CA1257131A - Total parenteral and enteral nutrition composition - Google Patents

Abstract

ABSTRACT

A stable fat emulsion composition for parenteral or enternal nutrituion is disclosed containing amino acids, fat and carbohydrates. The emulsion is stabilized by a combination of co-emulsifiers comprising a phosphatide such as egg or soybean phosphatide and a fatty acid-amino acid peptide wherein the fatty acid component of the peptide is a saturated or unsaturated fatty acid having from 16 to 22 carbon atoms.

Description

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., ~ -This invention relates to an improved composition f or total parenteral or enteral nutrition, and rnore particularly, to a composition 10 containing amino acids, fat ard carbohydrates and a means for emulsifying such a composition.

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Total parenteral nutrition (TPN) is a technique employed to sustain life and/or accelerate recovery in patients who cannot consurne foods due to primary diseases. To provide TPN, a~ueous solutions of amino acids, fat, carbohydrate, vitamins and electrolytes are typically admixed uncler an aseptic environment in the pharmacy prior to intraYenous administration in 20 patients. This practice not only increases hospital cost in terms of ordering, stocking and admixin~, but also introduces a posslbility of microbial contamination, thereby exposing patients to a higher risk of in~ection.

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Furthermore, the current TPN practice requires a central vein 25 catheter for administration. ~he sur~ical procedures for catheter place-ment frequently present a problem in many rural and community hospitals.
Patients in these situations may be deprived of optimal medical care. Thus, the development of a TPN solution which does not require admixlng and can be administered through a peripheral Yein becomes a vital solution to the 3û problems encountered in small hospitals.

A typical TPN infusate should contain protein sources in the form of amino acids, together with fat and carbohydrate. Amino acids are used to synthesi~e body protein, while fat and carbohydrate are sources of energy ~3 ` :IL2S~L31 for vital processes. To synthesize body proteins effectively, all of the 20 pro~eln amino acids are required to be present in an optimal proportion in organs and tissues. Although certain of these amino acids are considered non-essential, that is they can be synthesized in the body9 it is necessary to receive from an external source the essential amino acids which cannot be synthesized in the body ~rom a TPN infusate.

As fat is no~ water soluble, a stable oil-in-wa~ter emulsion is required for intravenous infusion. It has been found from previous laboratory work that two amino acids, lysine, which is an essential amino acid, and arginine, which is a semi-essential amino acid9 destabilize fat emulsions containing other essential nutrients. Thus, It has been difficult heretofore to manu-~acture a stable TPN infusate containing these amino acids in a fat emulsion.
There are currently at least two products known to exist which include in a single emulsion9 fat, amino acids and carbohydrate. These are Trieve lO00 TM manufactured by Laboratoire Egic in France and NutrifundinTM manufactured by B. E~raun in West Germany. Both composi-tions contain soy bean oil as the fat source and use soy bean phosphatides as an emulsifier. Use of the soy bean phosphatides as the emulsifier has at least two drawbacks. First9 the soy bean phosphatide can resul~ in undesirable side effects and may be nutritionally undesirable. Further, the use of soy bean phosphatides as the sole emulsifier does not permit the inclusion of a sufficient amount of ar~inine and thus the amino acid composition of these two products is lmdesirable due to their very low concentration or total absence of arginine.

A similar composition has been described in U.S. Patent No.

3,793,450 to Schnell. The composition described in this patent contains various amino acids, ~a~ and either soy or e~g yolk phosphatide as an emulsl~ier. Again, however, the use of only the soy or e~g phosphatide is not sufficient to stabilize a solution containin~ ar~inine with fat. All of the -~257~31 examples described in this paten~ include diaminovaleric acid (ornithine), apparently as a substitute ~or arginine.

U.S. Patent No. 3,873,720 to Suzuki, e~ al., teaches the use of a fa~ty S acid ~or i~s basic amlno acid salt~ as a co-emulsifier with egg-yQlk phospholipids. The salt disclosed in Suzuki would dissociate in solution and is not really different from the use of the ~atty acid alvne in an amino acid containing emulsion. However, the use of the fatty acid-amino acid peptide, as opposed to the mere salt which dissociates in solutlon~ has been 10 found to provide additional stabilization advantages, including increased water solubility and lower requirements for effectiveness. A combination of f~ty acids together with soybean phosphatides was not able to sufficiently stabilize a fat emulsion containing arginine together with other nutrients.

The same considerations apply in formulating a composition for oral and entera! use. Where such a composition contains all o~ the essential arnino acids ~ogether with fat and carbohydrate, it is necessary to provide a compatible means for stabilizing a fat/water emulsion, particularly one containing arginine with fat.
BRIEF SVMMARY OF THE INVENTION

It is therefore an object of this imention to provide a stable composition for total parenteral and/or enteral nutrition containing fat, 25 amino acids and carbohydrate.

It is a further object of this invention to provide such a composition which includes the emulsion destabilizing amino acids Iysine and arginine.

The composition of the present in~ention involves the use of disodium salts or other cation salts of a fatty acid-amino acld peptide alone and in combination w;th egg or other phosphatldes as co-emulsif iers. The ~;~57~3~
remainder of the fat emulsion contains fat, amino acids, including lysine and arginine, and other essential nutrients for TPN and enteral nutritional use.

It has been discovered that the fatty acid-amlno acid peptide may be S used as an emulsification agent to pro~ide improved stability to a fat emulsion beyond that provided by the mere salt o thç iEatty acid and the amino acid. This was surprising in that previous laboratory tests have indicated that fatty acid-arnlno acid peptides, such as linoleoyl glutamate, when adrninistered in a saline solution can be hemolytic and ~oxic.
10 However, when included in the fat emulsion of the present invention, the peptide is physiologically acceptable and combines with the phosphatide to stabilize the fat emulsion. It has further been discovered that the use of the fatty acid-amino acid peptide together with a phosphatide proYides a synergistic emulsification wh;ch pe~mits the preparation of a s~able ~at 15 emulsion containing Iysine and arginine.

The parenteral or enteral composition of the present inven~ion contains the iollowing ingredients in cssentially the indicated weight proportions.
~ Wei~ht Proportion Fat 3-30 Phosphatide 0.5 - 5 Fatty Acid-Amino Acid Peptide 0.05 - 0.5 ~-Lysine Acetate 0.2 - 2.0 L-Ar~inine û.2 - ~.0 Remaining Amino Acids * 2 - 20 Sugar Alcohols ** 3 - 30 ~ The amino acids used in the invention are the L-isomers and glycine 30 which are utilized for protein synthesis or performing biological functions in mammals. ~iologically available precusors of these amino acids in the form of derivatives and peptides may also be included.
~* Sugar alcohols such as glycerol and sorbitol included in the present 35 invention are those which can be metabolized to generate biologically available energy in the mammalian species, and are chemically compatible with amino acids durin~ heat sterilization and/or are s~able during shelf life storage. The reducing su~ars, such as glucose, generally resul~ in undesir-able reactions with amino acids during heat sterilization.

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While the composition of the present invention, in order to be comple~e for total nutrition, preferrably contains carbohydrate as an energy source, the inclusion or exclusion of such does not affect the use of the fatty acid-amino acid peptide and e~ phosphatides as co-emulsifiers in oil in water emulsions.

The fatty acid-amino acid peptide useful with the present invention is a compound which contains a peptide bond linking the carboxylic group of lO a long chain fatty acid with the amino g~oup of an amino acid. Examples of long chain fatty acids useful with the present invention consist of saturated and unsaturated acids with 16 - 22 carbon atoms including palmitic acid, stearic acid~ arachidic acid, lignoceric acid; palmitoleic acid, oleic acid, linoleic acid, linolenic acid, arachidonic acid, and clupanodonic acid.
Amino acids which may be used as part of the peptides may include leucine, isoleucine, valine, methionine, phenylalanine, tryptophan, threonine, Iysine, arginine, histidine, alanine, proline, serine, cysteine, cystine, tyrosine, aspartic acid, glutamic acid, and glycine. It is also 20 contemplated that the peptides be used either as the salt or the ~ree acid.

The novel features which are belie~ed to be characteristic of the present invention, both as to its composition and method of preparation, to~ether with further objectives and advantages thereof will be better 25 understood from the following description in whish presently preferred embodiments of the invention are illustrated by way of example. It is to be expressly understood, however, that the specific embodiments are for the purposes of illustration and description only, and are not intended as a de~inition of the limits of the invention.

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The total parenteral or enteral nutrition composition of the present inventlon comprises a combination of amino acids~ Eat and earbohydrates in S a fat~water emulsion. In particular, it has been surprisingly found that a fatty acid-amino acid peptide may be used as an emulsifier and that a combination of co-emulsi~iers can be advantageously used to provide a stable emulsion even when the amino acids lysine and arginine are included.

The co-emulsifiers of the present invention comprise a combination of a fatty acid-amino acid peptide together with a phosphatide such as egg or soybean phosphatide. The use of these c~emulsifiers in combination, provides a synergistic stability ~o the emulsion not obtainable by using either emulsifier alone.
The ability to use a fatty acid-amino acid peptide as an emulsifier in a parenteral solution is unexpected in itself. Tests involvin~ the administra-tion of disodium linoleoyl glutamate, an example of a peptide pursuant ~o the present invention, In a saline solution to mice clearly showed the 20 undesirable properties of such parenteral administration of a f atty acid-amino acid peptide. A saline solution containing 0.1% disodium linoleoyl glutamate was injected into the tails of laboratory mice.
Hemolysis from this injectate was observed in the tails of ~he animals.
After five days of 50 ml/kg injections, the entire tail was necrotic. The 25 results of these tests clearly su~gested that $he use of a fatty acid-amino acid peptide in an aqueous parenteral solu$ion would be undesirable.

Tests usin~ disodium linoleoyl glutamate in fat-water emulsions, however, unexpectedly showed no adverse affects. No hemolysis was 30 observed as with the linoleoyl glutamate in normal saline.

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3~l A ~at/amino acid emulsion having a composition as stated in Table 1 was prepared. The amolmts of egg yolk phosphatide and disodium linoleoyl~ glutamate were varied tv assess the stability of the composi~ion.
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TAE~LE 1 ~ ~ 00 ml L-Threonine 0O 18 L-Serine 0.,26 L-Proline 0.50 (;lycine 0.63 L-Alanine 0.32 L-V~line Q.30 L-Methionine 0.24 L-lsoleucine 0.3 1 L-l,eucine 0.41 L-Phenylalanine 0.2S
L Tryptophan 0.07 L-Lysine Acetate 0.46 L-Histidine 0.13 L-Ar~inine 0.43 L-Cysteine HCl H2O 0.02 Soybean Oil 5.0 Egg Yolk Phosphatide 0 - 2.0 Glycerol 3-0 Sorbitol 3.0 Disodium Linoleoyl-L-Glutamate 0- 0.4 ~ ;~5~131 .
The compositions of Table 1 were placed in vials pur~ed with nitrogen~ capped and steriliæed statically at 120C for 20 minutes. The stability of ~he emulsion was determined by measuring the "M-value" of each sample. The M-values were determined by diluting a 100 ml aliquot

5 with distilled water and obtaining an absorbance reaLding in a 1 cm cuYette at S00 nm versus a distilled water blank. The actual M-value which is proportional to the stability of the emulsion is then computed by multiplying the absorbance reading by the dilution factor. llle results of the study are set forth in Table 2.

C~e~h~ M-values (X1000) 4 month LG Conc, EYP* Pre Post storage 15 ~ C
0.0 14006 169 Separated 0.0 2 24.6 120 Separated 0.1 0.539.2 64.1 66.2 0. 1 1 .037.8 53.3 5~ .
0.1 1.538~7 ~6.8 45.7 0.1 2.038.0 40.7 42.0 0.2 0.530.0 44.2 ~4.6 0.2 1.027.6 33.1 31.6 ~5 0.~ 1.533.2 33.0 32.2 0.2 2.035.2 34.1 35.0 0.3 0.517.1 39.7 42.8 0.3 1.018.1 20.8 22.2 0.3 1.519.3 18.3 18.9 0.3 2.016.6 18.8 18.6 0.~ 0.514.3 64.3 59.~
0.4 1.010.6 14.8 ~ 15.3 ~.4 1.~9.3 10.7 12.1 0.4 2.010.6 1 1.0 1 1.3 *EYP - Egg yolk phosphatide As can be seen from ~he results o~ the above study, the ~ombination of the fatty acid amino acid peptide with egg yolk phosphatide as c~
emulsiiers provides a syner~istic effect in stabilizing the fat/amino acid emulsion. From Table 2 it can be seen that it is desirable to use at least approximately 1.0 g/100 ml of the egg yolk phosphatide. The stability OI the ~i 2C3~

emulsion increases with an increasing amount of the fa$ty acid-amino acid peptide. The specific desired amount wDuld depend on a number of factors including cost and the stability desired. For purposes of parenteral administration of the emulsion, it is preferred to use approximately 0.1 -5 0.2 g/100 ml of the pep~ide.

All of the components listed in Table 1 are available commercially with the exception of disodium linoleoyl-L-glutamate. The synthesis of linoleoyl glutamate is well known in the art. The particular synthetic 10 process used is described by J. R. Vaughn and R. L. Ostato in the 30urnal of the American Chemical Socie~y, 74:676 (1952).

As discussed above, a number of variations can be made in the above composition without departin~ f rom the spirit or scope of the present 15 invention. For example, different sources of fat may be used other than soy bean oil. These may include corn oil, other vegetable oils or other nutritionally acceptable fat sources. Further, different phosphatides may be used o~her than ~hose found in egg. An example is soy bean phosphatide or lecithin. Various supplemental components such as electrolytes and 20 vitamins may also be added for complete nutrition.

A number of fatty acid-amino acid peptides may be used o~her than linoleoyl-L-glutamate~ Preferably, the group of long chain fatty acids which may be used as part of the peptide consists of saturated and 25 unsaturated acids with 16 to 22 carbon atoms. These include palmitlc acid, stearic acid, arachidic acid, lignoceric acid, palmitoleic acid, oleic acid, linoleic acid, llnolenic acid, arachidonic acid, and clupanodonic acid~

Amino acids which may be used as part of the peptides may include 30 leucine, isoleucine, valine, methionine, phenylalanine, tryptophan, threonine, lysine, arginine, histidine, alanine, proline, serine, cysteine, cystine, tyrosine, aspartic acid, glutamic acid, and glycine. It is preferable to use the l.-isomer of the amino acids which is biologically active and therefore ~~"
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will also have nutritional value. However9 the D~isomer or a racemic mix may also be used while retaining the desired emulsification characteristics.

It is also contemplated that the peptides may be used e~ther as the 5 salt or the free acid.

The specif ic amino acid cornposition of the emulsion as a whole is not cri~ical to the present invention. However9 the maximum benefits are realized by the ability to include arginine and Iys;ne in the fat emulsion.
10 The remaining ingredients are desirable for a total nutritional formulation.
However, their presence is not necessary in order to obtain the specific benefits of the present imention.

The ranges of proportions of ingredients which may be used in a tota}
15 parenteral or enteral nutrition composition according to the present inven-tion are set forth in Table 3. Since it is ~he interaction of the various components which provides the stability of the emulsion, lt is ~he relative amounts of each ingredient which are important rather than the absolute arnounts present in the emulsion. In other words, the concentration of the 20 overall composition may vary within pharmaceutically acceptable ranges, provided that the relative amounts of each component remain within the ranges stated below.

Operative Preferred ~ . ~ ~
Fat 3 - 30 4 - 8 3a Phosphatide 0.5 - 5.0 1- 2 Fatty Acid-Amino Acid Peptide 0.05 - 0.5 0.1- û.2 L-Lysine Acetate 0.2 - 2.0 0.40 - 0.52 L-Arginine 0.2 - 2.0 0.37 - 0.49 Remaining Amino Acids 2 - 20 3 - 6 Sugar Alcohols 3 - 30 4 - 8 ~5~

A total parenteral nutrition composition was prepared contairling the îollowing ingredientst s 5~me~ ~ '' L-Threonine Q 18 L-Serine 0~26 L Proline t).50 Glycine 0.63 I 0 L-Alanine 0.3~
L-Valine 1).30 L-Methionine 0.24 ~-lsoleucine l).31 L-Leucine 0.41 L-Phenylalanine 0 25 L-Tryptophan 0.07 L-Lysine Acetate 0.46 L-Histidine 0~ 13 L-Arginine 0.43 L-C:ysteine HCl H20 0.02 ~Coybean Oil Egg Yolk Phosphatide 1.0 Glycerol 3-0 Sorbitol 3.0 Disodi~m Linoleoyl-L-Glutamate 0.2 The egg yolk phosphatide was dissolved in soy bean oil by stirring at 600 rpm at 80C for ten minutes. USP grade wa~er warmed to 80C was then added to the oil mixture under continuous agitation until all egg 30 phospha~ide was dissolved. A primary dispersion was then made by high shear mixing IJnder nitrogen purge at 8~S00 rpm at ~0C for twenty minutes.
The dispersion was ~hen subjected to high pressure homogenizaSion at 530 kg/cm2 and 50C for ten cycles. An aqueous solution previously made to contain appropriate amounts of glycerol, sorbitol, amino aclds, in~luding 35 Iysine and arginine, and disodium linoleoyl-L glutamate was then added to the primary dispersion and further homogenized under high pressure for ten cycles. After cooling to room temperature, the emulsion was adjusted to an appropria~e physiological pH (from about S to 9) using means known in the art and filtered through a û.8 micron filter under O~S kg per square 40 centimeter nitrogen pressure. The emulsion was then placed in appropriate 5~3~
containers and may be sterilized using conventional techniques. This may include heat or f il$er sterilization. The resultin~ emulsion was stable, non-pyrogenic and suitable ~or intravenous administration to human patients.

EXAMPI,E 2 A composition useful for enteral nutrition may be prepared using similar processing steps to those described in Example 1 and containing the 10 following ingredients:
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L-lsoleucine 0.44 L.-Leucine 0.69 L-Methionine 0.69 L-Phenylalanine 0.69 l-Threonine 0.315 I,-Tryptophan 0.157 l-Valine 0.Sû4 1 -Lysine Acetate 0.705 L-Histidine 0. 158 Corn Oil 13.0 I,ecithin 0. 187 Mon~ and Diglycerides 0.373 Maltodextrin 16.0 Sucrose 3.3 - Disodiurn 1 inoleoyl-L-Glutamate 0.109 It should be noted that the amount of heat applied to sterilized enteral compositions is gençrally less than that required for parenteral compositions. Furthermore, glucose polymers such as maltodextrins and starches can be included in enteral compositions to achieve the desired 35 nutritional effecSs. It is possible to sterilize enteral compositions containing glucose polymers and amino acids without adverse chemical reactions which may compromise ~he nutritional properties of the composition.

EXA
Another composition suitable for enteral nutrition according to the present invention also contains a nun ber of vitamins and electrolytes. It has the following composition:
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Disodium Linoleoyl ~;lutamate 148 mg (::orn Oil 3. 0 g Medium Chain Triglycerides 2. 0 g Lecithin 262 mg Polysorbate 80 39 mg Maltodextrin 18 . O g Carrageenan 190 mg Citric Acid 114 mg Eg~ ~Ibumin Hydrolysate7.3 g I,-Valine 1.1 g L-Leucine 1.8 g L-Isoleucine 0.95 g Vitamin A 364 IU
Vitamin D3 27 IU
Vitamin E 4 IU
Vitamin Kl 12 mcg Vitamin C 13 mg Thiamine 121 mcg Riboflavin 121 mcg Niacinamide 1~34 mg Vitamin B6 176 mcg Folic Acid 38 mcg Vitamin~l2 0.42 mcg Biotin 21 mcg 3û Pantothenic Acid 791 mcg Potassium lodide 10 mcg Chromium Chloride 13 mcg Sodium Molybdate 20 mcg Selenium Dioxide 11 mcg Dicalcium Phosphate113 mg Monocalcium Phosphate64 mg Ma~neslum Oxide 2~ mg Man~anous Sulfate H2O245 mcg Ferrous Gluconate 7 mg Copper Gluconate 111 mcg Zinc Oxide 902 mcg Sodium Chloride 147 mg Potassium Citrate H2O307 mg Potassium Chloride 31 mg While a wide variety of materials and prepara$ion procedures may be used in the present invention, it should be understood that changes can be ~57~L3~L
made without departing from the spirit or scope thereof. This invention therefore~ is not ~o be limited to the ~pecific embodiments discussed herein.

Claims (65)

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

1. A stable aqueous fat emulsion comprising a fat suitable for human nutrition, one or more nutritive amino acids and two or more co-emuisifiers wherein at least one of said co-emulsifiers is a pharmaceutically acceptable phosphatide and at least one other of said co-emulsifiers is a fatty acid-amino acid peptide or a pharmaceutically acceptable salt thereof and wherein the fatty acid component of said peptide is selected from the group consisting of saturated and unsaturated fatty acids having from 16 to 22 carbon atoms and the amino acid component of said peptide is a pharma-ceutically acceptable amino acid.

2. An emulsion according to Claim 1 wherein said fatty acid com-ponent of said peptide is selected from the group consisting of palmitic acid, stearic acid, arachidic acid, lignoceric acid, palmitoleric acid, oleic acid, linoleic acid, linolenic acid, arachidonic acid, and clupanodonic acid.

3. An emulsion according to Claim 1 wherein said amino acid com-ponent of said peptide is selected from the group consisting of leucine, isoleucine, valine, methionine, phenylalanine, tryptophan, threonine, lysine, arginine, histidine, alanine, proline, serine, cysteine, cystine, tyrosine, aspartic acid, glutamic acid, and glycine.

4. An emulsion according to Claim 1 wherein said fatty acid com-ponent of said peptide is linoleic acid.

5. An emulsion according to Claim 1 wherein said amino acid com-ponent of said peptide is glutamic acid.

6. An emulsion according to Claim 1 wherein at least one of said co-emulsifiers is disodium linoleoyl-L-glutamate.

7. An emulsion according to Claim 1 wherein said phosphatide is selected from the group consisting of egg phosphatide and soybean phosphatide.

8. An emulsion according to Claim 1 wherein one of said nutritive amino acids is L-arginine.

9. An emulsion according to Claim 1 wherein one of said nutritive amino acids is L-lysine.

10. An emulsion according to Claim 1 wherein said fat is a vegetable oil.

11. An emulsion according to Claim 1 wherein said emulsion is non-pyrogenic, has a pH range of about 5 to 9, and is suitable for intravenous administration to humans.

12. An emulsion according to Claim 1 wherein said fat, said peptide, said phosphatide, and said amino acids are present in approximately the following relative weight proportions:

13. An emulsion according to Claim 12 wherein said relative weight proportions are:

14. A stable aqueous fat emulsion suitable for human nutrition comprising 3-30 w/v% based on the emulsion of a fat suitable for human nutrition, 0.05-0.5 w/v% of a fatty acid-amino acid peptide or a pharma-ceutically acceptable salt thereof, 0.5-5.0 w/v% of a phosphatide and 2-24 w/v% of one or more nutritive amino acids.

15. An emulsion according to Claim 14 wherein the fatty acid com-ponent of said peptide is selected from the group of saturated and unsaturated fatty acids having from 16 to 22 carbon atoms.

16. An emulsion according to Claim 15 wherein said fatty acid component is selected from the group consisting of palmitic acid, stearic acid, arachidic acid, lignoceric acid, palmitoleric acid, oleic acid, linoleic acid, linolenic acid, arachidonic acid, and clupanodonic acid.

17. An emulsion according to Claim 14 wherein the amino acid com-ponent of said peptide is selected from the group consisting of leucine, isoleucine, valine, methionine, phenylalanine, tryptophan, threonine, lysine, arginine, histidine, alanine, proline, serine, cysteine, cystine, tyrosine, aspartic acid, glutamic acid, and glycine.

18. An emulsion according to Claim 14 wherein said fatty acid com-ponent of said peptide is linoleic acid.

19. An emulsion according to Claim 14 wherein said amino acid com-ponent of said peptide is glutamic acid.

20. An emulsion according to Claim 14 wherein said peptide is disoldium linoleoyl-L-glutamate.

21. An emulsion according to Claim 14 wherein said phosphatide is selected from the group consisting of egg phosphatide and soybean phosphatide.

22. An emulsion according to Claim 14 wherein one of said nutritive amino acids is L-arginine.

23. An emulsion according to Claim 14 wherein one of said nutritive amino acids is L-lysine.

24. An emulsion according to Claim 14 wherein said fat is a vegetable oil.

25. An emulsion according to Claim 14 wherein said emulsion is non-pyrogenic and is suitable for intravenous administration to humans.

26. A stable, non-pyrogenic aqueous fat emulsion suitable for parent-eral administration to humans comprising 3-30 w/v% based on the emulsion of a fat suitable for human nutrition, 0.05-0.5 w/v% of a fatty acid-amino acid peptide or a pharmaceutically acceptable salt thereof, 0.5-5.0 w/v% of a phosphatide and 2-24 w/v% of one or more nutritive amino acids.

27. An emulsion according to Claim 26 wherein the fatty acid com-ponent of said peptide is selected from the group of saturated and unsaturated fatty acids having from 16 to 22 carbon atoms.

28. An emulsion according to Claim 26 wherein said fatty acid component is selected from the group consisting of palmitic acid, stearic acid, arachidic acid, lignoceric acid, palmitoleric acid, oleic acid, linoleic acid, linolenic acid, arachidonic acid, and clupanodonic acid.

29. An emulsion according to Claim 26 wherein the amino acid com-ponent of said peptide is selected from the group consisting of leucine, isoleucine, valine, methionine, phenylalanine, tryptophan, threonine, lysine, arginine, histidine, alanine, proline, serine, cysteine, cystine, tyrosine, aspartic acid, glutamic acid, and glycine.

30. An emulsion according to Claim 26 wherein said fatty acid com-ponent of said peptide is linoleic acid.

31. An emulsion according to Claim 26 wherein said amino acid com-ponent of said peptide is glutamic acid.

32. An emulsion according to Claim 26 wherein said peptide is disoldium linoleoyl-L-glutamate.

33. An emulsion according to Claim 26 wherein said phosphatide is selected from the group consisting of egg phosphatide and soybean phosphatide.

34. An emulsion according to Claim 26 wherein one of said nutritive amino acids is L-arginine.

35. An emulsion according to Claim 26 wherein one of said nutritive amino acids is L-lysine.

36. An emulsion according to Claim 26 wherein said fat is a vegetable oil.

37. A method of stabilizing an aqueous fat emulsion containing nutritive amino acids and suitable for human nutrition comprising including in said emulsion two or more co-emulsifiers in effective amounts wherein at least one of said co-emulsifiers is a phosphatide and at least one other of said co-emulsifiers is a fatty acid-amino acid peptide or a pharmaceutically acceptable salt thereof and the fatty acid component of said peptide is selected from the group consisting of saturated and unsaturated fatty acids having from 16 to 22 carbon atoms and the amino acid component of said peptide is a pharmaceutically acceptable amino acid.

38. A method according to Claim 37 wherein said fatty acid com-ponent of said peptide is selected from the group consisting of palmitic acid, stearic acid, arachidic acid, lignoceric acid, palmitoleric acid, oleic acid, linoleic acid, linolenic acid, arachidonic acid, and clupanodonic acid.

39. A method according to Claim 37 wherein said amino acid com-ponent of said peptide is selected from the group consisting of leucine, isoleucine, valine, methionine, phenylalanine, tryptophan, threonine. lysine, arginine, histidine, alanine, proline, serine, cysteine, cystine, tyrosine, aspartic acid, glutamic acid, and glycine.

40. A method according to Claim 37 wherein said fatty acid com-ponent of said peptide is linoleic acid.

41. A method according to Claim 37 wherein said amino acid com-ponent of said peptide is glutamic acid.

42. A method according to Claim 37 wherein at least one of said co-emulsifiers is disodium linoleoyl-L-glutamate.

43. A method according to Claim 37 wherein said phosphatide is selected from the group consisting of egg phosphatide and soybean phosphatide.

44. A method according to Claim 37 wherein one of said nutritive amino acids is L-arginine.

45. A method according to Claim 37 wherein one other of said nutritive amino acids is L-lysine.

46. A method according to Claim 37 wherein said fat is a vegetable oil.

47. A method according to Claim 37 wherein said emulsion is non-pyrogenic and is suitable for intravenous administration to humans.

48. A method according to Claim 37 wherein said fatty acid-amino acid peptide is present in an amount of from 0.05 to 0.5 w/v% based on the emulsion.

49. A method according to Claim 48 wherein said phosphatide is present in an amount of from 0.5 to 5.0 w/v% based on the emulsion.

50. A method according to Claim 48 wherein said nutritive amino acids are present in amount of from 2 to 24 w/v% based on the emulsion.

51. A stable aqueous fat emulsion comprising a fat suitable for human nutrition, and an emulsifier comprising a fatty acid-amino acid peptide or a pharmaceutically acceptable salt thereof wherein the fatty acid component of said peptide is selected from the group consisting of saturated and unsaturated fatty acids having from 16 to 22 carbon atoms and the amino acid component of said peptide is a pharmaceutically acceptable amino acid.

52. An emulsion according to Claim 51 wherein said fatty acid component of said peptide is selected fron the group consisting of palmitic acid, stearic acid, arachidic acid, lignoceric acid, palmitoleric acid, oleic acid, linoleic acid, linolenic acid, arachidonic acid, and clupanodonic acid.

53. An emulsion according to Claim 51 wherein said amino acid component of said peptide is selected from the group consisting of leucine, isoleucine, valine, methionine, phenylalanine, tryptophan, threonine, lysine, arginine, histidine, alanine, proline, serine, crysteine, cystine, tyrosine, aspartic acid, glutamic acid, and glycine

54. An emulsion according to Claim 51 wherein said fatty acid component of said peptide is linoleic acid.

55. An emulsion according to Claim 51 wherein said amino acid component of said peptide is glutamic acid.

56. An emulsion according to Claim 51 wherein said emulsifier is disodium linoleoyl-L-glutamate.

57. An emulsion according to Claim 51 further comprising one or more nutritive amino acids.

58. A method of stabilizing an aqueous fat emulsion suitable for human nutrition comprising including in said emulsion an emulsifier in an effective amount wherein said emulsifier is a fatty acid-amino acid peptide or a pharmaceutically acceptable salt thereof and the fatty acid component of said peptide is selected from the group consisting of saturated and unsaturated fatty acids having from 16 to 22 carbon atoms and the amino acid component of said peptide is a pharmaceutically acceptable amino acid.

59. A method according to Claim 58 wherein said fatty acid component of said peptide is selected from the group consisting of palmitic acid, stearic acid, arachidic acid, lignoceric acid, palmitoleric acid, oleic acid, linoleic acid, linolenic acid, arachidonic acid, and clupanodonic acid.

60. A method according to Claim 58 wherein said amino acid component of said peptide is selected from the group consisting of leucine, isoleucine, valine, methionine, phenylalanine, tryptophan, threonine, lysine, arginine, histidine, alanine, proline, serine, cysteine, cystine, tyrosine, aspartic acid, glutamic add, and glycine.

61. A method according to Claim 58 wherein said fatty acid component of said peptide is linoleic acid.

62. A method according to Claim 58 wherein said amino acid component of said peptide is glutamic acid.

63. A method according to Claim 58 wherein at least one of said co-emulsifiers is disodium linoleoyl-L-glutamate.

64. A method according to Claim 58 wherein said fatty acid-amino acid peptide is present in an amount of from 0.05 to 0.5 w/v% based on the emulsion.

65. A method according to Claim 58 wherein said emulsion further comprises one or more nutritive amino acids.