Structured triglycerides and emulsions comprising same

Abstract

The present invention relates to structured triglycerides, to parenteral nutrition emulsions of the same, and uses thereof. In particular, the invention relates to structured triglycerides that include at least one medium chain C 6 -C 12 fatty acid and at least one fatty acid selected from long chain C 14 -C 18 or very long chain C 20 -C 22 fatty acids. Preferably, each fatty acid is present in a predetermined position of the glycerol backbone. The parenteral nutrition emulsions are particularly useful for nourishing preterm- and term-infants, children, critically ill patients, and cancer patients.

1 . A structured triglyceride comprising a glycerol backbone having three fatty acid residues esterified thereto, wherein two fatty acid residues selected from the group consisting of C 6 -C 12  fatty acids and active derivatives thereof are esterified to the internal position and to a first external position of the triglyceride backbone, and one fatty acid residue selected from the group consisting of C 14 -C 18  fatty acids, C 20 -C 22  fatty acids, and active derivatives thereof is esterified to a second external position of the triglyceride backbone. 
     
     
         2 . The structured triglyceride according to  claim 1 , wherein the C 14 -C 18  fatty acids are selected from the group consisting of myristic acid, palmitic acid, palmitoleic acid, stearic acid, oleic acid, linoleic acid, alpha linolenic acid, and any combination thereof. 
     
     
         3 . The structured triglyceride according to  claim 1 , wherein the C 20 -C 22  fatty acids are selected from the group consisting of arachidonic acid, eicosapentaenoic acid, docosahexaenoic acid, and any combination thereof. 
     
     
         4 . The structured triglyceride according to  claim 1 , wherein the C 14 -C 18  fatty acids and the C 20 -C 22  fatty acids are selected from the group consisting of ω-3, ω-6, ω-9 fatty acids, and any combination thereof. 
     
     
         5 . A parenteral nutrition emulsion composition comprising a structured triglyceride according to  claim 1 . 
     
     
         6 . The parenteral nutrition emulsion composition according to  claim 5 , wherein the structured triglyceride is present in an amount of about 80% to about 100% of total triglycerides of said emulsion. 
     
     
         7 . The parenteral nutrition emulsion composition according to  claim 5 , wherein the C 14 -C 18  fatty acids and the C 20 -C 22  fatty acids are selected from the group consisting of ω-3, ω-6, ω-9 fatty acids, and any combination thereof. 
     
     
         8 . The parenteral nutrition emulsion composition according to  claim 5 , comprising from about 9% to about 90% by weight C 6 -C 12  fatty acids based on the weight of total fatty acids. 
     
     
         9 . The parenteral nutrition emulsion composition according to  claim 5 , comprising from about 9% to about 90% by weight C 14 -C 18  fatty acids based on the weight of total fatty acids. 
     
     
         10 . The parenteral nutrition emulsion composition according to  claim 5 , comprising from about 1% to about 10% by weight C 20 -C 22  fatty acids based on the weight of total fatty acids. 
     
     
         11 . The parenteral nutrition emulsion composition according to  claim 7 , wherein the ω-6 fatty acids and the ω-3 fatty acids are in a ratio of about 7:1 to about 1:1. 
     
     
         12 . The parenteral nutrition emulsion composition according to  claim 5 , wherein the structured triglyceride constitutes from about 10% to about 40% (w/v) of the composition. 
     
     
         13 . The parenteral nutrition emulsion composition according to  claim 5 , wherein a droplet size of said emulsion is lower than about 1 μm. 
     
     
         14 . The parenteral nutrition emulsion composition according to  claim 5 , further comprising tocopherol. 
     
     
         15 . The parenteral nutrition emulsion according to  claim 14 , wherein the tocopherol is alpha tocopherol. 
     
     
         16 . The parenteral nutrition emulsion according to  claim 5 , further comprising at least one component selected from the group consisting of emulsifiers, surfactants, carbohydrates, vitamins, amino acids, trace minerals, osmolality modifiers and water. 
     
     
         17 . The parenteral nutrition emulsion according to  claim 5  comprising:
 (a) 20% (w/v) structured triglycerides comprising:
 about 40-50% by weight C 6 -C 12  fatty acids based on the weight of total fatty acids, wherein the C 6 -C 12  fatty acids comprise 0-5% caproic acid, 20-30% caprylic acid, 10-30% capric acid, and 0-5% lauric acid by weight based on the weight of total fatty acids; 
 about 35-55% by weight C 14 -C 18  fatty acids based on the weight of total fatty acids, wherein the C 14 -C 18  fatty acids comprise 0-5% mystiric acid, 5-30% palmitic acid, 0-5% palmitoleic acid, 0-5% stearic acid, 10-30% oleic acid, 10-30% linoleic acid, and 5-15% alpha linolenic acid by weight based on the weight of total fatty acids; and 
 about 1-10% C 20 -C 22  by weight fatty acids based on the weight of total fatty acids, wherein the C 20 -C 22  fatty acids comprise 1-5% AA, 0-5% EPA, and 1-5% DHA by weight based on the weight of total fatty acids, wherein the ratio of ω-6 to ω-3 fatty acids is 1:1-2:1; 
 
 (b) 1.2% (w/v) phospholipids; 
 (c) 1.8-2.0 mg/1 g of fatty acids alpha tocopherol; 
 (d) 0-25 g/L glycerin; and 
 (e) water. 
 
     
     
         18 . The parenteral nutrition emulsion composition according to  claim 5  comprising:
 (a) about 20% (w/v) structured triglycerides comprising:
 about 45% by weight C 6 -C 12  fatty acids based on the weight of total fatty acids, wherein the C 6 -C 12  fatty acids comprise 2.5% caproic acid, 30% caprylic acid, 10% capric acid, and 2.5% lauric acid by weight based on the weight of total fatty acids; 
 about 50% by weight C 14 -C 18  fatty acids based on the weight of total fatty acids, wherein the C 14 -C 18  fatty acids comprise 10% palmitic acid, 2.5% stearic acid, 15% oleic acid, 16% linoleic acid, and 7% alpha linolenic acid by weight based on the weight of total fatty acids; and 
 about 5% by weight C 20 -C 22  fatty acids based on the weight of total fatty acids, wherein the C 20 -C 22  fatty acids comprise 1.5% AA, 1.5% EPA, and 1.5% DHA by weight based on the weight of total fatty acids, wherein the ratio of ω-6 to ω-3 fatty acids is 1.75; 
 
 (b) about 1.2% (w/v) phospholipids; 
 (c) about 1.8 mg/1 g of fatty acids alpha tocopherol; 
 (d) about 10-25 g/L glycerin; and 
 (e) water. 
 
     
     
         19 . A process of synthesizing a structured triglyceride according to  claim 1  comprising the step of performing an acidolysis reaction. 
     
     
         20 . The process according to  claim 19 , wherein the acidolysis reaction is catalyzed by a lipase. 
     
     
         21 . The process according to  claim 19 , wherein the triglyceride is a medium chain triglyceride. 
     
     
         22 . The process according to  claim 19 , wherein the fatty acid is selected from the group consisting of C 14 -C 18  fatty acids, C 20 -C 22  fatty acids, and active derivatives thereof. 
     
     
         23 . The process according to  claim 19  further comprising a step of distilling the reaction mixture to remove non-reacted medium chain triglyceride and fatty acid. 
     
     
         24 . A process of preparing a parenteral nutrition emulsion composition according to  claim 5  comprising the step of reducing the droplet size of the emulsion below of about 1 μm. 
     
     
         25 . A method of providing nutrition to a subject in need thereof comprising parenterally administering to the subject a parenteral nutrition emulsion composition according to  claim 5 . 
     
     
         26 . The method according to  claim 25 , wherein the subject is a preterm infant, a term infant, a child, an adult, a critically ill patient, a cancer patient, or a patient suffering from one of the conditions selected from trauma, burns, malnutrition, starvation, aging, and immunosuppression. 
     
     
         27 . The method according to  claim 25 , wherein the subject is an AIDS patient.