Compositions providing parenteral nutrition and trace elements

Abstract

The present invention relates to lipid emulsions for parenteral administration comprising an oil phase and a pharmaceutically acceptable form of selenium, as well as to containers comprising, in separate chambers, said emulsions and an amino acid solution for parenteral administration and / or a glucose solution for parenteral administration.

Description

Compositions providing parenteral nutrition and trace elementsField of the inventionThe invention relates to the provision of parenteral nutrition comprising amino acids, glucose, lipids, and trace elements.Background of the inventionParenteral nutrition is an essential component in the treatment of patients, where oral or enteral feeding is not sufficient to meet nutritional needs or for other reasons impossible, e.g., in intensive care patients, in patients with short bowel syndrome, or in patients undergoing abdominal surgery, chemotherapy or bone marrow transplantation.Standard compositions for providing parenteral nutrition to adults comprising amino acid solutions, glucose solutions and lipid emulsions, comprised in 3- chamber bags, are commercially available. However, these bags do not usually comprise trace elements. These currently need to be administered separately or added to the standard compositions respectively. This does not only require additional time, attention, thought and effort for the medical staff but is also associated with risks and potential mistakes, e.g., in that the trace elements might be over- or underdosed and / or in that microbial contamination may occur and / or in that instability may be caused, e.g., where the products that are being combined are not compatible.Hence, there is a need for compositions for use in providing parenteral nutrition comprising a glucose solution, an amino acid solution and a lipid emulsion conveniently provided in ready-to-use bags, wherein the bags further contain all required trace elements.Due to the various stability and compatibility issues that may arise, the provision of such a bag is a technical challenge.This is confirmed e.g., in WO2023 / 107913 Al, paragraph

[0274] , where the difficulties, particularly with respect to the stable incorporation of selenium, iodine, fluorine and copper are highlighted. The potential solution offered there resides in the provision of specific bags with at least 5 chambers.FK99239-15-PAT-WOSimilar findings and concerns are described in WO2022 / 251810 in view of selenium and the sterilization process. The potential solution discussed there is the provision of a bag with chambers possessing differential gas permeabilities and the adjustment of the pH in the specific chamber / solution to acidic values while at the same time ensuring a dissolved oxygen content between 0.5 and 8 ppm within the respective solution.WO2022 / 251106 is concerned with the incorporation of copper, chromium, iron, manganese, molybdenum, zinc, selenium, and iodine into parenteral nutrition compositions. The difficulties are highlighted in paragraphs

[0012] to

[0019] . In particular, the heat sterilization process and the loss of selenium and iodine, e.g., due to absorption to the plastic material of the bag and the volatility of their potential reaction products are described as critical, while copper is identified as a reactive entity catalyzing various chemical reactions adversely affecting the chemical stability of the parenteral nutrition compositions. The potential solution outlined in WO2022 / 251106 is the provision of a bag comprising at least five chambers.As these approaches require fundamental changes to the existing packaging concept and technology, inter alia necessitating the qualification of new polymeric materials and the setup and approval of new filling lines, they are not favored both from a manufacturing and a regulatory point of view.Accordingly, the present inventors have been pursuing a formulation-related approach instead and surprisingly found that the required trace elements may be advantageously incorporated by differentially distributing them into the three macronutrient formulations.Description of the inventionThe present inventors have surprisingly found that a bag comprising the macronutrients glucose, amino acids, and lipids as well the trace elements iron, copper, chromium, manganese, molybdenum, zinc, selenium, iodine and fluorine may be provided by differentially distributing the trace elements into the 3 macronutrient compositions.In one aspect, the present invention relates to a lipid emulsion, in particular to an oil-in water emulsion, comprising selenium. In a second aspect the presentFK99239-15-PAT-WO invention relates to a glucose solution comprising iron. In a third aspect, the present invention relates to an amino acid solution comprising copper.In particular, the present inventors surprisingly found that selenium, molybdenum, and iodine may be comprised in the lipid emulsion, that iron, copper, molybdenum, manganese, chromium, zinc, and fluorine may be comprised in the glucose solution and that zinc, copper, molybdenum, iodine, manganese, chromium, and fluorine may be comprised in the amino acid solution.Accordingly, the present invention relates to a glucose solution comprising iron and / or copper and / or molybdenum and / or manganese and / or chromium and / or zinc and / or fluorine, to an amino acid solution comprising zinc and / or copper and / or molybdenum and / or iodine and / or manganese and / or chromium and / or fluorine and to a lipid emulsion comprising selenium, and / or molybdenum and / or iodine and / or fluorine.In another preferred embodiment, the present invention relates to a glucose solution comprising copper, wherein the glucose solution is comprised in a non- sulfur-cured container, preferably in a non-sulfur cured plastic bag comprising an injection port and an infusion port, wherein the sealing elements of the ports are made of non-sulfur-cured rubber material, preferably, peroxide-cured rubber material.In another preferred embodiment, the present invention relates to an amino acid solution comprising zinc and copper.In yet another preferred embodiment, the present invention relates to a lipid emulsion comprising selenium and iodine.The trace elements comprised in the glucose solution, in the amino acid solution, and in the lipid emulsion remain stable for at least 3 months, preferably for at least 6 months, more preferably for at least 12 months, e.g., at least 18 months or at 24 months, when stored at 25 °C at 40 % relative humidity. In this context, the term "stable" means that the contents of a given trace element do not decrease to less than 90 % of the initial contents. Also the glucose solution, the amino acid solution, and the lipid emulsion, in the presence of the trace elements, remain stable for at least 3 months, preferablyFK99239-15-PAT-WO for at least 6 months, more preferably for at least 12 months, when stored at 25 °C at 40 % relative humidity. In other words, each of the glucose solution, the amino acid solution, and the lipid emulsion, is storage-stable.Preferably, the trace elements comprised in the glucose solution, in the amino acid solution, and in the lipid emulsion, remain stable for at least 1 month, more preferably for at least 3 months, most preferably for at least 6 months, when stored at 40 °C at < 25 % relative humidity. In this context, the term "stable" means that the content of a given trace element does not decrease to less than 90 % of its initial content. Preferably, also the glucose solution, the amino acid solution, and the lipid emulsion, in the presence of the trace elements, remain stable for at least 1 month, more preferably for at least 3 months, most preferably for at least 6 months, when stored at 40 °C and < 25 % relative humidity. In some other preferred embodiments, the trace elements comprised in the glucose solution, in the amino acid solution, and in the lipid emulsion, remain stable for at least 1 week, preferably for at least 2 weeks, most preferably for at least 1 month, when stored at 60 °C. In this context, the term "stable" means that the content of a given trace element does not decrease to less than 90 % of its initial content. Preferably, also the glucose solution, the amino acid solution, and the lipid emulsion, in the presence of the trace elements, remain stable for at least 1 week, more preferably for at least 2 weeks, most preferably for at least 1 month, when stored at 60°C. A "stable glucose solution" as used herein is a glucose solution in which the glucose content does not decrease to less than 95% of its initial contents, in which the concentration of 5-HMF does not exceed 0.1 wt.% based on the weight of the glucose, in which the fructose concentration does not exceed 1 wt.% based on the weight of the glucose, and in which no physical deterioration can be observed (e.g., that no visible particles are formed). A "stable amino acid solution" as used herein is an amino acid solution in which the amino acid contents does not decrease to less than 95 % of its initial contents, and in which no physical deterioration can be observed (e.g., that no visible particles are formed). A "stable lipid emulsion" as used herein is a lipid emulsion that does not chemically or physically deteriorate, i.e., that the PFAT5value remains below 0.05 %, that the peroxide value remains below 2 mmol / L, that the mean droplet size does not change by more than 5% and that the mean droplet size does not exceed 500 nm.FK99239-15-PAT-WOThe present invention further relates to a bag comprising in separate chambers a glucose solution, an amino acid solution, and a lipid emulsion and further comprising the trace elements iron, copper, selenium, molybdenum, , manganese, zinc, iodine and optionally chromium and / or fluorine, wherein selenium is comprised in the lipid emulsion, wherein iron is comprised in the glucose solution, wherein copper is comprised in the glucose solution and / or in the amino acid solution, wherein molybdenum is comprised in the lipid emulsion and / or in the glucose solution and / or in the amino acid solution, wherein iodine is comprised in the lipid emulsion and / or in the amino acid solution, wherein manganese and chromium, if present, are comprised in the glucose solution and / or in the amino acid solution, wherein zinc is comprised in the amino acid solution and / or in the glucose solution, and wherein fluorine, if present, is comprised in the lipid emulsion, in the glucose solution and / or in the amino acid solution.In a preferred embodiment, the present invention relates to a bag comprising in separate chambers a glucose solution, an amino acid solution, and a lipid emulsion and further comprising the trace elements iron, copper, selenium, molybdenum, chromium, manganese, zinc, iodine and optionally fluorine, wherein selenium and iodine are comprised in the lipid emulsion, wherein iron, copper, chromium, molybdenum and manganese are comprised in the glucose solution, wherein zinc is comprised in the amino acid solution, and wherein fluorine, if present, is comprised in the lipid emulsion.In another preferred embodiment, the present invention relates to a bag comprising in separate chambers a glucose solution, an amino acid solution, and a lipid emulsion and further comprising the trace elements iron, copper, selenium, molybdenum, chromium, manganese, zinc, iodine and optionally fluorine, wherein selenium is comprised in the lipid emulsion, wherein iron, chromium, molybdenum and manganese are comprised in the glucose solution, wherein zinc, iodine and copper are comprised in the amino acid solution, and wherein fluorine, if present, is comprised in the amino acid solution.In still another preferred embodiment, the present invention relates to a bag comprising, in separate chambers, a glucose solution comprising iron, an amino acid solution comprising copper and a lipid emulsion comprising selenium.FK99239-15-PAT-WOPreferably, the bag provides 100 pg to 10 mg iron, 100 pg to 4 mg copper, 10 pg to 150 pg selenium, 2 pg to 50 pg molybdenum, 1 pg to 30 pg chromium, 10 pg to 200 pg manganese, 1 mg to 25 mg zinc, 20 pg to 250 pg iodine and optionally 100 pg to 2 mg fluorine.More preferably, the bag provides 300 pg to 5 mg iron, 200 pg to 2 mg copper, 30 pg to 130 pg selenium, 5 pg to 40 pg molybdenum, 2 pg to 20 pg chromium, 20 pg to 150 pg manganese, 2 mg to 20 mg zinc, 80 pg to 200 pg iodine and optionally 700 pg to 1.2 mg fluorine.Most preferably, the bag provides 400 pg to 2 mg iron, 300 pg to 600 pg copper, 60 pg to 100 pg selenium, 10 pg to 30 pg molybdenum, 5 pg to 15 pg pg chromium, 40 pg to 70 pg manganese, 3 mg to 15 mg zinc, 110 pg to 150 pg iodine and optionally 800 pg to 1.1 mg fluorine.In a particularly preferred embodiment, the bag provides 1.1 mg iron, 380 pg copper, 79 pg selenium, 19 pg molybdenum, 10 pg chromium, 55 pg manganese, 7.7 mg zinc, 127 pg iodine and optionally 950 pg fluorine.According to the present invention the trace elements are provided in pharmaceutically acceptable form.Preferably, selenium is provided in form of Se(IV), more preferably in form of a salt comprising selenite ions, most preferably as anhydrous sodium selenite.Preferably, iron is provided in form of iron(III), e.g., as iron(III) sulfate, iron(III) oxide, sodium iron(III) gluconate, iron (III) citrate, ammonium iron(III) citrate, iron(III) oxide-hydroxide, iron (III) fumarate, ammonium Iron (III) sulfate, iron sorbitol citrate, iron(III) hydroxide saccharose, iron(III) carboxymaltose or iron(III) chloride, in different hydrate or anhydrous forms respectively. More preferably, the pharmaceutically acceptable form of iron is iron(III) chloride, most preferably iron(III) chloride hexahydrate.Preferably, copper is provided in form of Cu(II), e.g., as copper(II) sulfate, copper(II) gluconate, copper(II) acetate and copper(II) chloride, in different hydrate or anhydrous forms respectively. More preferably, the pharmaceutically acceptable form of copper is copper(II) chloride, most preferably copper(II) chloride dihydrate.FK99239-15-PAT-WOPreferably, molybdenum is provided as Mo(VI), more preferably the pharmaceutically acceptable form of molybdenum is a salt of molybdenum comprising molybdate ions, e.g., an alkali metal salt, most preferably the pharmaceutically acceptable form of molybdenum is sodium molybdate. In a particularly preferred embodiment, the pharmaceutically acceptable form of molybdenum is sodium molybdate dihydrate.Preferably, chromium is provided in form of Cr(III), e.g., as chromium(III) picolinate, chromium(III) gluconate, chromium(III) sulfate and chromium(III) chloride, in different hydrate or anhydrous forms respectively. More preferably, the pharmaceutically acceptable salt of chromium is chromium(III) chloride, most preferably chromium(III) chloride hexahydrate.Preferably, manganese is provided in a pharmaceutically acceptable form selected from the group consisting of manganese(II) sulfate, manganese(II) chloride, and manganese(II) gluconate, in different hydrate or anhydrous forms respectively. More preferably, the pharmaceutically acceptable form of manganese is a halogenide salt comprising Mn2+ions, most preferably manganese chloride (MnCIz), e.g., manganese chloride tetrahydrate.Preferably, zinc is provided in a pharmaceutically acceptable form selected from the group consisting of zinc acetate, zinc gluconate, zinc sulfate and zinc chloride, in different hydrate or anhydrous forms respectively. More preferably, the pharmaceutically acceptable form of zinc is zinc chloride, most preferably anhydrous zinc chloride.Preferably, iodine is provided in a pharmaceutically acceptable form selected from sodium iodide and potassium iodide. More preferably, the pharmaceutically acceptable form of iodine is potassium iodide, most preferably anhydrous potassium iodide.Preferably, where a pharmaceutically acceptable form fluorine is provided, the pharmaceutically acceptable form of fluorine is selected from the group consisting of ammonium fluoride, potassium fluoride, magnesium fluoride and sodium fluoride. More preferably, the pharmaceutically acceptable form of fluorine is sodium fluoride, most preferably anhydrous sodium fluoride.FK99239-15-PAT-WOIn a particularly preferred embodiment, the bag comprises 5.4 mg iron chloride hexahydrate, , 1.0 mg copper chloride dihydrate, 173 pg anhydrous sodium selenite, 198 pg manganese chloride dihydrate, 10.5 mg anhydrous zinc chloride, 48.5 pg sodium molybdate dihydrate, 166 pg anhydrous potassium iodide, and optionally 2.1 mg anhydrous sodium fluoride and / or 53.3 pg chromium chloride hexahydrate.The glucose solution, the amino acid solution and the lipid emulsion, as well as the bag according to the present invention are for use in providing parenteral nutrition, preferably to adults and children aged 12 years or more. Hence, the glucose solution, the amino acid solution and the lipid emulsion, as well as the bag according to the present invention are adapted for parenteral administration. If comprised in one bag, the glucose solution, the amino acid solution and the lipid emulsion are comprised in separate chambers of the bag and are administered after the contents of the separate chambers have been mixed.Preferably, the mixture is administered intravenously, either through a peripheral or a central vein.Preferably, the mixture, if administered through a peripheral vein, has an osmolarity of not more than 1000 mOsmol / kg, more preferably not more than 950 mOsmol / kg, most preferably not more than 900 mOsmol / kg. Preferably, the osmolarity of the mixture is between 800 and 1000 mOsmol / kg, more preferably between 800 and 950 mOsmol / kg, most preferably between 800 and 900 mOsmol / kg. In a particularly preferred embodiment, the mixture, if administered through a peripheral vein, has an osmolarity of 850 mOsmol / kg.Preferably, the mixture, if administered through a central vein, has an osmolarity of not more than 1700 mOsmol / kg, more preferably not more than 1600 mOsmol / kg, most preferably not more than 1550 mOsmol / kg. Preferably, the osmolarity of the mixture is between 1000 and 1700 mOsmol / kg, more preferably between 1100 and 1600 mOsmol / kg, most preferably between 1200 and 1500 mOsmol / kg. In a particularly preferred embodiment, the mixture, if administered through a central vein, has an osmolarity of 1500 mOsmol / kg.FK99239-15-PAT-WOThe pH of the mixture is preferably between 4.5 and 7.5, more preferably between 5.0 and 7.0, most preferably between 5.4 and 6.2. In a particularly preferred embodiment, the pH of the mixture is 5.5 to 5.8. In another preferred embodiment, the pH of the mixture is between 4.8 and 5.3.The glucose solutionThe glucose solution comprises glucose, a pharmaceutically acceptable form of iron and optionally a pharmaceutically acceptable form of copper and / or a pharmaceutically acceptable form of molybdenum and / or a pharmaceutically acceptable form of chromium and / or a pharmaceutically acceptable form of manganese and / or a pharmaceutically acceptable form of zinc and / or a pharmaceutically acceptable form of fluorine.Preferably, the glucose solution comprises 10 g to 45 g glucose per 100 ml of the glucose solution.In a preferred embodiment, the glucose solution comprises 10 g to 15 g glucose per 100 ml of the glucose solution. In a particularly preferred embodiment, the glucose solution comprises 13 g glucose per 100 ml of the glucose solution.In another preferred embodiment, the glucose solution comprises 40-45 g glucose per 100 ml of the glucose solution. In another particularly preferred embodiment, the glucose solution comprises 42 g glucose per 100 ml of the glucose solution.The glucose solution preferably has a pH of 2.0 to 7.0, more preferably, the glucose solution has a pH of 2.5 to 6.5, e.g., 3.0 or 3.5 or 4.0 or 4.5 or 5.0.Most preferably, the glucose solution has a pH of 3.0 to 4.0, e.g., 3.0 or 3.5 or 4.0.The pH may be adjusted, e.g., by adding an aqueous solution of HCI and / or NaOH.The glucose solution comprises a pharmaceutically acceptable form of iron.Preferably, the pharmaceutically acceptable form of iron comprises iron in the form iron(III) and is preferably selected from the group consisting of iron(III) sulfate, i ron(III) oxide, sodium iron(III) gluconate, iron (III) citrate, ammoniumFK99239-15-PAT-WO iron(III) citrate, iron(III) oxide-hydroxide, iron (III) fumarate, ammonium Iron (III) sulfate, iron sorbitol citrate, iron(III) hydroxide saccharose, iron(III) carboxymaltose and iron(III) chloride, in different hydrate or anhydrous forms respectively. More preferably, the pharmaceutically acceptable form of iron is iron(III) chloride, most preferably iron(III) chloride hexahydrate.Preferably, the glucose solution provides 100 pg to 10 mg iron, more preferably, 300 pg to 5 mg iron, most preferably, 400 pg to 2 mg iron.In a particularly preferred embodiment, the glucose solution provides 1.1 mg iron, corresponding to 5.4 mg iron chloride hexahydrate.Preferably, the iron concentration ranges from 1.6 pg to 3.4 mg per 100 ml of the glucose solution, preferably provided as 7.7 pg to 16.5 mg iron(III) chloride hexahydrate per 100 ml of the glucose solution.For example, the glucose solution provides 171 pg, 142 pg, 108 pg, 37.4 pg, 25.1 pg, or 18.8 pg iron per 100 ml of the glucose solution. This may be provided, e.g., as 823 pg, 685 pg, 521 pg, 1810 pg, 1210 pg, or 908 pg mg iron chloride hexahydrate per 100 ml of the glucose solution.The glucose solution may comprise a pharmaceutically acceptable form copper.Where the glucose solution comprises a pharmaceutically acceptable form of copper, the pharmaceutically acceptable form of copper preferably comprises copper in the form of Cu(II) and is preferably selected from the group consisting of copper(II) sulfate, copper(II) gluconate, copper(II) acetate and copper(II) chloride, in different hydrate or anhydrous forms respectively. More preferably, the pharmaceutically acceptable form of copper is copper chloride, most preferably copper chloride dihydrate.Preferably, the glucose solution provides 100 pg to 4 mg copper, more preferably, 200 pg to 2 mg copper, most preferably, 300 pg to 600 pg copper.In a particularly preferred embodiment, the glucose solution provides 380 pg copper corresponding to 1020 pg copper chloride dihydrate.FK99239-15-PAT-WOPreferably, the copper concentration ranges from 9.7 pg to 1.4 mg per 100 ml of the glucose solution, preferably provided as 26.0 pg to 3.8 mg copper chloride dihydrate per 100 ml of the glucose solution.For example, the glucose solution provides 57.9 pg, 48.2 pg, 36.7 pg, 128 pg, 85.2 pg, or 63.9 pg copper per 100 ml of the glucose solution. This may be provided, e.g., as 155 pg, 129 pg, 98 pg, 342 pg, 229 pg, or 171 pg copper chloride dihydrate per 100 ml of the glucose solution.The glucose solution may further comprise a pharmaceutically acceptable form of molybdenum.Where the glucose solution further comprises a pharmaceutically acceptable form of molybdenum, the pharmaceutically acceptable form of molybdenum preferably comprises molybdenum as Mo(VI), more preferably the pharmaceutically acceptable form of molybdenum is a salt of molybdenum comprising molybdate ions, e.g., an alkali metal salt, most preferably the pharmaceutically acceptable form of molybdenum is sodium molybdate. In a particularly preferred embodiment, the pharmaceutically acceptable salt of molybdenum is sodium molybdate dihydrate.Preferably, the glucose solution provides 2 pg to 50 pg molybdenum, more preferably, 5 pg to 40 pg molybdenum, most preferably, 10 pg to 30 pg molybdenum.In a particularly preferred embodiment, the glucose solution provides 19 pg molybdenum corresponding to 48.5 pg sodium molybdate dihydrate.Preferably, the molybdenum concentration ranges from 0.2 pg to 17.4 pg per 100 ml of the glucose solution, preferably provided as 0.5 pg to 43.9 pg sodium molybdate dihydrate per 100 ml of the glucose solution.For example, the glucose solution provides 2.9 pg, 2.4 pg, 1.9 pg, 6.6 pg, 4.3 pg, or 3.2 pg molybdenum per 100 ml of the glucose solution. This may be provided, e.g., as 7.4 pg, 6.2 pg, 4.7 pg, 16.3 pg, 10.9 pg, or 8.2 pg sodium molybdate dihydrate per 100 ml of the glucose solution.The glucose solution may further comprise a pharmaceutically acceptable form of chromium.FK99239-15-PAT-WOWhere the glucose solution further comprises a pharmaceutically acceptable form of chromium, preferably, the pharmaceutically acceptable form of chromium comprises chromium in the form of Cr(III) and is preferably selected from the group consisting of chromium(III) picolinate, chromium(III) gluconate, chromium(III) sulfate and chromium(III) chloride, in different hydrate or anhydrous forms respectively. More preferably, the pharmaceutically acceptable salt of chromium is chromium(III) chloride, most preferably chromium(III) chloride hexahydrate.Preferably, the glucose solution provides 1 pg to 30 pg chromium, more preferably, 2 pg to 20 pg chromium, most preferably, 5 pg to 15 pg chromium.In a particularly preferred embodiment, the glucose solution provides 10 pg chromium corresponding to 53.3 pg chromium chloride(III) hexahydrate.Preferably, the chromium concentration ranges from 0.1 pg pg to 10.5 pg pg per 100 ml of the glucose solution.For example, the glucose solution provides 1.6 pg, 1.3 pg, 1.0 pg, 3.5 pg, 2.3 pg, or 1.8 pg chromium per 100 ml of the glucose solution. This may be provided, e.g., as 8.1 pg, 6.8 pg, 5.1 pg, 17.9 pg, 12.0 pg, or 9.0 pg chromium chloride hexahydrate per 100 ml of the glucose solution.The glucose solution may further comprise a pharmaceutically acceptable salt of manganese.Where the glucose solution further comprises a pharmaceutically acceptable form of manganese, the pharmaceutically acceptable form of manganese may be selected from the group consisting of manganese(II) sulfate, manganese(II) chloride, and manganese(II) gluconate, in different hydrate or anhydrous forms respectively. Preferably, the pharmaceutically acceptable form of manganese is a halogenide salt, more preferably a halogenide salt comprising Mn2+ions, most preferably manganese chloride (MnCL), e.g., manganese chloride tetrahydrate.Preferably, the glucose solution provides 10 pg to 200 pg manganese, more preferably, 20 pg to 150 pg manganese, most preferably, 40 pg to 70 pg manganese.FK99239-15-PAT-WOIn a particularly preferred embodiment, the glucose solution provides 55 pg manganese corresponding to 198 pg manganese chloride tetrahydrate.Preferably, the manganese concentration ranges from 1.0 pg to 66.9 pg per 100 ml of the glucose solution, preferably provided as 3.6 pg to 241 pg manganese chloride tetrahydrate per 100 ml of the glucose solution.For example, the glucose solution provides 8.4 pg, 7.0 pg, 5.3 pg, 18.4 pg, 12.3 pg, or 9.2 pg manganese per 100 ml of the glucose solution. This may be provided, e.g., as 30.2 pg, 25.1 pg, 19.1 pg, 66.4 pg, 44.4 pg, or 33.3 pg manganese chloride tetrahydrate per 100 ml of the glucose solution.The glucose solution may further comprise a pharmaceutically acceptable form of zinc.Where the glucose solution further comprises a pharmaceutically acceptable form of zinc, the pharmaceutically acceptable form of zinc is preferably selected from the group consisting of zinc acetate, zinc gluconate, zinc sulfate and zinc chloride, in different hydrate or anhydrous forms respectively. More preferably, the pharmaceutically acceptable form of zinc is zinc chloride, most preferably anhydrous zinc chloride.Preferably, where the glucose solution further comprises a pharmaceutically acceptable salt of zinc, the glucose solution provides 1 mg to 25 mg zinc, more preferably, 2 mg to 20 mg zinc, most preferably, 3 mg to 15 mg zinc.In a particularly preferred embodiment, the glucose solution provides 5 mg zinc corresponding to 10.5 mg anhydrous zinc chloride.Preferably, the zinc concentration ranges from 0.1 mg to 8.8 mg per 100 ml of the glucose solution.For example, the glucose solution provides 0.8 mg, 0.6 mg, 0.5 mg, 1.7 mg, 1.1 mg, or 0.8 mg zinc per 100 ml of the glucose solution. This may be provided, e.g., as 1.6 mg, 1.3 mg, 1.0 mg, 3.5 mg, 2.4 mg, or 1.8 mg anhydrous zinc chloride per 100 ml of the glucose solution.The glucose solution may further comprise a pharmaceutically acceptable form of fluorine.FK99239-15-PAT-WOWhere the glucose solution further comprises a pharmaceutically acceptable form of fluorine, the pharmaceutically acceptable form of fluorine is preferably selected from the group consisting of ammonium fluoride, potassium fluoride, magnesium fluoride and sodium fluoride. More preferably, the pharmaceutically acceptable form of fluorine is sodium fluoride, most preferably anhydrous sodium fluoride.Preferably, where the glucose solution further comprises a pharmaceutically acceptable salt of fluorine, the glucose solution provides 100 pg to 2 mg fluorine, more preferably 700 pg to 1.2 mg fluorine, most preferably, 800 pg to 1.1 mg fluorine.In a particularly preferred embodiment, the glucose solution comprises 950 pg fluorine corresponding to 2.1 mg (anhydrous) sodium fluoride.Preferably, the fluorine concentration ranges from 9.7 pg to 671.2 pg per 100 ml of the glucose solution.For example, the glucose solution provides 144.8 pg, 120.6 pg, 91.7 pg, 318.8 pg, 213.0 pg, or 159.7 pg fluorine per 100 ml of the glucose solution. This may be provided, e.g., as 320.1 pg, 266.5 pg, 202.7 pg, 704.7 pg, 470.9 pg, or 352.9 pg anhydrous sodium fluoride per 100 ml of the glucose solution.In a preferred embodiment, the present invention relates to a glucose solution comprising 10 g to 45 g glucose per 100 ml of the glucose solution and a pharmaceutically acceptable form of iron.In a particularly preferred embodiment, the present invention relates to a glucose solution comprising 10 to 45 g, preferably 10 to 15 g or 40 to 45 g, of glucose and 1.6 pg to 3.4 mg of iron per 100 ml of the glucose solution, wherein the iron is preferably provided as iron(III) chloride and wherein, preferably, the pH of the glucose solution is between 2.5 and 6.5, more preferably between 3.0 and 4.0.The inventors have found that where the glucose solution comprises a pharmaceutically acceptable form of copper and is stored at temperatures of 50°C or 60°C, copper is more stable in the absence of a sulfur source.FK99239-15-PAT-WOAccordingly, in another preferred embodiment, the present invention relates to a container comprising a glucose solution preferably comprising 10 g to 45 g glucose per 100 ml of the glucose solution and a pharmaceutically acceptable form of copper, wherein, preferably, the container is a plastic bag comprising at least one injection port and at least one infusion port, wherein the sealing elements of the ports are made of non-sulfur-cured rubber material, preferably, peroxide-cured rubber material.In another particularly preferred embodiment, the present invention relates to a container comprising a glucose solution comprising 10 to 45 g, preferably 10 to 15 g or 40 to 45 g, of glucose and 9.7 pg to 1.4 mg of copper per 100 ml of the glucose solution, wherein the copper is preferably provided as a salt selected from the group consisting of copper(II) sulfate, copper(II) gluconate, copper(II) acetate and copper(II) chloride and wherein the container preferably is a plastic bag comprising at least one injection port and at least one infusion port, wherein the sealing elements of the ports are made of non- sulfur-cured rubber material, preferably, peroxide-cured rubber material.In another preferred embodiment, the present invention relates to a container comprising a glucose solution comprising 10 g to 45 g glucose per 100 ml of the glucose solution, a pharmaceutically acceptable form of iron and a pharmaceutically acceptable form of copper, wherein preferably the container is a plastic bag comprising at least one injection port and at least one infusion port, wherein the sealing elements of the ports are made of non-sulfur-cured rubber material, preferably, peroxide-cured rubber material.In another particularly preferred embodiment, the present invention relates to a container comprising a glucose solution comprising 10 to 45 g, preferably 10 to 15 g or 40 to 45 g, glucose, 1.6 pg to 3.4 mg iron per 100 ml of the glucose solution, wherein the iron is preferably provided as iron(III) chloride, and 9.7 pg to 1.4 mg copper per 100 ml of the glucose solution, wherein the copper is preferably provided as a salt selected from the group consisting of copper(II) sulfate, copper(II) gluconate, copper(II) acetate and copper(II) chloride and wherein, preferably, the container is a plastic bag comprising at least one injection port and at least one infusion port, wherein the sealing elements of the ports are made of non-sulfur-cured rubber material, preferably, peroxide- cured rubber material.FK99239-15-PAT-WOIn still another particularly preferred embodiment, the present invention relates to a container comprising a glucose solution comprising 10 g to 45 g glucose per 100 ml of the glucose solution, 1.6 pg to 3.4 mg iron per 100 ml of the glucose solution, 9.7 pg to 1.4 mg copper per 100 ml of the glucose solution, wherein iron is provided as iron(III) chloride, wherein copper is provided as copper(II) chloride, wherein the glucose solution has a pH of 2.5 to 6.5 and wherein the container is a plastic bag comprising at least one injection port and at least one infusion port, wherein the sealing elements of the ports are made of non-sulfur-cured rubber material.The amino acid solutionThe amino acid solution comprises amino acids and optionally a pharmaceutically acceptable form of zinc and / or a pharmaceutically acceptable form of copper and / or a pharmaceutically acceptable form of molybdenum and / or a pharmaceutically acceptable form of manganese and / or a pharmaceutically acceptable form of iodine and / or a pharmaceutically acceptable form of fluorine.Preferably, the amino acid solution comprises 4 g to 18 g, more preferably 5 g to 15 g, amino acids per 100 ml of the amino acid solution.In preferred embodiments, the amino acid solution comprises 5 g, 8.5 g, 10 g, 11.4 g, 13.4 g, or 15 g amino acids per 100 ml of the amino acid solution.In a particularly preferred embodiment, the amino acid solution comprises 10 g amino acids per 100 ml of the amino acid solution.Preferably, the amino acid solution has a pH of 3.5 to 7.0, more preferably 4.5 to 6.5, most preferably 5.0 to 6.5.Preferably, the amino acid comprises L-histidine, L-isoleucine, L-leucine, L- lysine, L-threonine, L-tryptophan, L-valine, at least one of L-methionine and L- cysteine, and at least one of L-phenylalanine and L-tyrosine.Preferably, the amino acid solution provides L-Histidine, L-Isoleucine, L- Leucine, L-Lysine, L-Threonine, L-Tryptophane, L-Valine, at least one of L- Methionine, N-Acetyl-Methionine and L-Cysteine, at least one of L-FK99239-15-PAT-WOPhenylalanine and L-Tyrosine, and preferably L-Alanine, L-Arginine, Glycine, L- Proline, L-Serine, Taurine, L-Aspartic acid and / or L-glutamic acid.Preferably, the amino acid solution comprises 10-18 wt.% L-alanine, 8-14 wt.% L-arginine, 0-2 wt.% L-Cysteine and / or L-Cystine, 7-15 wt.% Glycine, 2- 6 wt.% L-Histidine, 3-7 wt.% L-Isoleucine, 5-10 wt.% L-Leucine, 4-10 wt.% L- Lysine, 3-6 wt.% L-Methionine, 3-7 wt.% L-Phenylalanine, 5-14 wt.% L- Proline, 3-9 wt.% L-Serine, 2-7 wt.% L-Threonine, 1-3 wt.% L-Tryptophan, 0.2-2 wt.% L-Tyrosine, 4-9 wt.% L-Valine, 0-2 wt.% Taurine, 0-3 wt.% L- Aspartic acid, and 0-5 wt.% L-glutamic acid based on the total weight of the amino acids.Preferably, the amino acid solution comprises 12-17 wt.% L-alanine, 9-13 wt.% L-arginine, 0-1 wt.% L-Cysteine and / or L-Cystine, 7-12 wt.% Glycine, 3-6 wt.% L-Histidine, 4-7 wt.% L-Isoleucine, 5-9 wt.% L-Leucine, 5-8 wt.% L- Lysine, 4-6 wt.% L-Methionine, 4-7 wt.% L-Phenylalanine, 5-12 wt.% L- Proline, 3-7 wt.% L-Serine, 4-6 wt.% L-Threonine, 1-2 wt.% L-Tryptophan, 0.2-2 wt.% L-Tyrosine, 5-8 wt.% L-Valine, 0-2 wt.% Taurine, 0-3 wt.% L- Aspartic acid, and 0-5 wt.% L-glutamic acid based on the total weight of the amino acids.In a particularly preferred embodiment, the amino acid solution comprises 14 wt.% L-alanine, 12 wt.% L-arginine, 11 wt.% Glycine, 3 wt.% L-Histidine, 5 wt.% L-Isoleucine, 7.4 wt.% L-Leucine, 6.6 wt.% L-Lysine, 4.3 wt.% L- Methionine, 5 wt.% L-Phenylalanine, 11.2 wt.% L-Proline, 6.5 wt.% L-Serine, 4.4 wt.% L-Threonine, 2 wt.% L-Tryptophan, 0.4 wt.% L-Tyrosine, 6.2 wt.% L-Valine, and 1 wt.% Taurine, based on the total weight of the amino acids.This amino acid solution comprises 5 g, 10 g, or 15 g of amino acids per 100 ml of the amino acid solution.In another particularly preferred embodiment, the amino acid solution comprises 14 wt.% L-alanine, 10 wt.% L-arginine, 0-0.5 wt.% L-Cysteine,7 wt.% Glycine, 6 wt.% L-Histidine, 5 wt.% L-Isoleucine, 7 wt.% L-Leucine,8 wt.% L-Lysine, 5 wt.% L-Methionine, 7 wt.% L-Phenylalanine, 6 wt.% L- Proline, 4 wt.% L-Serine, 5 wt.% L-Threonine, 1.7 wt.% L-Tryptophan,FK99239-15-PAT-WO0.2 wt.% L-Tyrosine, 6.5 wt.% L-Valine, 5 wt.% L-glutamic acid, and 3 wt.% L-aspartic acid based on the total weight of the amino acids.This amino acid solution comprises 8.5 g, or 11.4 g of amino acids per 100 ml of the amino acid solution.In yet another particularly preferred embodiment, the amino acid solution comprises 11.9 wt.% L-Alanine, 8.4 wt.% L-Arginine, 2.5 wt.% L-Aspartic acid, 4.2 wt.% L-Glutamic acid, 7.7 wt.% Glycine and 14.9 wt.% L-Glutamine as Glycyl-Glutamine (monohydrate), 0.7 wt.% Glycine and 1.7 wt.% Tyrosine as Glycyl-Tyrosine (dihydrate), 5.1 wt.% L-Histidine, 4.2 wt.% L-Isoleucine, 5.9 wt.% L-Leucine, 6.7 wt.% L-Lysine, preferably as L-Lysine acetate, 4.2 wt.% L-Methionine, 4.4 wt.% L-Phenylalanine, 5.1 wt.% L-Proline, 3.4 wt.% L- Serine, 4.2 wt.% L-Threonine, 1.4 wt.% L-Tryptophan, , and 5.5 wt.% L-Valine based on the total weight of the amino acids.This amino acid solution comprises 13.4 g of amino acids per 100 ml of the amino acid solution.Preferably, the osmolarity of the amino acid solution is between 450 and 1600 mOsmol / kg, e.g., between 470 and 530 mOsmol / kg, or between 960 and 1020 mOsmol / kg or between 1450 and 1550 mOsmol / kg.The amino acid solution may further comprise electrolytes.In certain embodiments, the amino acid solution further comprises Ca2+, Mg2+, Na+, K+, Cl’, sulfate, acetate, and phosphate.In preferred embodiments, the amino acid solution comprises 1-7 mmol Ca2+, 2-12 mmol Mg2+, 20-90 mmol Na+, 20-70 mmol K+, 30-80 mmol Cl’, 20- 100 mmol acetate, 10-30 mmol phosphate, and 2-12 mmol sulfate per liter of the amino acid solution.Where the amino acid solution further comprises electrolytes, the osmolarity is between 500 and 1700 mOsmol / kg, e.g., between 550 and 650 mOsmol / kg, or between 1000 and 1100 mOsmol / kg, or between 1550 and 1650 mOsmol / kg.Where the amino acid solution further comprises a pharmaceutically acceptable form of zinc, the pharmaceutically acceptable form of zinc is preferably selectedFK99239-15-PAT-WO from the group consisting of zinc acetate, zinc gluconate, zinc sulfate and zinc chloride, in different hydrate or anhydrous forms respectively. More preferably, the pharmaceutically acceptable form of zinc is zinc chloride and / or zinc sulfate, most preferably anhydrous zinc chloride and zinc sulfate heptahydrate.Preferably, where the amino acid solution further comprises a pharmaceutically acceptable form of zinc, the amino acid solution provides 1 mg to 25 mg, more preferably 2 mg to 20 mg, most preferably 3 mg to 15 mg zinc.In a particularly preferred embodiment, the amino acid solution provides 5 mg zinc in the form of 10.5 mg anhydrous zinc chloride. In this particularly preferred embodiment, the amino acid solution further provides 523 pg zinc per 100 ml of the amino acid solution corresponding to 2.3 mg zinc sulfate heptahydrate per 100 ml of the amino acid solution.Preferably, the overall zinc concentration ranges from 133 pg to 3.6 mg per 100 ml of the amino acid solution.For example, the amino acid solution provides 1.9 mg, 1.6 mg, 1.4 mg, 1.5 mg, 1.2 mg, 1.0 mg zinc per 100 ml of the amino acid solution.Where the amino acid solution comprises a pharmaceutically acceptable form of copper, the pharmaceutically acceptable form of copper comprises copper in the form of Cu(II) and is preferably selected from the group consisting of copper(II) sulfate, copper(II) gluconate, copper(II) acetate and copper(II) chloride, in different hydrate or anhydrous forms respectively. More preferably, the pharmaceutically acceptable form of copper is copper chloride, most preferably copper chloride dihydrate.Preferably, the amino acid solution provides 100 pg to 4 mg copper, more preferably, 200 pg to 2 mg copper, most preferably, 300 pg to 600 pg copper.In a particularly preferred embodiment, the amino acid solution provides 380 pg copper corresponding to 1020 pg copper chloride dihydrate.Preferably, the copper concentration ranges from 10 pg to 1.1 mg per 100 ml of the amino acid solution.FK99239-15-PAT-WOFor example, the amino acid solution provides 38.0 pg, 50.7 pg, 63.3 pg, 76.0 pg, 83.3 pg, or 100.0 pg copper per 100 ml of the amino acid solution. This may be provided, e.g., as 102.0 pg, 136.0 pg, 170.0 pg, 204.0 pg, 223.7 pg, or 268.4 pg copper chloride dihydrate per 100 ml of the amino acid solution.Where the amino acid solution further comprises a pharmaceutically acceptable form of chromium, the pharmaceutically acceptable form of chromium preferably comprises chromium in the form of Cr(III) and is preferably selected from the group consisting of chromium(III) picolinate, chromium(III) gluconate, chromium(III) sulfate and chromium(III) chloride, in different hydrate or anhydrous forms respectively. More preferably, the pharmaceutically acceptable form of chromium is chromium(III) chloride, most preferably chromium(III) chloride hexahydrate.Preferably, the amino acid solution provides 1 pg to 30 pg chromium.More preferably, the amino acid solution provides 2 pg to 20 pg chromium.Most preferably, the amino acid solution provides 5 pg to 15 pg chromium.In a particularly preferred embodiment, the amino acid solution provides 10.4 pg chromium corresponding to 53.3 pg chromic chloride hexahydrate.Preferably, the chromium concentration ranges from 0.1 pg to 7.8 pg per 100 ml of the amino acid solution.For example, the amino acid solution provides 1.0 pg, 2.0 pg, 2.2 pg, 1.7 pg, 1.3 pg or 2.6 pg chromium per 100 ml of the amino acid solution.Where the amino acid solution further comprises a pharmaceutically acceptable form of manganese, the pharmaceutically acceptable form of manganese may be selected from the group consisting of manganese(II) sulfate, manganese(II) chloride, manganese(II) gluconate and manganese chloride, in different hydrate or anhydrous forms respectively.Preferably, the pharmaceutically acceptable form of manganese is a halogenide salt, more preferably a halogenide salt comprising Mn2+ions, most preferably manganese chloride (MnCIz), e.g., manganese chloride tetrahydrate.FK99239-15-PAT-WOPreferably, where the amino acid solution further comprises a pharmaceutically acceptable form of manganese, the amino acid solution provides 10 pg to 200 pg manganese.More preferably, the amino acid solution provides 20 pg to 150 pg manganese.Most preferably, the amino acid solution provides 40 pg to 70 pg manganese.In a particularly preferred embodiment, the amino acid solution provides 55 pg manganese corresponding to 198 pg manganese chloride tetrahydrate.Preferably, the manganese concentration ranges from 1 pg to 52.7 pg per 100 ml of the amino acid solution.For example, the amino acid solution provides 14.5 pg, 12.1 pg, 11.0 pg, 9.1 pg, 7.3 pg, or 5.5 pg manganese per 100 ml of the amino acid solution.Where the amino acid solution further comprises a pharmaceutically acceptable form of molybdenum, the pharmaceutically acceptable form of molybdenum preferably comprises molybdenum as Mo(VI), more preferably the pharmaceutically acceptable form of molybdenum comprises molybdate ions, e.g., in form of an alkali metal salt, most preferably the pharmaceutically acceptable form of molybdenum is sodium molybdate. In a particularly preferred embodiment, the pharmaceutically acceptable form of molybdenum is sodium molybdate dihydrate.Preferably, the amino acid solution provides 2 pg to 50 pg molybdenum, more preferably 5 pg to 40 pg molybdenum, most preferably 10 pg to 30 pg molybdenum.In a particularly preferred embodiment, the amino acid solution provides 19.2 pg molybdenum corresponding to 48.5 pg sodium molybdate dihydrate.Preferably, the molybdenum concentration ranges from 0.2 pg to 13.2 pg per 100 ml of the amino acid solution.For example, the amino acid solution provides 5.0 pg, 4.2 pg, 3.8 pg, 3.2 pg, 2.5 pg, or 1.9 pg molybdenum per 100 ml of the amino acid solution.FK99239-15-PAT-WOWhere the amino acid solution further comprises a pharmaceutically acceptable form of iodine, the pharmaceutically acceptable form of iodine is preferably selected from the group consisting of sodium iodide and potassium iodide. More preferably, the pharmaceutically acceptable form of iodine is potassium iodide, most preferably anhydrous potassium iodide.Preferably, where the amino acid solution further comprises a pharmaceutically acceptable form of iodine, the amino acid solution provides 20 pg to 250 pg iodine, more preferably 80 pg to 200 pg iodine, most preferably 110 pg to 150 pg iodine.In a particularly preferred embodiment, the amino acid solution provides 127 pg iodine corresponding to 166 pg anhydrous potassium iodide.Preferably, the iodine concentration ranges from 2.0 pg to 65.8 pg per 100 ml of the amino acid solution.For example, the amino acid solution provides 34.2 pg, 28.5 pg, 26.0 pg, 21.6 pg, 17.3 pg, or 13.0 pg iodine per 100 ml of the amino acid solution.Where the amino acid solution further comprises a pharmaceutically acceptable form of fluorine, the pharmaceutically acceptable form of fluorine is preferably selected from the group consisting of ammonium fluoride, potassium fluoride, magnesium fluoride and sodium fluoride. More preferably, the pharmaceutically acceptable form of fluorine is sodium fluoride, most preferably anhydrous sodium fluoride.Preferably, where the amino acid solution further comprises a pharmaceutically acceptable form of fluorine, the amino acid solution provides 100 pg to 2 mg fluorine, more preferably 700 pg to 1.2 mg fluorine, most preferably 800 pg to 1.1 mg fluorine.In a particularly preferred embodiment, the amino acid solution provides 950 pg fluorine corresponding to 2.1 mg (anhydrous) sodium fluoride.Preferably, the fluorine concentration ranges from 10 pg to 526 pg pg per 100 ml of the amino acid solution.FK99239-15-PAT-WOFor example, the amino acid solution provides 205 pg, 208.3 pg, 190 pg, 158.3 pg, 126.7 pg, or 95 pg fluorine per 100 ml of the amino acid solution.In a preferred embodiment, the amino acid solution comprises 4 to 18 g of amino acids per 100 ml of the amino acid solution, and a pharmaceutically acceptable form of copper.In another preferred embodiment, the amino acid solution comprises 5 g to 15 g amino acids per 100 ml of the amino acid solution and a pharmaceutically acceptable form of copper providing 10 pg to 1.1 mg copper per 100 ml of the amino acid solution, wherein the amino acid solution optionally further comprises a pharmaceutically acceptable form of zinc providing 133 pg to 3.6 mg zinc per 100 ml of the amino acid solution and wherein, preferably, the pH of the amino acid solution is between 5.0 and 6.5.The present inventors surprisingly found that - despite the presence of a sulfur- containing amino acid in the amino acid solution - copper remained stable in the amino acid solution.Accordingly, in another preferred embodiment, the present invention relates to an amino acid solution comprising at least one of L-methionine, L-cysteine and cystine and further comprising a pharmaceutically acceptable form of copper.In a particularly preferred embodiment, the amino acid solution comprises 10- 18 wt.% L-alanine, 8-14 wt.% L-arginine, 0-2 wt.% L-Cysteine and / or L- Cystine, 7-15 wt.% Glycine, 2-6 wt.% L-Histidine, 3-7 wt.% L-Isoleucine, 5- 10 wt.% L-Leucine, 4-10 wt.% L-Lysine, 3-6 wt.% L-Methionine, 3-7 wt.% L- Phenylalanine, 5-14 wt.% L-Proline, 3-9 wt.% L-Serine, 2-7 wt.% L-Threonine, 1-3 wt.% L-Tryptophan, 0.2-2 wt.% L-Tyrosine, 4-9 wt.% L-Valine, 0-2 wt.% Taurine, 0-3 wt.% L-Aspartic acid, and 0-5 wt.% L-glutamic acid based on the total weight of the amino acids, and a pharmaceutically acceptable form of copper.In another preferred embodiment, the amino acid solution comprises 12- 17 wt.% L-alanine, 9-13 wt.% L-arginine, 0-1 wt.% L-Cysteine and / or L- Cystine, 7-12 wt.% Glycine, 3-6 wt.% L-Histidine, 4-7 wt.% L-Isoleucine, 5- 9 wt.% L-Leucine, 5-8 wt.% L-Lysine, 4-6 wt.% L-Methionine, 4-7 wt.% L- Phenylalanine, 5-12 wt.% L-Proline, 3-7 wt.% L-Serine, 4-6 wt.% L-Threonine,FK99239-15-PAT-WO1-2 wt.% L-Tryptophan, 0.2-2 wt.% L-Tyrosine, 5-8 wt.% L-Valine, 0-2 wt.% Taurine, 0-3 wt.% L-Aspartic acid, and 0-5 wt.% L-glutamic acid based on the total weight of the amino acids, and a pharmaceutically acceptable form of copper.In another particularly preferred embodiment, the amino acid solution comprises 5 g to 15 g of amino acid per 100 ml of the amino solution comprising 10-18 wt.% L-alanine, 8-14 wt.% L-arginine, 0-2 wt.% L-Cysteine and / or L- Cystine, 7-15 wt.% Glycine, 2-6 wt.% L-Histidine, 3-7 wt.% L-Isoleucine, 5- 10 wt.% L-Leucine, 4-10 wt.% L-Lysine, 3-6 wt.% L-Methionine, 3-7 wt.% L- Phenylalanine, 5-14 wt.% L-Proline, 3-9 wt.% L-Serine, 2-7 wt.% L-Threonine, 1-3 wt.% L-Tryptophan, 0.2-2 wt.% L-Tyrosine, 4-9 wt.% L-Valine, 0-2 wt.% Taurine, 0-3 wt.% L-Aspartic acid, and 0-5 wt.% L-glutamic acid based on the total weight of the amino acids, and a pharmaceutically acceptable form of copper providing 10 pg to 1.1 mg copper per 100 ml of the amino acid solution.In yet another particularly preferred embodiment, the amino acid solution comprises 5 g to 15 g amino acids per 100 ml of the amino acid solution comprising 10-18 wt.% L-alanine, 8-14 wt.% L-arginine, 0-2 wt.% L-Cysteine and / or L-Cystine, 7-15 wt.% Glycine, 2-6 wt.% L-Histidine, 3-7 wt.% L- Isoleucine, 5-10 wt.% L-Leucine, 4-10 wt.% L-Lysine, 3-6 wt.% L-Methionine, 3-7 wt.% L-Phenylalanine, 5-14 wt.% L-Proline, 3-9 wt.% L-Serine, 2-7 wt.% L-Threonine, 1-3 wt.% L-Tryptophan, 0.2-2 wt.% L-Tyrosine, 4-9 wt.% L- Valine, 0-2 wt.% Taurine, 0-3 wt.% L-Aspartic acid, and 0-5 wt.% L-glutamic acid based on the total weight of the amino acids, a pharmaceutically acceptable form of copper providing 10 pg to 1.1 mg copper per 100 ml of the amino acid solution, a pharmaceutically acceptable form of zinc providing 133 pg to 3.6 mg zinc per 100 ml of the amino acid solution, wherein the pH of the amino acid solution is between 5.0 and 6.5.The lipid emulsionThe lipid emulsion is an oil-in-water emulsion and comprises 5 to 30 wt.%, more preferably 10 to 20 wt.%, most preferably 10 wt.% or 20 wt.% of an oil phase based on the total weight of the emulsion and a pharmaceutically acceptable form of selenium.FK99239-15-PAT-WOThe lipid emulsion may further comprise a pharmaceutically acceptable form of molybdenum and / or a pharmaceutically acceptable form of fluorine and / or a pharmaceutically acceptable form of iodine.Preferably, the lipid emulsion further comprises a pharmaceutically acceptable form of fluorine and a pharmaceutically acceptable form of iodine.The trace elementsThe lipid emulsion comprises a pharmaceutically acceptable form of selenium, preferably comprising selenium as Se(IV), more preferably in form of a salt comprising selenite ions, most preferably as anhydrous sodium selenite.The lipid emulsion provides 10 pg to 150 pg, preferably 30 pg to 130 pg, most preferably 60 pg to 100 pg selenium.In a particularly preferred embodiment, the lipid emulsion provides 79 pg selenium corresponding to 173 pg anhydrous sodium selenite.Preferably, the selenium concentration ranges from 2.7 pg to 88.3 pg per 100 ml of the lipid emulsion, preferably provided as 5.9 pg to 193.4 pg anhydrous sodium selenite per 100 ml of the lipid emulsion.For example, the lipid emulsion provides 42.0 pg, 28.1 pg, 21.1 pg, 46.5 pg, 38.7 pg, or 29.5 pg selenium per 100 ml of the lipid emulsion.This may be provided, e.g., as 92.0 pg, 61.6 pg, 46.1 pg, 101.8 pg, 84.8 pg, or 64.6 pg anhydrous sodium selenite per 100 ml of the lipid emulsion.Where the lipid emulsion further comprises a pharmaceutically acceptable form of molybdenum, the pharmaceutically acceptable form of molybdenum the pharmaceutically acceptable form of molybdenum preferably comprises molybdenum as Mo(VI), more preferably the pharmaceutically acceptable form of molybdenum comprises molybdate ions, e.g., in form of an alkali metal salt, most preferably the pharmaceutically acceptable form of molybdenum is sodium molybdate. In a particularly preferred embodiment, the pharmaceutically acceptable form of molybdenum is sodium molybdate di hydrate.FK99239-15-PAT-WOPreferably, where the lipid emulsion further comprises a pharmaceutically acceptable form of molybdenum, the lipid emulsion provides 2 pg to 50 pg, more preferably, 5 pg to 40 pg, most preferably 10 pg to 30 pg molybdenum. In a particularly preferred embodiment, the lipid emulsion provides 19 pg molybdenum corresponding to 48.5 pg sodium molybdate dihydrate.Preferably, the molybdenum concentration ranges from 0.5 pg to 29.5 pg per 100 ml of the lipid emulsion.For example, the lipid emulsion provides 10.1 pg, 6.8 pg, 5.1 pg, 11.2 pg, 9.3 pg, or 7.1 pg molybdenum per 100 ml of the lipid emulsion corresponding to1.3 pg to 75.3 pg sodium molybdate dihydrate.Where the lipid emulsion further comprises a pharmaceutically acceptable salt of iodine, the pharmaceutically acceptable salt of iodine is preferably selected from the group consisting of sodium iodide and potassium iodide. More preferably, the pharmaceutically acceptable salt of iodine is potassium iodide, most preferably anhydrous potassium iodide.Preferably, where the lipid emulsion further comprises a pharmaceutically acceptable salt of iodine, the lipid emulsion provides 20 pg to 250 pg, more preferably, 80 pg to 200 pg, most preferably, 110 to 150 pg iodine.Preferably, the iodine concentration ranges from 5.3 pg to 147.1 pg per 100 ml of the lipid emulsion, preferably provided as 6.9 pg to 192.4 pg potassium iodide per 100 ml of the lipid emulsion.For example, the lipid emulsion provides 67.6 pg, 45.2 pg, 33.9 pg, 74.7 pg,62.3 pg, or 47.4 pg iodine per 100 ml of the lipid emulsion. This may be provided, e.g., as 88.3 pg, 59.1 pg, 42.3 pg, 97.7 pg, 81.4 pg, or 61.9 pg anhydrous potassium iodide per 100 ml of the lipid emulsion.Where the lipid emulsion further comprises a pharmaceutically acceptable form of fluorine, the pharmaceutically acceptable form of fluorine is preferably selected from the group consisting of ammonium fluoride, potassium fluoride, magnesium fluoride and sodium fluoride. More preferably, the pharmaceutically acceptable form of fluorine is sodium fluoride, most preferably anhydrous sodium fluoride.FK99239-15-PAT-WOPreferably, where the lipid emulsion further comprises a pharmaceutically acceptable salt of fluorine, the lipid emulsion provides 100 pg to 2 mg, more preferably, 700 pg to 1.2 mg fluorine, most preferably 800 pg to 1.1 mg fluorine.Preferably, the fluorine concentration ranges from 26.7 pg to 11.8 mg per 100 ml of the lipid emulsion.For example, the lipid emulsion provides 505.3 pg, 338.1 pg, 253.3 pg, 558.8 pg, 465.7 pg, or 354.5 pg fluorine per 100 ml of the lipid emulsion. This may be provided, e.g., as 1.1 mg, 747.3 pg, 560 pg, 1.2 mg, 1.0 mg, or 783.6 pg anhydrous sodium fluoride per 100 ml of the lipid emulsion.The oil phaseThe oil phase of the oil-in-water-emulsion according to the present invention may comprise any pharmaceutically acceptable oil suitable for parenteral administration. The oil phase may also comprise mixtures of pharmaceutically acceptable oils suitable for parenteral administration.Pharmaceutically acceptable oils suitable for parenteral administration are known in the art and may be selected from plant oils, such as e.g., olive oil, rapeseed oil, maize kernel oil, coconut oil, sunflower oil or soybean oil, animal oils, such as e.g., fish oil, fish oil extract or krill oil and microbial oils, such as e.g., algae oil, or fungal oils.Preferably, the oil phase is composed such that it comprises oleic acid (OA), linoleic acid (LA), eicosapentaenoic (EPA) acid and docosahexaenoic acid (DHA), wherein preferably 90 to 100 wt.% of these fatty acids are present in triglyceride-bound form.More preferably, the oil phase further comprises caprylic acid and capric acid, wherein preferably 90 to 100 wt.% of these fatty acids are present in triglyceride-bound form.The oil phase may further comprise palmitic acid (PA) and / or alpha-linolenic acid (ALA), wherein preferably 90 to 100 wt.% of theses fatty acids are present in triglyceride-bound form.T1FK99239-15-PAT-WOIn preferred embodiments, the oil phase comprises 14-19 wt.% caprylic acid, 10-14 wt.% capric acid, 24-29 wt.% oleic acid, 16-21 wt.% linoleic acid, 1.5- 3.5 wt.% eicosapentaenoic acid and 2-3 wt.% docosahexaenoic acid based on the total weight of the oil phase, wherein preferably 90 to 100 wt.% of the fatty acids are present in triglyceride-bound form.In this context it is to be understood that the lipid emulsion may comprise minor amounts of non-esterified fatty acids, the minor amounts being within the compendial limits. Preferably, in the context of the present invention, in the lipid emulsion according to the present invention, the total amount of non- esterified fatty acids does not exceed 2.8 g, more preferably 2.2 g, per liter of the lipid emulsion.In a particularly preferred embodiment, the oil phase comprises soybean oil, olive oil, fish oil, and medium chain triglycerides.In an even more preferred embodiment, the oil phase comprises 20 wt.% to 40 wt.%, preferably 30 wt.%., soybean oil, 20 wt.% to 40 wt.%, preferably 30 wt.%, medium-chain triglycerides, 20 wt.% to 30 wt.%, preferably 25 wt.%, olive oil and 10 wt.% to 30 wt.%, preferably 15 wt.%, fish oil based on the total weight of the oil phase.The term "fish oil" refers to "purified fish oil" and to "purified fish oil rich in omega 3 fatty acids", the latter according to the European Pharmacopoeia 6.0 comprising at least 9 % (w / w) of the omega-3-fatty acid docosahexaenoic acid (DHA) and at least 13 % (w / w) of the omega-3 fatty acid eicosapentaenoic acid (EPA) expressed as triglycerides. Fish oils suitable for parenteral administration are commercially available.In the context of the present disclosure the term "fish oil" also refers to fish oil extracts that may be further enriched or downgraded respectively in certain fatty acids. Such fish oil extracts are commercially available, e.g., from Solutex S.L.The term "medium chain triglycerides" (MCT) refers to triglycerides of fatty acids having 6 to 12 carbon atoms, including caproic acid, caprylic acid, capric acid and lauric acid. MCT suitable for parenteral administration are commercially available.FK99239-15-PAT-WOThe droplet sizeAs the lipid emulsion comprised in the compositions according to the present invention is an oil-in-water emulsion, the continuous phase is aqueous and comprises oil droplets. These oil droplets are stabilized within the aqueous phase by at least one emulsifier and optionally further additives. The size of the oil droplets depends on the qualitative and quantitative composition of the emulsion and its preparation.The oil droplets of the emulsion preferably have a mean diameter (volume based) of 130 to 450 nm, preferably 150 to 400 nm, more preferably 180 to 350 nm, when measured directly upon sterilization using, e.g., a Mastersizer 2000 or 3000 (Malvern) according to USP <729>.The PFAT5valueAccording to the USP in an oil-in-water emulsion for parenteral administration the percentage of fat residing in oil droplets larger than 5 pm in diameter (PFAT5value) must not exceed 0.05%.Where an emulsion for parenteral administration is mixed with an amino acid solution and / or a glucose solution before administration, the PFAT5value should remain below 0.05 % for at least 24 hours, preferably for at least 48 hours after the emulsion has been mixed with the amino acid solution and / or the glucose solution.The PFAT5value is measured according to one of the methods according to USP<729>.The lipid emulsion comprised in the compositions according to the present invention has a PFATs value below 0.05 %, preferably below 0.04 %, more preferably below 0.3 %. The PFAT5value remains below 0.05 %, preferably below 0.04 %, more preferably below 0.03 %, during the shelf life of the emulsion. The shelf life of the emulsion is preferably at least 1 year, more preferably at least 1.5 years, more preferably at least 2 years, when stored at 5°C to 25°C at a relative humidity of 40 to 60 %.The PFAT5value of the lipid emulsion comprised in the compositions according to the present invention remains below 0.05 % for at least 24 hours, preferably for at least 48 hours, after it has been mixed with the amino acid solution and / orFK99239-15-PAT-WO the glucose solution comprised in the composition according to the present invention.The emulsifierThe lipid emulsion comprised in the compositions according to the present invention comprises at least one pharmaceutically acceptable emulsifier. The term "emulsifier" refers to compounds which stabilize the composition by reducing the interfacial tension between the oil phase and the water phase and which typically comprise at least one hydrophobic group and at least one hydrophilic group. These emulsifiers (which may also be referred to as surfactants) are preferably used in amounts effective to provide, optionally together with further surfactants present, a stable and even distribution of the oil phase within the aqueous phase.The at least one emulsifier comprises at least one phospholipid. Within the meaning of the present disclosure the term "phospholipid" refers to naturally occurring or synthetic phospholipids that may be suitably refined. Suitable phospholipids include, but are not limited to, phospholipids derived from corn, soybean, egg or other animal origin, or mixtures thereof. Phospholipids typically comprise mixtures of diglycerides of fatty acids linked to the choline ester of phosphoric acid and can contain differing amounts of other compounds depending on the method of isolation. Typically, commercial phospholipids are a mixture of acetone-insoluble phosphatides. Preferably, the phospholipids are obtained from egg or other animal origin, or from seeds including soybean and corn, using methods well known in the art. Phospholipids obtained from soybean are referred to herein as soy phospholipids. Phospholipids obtained from egg are referred to herein as egg phospholipids.The lipid emulsion comprised in the compositions according to the present invention comprises phospholipids as emulsifier, more preferably the phospholipids are selected from the group consisting of egg phospholipids, soy phospholipids, and mixtures thereof, most preferably the phospholipids are egg phospholipids.Such emulsifiers are commercially available.FK99239-15-PAT-WOPreferably, the emulsifier is used in an amount of 0.5 to 5 % (w / v), more preferably 0.5 to 3 %(w / v), most preferably 1.0 to 2.0 %(w / v) based on the total volume of the emulsion.The co-surfactantThe lipid emulsion comprised in the compositions according to the present invention may further comprise a pharmaceutically acceptable co-surfactant.A co-surfactant is an amphiphilic molecule, i.e., a molecule that contains both hydrophilic and lipophilic groups. Usually, a co-surfactant substantially accumulates with the emulsifier at the interfacial layer. The hydrophile-lipophile balance (HLB) number is used as a measure of the ratio of hydrophilic and lipophilic groups present in a surfactant or co-surfactant, respectively. Preferably, a co-surfactant with a very low HLB value (thus with a relatively high affinity to oil) is used together with an emulsifier with a high HLB to modify the overall HLB of the system. Unlike the emulsifier, the co-surfactant may not be capable of forming self-associated structures, like micelles, on its own. Several kinds of molecules including nonionic emulsifiers, alcohols, amines, and acids, can function as co-surfactants in a given system. The co-surfactant is usually used in a lower amount than that of the emulsifier. Apart from modifying the overall HLB value of the system, the co-surfactant has the effect of further reducing the interfacial tension and increasing the fluidity of the interface. Cosurfactants may also adjust the curvature of the interfacial film by partitioning between the tails of the emulsifier chains, allowing greater penetration of the oil between the emulsifier tails.Preferably, the co-surfactant is a free long chain fatty acid or a salt thereof, preferably a free unsaturated fatty acid or a salt thereof, preferably an omega- 9 fatty acid or a salt thereof, more preferably a monounsaturated omega-9 fatty acid or a salt thereof, more preferably oleic acid or sodium oleate.The total amount of the co-surfactant is preferably in the range of from 0.01 % to 1 %, more preferably in the range of from 0.02 % to 0.5 %, more preferably in the range of from 0.02 % to 0.2 % based on the total volume of the emulsion (w / v).FK99239-15-PAT-WOThe tonicity agentThe lipid emulsion comprised in the compositions according to the present invention may comprise at least one pharmaceutically acceptable tonicity agent. Tonicity agents are used to confer tonicity. Suitable tonicity agents may be selected from the group consisting of sodium chloride, mannitol, lactose, dextrose, sorbitol, glycerol, and mixtures thereof. Preferably, the tonicity agent is glycerol.Preferably, the total amount of tonicity agents is in the range of 0.1 to 10 %, more preferably from 1 % to 5 %, more preferably from 1 % to 4 %, more preferably 1 % to 3 %, more preferably from 1.5 % to 2.8 %, and even more preferably from 2.0 % to 2.5 % based on the total volume of the emulsion (w / v).In case the tonicity agent is glycerol the preferred amount is 2.0 % to 2.8 %, the most preferred amount is 2.1 % to 2.6 % based on the total volume of the emulsion (w / v).Preferably, the lipid emulsion has an osmolality in the range of 200 to 400 mOsmol / kg, more preferably between 250 and 350 mOsmol / kg, most preferably between 250 and 300 mOsmol / kg.The antioxidantThe lipid emulsion comprised in the compositions according to the present invention may comprise at least one pharmaceutically acceptable antioxidant.An antioxidant may be any pharmaceutically acceptable compound having antioxidant activity, for example, the antioxidant may be selected from the group consisting of sodium metasulfite, sodium bisulfite, sodium sulfite, sodium thiosulfate, thioglycerol, thiosorbitol, thioglycolic acid, cysteine hydrochloride, n-acetyl-cysteine, citric acid, alpha-tocopherol, beta-tocopherol, gammatocopherol, delta-tocopherol, tocotrienols, soluble forms of vitamin E, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), t-butylhydroquinone (TBHQ), monothioglycerol, propyl gallate, histidine, enzymes such as superoxide dismutase, catalase, selenium glutathione peroxidase, phospholipid hydroperoxide and glutathione peroxidase, Coenzyme Q10, carotenoids,FK99239-15-PAT-WO quinones, bioflavonoids, polyphenols, bilirubin, ascorbic acid, isoascorbic acid, uric acid, metal-binding proteins, ascorbic acid palmitate, and mixtures thereof.The at least one antioxidant is particularly selected from the group consisting of alpha tocopherol, beta tocopherol, gamma tocopherol, delta tocopherol, tocotrienols, ascorbic acid, and mixtures of two or more thereof. Preferably, the antioxidant is alpha tocopherol or mixture of alpha-, beta- and gammatocopherol.If present, the total amount of agents with antioxidant activity is preferably in the range of from 0.01 % to 0.05 %, more preferably from 0.01 % to 0.04 %, more preferably from 0.01 % to 0.03 %, and even more preferably from 0.015 % to 0.025 % based on the total volume of the emulsion (w / v).The pH adjusting agentThe pH of the lipid emulsion comprised in the compositions according to the present invention may be adjusted by adding solutions of conventionally known acids or bases such as HCI and NaOH or by using buffers, such as phosphate buffers.The final pH of the emulsion is preferably in the range of 7.0 to 10.0, more preferably 7.5 to 9.5, most preferably 7.5 to 9.0.Preferably, the pH of the oil-in-water emulsions manufactured according to the process of the present invention is adjusted using a solution of NaOH.The preservativeThe lipid emulsion comprised in the compositions according to the present invention may further comprise a pharmaceutically acceptable preservative.Suitable preservatives are 4-hydroxybenzoic acid as well as salts and esters thereof, sorbic acid as well as salts and derivatives thereof, thiomersal, chlorbutanol, chlorhexidine and salts thereof, phenylmercury salts, p- chlorocresol, ethylenediamine-tetraacetic acid and salts thereof, phenoxyethanol or mixtures thereof.Typically, the preservative is used in concentrations between 0.001 and 2.0 wt.% based on the total weight of the emulsion.FK99239-15-PAT-WOPreferably, the preservative is ethylenediaminetetraacetic acid or a pharmaceutically acceptable salt thereof.Where the preservative is ethylenediaminetetraacetic acid or a pharmaceutically acceptable salt thereof, it is preferably used in a concentration of 0.05 to 0.8 wt.%, preferably 0.1 to 0.7 wt.%, based on the total weight of the emulsion.Preparation of the lipid emulsionThe lipid emulsion is manufactured by a process comprising the following steps:(a) providing an oil phase comprising 14-19 wt.% caprylic acid, 10-14 wt.% capric acid, 24-29 wt.% oleic acid, 16-21 wt.% linoleic acid, 1.5-3.5 wt.% eicosapentaenoic acid and 2-3 wt.% docosahexaenoic acid based on the total weight of the lipids, wherein the fatty acids are present in triglyceride-bound form,(b) providing an aqueous phase 1 comprising water,(c) obtaining a pre-emulsion by mixing the oil phase provided in step a) with the aqueous phase 1 provided in step b),(d) obtaining a first emulsion by homogenizing the pre-emulsion obtained in step c),(e) providing an aqueous phase 2 comprising water,(f) obtaining the oil-in-water emulsion by mixing the first emulsion obtained in step d) with the aqueous phase 2 provided in step e) and(g) sterilizing the oil-in-water emulsion obtained in step f) and filling it into a suitable container either before or after sterilization.Step a - providing the oil phaseStep a) is preferably carried out by mixing the oil or oils and optionally a pharmaceutically acceptable antioxidant and / or a pharmaceutically acceptable co-surfactant. This step is preferably carried out by mixing, e.g., by means ofFK99239-15-PAT-WO an Ultra-Turrax, e.g., at 5000 rpm, e.g., for 5 minutes, at a temperature of 55 to 85 °C, e.g., at 60 to 70 °C, until a homogeneous and clear phase is obtained.It is to be understood that the at least one pharmaceutically acceptable emulsifier may be added either in step a) or in step b).Preferably, where the emulsifier is added in step a) the emulsifier is added after the oil phase has been heated to 55 to 85 °C.Step b - providing the aqueous phase 1Step b) is preferably carried out by providing water for injection and optionally adding a pharmaceutically acceptable tonicity agent and / or a pharmaceutically acceptable co-surfactant and / or a pharmaceutically acceptable preservative and / or the pharmaceutically acceptable form of selenium and / or a pharmaceutically acceptable form of iodine, and / or a pharmaceutically acceptable form of fluorine and / or a pharmaceutically acceptable form of molybdenum.Optionally, the pH of the aqueous phase 1 is adjusted to 8.5-10.0, preferably to 9.0 to 10.0.The aqueous phase is then heated to a temperature of 55 to 85 °C, e.g., to 60 to 70 °C.It is to be understood that the at least one pharmaceutically acceptable emulsifier may be added either in step a) or in step b).Preferably, where the emulsifier is added in step b) the emulsifier is added after the aqueous phase has been heated to 55 to 85 °C.It is to be understood that the pharmaceutically acceptable form of selenium and / or a pharmaceutically acceptable form of iodine, and / or a pharmaceutically acceptable form of fluorine and / or a pharmaceutically acceptable form of molybdenum may be added in step b), e) or f) and that this may be done either by adding these trace elements as solids and dissolving them in the water phase 1 (step b) or in the water phase 2 (step e) or in the lipid emulsion (step f) or by providing them in form of pre-formed stock solutions.FK99239-15-PAT-WOStep c - obtaining the pre-emulsionIn step c) the oil phase provided in step a) is mixed with the aqueous phase 1 provided in step b) thereby forming a pre-emulsion. The mixing may be carried out by any method known to those skilled in the art, e.g., by means of an Ultra- Turrax, e.g., for 5 to 15 minutes, e.g., for 10 to 12 minutes at e.g., 5000 to 15000 rpm, e.g., at 10000 rpm.Preferably, the oil phase is added to the aqueous phase or vice-versa at a temperature in the range of from 55 to 85 °C, e.g., at a temperature between 60 and 70 °C.Optionally, the pH of the pre-emulsion may be adjusted to a pH in the range of from 8.5 to 10.0, preferably to pH from 9.0 to 10.0.Optionally, water for injection is added to compensate for the potential loss of water during processing the pre-emulsion.Optionally, the pharmaceutically acceptable form of selenium and / or a pharmaceutically acceptable form of iodine, and / or a pharmaceutically acceptable form of fluorine and / or a pharmaceutically acceptable form of molybdenum may be added in this step.The concentration of the oil phase in the pre-emulsion obtained in step c) and in the first emulsion obtained n step d) is higher than the concentration of the oil phase in the emulsion obtained in step f). This is because in step f) the first emulsion obtained in step d) is diluted with the aqueous phase 2 provided in step e).Preferably, the concentration of the oil phase in steps c) and d) is at least 130% of the concentration of the oil phase in the emulsion obtained in step f), e.g., 130 % to 330 % of the concentration of the oil phase in the emulsion obtained in step f).More preferably, the concentration of the oil phase in steps c) and d) is at least 150 % of the concentration of the oil phase in the emulsion obtained in step f), e.g., 150 % to 330 % of the concentration of the oil phase in the emulsion obtained in step f).FK99239-15-PAT-WOMost preferably, the concentration of the oil phase in steps c) and d) is at least 180 % of the concentration of the oil phase in the emulsion obtained in step f), e.g., 180 % to 330 %, 180 % to 300 % or 180 % to 250 % of the concentration of the oil phase in the emulsion obtained in step f).In a particularly preferred embodiment, the concentration of the oil phase in steps c) and d) is 200 % of the concentration of the oil phase in the emulsion obtained in step f).Step d - obtaining the first emulsionIn step d) the pre-emulsion obtained in step c) is homogenized, e.g., by means of a high-pressure homogenizer or a counter-jet disperser, preferably at a temperature of 40 to 80°C, more preferably at a temperature of 50 to 75 °C, most preferably at a temperature of 60 to 70 °C.Optionally, in step d) the pH is adjusted to values between 8.5 and 10.0, preferably to values between 9.0 and 10.0.Step e - providing the aqueous phase 2Step e) is preferably carried out by providing water for injection and optionally adding a pharmaceutically acceptable tonicity agent and / or a pharmaceutically acceptable co-surfactant and / or a pharmaceutically acceptable preservative and / or the pharmaceutically acceptable form of selenium and / or a pharmaceutically acceptable form of iodine, and / or a pharmaceutically acceptable form of fluorine and / or a pharmaceutically acceptable form of molybdenum.Optionally, the pH of the aqueous phase 2 is adjusted to 8.5 to 10.0, preferably to 9.0 to 10.0.Step f - obtaining the emulsionIn step f) the first emulsion obtained in step d) is mixed with the appropriate amount of aqueous phase 2 provided in step e) to obtain the oil-in-water emulsion with desired concentration of oil phase being 20 to 22 wt.% based on the total weight of the emulsion.Preferably, the first emulsion obtained in step d) is cooled to 20 to 40°C before it is mixed with the water phase 2.FK99239-15-PAT-WOOptionally, the pH of the emulsion is adjusted to 8.5 to 10.0, preferably to 9.0 to 10.0.Optionally, the pharmaceutically acceptable form of selenium and / or a pharmaceutically acceptable form of iodine, and / or a pharmaceutically acceptable form of fluorine and / or a pharmaceutically acceptable form of molybdenum may be added in this step.Step g - sterilizing the emulsionIn step g) the oil-in-water emulsion obtained in step f) is further sterilized to ensure its suitability for parenteral administration.The sterilization may be carried out by any suitable method known to those skilled in the art.Preferably, the sterilization is carried out by autoclaving, preferably at a temperature in the range of from 119 to 122 °C, more preferably at a temperature around 121 °C, preferably for 1 minute to 30 minutes, preferably for 10 to 15 minutes.In a particularly preferred embodiment, the present invention relates to a lipid emulsion comprising 10 to 20 wt.% of an oil phase comprising the fatty acids OA, LA, EPA and DHA and a pharmaceutically acceptable form of selenium providing 2.7 pg to 88.3 pg of selenium per 100 ml of the lipid emulsion, wherein the oil phase of the lipid emulsion comprises 90 to 100 % of the fatty acids OA, LA, EPA and DHA in triglyceride bound form and wherein, preferably, the pharmaceutically acceptable form of selenium comprises selenium in form of selenium(IV), more preferably as a salt comprising selenite ions.The dosageWhere the amino acid solution comprises a pharmaceutically acceptable form of copper, the amino acid solution is dosed such that it provides 100 pg to 4 mg copper, more preferably 200 pg to 2 mg copper, most preferably, 300 pg to 600 pg copper, per day.Where the amino acid solution comprises a pharmaceutically acceptable form of copper and a pharmaceutically acceptable form of zinc, the amino acid solution is dosed such that it provides 100 pg to 4 mg copper and 1 mg to 25FK99239-15-PAT-WO mg zinc, more preferably 200 pg to 2 mg copper and 2 mg to 20 mg zinc, most preferably 300 pg to 600 pg copper and 3 mg to 15 mg zinc, per day.Where the amino acid solution comprises a pharmaceutically acceptable form of copper, a pharmaceutically acceptable form of zinc, a pharmaceutically acceptable form of iodine and a pharmaceutically acceptable form of fluorine, the amino acid solution is dosed such that it provides 100 pg to 4 mg copper, 1 mg to 25 mg zinc, 20 pg to 250 pg iodine and 100 pg to 2 mg fluorine, preferably 200 pg to 2 mg copper, 2 mg to 20 mg zinc, 80 pg to 200 pg iodine and 700 pg to 1.2 mg fluorine, more preferably 300 pg to 600 pg copper, 3 mg to 15 mg zinc, 110 pg to 150 pg iodine and 800 pg to 1.1 mg fluorine, most preferably 380 pg copper, 7.7 mg zinc, 127 pg iodine and 950 pg fluorine, per day.Preferably, the glucose solution is dosed such that it provides 100 pg to 10 mg iron, more preferably 300 pg to 5 mg iron, most preferably 400 pg to 2 mg iron, per day.Where the glucose solution further comprises a pharmaceutically acceptable form of molybdenum, a pharmaceutically acceptable form of chromium, and a pharmaceutically acceptable form of manganese, the glucose solution is dosed such that it provides 100 pg to 10 mg iron 2 pg to 50 pg molybdenum, 1 pg to 30 pg chromium, and 10 pg to 200 pg manganese, preferably 300 pg to 5 mg iron, 5 pg to 40 pg molybdenum, 2 pg to 20 pg chromium, and 20 pg to 150 pg manganese, more preferably 400 pg to 2 mg iron, 10 pg to 30 pg molybdenum, 5 pg to 15 pg pg chromium, and 40 pg to 70 pg manganese, most preferably 1.1 mg iron, 19 pg molybdenum, 10 pg chromium, and 55 pg manganese, per day.Preferably, the lipid emulsion is dosed such that it provides 10 pg to 150 pg selenium, more preferably 30 pg to 130 pg selenium, most preferably 60 pg to 100 pg selenium, per day.In particularly preferred embodiment, the lipid emulsion is dosed such that, per day, 79 pg selenium, are provided.Preferably, the amino acid solution, the glucose solution and the lipid emulsion are dosed such that, per day, 100 pg to 10 mg iron, 100 pg to 4 mg copper, 10FK99239-15-PAT-WO pg to 150 pg selenium, 2 pg to 50 pg molybdenum, 1 pg to 30 pg chromium, 10 pg to 200 pg manganese, 1 mg to 25 mg zinc, 20 pg to 250 pg iodine and optionally 100 pg to 2 mg fluorine, are provided.More preferably, the amino acid solution, the glucose solution and the lipid emulsion are dosed such that, per day, 300 pg to 5 mg iron, 200 pg to 2 mg copper, 30 pg to 130 pg selenium, 5 pg to 40 pg molybdenum, 2 pg to 20 pg chromium, 20 pg to 150 pg manganese, 2 mg to 20 mg zinc, 80 pg to 200 pg iodine and optionally 700 pg to 1.2 mg fluorine are provided.Most preferably, the amino acid solution, the glucose solution and the lipid emulsion are dosed such that, per day, 400 pg to 2 mg iron, 300 pg to 600 pg copper, 60 pg to 100 pg selenium, 10 pg to 30 pg molybdenum, 5 pg to 15 pg pg chromium, 40 pg to 70 pg manganese, 3 mg to 15 mg zinc, 110 pg to 150 pg iodine and optionally 800 pg to 1.1 mg fluorine are provided.In particularly preferred embodiments, the amino acid solution, the glucose solution, and the lipid emulsion are dosed such that, per day, 1.1 mg iron, 380 pg copper, 79 pg selenium, 19 pg molybdenum, 10 pg chromium, 55 pg manganese, 7.7 mg zinc, 127 pg iodine and optionally 950 pg fluorine are provided.The bagThe glucose solution, the amino acid solution and the lipid emulsion according to the present invention are comprised in bags, preferably wherein a first chamber comprises 200 ml to 1200 ml, more preferably 298 ml to 1036 ml of a glucose solution according to the present invention, preferably wherein a second chamber comprises 300 ml to 1100 ml, more preferably 380 ml to 1000 ml of an amino acid solution according to the present invention, and preferably wherein a third chamber comprises 150 ml to 400 ml, more preferably 170 ml to 375 ml of a lipid emulsion according to the present invention.In a particularly preferred embodiment, the bag in a first chamber comprises 298 ml of a glucose solution according to the present invention, in a second chamber comprises 500 ml of an amino acid solution according to the present invention, and in a third chamber comprises 188 ml of a lipid emulsion according to the present invention.FK99239-15-PAT-WOIn another particularly preferred embodiment, the bag in a first chamber comprises 446 ml of a glucose solution according to the present invention, in a second chamber comprises 750 ml of an amino acid solution according to the present invention and in a third chamber comprises 281 ml of a lipid emulsion according to the present invention.In another particularly preferred embodiment, the bag in a first chamber comprises 595 ml of a glucose solution according to the present invention, in a second chamber comprises 1000 ml of an amino acid solution according to the present invention and in a third chamber comprises 375 ml of a lipid emulsion according to the present invention.In another particularly preferred embodiment, the bag in a first chamber comprises 656 ml of a glucose solution according to the present invention, in a second chamber comprises 380 ml of an amino acid solution according to the present invention and in a third chamber comprises 170 ml of a lipid emulsion according to the present invention.In another particularly preferred embodiment, the bag in a first chamber comprises 788 ml of a glucose solution according to the present invention, in a second chamber comprises 456 ml of an amino acid solution according to the present invention and in a third chamber comprises 204 ml of a lipid emulsion according to the present invention.In another particularly preferred embodiment, the bag in a first chamber comprises 1036 ml of a glucose solution according to the present invention, in a second chamber comprises 600 ml of an amino acid solution according to the present invention and in a third chamber comprises 268 ml of a lipid emulsion according to the present invention.The bags may be made of any suitable material substantially inert against the ingredients of the composition according to the invention, preferably even upon heat treatment, more preferably sterilization. Preferably, the bag material is plastic. In other words, the walls of the bag are made of a plastic material, e.g., a thermoplastic elastomer. The plastic material may preferably comprise one or more polymers and optionally further additives. In a further preferred embodiment, the container is transparent or tinted. In particular, a tintedFK99239-15-PAT-WO plastic bag, preferably a plastic bag with a tinted outer layer, advantageously reduces the amount of UV radiation that may reach the contents of the container. However, even a transparent container may comprise means to block and / or absorb UV radiation. In a further preferred embodiment, the plastic container material comprises 3 layers. In other words, the walls of the container comprise 3 layers of plastic material. The first layer is also referred to as the inner layer. The second layer is also referred to as the middle layer, and the third layer is also referred to as the outer layer. Preferably, the first or inner layer is in direct contact with the contents of the plastic bag. The second layer and the third layer are preferably not in direct contact with the contents of the plastic bag. Preferably, the middle layer is thicker than the inner layer and the outer layer, providing for requisite stability. In addition, it was found that the increased thickness of the middle layer provides for an enhanced protection against oxygen permeation from the outside to the inside of the bag. Preferably, the inner, the middle and the outer layer all comprise a thermoplastic elastomer (TPE), wherein preferably, the content in TPE is highest in the middle layer, warranting the required flexibility. The inner layer, in addition to the TPE, preferably comprises a polyolefine co-polymer. Preferably, the polyolefine copolymer comprises a polypropylene-polyethylene co-polymer. Preferably, the TPE is a styrenic block co-polymer, more preferably Styrene-Ethylen- ButylenStyrene (SEBS). The inner layer preferably comprises 70 to 90 wt. % of the polyolefine co-polymer and 10 to 30 wt. % of the TPE, more preferably 80 wt. % of the polyolefine co-polymer and 20 wt. % of the TPE. Preferably, the inner layer has a thickness of 10 to 90 pm, more preferably 10 to 70 pm, more preferably 10 to 50 pm, more preferably 20 to 40 pm. Most preferably, the inner layer has a thickness of 30 pm. The middle layer, in addition to the TPE, preferably comprises a polyolefine co-polymer. Preferably, the polyolefine copolymer comprises a polypropylene-polyethylene co-polymer. Preferably, the TPE comprises a styrenic block co-polymer, more preferably 2 styrenic block co-polymers, most preferably Styrene-Ethylen-Butylen-Styrene (SEBS) and Styrene-IsoprenStyrene (SIS). The middle layer preferably comprises 40 to 70 wt. %, more preferably 50 to 60 wt. % of the polyolefine co-polymer and 30 to 60 wt. %, more preferably 40 to 50 wt. % of the TPE. Most preferably the middle layer comprises 55 wt. % of the polyolefine co-polymer and 45 wt. % of the TPE. Preferably, the middle layer has a thickness of 30 to 200 pm, moreFK99239-15-PAT-WO preferably 50 to 190, even more preferably 70 to 180 pm, even more preferably 100 to 150 pm and most preferably 125 pm. The outer layer, in addition to the TPE preferably comprises a polyolefine. Preferably, the polyolefine comprises polypropylene, preferably an isotactic polypropylene. Even more preferably the polypropylene has UV absorption maxima at a wavelength of 290-300 nm, 330 nm, and 370 nm. This allows for an improved protection of the contents of the bag.Where the bag has more than one chamber, the chambers of the bag are preferably separated by seals, more preferably by leak tight and / or peelable seals. The seals can be made by any means that allows for a separation of the contents of the container in their respective chambers during heat treatment, storing and / or transport of the container while allowing a rupturing (and thus mixing of the contents of the container) when the container is to be used as intended. Preferably, the seals are formed by fusion, preferably by welding, of regions of the opposing inner layers of the container. Such regions preferably have the shape of lines. Peelable seals preferably comprise rupture zones that allow for an easier rupturing of the seals at predetermined positions. The term leak tight seal is meant to refer to a seal which is suitable to reliably separate at least two chambers of a multi-chamber container during production, heat treatment and / or transport of the container. While the leak tight seals may be opened by any suitable means the term peelable seal is meant to refer to a leak tight seal which can be opened, preferably by application of external pressure to the container. More preferably the amount of pressure needed to open the peelable seal is low enough to easily open the seal by manually applying an external force to the container, most preferably by means of rolling up the container. The peelable seal furthermore preferably comprises a rupture zone which can also be described as a predetermined breaking point. Such rupture zones can, e.g., be generated by a stronger curvature of the seal and allow for a reliable opening of the seal upon application of external pressure to the container. Preferably, the container comprises at least two leak tight seals, more preferably three leak tight seals to separate a first, second, and third chamber. In one preferred embodiment a first and a second chamber are separated by a first leak tight seal and a second and third chamber are separated by a second leak tight seal. In a further and more preferred embodiment a first and second chamber are separated by a first leak tight seal,FK99239-15-PAT-WO a second and third chamber are separated by a second leak tight seal and a first and third chamber are separated by a third leak tight seal. Even more preferred, a first and / or , second and / or third leak tight seal is / are a peelable seals. Preferably, the container according to the invention further comprises a suspension means, preferably in the form of an opening. The suspension means allows to hang the container and to withdraw the contents more easily and completely. Most preferably, the suspension means allows for the bedside administration of the contents of the container to a patient. The suspension means is therefore preferably located at the top of the container, more preferably at the top short edge of an essentially rectangular shaped container or bag. In a further preferred embodiment, the peelable seals of the container rupture upon application of external pressure to the container. The external pressure can be provided by any suitable means, e.g., by squeezing of the bag. Even more preferably the peelable seals of the container rupture upon rolling up the container. If the container is in the form of a bag with an essentially rectangular shape the rolling up is preferably started from a short edge of the container into the direction of the opposing second short edge of the container. Even more preferably the rolling up is started from the top of the container. In a further preferred embodiment, the peelable seals of the container more preferably rupture consecutively, most preferably if the external pressure is applied by a rolling up of the container. This allows for a sequential mixing of the components comprised by the container. The bag may optionally further be comprised in an overpouch. The overpouch may comprise several layers comprised of different materials. Preferably, the overpouch is transparent and / or impermeable to oxygen.Each chamber comprises one port which serves as a port for filling the corresponding chamber of the bag.The ports are welded into a weld seam of the bag. For this purpose, each port comprises a corresponding weld-in section. In one embodiment the weld-in section has an elongated, in particular, ship-shaped, design. Preferably, the ports are welded into a transverse weld seam of the bag such that the ports are positioned on the bag side which is opposite to the bag side where the suspension means are located.FK99239-15-PAT-WOThe weld-in section merges into a flexible, clampable area. During bag filling process, this area can be clamped off and therefore provides a valve function. After completion of the bag filling, the clampable area can be pressed shut until an upper part is positioned onto the port (as a lower part) to close the inlet to each chamber.The upper part is fixed to the lower part by a snap-on connection. Each upper part carries a sealing element for sealing the port and therefore the inlet to the chamber. The sealing element is positioned between the lower part and the upper part and fixed by clamping between the lower part and the upper part.One first port, preferably a lateral outer port, provides the lower part of a blind port. The blind port is used to fill the chamber only, but not to add or remove any liquid. Therefore, the blind port is closed with a cap as an upper part only.One second port, preferably the middle port, provides the lower part of a connector serving as an injection port. The connector further comprises the upper part. The upper part is provided with a break-off part, for instance provided as a cap. In one embodiment the break-off part contains an arrow pointing to the container and thereby indicating the connector as an injection port. After removal of the break-off part the upper part serves as a connector part for connecting an injection device. The injection of an active ingredient, for example, can take place by means of a needle syringe. In one embodiment the lower part additionally comprises an internal tube for guiding the needle insertion. This reduces the risk of needle piercing the wall of the lower part of the injection port.One third port, preferably the opposite lateral outer port, provides the lower part of a connector serving as an infusion port. The connector further comprises the upper part. The upper part is provided with a break-off part, for instance provided as a cap. In one embodiment the break-off part contains an arrow pointing away from the container and thereby indicating the connector as an infusion port. After removal of the break-off part the upper part serves as a connector part for connecting an infusion device. The infusion respectively removal of liquid is generally carried out by inserting a spike as an infusion device. The spike is connected to an administration set to transfer the liquid from the bag into the patient.FK99239-15-PAT-WOThe sealing elements of the injection port and of the infusion are preferably of different design. The sealing element of the injection port is a resealable sealing element adapted to be pierced by a needle in a fluid-tight fashion and adapted to reseal after the removal of the needle. The sealing element of the infusion port is a resealable sealing element adapted to be pierced by a spike in a fluid- tight fashion and adapted to reseal after the removal of the spike.In a preferred embodiment, the present invention relates to a plastic bag comprising, in separate chambers, a glucose solution comprising 10 to 45 g glucose per 100 ml of the glucose solution and a pharmaceutically acceptable form of iron, an amino acid solution comprising 4 to 18 g amino acids per 100 ml of the amino acid solution and a pharmaceutically acceptable form of copper, and an oil-in-water emulsion comprising 10 wt.% to 20 wt.% of an oil-phase based on the total weight of the emulsion and a pharmaceutically acceptable form of selenium.FK99239-15-PAT-WOEmbodiments1) Oil-in-water emulsion for parenteral administration comprising 5 wt.% to 30 wt.%, preferably 10 wt.% to 20 wt.%, more preferably 10 wt.% or 20 wt.%, most preferably 20 wt.%, of an oil phase based on the total weight of the emulsion and a pharmaceutically acceptable form of selenium.2) Oil-in-water emulsion according to embodiment 1, wherein the oil phase is composed such that it comprises oleic acid (OA), linoleic acid (LA), eicosapentaenoic (EPA) acid and docosahexaenoic acid (DHA), wherein preferably 90 to 100 wt.% of these fatty acids are present in triglyceride- bound form.3) Oil-in-water emulsion according to any of the preceding embodiments, wherein the oil phase further comprises caprylic acid and capric acid, wherein preferably 90 to 100 wt.% of these fatty acids are present in triglyceride-bound form.4) Oil-in-water emulsion according to any of the preceding embodiments, wherein the oil phase further comprises palmitic acid (PA) and / or alphalinolenic acid (AI_A), wherein preferably 90 to 100 wt.% of these fatty acids are present in triglyceride-bound form.5) Oil-in-water emulsion according to any of the preceding embodiments, wherein the oil phase comprises 14-19 wt.% caprylic acid, 10-14 wt.% capric acid, 24-29 wt.% oleic acid, 16-21 wt.% linoleic acid, 1.5- 3.5 wt.% eicosapentaenoic acid and 2-3 wt.% docosahexaenoic acid based on the total weight of the oil phase, wherein preferably 90 to 100 wt.% of the fatty acids are present in triglyceride-bound form.6) Oil-in-water emulsion according to any of the preceding embodiments, wherein the oil phase comprises 20 wt.% to 40 wt.% soybean oil, 20 wt.% to 40 wt.% medium-chain triglycerides, 20 wt.% to 30 wt.% olive oil and 10 wt.% to 30 wt.% fish oil based on the total weight of the oil phase.7) Oil-in-water emulsion according to any of the preceding embodiments, wherein the pharmaceutically acceptable form of selenium comprises selenium as Se(IV), preferably in form of a salt comprising selenite ions, more preferably as sodium selenite, most preferably as anhydrous sodium selenite.FK99239-15-PAT-WO8) Oil-in-water emulsion according to any of the preceding embodiments, wherein the selenium concentration ranges from 2.7 pg to 88.3 pg per 100 ml of the lipid emulsion, preferably provided as 5.9 pg to 193.4 pg anhydrous sodium selenite per 100 ml of the lipid emulsion.9) Oil-in-water emulsion according to any of the preceding embodiments further comprising a pharmaceutically acceptable form of iodine, preferably selected from the group consisting of sodium iodide and potassium iodide, more preferably potassium iodide, most preferably anhydrous potassium iodide.10) Oil-in-water emulsion according to embodiment 9, wherein the iodine concentration ranges from 5.3 pg to 147.1 pg per 100 ml of the lipid emulsion, preferably provided as 6.9 pg to 192.4 pg potassium iodide per 100 ml of the lipid emulsion.11) Oil-in-water emulsion according to any of the preceding embodiments, wherein the oil-in-water emulsion has a pH of 7.0 to 10.0, preferably 7.5 to 9.5, more preferably 7.5 to 9.0.12) Container, preferably a plastic bag, comprising in separate chambers an oil-in-water emulsion according to any of embodiments 1 to 11 and a glucose solution for parenteral administration comprising 10 g to 45 g glucose per 100 ml of the glucose solution.13) Container according to embodiment 12, further comprising, in a separate chamber, an amino acid solution for parenteral administration comprising 4 g to 18 g amino acids per 100 ml of the amino acid solution.14) Container according to embodiment 12 or 13, wherein the glucose solution further comprises a pharmaceutically acceptable form of iron.15) Container according to embodiment 13 or 14, wherein the amino acid solution further comprises a pharmaceutically acceptable form of copper.16) Container according to any of embodiments 12 to 15 comprising the trace elements selenium, copper, zinc, iron, manganese, molybdenum, chromium and iodine, in pharmaceutically acceptable form.17) Container according to any of embodiments 14 to 16, wherein the pharmaceutically acceptable form of iron comprises iron in the form of iron(III), preferably wherein the pharmaceutically acceptable form ofFK99239-15-PAT-WO iron is selected from the group consisting of iron(III) sulfate, iron(III) oxide, sodium iron(III) gluconate, iron (III) citrate, ammonium iron(III) citrate, iron(III) oxide-hydroxide, iron (III) fumarate, ammonium iron (III) sulfate, iron(III) sorbitol citrate, iron(III) hydroxide saccharose, iron(III) carboxymaltose and iron(III) chloride, more preferably wherein the pharmaceutically acceptable form of iron is iron(III) chloride, most preferably iron(III) chloride hexahydrate.18) Container according to any of embodiments 15 to 17, wherein the pharmaceutically acceptable form of copper comprises copper in the form of Cu(II), preferably wherein the pharmaceutically acceptable form of copper is selected from the group consisting of copper(II) sulfate, copper(II) gluconate, copper(II) acetate and copper(II) chloride, more preferably wherein the pharmaceutically acceptable form of copper is copper chloride, most preferably copper chloride dihydrate.19) Container according to any of embodiments 16 to 18, wherein the pharmaceutically acceptable form of zinc, preferably selected from the group consisting of zinc acetate, zinc gluconate, zinc sulfate and zinc chloride, more preferably zinc chloride, most preferably anhydrous zinc chloride, is comprised in the amino acid solution.20) Container according to any of embodiments 16 to 19, wherein the pharmaceutically acceptable form of manganese, preferably a halogenide salt of manganese, more preferably a halogenide salt comprising Mn2+ions, most preferably manganese chloride (MnCI2), is comprised in the glucose solution.21) Container according to any of embodiments 16 to 20, wherein the pharmaceutically acceptable form of molybdenum, preferably comprising molybdenum as Mo(VI), more preferably as molybdate ions in form of an alkali metal salt, most preferably as sodium molybdate, is comprised in the glucose solution.22) Container according to any of embodiments 16 to 21, wherein the pharmaceutically acceptable form of chromium comprises chromium in the form of chromium(III), preferably wherein the pharmaceutically acceptable form of chromium is selected from the group consisting of chromium(III) picolinate, chromium(III) gluconate, chromium(III) sulfate and chromium(III) chloride, more preferably wherein theFK99239-15-PAT-WO pharmaceutically acceptable form of chromium is chromium(III) chloride, most preferably chromium(III) chloride hexahydrate, and is comprised in the glucose solution.FK99239-15-PAT-WOExamplesExamples la, lb, 1c, Id, le, IfThe lipid emulsion was prepared as an oil-in-water emulsion from the ingredients listed in table 1.Table 1The lipid emulsion was prepared according to the following process:Glycerol, sodium oleate and 325 ml of water for injection were mixed and heated to 60 to 70 °C. Then, the emulsifier was added under stirring by means of an Ultra-Turrax (T50) at 5000 rpm for 5 minutes to obtain the water phase 1.The pH of the water phase 1 was adjusted to 9.0 to 10.0 by adding a solution of sodium hydroxide.The oil phase was provided by mixing the four oils and alpha tocopherol. The oil phase was heated to 60 to 70 °C. The oil phase and the water phase 1 were mixed at 60 to 70 °C by means of an Ultra-Turrax (T50) for 10 to 12 minutes at 10000 rpm. The pH was adjusted to 9.0 to 10.0 by adding a solution of sodium hydroxide.FK99239-15-PAT-WOThe pre-emulsion was then homogenized in a high-pressure valve homogenizer in 6 cycles at a pressure of 560 bar in the first stage and at a pressure of 120 bar in the second stage (APV-1000, SPX Flow Technology).Sodium selenite was dissolved in water for injection to form a stock solution which was added to the emulsion in an amount to adjust the following concentrations of selenium per 100 ml of the lipid emulsion (table 2):Table 2The residual water for injection (= water phase 2) was added to adjust the volume of the emulsion to 2 liters, and the pH was adjusted to 9.0 to 10.0.Examples 2a-lAn amino acid solution comprising 100.0 g amino acids per liter was prepared by dissolving 14.0 g L-alanine, 12.0 g L-arginine, 11.0 g glycine, 3.0 g L- histidine, 5.0 g L-isoleucine, 7.4 g L-leucine, 6.6 g L-lysine (as 9.3 g L-lysine acetate), 4.3 g L-methionine, 5.1 g L-phenylalanine, 11.2 g L-proline, 6.5 g L- serine, 1.0 g taurine, 4.4 g L-threonine, 2.0 g L-tryptophan, 0.4 g L-tyrosine, 6.2 g L-valine, 740 mg calcium chloride dihydrate, 4.18 g sodium glycerophosphate, 2.47 g magnesium sulfate heptahydrate, 4.48 g potassium chloride, 5.60 g sodium acetate trihydrate in approximately 800 mL of water for injection.Zinc(II) chloride and zinc(II) sulfate, potassium iodide, sodium fluoride, and copper(II) chloride were added and dissolved to adjust the following concentrations of zinc, iodine, fluorine, and copper per 100 ml of the amino acid solution (table 3):FK99239-15-PAT-WOTable 3Water for injection was added to adjust the final volume to 1000 ml. The pH of the solution was adjusted to 5.7 by adding a solution of acetic acid, the osmolarity was 520 mOsmol / kg.Example 3a-lGlucose solutions comprising 42 g glucose (examples 3a-c and 3g-i) or 13 g glucose (examples 3d-f and 3j-l) per 100 ml were prepared by dissolving 46.2 g glucose monohydrate or 14.3 g glucose monohydrate respectively in approximately 500 mL of water for injection. The solutions were heated to 50°C to 60°C to achieve a rapid complete dissolution. The solution was cooled to 20°C to 30°C.Iron(III) chloride hexahydrate, manganese(II) chloride tetrahydrate, copper(II) chloride dihydrate, sodium molybdate dihydrate, and chromic(III) chloride hexahydrate were dissolved in of water for injection to obtain stock solutions. The stock solution containing iron chloride hexahydrate was acidified by adding hydrochloric acid (1 molar) to avoid formation and precipitation of iron oxyhydroxide.The stock solutions were added to the glucose solution in amounts to provide the following concentrations of iron, manganese, copper, molybdenum, and chromium per 100 ml of the glucose solution (table 4).FK99239-15-PAT-WOTable 4The pH was adjusted to 3.5 using 1 molar hydrochloric acid, and water for injection was added to adjust the final volume to 1000 ml. Example 4a-lBags were filled to comprise in separate chambers a lipid emulsion, an amino acid solution, and a glucose solution according to table 5.The bags were autoclaved at > 121.1 °C for > 12 minutes.Table 5FK99239-15-PAT-WOExample 5Aliquots of a lipid emulsion according to example la, of an amino acid solution according to example 2g, and of a glucose solution according to example 3a were filled into bags comprising 3 chambers. Each bag was placed in an overpouch together with an oxygen absorber. The overpouches were sealed and the bags were autoclaved at > 121°C for > 12 minutes. Samples were analyzed prior to sterilization, directly after sterilization and after 4 weeks of storage at 60°C and 50°C as well as after 6 months of storage at 40°C and 25°C (Figure 1). Surprisingly, all trace elements remained stable during storage at 25°C and 40°C, i.e., no significant decrease of the trace elements concentrations was observed during autoclavation or during storage. During storage at 50 °C and 60°C only the copper concentration decreased.The instability of the copper during storage at 50°C and 60°C was unexpected, as in previous studies it had been found to be stable in the glucose solution when tested in a single chamber.Example 5aWithout being bound by theory the inventors believe that the stability of the copper might be impaired by the presence of a source of sulfur, probably being a sulfide or thiol.Accordingly, another series of experiments was conducted with the glucose solution according to example 3a, the only difference being that peroxide cured stoppers were used instead of sulfur cured stoppers. Indeed, stability of copper was improved in the presence of peroxide cured stoppers as compared to sulfur cured stoppers (table 6).Table 6It has long been known that copper(I) sulfide and copper(II) sulfide are poorly soluble in water. The present inventors therefore believe that in the presence of a sulfur source such copper sulfides might be formed and precipitate or adsorb to the inner surface of the container in which the solution is stored.FK99239-15-PAT-WOHowever, in the present case no sulfur source could be identified in the first place.In theory, in amino acid solutions containing cysteine or acetylcysteine hydrogen sulfide (H2S) may be formed upon heating e.g. during autoclavation. H2S, being a gas at room temperature, could diffuse through the semi- permeable container walls and react with copper in the glucose chamber causing precipitation.However, the tested amino acid solution did not contain any cysteine or acetylcysteine. The only sulfur-containing ingredient was methionine.The present inventors do not believe that significant amounts of hydrogen sulfide are formed from methionine, however they hypothesized that under certain conditions methanethiol - which just like H2S is a gas at room temperature - might be formed.Therefore, in still another series of experiments it was tested whether methanethiol causes copper loss in the glucose solution. The test was conducted by adding 25 mg of sodium methanethiolate (the sodium salt of methanethiol) to the glucose formulation according to example 3a. The observed copper loss (table 7) indicates that methanethiol can indeed react with copper forming an insoluble precipitate under these conditions, confirming traces of methanethiol, formed in the amino acid solution, as a potential cause of copper instability in the glucose solution.Table 7In still another series of experiments it was tested whether replacing L- methionine by N-acetyl-methionine, a more stable derivative of L-methionine, would lead to a reduction in the amount of thiol gasses generated and a stabilization of copper in the glucose solution accordingly. Three-chamber-bags filled with aliquots of the lipid emulsion according to example la, the glucose solution according to example 3a, and the amino acid solution according to 2g,FK99239-15-PAT-WO in which L-methionine was replaced by an equimolar amount of N-Acetyl- Methionine, were sterilized and stored for 4 weeks at 60°C. Then, the copper content in the glucose solution was analyzed. The exchange of L-methionine by N-acetyl-methionine indeed appeared to improve the copper stability - interestingly to the same extent as in the negative control (no L-Methionine, i.e., no source of sulfur at all, in the amino acid solution; table 8).Table 8In another series of experiments, the effect of adding sulfide / thiol scavengers into the overpouch of the bags was examined. Small pouches made of filter paper, containing 200 mg of finely grinded copper(I) chloride or copper(II) chloride dihydrate were placed inside the overpouch of three-chamber-bags which were filled with the lipid emulsion according to example la, the amino acid solution according to example 2g and the glucose solution according to example 3a. The bags were terminally heat sterilized and stored for 4 weeks at 60°C. The addition of copper(I) chloride and copper(II) chloride into the overpouch improved the stability of copper in the glucose solution (table 9).Table 9Without being bound by theory the inventors believe that in addition to the presence of a sulfur source the presence or absence of oxygen may influence the stability of the copper in the glucose solution in that Cu2+is not being reduced to Cu+which more easily precipitates (presumably as CU2S) than Cu2+.Accordingly, a series of experiments was conducted in which the three- chamber-bags to be filled with the lipid emulsion according to example la, theFK99239-15-PAT-WO amino acid solution according to example 2a and the glucose solution according to example 3a were before being stored for 4 weeks at 60°C, were not handled under nitrogen atmosphere but under ambient air and without the addition of an oxygen scavenger.It turned out that in the presence of oxygen, copper stability was improved (table 10).Table 10In another series of experiments, it was tested whether the addition of a complexing agent could stabilize copper in the glucose solution. Three- chamber-bags filled with the lipid emulsion according to example la, the amino acid solution according to example 2g and the glucose solution according to example 3a, to which ethylenediaminetetraacetic acid disodium was added at a concentration of 50 mg / 100 ml. The bags were sterilized and stored for 4 weeks at 60 °C, and it turned out that copper stability was improved (table 11).Table 11In another series of experiments, three-chamber-bags were filled with the lipid emulsion according to example la, the amino acid solution prepared according to example 2a but containing additional copper(II) with an overall copper concentration of 76.4 pg / 100 mL and the glucose solution according to example 3g, heat sterilized and stored for 4 weeks at 60 °C.Given the previous tests described above, this test was counter-intuitive in the first place. But on top of this, it surprisingly turned out that copper stability was improved when included in the amino acid solution as compared to being present in the glucose solution (table 12).FK99239-15-PAT-WOTable 12Example 6Aliquots of 100 ml of the amino acid solution according to example 2g additionally comprising 2.0 pg / 100 ml chromium and 3.8 pg / 100 ml molybdenum were filled into plastic bags.Each bag was placed in an overpouch together with an oxygen absorber. The overpouches were sealed and the bags were autoclaved at >121° for >12 minutes. Samples were analyzed prior to sterilization, directly after sterilization and after 4 weeks of storage at 60°C. The trace element assay shows that Cr, Zn, Mo, I, F are stable in the amino acid solution during heat sterilization and during 4 weeks of storage at 60°C (table 13).Table 13The physicochemical parameters indicate that no deterioration of the amino acid solution took place (table 14).Table 14FK99239-15-PAT-WOAccording to the amino acid assay all amino acids remained stable (figure 2).Example 7Aliquots of 100 ml of the glucose solution according to example 3a additionally comprising 1.7 mg / 100 ml zinc were filled into plastic bags. Each bag was placed in an overpouch together with an oxygen absorber. The overpouches were sealed and the bags were autoclaved at >121° for >12 minutes. Samples were analyzed prior to sterilization, directly after sterilization and after 4 weeks of storage at 60°C.The trace element assay shows that Cr, Mn, Fe, Cu, Zn, Mo remained stable in the glucose solution during heat sterilization and incubation for 4 weeks at 60°C (table 15).Table 15Physicochemical parameters do not indicate any significant impact of the trace elements on the glucose solution (table 16).Table 16The trace elements did not appear to impact glucose stability (glucose assay and impurity analysis; table 17).FK99239-15-PAT-WOTable 17Example 8Aliquots of 100 ml of the lipid emulsion according to example la additionally comprising 10.1 pg / 100 ml molybdenum, 67.6 pg / 100 ml iodine, and 505.3 pg / 100 ml fluorine were filled into plastic bags.Each bag was placed in an overpouch together with an oxygen absorber. The overpouches were sealed and the bags were autoclaved at >121° for >12 minutes. Samples were analyzed prior to sterilization, directly after sterilization and after 4 weeks of storage at 60°C. The trace element assay shows that selenium, molybdenum, iodine and fluorine remained stable in the lipid emulsion during heat sterilization and incubation for 4 weeks at 60°C (table 18).Table 18 The physicochemical stability of the lipid emulsion does not appear to be affected by the presence of the trace elements (table 19).Table 19

Claims

FK99239-15-PAT-WOClaims1) Oil-in-water emulsion for parenteral administration comprising 5 wt.% to 30 wt.%, preferably 10 wt.% to 20 wt.%, more preferably 10 wt.% or 20 wt.%, most preferably 20 wt.%, of an oil phase based on the total weight of the emulsion and a pharmaceutically acceptable form of selenium.2) Oil-in-water emulsion according to claim 1, wherein the oil phase is composed such that it comprises oleic acid (OA), linoleic acid (LA), eicosapentaenoic (EPA) acid and docosahexaenoic acid (DHA), wherein 90 to 100 wt.% of these fatty acids are present in triglyceride-bound form.3) Oil-in-water emulsion according to any of the preceding claims, wherein the oil phase further comprises caprylic acid and capric acid, wherein preferably 90 to 100 wt.% of these fatty acids are present in triglyceride- bound form.4) Oil-in-water emulsion according to any of the preceding claims, wherein the oil phase further comprises palmitic acid (PA) and / or alpha-linolenic acid (ALA), wherein 90 to 100 wt.% of these fatty acids are present in triglyceride-bound form.5) Oil-in-water emulsion according to any of the preceding claims, wherein the oil phase comprises 14-19 wt.% caprylic acid, 10-14 wt.% capric acid, 24-29 wt.% oleic acid, 16-21 wt.% linoleic acid, 1.5-3.5 wt.% eicosapentaenoic acid and 2-3 wt.% docosahexaenoic acid based on the total weight of the oil phase, wherein preferably 90 to 100 wt.% of the fatty acids are present in triglyceride-bound form.6) Oil-in-water emulsion according to any of the preceding claims, wherein the oil phase comprises 20 wt.% to 40 wt.% soybean oil, 20 wt.% to 40 wt.% medium-chain triglycerides, 20 wt.% to 30 wt.% olive oil and 10 wt.% to 30 wt.% fish oil based on the total weight of the oil phase.7) Oil-in-water emulsion according to any of the preceding claims, wherein the pharmaceutically acceptable form of selenium comprises selenium as Se(IV), preferably in form of a salt comprising selenite ions, more preferably as sodium selenite, most preferably as anhydrous sodium selenite.FK99239-15-PAT-WO8) Oil-in-water emulsion according to any of the preceding claims, wherein the selenium concentration ranges from 2.7 pg to 88.3 pg per 100 ml of the lipid emulsion, preferably provided as 5.9 pg to 193.4 pg anhydrous sodium selenite per 100 ml of the lipid emulsion.9) Oil-in-water emulsion according to any of the preceding claims further comprising a pharmaceutically acceptable form of iodine, preferably selected from the group consisting of sodium iodide and potassium iodide, more preferably, potassium iodide, most preferably anhydrous potassium iodide.10) Oil-in-water emulsion according to claim 9 comprising a pharmaceutically acceptable form of iodine, wherein the iodine concentration ranges from 5.3 pg to 147.1 pg per 100 ml of the lipid emulsion, preferably provided as 6.9 pg to 192.4 pg potassium iodide per 100 ml of the lipid emulsion.11) Oil-in-water emulsion according to any of the preceding claims, wherein the oil-in-water emulsion has a pH of 7.0 to 10.0, preferably 7.5 to 9.5, more preferably 7.5 to 9.0.12) Container, preferably a plastic bag comprising in separate chambers an oil-in-water emulsion according to any of claims 1 to 11, a glucose solution for parenteral administration comprising 10 g to 45 g glucose per 100 ml of the glucose solution and / or an amino acid solution for parenteral administration comprising 4 g to 18 g amino acids per 100 ml of the amino acid solution.13) Container according to claim 12, wherein the glucose solution further comprises a pharmaceutically acceptable form of iron and / or wherein the amino acid solution comprises a pharmaceutically acceptable form of copper.14) Container according to claim 12 or 13 comprising at least the trace elements selenium, copper, zinc, iron, manganese, molybdenum, chromium and iodine, in pharmaceutically acceptable form.15) Container according to claim 13 or 14, wherein the pharmaceutically acceptable form of iron comprises iron in the form of iron(III), preferably wherein the pharmaceutically acceptable form of iron is selected from the group consisting of iron(III) sulfate, iron(III) oxide, sodium iron(III) gluconate, iron (III) citrate, ammonium iron(III)FK99239-15-PAT-WO citrate, iron(III) oxide-hydroxide, iron (III) fumarate, ammonium iron (III) sulfate, iron(III) sorbitol citrate, iron(III) hydroxide saccharose, iron(III) carboxymaltose and iron(III) chloride, more preferably wherein the pharmaceutically acceptable form of iron is iron(III) chloride, most preferably iron(III) chloride hexahydrate.16) Container according to any of claims 13 to 15, wherein the pharmaceutically acceptable form of copper comprises copper in the form of Cu(II), preferably wherein the pharmaceutically acceptable form of copper is selected from the group consisting of copper(II) sulfate, copper(II) gluconate, copper(II) acetate and copper(II) chloride, more preferably wherein the pharmaceutically acceptable form of copper is copper(II) chloride, most preferably copper(II) chloride dihydrate.17) Container according to any of claims 14 to 16, wherein the pharmaceutically acceptable form of zinc, preferably selected from the group consisting of zinc acetate, zinc gluconate, zinc sulfate and zinc chloride, more preferably zinc chloride, most preferably anhydrous zinc chloride, is comprised in the amino acid solution.

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