Note: Descriptions are shown in the official language in which they were submitted.
CA 02267929 1999-04-06
PREPARATION OF SATURATED PHYTOSTEROLS
FIELD OF THE INVENTION
The present invention relates to the preparation of saturated phytosterols
and, more
particularly, to a method of preparing an end product mixture of saturated
phytosterols, at
s least a substantial of the mixture consisting of saturated phytosterols,
from a raw material
mixture of phytosterols derived from tall oil, at least a substantial portion
of the raw material
mixture consisting of unsaturated phytosterols.
BACKGROUND TO THE INVENTION
It has been known for many years that plant sterols or phytosterols can serve
to
to effectively reduce serum cholesterol levels. In various studies, (3--
sitosterol and, even
moreso, its hydrogenated form (13-sitostanol), has been recognized as
particularly efficacious.
One important source of phytosterols is tall oil, and there are known methods
for
isolating phytosterols and their saturated or hydrogenated (stanol) forms
either from tall oil
soap (sometimes referred to as soap skimmings) or from tall oil pitch.
15 When phytosterols are isolated from tall oil, a portion of the isolated mix
(normally
including l~sitosterol and campesterol) will typically include at least some
hydrogenated
forms of the sterols (viz. f3-sitostanol and campestanol). However, given the
higher efficacy
of 13--sitostanol compared to 13-sitosterol, it is desirable that
substantially all 13-sitosterols
present in any such mix should be converted to f~sitostanols.
2o The conversion of a sterol to a stanol is, by definition, hydrogenation.
Generally, it is
known to hydrogenate a phytosterol or a phytosterol mixture by mixing the
phytosterol with
a solvent in a reactor in the presence of an appropriate catalyst. However,
while
hydrogenation is mandated, relatively little attention has been paid to how
hydrogenation
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CA 02267929 1999-04-06
may best be achieved, including which solvent may be best suited to the
hydrogenation
process.
From an economic or commercial point of view, it is highly desirable to effect
the
hydrogenation of a phytosterol or a phytosterol mix as quickly as possible. In
this regard, it
is recognized that one possible way to accelerate the hydrogenation process is
to carry out the
process at an elevated temperature or at an elevated temperature and pressure.
However, if
the temperature is excessive, then the phytosterols will degrade or break
down.
Further, and again from an economic or commercial point of view, it is highly
desirable to be able to produce high purity saturated phytosterols while
recycling or reusing
1o the hydrogenation solvent with many successive batches of raw material
phytosterols.
However, the ability to do so can be impaired if the execution of the
hydrogenation process
introduces impurities or contaminants either as the result of phytosterol
break down or
otherwise. Impurities or contaminants that are carried with the saturated
phytosterols may, at
added cost, require removal. Likewise, to extend the lifetime of the
hydrogenation solvent,
~ 5 any impurities or contaminants that are carried with the solvent may
require removal before
the solvent is recycled.
A further important factor that contributes to the overall cost of producing
saturated
phytosterols is the time that it takes to dry or sufficiently remove the
presence of solvent
from the end product. When saturated phytosterols are to be used in the
preparation of food
20 additives or dietary supplements, government regulations typically will
permit the presence
of only a very small amount of solvent residue (for example, SO parts per
million).
Accordingly, a primary object of the present invention is to provide a new and
improved method for efficiently preparing a high purity end product mixture of
saturated
phytosterols from a raw mixture of phytosterols derived from tall oil - and
one which
25 converts a high percentage of unsaturated phytosterols present in the raw
material mixture to
corresponding saturated phytosterols.
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SUMMARY OF THE INVENTION
In accordance with a broad aspect of the present invention, there is provided
a method
for the preparation of an end product mixture of phytosterols, at least a
substantial portion of
the mixture consisting of saturated phytosterols, from a raw material mixture
of phytosterols
derived from tall oil, at least a substantial portion of the raw material
mixture consisting of
unsaturated phytosterols, such method comprising the steps of
(a) hydrogenating the raw material mixture in a solvent substantially
comprising ethyl
acetate while in the presence of a hydrogenation catalyst to produce a
hydrogenation
product comprising the end product mixture in the solvent; and,
to (b) filtering and drying the hydrogenation product to separate the end
product mixture
from the solvent and to thereby leave an amount of solvent residue in the end
product
mixture that is not greater than a predetermined amount.
During hydrogenation, the temperature is greater than 35 deg. C. (preferably
about 40
deg. C. or higher) and the pressure is greater than standard pressure
(preferably about 20 psi
15 or higher). Suitable catalysts include platinum dioxide and palladium.
However, by reason
of its lower cost, the latter is preferred.
After filtering and drying to reduce the amount of solvent and solvent
residue, the
resulting end product mixture of saturated phytosterols may be used for
various purposes
including the manufacture of food additives or dietary supplements with a view
to facilitating
?o the reduction of serum cholesterol levels.
Herein, and in the claims, it is to be understood that pressures when
expressed as
"psi" are pressures relative to standard pressure. Thus, for example, 20 psi
as used above
means 20 psi in excess of standard pressure. Standard pressure is about 14.7
pounds per
square inch absolute.
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Solvents other than ethyl acetate may be used to prepare a mixture of
saturated
phytosterols from a mixture of unsaturated phytosterols derived from tall oil.
Such other
solvents include ethanol and isopropanol. However, ethyl acetate has been
found to produce
surprisingly unique results. With ethyl acetate, it is possible not only to
achieve conversion
ratios above 97% and approaching 99% or higher but, in so doing, to produce a
resulring
saturated phytosterol mixture that has particularly high purity. Moreover, it
has been found
that a saturated phytosterol mixture produced with ethyl acetate as the
solvent can be filtered
and dried (e.g. to less than 50 ppm solvent residue) substantially more
efficiently than when
produced with solvents such as ethanol or isopropanol.
to BRIEF DESCRIPTION OF THE DRAWINGS
The FIGURE is a representation of a gas chromatograph (GC) trace obtained upon
hydrogenation of a raw material mixture of phytosterols as described below, in
part serving
to illustrate results that are achieved when (in accordance with the present
invention) ethyl
acetate is used as the hydrogenation solvent, and also serving to illustrate
results that are
15 achieved when (not in accordance with the present invention) ethanol or
ispropanol is used as
the hydrogenation solvent.
DETAILED DESCRIPTION
As noted above, raw material phytosterol mixtures that are isolated from tall
oil
typically will include both unsaturated and saturated phytosterols. In more
detail, Table 1
?o below indicates characteristics of raw material crystalline mixes that may
be derived from
softwood trees indigenous to northern British Columbia (including spruce,
lodgepole pine
and sub-alpine fir).
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TA BLE 1.
T_y ip cal Values
Phytosterols: > 95% by weight
(3--sitosterol 55 - 60% by weight
l~sitostanol 12 - 18% by weight
campesterol 12 - 17% by weight
campestanol 2 - 4% by weight
other sterols < 3% by weight
Melting Point 132 - 140 deg. C.
to Phytosterol mixtures as indicated in Table 1 may be used in the manufacture
of
cholesterol lowering agents without any hydrogenation step. However,
hydrogenation is
desirable because 13-sitostanol is recognized as having an efficacy
significantly higher and an
absorption rate significantly lower than f3-sitosterol.
Raw material mixtures as indicated in Table 1 are themselves considered useful
to be
used directly for the manufacture of food additives or dietary supplements
that have serum
cholesterol lowering properties. However, hydrogenation is desirable because
13--sitostanol is
recognized as having particularly high efficacy and because f3-sitosterol is
the most plentiful
unhydrogenated phytosterol.
Several tests were conducted under various conditions of temperature and
pressure
2o utilizing raw material (RM) mixes like that indicated in Table 1. In each
case, the raw
material mixture was first mixed with ethyl acetate (ETAC), then introduced
together with a
hydrogenation catalyst (CAT) to a stirred reactor where hydrogenation took
place under
controlled conditions of temperature and pressure. The catalyst used was 5%
palladium on a
carbon support. Thereafter, the hydrogenation product (viz. the end product
mixture of
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phytosterols
in
the
solvent)
was
filtered,
cooled,
separated
and
dried
by
conventional
means
well nown to thoseled in
k skil the art.
GC analysis then usedanalyze the ure and
was to end product to calculate
mixt the
percen tage of stanols Table 2 summarizes conditions
present the and results.
therein. test
TABLE 2
Test RM/SOL CAT/RM H2 press. Temp. Run Time Conversion
(wt %) (wt %) (psi) (C) (min.) (%)
2.01 8 10 20 20 1.20 50
2.02 8 10 20 30 I20 73
2.03 8 10 20 40 120 98
2.04 8 10 20 50 120 99
2.05 8 10 40 SO 120 99
2W 8 10 40 65 120 99
2.07 8 10 65 65 120 99
2.08 8 6 75 100 120 97
2.09 8 6 75 100 120 97
2.10 8 6 75 100 120 98
2.11 8 9 75 100 120 97
2.12 8 10 7S 100 120 99
2.13 15 10 75 100 120 99
2.14 15 10 75 100 240 100
2.15 8 10 75 100 120 98
In Table 2, the column headed "Conversion" is a calculation of 100% times the
amount of saturated phytosterols present in the end product mixture divided by
the sum of
such amount and the amount of unsaturated phytosterols present in the end
product mixtures.
The amounts were determined in mg/g from the analysis of the GC traces.
1o From Table 2, it will be noted that there is a rapid decrease in percent
conversion as
the temperature of hydrogenation drops below 40 deg. C. For this reason, the
temperature
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used in accordance with the invention is greater than 35 deg. C, and
preferably about 40 deg.
C. or higher where the percent conversion is in the high 90% range.
Further, although a relatively high percent conversion is shown at 40 deg. C
and a
hydrogen pressure of 20 psi, it is noteworthy that the percent conversion
remains high at
elevated temperatures and pressures. This indicates a substantial absence of
phytosterol
break down under such elevated conditions. Further, since conversion
efficiency is
approximately the same at 75 psi and 100 deg. C as it is at 20 psi and 40 deg.
C, and since the
conversions taking place may be accelerated at higher temperatures and
pressures, it follows
that comparable results should be achieved with run times less than 120
minutes as used in
i o most of the tests.
Apart from the high conversion efficiencies that can be achieved while using
ethyl
acetate as the hydrogenation solvent, it has also been found that required
drying times are
significantly less than is required with other solvents such as ethanol and
isopropanol. By
way of example, a sample of raw material like that shown in Table 1 that was
hydrogenated
in ethyl acetate in the manner described above was dried for 2 hours at 105
deg. C under an
absolute pressure of 25 mmhg. The result was fine white phytosterol crystals
containing less
than 50 ppm ethyl acetate. In comparison, the amount of solvent residue
remaining in like
samples that were hydrogenated in ethanol and in isopropanol exceeded ten
times this
amount after drying for twice as long.
2o Reduced drying time represents a significant advantage that ethyl acetate
provides
over solvents such as ethanol and isopropanol. However, it has also been found
the use of
ethyl acetate mitigates against impurities that tend to appear in the end
product mixture when
ethanol or isopropanol is used.
More particularly, reference is now made to the FIGURE. Except as noted below,
the
FIGURE is generally representative of GC traces that will be obtained upon
hydrogenation of
a raw material mixture like that indicated in Table 1. As shown, the trace
includes three
major peaks:
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Peak 1 Internal Standard (cholesterol)
Peak 2 Campestanol
Peak 3 13-sitostanol
Smaller peak 4 to the right of peak 3 is representative of other sterols. Peak
5 to the
left of peak 1 represents undesirable impurities. Although there is a degree
of uncertainty, it
is thought to be generated by dehydroxylated forms of sterols (campestane and
stigmastane).
In relation to the present invention, the most significant observation to be
made with
respect to the FTGURE is that peak S indicating the presence of impurities
does not appear in
the case of hydrogenation with ethyl acetate whereas it does appear in the
cases of
hydrogenation with either ethanol or isopropanol.
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