TRIGLYCERIDE PREPARATIONS FOR THE PREVENTION OF CATABOLISM

Abstract: Chemically synthesized structured triglycerides (lipids) for enteral or parentral administration as the lipid calorie source, in subjects undergoing 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 condi¬ tions/ 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 meta¬ bolic 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 under¬ standing cause and effect/ as it related to biochem¬ istry 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 condi¬ tions. 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 inten¬ sive 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. Ele¬ vated 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 labora¬ tory 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 admini¬ stration as the lipid calorie source/ in subjects under¬ going 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 re¬ presented by the following formula/ CH 2 OCOR 3 wherein R, and R 2 may be independently a C g to C, 2 acid/ or a C- 2 to C, g - acid/ and R_ may be a C, a " or C, a "» acid. Preferably/ R, may be a Cg to C, 2 acid/ and R 2 a C 12 to C,g acid. C. '/ C, g " and C, 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 pre¬ ferred 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 pre¬ parations 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 intragaβtric 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% Travamulsioπ®, 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. su B sτi T UT _ SHEET The results show the structured lipids of this invention have oxidation rate that falls between the medium chain triglycerides and the long chain trig¬ lycerides. 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 R, and R 2 may be independently a C g to C 12 acid or a C, 2 to C, ' acid/ and R 3 may be a C, " or C '"acid. 2. The method according to. claim 1 wherein R, is a C 6 to C. 2 acid/ and R 2 is a C- 2 to C, β ' acid. 3. The method according to claim 1 wherein the structured lipid is a mixture of medium chain trigly¬ cerides (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, ;H 2 OCOR 1 JH 2 OCOR 2 -H 2 OCOR 3 wherein R. and R 2 may be independently a C g to C- 2 acid or a C, 2 to C, ' acid, and R 3 may be a C,„" or C, a H, acid. 10. The method according to claim 9 wherein R, is a C_6. to C1,2 acid/ and R2- is a C1,2« to C1,8' 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.

Inventors: BABAYAN VIGEN K, BLACKBURN GEORGE L, BABAYAN, VIGEN, K., BLACKBURN, GEORGE, L.
Applicants: NUTRITIONAL RES CHARITABLE TRU, NUTRITIONAL RES CHARITABLE TRUST
Application year: 1985
Main classification: A61K31
IPC codes: A61K31