Patent Publication Number: US-5840757-A

Title: Lipid emulsion intended for parenteral or enteral feeding

Description:
This application is a continuation of application Ser. No. 453,359, filed Dec. 19, 1989, now abandoned, which is a continuation of application Ser. No. 223,120, filed Jul. 22, 1988, now abandoned. 
    
    
     The present invention relates to a lipid emulsion suitable for use as a parenteral or enteral foodstuff and to compositions containing it. 
     Justification for the use of lipids in parenteral feeding rests on the following arguments: 
     a mixed carbohydrate/Lipid intake is more physiological than an exclusive carbohydrate intake, 
     lipids supply essential fatty acids which the body is incapable of synthesizing, 
     a high calorific power combined with a low osmolarity enables a large amount of calories to be administered peripherally in a small volume. 
     The soybean and safflower oils currently used in injectable lipid emulsions are characterized by a high content of polyunsaturated fatty acids (approximately 60 % and 75 %, respectively), which enable the essential fatty acid requirements of patients needing intravenous feeding to be covered amply. 
     However, in the context of total parenteral feeding, where the lipid intake represents 30 to 50% of the carbohydrate/lipid calories, the composition of these oils is unsuitable for the following reasons: 
     the high proportion of essential fatty acids appears likely to inhibit partially their desaturation/elongation to form active higher metabolites (S. INNIS, Lipids, 1986, 21, 132-138). 
     the high linoleic acid content of these oils has been held responsible for immuno-suppressant effects, which may interact with the inflammatory phenomena pre-existing in patients in a stress situation. 
     the fatty acid composition of safflower and soybean oils makes them very sensitive to peroxidation. 
     LinoLeic and α-linolenic acids are very sensitive to peroxidation as a result of the presence of several double bonds in their structure. The peroxidation of fatty acids generates the formation of various compounds which are poorly metabolized by the body. 
     Some oxidation derivatives of fatty acids react with proteins to give rise to fluorescent condensation products known as lipofuscins, which deposit in the tissue. Such treatments have been described in the context of parenteral feeding. 
     According to some authors, they could be responsible for certain liver abnormalities observed in patients receiving parenteral feeding. 
     An increase in lipid peroxidation during the administration of lipid emulsions has been demonstrated both in man and in animals (J. R. WISPE, Ped., 1985, 19, 374-379). These peroxidation phenomena risk being magnified in subjects in a stress situation, where the production of free radicals is increased with, in some instances, a decrease in activity of the antioxidant protection mechanisms (M. HIRAMATSU, Burns, 1984, 11, 111-116). 
     The present invention seeks to provide a more balanced Lipid emulsion having a lower content of poly-unsaturated fatty acids, which, while ensuring that the essential fatty acid requirements are covered, has the following advantages: 
     better utilization of the essential fatty acids to form their higher derivatives, avoiding the risk of inhibition of conversion of the fatty acids by excess substrate, 
     smaller intake of polyunsaturated fatty acids, enabling lipid peroxidation to be limited, in particular in subjects suffering from inflammatory syndromes, with the production of free radicals. 
     The present invention provides a lipid emulsion suitable for use as a parenteral or enteral foodstuff, wherein the lipid phase is a mixture of long-chain fatty acids in which 15 to 45% of the total fatty acids are essential fatty acids. 
     The lipid phase preferably comprises a mixture of two or more oils selected from apricot, almond, groundnut, avocado, wheat, safflower, rapeseed, coconut, cottonseed, lupin, maize, hazelnut, walnut, olive, oenothera, palm, palm-kernel, peach, grape, rice, rye, sesame, soybean, sunflower, tomato, linseed and citrus oils. 
    
    
     Examples of suitable lipid phases are shown below in a Table. 
     
                       TABLE                                                       
______________________________________                                    
LIPID PHASE          Essential fatty acids as                             
(MIXTURE OF OILS)    % of total fatty acids                               
______________________________________                                    
AVOCADO (46%) - SOYBEAN (54%)                                             
                     40                                                   
OLIVE (47%) - SOYBEAN (53%)                                               
                     40                                                   
AVOCADO (60%) - WALNUT (40%)                                              
                     40                                                   
AVOCADO (89%) - WALNUT (11)                                               
                     20                                                   
WALNUT (11%) - OLIVE (89%)                                                
                     26                                                   
OLIVE (85%) - SOYBEAN (15%)                                               
                     20                                                   
WALNUT (40%) - OLIVE (60%)                                                
                     40                                                   
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     Variations in the composition of the oils may be observed in accordance with their origin. The mixtures will hence be adapted to obtain the requisite essential fatty acid composition. 
     The lipid emulsions of the invention are preferably emulsions in water, for example comprising from 5 to 50% by weight, relative to the total weight of the emulsion, of the lipid phase in water. The emulsions may contain emulsifying agents, for example, plant, animal or synthetic phospholipids, which are generally present in a proportion of from 0.5 to 5% by weight, relative to the total weight of the emulsion. 
     The lipid emulsion of the invention may also, for example, comprise a tonicity-regulating agent such as glycerol, glucose, a polyol or an amino acid. 
     The lipid emulsion of the invention may be used as an enteral or parenteral foodstuff as it is, or as a lipid constituent of a complete emulsion or solution, which may also, for example, comprise amino acids, carbohydrates, vitamins, carnitine, trace elements or keto analogues of amino acids. 
     The present invention also provides a pharmaceutical composition which comprises a lipid emulsion as defined above and a solvent or adjuvant. The present invention further provides a dietetic composition which comprises lipid emulsion as defined above and a solvent or adjuvant. 
     The lipid emulsions of the invention may be used for achieving a parenteral or enteral intake of calories and of essential fatty acids when oral feeding is impossible.