EP0168425A4 - Parenterale nährung mit mittel- und langkettigen triglyceriden. - Google Patents

Parenterale nährung mit mittel- und langkettigen triglyceriden.

Info

Publication number
EP0168425A4
EP0168425A4 EP19850900428 EP85900428A EP0168425A4 EP 0168425 A4 EP0168425 A4 EP 0168425A4 EP 19850900428 EP19850900428 EP 19850900428 EP 85900428 A EP85900428 A EP 85900428A EP 0168425 A4 EP0168425 A4 EP 0168425A4
Authority
EP
European Patent Office
Prior art keywords
mcts
composition
lcts
emulsion
acid
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.)
Ceased
Application number
EP19850900428
Other languages
English (en)
French (fr)
Other versions
EP0168425A1 (de
Inventor
George L Blackburn
Vigen K Babayan
Bruce R Bistrian
Lyle L Moldawer
Richard Cotter
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.)
Clintec Nutrition Co
Beth Israel Deaconess Medical Center Inc
Original Assignee
Beth Israel Deaconess Medical Center Inc
Baxter Travenol Laboratories Inc
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 Beth Israel Deaconess Medical Center Inc, Baxter Travenol Laboratories Inc filed Critical Beth Israel Deaconess Medical Center Inc
Publication of EP0168425A1 publication Critical patent/EP0168425A1/de
Publication of EP0168425A4 publication Critical patent/EP0168425A4/de
Ceased legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
    • A61K31/23—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin of acids having a carboxyl group bound to a chain of seven or more carbon atoms

Definitions

  • This relates to total parenteral nutrition of patients with liver disease or septicemia. It is particularly concerned with providing such nutrition via lipid emulsions.
  • Lipid emulsions for parenteral nutrition are available commercially or can be manufactured in accordance with known processes. Generally, such emulsions have been made using the triglycerides of long chain fatty acids (LCTs). LCTs are obtained conventionally from soybean or safflower oil. Long chain fatty acids are fatty acids having 14 or more carbon atoms, usually 16 or 18 carbon atoms.
  • MCTs medium chain fatty acids
  • Emulsions of this type are disclosed in European Patent Application 0071995 and Eckart et al., "J. Parenteral and Enteral Nutrition” 4(4):360-366 (1980).
  • MCT-derived fatty acids are absorbed by the intestinal cell at a rate twice the absorption rate of LCT-derived fatty acids.
  • the most striking difference between MCT and LCT was shown to be the mechanism of transport to sites of utilization and, as a result, their predominant mode of utilization.
  • MCT-derived fatty acids pass through the intestinal epithelial cell without reesterlflcation to MCT. They then enter the portal vein, bind to albumin, and are transported in this bound form in the bloodstream.
  • LCT-derived fatty acids after absorption are reesterified in intestinal cells to form LCT and packaged with protein and phospholipids to form lipid particles (chylomicrons) that enter the lymph system and, later, the circulatory system for distribution to the tissues of utilization.
  • chylomicrons lipid particles
  • MCTs are much more readily utilized for caloric energy, but are less effectively incorporated into tissue lipids. MCTs, when administered orally, are believed to be metabolized primarily in the liver, while LCTs are metabolized throughout the body (Scheig, R. In: Medium Chain Triglycerides, J.R. Senior, Ed. pp 39-49 [1968]).
  • Liver disease as this term is used herein means a primary or secondary disorder of the liver parenchyma that results in reduced hepatic function.
  • the etiology of the disease may include but not be limited to any one of the following common disorders: Alcoholic cirrhosis, acute hepatocellular damage secondary to drug abuse or poisoning, genetic deficiencies such as tyrosinosis, trauma to the liver, hepatitis, primary biliary cirrhosis, liver abscess, Budd-Chiarf syndrome, Wilson's disease, or primary or secondary liver neoplasms.
  • liver function tests such as serum glutamate-oxaloacetate transaminase, serum glutamate-pyruvate transaminase and billrubin, reductions in indocyanin green or bromosulphopthalein clearance, tissue biopsy, and/or neurological manifestations such as encephalopathy.
  • Liver disease as defined herein excludes the subclinically mild and reversible hepatic dysfunction induced by parenteral nutrition (Eckart et al. Ibid).
  • Patients with septicemia include patients having subclinical septicemia or susceptibility to septicemia. Patients in this group include patients recuperating from abdominal surgery, patients with respiratory diseases and those with active infections such as abcesses or infected wounds.
  • Intravenous calorie intake in liver diseased patients is hampered by chronic carbohydrate and fluid intolerance.
  • current LCT emulsions although calorically dense, are contraindicated in liver disease because liver dysfunction is frequently associated with an impaired ability to metabolize LCT.
  • MCTs have been included in oral formulations for the nutrition of stressed (including liver diseased) patients.
  • An example is the Travasorb ® Hepatic formulation sold by Travenol Laboratories, Inc.
  • the doses of MCT to be delivered with such formulations have been low, however, on the order of about 0.2 mg MCT/Kg body weight (BW)/min. when following the instructions for use.
  • MCTs are added to these nutrient formulations because they are believed necessary to circumvent the maladsorption of LCTs that accompanies deficient bile secretion by diseased livers.
  • the low doses were believed mandated by the prevalent belief in the art that MCTs are harmful to liver diseased patients. See, for example, N. Greenberger et al. "Ann.
  • MCTs can be parenterally administered to recipients with liver disease or septicemia, and in dosages heretofore believed to be potentially hazardous, without toxic side effects.
  • MCTs can supply nutritionally adequate calories to such patients without resulting in the liver fatty deposits or the reductions in the efficacy of the reticuloendothelial system (RES) noted when supplying LCTs as a significant calorie source.
  • RES reticuloendothelial system
  • the improvement herein comprises parenterally administering a composition comprising MCTs to a liver diseased patient or a patient with septicimia. It further comprises administering greater than about 0.35 mg MCTs/Kg BW/min. to such patients, preferably about from 0.5 to 2 mg MCTs/Kg BW/min., and selecting a weight proportion of MCTs to LCTs no greater than about 3 to 1.
  • compositions including (1) a composition comprising (a)lipids wherein about from 25% to 75% by weight of the lipids are MCTs and the remainder are LCTs and (b)the branched chain amino acids, valine, leucine and/or isoleucine or the keto analogues of valine, leucine and/or valine.
  • composition comprising MCTs and at least one branched chain amino acid, or preferably an amino acid mixture in which greater than about 35% of the mole weight of amino acids are valine, isoleucine and/or leucine or the keto analogues of valine, isoleucine and/or leucine.
  • the MCTs to be used herein will be C 6 , C 8 , C 10 and/or C 12 mixtures in proportions ranging in weight percent about from 0% to 3%, 50% to 100%, 50% to 100%, and 0% to 3%, respectively.
  • C 8 and C 10 fatty acids will be present, in ratios of about from 1:3 to 3:1.
  • the proportions C 6 , C 8 , C 10 and C 12 fatty acids will be ⁇ 2%, 65-80%, 20-35%, and ⁇ 2%.
  • the MCT compositions can contain free fatty acids at up to about 0.005/mEq/g (USP), will have a saponification value of about from 325-365 (USP) and an iodine value (USP Method II) of up to about 1.0 gl 2 /100g. Color (Lovibond, AOCS Cc 13h.45) is preferably 1.0 R. Unsaponifiable matter (USP), hydroxyl value (USP), and heavy metals (USP Method II) should be less than about 1.0%, 10.0 and 10 ppm, respectively.
  • the refractive index (USP) and specific gravity (USP) range from about 1.440 to 1.460 and 0.920 to 0.960, respectively. These specifications are not critical.
  • MCT oils of this type are commercially available as lauric oils from coconut oil.
  • the MCTs are used alone or incorporated with minor proportions of LCTs into the oil phase of an oil-in-aqueous emulsion.
  • the proportion of MCTs to LCTS is preferably no more than about 3:1 by weight.
  • emulsions containing MCTs as the sole lipid source are suitable for use at physiologic nonprotein calorie intakes for the nutrition of liver diseased patients.
  • MCT dosages of up to about 4mg MCTs/Kg/hr can be administered on a continuous basis, although the physician will need to tailor the maximum dose to the capabilities of the patient and be observant for toxicity symptoms such as vomiting and lethargy.
  • MCT toxicity can be ameliorated by supplying a proportion of non-protein calories as LCTs.
  • a given hyperphysiological dose of MCTs may result in MCT toxicity symptoms, but the same dose accompanied by an approximately equal or minor proportion of LCTs will not produce the symptoms.
  • the MCT emulsions contain a proportion of LCTs, i.e., about from 15% to 50% by weight of the total lipids.
  • the MCT-containing emulsions may contain other substances besides LCTs. These include surfactants such as egg or soya phospholipid, tonicity adjusting agents such as glycerol, carbohydrate nutrients such as dextrose, and electrolytes, amino acids, vitamins and trace minerals.
  • surfactants such as egg or soya phospholipid
  • tonicity adjusting agents such as glycerol
  • carbohydrate nutrients such as dextrose
  • electrolytes amino acids
  • vitamins and trace minerals trace minerals.
  • concentration by weight of the oil in the emulsion is about from 5% to 20%, with 20% being preferred.
  • the amino acid compositions used in the a ⁇ ueous phase of the emulsions for use with liver diseased patients preferably will have one or more of the following characteristics: (a) The total mole percent of the amino acids serine, glycine, threonine, tryptophan, glutamine and histidine will range about from 8% to 16%;
  • the amino acid compositions optimally will include essential and nonessential amino acids, in the latter group especially arginine and histidine. These last two amino acids are known to be desirable in the nutrition of liver diseased patients.
  • a representative amino acid composition is disclosed in PCT International Application published as WO 83/00085.
  • Other representative compositions that have been urged to be useful in the nutrition of liver diseased patients are disclosed in U.S. patents 3,950,529; 4,100,293; 3,832,465; and 4,259,353; and U.K. patent 2,037,161A, all of the foregoing being incorporated by reference.
  • the amino acids are desirably supplied in the crystalline form rather than as protein hydrolysates. The amount of amino acids included in the emulsions will be sufficient to maintain patients' nitrogen requirements at the planned rate of infusion of MCT and/or LCT calories.
  • the lipid particles in the emulsion will have a diameter of less than about 0.75 ⁇ m and preferably less than about 0.5 ⁇ m.
  • the emulsions will be sterile and ordinarily are packaged in glass containers. They can be made by known methods. For example see U.S. patent 3,169,094 and European Patent Application 0071995.
  • MCT dosage may vary about from 0.35 mg/Kg BW/min. to 2.05 mg/Kg BW/min., preferably about from 0.4 mg/Kg BW/min. to 1.00 mg/Kg BW/min. and optimally about from 0.5 to .75 mg/Kg BW/min.
  • the remaining nonprotein calories are carbohydrates or a mixture of LCTs and carbohydrates.
  • a convenient method for preparing and administering the emulsion herein is for the hospital or user pharmacy to sterile mix the emulsion components using commercially available equipment.
  • the MCT and LCT emulsions are mixed with sterile aqueous solutions of other desirable additives: Amino acids in proportions suitable for disease nutrition, vitamins, carbohydrates such as dextrose, electrolytes such as potassium and sodium chloride drugs, and trace minerals such as zinc ions.
  • the resulting product is a sterile, emulsion of MCTs and LCTs, in an aqueous solution containing amino acids in proportions characterized above, carbohydrate and, optionally, drugs, trace minerals and vitamins.
  • the MCTs and LCTs can be mixed as oils, then emulsified and combined with the other additives noted above.
  • Drugs which have heretofore been conventionally administered to liver disease patients (cymeditine or steroids) or septictmia patients (antibiotics) may be included in the emulsion.
  • the emulsions herein are packaged and stored in hermetically sealed containers for long or short term storage.
  • the additives to be included in the emulsions will depend upon how long the emulsions are to be stored. Long term storage is acceptable for emulsions with aqueous phases containing sugar, the amino acids and some electrolytes. Dextrose should not be included in emulsions prepared for long term storage. They are administered continuously or discontinuously by infusion into the subclavian vein as is the conventional practice in total parenteral nutrition. When LCT and MCT emulsions are combined in pharmacies or are mixed with other solutions for short-term storage as discussed above they may be stored in flexible containers now available commercially for temporary storage of LCT emulsion admixtures.
  • a suitable mixing vessel 2.0 kg of MCT oil consisting of approximately 75% octanoic acid and 25% decanoic acid, 120 g of purified egg phospholipids, 225 g of glycerol, USP, and a suitable quantity of water for injection, USP, are mixed to produce a coarse emulsion.
  • This emulsion is then homogenized repeatedly at high pressure to produce an emulsion of mean particle diameter of less than 0.75 ⁇ m.
  • the pH of the emulsion is adjusted to a physiological range with sodium hydroxide.
  • the final volume is adjusted, if necessary, with water for injection, USP, to 10 L and the emulsion filtered Into glass containers and heat sterilized by the normal procedure.
  • a 2 L plastic bag suitable for intravenous admixtures (TravamulsionTM container) is added 385 mis of a 10% crystalline amino acid solution (Travasol ® 10%; Travenpl Laboratories, Inc.), 535 mis of 4% isomolar branched amino acid (leucine, isoleucine, and valine) solution, 430 mis of 70% hydrous dextrose, 63 mis of 20% soybean oil emulsion (TravamulslonTM 10%; Travenol Laboratories, Inc.), 217 mis of a 20% MCT oil emulsion of Example 1 and 90 mis of a solution containing appropriate electrolytes, trace minerals and vitamins.
  • the solution is mixed by hand and is connected to an infusion pump suitable for administration into a patient.
  • the solution contains 60 gms of amino acids and a total of 1800 kcals. 65% of the nonprotein calories are hydrous dextrose and 35% of the nonprotein calories are lipid.
  • the solution may be administered to a hospitalized patient over 24 hours at a constant rate of 72 mls/hr.
  • a suitable mixing vessel approximately 1.5 kg of MCT oil and 0.5 kg of soybean oil, 120 g of purified egg phospholipids, 225 g of glycerol, USP, and a suitable quantity of water for injection, USP, are mixed to produce a coarse emulsion.
  • This emulsion is then homogenized repeatedly at high pressure to produce an emulsion of mean particle diameter of less than 0.75 ⁇ m.
  • the pH of the emulsion is adjusted to a physiological range with sodium hydroxide.
  • the final volume is adjusted, if necessary with water for injection, USP, to 10 L and the emulsion filtered into glass containers and heat sterilized by the normal procedure.
  • a 2 L container suitable for intravenous infusions of admixtures (TravamulsionTM container) is added 385 mis of a crystalline amino acid solution (Travasol® 10%; Travenol Laboratories, Inc.), 535 mis of 4% isomolar branched chain amino acid (leucine, isoleucine, and valine) solution, 430 mis of hydrous dextrose, 560 mis of 10% lipid emulsion comprised of 75% MCT oil and 25% soybean oil (Example 3) and 90 mis of a solution containing appropriate electrolytes, trace minerals and vitamins.
  • the resulting solution is mixed by hand and is connected to an infusion pump suitable for administration into a patient.
  • the solution contains 60 gms of amino acid and a total of 1800 kcals. 65% of the nonprotein calories are hydrous dextrose and 35% of the nonprotein calories are lipid in the form of a 75% MCT oil emulsion and 25% soybean oil emulsion.
  • the solution may be administered to a hospitalized patient over a 24-hour period at a constant rate of 72 mis/hour.
  • Hepatic insufficiency was induced in previously healthy Sprague-Dawley CR1:CD rats by portacaval anastomosis.
  • An end-to side portacaval anastomosis (shunt) was induced by a nonsuture method using Teflon tubing.
  • the rats were returned to stainless steel cages and allowed to consume laboratory chow, ad libitum. After that period in time, 24 animals were fasted overnight and hepatic function assessed by both static and dynamic indices. Results were compared to 20 similar animals that received only a sham operation.
  • hepatic reticuloendothelial system function was evaluated in 12 additional portacaval shunted rats and 10 sham operated rats.
  • the portacaval shunt model in the rat produced a hepatic insufficiency model which mimics in many ways the clinical conditions seen in human liver disease.
  • Sprague-Dawley CR1:CD rats underwent portacaval anastomosis and splenectomy and were returned to their metabolic units for 3 weeks. Following the recovery period, the rats were randomized to receive total parenteral nutrition for four days. All of the diets delivered 300 kcals/Kg BW/day and 12.5 g amino acid/day except for the dextrose only group ("D only") which received only 300 dextrose kcals/Kg BW/day. One group of animals received all of the nonprotein calories as dextrose (AA+D) whereas the remaining two groups received half of their nonprotein calories as lipid.
  • One of the lipid groups received its fat calories as a soybean (LCT) oil emulsion (AA+D+L) while the remaining lipid group received one-half of the fat calories as the 20% MCT oil emulsion of example 1 and the other half as a 20% soybean oil emulsion (AA+D+PM).
  • LCT soybean
  • AA+D+PM soybean oil emulsion
  • the improved liver morphology and albumin concentration in the rats given the 50:50 physical mix of soybean oil emulsion and MCT oil emulsion support the conclusion that MCTs as a component of total parenteral nutrition are an effective energy source during hepatic dysfunction.
  • the effect of MCT emulsions on reticuloendothelial system function was investigated in 24 additional portacaval shunted rats that had also undergone splenectomy. Seven weeks following portacaval anastomosis and splenectomy, all animals received diets that delivered 200 kcals/Kg BW/day and 8.3 g amino acid/Kg BW/day.
  • Lipid was given at 50% of the total nonprotein calorie intake as either a 10% soybean oil emulsion (AA+D+LCT) or a 10% MCT oil emulsion (AA+D+MCT).
  • AA+D+LCT 10% soybean oil emulsion
  • AA+D+MCT 10% MCT oil emulsion
  • This contemplated example demonstrates the use of an MCT emulsion in providing parenteral nutrition to a liver diseased patient.
  • a 47-year-old white male (62 Kg) is admitted to the hospital because of delirium and hematemesis.
  • the patient had a 25 year history of alcohol abuse and on a previous admission had biopsy proven alcoholic cirrhosis. Gastroscopy had demonstrated the presence of extensive esophageal varices.
  • Serum albumin concentration was 1.9 g/dl (normal greater than 3.5 g/dl) and total protein 4.4 g/dl (normal greater than 6 g/dl) reflecting visceral protein attrition. Abnormalities in the serum amino acid pattern were also evident with L-tyrosine being 274 nmols/ml (normal 50-100 nmols/ml) and L-phenylalanine being 332 nmols/ml (normal 50-100 nmols/ml). The serum aromatic to branched chain amino acid ratio was 2.74 with normal being less than 0.80.
  • Nutritional support for the patient was set at a total calorie intake of 30 kcals/Kg BW/day and protein (as amino acid equivalents) at 1.0g/Kg BW/day.
  • the amino acid source was a standard amino acid mixture (Travasol amino acids) supplemented with the branched chain amino acids, leucine, isoleucine, and valine so that the total branched chain proportion was 50% of the total amino acids by weight.
  • the remaining 26 kcals/Kg BW/day were administered as 65% hydrous glucose and 35% as a physical mixture of 20% MCT oil emulsion and 20% soybean oil emulsion. 75% of the lipid calories were given as the medium chain triglyceride oil emulsion and 25% of the lipid calories as a soybean oil emulsion.
  • Actual daily intake of the hydrous glucose was 3.5 mg/Kg/min, of the soybean oil emulsion was 0.174 mg/Kg/min and of the MCT oil emulsion, 0.585 mg/Kg/min. Electrolytes, trace minerals, and vitamins were adjusted daily to meet the established requirements of the patient.
  • the entire formula was administered in a course of therapy commencing with 1720 ml of fluid continuously over a 24 hour period at a rate of 72 mls/hr through the subclavian vein catheter.
  • the patient's condition was considered to have improved after treatment with the regimen of this Example.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Emergency Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical & Material Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
EP19850900428 1984-01-16 1984-12-18 Parenterale nährung mit mittel- und langkettigen triglyceriden. Ceased EP0168425A4 (de)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US57102184A 1984-01-16 1984-01-16
US571021 1984-01-16

Publications (2)

Publication Number Publication Date
EP0168425A1 EP0168425A1 (de) 1986-01-22
EP0168425A4 true EP0168425A4 (de) 1989-03-09

Family

ID=24282010

Family Applications (1)

Application Number Title Priority Date Filing Date
EP19850900428 Ceased EP0168425A4 (de) 1984-01-16 1984-12-18 Parenterale nährung mit mittel- und langkettigen triglyceriden.

Country Status (5)

Country Link
EP (1) EP0168425A4 (de)
JP (1) JPS61501558A (de)
CA (1) CA1242974A (de)
WO (1) WO1985003002A1 (de)
ZA (1) ZA85202B (de)

Families Citing this family (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4678807A (en) * 1984-03-01 1987-07-07 Baxter Travenol Laboratories, Inc. Method for directed visceral metabolism of medium chain triglycerides
SE8803141L (sv) * 1988-09-07 1990-03-08 Kabivitrum Ab Naeringsmedel foer maenniskor och djur
SE8803142L (sv) * 1988-09-07 1990-03-08 Kabivitrum Ab Nya energisubstrat
EP0537113A1 (de) * 1991-10-10 1993-04-14 SANDOZ NUTRITION Ltd. Energie-Ergänzungsnahrung
JP2990686B2 (ja) * 1994-11-17 1999-12-13 田辺製薬株式会社 水溶性ビタミンｂ類配合総合輸液
US6835408B2 (en) * 1998-11-13 2004-12-28 The Nisshin Oillio Group, Ltd. Oil or fat composition
WO2010005961A2 (en) 2008-07-07 2010-01-14 Pentech Health, Inc. Nutritive compositions and methods of using same
US20140066439A1 (en) 2010-11-10 2014-03-06 Katholieke Universiteit Leuen, K.U.Leuven R&D Osteoclast activity
PT3664628T (pt) * 2017-08-10 2024-12-31 Childrens Medical Ct Corp Métodos e composições relacionados com emulsões compreendendo óleo de peixe e/ou ácidos gordos ómega-3
US20190183832A1 (en) * 2017-12-20 2019-06-20 Michael Guarnieri Nutritional bolus for animals
US12090151B1 (en) 2023-05-12 2024-09-17 Michael Guarnieri Injectable sustained release buprenorphine formulation

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2084172A (en) * 1980-09-24 1982-04-07 Roussel Uclaf Lipid compositions useful in dietetics
EP0071995A2 (de) * 1981-08-08 1983-02-16 B. Braun Holding AG Fettemulsion für parenterale Ernährung

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS537492B2 (de) * 1973-02-12 1978-03-18
US4112123A (en) * 1976-07-21 1978-09-05 Beatrice Foods Co. Nutritionally balanced single food composition and method of production
US4296127A (en) * 1979-04-18 1981-10-20 The Johns Hopkins University Mixed salts of essential or semi-essential amino acids and nitrogen-free analogs thereof
JPS5681515A (en) * 1979-12-07 1981-07-03 Tanabe Seiyaku Co Ltd Amino acid transfusion
JPS58126767A (ja) * 1982-01-22 1983-07-28 Ajinomoto Co Inc 肝臓病患者用栄養組成物
ATE24266T1 (de) * 1982-04-16 1987-01-15 Nestle Sa Lipidhaltige zusammensetzung fuer die orale, enterale oder parenterale ernaehrung.

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2084172A (en) * 1980-09-24 1982-04-07 Roussel Uclaf Lipid compositions useful in dietetics
EP0071995A2 (de) * 1981-08-08 1983-02-16 B. Braun Holding AG Fettemulsion für parenterale Ernährung

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See also references of WO8503002A1 *

Also Published As

Publication number Publication date
JPS61501558A (ja) 1986-07-31
ZA85202B (en) 1985-09-25
WO1985003002A1 (en) 1985-07-18
CA1242974A (en) 1988-10-11
EP0168425A1 (de) 1986-01-22

Similar Documents

Publication Publication Date Title
US4703062A (en) Parenteral nutrition with medium and long chain triglycerides
JP6682596B2 (ja) ω３脂肪酸の自己乳化組成物
CN102348469B (zh) 富含omega-3的水包鱼油非口服营养乳状液
AU663923B2 (en) Method and composition for treating immune disorders, inflammation and chronic infections
TWI749451B (zh) 包含ω脂肪酸的醫藥組合物及包含彼之輸液製劑
US20060088502A1 (en) Drug for reducing side effects in ribavirin interferon combination therapy
CA1242974A (en) Parenteral nutrition with medium and long chain triglycerides
US5276018A (en) Composition comprising amino acids and methods for decreasing muscle breakdown
Mullen et al. Role of nutrition in hepatic encephalopathy
JP2509810B2 (ja) 中鎖トリグリセライドの内臓へ向けられた代謝のための非経口脂質エマルジョン
Heizer et al. Parenteral nutrition at home for 5 years via arteriovenous fistulae: supplemental intravenous feedings for a patient with severe short bowel syndrome
Fleming et al. Subject review: total parenteral nutrition
Galambos et al. Hyperalimentation in alcoholic hepatitis.
EP0401056B1 (de) Glutamin zur Behandlung von beeinträchtigten Abwehrkräften
JP4394174B2 (ja) 炎症性腸疾患治療剤
AU580278B2 (en) Treating liver diseases in patients by administering compositions of medium and long chain triglycerides
US5567736A (en) Use of a choline salt to inhibit fatty liver in patients receiving total parenteral nutrition
BRPI0915744A2 (pt) composição nutriente, forma bde dosagem e método de uso da mesma
US4567045A (en) Isotonic glycerol free intravenous fat emulsion
Bailey et al. Total parenteral nutrition with short-and long-chain triglycerides: triacetin improves nitrogen balance in rats
CN116407502B (zh) 高epa含量的口服微乳及其制备方法和应用
AU602772B2 (en) Lipid emulsion and method for intravenous infusion
CN101317818B (zh) 甲氨喋呤脂肪乳剂、其冻干剂、其制备方法及应用
Trimbo et al. Use of a new olive oil-based emulsion as an alternative to soy based emulsions in long term TPN: favorable effects on plasma fatty acid profiles
JP2002338463A (ja) コリン配合輸液剤

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

17P Request for examination filed

Effective date: 19850820

AK Designated contracting states

Designated state(s): BE CH DE FR GB LI SE

A4 Supplementary search report drawn up and despatched

Effective date: 19890309

RAP1 Party data changed (applicant data changed or rights of an application transferred)

Owner name: NEW ENGLAND DEACONESS HOSPITAL

Owner name: BAXTER INTERNATIONAL INC. (A DELAWARE CORPORATION)

17Q First examination report despatched

Effective date: 19900112

RAP1 Party data changed (applicant data changed or rights of an application transferred)

Owner name: NEW ENGLAND DEACONESS HOSPITAL

Owner name: CLINTEC NUTRITION COMPANY

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

Free format text: STATUS: THE APPLICATION HAS BEEN REFUSED

18R Application refused

Effective date: 19940127

APAF Appeal reference modified

Free format text: ORIGINAL CODE: EPIDOSCREFNE

RIN1 Information on inventor provided before grant (corrected)

Inventor name: MOLDAWER, LYLE, L.

Inventor name: BABAYAN, VIGEN, K.

Inventor name: BISTRIAN, BRUCE, R.

Inventor name: COTTER, RICHARD

Inventor name: BLACKBURN, GEORGE, L.