U.S. patent application number 09/367836 was filed with the patent office on 2002-04-18 for process for the preparation of stanol esters.
Invention is credited to EKBLOM, JARI.
Application Number | 20020045773 09/367836 |
Document ID | / |
Family ID | 8548283 |
Filed Date | 2002-04-18 |
United States Patent
Application |
20020045773 |
Kind Code |
A1 |
EKBLOM, JARI |
April 18, 2002 |
PROCESS FOR THE PREPARATION OF STANOL ESTERS
Abstract
The invention relates to a process for the preparation of stanol
esters by hydrogenating a sterol blend in a hydrogenation solvent
and at an elevated temperature in the presence of a hydrogenation
catalyst, by removing the hydrogenation catalyst from the obtained
hot reaction solution, by transesterifying the intermediate stanol
blend with a fatty acid methyl ester at an elevated temperature and
in the presence of a transesterification catalyst, and by finally
purifying the stanol ester blend thus obtained. According to the
invention, the intermediate stanol blend is neither crystallized
nor removed from the reaction solution but the hydrogenation
solvent is replaced therein at least in part by a
transesterification reagent. Alternatively, the hydrogenation
solvent may also be used as the transesterification solvent, and
preferably also as the transesterification reagent.
Inventors: |
EKBLOM, JARI; (RASIO,
FI) |
Correspondence
Address: |
NIKAIDO MARMELSTEIN MURRAY & ORAM
METROPOLITAN SQUARE
655 FIFTEENTH STREET NW
SUITE 330 G STREET LOBBY
WASHINGTON
DC
200055701
|
Family ID: |
8548283 |
Appl. No.: |
09/367836 |
Filed: |
November 22, 1999 |
PCT Filed: |
February 25, 1998 |
PCT NO: |
PCT/FI98/00166 |
Current U.S.
Class: |
552/544 |
Current CPC
Class: |
C07J 9/00 20130101 |
Class at
Publication: |
552/544 |
International
Class: |
C07J 009/00 |
Foreign Application Data
Date |
Code |
Application Number |
Feb 26, 1997 |
FI |
970802 |
Claims
1. A process for the preparation of stanol esters by hydrogenating
at least one sterol in a solvent and at an elevated temperature in
the presence of a hydrogenation catalyst, to form respectively at
least one stanol, by removing the hydrogenation catalyst from the
obtained reaction solution, by transesterifying the said at least
one stanol with a lower alkyl ester at an elevated temperature and
in the presence of a transesterification catalyst, and by purifying
the stanol ester or stanol ester blend thus obtained, characterized
in that the hydrogenation solvent is left in the reaction solution
from which the hydrogenation catalyst has been removed, and the
hydrogenation solvent a) is replaced therein at least in part by a
transesterification reagent and/or b) is used as a solvent also in
the transesterification and preferably at the same time as the
transesterification reagent.
2. A process according to claim 1, characterized in that a fatty
acid methyl ester of vegetable oil origin is used as the
transesterification reagent and possibly as the hydrogenation
solvent.
3. A process according to claim 2, characterized in that the
hydrogenation solvent is lower boiling than the transesterification
reagent and is removed by fractional distillation from the reaction
solution, to which a transesterification reagent is added or has
been added.
4. A process according to claim 3, characterized in that a coconut
fatty acid methyl ester is used as the hydrogenation solvent and a
rapeseed oil fatty acid methyl ester as the transesterification
reagent.
5. A process according to claim 1, characterized in that an alcohol
or a high boiling aliphatic hydrocarbon free of aromatic compounds
is used as the hydrogenation solvent and at the same time as the
transesterification solvent.
6. A process according to any of the above claims, characterized in
that a noble metal catalyst, preferably palladium on carbon or on
an organic polymer compound, is used as the hydrogenation
catalyst.
7. A process according to claim 6, characterized in that the
hydrogen catalyst is used in an amount of 0.1-2% active ingredient
of the weight of the sterol to be hydrogenated.
8. A process according to any of the above claims, characterized in
that the hydrogenation is carried out at a temperature of at most
about 120.degree. C., and the hydrogenation catalyst is removed
from the hot reaction solution, preferably by filtration.
9. A process according to any of the above claims, characterized in
that an alkali metal alcoholate, preferably sodium methylate or
sodium ethylate, is used as the transesterification catalyst.
10. A process according to claim 9, characterized in that the
transesterification catalyst is used in an amount of 0.1-1% of the
weight of the reaction solution.
11. A process according to any of the above claims, characterized
in that the transesterification is carried out at 100-130.degree.
C. and by using a stoichiometric excess of the transesterification
catalyst relative to the stanol or the stanol blend.
12. A process according to any of the above claims, characterized
in that a sterol blend is hydrogenated which contains primarily
sitosterol and additionally campesterol and possibly
stigmasterol.
13. A process according to claim 12, characterized in that a sterol
blend based on tall oil or vegetable oil is hydrogenated.
Description
[0001] The present invention relates to a process for the
preparation of stanol esters, and in particular to a process
wherein stanol esters are prepared by hydrogenating at least one
sterol in a solvent and at an elevated temperature in the presence
of a hydrogenation catalyst to the corresponding stanol or stanol
blend, by removing the hydrogenation catalyst from the obtained
reaction solution, by transesterifing the stanol or the stanol
blend with a lower alkyl ester at an elevated temperature and in
the presence of a transesterification catalyst, and by finally
purifying the stanol ester or stanol ester blend thus obtained.
[0002] Sterols are compounds commonly present in plants and
animals, although in small concentrations. The sterol compound most
commonly present in animals is cholesterol. The sterol material
present in plants is usually composed of several sterol structures
which resemble each other structurally. The most common of the
latter are .beta.-sitosterol, campesterol and stigmasterol.
Depending on the plant species, there may also be present numerous
other compounds resembling the above-mentioned sterols, for example
brassicasterol in rape, .alpha.-sitosterol and betulinol in birch,
methylene cycloartanol and cycloartenol, avenasterols, etc.
[0003] The sterols of wood material also include saturated sterol
compounds wherein particularly the double bond between carbon atoms
5 and 6 of the sterol structure is hydrogenated to a saturated
carbon-carbon bond. These compounds are called stanols. The stanol
corresponding to the most common plant sterol, .beta.-sitosterol,
is thus .beta.-sitostanol. Hydrogenation of sterols is described
e.g. in Organic Preparations and Procedures 1 (2) (1969) 107-109
(Augustine, R. L. and Reardon Jr. E. J.: The Palladium catalyzed
hydrogenation of cholesterol) and Atherosclerosis 24 (1975) 301-309
(Sugano, M. et al.: Lipid-lowering activity of phytosterols in
rats).
[0004] Cholesterol is a compound indispensable for human subjects,
as for other vertebrates, for example as an ingredient of cell
structures. In high concentrations, however, cholesterol is
detrimental, since it accumulates on the walls of blood vessels and
thereby increases the risk of cardiovascular diseases.
[0005] It has been observed in investigations that plant sterol
compounds, and in particular plant stanol compounds, added to the
diet lower the blood serum cholesterol concentration in human
subjects. When it is desired to use compounds derived from plant
sterols for the lowering of cholesterol levels, it is important in
terms of the efficacy and usability of the said compounds that they
are in a suitable chemical and physical form.
[0006] U.S. Pat. No. 5,502,045 (Miettinen, T., et al.) suggests
that the most advantageous form of use of plant sterol compounds is
the intake of these compounds in the form saturated to stanols and
esterified with fatty acids, in which case, on the one hand, the
functional efficacy of the compounds is highest and, on the other
hand, being fat-soluble they can easily be added to various
foods.
[0007] The method conventionally used for preparing the compounds
concerned, so-called stanol esters, is a procedure according to
which the sterol is first hydrogenated catalytically in a
hydrogenation solvent. The hydrogenated sterol (stanol) is
crystallized and subsequently isolated by filtration from the
reaction mixture, and is thereafter transferred to a
transesterification process, in which the transesterification
reagent is typically a vegetable oil methyl ester. (South African
patent ZA 96/7616, Wester, I. et al.).
[0008] The preparation method described above, known per se, has
the disadvantage that the price of the stanol ester produced by the
method becomes relatively high owing to the high investment costs
required by the filtration of the crystallized stanol intermediate.
It has been thought that in order to obtain a sufficiently pure end
product the stanol intermediate must be isolated from the reaction
mixture before the transesterification process.
[0009] The object of the present invention is thus to provide a
more advanced method than previously for the preparation of
fat-soluble stanol esters, simplifying the preparation process of
stanol esters and thereby lowering the investment costs of the
plant for the preparation of stanol esters and, owing to the almost
quantitative yield, at the same time maximizing the production of a
stanol ester end product of a sufficiently high quality.
[0010] The present invention thus provides a stanol ester
preparation method of the type mentioned in the preamble, the
principal characteristics of the process being stated in the
accompanying claims.
[0011] The invention is based on the idea that the investment costs
of a plant for the preparation of stanol esters can be lowered
substantially by omitting the crystallization of the stanol
intermediate and the filtration of the crystalline stanol
intermediate from the reaction mixture, when the hydrogenation
solvent is left in the reaction solution from which the
hydrogenation catalyst has been removed. When necessary, the
hydrogenation solvent is removed from the reaction mixture only
after adding the transesterification reagent and the
transesterification solvent, if any, to the reaction mixture.
Preferably, however, the hydrogenation solvent used is one which
serves as the solvent and reagent also in the
transesterification.
[0012] When the stanol formed as an intermediate in the
hydrogenation reaction is not isolated from the reaction mixture
before the transesterification step, there is achieved not only a
lowering of the investment costs but also a nearly quantitative
yield of the end product, since yield losses relating to the
intermediate are avoided, which losses would otherwise be
inevitable in the isolation and filtration of the crystalline
intermediate.
[0013] In an especially preferred embodiment of the invention, a
fatty acid methyl ester of vegetable oil origin is used as the
transesterification reagent and possibly as the hydrogenation
solvent. It is especially advantageous to use a hydrogenation
solvent having a lower boiling point than the transesterification
reagent, in which case the hydrogenation solvent can be removed by
distillation from a reaction solution to which the
transesterification reagent is added or has been added. In this
manner, the passing of saturated fatty acids to the stanol ester
end product is avoided. In this case the hydrogenation solvent used
is preferably a methyl ester of coconut fatty acids or palm kernel
oil fatty acids, whereas the transesterification reagent is a
methyl ester of rapeseed oil fatty acids. The source of the fatty
acid or fatty acid blend alcohol ester used as the
transesterification reagent may be the fatty acids of any fat, oil,
or blends thereof.
[0014] Stanol esters can indeed be prepared according to the
invention, without the crystallization and isolation of stanols,
also by using conventional hydrogenation solvents instead of fatty
acid methyl esters. In this case the suitable solvents include
alcohols, hydrocarbons and ethers, such as tetrahydrofuran. It is
particularly advantageous to use a high boiling aromate-free and
thus inert aliphatic hydrocarbon as the hydrogenation solvent,
since it does not react with the transesterification reagent in the
transesterification step. This alternative is preferable when it is
desired to prevent the incorporation of saturated fatty acids into
the stanol ester product. In this case, the fatty acid methyl ester
used in the transesterification is added to the post-hydrogenation
reaction mixture from which the hydrogenation catalyst has been
removed, and thereafter the hydrogenation solvent is removed by
distillation before the actual transesterification. The use of
fatty acid methyl esters can, however, be justified, since they
have a higher flash point than have conventional solvents, such as
n-propanol, which means improved fire safety.
[0015] The hydrogenation catalyst used is preferably a noble metal
catalyst, such as palladium on carbon or on an organic polymer
compound. The hydrogenation is preferably carried out at a
temperature of at most about 120.degree. C., but the hydrogen
pressure may vary in a wide range. Also the amount of the
hydrogenation catalyst used in the reaction may vary, but may
preferably be used in an amount of 0,1-2% active ingredient of the
weight of the sterol to be hydrogenated. By this selection of
hydrogenation conditions, the hydrogenation can be carried out at a
high concentration of solids, rapidly, and without the formation of
detrimental degradation products.
[0016] At the end of the hydrogenation reaction, the hydrogenation
catalyst is removed by filtration from the hot reaction mixture.
The filtration of the hydrogenation catalyst is problem-free and
does not require high investments.
[0017] The transesterification catalyst used is preferably an
alkali metal alcoholate, such as sodium methylate or sodium
ethylate. In this case the amount of transesterification catalyst
is preferably 0.1-1% of the weight of the reaction solution.
[0018] The transesterification is preferably carried out at
100-130.degree. C. and by using a stoichiometric excess of the
transesterification reagent, for example a double excess, relative
to the stanol or the stanol blend.
[0019] In the process according to the invention, the starting
substance used may be any sterol or sterol blend obtainable from
plants, and in principle also animal sterols, for example
cholesterol or lanosterol. Preferably, however, a sterol blend is
hydrogenated which contains mainly sitosterol and additionally
campesterol and possibly stigmasterol. Especially preferably, a
sterol blend based on tall oil or vegetable oil is
hydrogenated.
[0020] It has now been shown, surprisingly, that even if the
crystallization of the stanol intermediate and the removal of the
crystals by filtration, regarded as indispensable in the prior
known method for the preparation of stanol esters, are omitted, the
stanol ester end product can, however, be recovered in a
sufficiently pure state and, above all, with a higher yield, by
using after the transesterification step purification processes
known per se. Even if the concentration of impurities (e.g.
dehydrogenation products of tocopherols and sterols, long-chained
hydrocarbons, and fatty alcohols) formed in the reaction and
brought in by the raw materials were rather high, their removal by
the method according to the invention is possible by using, for
example, steam distillation and adsorption, known per se. In
addition to these purification procedures, for example, thin film
evaporation can also be used.
Detailed Description of the Invention
[0021] In the first step of the reaction series, the hydrogenation,
it is preferable to use as catalyst a noble metal catalyst such as
palladium, platinum or ruthenium. Also possible is, for example,
Raney nickel, cobalt, or copper chromite compounds. The catalyst
support may be, for example, carbon, alumina, silica gel, or an
organic polymeric compound.
[0022] The hydrogenation is most preferably carried out at a
temperature below about 120.degree. C. The pressure in the reaction
mixture may vary widely. The catalyst concentration may also vary
within a wide range. By keeping the temperature about the above
mentioned level the formation of by-products (e.g. splitting off
reactions of hydroxyl) is most effectively avoided.
[0023] By an appropriate selection of the hydrogenation conditions,
a situation is thus arrived at wherein the hydrogenation can be
carried out at a high solids concentration, rapidly, and without
the formation of detrimental degradation products.
[0024] When the hydrogenation reaction has been brought to
completion, the hydrogenation catalyst is removed from the hot
reaction mixture by filtration.
[0025] If the removal of a portion of the hydrogenation solvent
(methyl ester or some other solyent) is desired before the
transesterification, it must be done in the subsequent step. This
is done by adding the fatty acid methyl ester to be used in the
transesterification to the hydrogenation reaction mixture before
the distillation or simultaneously with the distillation. The
conditions used in the distillation of the solvent are, of course,
dependent on the physical properties of the solvent used. It is,
however, a marginal condition that the boiling point of the
hydrogenation solvent must deviate sufficiently (must be lower)
from the boiling point of the fatty acid ester serving as the
reagent, in order for fractional removal of the hydrogenation
solvent to be possible.
[0026] The next step in the preparation of stanol ester is the
transesterification of the stanol with the fatty acid ester
contained in the reaction solution.
[0027] The esterification reaction per se may take place under the
effect of any reagent catalyzing transesterification (examples
include inorganic acids, toluene sulfonic acids, organostannates or
alkaline catalysts). However, it is especially preferable to use in
the transesterification alkali metal alcoholates, for example,
sodium methylate or sodium ethylate, transesterification catalysts
well known per se from the literature in the field. The catalyst
concentration and the other reaction conditions required vary
largely as a function of the type of catalyst used. In a reaction
occurring under the effect of sodium methylate it is preferable to
use the catalyst in an amount of approx. 0.1-1% of the amount of
the reaction mixture. The temperature being approx. 100-130.degree.
C., the reaction occurs completely within approx. 60-180 min when
an approx. double stoichiometric excess of the fatty acid methyl
ester relative to the stanol amount is used in the
transesterification.
[0028] After the reaction step, the impurities formed in the
reaction and brought in with the raw material (catalysts, sterol
degradation products, etc.) can be removed by means of water washes
and by water vapor distillation and additionally, when necessary,
by causing the impurities to be absorbed into a suitable absorbent
material (examples include activated carbon and/or bleaching
earth). Steam distillation is a necessary purification step also
for the removal of any reagent excess. Suitable conditions in the
steam distillation step, when the reagent is the methyl ester of
rapeseed fatty acids, are: temperature 180-230.degree. C., pressure
1-10 mbar, and the amount of steam to be fed approx. 2-10% of the
total amount of the reaction mixture.
[0029] Examples on the preparation of stanol esters according to
the invention are presented below.
EXAMPLE 1
[0030] 300 g of a sterol derived from tall oil (10%
campesterol/stanol, 90% .beta.-sitosterol/stanol) was slurried into
700 g of coconut fatty acid methyl ester (which contains primarily
C.sub.6-C.sub.14 fatty acid esters). A Pd catalyst bound to
polypropylene fiber, Smop-20 (manufacturer Smoptech, Turku,
Finland), was added in an amount of 0.7% of the amount of sterol,
the temperature was raised to 120.degree. C., and the reaction
autoclave was rinsed with nitrogen. Thereafter hydrogen was
directed to the reaction mixture for 130 min. During the
hydrogenation the pressure of the reaction mixture varied within a
range of 1-2 atm. The hydrogenation catalyst was removed by
distillation from the hot reaction mixture. Thereafter 360 g of
rapeseed oil fatty acid methyl ester was directed to the reaction
mixture, and the coconut methyl ester which had served as a solvent
was removed by distillation at a temperature of 140.degree. C. and
a pressure of 8 mbar. Thereafter 3 g of sodium methylate was added
as an esterification catalyst, and the esterification reaction was
allowed to occur at 120.degree. C. for 1.5 h at a pressure of 5
mbar. The ester product was washed twice with water, and the excess
methyl ester reagent and impurities were steam distilled at a
temperature of 200.degree. C. and a pressure of 3 mbar. The product
was filtered while hot through bleaching earth and a layer of
activated carbon. The stanol ester product contained free fatty
acids 0.02%, fatty acid methyl esters 0.3%, and unesterified
sterol-derived compounds 0.8%. The melting point of the stanol
ester was 36-39.degree. C. according to DSC determination.
EXAMPLE 2
[0031] 295 g of a sterol derived from vegetable oil (25%
campesterol, 55% .beta.-sitosterol and 15% stigmasterol) was
slurried into 705 g of coconut fatty acid methyl ester (which
contains primarily C.sub.6-C.sub.14 fatty acid esters). A Pd/C
catalyst was added (5% Pd on a carbon support, 0.2% palladium of
the amount of sterol), the temperature was raised to 120.degree.
C., and the reaction autoclave was rinsed with nitrogen. After the
nitrogen had first been replaced by a hydrogen atmosphere, hydrogen
was directed to the reaction mixture for 110 min. During the
hydrogenation the pressure of the reaction mixture was 1-2 atm.
[0032] The hydrogenation catalyst was removed from the hot reaction
mixture by filtration.
[0033] Thereafter 3 g of sodium methylate was added as the
esterification catalyst, and the esterification reaction was
allowed to occur at a temperature of 125.degree. C. for 1.5 h at a
pressure of 5 mbar, whereby the formed methanol was at the same
time removed. The ester product was washed twice with water, and
the excess methyl ester reagent and impurities were steam distilled
first at a temperature of 140-145.degree. C. and a pressure of 7-9
mbar. Finally the temperature was raised to 200-205.degree. C.
(pressure 34 mbar) in order to remove the higher boiling
impurities. The product was filtered while hot through bleaching
earth and a layer of activated carbon. The stanol ester product
contained free fatty acids 0.025%, fatty acid methyl esters 0.3%,
and unesterified sterol-derived products 0.6%. The melting point of
the stanol ester was 93-97.degree. C. according to DSC
determination.
EXAMPLE 3
[0034] In a process according to Example 2, rapeseed oil methyl
ester was used as the hydrogenation solvent and at the same time as
the esterification reagent instead of coconut fat methyl ester. The
reaction and the purification steps were carried out as in Example
2 (however, the temperature and pressure were 200-205.degree.
C./3-4 mbar throughout the steam distillation). The product
obtained was a wax having a melting range of 98-104.degree. C.
EXAMPLE 4
[0035] In this example, the hydrogenation solvent used was coconut
fatty acid methyl ester, which was partly removed by distillation
and replaced with rapeseed oil methyl ester before the
transesterification. 250 g of a sterol derived from vegetable oil
was slurried into 650 g of coconut fatty acid methyl ester. A Pd/C
catalyst was added in an amount of 0.2%, and the sterol was
hydrogenated as in the preceding examples. The hydrogenation
catalyst was removed from the hot reaction mixture by filtration.
Thereafter, 300 g of rapeseed oil methyl ester was added to the
reaction mixture, and 300 g of the saturated coconut fatty acid
ester was distilled at a temperature of 140-150.degree. C. and a
pressure of 7-9 mbar. The mixture was transesterified and purified
in the manner described in the preceding examples. The reaction
product was a light yellow wax having a melting range of
69-74.degree. C.
EXAMPLE 5
[0036] In the process according to Example 1, a high boiling
(distillation range 180-210.degree. C.) aliphatic hydrocarbon free
of aromatic compounds was used as the hydrogenation solvent instead
of coconut fatty acid ester. The reactions and purification
processes were carried out substantially in the manner described in
Example 1. The reaction product obtained was a wax corresponding to
the product of Example of 1 and having a melting range of
37-40.degree. C.
* * * * *