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oearcn K0011
Patented Dec. 17, 1946
2,412,766
UNITED STATES PATENT OFFICE
2,412,766
PROCESS OF PRODUCING VITAMIN
CONCENTRATES
Loran 0. Buxton, Newark, N. J., assignor to
National Oil Products Company, Harrison,
N. J ., a corporation of New Jersey
Application July 13, 1942, Serial No. 450,757
1
6 Claims. (Cl. 167-81)
2
This invention relates to the production of con
and will hereinafter be termed "saturated glyc
centrates of fat-soluble vitamins from natural
erides.”
oils and fats containing the same, and particu
Fat soluble vitamin concentrates are also pre
larly to the production of such concentrates in
pared by high vacuum distillation of ?sh liver oils.
which the vitamins are in the ester form.
91 This process is endowed with many disadvan
The natural vitamin-bearing oils are complex
tages in that the undesirable odor and taste bod
mixtures containing free fatty acids; fatty acid
ies go over into the distillate (the concentrate)
glycerides; fatty acid esters of vitamins A and D,
and loss of potency is encountered due to poly
vitamin A and D in alcoholic form and other
merization of the vitamins caused by the heat
higher alcohols including sterols and ether al
cohols; and other unsaponi?able matter such as
hydrocarbons, etc. Vitamin concentrates are
conmionly prepared from these oils by subjecting
them to complete saponi?cation, whereby the free
10
necessarily applied during distillation. Moreover,
the process is costly due to the equipment needed
and the e?iciency oi.’ the process as a whole is
commercially unsatisfactory.
Accordingly, it is an object of this invention to
fatty acids are converted to soaps, the glycerides 15 prepare highly potent concentrates of the fat
are converted to soaps and glycerine, and the
soluble vitamins, and particularly to prepare such
vitamin and other higher alcohol esters are con
concentrates in which the vitamins will be in the
verted to soaps, vitamin alcohols and other higher
esteri?ed form.
alcohols. The saponi?ed mass is then extracted
Another object is to provide highly potent con
with a‘ suitable solvent which dissolves the vita
centrates of fat-soluble vitamins which do not
min alcohols, the other higher alcohols and the
have the characteristic "concentrate” taste.
other unsaponi?able matter, leaving behind the
A further object is to avoid the manipulative
soaps and glycerine. The solvent is evaporated
di?iculties incident to earlier processes.
o? from the extract to yield a highly potent vita
A still further object is to minimize the con
min concentrate. It will be noted that in such 25 version of vitamin esters to alcohols in saponi?
processes the natural vitamin esters are con
cation processes.
verted into their less desirable alcoholic form.
The objects above set forth are achieved by
Further, the action of the saponifying agent de
this invention in a process which involves par
velops a characteristic bitter “concentrate” taste
tially and selectively saponifying a fat-soluble
which is very di?icult to remove by subsequent 30 vitamin-bearing marine oil under conditions such
treatment.
as to saponify a major portion of the saturated
Vitamin concentrates are also prepared by con
glycerides, a somewhat lesser portion of the un
tacting the natural vitamin oils with polar sol
saturated glycerides and a still smaller portion
vents, which preferentially extract the vitamin
of the vitamin esters; thereafter extracting, the
esters and alcohols from the oil, leaving behind 35 partially saponi?ed mass with a non-polar sol
a considerable portion of the inert materials.
vent to recover an extract containing the un
Such processes, being physical, have the ad~
saponi?ed unsaturated glycerides, vitamin es
vantage that the vitamin esters are extracted as
ters, vitamin alcohols (either naturally-occurringv
such from the oil. However, such processes have
or those split during the sapom‘?cation step) and
certain limitations, among which are those due 40 other unsaponi?ed and unsaponi?able matter,
to the dilute state of the vitamins in most raw
leaving behind the glycerine and the soaps of
oils. As a consequence large quantities of oil
fatty radicals split off from those components
must be handled; the oil retains a relatively large
which yielded to the saponi?cation reaction; and
portion of the vitamins; the solvent extracts con
evaporating off the solvent to leave a vitamin
siderable inert material; and the end product is
product which has been to a. large degree con
relatively low in yield and concentration. An
centrated and puri?ed by the almost complete
other dif?culty is the tendency of stearins and
removal of the saturated glycerides and the con
similar components of the oil to entrain the ex
siderable removal of the other fatty constituents.
tracting solvent and render separation di?icult.
This step product will hereinafter be termed a
Further, these components, having relatively high 50 “semi-concentrate.” This semi-concentrate is
melting points, cause the products containing
then further concentrated or fractionated by any
them to cloud and thicken in the cold. In gen
suitable process such as high vacuum distilla
eral, these components (saturated and slightly
tion, adsorption or, preferably, selective frac
unsaturated triglycerides) are characterized by
tionation oi the vitamins by means of polar sol
low iodine value and high saponi?cation value, 55 vents,
2,412,766
3
Contrary to the general belief I have found that
4
about 75% to obtain the most ef?cient selective
saponi?cation. The retarded preferential sapon
in partially saponifying a ?sh or ?sh liver oil the
saturated and slightly unsaturated glycerides are
selectively saponi?ed i. e. the saturated and
i?cation can also be brought about by reducing or
slightly unsaturated glycerides take precedence
cation reaction.
ling cod liver oil, pollack liver oil, tuna liver oil,
shark liver oil, dogflsh liver oil, mackerel liver
oil, sword?sh liver oil, spear?sh liver oil, sole
tors-solvent concentration, catalyst concentra-'
tion, and caustic concentration-may be concur
eliminating the catalyst employed in the saponi?
In the saponi?cation of vitamin
over unsaturated glycerides in order of reactions
containing oils, it is the usual practise to add
with alkali or alkaline agents. This result may
about 2% to 5% of isopropanol or other polar cat
be due to the fact that in marine oils the unsatu
alyst to allow the saponi?cation to proceed at low
rated glycerides have higher molecular Weights
temperatures. The use of a lesser quantity of
than the more saturated glycerides present 10 catalyst, for instance between about 1/2 and 1%,
therein.
will, when less than the stoichiometric amount
As raw materials in the above briefly outlined
of caustic is used, bring about a highly selective
process there may be used any of the numerous
preferential saponi?cation. Similarly, the use of
marine oils containing fat-soluble vitamins, es
a less concentrated caustic will bring about the
pecially the ?sh liver oils such as cod liver oil,
same general result. Obviously, all three fac
rently adjusted so as to bring about a retarded
liver oil and halibut liver Oil; and the marine
preferential saponi?cation of the oil. It is to be
oils such as sardine oil, pilchard oil, herring oil, 20 understood that it is not necessary to carry out
seal oil and whale oil. Solvent extracts, such as
the partial saponi?cation step in the presence of
the isopropanol extracts, of the foregoing and
either a catalyst or solvent medium.
similar oils may also be used.
a The step of extracting the semi-concentrate
With reference to the partial selective saponi
from the selectively partially saponified mass
?ication step, this is carried out by treating a vi 25 may be carried out by the use of non-polar sol
tamin-containing oil with caustic in the manner
vents in a manner paralleling the usual saponi
usual in preparing vitamin concentrates, with
?cation and extraction procedures. In cases
the exception that the amount of caustic used
where a solvent is used to retard the partial sa
is insumcient to completely saponify the oil. It >
poni?cation reaction, it is preferable to use the
has been discovered by this invention that under 20 same solvent in the extraction step to simplify re
these conditions a substantial proportion of the
covery of the solvent. After the extract-solvent
vitamin esters remains intact and that the satu
solution has been separated from the saponi?ed
rated glycerides are substantially completely sa
mass the‘ solvent is removed from the solution
poni?ed along with a portion of the unsaturated
thus leaving the so-called “semi-concentrate."
glycerides. The partially saponi?ed mass con 35 The “semi-concentrate” which is substantially
tains vitamin alcohols, both those occurring nat
urally in the oil and those resulting from saponi
?cation of a small amount of the vitamin esters,
together with a preponderant amount of the unat
free of saturated glycerides, is composed essen
tially of vitamin A and D esters, vitamin A and
D alcohols, sterols and the glycerides which es
caped saponi?cation.
tacked, naturally occurring vitamin esters; a part (0 Due to the mild character of the saponi?cation
of the unsaturated glycerides present in the orig
step, the semi-concentrate is substantially free of
inal oil, unsaponi?able matter, glycerine, soaps
the usual characteristic bitter “concentrate” taste
derived from the saturated glycerides and soap
normally associated with vitamin concentrates
derived from that portion of the unsaturated
prepared by the heretofore known saponi?cation
glycerides which yielded to the saponi?cation.
processes.
This selective saponi?cation can be obtained in
The next step in the process of the invention
some measure with any degree of saponi?cation
of the oil up to that approximating complete sa
poni?cation i. e. 98%. In general, the amount
of caustic employed and the consequent degree
of saponi?cation will be adjusted according to
the products desired, larger amounts of caustic
increasing the potency of the products while re
ducing the net yield of the esteri?ed forms of the
vitamins. In usual practise, su?icient caustic
will be employed to saponify from about 60% to
about 95% of the saponi?able matter in the oil.
As just stated, this preferential selective saponi
involves subjecting the semi-concentrate to a
fractionation procedure which is preferably ac
complished by selective extraction of the vitamin
alcohols from the vitamin esters by means of
polar solvents. As mentioned hereinbefore this‘
semi-concentrate can be conveniently fraction
ated by processes other than selective solvent ex
traction, namely, high vacuum distillation, ad
sorption, etc. The semi-concentrate has‘ been
found to be in a particularly favorable condition
for such treatments due to its substantial freedom
from saturated glycerides, The fractionation by
?cation occurs in substantially all cases where a
selective extraction with polar solvents may be
vitamin oil is saponi?ed with a lesser amount of 60 carried out in one of several alternative ways;
?rst, the semi-concentrate may be contacted and
caustic than the amount theoretically required
exJ-racted with a highly polar solvent like meth
to completely saponify the oil. It has been dis
anol, which will extract principally the alcoholic
covered further, however, that by this invention
vitamins, leaving behind the esteri?ed vitamins
the selectivity can be enhanced by carrying out
the saponi?cation under conditions such that the 65 in the semi-concentrate; or second, the semi-con
centrate may be contacted and extracted with a
action of the caustic is retarded. For instance,
solvent of lesser polarity, such as isopropanol,
this retarded preferential saponi?cation can be
which will extract out both the alcoholic and
obtained by diluting the oil With' a suitable inert
solvent, such as a non-polar solvent on the order
esteri?ed forms of the vitamins to provide a con
of ethylene dichloride, heptane, trichlorethylene
centrate having a potency higher than that of
the semi~concentrate; or third, the alcoholic
vitamin may be extracted from the semi-concen
trate by means of a highly polar solvent like
methanol and thereafter a highly potent vitamin
hexane, cyclohexane, methyl cyclohexane, or a
mixture of two or more of these or like solvents.
- Based on the weight of oil treated, the weight of
solvent employed should range from about 15%
to about 99%, and preferably from about 25% to
ester concentrate produced by extracting the
2,412,100
5
residual semi-concentrate with a moderately polar
solvent like isopropanol; or fourth, both the alco
in alcoholic form) were individually saponii‘led to
varying degrees and under varying conditions of
holic and esteri?ed forms of the vitamins may be
extracted from the semi-concentrate by means
of a moderately polar solvent such as isopropanol,
and the resultant extract separated into ester and _
alcohol concentrates by fractionation with a very
highly polar solvent such as methanol.
Reference has beenmade above to the frac
tionation of a fat-soluble vitamin concentrate to
separate the vitamin alcohols from the vitamin
catalyst and solvent concentrations and the per
centage of vitamin A ester split in each case
was determined and recorded. The results are
shown graphically in the accompanying draw
ing, wherein, for each case, the ordinate indi
cates the percentage of vitamin A remaining in
esterified form; the abscissa indicates the total
quantity of all esters split, as a chemical-equiv
alent-percentage of all saponi?able matter pres
esters. The preferred solvents employed in this
ent; and the curves Hi to 19 indicate several ex—
periments as follows: Curve l6 represents experi
step are methanol and ethanol, however, any
other solvent which is characterized by being
ments carried out in the absence of any saponi
miscible (a solvent for) with vitamin alcohols 15 ?cation catalyst; curve "represents experiments
but immiscible (a non-solvent for) with vitamin
in which 0.75% of isopropanol saponi?cation cat
esters may be employed in lieu of or in combina
alyst was used, based on weight of the oil treated;
tion with methanol or ethanol. Such solvents
curve l8 represents experiments in which 3.00%
of isopropanol catalyst was used, based on the
include, among others, isopropanol, isobutanol,
n-butanol, acetone and diacetone alcohol each 20 weight of the oil treated and curve l9 represents
of which has been modi?ed by the addition of
experiments in which 3.00% of isopropanol cata
lyst was used along with 50% of ethylene di
at least 9% water, methanol and/or ethanol. In
those cases where the vitamin potency of the
chloride solvent, both based on the weight of the
semi-concentrate containing both vitamin alco
. oil treated. It will be seen that in each case the
hols and esters or the residual portion remaining
vitamin esters were split to a lesser degree than
after the removal of vitamin alcohols therefrom
the other esters present in the oil. From a com
is to be increased a solvent such as isopropanol
parison of the several, curves it will be seen that
is preferably used, however, any suitable organic
retarding conditions, i'. e., the presence of solvent
and diminution or omission of catalyst,»delay the
downward break of the curves, so that a higher
degree of saponi?cation of the non-vitamin esters
in the oil for any given degree of vitamin ester
splitting is possible under these retarding condi
aliphatic polar solvent characterized by being
miscible with the semi-concentrate or the afore
said residual portion thereof at temperatures
above room temperature and at least partially
immiscible therewith at temperatures below room
temperature may be used. Such solvents include,
tions.
inter alia, acetone, diacetone alcohol and n-buta 35
Example II
me]. For the purposes of this disclosure room
100
parts
of
shark
liver oil containing 99,000
temperature is assumed to be 20° C.
units of vitamin A per gram, 50 parts of ethylene
In carrying out the partial saponi?cation step
dichloride and 3 parts of isopropanol were mixed,
by means of an alkaline agent it is preferred to
and nitrogen gas bubbled through to deaerate the
employ potassium hydroxide, it being understood,
mixture. 34 parts of 46% KOH (85% of the
however, that any suitable alkaline agent may be
amount required to completely saponify the oil)
used in lieu of KOH such as sodium hydroxide,
were added slowly, with stirring. Stirring was
sodium carbonate, potassium carbonate, etc.
Vitamin concentrates prepared as outlined
continued for about 20 minutes, after which the
above are all highly potent, the vitamin ester - thickened mass was insulated against heat loss
concentrates in particular being more potent
and allowed to stand for 16 hours. The mass was
than any other similar concentrates heretofore
then heated to 60° C. and stirred for one-half
prepared. The ester concentrates are all bland
hour, after which it was cooled .to 50° C. 400
and pleasant tasting, and remain clear and liquid
parts of ethylene dichloride were added to ef
even at low temperatures of about 0° C. The
fect partial solution of the mass, after which 13
procedures involved in the practise of this inven
parts of water were added to increase the water
tion can be very expeditiously carried out and
content of the soap-mass to about 24% to cause
require only simple and conventional equipment.
precipitation of the soap. After cooling the en
The various extractions and separations may be
tire mass to room temperature the soap and so]
performed with a minimum of di?iculty. For , vent phases were allowed to separate for 30 min
instance, the extraction of the semi-concentrate
utes, and the latter phase, then drawn off. The
from the partially saponifled mass in the process
soap phase was thereafter extracted seven times
of the present invention is more readily carried
with successive ‘100-part portions of ethylene di
out than corresponding extractions from com
chloride, and all of these extracts were combined
pletely saponi?ed masses produced according to
earlier processes. Further, the polar solvent ex
traction and fractionation is greatly facilitated
by the removal of the saturated glycerides which
further reduces the quantit: of oil to be handled.
With the above discussion in mind, there are
given hereinafter speci?c examples of procedures
according to the invention, which procedures are
to be taken as illustrative only and not in a limit
ing sense.
All parts given are by weight; the
vitamin units referred to are the U. S. P. vitamin
units.
Example I
with the solvent phase originally separated from
the saponi?cation mass, ?ltered, and heated un_
der reduced pressure to drive off the solvent thus
leaving a semi-concentrate, hereinafter desig
nated M, having a potency of 466,000 units of
vitamin A per gram.
100 parts of the semi-concentrate M prepared
as just described were mixed with 400 parts of
methanol, and heated to 50° C. to dissolve as
much as possible of the semi-concentrate. The
mixture was then cooled to —18° C. The super
natant solvent layer, which was entirely free of
suspended matter, was decanted from the solid
i?ed oil layer. The oil layer, hereinafter denoted
Several samples of the same batch of shark
N, was treated twice again with 400-part por
liver 011 containing 103,000 units of vitamin A per
gram (91% of which was in ester form and 9% 75 tions of methanol in the same way. The de
2,412,766
7
8
canted methanol extracts were combined and the
methanol removed by vacuum distillation to leave
min A associated with the isopropanol-soluble
material Q used. The methanol-insoluble resi
a vitamin concentrate of a potency of 1,250,000
units 01.’ vitamin A per gram, largely in the al
due R had a potency of 460,000 units of vitamin A
per gram, largely in esteri?ed i'orm, and con
tained about 49% of the vitamin A associated
coholic form, containing about 49.5% of the vita
min A in the semi-concentrate used. The undis
with the isopropanol-soluble material used. This
solved residue N from the methanol extraction
highly-potent ester product was devoid of un
had a potency of 272,000 units of vitamin A per
pleasant taste and odor and remained clear and
gram, predominantly in the esteri?ed form, and
?uid in the vicinity of 0° C.
contained about 50% of the vitamin associated 10
Example IV
with the semi-concentrate used. This residue
A semi-concentrate M containing 466,000 vita
was devoid of disagreeable taste and odor, re
min A units per gram was prepared as described
mained clear and ?uid at 0° C.
in Example II. 100 parts of the semi-concen
100 parts of a vitamin A ester methanol-insol
trate and 400 parts of methanol were mixed and
uble extraction residue N prepared as just de
agitated at room temperature. The agitation was ’
scribed were mixed with 400 parts of isopropanol,
ceased, and the methanol extract layer allowed
and the mixture heated to 41° C. to effect a ho—
to separate from the residual oil layer and demogeneous solution. The mixture was .then
canted off. The oil layer was twice again ex
cooled to —18° C. and ?ltered. The insoluble ma
terial O retained on the ?lter was twice extracted 20 tracted with methanol in the same way at room
temperature, and all the decanted methanol ex
with isopropanol in the same manner as the ma
tract layers were combined. The methanol was
terial N just described. The isopropanol ?l
driven off from the combined extracts by vacuum
trates were combined, and the isopropanol dis
distillation, leaving a residue having a potency
tilled off under reduced pressure in the presence
of 1,320,000 vitamin A units per gram, largely in
of N2 gas to leave a vitamin A ester concentrate
alcoholic form, and containing about 52% of the
having a potency of 530,000 units of vitamin A per
vitamins originally present in the semi-concen
gram. and containing about 39% of the vitamin
trate used. This residue was suitable for use as a
A present in the methanol-insoluble residue N
highly potent vitamin A alcohol concentrate, and
employed. The insoluble material 0 left on the
?lter by the isopropanol extraction had a potency 30 remained clear and ?uid at low temperatures.
The oil layer insoluble in methanol had a potency
of 160,000 units of vitamin A per gram, largely in
of 262,000 vitamin A units per gram, largely in
esteri?ed form, and contained about 61% of the
the esteri?ed form, and contained about 48% 01'
vitamin A present in the undissolved methanol
the vitamins in the semi-concentrate used. This
extraction residue N employed. Both of these
last products were completely devoid of unpleas 35 all was bland tasting, remained clear and ?uid at
0° C.
ant taste and odor, and remained clear and liquid
Example V
at low temperatures.
100
parts
of
crude
shark liver oil having a po
Example III
tency of 60,000 vitamin A units per gram, 50 parts
100 parts of the semi-concentrate M containing 40 of ethylene dichloride, and 3 parts of isopropanol
were mixed, and nitrogen gas bubbled through
466,000 units of vitamin A per gram as prepared
from shark liver oil in the manner described in
Example II and 400 parts of isopropanol were
mixed and warmed su?iciently to effect solution.
The mixture was then cooled to —18° C. and ?l
tered. The insoluble residue P retained on the
?lter was twice treated with isopropanol in the
the mixture to deaerate the same.
36 parts of
45% KOH (90% of amount required to complete
ly saponify the oil) were added with stirring.
Stirring was continued for about 20 minutes,
after which the thickened mass was insulated
against heat loss and allowed to stand for 16
same manner as the semi-concentrate M. The
hours. The mass was then heated to 60° C, and
isopropanol ?ltrates were combined and distilled
stirred for one-half hour, after which it was
under reduced pressure'in the presence of N2 gas cooled to 50° C. 400 parts of ethylene dichloride
to remove the isopropanol, leaving a concentrate
were mixed in to e?ect partial solution of the
Q having a potency of 1,030,000 units of vitamin
mass, after which 13 parts of water were added
‘ A per gram, both in esterifled and alcoholic forms,
to cause precipitation of the soap in the form
and containing about 71% of the vitamin A in
of granular particles. After cooling to roomvtem
the semi-concentrate M used. The isopropanol 55 perature the soap and solvent phases were al
insoluble residue P had a potency of 210,000 units
lowed to separate for 30 minutes and the latter
of vitamin A per gram largely in ester?ed form
phase drawn oil‘. The soap-phase was thereafter
and contained 29.0% of the vitamin A in the
extracted seven times with successive 400-part
semi-concentrate M used. Both products re
portions of ethylene dichloride, and all of these
mained clear and ?uid at about 0° C.
60 extracts were combined with the solvent phase,
100 parts of an isopropanol-soluble ester-and
removed from the saponi?ed ,mass, ?ltered and
alcohol vitamin material Q prepared as just de
vacuum distilled to drive oil'the ethylene di
scribed were mixed with 400 parts of methanol
chloride and leave a semi-cor oentrate having a
and heated to 50° C. to dissolve as much as DOS
potency of 282,000 vitamin A units per gram.
sible of the material. The mixture was then 65
100 parts of a semi-concentrate prepared as
cooled to —18° C. The supernatant solvent layer,
just described were mixed with 400 parts of meth
which was entirely free of suspended matter, was
anol, and heated to 50° C. to dissolve as much as
decanted away from the solidi?ed oil layer RL‘
possible of the semi-concentrate. The mixture
This oil layer R was treated twice again with 400
was then cooled to —18° C. The supernatant
part portions of methanol in the same way, The 70 solvent layer, which was entirely free of sus
decanted methanol extracts were combined and
pended matter, was decanted from the solidi?ed
the methanol removed by vacuum distillation to
oil layer. The oil layer was treated twice again
-leave a vitamin concentrate of a‘ potency of.
with ‘100-part portions of methanol in the same 1,337,000 units of vitamin A per gram, mostly in
way. The decanted methanol extracts were com
alcohol form, containing about 1% of the vita 75 bined, and the methanol removed by vacuum dis
a
2,412,768
9
10
tillation to leave a vitamin concentrate having
for 15 hours. The mass was then heated to 60°
C. and stirred for one-half hour, after which it
was cooled to 50° C. 400 parts of ethylene di
chloride were mixed in to e?ect partial solution
of the mass after which 13 parts of water were
added to cause precipitation of the soap in the
form of granular particles. After cooling the mass
to room temperature the soap and solvent phases
a potency of 768,000 vitamin A units per gram,
largely in the alcoholic form, and containing
about 20% of the vitamin A in the semi-concen
trate used. The undissolved residue had a po
tency of 231,000 vitamin A units per gram, largely
in the esteri?ed form, and contained about 80%
of the vitamin associated with the semi-concen
trate used. This residue was devoid of disagree
were allowed to separate for 30 minutes, and the
able taste and odor, remained clear and fluid at 10 latter phase then drawn off. The soap-phase
low temperatures and was eminently suitable for
was thereafter extracted seven times with suc
use as a high potency vitamin A ester concen
trate.
cessive 400-part portions of ethylene dichloride,
and all of these extracts were combined with the
Example VI
solvent phase, ?ltered, and heated under reduced
100 parts of crude shark liver oil having a po 15 pressure to drive o? the solvent and leave a semi- .
concentrate having a potency of 264,000 units of
tency of 106,000 vitamin A units per gram, 50
vitamin A per gram.
parts of ethylene dichloride, and 3 parts of iso
100 parts of semi-concentrate prepared as just
propanol were mixed, and nitrogen gas bubbled
described were mixed with 400 parts of methanol,
through the mixture to deaerate the same. 24
parts of 45% KOH (70% of amount required to 20 and heated to 50° C. to dissolve as much as pos
sible of the semi-concentrate. The mixture was
completely saponify the oil) were added with stir
then cooled to —18° C. The supernatant solvent
ring. Stirring was continued for about 20 min
layer, which was entirely free of suspended mat
utes, after which the thickened mass was insu
ter, was decanted away from the solidi?ed oil
lated against heat loss and allowed to stand for
layer. The oil layer was treated twice again with
16 hours. The mass was then heated to 60° C.‘
400-part portions of methanol in the same way.
and stirred for one-half hour, after which it was
The decanted methanol extracts were combined
cooled to 50° C. 400 parts of ethylene dichloride
and the methanol removed by vacuum distil
were mixed in to effect partial solution of the
lation to leave a vitamin concentrate having a
mass, after which 13 parts of water were added
to cause precipitation of the soap in the form of 30 potency of 610,000 vitamin A units per gram,
largely in the alcoholic form, and containing about
granular particles. After cooling the mass to
48% of the vitamin A in the semi-concentrate
room temperature the soap and solvent phases
used. The undissolved residue had a potency
were allowed to separate for 30 minutes and the
of 168,500 units of vitamin A per gram, largely
latter phase drawn off. The soap-phase was
in the esteri?ed form, and contained about 52%
thereafter extracted seven times with successive
‘100-part portions of ethylene dichloride, and all
of the vitamin associated with the semi-concen
trate used. This residue was devoid of disagree
of these extracts were combined with the solvent
able taste and odor, remained clear and ?uid at
phase and vacuum distilled to drive off the eth
low temperatures, i. e. about 0° C.
ylene dichloride and leave a semi-concentrate
having a potency of 236,000 vitamin A units per 40
Example VIII
gram.
100 parts of a semi-concentrate prepared as
just described were mixed with 400 parts of meth
anol, and heated to 50° C. to dissolve as much as
200 parts of crude shark liver oil containing
103,000 units of vitamin A per gram, were mixed
with 1.5 parts of isopropanol while bubbling nitro
gen gas into the mixture.
58 parts of aqueous
possible of the semi-concentrate. The mixture
45% potassium hydroxide (75% of the amount
was then cooled to —18° C. The supernatant
theoretically required to saponify all the saponi
solvent layer, which was entirely free of sus
fiable matter in the oil) were added, and the
pended matter, was decanted away from the
mixture
stirred for 30 minutes. The semi-solid
solidi?ed oil layer. The oil layer was treated
mass was then insulated against
twice again with ‘100-part portions of methanol 50 saponi?cation
temperature change and left quiescent for 12
in the same Way. The decanted methanol ex
tracts were combined, and the methanol removed
by vacuum distillation to leave a vitamin concen
trate having a potency of 692,000 vitamin A units
per gram, largely in the alcoholic form and con
taining about 17% of the vitamin A in the semi
concentrate used. The undissolved residue had a
potency of 206,000 vitamin A units per gram,
hours. Thereafter the mass was heated to 60°
C. while stirring in the presence of nitrogen gas
for 15 minutes. 800 parts of ethylene dichloride
were added, and the mixture thoroughly agitated.
Sumcient water was then added to the mass to
increase the moisture content of the soap phase
therein to about 24% and the solvent-soap mass
cooled to about 25° C. After allowing the mass
largely in the esterified form, and contained
about 83% of the vitamin associated with the 60 to stand at this temperature for 30 minutes, the
clear solvent layer was drawn off. The soap mass
semi-concentrate used. This residue was devoid
was again extracted by adding 800 parts oi.’ eth
of disagreeable taste and odor and remained clear
yl"ne dichloride thereto, agitating the mass for
and ?uid in the vicinity of 0? 0.
15 minutes, allowing the ethylene dichloride to
Example VII
65 settle to the bottom, and drawing oil’ the ethylene
dichloride. This extraction was repeated 6 times
100 parts of crude shark liver oil. having a
more. All theethylene dichloride solutions re
potency of 23,900 vitamin A units per gram, 50
moved from the saponi?cation mass were com
parts of ethylene dichloride and 3 parts of iso
propanol were mixed and nitrogen gas bubbled
bined and ?ltered, and then evaporated under
through'the mixture to deaerate it. 28 parts of 70 reduced pressure to remove ethylene dichloride,
leaving a semi-concentrate of the vitamins con
45% KOH (95% of the amount required to com
pletely saponify the oil) were added slowly with
taining 338,000 vitamin A units per gram.
stirring. Stirring was continued for about 20
This semi-concentrate was then extracted with
minutes, after which the thickened mass was in
3 successive ‘100-part portions of methanol at
sulated against heat‘loss and allowed to stand 76 —18° C., the methanol extracts were combined
2,412,?“
11
and the methanol evaporated oil? under reduced
pressure to leave a concentrate having a potency
of 388,000 units of vitamin A per gram, largely
in the form of alcoholic vitamin, and containing
about 14% of the vitamins present in the semi
concentrate used.
The unextracted residue from the methanol
treatment had a potency of 332,000 units of vita
12
100 parts of the semi-concentrate prepared as
just described were extracted three times with
‘100-part portions of methanol. The extracted
methanol-soluble oil contained 448,000 units of
vitamin A per gram, largely in the form of vita
min A alcohol. The methanol-insoluble oil frac
tion contained 340,000 units of vitamin A per
gram, largely in the form of vitamin A ester.
About 43% of the vitamin A in semi-concentrate
min A per gram, largely in esterl?ed form, and
contained about 86% of the vitamin A present 10 was present as the ester while 57% was in the
in the semi-concentrate. This vitamin A ester
alcohol form.
product was light in color and substantially de
It will be evident from the foregoing descripvoid of taste and odor.
tion and examples that there is provided by this
invention a process whereby unusually potent
Example IX
15 concentrates of the vitamins in their several
200 parts of shark liver oil containing 100,000
forms may be obtained; whereby the development
units of vitamin A per gram were mixed with 6
of the usual bitter “concentrate” taste is sub
parts of 99% isopropanol and the mixture stirred
stantially avoided; and whereby the concentrates
for 5 minutes in the presence of N2 gas in order
may be obtained in high yield and with a mini
to remove any entrapped air. Su?icient 45% 20 mum of handling di?iculties.
aqueous KOH (63.5 parts) to saponify about 80%
While the only specific method of e?ecting sa
or the oil was added and the mixture stirred at
poni?cation (hydrolysis) of the esters contained
a medium rate for about 7 minutes. The tem
in marine oils has involved the use of an alkaline
perature at this point was 49° C. The stirring
agent, other methods to effect splitting of the
was discontinued and the mass insulated and 25 esters may be employed within the purview of this
invention and particularly enzyme saponi?cation
allowed to stand for 12 hours. 800 parts of eth
(hydrolysis) .
ylene dichloride were added and the mixture heat
Since certain changes in carrying out the above
ed, while stirring slowly, to about 60° C. Sur?
process and certain modi?cations in the compo
cient water was added to raise the moisture con
sition which embody the invention may be made
tent to about 25% and the mixture then cooled
without departing from its scope, it is intended
to about 27° C. Stirring was discontinued and
that all matter contained in the above description
the mass allowed to stand for 15 minutes. The
shall be interpreted as illustrative and not in a
lower clear solvent layer was removed and an
limiting sense.
other fresh batch of solvent added, stirred into
the saponi?ed mass, separated, and removed. In 35
Having described my invention, what I claim
as new and desire to secure by Letters Patent is:
this manner a total of eight extractions were
1. A process of producing fat-soluble Vitamin
made. The combined solvent extracts were ?l
tered and the solvent evaporated off under re
concentrates, one rich in vitamin esters and one
duced pressure and in the presence of N2 gas,
rich in vitamin alcohols, which comprises saponi
leaving a. semi-concentrate having a potency of 40 fying from 60% to 95% of the sapom'f'lable con
447,000 units of vitamin A per gram.
tent extracting
of a fat-solublejtagiifiontagiimarine
100 parts of the semi-concentrate prepared as
oil,
the res? ng saponaceoi?'masr"
above described were mixed with 400 parts of
with a water-immiscible solvent which will not
95% ethanol and the mixture warmed to about
dissolve the soap to recover the unsaponi?ed frac
50° C. while agitating in the presence of N2 gas.
tion containing vitamin alcohols and vitamin es
The mixture was then cooled to —-18° C. and
ters, extracting said unsaponifled fraction with a
?ltered. The insoluble oily layer was extracted
highly polar selective solvent which is character
twice more in the same manner with 400-part
ized by being miscible with the vitamin alcohols
portions of ethanol. The combined ethanol ex
but immiscible with the vitamin esters to recover
tracts were evaporated to drive off the ethanol. 50 a concentrate rich in vitamin alcohols, the residue
The extracted ethanol-soluble oil contained
being rich in vitamin esters, contacting the resi
460,000 units vitamin A per gram, largely in the
due rich in vitamin esters with an organic ali
form of vitamin A alcohol. The ethanol-insolu
phatic polar solvent characterized by being mis
ble oil was also evaporated to remove entrained
cible with said residue at temperatures substan
ethanol. This fraction contained 416,000 units
tially above room temperature and partially im
of vitamin A per gram, largely in the form of
miscible therewith at temperatures below room
vitamin A ester. ' About 70% of the vitamin A
temperature, cooling the mass to cause layer
present in the semi-concentrate was in the esteri
formations and separating the solvent layer con
?ed form, whereas about 30% of the vitamin A
was present in the alcohol form.
60 taining the extracted vitamin esters from the sol
Example X
400 parts of grey?sh liver oil containing 25,000
vent-insoluble portion of said residue.
"'
2. A process of producing fat-soluble vitamin
concentrates, one rich in vitamin esters and one
45% aqueous KOH (155.5 parts) to saponify
rich in vitamin alcohols, which comprises saponi
fying from 60% to 95% of the saponi?able con
tent of_ a fat-soluble vitamin-containing marine
oil, extracting the resulting saponaceous mass
about 95% of the oil was added and the mixture
stirred while bubbling N2 gas into the mixture for
with a water-immiscible solvent which will not
dissolve the soap to recover the unsaponi?ed
65 minutes, during which time the temperature 70
increased. from 28° C. to about 55° C. The soap
mass was treated further essentially as described
in Example VIII. The resultant semi-concen
trate contained 419,000 units of vitamin A per
gram.
75
fraction containing vitamin alcohols and vitamin
esters, extracting said unsapom'?ed fraction with
units of vitamin A per gram were stirred for 10
minutes in the presence of N2 gas at 28° C. in
order to remove any entrapped air.
Su?icient
methanol to recover a concentrate rich in vita
min alcohols, the residue being rich in vitamin
esters, contacting the residue rich in vitamin
esters with an organic aliphatic polar solvent
neuron nuu
2,412,766
'
.
13
characterized by being miscible with said residue
at temperatures substantially above room tem
perature and partially immiscible therewith at
temperatures below room temperature, cooling
the mass to cause layer formations and separat
ing the solvent layer containing the extracted
14
rating the isopropanol layer containing the ex
tracted vitamin esters from the isopropanol-in
soluble portion of said residue.
5. A process of producing (fat-soluble vitamin
G1 concentrates, one rich in vitamin esters and one
rich in vitamin alcohols, which comprises saponi
vitamin esters from the solvent-insoluble portion
fying from 60% to 95% of the saponi?able con
of said residue.
tent giggle, liyeiimoilk extracting the resulting
_
/
3. A process of producing’fat-soluble vitamin
sapon‘aceous‘winass with a water-immiscible sol
concentrates, one rich in'v'itamin esters and one 10 vent which will not dissolve the soap to recover
rich in vitamin alcohols, which comprises sapon
the unsaponi?ed fraction containing vitamin al
ifying from 60% to 95% of the saponi?able con
' cohols and vitamin esters, extracting said unsa
tent of a fat-soluble vitamin-containing marine
poni?ed fraction with methanol to recover a. con
oil, extracting the resulting saponaceous mass
centrate rich in vitamin alcohols, the residue be
with a water-immiscible solvent which will not 15 ing rich in vitamin esters, contacting the residue '
dissolve the soap to recover the unsaponi?ed
rich in vitamin esters with isopropanol, cooling
fraction containing vitamin alcohols and vitamin
the mass to cause layer formations and separat
esters, extracting said unsaponi?ed fraction with
ing the isopropanol layer containing the extract
methanol to recover a concentrate rich in vitamin
ed vitamin esters from the isopropanol-insoluble
alcohols, the residue ‘being rich in vitamin esters, 20 portion of said residue.
,
contacting the residue rich in vitamin esters with
6. A process of producing ?at-soluble vitamin
isopropanol, cooling the mass to cause layer for
concentrates, one rich in vitamin esters and one
mations and separating the isopropanol layer
rich in vitamin alcohols, which comprises saponi
containing the extracted vitamin esters from the
fying from 60% to 95% of the saponi?able con
isopropanol-insoluble portion of said residue.
25 tent of halibut liver oilkextracting the resulting
4. A process of producing fat-soluble vitamin
saponacwmaisywit? a water-immiscible sol
concentrates, one rich in vitamin esters and one
vent which will not dissolve the soap to recover
rich in vitamin alcohols, which comprises saponi
the unsaponi?ed fraction containing vitamin a1
fying from 60% to 95% of the saponi?able con
cohols and vitamin esters, extracting said unsa
tent of shark liver oil, extracting the resulting 30 poni?ed fraction with methanol to recover a con
sap‘onaceouFiHa'sWi't‘h a water-immiscible sol
centrate rich in vitamin alcohols, the residue
vent which will not dissolve the soap to recover
being rich in vitamin esters, contacting the resi
the unsaponi?ed fraction containing vitamin al
due rich in vitamin esters with isopropanol, cool
cohols and vitamin esters, extracting said unsa
ing the mass to cause layer formations and sepa
poni?ed fraction with methanol to recover a con
centrate rich in vitamin alcohols, the residue
being rich in vitamin esters, contacting the resi
due rich in vitamin esters with isopropanol, cool
ing the mass to cause layer formations and sepa
35 rating the isopropanol layer containing the ex
tracted vitamin esters from the isopropanol-in
soluble portion of said residue.
LORAN O. BUXTON.
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