CA1076138A

CA1076138A - Purification of nutritive oils

Info

Publication number: CA1076138A
Application number: CA233,395A
Authority: CA
Inventors: Stephen S. Chang
Original assignee: Vitrum AB
Current assignee: Vitrum AB
Priority date: 1974-08-19
Filing date: 1975-08-13
Publication date: 1980-04-22
Also published as: US4101673A; JPS5147005A; GB1522149A; DE2533612A1; FR2282266B1; SE7509201L; FR2282266A1

Abstract

SUBSTITUTE
REMPLACEMENT
SECTION is not Present Cette Section est Absente

Description

~ i ~)7~13~

BACKGROUND OF THE I~VENTION
1. Field of the Invent on This invention relates to a nutritive oil in water emulsion for use in parenteral administration, wherein said nutritive oil is sunflo~er oil. The invention further relates to the purification of nut_itive oils used in oil in water emulsions for parenteral feeding, such as soybean and sunflower oll, and in particular, the invention relates to the removal from such oils of undesirable components such as peroxides, pigments and thermal and oxidative decomposition Droducts and p~lymers. Autoxidation of the purified oil is prevented by adding to the purified oil a tocopherol antioxidant, preferably y-tocopherol, along with a metal scavenging agent such as ascorbyl palmitate.

2. The Prior Art ; Glucose in solution has long been used for the pur-pose of parenteral nutrition. However, emulsions of certain nutritive oils in water have certain definite advantages over glucose solutions for that purpose. Firstly, oil has a higher caloric content ~han does glucose. Secondly, since oil is insoluble in water, it does not exert an osmotic effect and thus, can be used in vivo at higher concentrations than can glucose. However, when oil in water emulsions are used for ` intravenous feeding, there are several distinct problems which must be contended with. Th~s, such oil ir water emulsions, when injected intravenously, can cause many adverse physio-logical effects, such as back pain, fever, chills, headache, dizziness, blood pressure fluctuations, liver damage, and the so-called "overloading svndrome", and also, the emulsion may be damaged during storage and transportation under v ~17f~1~8 refrigerated temperatures. It is an object of this inven-tion to provide a process for purifying such nutritive oils whereby to remove from the oils those subs~ances which are at least Fartially responsible for the problems associated with - their use in parenteral emulsions. Among these substances -e peroxides pigments, unsaponifiables such as sterols, and thenna} and oxidative decompositior. products and polymers.
It is a further object of the invention to provide a proc~ss whereby autoxidation of the purified oils may be retarded.
There are many techniques known in the art for puri-fying nutritive oils for use in oil in water emulsions for parenteral feeding, :;ut none of these techniques involves the use of silicic acid for removing the above-described impurities.
See, e.g., Singleton et al, "A Method For Adsorbent Fractiona-tion of Cottonseed Oil For Experimental Intravenous Fat Emulsions", The Journal of the American Oil Chemists' Society, Vol. 43, pp. 592-595 (1966), which describes, in connection with the preparation of aqueous cottonseed emulsions Lor - parenteral administration, removal of pigments and polar com-ponents oL cottonseed oil by sequentially treating the oil with bleaching earth and alumina adsorbents; and U.S. Patent

3,169,094 to Wretlind, which describes mild extraction of soybean oil with an organic solvent such as ethanol, ether, or petroleum ether, followed by preparing an aqueous emulsion of the thus treated soybean oil and egg phosphatides, this emulsion being suitable for parenteral administration.

5~M~ARY OF T~E INVENTION
According to one aspect of the present invention, there is provided an aqueous emulsion of 4~n~H~wer oil, which emulsion is highly advantageous for parenteral ad~.inistration.

1(~ 7~13~3 According to another aspect of the inventivn, there is provided a method of purifying nutritive oils to remove therefrom impurities such as peroxides, pigments, unsaponi-fiables such as sterols, and thermal and oxidative decompo-sition products and polymers by passing the oil through a column or a layer of a suitarle siliceous adsrobent, such as silicic acid or silica gel. The oil which has been thus puri-fied, while having considerably less of the above-mentioned impurities than does the original oil, may undergo autoxida-tion at a faster rate, with the possibility of forming more undesirable peroxides. In ordar to stabilize the thus purified oil and retard its tendency to~-ard undergoing autoxida-tion, the invention further provides a method for stabilizing the puri-fied oil which involves adding to the purified oil a tocopherol antioxidant, perferably y-tocopherol, desirably together with a scavenging agent such as ascorbyl palmitate, to thereby in-crease its resistance toward autoxida-tion. As a result of this stabilization, emulsions prepared from the puriied and stabilized oil may be stored and transported without undergoing i 20 an excessive degree of oxidative decomposition.

BRIEF DESCRIPTION OF THF DRAWINGS
PIGURE 1 is a photograph of a silicic acid thin layer r chromatogram of a soybean oil sample before and after purifica-tion on a silicic acid column;
FIGURE 2 is a photograph of a silicic acid thin layer chromatogram of a sunflower oil sample before and after purifica-tion on a silicic acid column;
FIGURE 3 is a photograph of a silicic acid thin layer chromatogram comparing individual samples of sunflower oil, name'y: original sunflower oil (A), a soybean oil isolated - r - _ -J ~

from a commercially available product (8), sunflower oil which has been purified hy passage through a silicic acid column (C), and soybean oil which has been purified by passage through a silicis acid column ~D); and FIG. 4 is a photograph of a silicic acid thin layer chromatogram comparing individual samples of sunflower oil, namely: original sunflower oil (A), sunflower oil purified by passage through a filtering pad of silicic acid (s, C, D), and sunflower oil purified by passage through a silicic acid column (E).

- D~TAILED DESCRIPTION OF THE INVENTION
There will now be given a detailed description of the invention, which description will be best understood when taken in conjunction with the accompanying drawings.

I. PURIFICATION OF OILS BY SILICIC ACID COLUMN C~ROMATOGR~PHY
l. Soybean Oil Silicic acid of 100 mesh particle size, such as the Analytical Reagent Grade manufactured by Mallinckrodt Chem.
Works, was washed and activated according to the method des-cribed by Sahasrabudhe et a~ in Jour. ~mer. Oil Chem. Soc.
` 38:88, 1961. Three hundred gm of the wasi:ed, activated silicic acid were used to pack a chromatograph column of 40 mm. diameter to an approximate height of 50 cm. A commercialiy refined, bleached and deodorized soybean oil was passed through the column by either applying vacuum at the bottom or pressure at the top, or both. The temperature of the column was maintained at room temperature throughout the procedure. If desired, the column m3y be wrapped with an electric heating tape to increase its temperature to about 60-80C, which has the effect of _ . -- -- , ~ _ . --lU~i138 significantly increasing the flow rate of the oil through the column. The oil can be passed through the column alone or in the form of a solution in a solvent, such as hexane. To prevent oxidation of the oil, the process may be conducted under an inert atmosphere such as nitrogen. When the oil or a solution thereof was passed through the column, the impurities in the oil which included peroxides, pigments, unsaponifiables, polar - monomers, and thermal and oxidative decomposition products and polymers were adsorbed on the column as a dark colored band.
The first 25 gm. or so of eluate were collected separately for later analysis. The oil or solution thereof was continuousiy fed into the column until the colored band moved dowr. the column. The passage of oil through the column was continued until the dark colored band approached the bottom of the col~unn. The eluate or purified oil, after passing through the silicic acid columrl was suitable for the preparation of oil in water emulsions for parenteral feeding.
The soybean oil, both before and after pasasage through the silicic acid column was analyzed for color by Official Method Cc-13c-50 of the American Oil Chemists' Society, un~aponifiable matter by Official Method Ca-6a-40 of the American Oil Chemists' Society, and non-urea-adduct-- forming esters by the method of Firestone described in Journal of the American Oil Chemists" Society 38, 418-422, 1961. The results of these analyses are shown in Tab_e I, and clearly indicate that purification by silicic acid column effectively removes most of the pigmer.ts, unsaponfiables and non-urea-adduct-forming esters which are present in the commercially refined, bleached and deodorized sobyean oil.
As can also be seen from the data in Table 1, slightly 107~;138 bet~er results are obtained when the soybean oil is passed througn the column in the form of a hexane solution thereof, although even by using t'.e oil alone on a dry column, the purified oil is considerably purer than either the starting oil (which is a commercially refined, 'oleached, and deodorized product) or a soybean oil isolated from a commercial oil in water emulsion.

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The effectiveness of the silicic acid column in purifying the soybean oil can also be shown by thin layer chromatographic analysis according to the method described by W. 5. Singleton, et al in Jour. Amer. Oil Chem. Soc. 43, 592-595, 1966. Using this technique, a sample of the original soybean oil (D), as well as samples of the first 25 gm of eluate (E) and the purified oil (F! were analyzed on silicic acid plates. Figure 1 is a photograph of the thin layer chroma-togram. As can be seen in Figure 1, sample (D) contains con-10 siderable amounts of slow moving impurities near the starting line. These impurities correspond to the dark colored band on the silicic acid column. Sample (E) contains only traces of these slower moving impurities, while sample (F) contains al-most none of these impurities.
It should be noted that although in the foregoing example reference was made to hexane as a suitable solvent for the nutritive oil, other alkane solvents may also be employed.
Thus, in general, suitable alkane solvents are those contain-`. ing from 5 to 18 carbon atoms, a preferred class of alkanes ; 20 being those containing from ~ to 10 carbon atoms. Mixtures of such alkanes may also be employed, e.g., petroleum ether.
of course, if alkane solvents are used that are gaseous at ambient temperatures, then they should be kept under pressure so as to be in liquid form.
Where a solution of nutritive oil in an alkane solvent is utilized, rather than the oil alone, the ratio by volume of solvent to oil is generally from about 10:1 to 0.1:1, a more preferable range being from 4:1 to 0.2:1.

1~76138 2 . Sunf lower oil The same experiments as described above were con-ducted with sunflower oil, and similar result~ were obtained as sho~- in Table II and ~IG. ~.

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~s can be seen from the data in Table II, the puri-fication of sunflower oil by silicic acid col~nn chromatograph effectively removes most of the in;purities present in the starting oil.
FIG. 2 is a photograph of a thin layer silicic acid chromatosram of a sample of the original sunflower oil (A), a sample of the first 25 gm. of eluate (B) and a sample of the purified oil (C). As can be seen in Figure 2, sample (A) contains considerable amounts of slow moving impurities wni-h are not present to any appreciable extent in sample (~).
Sample (B) contains minor amounts of these impurities.
In addition, reference should be had to Figure 3.
Figure 3 is a photograph of a silicic acid thin layer chroma-togram comparing (A) a sanple of the original sunflower oil;
(B) a sample of soybean oil isolated from Intra-li.pid, a commercial oil in water emulsion made from soybean oil;
(C) a sample of purified sunflower oil; and (D) a sample of purified soybean oil.
The oil (B), isolated from Intralipid, showed a sig-nificantly darker color and higher conten' of unsaponifiables : and non-urea-adduct-forming esters than either the soybean oil or sunflower oil purified by the silicic acid col-~mn, and also had more and denser spo,s due to impurities than either of the purified oils.

II PURIFICATION OF OILS BY SILICIC ACID FILTERING PAD
1. Sunflower oil In addition to the silicic acid column chromato-30 graphic technique described above, the present invention can ,~is¢::, :1~761~

also be performed using a pad of silicic acid. Thus, the treatment of the oil can be conveniently accomplished by filtering the oil through a l/2 in. thick layer of 5ilicic acid. When sunflower oil was filtered through a suchner funnel prepacked with a 1/2 in. thick layer of silicic acid, the filtrate had the same color as the oil purified by passage through a column of silicic acid. To insure complete puri-fication of the oil using this technique, the treatment can a:so be accomplished by filtering the oil several times ]0 through the silicic acid pad. When this is done, it is pre-ferred that a fresh pad of silicic ac d be used for the last filtration. (It should be noted that the foregoing techr.ique may also be performed using a solution of the nutritive oil in a suitable solvent such as those described at page 8, second paragraph.) Although the foregoing description referred tc a one half inch thic~ness for the silicic acid layer, it will, of courso, be apparent that this particular thickness is not critical. Thus, the thickness may be from about 1/8 to 4 inches, and p_eferably is from about 1/4 to 2 inches.
Table III gives the results of photometric analyses of sunflower oil purified by filtration through a pad of silicic acid. For comparison purposes, the data for the original sunflower oil as well as for sunflower oil purified by passage through a silicic column are given.

~07613E3 TABLE III
PURIFICATION OF SUNFLOWER OIL BY
FILTRATION THROUGH A LAYER OF SILICIC ACID

Photometric Col~r Q4~ 550 mu (A) Original Sunflower Oil ¦ 4.3 ~ 0.8 (B) Oil Fil,ered Once th-ough a 1.5 0.0 1/2~ Layer of silicjc Acid (C) Oil Filtered 3 Times through a l.'j 0.0 1/2" Layer of Silicic Acid (D) Oil Filtered 3 Times through a 1.5 0.0 1/2U Layer of Silicic Acid then through a Fr3sh Layer of Silicic (E~ Oil Purified by Dry Silic-c Acid 1.5 0.0 Column ~
.' I
Samples of each of these oils were analyzed by th n layer chromatography. Figure 4 i5 a photograph of the thin layer chromatogram. As can be seen therein, sunflower oil filtered through silicic acid, particu arly the oil which was filtered three times through a 1/2 in. layer of silic-c acid and then once through a fresh 1/2 in. layer of silicic acid (D) was practically as free of impurities as was the sun-flower oil purified by passage through a silicic acid column III EVALUATION OF OTHER r~DSORBF~TS
Several other adsorL~nts were tested to ascertain their efficacy in the purification of sunflower oil. The procedure followed was essentially the same as that described above in II, with no solvent used. Th2 oil used was a refined, . . , bleached and deodorized sunflower oil. The adsorbents tested were silicic acid, silicic acid with 4% water, cl--y, silica gel, Florisil, Alumina and active carbon. The data in Table IV clearly de~onstrate that silicic acid and silica gel are n.ost suitable for the p~-rification of oil for parenteral feeding, both fro!n the standpoint of effectiveness in remov-- ing impurities and capacity for amount of oil. Alumina is particula~ly unsuitable because it may induce addition-l o~idation, decomposition and polymerization of the oil during the purification process.

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IV PREVENTION OF AUTOXIDATION OF THE PURIFIED OILS
The soybean oil purified according to tne process described above., i.e., by passing same thLough a silicic acid column, was found to have a lower peroxide value than the original, unpurified oil, indicating that a substantial por~ion of the peroxides in the original oil was effectively removed by the silicic acid column. The pertinent data are given in Table V. Hcwever, the purified oil autoxidized faster than did the original oil during storage, as shown by the rate of increase in the peroxide value during storage of the oil at 60C. Although the explanation for this is not known with absolute certainty, it is believed that the more rapid autoxi-dation of the purified oil is pe;haps due to the removal of natural antioxidants, tocopherols, from the oil by tne column, or that it is due to contamination of the oil by trace metals, such as iron, from the silicic acid used in the column.
I have found that the purified oil can be prevented from undergoing autoxidation by adding a tocopherol antioxidant, preferably y-tocopherol, together with a metal scavenging age.-t - 20 such as accorbyl palmitate. The additives should be added to the purified oil as soon as it is eluted from the silicic acid co'umn.
As will be seen from a consideration of the data hereinafter, the use of (1) y-tocopherol as an antioxidant additive for the purified nutritive oil, together with (2) a metal scavenging agent such as ascorbyl palmitate, dramatically enhances the oil's resistance to autoxidation.
The amount of y-tocopherol which is added to the purified oil is generally from about 0.00~ to 0.200 weight ~0 percent, based on the oil, with a range of 0.002 to 0.100 10~;6~l38 percent being preferred, and a range of from about 0.005 to 0.05 weight percent being most preferred.
The metal scavenging agent, e.g., ascorbyl palmitate, citric acid, or the like, is employed in conjunction with the tocopherol. The amount of said scavenging agent employed is limited by its solubility in the oil. For citric acid, the amount employed typically is about 0.01 weight percent based on the oil. For ascorbyl palmitate, about 30 mg per lO0 g o4 oil is the limit of its solubility. In genera_, it is pre-ferred that the scavenging agent employed be present in anamount of zt least about 0.01 weight percent, based on the oil.
While ascorby3 pa3mitate is a preferred metal scaveng-ing agent, as previously noted, other metal scavengers may also be utilized, e.g., citric acid, Rosemary ~xtract, BHT (butylated hydroxytoluene), BHA lbutylated hydroxyanisole~, and the like.
As shown in Table V, 0.02~ of y-tocopherol and 30 mg/100 g. of ascorbyl palmitate, when added to the purified oil, can quite effectively stabilize the purified oil and pre-vent autoxidation thereof. In fact, the purified oil having these additives showed an even bet'er stability than the original untreated soybean oil.
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-1076~3c~ ' TABLE V

PREVENTION OF AUTOXIDATION OF PURIFIED SOYBEA~7 OIL
~7ITH ANTIOXIDANTS
I
Peroxide Number* After Aging i ~ C for Day , Original Oil l 0.12 0.75 3.39 Oil Purified with Silicic ¦ 0.06 5.45 9 98 Acid Column Purified Oil + 0.02~ a- ¦ - 4.14 8.45 tocopherol Purified Oil + 0.02% y- ¦ - 2.73 6.19 tocopherol I

Purified Oil ~ 0.02~ y- ¦ - 0.13 0.21 tocopherol + 30 mg./100 g.
ascorbyl palmitate ~ _ .
* Official Method Cd-8-53; American Oil Chemist's Society As shown in Table V, the original unpuriried soybean oil undergoes a considerable degree of autoxidation within six days as evidenced by an almost 30 fold increase in peroxide number. However, the oil which has been purified by passage through a silicic acid column undergoes an even greater degree of autoxidation. Thu~, while the purified oil has only half the peroxide content of the original, unpurified oil, it rapidly autoxidizes, so that after six days, there has been an almost 170 fold increase in peroxide nu~ber. The addition of ; 0.02% of either a- or y-tocopherol alone, ~hile slightly re-ducing the degree of autoxidation, is essentially ineffective in preventing autoxidation of the purified oil. However, when, in addition to 0.02% of y-tocopherol, there is also added 30 mg./100 g. of oil of ascorbyl palmitate, the autoxidation 107~ii3~ , of the purified oil is significantly retaraed.
Similar results were obtained with sunflower oil as shown in Table VI. The purified sunflower oil with both y-tocopherol and ascorbyl palmitate as antioxidants was more stable than the original unpurified sunflower oil.

TABLE VI

WITH ANTIOXIDANTS

Peroxide Number* After Aging at 60~C for Days Original Oil 0.32 1.214.77 oil Purified with Silicic 0.05 3.89 10.31 Acid Column Purified Oil + 0.02% ~- _ 3.19 9.04 tocopherol Purified Oil + 0.02~ y- _ 3.44 9.82 tocopherol Purified Oil + 0.023 y- _ 0.33 2.19 ! 20 tocopherol + 30 mg./100 g.
Ascorbyl Palmitate * Official Method Cd-8-52; A~erican Oil Chemist's Socie,v o -, The treatment of nutritive oils to remove the im-purities described above is a very important factor as regards - the suitability of such oils for intravenous feeding. Thus, the oils purified in accordance with the invention can be used to produce emulsions with fewer adverse physiological effects when used for intravenous feeding. ~he unsaponifiable matter ; which is removed from the oil by the process of the invention _ _ !

m761~s contains plant sterols, and it has been recently found that excessive amounts of plant sterols in an oil in water emulsion can cause adverse physiological effects wn~n the emulsion is used for intravenous feeding. Moreover, the non-urea-adduct-forming esters which are also removed from the oils by the invention contain oxidative and thermal decomposition products, cyclic and polar monomers and oxidative and thermal polymers.
The amount of such esters in commercial edible oils, such as soybean or sunflower oil, is usually about 1-23. These un-desirable compounds may be originally present in the oilseeds, but it is more likely that they are produced during the processing of the oil, including extraction, refining, bleach-ing and deodorization. Furthermore, even when the processing conditions are quite mild, such as those described in U.S.
Patent 3,169,094 and Swedish Patent 220,400, the oil isolated from a commercial sample of an oil in water emulsion manu-factured according to t~.ese patents, Intralipid, contained 1.26~ of non-urea-adduct-forming esters. This is considerably higher than the non-urea-adduct-formins esters found in the oil purified according to t-ais invention. Treatment of an - oil by heat or by heat and oxygen wsll increase its content of non-urea-adduct-forming esters even more.
The toxic effects resulting from the ingestion of these non-urea-adduct-forming esters has been well documented.
The symptoms include irritation of the digestive tract, organ enlargement (particularly enlargement of the liver), growth depression and in some cases death. These effects are summari-zed in a review by Artman, "P.dvance in Lipid Research~, Vol.
7, 245-330, 1960; while Firestone et al specifically reported the toxicity of non-urea-adduct-forming esters to rats; Jour.

__ 1(~7~13~3 Amer. Oil Chem. Soc. 38, 253-257, 1961. Thus, the process of the invention, according to which oils with non-urea-adduct-forming esters essentially removed, represents a significant advance in the art since it enables one to produce oil in water emulsions with fewer adverse physiological effects w~en they are used for intravei~us feeding.
There will now be given some preparative examples illustrating the preferred embodiments of the invention. These examples are merely for illustrative purposes and are not to be considered as a limitation upon the scope of the invention which is hereinafter claimed.

PURIFICATION OF SOYBEAN OIL WITS SILICIC ACID
E~A~PLE 1 300 g. of washed and activated 100 mesh Analytical Reagent grade silicic acid were used to pack a glass chroma-tographic column of 40 mm. in diameter. The column was equipped with a coarse sintered glass disc at the bottom. A
commercially refined, bleached, and deodorized soybean oil was passed through the column by applying a pressure of 10 psi to the top of the column. A vacuum created by a water aspirator was applied to the bottom of the column. The first 25 g. of - the eluate which passed through the column was discarded. The i passage of the soybean oil through the column was continued until the visible dark band in the column moved to a position near tha bottom of the column. At this time, approximately 1,500 g. of eluate were collected as purified soybean oil.

. EXA~PLE 2 The same procedure as described in Example 1 was con-ducted with the use of a commercially refined, bleached, and ~11'76138 deodorized sunflower oil.

A glass chromatographic column 4 cm. in diameter and 60 cm. in length, with a coarse sintered glass disc at the bottom was closed at the end with a 4 mm. bore stopcock.
Hexane was poured into the column to 10 cm. in height. 300 g.
of washed and activated 100 mesh Analytical Reagent grade silicic acid were made into a slurry with hexane and then poured into the column. The stopcock was adjusted so thnat a 2-3 cm. layer of hexane remained on top of the silicic acid column. A commercially refined, bleaehed, and deodorized soybean oil was mixed with hexane at a volume ratio of 1:1.
The hexane solution of the oil was then poured into the column.
A slight pressure was applied on top of the column to inerease the flow rate. The first 50 ml. of eluate were discarded.
The passing of the hexane solution of soybean oil through the eolumn was eontinued until the eolored band moved elose to the bottom of the eolumn. Approximately 10,000 ml. of the hexane solution were eolleeted up until thi~ point as eluate. The hexane was then removed from the solution under vacuum at 60~C.
- If necessary, the last traces of solvent may be removed by vaeuum steam distillation at temperatures below 60C. Approxi mately 1500 g. of purified soybean oil were thus obtained.

PURIFICATION OP SUNFLOWER OIL ON A SILICIC ACID FILTERING PAD

A buehner funnel of 600 ml. eapaeity with a 90 mm.
diameter eoarse fritted dise sealed in at the bottom was con-nected to a filtering flask. The flask was evaeuated by using ~

1~)7~13~
.
a water .~spirator. Washed and activated 100 mesh Analytical Reagent silicic 2cid was poured into the unnel and packed as a tight uniform l--~yer on the bottorn of the funnel to a depth of 0.5 inch. 500 g. of a commercially refined, bleached, and deodorized sunflower oil Jere filtered through the funnel to obtain purified oil. The filtrat on was repeated twice more through the silicic acid layer, and finally once more throuyh a fresh layer of silicic acid, whereby a purified sunflower oil was obtained.

:
sTAsILIzATIoN OF P~RIFIED SOY~EAN AND SUNFLOWER OILS

Samples of each of the purified oils produced in Examples 1-4 were, immediately after being obtained, subjected to stabilization to prevent autoxidation thereof. To each sample there were added 0.02~ of y-tocopherol and 300 mg./100 gm. of oil of ascorbyl palmitate.

PREPARATION OF OlL IN WATER EMnLSIONS WIT~ TREATED SUNFLOWER OIL
EXAMPLE 6 , 50 g. of sunflower oil which had been purified with a silicic acid column and to which had been added 0.02~ y-tocopherol and 30 mg./100 g. ascorbyl palmitate, were mixed with 6.~ g. of an active carbon bleached ethanol soluble frac~ion of egg ph~:sphatides, 25 g. of glucose, and 450 g. of - distilled, pyrogen-free water at approxi.nately 80C. until a coarse emulsion was obtained. The emulsion was then hcmogenized with ~he use of a Manton-Gaulin homogenizer at 5,000 psi at 50-60C. to obtain the desired emulsion~ The product was auto-- claved in a known manner to destroy possibly occurring bacteria ~07~ 3~;~

and spores. ~ oil in water emulsion suitable for parente~al feeding with no adverie physiological effects was thereby obtained.

PREP~TIO~ OF OIL IN WATER EMULSIONS WITH UNTREATED SUNFLOWER
OIL
EXA~PLE 7 50 9. of sunflower oil are mixed with 6.0 g. of an active carbon bleached ethanol soluble fraction of egg phospha-tides, 2S g. of glucose, and 450 g. of distilled, pyrogen-free water at approximately 80C until a coarse emulsion was obtain-ed. The emulsion is then homogenized with the use of a Manton-Gaulin homogenizer at 5,000 psi at 50-60C to obtain the desired emulsion. The product is autoclaved in a ~nown manner to destroy possibly occurring bacteria and spores. An oil in ~ater emulsion suitable for parenteral feeding is thereby ; ~ained.
-; Referring to ~xample 7, it is important to note that sunflower oil is superior to other nutritive oils such as, e.g., soybean oil and cottonseed oil. Thus, sunflower oil is easy to refine to a light colored product containing fewer undesirable impurities than other nutritive oils. It exhibits reasonably good stability against thermal and oxidation de-composition, since it contains very little linolenic acid.
Moreover, it contains a relatively high content of nutritious linoleic acid.
Although the purification method heretofore des-- cribed in accordance with one aspect of ~y invention has made reference to such nutritive oils as sunflower oil and soybean oil, it is to ba understood that my purification metnod is likewise applicable to other nutritive oils suitable fcr oil ., , ~, ... ~a in water emulsions for use in parenteral administration.
Examples of other suitable nutritive oils include cottonseed oil, corn oil, peanut oil, coconut oil, safflower oil, edible fats such as tallow and lard, and their fractionated products, etc.
The nutritive oil in water emulsions prepared in accordance with the present invention preferably contain the nutritive oil in an amount of from a~out 5 to SO weiyht percent, based on the overall emulsion, a more preferred range being from 10 to 25 weight percent.
Variations and modifications can, of course, be made without departing from the spirit and scope of my invention.

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Claims

THE EMBODIMENTS OF THE INVENTION IN WHICH AN EXCLUSIVE PROPERTY
OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:

1. A method of purifying a nutritive oil to re-move impurities therefrom, said method comprising subjecting a nutritive oil having impurities therein to adsorption with an adsorbant selected from the group consisting of silicic acid and silica gel to thereby adsorb the impurities contained in said oil on the adsorbant and recovering the thusly purified oil from the adsorbant.

2. The method of claim 1 wherein said adsorbant is silicic acid.

3. The method of claim 2 wherein the nutritive oil is soybean oil or sunflower oil.

4. The method of claim 1 wherein the adsorption is effected by adsorption chromatography on a silicic acid column.

5. The method of claim 4 wherein the silicic acid column is a dry column and the n??ritive oil is introduced to the top of the column in the absence of a solvent.

6. The method of claim 4 wherein the silicic acid column is in the form of a slurry in an alkane solvent and the nutritive oil is introduced to the top of the column in the form of a solution of said oil in an alkane, said alkane containing from 5 to 10 carbon atoms or being a mixture of alkanes containing from 5 to 10 carbon atoms.

7. The method of claim 6 wherein said alkane is hexane.

8. The method of claim 5 wherein the purified oil is recovered from the column by elution, - first portion of the eluate being discarded, and elution thereafter being con-tinued until a dark visible band representing the impurities in the oil has moved down the column toward the end thereof.

9. The method of claim 6 wherein the purified oil is recovered from the column by elution, a first portion of the eluate being discarded and elution thereafter being con-tinued until a dark visible band representing the impurities in the oil has moved down the column toward the end thereof.

10. The method of claim 1 wherein the adsorption is effected by adsorption on a filter pad of silicic acid.

11. The method of claim 10 wherein the filter pad is about 1/8 inch to 4 inches in thickness, said method further comprising filtering the oil through said filter pad a plurality of times.

12. The method of claim 11 wherein the final filtra-tion of said oil is effected using a fresh pad of silicic acid.

13. A method of purifying a nutritive oil in order to remove components therefrom which are toxic upon parental administration, which method comprises passing said oil through a siliceous adsorbent in the substantial absence of eluting solvents, said adsorbent selected from the group consisting of silicic acid and silica gel, and recovering the thusly purified oil from said adsorbent.

14. A method as described in claim 13, wherein a pressure gradient is applied to pass said oil through said siliceous adsorbent.

15. A method as described in claim 13, wherein the nutritive oil is sunflower seed ???.

16. A method as described in claim 15, where ?
said sunflower seed oil is passed through a bed of silicic acid.

17. A method as described in claim 16, wherein said sunflower seed oil is passed through a silicic acid bed a plurality of times.

18. A method as described in claim 16, wherein said sunflower seed oil is passed through a plurality of silicic acid beds.

19. A method as described in claim 18, wherein said sunflower seed oil is mixed with a solvent prior to passing through said siliceous adsorbent.

20. A method as described in claim 15, wherein at least 800 grams of sunflower seed oil is treated with each 300 grams of adsorbent.

21 a method as de???ibed in claim 13, wherein the nutritive oil is soybean oil.

22. A method as described in claim 21, wherein said soybean oil is passed through a bed of silicic acid.

23. A method as described in claim 22, wherein said soybean oil is pas??? through silicic acid bed a plur-ality of times.

24. A method as described in claim 22, wherein said soybean oil is passed through a plurality of silicic acid beds.

25. A method as described in claim 24, wherein said soybean oil is mixed with a solvent prior to passing through said siliceous adsorbent.

26. A method as described in claim 21, wherein at least 800 grams of said soybean oil is treated with each 300 grams of adsorbent.

27. A nutritive oil suitable for use in parental administration as an oil-in-water emulsion, said oil having reduced levels of impurities, said oil produced by the process of claim 1 or a chemically equivalent process.

28. A nutritive oil suitable for use in parental administration as an oil-in-water emulsion, said oil having a reduced level or toxic components, including a reduced level of peroxides, pigments, unsaponifiables, thermal decomposition products, oxidative decomposition products, polar monomers and polymers, said oil produced by the process of claim 13 or a chemically equivalent process.

29. A sunflower seed oil suitable for use in paren-tal administration as an oil-in-water emulsion, said oil being substantially free of peroxides, pigments, unsaponifiables, thermal decomposition products, oxidative decomposition produces, polar monomers and polymers, said oil produced by the process of claim 18 or a chemically equivalent process.

30. A sunflower seed oil suitable for use in paren-tal administration as an oil-in-water emulsion, wherein said oil has a reduced content of non-urea-adduct-forming esters, said oil produced by the process of claim 18 or a chemically equivalent process.

31. A sunflower seed oil suitable for use in paren-tal administration as an oil-in-water emulsion, wherein said oil contains no more than about 0.29% of non-urea-adduct-forming ester, said oil produced by the process of claim 18 or ? chemically equivalent process.

32. A sunflower seed oil suitable for use in paren-tal administration as an oil-in-water emulsion, wherein said oil contains no more than about 0.34% unsaponifiable matter, said oil produced by the process of claim 18 or a chemically equivalent process.

33. A sunflower seed oil suitable for use in paren-tal administration as an oil-in-water emulsion, which oil has a photometric index at 440 microns of no more than about 3.0 and a photometric index at 550 microns of no more than about 0.2, said oil produced by the process of claim 18 or a chemi-cally equivalent process.

34. A soybean oil suitable for use in parental administration as an oil-in-water emulsion, said oil being substantially free of peroxides, pigments, unsaponifiables, thermal decomposition products, oxidative decomposition products, polar monomers and polymers said oil produced by the process of claim 24 or a chemically equivalent process.

35. A soybean oil suitable for use in parental administration as an oil-in-water emulsion, wherein the oil has a reduced content of non-urea-adduct-forming esters, said oil produced by the process of claim 24 or a chemically equi-valent process.

36. A soybean oil suitable for use in parental administration as an oil-in-water emulsion, wherein said oil contains no more than about 0.35% of non-urea-adduct-forming ester, said oil produced by the process of claim 24 or a chemically equivalent process.

37. A soybean oil suitable for use in parental administration as an oil-in-water emulsion, wherein said oil contains no more than about 0.15% unsaponifiable matter, said oil produced by the process of claim 24 or a chemically equi-valent process.

38. A soybean oil suitable for use in parental administration as an oil-in-water emulsion, which oil has a photometric index at 440 microns of no more than about 6.0 and a photometric index at 550 microns of no more than about 0.3, said oil produced by the process of claim 24 or a chemically equivalent process.