Treatment of vegetable oils

A process for preparing triglycerides which are suitable as a lipid base for an injectable composition is described.

BACKGROUND OF THE INVENTION 
1. Field of the Invention 
This invention relates to oil-based compositions which are suitable for 
injection. 
2. Description of the Art Practices 
U.S. Pat. No. 4,280,996 issued July 28, 1981 to Okamoto et al, describes a 
stable fat emulsion which is suitable as a nutritive infusion fluid. The 
composition in the Okamoto et al patent is stated to be useful in that it 
is rapidly metabolized from the blood. The patent of Meyer et al, U.S. 
Pat. No. 2,977,283 issued Mar. 28, 1961, describes therapeutic fat 
products which are stated to be suitable for intravenous use in human 
beings. 
Phosphatide emulsifying agents are described by Meyer et al in U.S. Pat. 
No. 2,945,869 issued July 19, 1960. Further disclosures of oil-containing 
products are found in U.S. Pat. No. 2,819,199 issued Jan. 7, 1958 to 
Kalish. 
The purification of oils for the removal of undesirable colors and odors is 
described in U.S. Pat. No. 3,798,246 issued Mar. 19, 1974 to Shimazaki et 
al. In the U.S. Pat. No. 3,798,246, the use of silica gel in combination 
with an eluting organic solvent is described. Gunther, in U.S. Pat. No. 
4,425,276 issued Jan. 10, 1984 describes a separation of the various 
components of an oil through the use of silicic acid gels in combination 
with lower alkanols. Gunther suggests that the purified oils will be 
useful for pharmaceutical purposes. The oils of Gunther are processed at 
temperatures up to 70.degree. C. in the presence of the alkanol. 
Chang, in U.S. Pat. No. 4,101,673 issued July 18, 1978, states that the 
parental administrable oil-in-water emulsions from soybean oil may be 
obtained by first treating the oil with silicic acid or silica gel. Chang 
further describes including gamma tocopherol and ascorbyl palmitate to 
function respectively as an antioxidant and as a metal scavenging agent in 
his oil. The purification of triglycerides is suggested in an article 
entitled "Purification of Triglycerides With an Alumina Column" by Jensen 
et al which has been reported in Lipids, Vol. 1, No. 6, (1966) page 451 et 
seq. An article entitled "Isolation and Identification of 
trans-3,5-Dimethoxystilbene from High Quality Tall Oil Fatty Acids by 
Liquid Chromatography and Mass Spectrometry" describes the use of liquid 
column chromatography for low temperature solvent fractionation of an oil. 
The above article is published in J. Am. Oil Chem. Soc. (1972) Vol. 49 
(12), pp. 675-677 by Min et al. 
The treatment of cottonseed oil is reported in an article entitled "A 
Method for Adsorbent Fractionation of Cottonseed Oil for Experimental 
Intravenous Fat Emulsions" by Singleton et al, which is reported in J. Am. 
Oil Chem. Soc. (1966), Vol. 43 (10), pp. 592-595. The Singleton et al 
article describes the use of a mixture of bleaching earth and alumina as a 
fractionation method for removal of pigments and polar components of 
cottonseed oil. 
The foregoing references to the extent applicable to the present invention 
are herein incorporated by reference. Percentages and ratios given herein 
are by weight, temperatures are in degrees Celsius and pressures are in 
atmospheres above ambient unless otherwise indicated. 
SUMMARY OF THE INVENTION 
A process is described for preparing an injectable vegetable oil selected 
from the group consisting of soybean oil and sunflower oil and mixtures 
thereof which comprises: 
(a) first treating the oil with an acid clay; 
(b) deodorizing the vegetable oil; 
(c) treating the deodorized oil with an acid clay to reduce the content of 
a member selected from the group consisting of diglycerides, tocopherol 
components, and trilinolenin and mixtures thereof; and 
(d) thereafter conducting a particulate filtration to remove a substantial 
portion of the acid clay, 
thereby obtaining the injectable vegetable oil. 
An injectable oil product is described which is a triglyceride with each 
fatty acid in the ester having from 12 to 20 carbon atoms; having higher 
free fatty acid content; having reduced trilinolenin content; having 
reduced diglyceride content and reduced natural tocopherol content based 
on the starting oil. 
DETAILED DESCRIPTION OF THE INVENTION 
The present invention first requires an oil (triglyceride) which is 
suitable for injection. The present invention preferentially uses soy or 
sunflower oils as the raw material. Each of the oils are commercially 
available. A material such as cottonseed oil is undesirable due to its 
high gossypol content. The gossypol in cottonseed oil is toxic and 
therefore its inclusion requires a greater degree of processing to remove 
the toxicity from the oil to render the oil suitable for injection. As the 
oil is to be used for injectable purposes, the beneficiaries of this 
invention are persons who are ordinarily in a weakened state and anything 
other than a substantially pure oil is of critical importance. 
The oils as referred to above are triglyceride materials. The fatty acid 
portion of the esters is substantially the same as that found in 
commercial soy or sunflower seed oil, i.e. C.sub.12 to C.sub.20. In the 
present invention, the trilinolenin content is reduced in the processing 
and therefore this component is present in lower quantities than is 
ordinarily found in the starting oils. Trilinolenin is the trilinolenic 
acid ester of glycerin. 
Typically, the oil for use in the present invention has been obtained by 
crushing the oilseed followed by hexane extraction of the oil to give the 
crude oil. The crude oil is then hydrated with a small amount of water to 
remove the gum-forming components. Gum-forming components are synonymous 
with lecithin or phosphatides. The degummed oil is then caustic-refined to 
reduce the phosphatides further. Free fatty acids are also removed by the 
caustic-refining through saponification to a soap. 
In continuing with commercial processing, the once-refined oil, that being 
defined as the oil following caustic treatment, is bleached and then 
deodorized. 
In the present invention, the processing is substantially similar up to the 
point where the once-refined oil is obtained. Thereafter, the once-refined 
oil is treated with an acid clay. 
Suitable acid clays for use in the present invention include materials such 
as TONSIL OPTIMUM FF, TONSIL OPTIMUM EXTRA FF or TONSIL L-80. In 
particular, montmorillonite clays should be utilized and such materials 
typically have a constitution of from 60 to 85% by weight SiO.sub.2 ; 10 
to 20% aluminum oxide; 1 to 8% ferric oxide; 0.5 to 2.5% magnsium oxide; 
0.4 to 1.5% calcium oxide and 7.2% volatiles by ignition loss. Other 
suitable acid clays include any which exhibit typical acid behavior as 
does the aforedefined clay. It is necessary herein that an acid clay be 
utilized as it is desirable to increase the measured free fatty acid 
content of the end product beyond that which would be found in an 
ordinarily processed oil. 
The oil is acid clay treated as defined in step (a) of the present 
invention, preferably at a temperature of from about 80.degree. C. to 
about 130.degree. C., most preferably from about 95.degree. C. to about 
115.degree. C. The acid clay is added to the vegetable oil in the absence 
of any solvents and therefore, extraneous solvents are avoided. It is 
noted, however, that the oils of the present invention have been obtained 
by hexane extraction in the first instance, however, the hexane has been 
removed due to routine processing and any residual components are further 
removed by the processing of the present invention. 
The next step (b) of the present invention is to deodorize the vegetable 
oil. Deodorizing is commonly conducted on vegetable oils to make them 
palatable to the human taste. In the present case, the deodorizing is 
conducted to remove various unwanted pigments and other components. As the 
oils must be injectable, the deodorizing step herein is not conducted to 
make the oil palatable but rather to remove components which may otherwise 
interfere with the treatment prescribed by the injectable oil. The 
deodorization does remove a substantial amount of the free fatty acids, 
aldehydes, pigments and pest-control agents present in the oil. 
The deodorizing step in the present invention consists of treating the oil 
with steam and applying a vacuum to remove volatilized components. The 
deodorization step is conducted at from about 220.degree. C. to about 
280.degree. C., preferably from about 240.degree. C. to about 260.degree. 
C. 
After the vegetable oil has been steam-deodorized, a second treatment with 
an acid clay is conducted. The acid clay at this portion of the invention 
is conveniently added in a weight ratio to the oil of from about 1:99 to 
about 1:1, most preferably from about 1:19 to about 1:4. The purpose of 
the second acid clay treatment is to remove a member selected from the 
group consisting of diglycerides, tocopherol, and trilinolenin. 
The foregoing components are believed to be detrimental to the 
effectiveness of the oil as an injectable medium. It is also noted at this 
point that the free fatty acid content of the vegetable oils is slightly 
increased upon the second acid clay treatment. It is believed that the 
increase in free fatty acid content is partially due to acid hydrolysis of 
the triglyceride oil. Thus, the injectable oil of the present invention 
will have a higher free fatty acid content than is found in ordinary oils. 
The free fatty acid content of the injectable oil is from about 0.005% to 
about 0.015% by weight of the oil. 
The second treatment (c) with an acid clay is conducted at from about 
10.degree. C. to about 60.degree. C., preferably from about 25.degree. C. 
to about 45.degree. C. The second acid clay treatment of the oil is 
advantageously conducted at the lower temperature thereby ensuring that 
unwanted by-products do not form. One positive material which is formed 
during the acid clay treatment is the free fatty acids which are generated 
in amounts higher than that found in an ordinary vegetable oil. The 
process herein advantageously has a slightly higher than ordinary amount 
of fatty acids therein because the free fatty acids are already partially 
digested. Therefore, nutritional needs are fulfilled more easily by the 
body not having to hydrolyze triglyceride into the essential fatty acids. 
Trilinolenin breakdown would not produce any essential fatty acids. 
Diglycerides are known emulsifiers and may alter both the emulsion that is 
injected and affect absorption from the bloodstream into tissues. 
The final step in processing the injectable oil of the present invention is 
to conduct a filtration of the oil sufficient to remove substantially all 
of the acid clay utilized in the process. This, of course, ensures that no 
particles which could interfere with the desirable properties of the 
injectable oil will be present in the finished product. Preferably, the 
filtration is conducted through a pore size filter of from about 0.1 to 
0.45 microns, preferably from about 0.15 to about 0.25 microns. Suitable 
filtering materials include sterilized membrane cartridges supplied by 
Gelman Sciences Filtration Equipment, Inc. The filters are of a size that 
they function as microbial filters. 
A suggested embodiment of the present invention is hereafter disclosed. The 
injectable oil obtained from the example may be utilized in any 
conventional manner for forming an oil-based injectable composition.

EXAMPLE I 
A degummed and caustic refined triglyceride oil obtained from crushed 
soybeans is slurried with 0.5% acid clay by weight of the oil at 
115.degree. C. with agitation for about 30 minutes. The oil is then 
steam-deodorized. A column is prepared which is packed with 10 parts of 
montmorillonite clay having substantially the same composition as 
previously indicated in the specification. The oil at 90 parts is passed 
through the column using nitrogen at slightly greater than atmospheric 
pressure to elute the oil. The recovered oil is then passed through a 0.45 
micron membrane filter to remove the acid clay and any microorganisms. 
The oil has increased free fatty acid content and decreased tocopherol, 
diglyceride and trilinolenin contents. The recovered oil is suitable for 
use in an injectable composition. 
If desired, the tocopherol which is removed in the present invention may be 
added back as either a source of natural or synthetic vitamin E. 
EXAMPLE II 
A mixture of a triglyceride vegetable oil wherein the average carbon chain 
length of the fatty acid components of the triglyceride is from about 14 
to about 18 carbon atoms is mixed with 0.3% of Filtrol 105 acid clay by 
weight of the oil. The mixture is agitated at 115.degree. C. for one-half 
hour. The product is thereafter pumped through a plate and frame filter 
press at about 1.5 atmospheres over ambient. 
The oil is then sent to a steam distillation apparatus and steam-sparged to 
reduce the free fatty acid content. 
The oil at 90 parts is then mixed with Tonsil Optimum FF acid clay at 10 
parts and processed at 20.degree. C. to 45.degree. C. The oil is further 
recovered as previously described to give a suitable injectable oil. 
The foregoing example may be modified by passing the product through a 
column in the second step instead of mixing the oil with the acid clay. In 
either case, it is advantageous to process the oil through the acid clay 
at a temperature of from about 20.degree. C. to 45.degree. C. which is 
below the temperature first utilized for the acid clay treatment. 
The clays which are suitable herein are available from L. A. Salomon & 
Bro., Port Washington, N.Y. The clays have the following physical 
parameters in Table I. 
TABLE 1 
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OPTIMUM 
EXTRA OPTIMUM L-80 
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Bulk Density 0.02 lb/cu. in. 
0.020 0.023 
(max.) 
Free Moisture 12% 10% 10% 
(max.) 
Acidity 0.4% 0.04% 0.02% 
(max.) 
Filtration Speed 
2'/100 cm.sup.3 
2'/100 cm.sup.3 
2'/100 cm.sup.3 
(max.) 
Oil Retention 40% 40% 36% 
(max.) 
pH (max.) 3.5 4.5 7.0 
Surface area 200 m.sup.2 /g 
180 m.sup.2 /g 
160 m.sup.2 /g 
(min.) 
Particle Sizes 
Stays on mesh 4% 4% 3% 
100 (max.) 
Stays on mesh 20% 20% 20% 
200 (max.) 
Stays on mesh 25% 25% 25% 
230 (max.) 
Stays on mesh 40% 40% 35% 
325 (max.) 
Stays on 25 75% 75% 75% 
microns (max.) 
Chemical Analysis 
SiO.sub.2 % 68-73 69-74 68-73 
(min.-max.) 
Al.sub.2 O.sub.3 % 
9-12 10-13 11-14 
(min.-max.) 
Fe.sub.2 O.sub.3 % 
1-3 3-5 3-5 
(min.-max.) 
Na.sub.2 O % 0-1 0-2 0-2 
(min.-max.) 
MgO % 1-3 1-3 3-5 
(min.-max.) 
K.sub.2 O % 0-1 1-2 1-2 
(min.-max.) 
CaO % 3-5 1-2 2-4 
(min.-max.) 
Ignition Loss 12% 8% 8% 
(max.) 
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