Note : Les descriptions sont présentées dans la langue officielle dans laquelle elles ont été soumises.
Phospholipid Composition
This invention relates to a phospholipid composition having a
phosphatidylcholine content of at least 80% by weight with the
composition being free of additives, and to a process for the manufacture
of such a phospholipid composition.
Phospholipids occur in both animal and vegetable matter and have to be
isolated from these. The main source are eggs, soybean, oil seeds and oil
fruit, such as coconut copra, palm kernel, groundnuts, rape, sunflower
seeds, oil palms and olives.
Phospholipids are isolated from vegetable products by de-gumming the
corresponding vegetable oil with, for example, a small quantity of steam
or water. The phospholipid composition produced, as known as lecithin
sludge, generally contains ca. 8 to 59% by weight phospholipids and is
dried by various methods to yield crude lecithin on drying.
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Depending on the initial lecithin sludge used in each case
this crude lecithin will have a different chemical composi-
tion. Thus according to Weber E.J.; J.A. O.C.S. 58 898
(1981) the most important crude lecithin, soy (soybean)
lecithin, is composed, after drying, of ca.:
Triglycerides 34.2% phosphatidylcholine 19.1%
Diglycerides 0.4% lysophosphatidylcholine 0.7%
Free fatty acids 0.4% phosphatidylethanolamine 8.6%
Other neutral
lipids 0.8% phosphatidylinositol 8.8%
Glycolipids 6.5% phosphatidic acid 4.2%
Carbohydrate 6.7% N-acylphosphatidyl-
ethanolamine 1.0%
others 8.6%
Neutral lipids, such as, for example, triglycerides, digly-
cerides and the like, can be removed from the crude lecithin
by deoiling with acetone. The deoiled crude lecithin, also
referred to as pure lecithin, is a solid powder capable of
being poured, which is available commercially as lecithin
granules. The phosphatidylcholine content of pure lecithin
lies between ca. 25% by weight and 30% by weight.
The phosphatidylcholine in crude lecithin or pure lecithin
can be enriched by known processes. Preferably according to
the processes described in European Patents 00 54 770 or 00
54 769. Hereby the crude lecithin is extracted with alcohol.
The alcohol-soluble extraction phase is then chromatographed
on silicon dioxide at elevated temperatures. On account of
its high phosphatidylcholine content the phospholipid com-
position resulting from the aforesaid process is used for
pharmaceutical, cosmetic and dietetic applications. However
it exhibits the disadvantage that it is paste-like or waxy
depending on its chemical composition. The further
processing of this product is often accompanied by
considerable problems on account of its consistency which
makes it difficult to dose and cause it to stick to the
inside walls of vessels, so that the residues remaining in
the vessels make frequent and expensive cleaning of the
vessels necessary.
In order to eliminate the aforesaid disadvantages in the
handling of phospholipid compositions containing large
proportions of phosphatidylcholine attempts have already
been made to process these products in such a manner that
powdered or granule-like high purity lecithins or specific
high purity phospholipids are formed.
Thus German Patent 973 741 proposed deoiling crude lecithin
with a suitable solvent, for example acetone, separating
the deoiled lecithin from the oil extract, then loosening
the separated lecithin and drying it as a thin layer.
Thereafter the deoiled lecithin can be separated from the
layer support used in the form of flocks or leaflets.
However it is unlikely that such a process could be carried
out nowadays at an economically acceptable cost.
Furthermore the phosphatidylcholine content of 30% is too
low for the applications described above.
Processes involving the use of additives are also known (US
patents 20 57 695 and 30 12 888).
A similar process has been proposed in German patent 38 26
946. Here a special sugar mixture marketed under the
trade-mark PALATINIT is employed as an additive during the
manufacture of the high purity phospholipid composition in
order to yield powdered of granulated high purity specific
phospholipids or phospholipid compositions.
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However the aforesaid known methods possess the disadvantage
that additional effort is involved, namely that it is
necessary to add and work in an additive. Furthermore the
phospholipid compositions prepared by the known methods are
only of very restricted application on account of their
relatively low phosphatidylcholine concentrations.
The present invention is intended to make available a
phospholipid composition and a process for manufacturing such
a phospholipid composition, that is particularly simple to
carry out and leads to products which are stable on storage.
A phospholipidic powder or granulate according to the
invention has a phosphatidylcholine content of at least 80% by
weight, the phospholipidic powder or granulate being free of
additives, and the phospholipidic powder or granulate being
isolated from soybean lecithin and the powder or granulate
having a particle size or a crystallite size between 18 mm and
0.07 mm.
The powdered or granulated phospholipid composition according
to the invention exhibits a range of advantages. Thus it is
particularly easy to handle on account of its granule-like or
powdered consistency, so that the disadvantages described for
the state of the art do not occur. Unexpectedly it was also
found that the powdered or granule-like consistency is also
maintained when the processing temperature of the powdered or
granule-like composition rises to a temperature of about 30~C.
The phospholipid composition also possesses long storage
stability of up to several years without any changes occurring
in the chemical or physical structure. This is particularly
the case if the phospholipid composition is stored at a
temperature below 10~C,.......................................
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preferably at a temperature between 1 ~C and 6 ~C, prefer-
ably under an inert gas.
The aforesaid advantages of the phospholipid composition
according to the invention mean that this composition is
very readily applied to the manufacture of appropriate fin-
ished products, such as, for example, cosmetics, dietetic
preparations or pharmaceutical preparations. This is on
account of the fact that such powdered or granule-like
compositions are particularly simply dosed and can be weigh-
ed out with great accuracy and reproducibility, which is not
possible in the case of highly viscous or paste-like
products. On account of the absence of additives (solidi-
fiers) the composition according to the invention can also
be applied where the known phospholipid compositions cannot
be used on account of the additives they contain and/or
their low phosphatidylcholine content, that is, in particu-
lar, for pharmaceutical products.
A particularly suitable embodiment of the composition accor-
ding to the invention involves the composition according to
the invention that, as has already been described, contains
at least 80% by weight phosphatidylcholine, being predomin-
antly crystalline. Especially when the composition according
to the invention contains more than 80% by weight, and
preferably more than 90%, crystalline phosphatidylcholine
components, it is found that sllch a composition particularly
possesses the aforesaid advantages that have been described
in detail above. In other words such a composition according
to the invention contains at least 6g% by weight and prefer-
ably 72% by weight crystalline phosphatidylcholine compon-
ents on an absolute basis. Unexpectedly it could be demon-
strated that such a composition according to the invention,
that preferably was composed primarily of crystalline
CA 02073096 1998-10-19
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components, is excellently dispersible in water, which, for
example, considerably eases the manufacture of appropriate
aqueous suspensions of cosmetic dietetic or pharmaceutical
preparations. The aforesaid ready dispersibility is unknown
for phospholipid compositions according to the state of the
art which is attributable to the fact that such known
compositions are predominantly amorphous in nature.
A further embodiment of the composition according to the
invention proposes that this possesses a concentration of at
least 90~ by weight phosphatidylcholine.
Another embodiment of the aforesaid composition contains the
composition according to the invention
93% by wt. + 3% by wt. phosphatidylcholine and
3% by wt. + 3% by wt. lysophosphatidylcholine,
whereby the aforesaid values have been checked by a known
quantitative thin-layer chromatographic analysis method. Such
a composition preferably does not contain any phosphatidyle-
thanolamine and/or any phosphatidylinositol.
With respect to the particle size of the phospholipid
composition according to the invention it may be said that
this is adjusted according to the particular field of
application. As stated above, the phospholipid composition is
comminuted to a particle or crystallite size between 18 mm and
0.07 mm, and preferably between 6mm to 0.5mm.
The present invention also applies to a process for the
preparation of the aforesaid phospholipid compositions.
The process according to the invention for the preparation
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of a phospholipidic powder or granulate comprises so
comminuting a highly pure phospholipidic substance have a
phosphatidylcholine content of at least 80% by weight after
cooling to a temperature below -50~C that after the
comminution a phospholipidic powder or granulate results,
having a particle size or crystallite size between 18 mm and
0.07 mm.
Unexpectedly it could be established that phospholipid
compositions could be comminuted without problems under these
temperatures without the need for admixture of the solidifying
agents required in the known methods. In addition,
compositions that have been comminuted in this manner and that
contain at least 80% by weight phosphatidylcholine are stable
up to a temperature of 30~C for several months and years so
that chemical and physical changes do not occur.
A further specifically favoured embodiment of the process
according to the invention provides for the storage of the
phospholipid composition at temperatures between +5~C and
-60~C, particularly at temperatures between -10~C and -30~C
before comminution. Whereby the storage time varies between
one day and 150 days, preferably between 30 days and 70 days
depending on the storage temperature chosen. A phospholipid
composition stored in the aforesaid manner can be comminuted
to the initially mentioned particle size of 18 mm or 0.07 mm,
preferably of 6 mm to 0.5 mm within a very short time.
Depending on the particular phospholipid composition employed
a further method of execution of the process according to the
invention involves the comminution and/or storage of the
particular phospholipid composition at the aforesaid
temperatures and for the aforesaid storage time under inert
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gas. In particular the inert gas can be liquid nitrogen,
carbon dioxide, a noble gas or a mixture of the aforesaid
gases. This method of operation under inert gas prevents an
undesired oxidative modification of the phospholipid compos-
ition.
As already described above various highly purified phospho-
lipid compositions isolated from natural products can be
employed as starting materials for the process according to
the invention, provided that they contain at least 80% by
weight phosphatidylcholine. Such a composition can be iso-
lated preferably from eggs, oil seeds and oil fruit and
particularly soybean by the known procedures. However, it is
particularly suitable when a soy (soybean) lecithin whose
phosphatidylcholine content is at least 90% by weight and
preferably 93 + 3% by weight is employed in the process
according to the invention. Such a high purity soy lecithin
can, for example, be isolated by the methods as they are
described in the European patents 0 054 770 and 0 054 769.
In order to be able to store the powdered or granulated
product prepared by the process according to the invention
over a long period of time without chemical or physical
change a further embodiment of the process according to the
invention envisages storage at a temperature below 10 ~C and
preferably between 1 ~C and 6 ~C.
A further improvement in the storage stability is achieved
if the phospholipid composition is sealed into airtight
sachets, for example of appropriate aluminium foil, and
stored at the aforesaid temperatures.
A further embodiment of the aforesaid process envisages
displacing the air contained in the sachets after they have
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been filled with an inert gas, for example, nitrogen, a
noble gas, carbon dioxide or a mixture of the aforesaid
gases.
As already described above the powdered or granulated phos-
pholipid composition according to the invention is very easy
to handle and can be employed for various purposes. Thus,
for example, such a powdered or granulated phospholipid
composition can be used as solution promoter, natural sur-
factant and/or liposome former in cosmetic products andespecially in pharmaceutical products, since the phospho-
lipid composition according to the invention is free from
solidifying agents.
Advantageous further embodiments of the phospholipid com-
position according to the invention and the process accord-
ing to the invention are set out in the subsidiary claims.
The process according to the invention is further illus-
trated by the examples that follow.
Example 1
300 kg of a phospholipid composition containing 93% + 3% by
weight phosphatidylcholine that, for example, had been
isolated from soybeans according to the processes described
in European patents 00 54 770 or 00 54 769 was stored at
- 20 ~C for 2 months. Immediatley before the phospholipid
composition was comminuted it was brought to room tempera-
ture (17 ~C to 21 ~C). Then the composition was comminutedin a conventional cold milling plant with liquid nitrogen
cooling and sealed portionwise in aluminium sachets under
inert gase (nitrogen). The product that had been so packed
was stored at + 4 ~C.
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Stability tests revealed that the product retained its pow-
dered or granulated form at temperatures up to + 30 ~C.
Immediately before such a product is processed it is warmed
to room temperature to avoid the condensation of water onto
the comminuted product.
Example 2
As described above 100 kg of the aforesaid composition were
comminuted in the cold. However in contrast to example 1 the
storage time before comminution was one month at -17 ~C.
Stability tests revealed that there was no change in consis-
tency even after storage for 12 weeks at room temperature
(20 ~C + 2 ~C) after comminution and packing.
The powdered or granulated phospholipid composition so iso-
lated had the following chemical composition:
Phosphatidylcholine 94.2% by wt.
Phophatidylethanolamine not detectable
Phosphatidylinositol not detectable
Lysophosphatidylcholine 3.7% by wt.
Water 1.3% by wt.
Triglycerides (oils) 0.8% by wt.
Example 3
As previously described in example 1, 300 kg phospholipid
composition were comminuted together with 150 kg carbon
dioxide granules. Whereby the other conditions corresponded
to those described in example 1.
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Stability tests revealed that the composition prepared
according to example 3, which contained the aforesaid high
phosphatidylcholine content, also remained unchanged in
consistency even on storage for six months after comminu-
tion.
