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EP-4739288-A1 - LIPID EMULSIONS FOR PARENTERAL NUTRITION

EP4739288A1EP 4739288 A1EP4739288 A1EP 4739288A1EP-4739288-A1

Abstract

The present disclosure relates to improved lipid emulsions for providing parenteral nutrition, including ready-to-use parenteral nutrition formulations comprising such lipid emulsions. More particularly, the present disclosure is directed to improved lipid formulations or emulsions including multi-chamber containers comprising same, wherein the lipid emulsion contains DHA, EPA, and ARA in an optimized concentration and ratio, optionally in combination with choline and defined levels of phytosterols. The present disclosure further relates to methods of avoiding and/or treating liver damage and/or inflammation, and to methods for improving fatty acid profiles in plasma and certain tissues or organs especially of pediatric patients.

Inventors

  • ELOUAHABI, ABDELATIF
  • BOUREZG, Zouaoui
  • BODET, Baptiste
  • COSPIN, Nathalie
  • TROUILLY, JEAN-LUC
  • BROWN, Mary Hise
  • SENTERRE, Thibault

Assignees

  • Baxter International Inc.
  • BAXTER HEALTHCARE SA

Dates

Publication Date
20260513
Application Date
20240701

Claims (16)

  1. Claims 1. A lipid emulsion for parenteral nutrition comprising an aqueous phase and about 5% to about 35% by weight of an oil phase based on the total weight of the lipid emul- sion (w/w), wherein the lipid emulsion comprises from about 2.0 g/L to about 15.0 g/L of DHA; from about 0 g/L to about 1.2 g/L of EPA; and from about 5.0 g/L to about 20.0 g/L of ARA.
  2. 2. The lipid emulsion according to claim 1, wherein the ratio of DHA:ARA is from 1:0.5 to 1:2.
  3. 3. The lipid emulsion according to claim 1, further com- prising choline in an amount of from 0.5 g/L to 5.0 g/L.
  4. 4. The lipid emulsion according to claim 3, wherein the choline is selected from choline chloride and glycer- ophosphocholine.
  5. 5. The lipid emulsion according to claim 1, wherein the lipid emulsion contains phytosterols in an amount not exceeding 200 mg/L of the lipid emulsion.
  6. 6. The lipid emulsion according to claim 1, wherein the lipid emulsion contains phytosterols in an amount not to exceed 140 mg/mL.
  7. 7. The lipid emulsion according to claim 1, wherein the ratio of DHA to EPA is from 30:1 to 10:1.
  8. 8. The lipid emulsion according to claim 1, comprising linoleic acid in a concentration of from 25 to 50 g/L.
  9. 9. The lipid emulsion according to claim 1, comprising α- tocopherol in a concentration of from 100-300 mg/L.
  10. 10. The lipid emulsion according to claim 1, wherein the ratio of ω-6:ω-3 fatty acids is from 4:1 to 2:1.
  11. 11. The lipid emulsion according to claim 1 for the treat- ment of pediatric patients.
  12. 12. A multi-chamber bag for providing a parenteral nutri- tion formulation, wherein the multi-chamber bag com- prises a chamber containing a lipid emulsion according to claim 1.
  13. 13. A method of treating patients who require parenteral nutrition when oral and enteral nutrition is not pos- sible, insufficient, or contraindicated, with a lipid emulsion according to claim 1.
  14. 14. A method of preventing or ameliorating liver damage and/or inflammation in pediatric patients requiring parenteral nutrition, wherein the pediatric patients are parenterally administered a composition comprising a lipid emulsion according to claim 1.
  15. 15. A method of improving the fatty acid profile of pedi- atric patients requiring parenteral nutrition in the patients´ plasma and/or tissues, wherein the pediatric patients are parenterally administered a composition comprising a lipid emulsion according to claim 1.
  16. 16. The method of claim 15, wherein the tissues comprise t he tissue of lung, liver and/or retina.

Description

LIPID EMULSIONS FOR PARENTERAL NUTRITION Technical Field [0001] The present disclosure relates to improved lipid emulsions for providing parenteral nutrition, includ- ing ready-to-use parenteral nutrition formulations compris- ing such lipid emulsions. More particularly, the present disclosure is directed to improved lipid formulations or emulsions including multi-chamber containers comprising same, wherein the lipid emulsion contains DHA, EPA, and ARA in an optimized ratio optionally in combination with choline and defined levels of phytosterols. The present disclosure further relates to methods of avoiding and/or treating liver damage and/or inflammation especially in pediatric patients receiving parenteral nutrition, and to methods for improving fatty acid profiles in plasma and certain tissues and/or organs of the pediatric patients, including retina, liver, and lung. Description of the Related Art [0002] Lipids are a key energy source for patients who require parenteral nutrition, including newborn infants and provide for the essential omega-3 and omega-6 fatty acids that the human body is unable to produce. Lipids also provide important long-chain essential polyunsaturated fatty acids (LC-PUFAs) that are crucial for normal development of the central nervous system and other organ systems (Burrin et al., 2014, Impact of New-Generation Lipid Emulsions on Cel- lular Mechanisms of Parenteral Nutrition–Associated Liver Disease. Advances in Nutrition 5, 82-91). n-3 and n-6 PUFAs have received specific attention for their role in brain development and cellular functions. Docosahexaenoic acid (DHA, 22:6n-3) and arachidonic acid (ARA, 20:4n-6), for ex- ample, are always present in human milk. These fatty acids are discussed as key players in the structure and function of human tissues, immune function, and brain and retinal development especially during gestation and infancy. There is ongoing research into the potential of, for example, omega-3 PUFA and the benefit of enriching enteral nutrition (EN) and parenteral nutrition (PN) formulations with these compounds, with varying outcomes (see, for example, Singer et al., 2021, Enteral and supplemental parenteral nutrition enriched with omega-3 polyunsaturated fatty acids in inten- sive care patients - A randomized, controlled, double-blind clinical trial. Clinical Nutrition 40, 2544) that underline the persistent challenge of identifying and providing opti- mized PN formulations despite being aware of some or most of the key components in the nutrition of, for example, pedi- atric patients in need. [0003] There are various lipid emulsions on the mar- ket, including soybean oil-based or soybean oil/safflower oil-based formulations (Intralipid, Liposyn II), wherein In- tralipid, for example, is enriched with certain fatty acids. Both contain phytosterols which are natural components of vegetable oils. More recent lipid emulsions for parenteral nutrition are based on olive oil and soybean oil (e.g., ClinOleic), fish oil (e.g., Omegaven) or blends of soybean oil, olive oil, MCTs and fish oil (e.g., SMOFlipid). Lipid emulsions are either provided as such or are part of multi- chamber nutritional products that further comprise, in sep- arate chambers, carbohydrate and/or amino acid formulations that are admixed with the lipid emulsion formulation upon administration. The DHA, EPA, and ARA content of these avail- able lipid emulsions varies, depending, for example, on the source of the oils used for preparing the lipid emulsions. ARA and DHA have been added to infant formulas in the United States since 2001. In Europe, supplementation began at an even earlier time. Most infant formulas contain 0.2% to 0.4% of total fatty acids as DHA and between 0.35% and 0.7% of total fatty acids as ARA based on worldwide averages of DHA and ARA content in human milk. Human milk has a mean (±SD) concentration of DHA in breast milk (by weight) of 0.32 ± 0.22% and a mean (±SD) concentration of ARA of 0.47 ± 0.13%, indicating that the ARA concentration is on average lower than that of DHA (Brenna et al., 2007, Docosahexaenoic and arachidonic acid concentrations in human breast milk world- wide. The American Journal of Clinical Nutrition. 85(6), 1457). [0004] It is known that DHA (22:6n-3) and ARA (20:4n- 6) are present in human milk and play important roles in the structure and function of human tissues and immune function. Preterm infants who are born at a stage when the normal placental transfer and deposition of DHA in fetal tissues, for example, is not yet completed, DHA seems to be especially relevant. [0005] Also, the role of EPA and ARA have been dis- cussed in the literature regarding metabolic health and risk of developing certain PN-related diseases such as inflamma- tion. [0006] Generally, the need for fulfilling the nutri- tional needs of a patient must be balanced against certain risks associated with a prolonged or extensive parenteral nutrition, including, for exampl