EP0188602A1 - Compositions pour l'alimentation parenterale et enterale - Google Patents

Compositions pour l'alimentation parenterale et enterale

Info

Publication number
EP0188602A1
EP0188602A1 EP85903930A EP85903930A EP0188602A1 EP 0188602 A1 EP0188602 A1 EP 0188602A1 EP 85903930 A EP85903930 A EP 85903930A EP 85903930 A EP85903930 A EP 85903930A EP 0188602 A1 EP0188602 A1 EP 0188602A1
Authority
EP
European Patent Office
Prior art keywords
acid
peptide
emulsion
emulsion according
phosphatide
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP85903930A
Other languages
German (de)
English (en)
Inventor
John Yol Park
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
American Hospital Supply Corp
Original Assignee
American Hospital Supply Corp
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by American Hospital Supply Corp filed Critical American Hospital Supply Corp
Publication of EP0188602A1 publication Critical patent/EP0188602A1/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/10—Dispersions; Emulsions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • A61K9/0029—Parenteral nutrition; Parenteral nutrition compositions as drug carriers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/01—Hydrolysed proteins; Derivatives thereof

Definitions

  • This invention relates to an improved composition for total parenteral or enteral nutrition, and more particularly, to a composition containing amino acids, fat and carbohydrates and a means for emulsifying such a composition.
  • Total parenteral nutrition is a technique employed to sustain life and/or accelerate recovery in patients who cannot consume foods due to primary diseases.
  • TPN Total parenteral nutrition
  • aqueous solutions of amino acids, fat, carbohydrate, vitamins and electrolytes are typically admixed under an aseptic environment in the pharmacy prior to intravenous administration in patients. This practice not only increases hospital cost in terms of ordering, stocking and admixing, but also introduces a possibility of microbial contamination, thereby exposing patients to a higher risk of in ection.
  • TPN practice requires a central vein catheter for administration.
  • the surgical 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.
  • development of a TPN solution which does not require admixing and can be administered through a peripheral vein becomes a vital solution to the 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 synthesize body protein, while fat and carbohydrate are sources of energy for vital processes.
  • To synthesize body proteins effectively, all of the 20 protein 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 body, it is necessary to receive from an external source the essential amino acids which cannot be synthesized in the body from a TPN infusate.
  • soy bean phosphatides can result 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 arginine and thus the amino acid composition of these two products is undesirable due to their very low concentration or total absence of arginine.
  • composition described in this patent contains various amino acids, fat and either soy or egg yolk phosphatide as an emulsifier. Again, however, the use of only the soy or egg phosphatide is not sufficient to stabilize a solution containing arginine with fat. All of the examples described in this patent include diaminovaleric acid (ornithine), apparently as a substitute for arginine.
  • U.S. Patent No. 3,273,720 to Suzuki, et al. teaches the use of a fatty acid (or its basic amino acid salt) as a co-emulsifier with egg-yolk phospholipids.
  • the salt disclosed in Suzuki would dissociate in solution and is not really dif erent from the use of the fatty acid alone in an amino acid containing emulsion.
  • the use of the fatty acid-amino acid peptide as opposed to the mere salt which dissociates in solution, has been found to provide additional stabilization advantages, including increased water solubility and lower requirements for effectiveness.
  • a combination of fatty acids together with soybean phosphatides was not able to sufficiently stabilize a at emulsion containing arginine together with other nutrients.
  • compositions for oral and enteral use contain all of the essential amino acids together with fat and carbohydrate, it is necessary to provide a compatible means for stabilizing a fat/water emulsion, particularly one containing arginine with fat.
  • composition of the present invention involves the use of disodium salts or other cation salts of a fatty acid-amino acid peptide alone and in combination with egg or other phosphatides as co-emulsifiers.
  • the remainder of the fat emulsion contains fat, amino acids, including lysine and arginine, and other essential nutrients for TPN and enteral nutritional use.
  • the fatty acid-amino acid peptide may be used as an emulsification agent to provide improved stability to a fat emulsion beyond that provided by the mere salt of the fatty acid and the amino acid. This was surprising in that previous laboratory tests have indicated that fatty acid-amino acid peptides, such as linoleoyl glutamate, when administered in a saline solution can be hemolytic and toxic. 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.
  • the parenteral or enteral composition of the present invention contains the following ingredients in essentially the indicated weight proportions.
  • amino acids used in the invention are the L-isomers and glycine which are utilized for protein synthesis or per orming biological functions in mammals. Biologically available precusors of these amino acids in the form of derivatives and peptides may also be included.
  • Sugar alcohols such as giycerol and sorbitol included in the present invention are those which can be metabolized to generate biologically available energy in the mammalian species, and are chemically compatible with amino acids during heat sterilization and/or are stable during shelf life storage.
  • the reducing sugars, such as glucose generally result in undesir ⁇ able reactions with amino acids during heat sterilization.
  • the composition of the present invention in order to be complete for total nutrition, pre errably 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 egg 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 car boxy lie group of a long chain fatty acid with the amino group of an amino acid.
  • 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, lysine, arginine, histidine, alanine, proline, serine, cysteine, cystine, tyrosine, aspartic acid, glutamic acid, and glycine. It is also contemplated that the peptides be used either as the salt or the ree acid.
  • the total parenteral or enteral nutrition composition of the present invention comprises a combination of amino acids, fat and carbohydrates in a fat-water emulsion.
  • a fat-water emulsion it has been surprisingly found that a
  • fatty acid-amino acid peptide may be used as an emulsifier and that a combination of co-emulsifiers 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.
  • a phosphatide such as egg or soybean phosphatide.
  • compositions of Table 1 were placed in vials purged with nitrogen, capped and sterilized statically at 120°C for 20 minutes.
  • the stability of the emulsion was determined by measuring the "M-value" of each sample.
  • the M-values were determined by diluting a 100 ml aliquot with distilled water and obtaining an absorbance reading in a 1 cm cuvette at 500 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.
  • the results of the study are set forth in Table 2.
  • the combination of the fatty acid-amino acid peptide with egg yolk phosphatide as co- emulsifiers provides a synergistic effect in stabilizing the fat/amino acid emulsion.
  • 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 of the emulsion increases with an increasing amount of the fatty acid-amino acid peptide. The specific desired amount would 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 - 0.2 g/100 ml of the peptide.
  • soy bean oil may include corn oil, other vegetable oils or other nutritionally acceptable fat sources.
  • phosphatides may be used other than those found in egg.
  • An example is soy bean phosphatide or lecithin.
  • Various supplemental components such as electrolytes and vitamins may also be added or complete nutrition.
  • a number of fatty acid-amino acid peptides may be used other than linoleoyl-L-glutamate.
  • the group of long chain fatty acids which may be used as part of the peptide consists of saturated and unsaturated acids with 16 to 22 carbon atoms. These include 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, isoieucine, 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 will also have nutritional value. However, the D-isomer or a racemic mix may also be used while retaining the desired emulsification characteristics.
  • peptides may be used either as the salt or the free acid.
  • the specific amino acid composition of the emulsion as a whole is not critical to the present invention. However, the maximum benefits are realized by the ability to include arginine and lysine in the fat emulsion. 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 invention.
  • a total parenteral nutrition composition was prepared containing the following ingredients:
  • the egg yolk phosphatide was dissolved in soy bean oil by stirring at 600 rpm at 80°C for ten minutes. USP grade water warmed to 80°C was then added to the oil mixture under continuous agitation until all egg phosphatide was dissolved. A primary dispersion was then made by high shear mixing under nitrogen purge at 8,500 rpm at 40°C for twenty minutes. The dispersion was then subjected to high pressure homogenization at 530 kg/cm 2 and 50°C for ten cycles.
  • aqueous solution previously made to contain appropriate amounts of glycerol, sorbitol, amino acids, including lysine and arginine, and disodium linoleoyl-L-glutamate was then added to the primary dispersion and further homogenized under high pressure for ten cycles.
  • the emulsion was adjusted to an appropriate physiological pH (from about 5 to 9) using means known in the art and filtered through a 0.8 micron filter under 0.5 kg per square centimeter nitrogen pressure.
  • the emulsion was then placed in appropriate containers and may be sterilized using conventional techniques. This may include heat or filter sterilization.
  • the resulting emulsion was stable, non-pyrogenic and suitable for intravenous administration to human patients.
  • composition useful for enteral nutrition may be prepared using similar processing steps to those described in Example 1 and containing the following ingredients:
  • the amount of heat applied to sterilized enteral compositions is generally less than that required for parenteral compositions.
  • glucose polymers such as maltodextrins and starches can be included in enteral compositions to achieve the desired nutritional effects. It is possible to sterilize enteral compositions containing glucose polymers and amino acids without adverse chemical reactions which may compromise the nutritional properties of the composition.
  • composition suitable for enteral nutrition according to the present invention also contains a number of vitamins and electrolytes. It has the following composition:

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • General Health & Medical Sciences (AREA)
  • Epidemiology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Immunology (AREA)
  • Nutrition Science (AREA)
  • Dermatology (AREA)
  • Dispersion Chemistry (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicinal Preparation (AREA)

Abstract

Une émulsion de graisses stable pour l'alimentation parentérale ou entérale, contenant des amino-acides, des graisses et des hydrates de carbone. L'émulsion est stabilisée par une combinaison de co-émulgateurs comprenant un phosphatide tel qu'un phosphatide d'oeufs ou de soja et un peptide à acide gras/amino-acide dans lequel le composant acide gras du peptide est de l'acide saturé ou non saturé possédant de 16 à 22 atomes de carbone.
EP85903930A 1984-07-27 1985-07-24 Compositions pour l'alimentation parenterale et enterale Withdrawn EP0188602A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US63508984A 1984-07-27 1984-07-27
US635089 1984-07-27

Publications (1)

Publication Number Publication Date
EP0188602A1 true EP0188602A1 (fr) 1986-07-30

Family

ID=24546409

Family Applications (1)

Application Number Title Priority Date Filing Date
EP85903930A Withdrawn EP0188602A1 (fr) 1984-07-27 1985-07-24 Compositions pour l'alimentation parenterale et enterale

Country Status (6)

Country Link
EP (1) EP0188602A1 (fr)
JP (1) JPS61502822A (fr)
KR (1) KR860000862A (fr)
CA (1) CA1257131A (fr)
WO (1) WO1986000810A1 (fr)
ZA (1) ZA855604B (fr)

Families Citing this family (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
SE8505047L (sv) * 1985-10-25 1987-04-26 Nutritional Int Res Inst Fettemulsion
US5684050A (en) * 1986-01-24 1997-11-04 Hemagen/Pfc Stable emulsions of highly fluorinated organic compounds
US5514720A (en) * 1986-07-09 1996-05-07 Hemagen/Pfc Stable emulsions of highly fluorinated organic compounds
GB8719988D0 (en) * 1987-08-25 1987-09-30 Efamol Ltd Chemical compounds
US5171755A (en) * 1988-04-29 1992-12-15 Hemagen/Pfc Emulsions of highly fluorinated organic compounds
US5403575A (en) * 1991-12-12 1995-04-04 Hemagen/Pfc Highly fluorinated, chloro-substituted organic compound-containing emulsions and methods of using them
EP1521735A2 (fr) * 2001-05-25 2005-04-13 Ceremedix, Inc Composes a base d'un sel acide amine permettant de parer aux effets des especes d'oxygene reactif et des radicaux libres
KR200453914Y1 (ko) * 2009-09-03 2011-06-03 권영철 천정재 인쇄용 지지장치
US20110240050A1 (en) * 2010-04-01 2011-10-06 L'oreal S.A. Cosmetic compositions containing a fatty acid, arginine, and a co-emulsifier

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB1256162A (en) * 1968-08-16 1971-12-08 Braun Fa B Improvements in and relating to liquid products for intravenous administration
JPS537492B2 (fr) * 1973-02-12 1978-03-18
JPS51115909A (en) * 1975-04-01 1976-10-13 Otsuka Pharmaceut Factory Inc A process for preparing amino acid parenteral injection mixed with a r educing sugar
US4126628A (en) * 1977-03-28 1978-11-21 Canadian Patents And Development Limited Acylation of amino acids
JPS6030652B2 (ja) * 1979-05-07 1985-07-17 株式会社ミドリ十字 静脈注射用脂肪乳剤

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO8600810A1 *

Also Published As

Publication number Publication date
JPS61502822A (ja) 1986-12-04
ZA855604B (en) 1986-08-27
CA1257131A (fr) 1989-07-11
WO1986000810A1 (fr) 1986-02-13
KR860000862A (ko) 1986-02-20

Similar Documents

Publication Publication Date Title
EP0312612B1 (fr) Emulsion nutritive
EP0347890B1 (fr) Compositions nutritives contenant des acides aminés
EP0220153B1 (fr) Emulsion nutritive capable de transporter de l'oxygène et son procédé de préparation
JP7438982B2 (ja) Ｇｐｃを含有する非経口栄養のための脂質エマルション
US3873720A (en) Nutrient fat emulsion
JP2728134B2 (ja) 非経口栄養サポート用アミノ酸組成物
EP0176094B1 (fr) Solution parentérale alimentaire
DE69006395T2 (de) Nährstoff-Zusammensetzungen für die Ergänzung an Aminosäuren bei Säugetieren.
US5206220A (en) Soluble and stable sources of tyrosine, cysteine and glutamine for total parenteral nutrition
CA1257131A (fr) Compose pour nutrition parenterale et enterale totale
CA1217725A (fr) Emulsion huileuse renfermant des acides amines
JPH06312923A (ja) 末梢静脈投与用栄養輸液
JP3182564B2 (ja) 栄養組成物
JP3132085B2 (ja) 脂肪乳剤
JP3097196B2 (ja) 脂肪乳剤の安定化法
JP2537406B2 (ja) 癌用アミノ酸製剤
JP3430965B2 (ja) 安定化された脂肪乳剤含有溶液
EP0608217A1 (fr) Sources stables et solubles de tyrosine, de cysteine et de glutamine pour une alimentation parenterale totale
JP3429327B2 (ja) 癌用アミノ酸輸液剤
JP3711400B2 (ja) 輸液製剤
JP6647656B1 (ja) 輸液製剤
FR2561522A1 (fr) Solution injectable, notamment pour le traitement de la cetose et son procede de preparation
JP2744662B2 (ja) 栄養組成物
JP3049280B2 (ja) 栄養輸液入りバッグ
JPH0532540A (ja) 輸液製剤

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): AT BE CH DE FR GB IT LI LU NL SE

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN

18D Application deemed to be withdrawn

Effective date: 19860711

RIN1 Information on inventor provided before grant (corrected)

Inventor name: PARK, JOHN, YOL