wt.% Contain conjugated linoleic acid. The reaction takes place without the use of inert gas controlled conditions. The reaction is preferably carried out at a temperature in the Range of 80 to 120 ° C, preferably 85 to 100 ° C, particularly preferably 88 to 95 ° C. carried out. The glycerol accumulating during the reaction is passed through a coalescence separator withdrawn continuously and about two thirds of the total amount of catalyst are added continuously during the reaction. Suitable as catalysts alkali and / or alkaline earth metal alkoxides or hydroxides, especially sodium methoxide and / or sodium glycerate, and more preferably sodium ethylate. The Reaction proceeds over 4 to 7 hours, preferably 5 to 6 hours. In the last step the transesterification, the reaction mixture is neutralized with citric acid. Considering the preferred reaction products used the process is particularly preferred for the preparation of a safflorethyl ester with a low content on undesired isomers.
Die Destillation des umgeesterten Reaktionsgemisches dient der Abtrennung von anfallenden Glyceriden, freiem Glycerin und Seifen. Das Reaktionsprodukt bekommt außerdem eine ansprechendere Farbe. In Abhängigkeit vom Rohstoff kann bei der Produktdestillation des Weiteren der Gehalt an Palmitinsäure gesenkt und der Gehalt an Linolsäure gesteigert werden. Beginnend wird nach Anlegen eines Vakuums von 100 bis 300 mbar der überschüssige Ethanol abdestilliert. Zusätzlich bei der Ethanoldestillation anfallendes freies Glycerin wird über den Abscheider abgetrennt. Im weiteren Verlauf wird bei einem Vakuum von 1 bis 3 mbar die Temperatur auf 150 bis 200 °C, bevorzugt 160 bis 180 °C angehoben. 5 bis 10 % Vorlauf werden entnommen und das Produkt bis auf 5 bis 10% Rückstand destilliert. Um eine möglichst hohe Ausbeute zu erlangen, kann vorzugsweise eine fraktionierte Destillation angewendet werden. Zur gleichzeitigen Absenkung des C16-Gehaltes und Anreicherung des C18:2-Anteils hat es sich ferner als vorteilhaft erwiesen, entweder eine Batch-Destillation aus einem Reaktor mit aufgesetzter Kolonne durchzuführen, was dazu führt, dass der C16-Gehalt im Vorlaufdestillat ansteigt, oder die Destillation zweistufig durchzuführen, wobei man etwa 5 bis 10 Vol.-% des Vorlaufs von der Fraktionierkolonne abnimmt und den Hauptlauf über den Kolonnenkopf destilliert. Insbesondere bei letzterer lässt sich der Gehalt an C16 im Hauptlauf gegenüber einem Ausgangswert von 6,5 bis auf 0,7 Gew.-% erniedrigen, während gleichzeitig die Menge an C18:2 von 75,5 auf 81,4 Gew.-% ansteigt. The distillation of the transesterified reaction mixture is used to separate off any resulting Glycerides, free glycerin and soaps. The reaction product gets as well a more appealing color. Depending on the raw material can during product distillation further decreased the content of palmitic acid and the content of linoleic acid be increased. Starting after applying a vacuum of 100 to 300 mbar distilled off the excess ethanol. Additionally incurred in the ethanol distillation free glycerol is separated via the separator. In the further course becomes at a vacuum of 1 to 3 mbar, the temperature to 150 to 200 ° C, preferably 160 raised to 180 ° C. 5 to 10% flow are taken and the product up on Distilled 5 to 10% residue. In order to achieve the highest possible yield, can preferably a fractional distillation can be used. For simultaneous lowering of the C16 content and enrichment of the C18: 2 portion, it has also as proved advantageous, either a batch distillation from a reactor with attached Carry out column, which causes the C16 content in the feed distillate increases, or to carry out the distillation in two stages, whereby about 5 to 10% by volume of the forerun from the fractionation column decreases and the main run over the top of the column distilled. Especially with the latter, the content of C16 in the main run can be decrease from an initial value of 6.5 to 0.7% by weight while at the same time the amount of C18: 2 increases from 75.5 to 81.4 wt .-%.
Unter konjugierter Linolsäure sind erfindungsgemäß vorzugsweise die Hauptisomeren 9cis,11trans Octadecadiensäure und 10trans,12cis sowie jedoch beliebige Isomerenmischungen, wie sie üblicherweise bei der Herstellung konjugierter Linolsäure anfallen. Die durch das erfindungsgemäße Verfahren hergestellten Rohstoffe sollen bereits einen hohen Anteil der bevorzugten Isomere enthalten.Among conjugated linoleic acid according to the invention are preferably the main isomers 9cis, 11trans octadecadienoic acid and 10trans, 12cis and also any isomer mixtures, as they usually occur in the production of conjugated linoleic acid. The The raw materials produced by the process according to the invention should already have a high Contain proportion of preferred isomers.
Das erfindungsgemäße Verfahren dient der Herstellung von Rohstoffen zur Gewinnung von konjugierter Linolsäure (CLA). Der geringe Anteil an unerwünschten Isomeren im Rohprodukt erspart weitere Schritte zur Isomerentrennung und -reinigung bei der Herstellung der CLA. Die aus den Rohstoffen hergestellte CLA kann in all jenen Bereichen, die aus der Literatur für konjugierte Linolsäure bereits bekannt sind, zum Beispiel in Lebensmitteln, vorzugsweise sogenannten "Functional Foods" sowie in Pharmaka, hierbei insbesondere als unterstützendes Agens bei der Tumorbehandlung oder auch zur Behandlung von Personen die an katabolischen Zuständen leiden, Einsatz finden. The process of the invention is used to produce raw materials for recovery of conjugated linoleic acid (CLA). The low proportion of unwanted isomers in Crude product saves further steps for isomer separation and purification during production the CLA. The CLA produced from the raw materials can be used in all those areas which are already known from the literature for conjugated linoleic acid, for example in foods, preferably so-called "functional foods" and in pharmaceuticals, hereby in particular as a supportive agent in the treatment of tumors or for treatment of persons suffering from catabolic states.
Beispiel 1 (Umesterung). Der Versuchsaufbau für die Umesterung bestand aus einem
2 l Reaktor (Doppelmantel) mit Rückflußkühler, Koaleszenzabscheider im Recyclekreislauf
und Vakuumpumpe. Als Einsatzstoffe wurden 1500 g Saffloröl, 240 g Ethanol,
47 g Natriumethylat in Form einer 20 gew.-%igen ethanolischen Lösung (z.T. während
der Reaktion nachträglich zudosiert) und Citronensäure, ebenfalls in einer 20 Gew.-%igen
ethanolischen Lösung eingesetzt). Die Reaktion wurde bei Umgebungsdruck
durchgeführt. Dazu wurde das linolreiche Öl vorgelegt, auf 60 °C erwärmt und Ethanol
und ungefähr ein Drittel der Na-Ethylat-Menge hinzugegeben. Der Reaktorinhalt wurde
auf ca. 90 °C Reaktionstemperatur aufgeheizt und die Reaktion unter Rückfluß betrieben.
Unter laufender Umwälzpumpe (Umwälzrate 8 l/h) wurde während der Reaktion die
anfallende Glycerinphase abgezogen und kontinuierlich alle 30 min. ca. 4 g KatalysatorLösung
zudosiert. Die Reaktionszeit betrug 5,5 h. Das Reaktionsgemisch wurde anschließend
mit Citronensäure neutralisiert. Zur Abtrennung von Glyceriden, freiem Glycerin
und Seifen wurde eine Destillation angeschlossen. Bei 100-300 mbar Vakuum wurde der
überschüssige Ethanol entfernt. Außerdem wurde durch Auskreisen über den Abscheider
zusätzliches freies Glycerin, das durch die Ethanoldestillation anfiel, abgetrennt. Die
Sumpftemperatur wurde dann bei einem Vakuum von 1-3 mbar auf 160-180°C angehoben,
5-10 % Vorlauf entnommen und danach der Hauptlauf bis auf 5 -10 % Rückstand
destilliert. Die Bestimmung der Isomeren und Fettsäurefraktionen wurde mit einem
chromatographischen Verfahren durchgeführt. Verwendet wurde eine 120m lange Silicasäule
(120m*0.25mm Permabond® FFAP - 0.25 µm, Bezug: Macherey Nagel) mit Wasserstoff
als Trägergas. Die Zusammensetzung des Produktes ist in Tabelle 1 wiedergegeben:
Vergleichsbeispiel V1 (Veresterung). Der Versuchsaufbau für die Veresterung (Betrieb
nach dem Blasenreaktorprinzip) bestand aus einem beheizbaren 2l Reaktor mit
aufgesetztem Destillatkühler und -falle, Sumpftemperaturmessung und -regelung über
Heizpilz, Tauchrohr für N2-Eintrag, Glasfritte und Dosimat für Ethanolzudosierung und
einer Vakuumpumpe. Als Einsatzstoffe wurden 1000 g Sonnenblumenöl-Fettsäure (Edenor®
Sb, Cognis GmbH Deutschland), 1000 g Ethanol (kontinuierlich zudosiert), 2,5 g p-Toluolsulfonsäure
und Natronlauge in Form einer 6 Gew.-%igen wässrigen Lösung verwendet.
Die Reaktion wurde bei Umgebungsdruck betrieben. Dazu wurden Edenor® Sb
und p-Toluolsulfonsäure im Reaktor vorgelegt, Stickstoff kontinuierlich über ein Tauchrohr
zugeführt und der Reaktorinhalt auf 170 °C aufgeheizt. Es wurde begonnen mit
einer Ethanol-Zudosierung von 170 ml/h und durch Unterbrechung der Ethanolzudosierung
der Reaktionsabbruch bei einer Säurezahl von < 1 nach etwa 6 h vollzogen. Der
überschüssige Ethanol wurde abdestilliert und der Reaktor auf 80 °C abgekühlt. Nach
der Wäsche mit Natronlauge( doppelte stöchiometrische Menge an Lauge) wurde das
Produkt bei 200 mbar getrocknet. Die Sumpftemperatur wurde bei einem Vakuum von 1-3
mbar auf 160-180°C angehoben, 5-10 % Vorlauf entnommen und danach der Hauptlauf
bis auf 5 -10 % Rückstand destilliert. Die Zusammensetzung des Produktes ist in
Tabelle 2 wiedergegeben:
Vergleich Veresterung und Umesterung. In Tabelle 3 ist ein Vergleich der Isomere
und CLA aus dem Reaktionsprodukt der Umesterung und der Veresterung unter Berücksichtigung
des unterschiedlichen Ölsäure/Linolsäure-Verhältnisses in den eingesetzten
Rohstoffen angegeben:
Claims (7)
- A process for the production of raw materials for the production of conjugated linoleic acid, characterized in that(a) triglycerides containing at least 60% by weight linoleic acid are transesterified with ethanol at a temperature of 80 to 120°C and(b) the transesterification mixture thus obtained is subjected to distillation.
- A process as claimed in claim 1, characterized in that sunflower oil is used as the triglyceride.
- A process as claimed in claims 1 and/or 2, characterized in that safflower oil is used as the triglyceride.
- A process as claimed in at least one of claims 1 to 3, characterized in that sodium methylate is continuously added as catalyst during the reaction.
- A process as claimed in at least one of claims 1 to 4, characterized in that(a) an oil rich in linoleic acid is heated to 50 - 70°C and ethanol and sodium ethylate are added,(b) the entire contents of the reactor are then heated to 80 - 120°C and the reaction(c) is carried out under reflux over 5 to 6 hours with removal of the glycerol phase accumulating while catalyst solution is continuously added and(d) the reaction mixture is then neutralized with citric acid.
- A process as claimed in at least one of claims 1 to 5, characterized in that, after the transesterification, residual glycerides, free glycerol and soaps are removed by(a) distilling off the excess ethanol under a vacuum of 100 to 300 mbar and(b) then distilling the remaining product to a residue of 5 to 10% under a vacuum of 1 to 3 mbar and at a temperature of 150 to 200°C.
- A process as claimed in at least one of claims 1 to 6, characterized in that the transesterification mixture obtained is subjected to fractional distillation.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE10046402 | 2000-09-18 | ||
| DE10046402A DE10046402B4 (en) | 2000-09-18 | 2000-09-18 | Process for the preparation of raw materials for the production of conjugated linoleic acid |
| PCT/EP2001/010377 WO2002022768A1 (en) | 2000-09-18 | 2001-09-08 | Method for producing starting materials for obtaining conjugated linoleic acid |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| EP1319057A1 EP1319057A1 (en) | 2003-06-18 |
| EP1319057B1 true EP1319057B1 (en) | 2005-11-23 |
Family
ID=7656835
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EP01972028A Expired - Lifetime EP1319057B1 (en) | 2000-09-18 | 2001-09-08 | Method for producing starting materials for obtaining conjugated linoleic acid |
Country Status (9)
| Country | Link |
|---|---|
| US (1) | US6762313B2 (en) |
| EP (1) | EP1319057B1 (en) |
| JP (1) | JP2004529211A (en) |
| AT (1) | ATE310790T1 (en) |
| CA (1) | CA2422804C (en) |
| DE (2) | DE10046402B4 (en) |
| ES (1) | ES2252296T3 (en) |
| NO (1) | NO20031225L (en) |
| WO (1) | WO2002022768A1 (en) |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE10225117A1 (en) * | 2002-06-06 | 2004-01-08 | Cognis Deutschland Gmbh & Co. Kg | Process for the production of conjugated linoleic acid |
| BR0318676A (en) * | 2003-12-23 | 2006-11-28 | Stepan Co | production and purification of conjugated linoleic acid esters |
| US7767713B2 (en) * | 2004-08-05 | 2010-08-03 | Palo Alto Investors | Linoleic acid active agents for enhancing probability of becoming pregnant |
| KR101282098B1 (en) * | 2005-02-04 | 2013-07-04 | 안칭 중창 바이오테크놀로지 컴파니 리미티드 | Process for the preparation of fatty acids |
| US20070087085A1 (en) * | 2005-10-17 | 2007-04-19 | Bunge Oils, Inc. | Protein-containing food product and coating for a food product and method of making same |
| US20080113067A1 (en) * | 2005-10-17 | 2008-05-15 | Monoj Sarma | Protein-Containing Food Product and Coating for a Food Product and Method of Making Same |
| WO2007070302A2 (en) | 2005-12-05 | 2007-06-21 | Stepan Company | Process for preparing conjugated linoleic acid and derivatives thereof from ricinoleic acid |
| US20070148311A1 (en) * | 2005-12-22 | 2007-06-28 | Bunge Oils, Inc. | Phytosterol esterification product and method of make same |
| JP5282951B2 (en) * | 2008-10-01 | 2013-09-04 | 国立大学法人山口大学 | Method for producing fatty acid alkyl ester |
| CN105481682A (en) * | 2014-09-19 | 2016-04-13 | 浙江医药股份有限公司新昌制药厂 | Method for preparing high-content conjugated linoleic acid using vegetable oil as raw material by means of purification |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ZA816488B (en) | 1980-09-18 | 1982-09-29 | Chemical Services Pty Ltd | Liquid fuel |
| DE4124517A1 (en) | 1991-07-24 | 1993-01-28 | Battelle Institut E V | Sepn. of reactive fatty acids or ester(s) from their mixts. - by fractional distn. under vacuum of mixt. obtd. by saponification or transesterification of natural oil |
| ES2065666T3 (en) * | 1991-09-02 | 1995-02-16 | Primavesi Markus | PROCEDURE AND DEVICE FOR THE CONTINUOUS PREPARATION OF ESTERS OF FATTY ACIDS. |
| US5554646A (en) | 1992-04-29 | 1996-09-10 | Wisconsin Alumni Research Foundation | Method for reducing body fat in animals |
| US5430066A (en) | 1992-04-29 | 1995-07-04 | Wisconsin Alumni Research Foundation | Methods for preventing weight loss, reduction in weight gain, and anorexia due to immune stimulation |
| US5428072A (en) | 1992-04-29 | 1995-06-27 | Wisconsin Alumni Research Foundation | Method of increasing the efficiency of feed conversion in animals |
| EP0866874B2 (en) | 1995-11-14 | 2005-06-22 | Loders Croklaan B.V. | Process for the preparation of materials with a high content of isomers of conjugated linoleic acid |
| CA2246085C (en) | 1997-09-12 | 2004-04-27 | Krish Bhaggan | Production of materials rich in conjugated isomers of long chain polyunsaturated fatty acid residues |
| US7078051B1 (en) * | 1998-08-11 | 2006-07-18 | Natural Asa | Conjugated linoleic acid alkyl esters in feedstuffs and food |
| US6015833A (en) * | 1998-03-17 | 2000-01-18 | Conlinco., Inc. | Conjugated linoleic acid compositions |
| JP2000516480A (en) | 1998-03-17 | 2000-12-12 | コンリンコ，インコーポレイテッド | Conjugated linoleic acid composition |
-
2000
- 2000-09-18 DE DE10046402A patent/DE10046402B4/en not_active Expired - Fee Related
-
2001
- 2001-09-08 CA CA2422804A patent/CA2422804C/en not_active Expired - Lifetime
- 2001-09-08 DE DE50108194T patent/DE50108194D1/en not_active Expired - Lifetime
- 2001-09-08 AT AT01972028T patent/ATE310790T1/en not_active IP Right Cessation
- 2001-09-08 US US10/380,564 patent/US6762313B2/en not_active Expired - Lifetime
- 2001-09-08 JP JP2002527007A patent/JP2004529211A/en active Pending
- 2001-09-08 WO PCT/EP2001/010377 patent/WO2002022768A1/en active IP Right Grant
- 2001-09-08 EP EP01972028A patent/EP1319057B1/en not_active Expired - Lifetime
- 2001-09-08 ES ES01972028T patent/ES2252296T3/en not_active Expired - Lifetime
-
2003
- 2003-03-17 NO NO20031225A patent/NO20031225L/en not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| NO20031225D0 (en) | 2003-03-17 |
| EP1319057A1 (en) | 2003-06-18 |
| WO2002022768A1 (en) | 2002-03-21 |
| US6762313B2 (en) | 2004-07-13 |
| DE10046402B4 (en) | 2006-04-20 |
| ES2252296T3 (en) | 2006-05-16 |
| JP2004529211A (en) | 2004-09-24 |
| NO20031225L (en) | 2003-03-17 |
| CA2422804A1 (en) | 2003-03-18 |
| DE50108194D1 (en) | 2005-12-29 |
| US20030181522A1 (en) | 2003-09-25 |
| DE10046402A1 (en) | 2002-04-04 |
| CA2422804C (en) | 2011-08-02 |
| ATE310790T1 (en) | 2005-12-15 |
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