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EP-4736843-A2 - PARENTERAL NUTRITION SOLUTION COMPRISING A SELENIUM SOURCE

EP4736843A2EP 4736843 A2EP4736843 A2EP 4736843A2EP-4736843-A2

Abstract

The invention relates to a medical product for preventing or correcting selenium deficiency in a patient comprising a solution provided in a flexible container characterized in that the solution comprises at least one of a selenate salt and/or a seleno-amino acid, such as selenomethionine or selenocysteine.

Inventors

  • DUPONT, Caroline
  • BOUREZG, Zouaoui

Assignees

  • Baxter International Inc.
  • BAXTER HEALTHCARE SA

Dates

Publication Date
20260506
Application Date
20201217

Claims (13)

  1. A multi-chamber container, wherein the multi-chamber container comprises: a first chamber; and a sterilized solution disposed within the first chamber, wherein the sterilized solution has an acidic pH in a range of from 1 to 4, wherein the sterilized solution comprises at least one selenium-containing compound selected from the group consisting of: (a) a selenate salt selected from sodium selenate, potassium selenate, barium selenate and ammonium selenate, and (b) a seleno-amino acid selected from selenomethionine and selenocysteine, and wherein the at least one selenium-containing compound is stable in the sterilized solution for at least three months when stored at a temperature of between 1 and 50 °C.
  2. The multi-chamber container according to claim 1, wherein the at least one selenium-containing compound is stable in the sterilized solution for at least 6 months, preferably 12 months, more preferably 18 months, most preferably 24 months, at a temperature of from about 18°C to 25°C.
  3. The multi-chamber container according to any one of the preceding claims, wherein the sterilized solution comprises at least one additional trace element, preferably selected from the group comprising zinc, iron, copper, manganese, chromium, iodine, fluoride and molybdenum, preferably zinc, iron, manganese and/or copper.
  4. The multi-chamber container according to any one of the preceding claims, wherein the sterilized solution comprises an acid, preferably an organic acid selected from the group comprising malic acid, tartaric acid, citric acid, maleic acid, fumaric acid, more preferably malic acid, wherein the concentration of the organic acid is preferably in a range of from 50 mM to 400 mM, preferably from 190 mM to 220 mM, and more preferably about 200 mM.
  5. The multi-chamber container according to any one of the preceding claims, wherein the sterilized solution comprises malic acid.
  6. The multi-chamber container according to any one of the preceding claims, wherein the sterilized solution has an acidic pH from 2 to 3.5, more preferably from about 2.2 to 3.2.
  7. The multi-chamber container according to any one of the preceding claims, wherein the sterilized solution does not comprise macronutrients selected from the group comprising carbohydrates, proteins and lipids, and wherein preferably the sterilized solution does not comprise any other nutrients.
  8. The multi-chamber container according to any one of the preceding claims, wherein the sterilized solution is configured for parenteral administration.
  9. The multi-chamber container according to any one of the preceding claims, wherein the sterilized solution comprises the at least one selenium-containing compound in an amount corresponding to 10-200 µg, preferably 40-100 µg, more preferably about 55 - 75 µg, of selenium.
  10. The multi-chamber container according to any one of the preceding claims, wherein the sterilized solution is contained in the first chamber of a multi-chamber container having at least two, at least three, at least four, at least five or at least six chambers.
  11. The multi-chamber container according to any one of the preceding claims, wherein the multi-chamber container comprises a second chamber and a third chamber, wherein one of the first chamber, the second chamber, or the third chamber contains a carbohydrate formulation, one of the first chamber, the second chamber, or the third chamber contains an amino acid formulation, and one of the first chamber, the second chamber, or the third chamber contains a lipid formulation, wherein the carbohydrate formulation, the amino acid formulation, and the lipid formulation are each contained in a different one of the first chamber, the second chamber, and the third chamber, and wherein at least one of the chambers comprises the at least one selenium-containing compound.
  12. The multi-chamber container according to any one of claims 10 or 11, wherein the at least one selenium-containing compound is sodium selenate or potassium selenate.
  13. The multi-chamber container according to any one of the preceding claims, wherein at least one of the first chamber, the second chamber, or the third chamber comprise electrolytes and/or vitamins.

Description

DESCRIPTION The invention relates to the field of clinical nutrition, corresponding medical products and nutritional solutions. The invention relates to a medical product for preventing or correcting selenium deficiency in a patient comprising a solution provided in a flexible container characterized in that the solution comprises at least one of a selenate salt and/or a seleno-amino acid, such as selenomethionine or selenocysteine. In embodiments of the invention, the solution of the medical product of the invention comprises at least one additional trace element. The solution may be contained in one chamber of a multi chamber container having at least two, at least three, at least four, at least five or at least six chambers. Furthermore, the invention relates to a method of preparing a medical product of the invention. BACKGROUND OF THE INVENTION Parenteral Nutrition aims to supply nutrients to patients by venous access. Nutrients are composed of macronutrients (lipids, amino acid or protein and dextrose or carbohydrates), micronutrients (vitamins and trace elements) and electrolytes. Parenteral nutrition, such as in the form of one or more solutions, can be provided in the form of flexible bags, either in the form of single flexible bags containing glucose, amino acids or lipids with or without electrolytes, which can be mixed together prior administration, or multi chamber flexible bags providing separated macronutrients and electrolytes, in a ready to use format. The bags are typically made of a synthetic or plastic material, for example materials such as polypropylene (PP), polyethylene (PE), ethylene vinyl alcohol (EVOH), ethylene-vinyl acetate (EVA) and all possible copolymers, essentially any synthetic material suitable for containing the components to be administered. In embodiments, the material is oxygen-impermeable. In the state of the art, micronutrients are typically added to nutrition bags directly before administration. For this purpose, vitamins can be provided in glass vials in the form of lyophilizates or solutions to be reconstituted and/or mixed into the nutrition/infusion bags. Trace elements are also provided in glass vials or polypropylene ampules meant to be mixed into infusion bags prior to administration. Prior to usage, meaning administration to patient, the micronutrients are sometimes added in the mixture or macronutrients via an injection port of the container or bag (septum) or are added via a Y-connector to the infusion line. This process takes time and several handling steps increasing the risk of errors or contamination. To avoid these potential problems, products have been developed that already contain some trace elements in nutrition multi-chamber bags, such as, for example, Pediaven, a parenteral nutrition binary solution intended for infants, children and adolescents, which contains trace elements in the glucose chamber. However, it has been reported that the trace element selenium, provided as selenium dioxide in the product, is absent in the finished product potentially due to degradation, as announced in July 2014 (http://www.pharmacovigilance-tours.fr/490.html). Another product, Elneopa, from Otsuka Pharmaceuticals, contains certain trace elements in a small dedicated chamber as part of a multi-chamber bag. However, this product does not contain selenium. It is known in the art that selenium, iodine and copper are difficult to include in nutrition bags, as they can undergo chemical reactions, especially under extreme conditions such as a heat sterilization step and during the storage period [for example, Allwood et al. Compatibility and Stability of Additives in Parenteral Nutrition Admixtures. Nutrition 1998, Vol. 14, No. 9, pp. 697-706; Eisenberg et al. Stability of selenium sources reviewed. Feedstuffs, June 18, 2012]. Furthermore, in various formulation studies, when attempting to introduce trace elements into nutrition multi-chamber bags, serious stability issues have been experienced, in particular the loss of selenium has been observed. This may be due to the fact that selenium in the form of sodium selenite (and selenious acid) is prone to adsorption, for example to plastic materials or iron oxides; can be reduced into metallic selenium in the presence of reducing agents like ascorbic acid; can be reduced into hydrogen selenide, which is a volatile substance; and/or can be transformed into selenious dioxide at low pH, which is also a volatile substance under certain conditions. Furthermore, nutritional solutions comprising selenate salts are unknown in the state of the art. In addition to selenium, iodine, fluoride and copper also showed stability issues during formulation trials. Copper is a reactive entity and can catalyse various chemical reactions and it is known that it can precipitate. Iodide can be reduced into iodine, which is potentially volatile. Furthermore, fluoride showed a decreasing concentration over time. Accordingly, to date there is no