Parenteral nutrition formulation

Abstract

Parenteral nutrition formulations for pediatric patients are disclosed. The nutritional formulations include a lipid formulation that comprises an aqueous phase and an oil phase, wherein the lipid formulation is in the form of an oil-in-water emulsion. Multi-chamber containers for parenteral nutrition administration comprising a carbohydrate formulation present in a first chamber, an amino acid formulation present in a second chamber, and the lipid formulation present in a third chamber also are disclosed.

1 - 76 . (canceled) 
     
     
         77 . A multi-chamber container for parenteral administration comprising:
 (i) a carbohydrate formulation present in a first chamber;   (ii) an amino acid formulation present in a second chamber; and   (iii) a lipid formulation present in a third chamber;   wherein:
 the lipid formulation comprises an aqueous phase and about 5% to about 35% by weight of an oil phase based on the total weight of the lipid formulation; 
 the lipid formulation is present in the form of an oil-in-water emulsion; 
 the oil phase comprises docosahexaenoic acid (DHA) obtained from a single cell source, wherein the single cell source is an extract of microalgae and wherein DHA is present in a concentration of from 0.1 g to 5.0 g per 100 g of oil phase; 
 the lipid formulation includes about 70 mg phytosterols or less per 100 g of oil phase; and 
 the lipid formulation is essentially free of water soluble forms of choline, 
   wherein the carbohydrate formulation and/or the amino acid formulation comprises at least one water-soluble form of choline selected from the group consisting of choline chloride, choline bitartrate, choline citrate, choline gluconate, choline malate, choline cytidine diphosphate choline (CDP) salt and glycerophosphocholine, preferably glycerophosphocholine.   
     
     
         78 . The multi-chamber container of  claim 77 , wherein DHA is present in a concentration of from 0.25 g to 3.0 g per 100 g of oil phase. 
     
     
         79 . The multi-chamber container of  claim 77 , wherein DHA is present in a concentration of from 1.5 g to 2.5 g per 100 g of oil phase. 
     
     
         80 . The multi-chamber container of  claim 77 , wherein DHA is present in triglyceride form or ethyl ester form, preferably triglyceride form. 
     
     
         81 . The multi-chamber container of  claim 77 , wherein the lipid formulation comprises eicosapentaenoic acid (EPA) and the ratio of DHA to EPA in the lipid formulation is 10:1 to 1000:1 (w/w). 
     
     
         82 . The multi-chamber container of  claim 77 , wherein the lipid formulation comprises EPA and the ratio of DHA to EPA in the lipid formulation is 10:1 to 200:1. 
     
     
         83 . The multi-chamber container of  claim 77 , wherein the lipid formulation comprises EPA and the ratio of DHA to EPA in the lipid formulation is 20:1 to 150:1. 
     
     
         84 . The multi-chamber container of  claim 81 , wherein DHA and/or EPA are present in triglyceride form or ethyl ester form, preferably triglyceride form. 
     
     
         85 . The multi-chamber container of  claim 77 , wherein the lipid formulation is essentially free of EPA. 
     
     
         86 . The multi-chamber container of  claim 77 , wherein the microalgae is  Crypthecodinium cohnii  or  Schizochytrium  sp, preferably  Schizochytrium  sp. 
     
     
         87 . The multi-chamber container of  claim 77 , wherein the lipid formulation includes about 15 mg to about 35 mg phytosterols per 100 g of oil phase, preferably about 25 mg phytosterols or less per 100 g of oil phase. 
     
     
         88 . The multi-chamber container of  claim 77 , wherein the lipid formulation comprises one or more pharmaceutically acceptable surfactants selected from the group consisting of phospholipids, oleate salts, and combinations thereof. 
     
     
         89 . The multi-chamber container of  claim 88 , wherein the phospholipid is selected from the group consisting of egg phosphatide and soy lecithin. 
     
     
         90 . The multi-chamber container of  claim 77 , wherein the lipid formulation comprises one or more pharmaceutically acceptable isotonic agents. 
     
     
         91 . The multi-chamber container of  claim 90 , wherein the pharmaceutically acceptable isotonic agent is glycerol. 
     
     
         92 . The multi-chamber container of  claim 77 , wherein the lipid formulation comprises one or more pharmaceutically acceptable antioxidants selected from the group consisting of tocopherols, ascorbyl palmitate, and combinations thereof. 
     
     
         93 . The multi-chamber container of  claim 77 , wherein the lipid formulation has a pH in the range of about 6 to about 9, preferably about 7 to about 8. 
     
     
         94 . The multi-chamber container of  claim 77 , wherein the at least one water-soluble form of choline is present in a concentration of from 20 mg to 2000 mg choline equivalent per liter of a reconstituted multi-chamber container, such as 30 mg to 1000 mg choline equivalent per liter of a reconstituted multi-chamber container. 
     
     
         95 . A method of treating patients who require parenteral nutrition when oral and enteral nutrition is not possible, insufficient or contraindicated by using a multi-chamber container of  claim 77 . 
     
     
         96 . The method of  claim 95 , wherein the patients are pediatric patients. 
     
     
         97 . A multi-chamber container for parenteral administration comprising:
 (i) a carbohydrate formulation present in a first chamber;   (ii) an amino acid formulation present in a second chamber; and   (iii) a lipid formulation present in a third chamber;   wherein:
 the lipid formulation comprises an aqueous phase and about 5% to about 35% by weight of an oil phase based on the total weight of the lipid formulation; 
 the lipid formulation is present in the form of an oil-in-water emulsion; 
 the oil phase comprises docosahexaenoic acid (DHA) obtained from a single cell source, wherein the single cell source is an extract of microalgae and wherein DHA is present in a concentration of from 0.1 g to 5.0 g per 100 g of oil phase; 
 the lipid formulation includes about 70 mg phytosterols or less per 100 g of oil phase; and 
 the lipid formulation is essentially free of water soluble forms of choline, 
   wherein the carbohydrate formulation and/or the amino acid formulation comprises at least one water-soluble form of choline selected from the group consisting of choline chloride, choline bitartrate, choline citrate, choline gluconate, choline malate, choline cytidine diphosphate choline (CDP) salt and glycerophosphocholine, preferably glycerophosphocholine,   wherein the multi-chamber container comprises openable seals among the first chamber, the second chamber and the third chamber, and wherein the carbohydrate formulation, the amino acid formulation and the lipid formulation are admixed into a whole liquid solution after the openable seals are open for the parenteral administration.   
     
     
         98 . The multi-chamber container of  claim 97 , wherein the lipid formulation is essentially free of water soluble forms of choline and arachidonic acid (ARA).