PARENTERAL NUTRITION SOLUTION COMPRISING A SELENIUM SOURCE

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.

Claims

1. A medical product for preventing or correcting selenium deficiency in a patient, said product 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.

2. The medical product according to claim 1, wherein the selenate salt and/or seleno-amino acid are stable in the solution for at least three months when stored at a temperature of between 1 and 50° C.

3. The medical product according to claim 1, wherein the selenate salt and/or a seleno-amino acid are stable in the solution for at least 6 months at a temperature of from about 18° C. to 25° C.

4. The medical product according to claim 1, wherein the solution is a sterilized solution.

5. The medical product according to claim 1, wherein the solution comprises a selenate salt selected from the group consisting of sodium selenate, potassium selenate, barium selenate and ammonium selenate.

6. The medical product according to claim 1, wherein the solution comprises at least one additional trace element selected from the group consisting of zinc, iron, copper, manganese, chromium, iodine, fluoride and molybdenum.

7. The medical product according to claim 1, wherein the solution comprises an organic acid selected from the group consisting of malic acid, tartaric acid, citric acid, maleic acid and fumaric acid.

8. The medical product according to claim 1, wherein the solution comprises malic acid.

9. The medical product according to claim 1, wherein the solution has an acidic pH.

10. The medical product according to claim 1, wherein the solution does not comprise macronutrients selected from the group comprising carbohydrates, proteins and lipids.

11. The medical product according to claim 1, wherein the solution is configured for parenteral administration.

12. The medical product according to claim 1, wherein the solution comprises a selenate salt and/or a seleno-amino acid in an amount corresponding to 10-200 pg of selenium.

13. The medical product for preventing or correcting selenium deficiency in a patient according to claim 1, wherein the solution is 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.

14. The medical product according to claim 13, wherein the container comprises at least a first chamber containing a carbohydrate formulation, a second chamber containing an amino acid formulation, a third chamber containing a lipid formulation, optionally comprises electrolytes and/or vitamins in at least the first, second and/or third chamber, and wherein at least one chamber comprises a selenate salt and/or a seleno-amino acid.

15. The medical product according to claim 13, wherein the solution comprising a selenate salt and/or a seleno-amino acid is present in a fourth chamber.

16. The medical product according to claim 13, wherein the solution comprises sodium selenate or potassium selenate.

17. A method of preparing a medical product for preventing or correcting selenium deficiency in a patient according to claim 1, wherein the solution is prepared by the steps comprising a. dissolving a selenate salt and/or a seleno-amino acid in a liquid medium to produce a solution with a concentration of selenium between 0.28 and 28 mg/L, b. optionally adjusting the solution to an acidic pH by providing an organic acid and optionally adding at least one additional trace element selected from the group consisting of zinc, iron, copper, manganese, chromium, iodine, fluoride and molybdenum, and c. sterilizing the solution.

18. A method for correcting selenium deficiency in a patient, comprising parenteral administration of a sterilized solution comprising at least one selenate salt and/or a seleno-amino acid.

19. The medical product according to claim 1, wherein the seleno-amino acid is selenomethionine or selenocysteine.

20. The medical product according to claim 3, wherein the selenate salt and/or a seleno-amino acid are stable in the solution for at least 24 months.

21. The medical product according to claim 7, wherein the concentration of the organic acid is in the range of from 50 mM to 400 mM.

22. The medical product according to claim 9, wherein the solution has an acidic pH in the range of from 1 to 4.

Description

DESCRIPTION OF THE FIGURES

[0145] FIGS. 1-3: The recovery of the initial concentration of the different trace elements in percent (%) is indicated on the Y-axis of the Figures. The analyzed timepoints are is indicated on the X-axis. The timepoint −0.5 corresponds to the results of TE dosage on unsterilized sample at T0. Timepoint 0 corresponds to the results of TE dosage right after sterilization. Timepoint 0.5 correspond to the results of TE dosage after an accelerated stability stress cycle (i.e. three repetition of alternatively 5° C./50° C., 48 h/48 h). Timepoints 1, 3 and 6 correspond to the results of TE dosage after 1 month, 3 months and 6 months storage at 40° C./25% RH.

[0146] FIG. 1 refers to a solution containing selenium as sodium selenate.

[0147] FIG. 2 refers to a solution containing selenium as selenomethionine.

[0148] FIG. 3 refers to a solution containing selenium as selenite.

EXAMPLES

[0149] The invention is further described by the following examples. These are not intended to limit the scope of the invention but represent preferred embodiments of aspects of the invention provided for greater illustration of the invention described herein.

Example 1: Lab-Scale Manufacturing of a Selenium Containing Solution for Parenteral Nutrition or Administration

[0150] For preparing a selenium containing solution according to the invention the required amount of organic acid is dissolved in water for injection and the pH of the solution is adjusted to the target pH±0.5 with NaOH or HCl, as needed. In a next step the selenium as sodium selenate, selenomethionine or selenocysteine is introduced into the solution and stirred or agitated until complete dissolution. Afterwards, the pH is again controlled and, if needed, finally adjusted to the target pH±0.2 with NaOH or HCl. The solution is then filled into the container successively closed/sealed and can undergo a terminal heat sterilization.

Example 2: Lab-Scale Manufacturing of a Multi Trace Element Solution for Parenteral Nutrition or Administration Containing Selenium

[0151] For preparing a multi trace element selenium containing solution for parenteral nutrition/administration the required amount of organic acid is dissolved in water for injection and the pH of the solution is adjusted to the target pH±0.5 with NaOH or HCl, as needed. In a next step the required amount of each trace element (including sodium selenate and/or selenomethionine and/or selenocysteine) weighed in and added to the solution under constant stirring or agitation until complete dissolution. If, for certain trace elements, the required quantity is too low for weighing in the required amount, an intermediate concentrated solution can be previously prepared. A given volume of this intermediate solution will then be added to the final solution to reach the target concentration. Afterwards, the pH is again controlled and, if needed, finally adjusted to the target pH±0.2 with NaOH or HCl. Samples are filled and then the container is hermetically closed/sealed and can undergo to a terminal heat sterilization.

Example 3: Stabilization of Selenium by Using a Selenate Salt, Selenomethionine or Selenocysteine

[0152] Selenate was introduced with other trace elements into a separate chamber from macronutrients. A better stability of all the ingredients was achieved at acid pH 1 to 4 preferably between 2.2 and 3.5.

[0153] A better stability was achieved if an organic acid was added, for example malic acid, tartaric acid, citric acid, maleic acid or fumaric acid.

[0154] Each of sodium selenate, selenomethionine and selenocysteine remained stable when introduced into a specific separated chamber alone or together with other trace elements in solution (after 6 months storage at 40° C./25% RH).

[0155] Another way of introduction would be to include Sodium selenate and/or selenomethionine into the glucose, amino acid or lipid chamber.

Example 4: Assessment of Selenium Stability Using Solutions Containing Selenate, Selenomethionine or Selenite

[0156] FIGS. 1-3 illustrate the better stability of selenium when introduced as selenate (FIG. 1) or selenomethionine (FIG. 2) compared with selenite (FIG. 3) after storage for three months. Selenate and selenomethionine remained stable for up to 6 months. For selenite, analysis was stopped after three months due to lack of stability.

[0157] For the three tested solutions containing different forms of selenium, the selenium is mixed with other TE (Zn, Cu, Mn, F, I, Mo, Cr, Fe), which were introduced as chloride salts. The solutions were acidified to pH 2.2 using malic acid and underwent terminal heat sterilization prior to storage.

[0158] The results as shown in FIGS. 1-3 demonstrate that the selenium concentration remained stable in solutions comprising selenate or selenomethionine, whereas the selenium concentration decreased significantly in the solution comprising selenium as selenite. Concentrations of all other TE remained about stable under all tested conditions.