EP0193602A1 - Triglyceride preparations for the prevention of catabolism - Google Patents

Triglyceride preparations for the prevention of catabolism

Info

Publication number
EP0193602A1
EP0193602A1 EP19850904733 EP85904733A EP0193602A1 EP 0193602 A1 EP0193602 A1 EP 0193602A1 EP 19850904733 EP19850904733 EP 19850904733 EP 85904733 A EP85904733 A EP 85904733A EP 0193602 A1 EP0193602 A1 EP 0193602A1
Authority
EP
European Patent Office
Prior art keywords
oil
acid
structured lipid
chain triglyceride
pharmaceutical composition
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Withdrawn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
EP19850904733
Other languages
German (de)
French (fr)
Inventor
Vigen K. Babayan
George L. Blackburn
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.)
CENTER FOR NUTRITIONAL RESEARCH CHARITABLE TRUST
Original Assignee
CENTER FOR NUTRITIONAL RESEARCH CHARITABLE TRUST
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 CENTER FOR NUTRITIONAL RESEARCH CHARITABLE TRUST filed Critical CENTER FOR NUTRITIONAL RESEARCH CHARITABLE TRUST
Publication of EP0193602A1 publication Critical patent/EP0193602A1/en
Withdrawn legal-status Critical Current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 invention relates to triglyceride preparations for enteral or parentral administration to prevent catabolism and to increase protein synthesis in subjects undergoing severe metabolic stress.
  • This invention provides medium chain and long chain fatty acids chemically synthesized into structured triglycerides (lipids) for enteral or parentral administration as the lipid calorie source, in subjects undergoing severe metabolic stress.
  • lipids structured triglycerides
  • the structural lipids of this invention are randomly rearranged mixtures of medium chain triglycerides (MCT) and long chain triglycerides (LCT). They may be represented by the following formula,
  • R 1 and R 2 may be independently a C 6 to C 12 acid, or a C 12 to C 18 ' acid, and R 3 may be a C 18 " or C 18 " acid.
  • R 1 may be a C 6 to C 12 acid
  • R 2 a C 12 to C 18 acid.
  • C 18 ', C 18 " and C 18 " represent the number of double bonds in the fatty acid moiety being one, two and three double bonds respectively.
  • the medium chain triglycerides may be lauric oils such as, balassee oil, coconut oil, cohune oil, palm kernel oil, tucum oil and fractions thereof.
  • the preferred medium chain triglyceride oil is coconut oil.
  • the long chain triglycerides may be polyunsaturated vegetable oils such as, corn oil, peanut oil, safflower oil, soybean oil, sunflower seed oil, and fish oils.
  • the preferred long chain triglyceride oils are safflower oil, soybean oil, and sunflower seed oil.
  • the percent composition of mixtures of medium chain triglycerides to long chain triglycerides of this invention may be 70 to 30%, 80 to 20%, 85 to 15%, or 90 to 10%. The 80 to 20% and the 85 to 15% mixtures are most preferred.
  • the structured lipids of this invention may be mixtures of coconut oil and soybean oil, which lipids may have the following fatty acid carbon chain length (CCL) composition.
  • CCL fatty acid carbon chain length
  • the present invention provides enteral and parenteral preparations for use in stressed patients to prevent catabolism and to increase protein synthesis.
  • the preparations provide from about 15 to 85% of the fat calories required in the stressed patient.
  • compositions of this invention provide in a 70 Kg man, from about 0.7 gms of fat/Kg of body weight day to about 4.0 gms of fat/Kg of body weight/day.
  • the lipid compositions are preferably administered with additional amino acids, vitamins and minerals as required. Modified amino acid formulas specifically designed for stressed subjects are preferred.
  • the amino acids, vitamins and minerals can be administered in the same solution as the structured lipids or separately. It is preferred that the component groups be separately packaged to facilitate tailoring the diet to the patients specific needs.
  • formulations may include preservatives or stablizers, as required.
  • a structural lipid preparation of this invention is compared with a medium chain lipid, and a long chain lipid for the oxidation of lipids in traumatized animals.
  • Group I a 20% medium chain lipid emulsion composed of 72.5% capric acid (C 8:0) and 27.5% coprylic acid (C 10:0) (obtained from Travenol Laboratories, Inc; Deerfield/ Illinois).
  • Group II a 20% long chain triglyceride emulsion (20% Travamulsion®, Travenol Laboratories)
  • Group III a 20% lipid emulsion composed of structured triglycerides chemically synthesized from 80% coconut oil and 20% soybean oil.
  • Captex 710A Lot No. KH4022A Capital City Products Co., Columbus, Ohio
  • the rats were placed in metabolic chambers that permitted the collection and analysis of their expired breath. At 15 minute intervals for twelve hours, the specific activity of expired carbon dioxide was determined. At the end of the study, the animals were sacrificed
  • Such structured lipids should be preferable and suitable for both enteral and parenteral nutrition.

Landscapes

  • Health & Medical Sciences (AREA)
  • Emergency Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

Des triglycérides structurées (lipides) chimiquement synthétisées sont utilisées comme source lipidique de calories administrées par voie orale ou parentérale à des patients soumis à un stress métabolique grave.Chemically synthesized structured triglycerides (lipids) are used as a lipid source of calories administered orally or parenterally to patients under severe metabolic stress.

Description

TRIGLYCERIDE PREPARATIONS FOR THE PREVENTION OF CATABOLISM
This invention relates to triglyceride preparations for enteral or parentral administration to prevent catabolism and to increase protein synthesis in subjects undergoing severe metabolic stress.
Under normal nutritional and physiological conditions, fuel requirements of the body are largely met by glucose and fatty acids metabolism. The body's amino acids generally contribute little towards overall fuel economy at these times. However, during abnormal metabolic stress states induced by trauma or sepsis, fat mobilization and utilization and glucose utilization are decreased due to hormonal changes precipitated by the stress. Under these conditions, an extremely high and rapid rate of muscle protein catabolism occurs.
Over the last several years, investigators have studied the metabolic consequences of trauma in man. Most of these studies concerned themselves with understanding cause and effect, as it related to biochemistry and metabolism, and subsequent physiological responses. Investigators have found for example that large (e.g. 25%) body surface area burns increases basal energy expenditure as much as two fold. The release rate of peripheral amino acids also increases approximately 3-4 times under similar traumatic conditions. These changes, if persistent, may result in protein malnutrition, alterations in essential organ functions, and, finally, multiple organ failure. For these reasons most clinicians have recommended intensive nutritional therapy for the severely injured or burned patient. Wilmore D.W. "Panel Report on Nutritional Support of Patients with Trauma or Infection:, Am.J.Clin.Nutr., 34:1213-22, 1981, has suggested that exogenous glucose administration at intakes exceeding energy expenditure may be of little benefit in severely stressed patients. An already abundant supply of glucose is present in these patients due to their hyperglycemic state. Elevated insulin levels associated with hyperglycemia appear to reduce the availability of free fatty acid by limiting lipodysis.
Wannenmacher, R.W., Kaminski, M.V., "Use of Lipid Calories During Pneumoccal sepsis in the Rhesus Monkey. Par. Ent. Nut. 6:100-105, 1982, have suggested the energy needs of stressed patients may be optimally provided when fat is incorporated into the parental regimen. However, controversy exists over the value of lipid emulsions because their use has been implicated in Reticulo Endothelial System (RES) system blockage, increased prostaglandin production and development of Acute Respiratory Distress Syndrome (ARDS). These complications have been thought to be a result of reduced clearance of lipid chylomicrons as well as the high percentage of polyunsaturated fatty acids and arachidonic acid precursors in the lipid source.
Moreover, controlled trials in injured laboratory animals with triglyceride emulsions containing medium chain fatty acids exclusively, have failed to show any benefit over current long chain triglyceride emulsions. This invention provides medium chain and long chain fatty acids chemically synthesized into structured triglycerides (lipids) for enteral or parentral administration as the lipid calorie source, in subjects undergoing severe metabolic stress.
The structural lipids of this invention are randomly rearranged mixtures of medium chain triglycerides (MCT) and long chain triglycerides (LCT). They may be represented by the following formula,
wherein R1 and R2 may be independently a C6 to C12 acid, or a C12 to C18' acid, and R3 may be a C18" or C18" acid. Preferably, R1 may be a C6 to C12 acid, and R2 a C12 to C18 acid. C18 ', C18" and C18"represent the number of double bonds in the fatty acid moiety being one, two and three double bonds respectively.
The medium chain triglycerides may be lauric oils such as, balassee oil, coconut oil, cohune oil, palm kernel oil, tucum oil and fractions thereof. The preferred medium chain triglyceride oil is coconut oil.
The long chain triglycerides may be polyunsaturated vegetable oils such as, corn oil, peanut oil, safflower oil, soybean oil, sunflower seed oil, and fish oils. The preferred long chain triglyceride oils are safflower oil, soybean oil, and sunflower seed oil. Preferably, the percent composition of mixtures of medium chain triglycerides to long chain triglycerides of this invention may be 70 to 30%, 80 to 20%, 85 to 15%, or 90 to 10%. The 80 to 20% and the 85 to 15% mixtures are most preferred.
Typically, the structured lipids of this invention may be mixtures of coconut oil and soybean oil, which lipids may have the following fatty acid carbon chain length (CCL) composition.
The present invention provides enteral and parenteral preparations for use in stressed patients to prevent catabolism and to increase protein synthesis. The preparations provide from about 15 to 85% of the fat calories required in the stressed patient.
Typically, the compositions of this invention provide in a 70 Kg man, from about 0.7 gms of fat/Kg of body weight day to about 4.0 gms of fat/Kg of body weight/day.
The lipid compositions are preferably administered with additional amino acids, vitamins and minerals as required. Modified amino acid formulas specifically designed for stressed subjects are preferred. The amino acids, vitamins and minerals can be administered in the same solution as the structured lipids or separately. It is preferred that the component groups be separately packaged to facilitate tailoring the diet to the patients specific needs.
In addition to the above, the formulations may include preservatives or stablizers, as required.
The following example further illustrates the present invention but is not meant to be limiting.
EXAMPLE
In this example, a structural lipid preparation of this invention is compared with a medium chain lipid, and a long chain lipid for the oxidation of lipids in traumatized animals.
In this test, 18 male Sprague-Dawley rates were housed in suspension cages and allowed free access to food and water. When a proper weight of 200 grams was attained, the animals received a 25% full thickness scald burn on the dorsum for 15 seconds, under diethyl ether anesthesia. The rats were then returned to their cages and fasted overnight, but allowed to drink tap water ad libitum. On the day of the study, the animals were randomized into one of three groups to receive a
25 Kcal/Kg body weight intragastric bolus injection of lipid containing 5 u Ci (microcuriea) of labeled oil.
Group I: a 20% medium chain lipid emulsion composed of 72.5% capric acid (C 8:0) and 27.5% coprylic acid (C 10:0) (obtained from Travenol Laboratories, Inc; Deerfield/ Illinois).
Group II: a 20% long chain triglyceride emulsion (20% Travamulsion®, Travenol Laboratories)
Group III: a 20% lipid emulsion composed of structured triglycerides chemically synthesized from 80% coconut oil and 20% soybean oil. Captex 710A Lot No. KH4022A (Capital City Products Co., Columbus, Ohio)
Immediately following the bolus administration of the lipid source, the rats were placed in metabolic chambers that permitted the collection and analysis of their expired breath. At 15 minute intervals for twelve hours, the specific activity of expired carbon dioxide was determined. At the end of the study, the animals were sacrificed
The results show the structured lipids of this invention have oxidation rate that falls between the medium chain triglycerides and the long chain triglycerides. Such structured lipids should be preferable and suitable for both enteral and parenteral nutrition.

Claims

WHAT IS CLAIMED IS:
1. A method of preventing catabolism and increasing protein synthesis in a subject undergoing metabolic stress, which comprises administering enterally or parenterally to the subject from about 0.7 gms of fat/Kg of body weight/day to about 4.0 gms of fat/Kg of body weight/ day of a structured lipid of the formula.
wherein R1 and R2 may be independently a C6 to C12 acid or a C12 to C1 8' acid, and R3 may be a C18" or C18'"acid.
2. The method according to claim 1 wherein R1 is a C6 to C12 acid, and R2 is a C12 to C18' acid.
3. The method according to claim 1 wherein the structured lipid is a mixture of medium chain triglycerides (MCT) and long chain triglycerides (LCT) having a percent composition of MCT to LCT of 70 to 30%, 80 to 20%, 85 to 15% or 90 to 10%.
4. The method according to claim 4 wherein the percent composition of MCT to LCT is 80 to 20% or
85 to 15%.
5. The method according to claim 3 wherein the structured lipid comprises a medium chain triglyceride having a high lauric acid content and the long chain triglyceride has a high polyunsaturated acid content.
6. The method according to claim 5 wherein the medium chain triglyceride oils are balassee oil, coconut oil, cohune oil, palm kernel oil, tucum oil, and fractions thereof, and the. long chain triglyceride oils are corn oil, peanut oil, safflower oil, soybean oil, sunflower seed oil and fish oil.
7. The method according to Claim 6 wherein the structured lipid is 80% coconut oil and 20% soybean oil.
8. A pharmaceutical composition for entral or parentral administration in preventing catabolism and increasing protein synthesis in a subject undergoing metabolic stress which comprises a structured lipid in an amount sufficient to provide from about 0.7 gms of fat/Kg of body weight/day to about 4.0 gms of fat/KG of body weight/day.
9. The pharmaceutical composition according to claim 8 wherein the structured lipid comprises a structured lipid of the formula,
wherein R1 and R2 may be independently a C6 to C12 acid or a C12 to C18' acid, and R3 may be a C18" or C18'"acid.
10. The method according to claim 9 wherein R1 is a C6 to C12 acid, and R2 is a C12 to C18' acid.
11. The pharmaceutical composition according to claim 9 wherein the structured lipid comprises a medium chain triglyceride having a high lauric acid content and the long chain triglyceride has a high polyunsaturated acid content.
12. The pharmaceutical composition according to claim 11 wherein the medium chain triglyceride oils are balassee oil, coconut oil, cohune oil, palm kernel oil, tucum oil, and fractions thereof, and the long chain triglyceride oils are corn oil, peanut oil, safflower oil, soybean oil, sunflower seed oil and fish oil.
13. The pharmaceutical composition according to claim 12 wherein the structured lipid is 80% coconut oil and 20% soybean oil.
14. The pharmaceutical composition according to claim 13 in which amino acids, vitamins and minerals in amounts effective for the treatment of the stressed subject are administered.
EP19850904733 1984-09-13 1985-09-13 Triglyceride preparations for the prevention of catabolism Withdrawn EP0193602A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US65077184A 1984-09-13 1984-09-13
US650771 1984-09-13

Publications (1)

Publication Number Publication Date
EP0193602A1 true EP0193602A1 (en) 1986-09-10

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ID=24610217

Family Applications (1)

Application Number Title Priority Date Filing Date
EP19850904733 Withdrawn EP0193602A1 (en) 1984-09-13 1985-09-13 Triglyceride preparations for the prevention of catabolism

Country Status (2)

Country Link
EP (1) EP0193602A1 (en)
WO (1) WO1986001715A1 (en)

Families Citing this family (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5227403A (en) * 1986-10-01 1993-07-13 The Nisshin Oil Mills, Ltd. Fats and oils having superior digestibility and absorptivity
JPH0832628B2 (en) * 1986-12-17 1996-03-29 株式会社ミドリ十字 Triglyceride composition
US4810726A (en) * 1987-04-01 1989-03-07 New England Deaconess Hospital Corporation Kernel oils and disease treatment
FR2618332B1 (en) * 1987-07-23 1990-04-27 Synthelabo LIPID EMULSION FOR PARENTERAL OR ENTERAL NUTRITION
US6013665A (en) * 1997-12-16 2000-01-11 Abbott Laboratories Method for enhancing the absorption and transport of lipid soluble compounds using structured glycerides
FR2877577A1 (en) * 2004-11-09 2006-05-12 Jean Pierre Maloisel Oral compositions, used to treat benign prostatic hyperplasia and chronic or acute inflammatory pathologies, comprise oil extract of Astrocaryum aculeatum, obtained by first cold pressure or vapor extraction
JP5707026B2 (en) * 2005-12-24 2015-04-22 ディーエスエム アイピー アセッツ ビー．ブイ． Long-term weight maintenance
WO2011115184A1 (en) * 2010-03-18 2011-09-22 日清オイリオグループ株式会社 Inhibitor of in vivo proteolysis

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3268340A (en) * 1965-08-30 1966-08-23 Drew Chem Corp Margarine oil and margarine made therefrom
US4329359A (en) * 1979-12-28 1982-05-11 University Of Kentucky Research Foundation Method for improving the metabolic stability and survival of newborn pigs
US4282265A (en) * 1980-01-14 1981-08-04 Bristol-Myers Company Fat compositions for infant formulas

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO8601715A1 *

Also Published As

Publication number Publication date
WO1986001715A1 (en) 1986-03-27

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Inventor name: BABAYAN, VIGEN, K.