WO2022003027A1

WO2022003027A1 - Kit for coloring tube feeds

Info

Publication number: WO2022003027A1
Application number: PCT/EP2021/068007
Authority: WO
Inventors: Julia HECKMANN; Nadja SIEGERT
Original assignee: Fresenius Kabi Deutschland Gmbh
Priority date: 2020-07-02
Filing date: 2021-06-30
Publication date: 2022-01-06
Also published as: EP4175491A1

Abstract

The present invention relates to a kit for coloring tube feed compositions comprising a tube feed and a colorant, a device for the administration of a colorant into a tube feed composition and a method for preparing a colored tube feed composition.

Description

KIT FOR COLORING TUBE FEEDS

FIELD OF THE INVENTION

[0001] The present invention relates to a kit for coloring tube feed compositions comprising a tube feed and a colorant, to a device for the administration of a colorant into a tube feed composition and to a method for preparing a colored tube feed composition.

BACKGROUND OF THE INVENTION

[0002] Tube feeding is a well-established way of providing enteral nutrition to malnourished people, people with oral-food-intake difficulties due to e.g. swallowing difficulties or numerous other medical complications, which require nutritional support. Nasogastric and nasojejenual tubes are examples for providing tube feed compositions to the stomach or intestine of people in need thereof.

[0003] However, complications are sometimes associated with the use of tube feeding such as pulmonary aspiration due to reflux of gastric fluids through the esophagus or reflux from the digestive tract to the respiratory system in case of small bowel obstruction.

[0004] Tinting of tube feeds has been used for the monitoring of these complications. The coloring of tube feeds using appropriate dyes allows for a differentiation from secretions of the Gl tract. FD&C blue No.l, a commercially available methylene blue dye, which is also known as Brilliant Blue FCF, has been used although the colorant has not been approved for use in foods. This is problematic, as the use of this dye has been linked with severe side effects, including lethality (Maloney et al.; "Food Dye Use in Enteral Feedings: A Review and a Call for a Moratorium"; Nutrition in Clinical Practice 17:169-181, June 2002; DOI: 10.1177/0115426502017003169). Thus, there is a clear medical need for colorants that can be used for coloring of tube feeds without toxicological constraints and thereby provide colored tube feed compositions that allow for the safe monitoring of complications associated with reflux of tube feed contents from the gastro-intestinal tract to the respiratory system.

SUMMARY OF THE INVENTION [0005] The inventors have surprisingly found that colorants from the group consisting of copper complexes of chlorophyllins, copper complexes of chlorophylls, vegetable charcoal, anthocyanins, spirulina, and mixtures thereof are capable of coloring tube feed compositions and that the color of the resulting tube feed compositions is stable under the strongly acidic conditions of the stomach, i.e. at a pH- value of about 2.2. Furthermore, it has been found that these colorants are stable against secretions from the Gl tract such as gastric enzymes, bile, pancreatic enzymes and small intestine electrolyte solution (SIES). All colorants according to the invention are selected in a way that the color of the colored tube feed can be distinguished from the color of the physiological secretions in the Gl tract. Finally, the colorants of this invention are safe based on the fact that they are group II colorants, authorized "quantum satis" (i.e. without quantitative restriction) to be used in food for special medical purposes (FSMP), indicating their non-toxic properties. Consequently, they overcome the limitations of the colorants used for the coloring of tube feeds disclosed in the prior art.

[0006] Accordingly, in one aspect of the invention a kit for coloring tube feed compositions is provided, the kit for coloring tube feed compositions comprising at least a first and a second compartment, and, optionally, handling instructions; wherein the first compartment comprises a tube feed composition, the second compartment comprises at least one colorant selected from the group consisting of copper complexes of chlorophyllins, copper complexes of chlorophylls, vegetable charcoal, anthocyanins, spirulina, and mixtures thereof; and wherein the at least one colorant is transferable from the second compartment to the first compartment to allow a mixing of the at least one colorant with the tube feed composition.

[0007] In a second aspect the invention provides a device for the administration of at least one colorant into a tube feed composition, wherein the device is connectable to a compartment comprising a tube feed composition, optionally via a coupling link, the device comprises at least one colorant, and, wherein the at least one colorant is selected from the group consisting of copper complexes of chlorophyllins, copper complexes of chlorophylls, vegetable charcoal, anthocyanins, spirulina, and mixtures thereof.

[0008] The present invention also relates in a third aspect to a method for preparing a colored tube feed composition comprising the steps of a) providing a first compartment comprising a tube feed composition, b) providing a second compartment comprising at least one colorant selected from the group consisting of copper complexes of chlorophyllins, copper complexes of chlorophylls, vegetable charcoal, anthocyanins, spirulina, and mixtures thereof, c) transferring the at least one colorant from the second compartment to the first compartment, optionally by means of a third compartment, to allow a mixing of the at least one colorant with the tube feed composition to obtain a colored tube feed composition. DETAILED DESCRIPTION OF THE INVENTION

Definitions

[0009] Colorant or colorants as used herein refers to one Group II colorant or a mixture of different Group II colorants as well as Group II colorant compositions suitable for tinting tube feed compositions, that comprise one or more ingredients other than the Group II colorants, which are required for instance for the stabilization of those compositions, such as additives or adjuvants.

[0010] Color Index™ Number (C.l. No.) as used herein refers to the "The Color Index™ https://colour- index.com published online by the Society of Dyers and Colourists and the American Association of Textile Chemists and Colorists".

[0011] Copper Chlorophyllin as used herein refers to a colorant comprising copper complexes of chlorophyllin such as the sodium or potassium salts of Copper Chlorophyllin or mixtures thereof. Copper Chlorophyllin is commercially available for instance from Sensient Colors Europe GmbH, Geesthachter Str. 103, 21502 Geesthacht, Germany, Product number 503523. Copper Chlorophyllin refers to E141(ii) in the E-number codes for substances used as food additives for use within the European Union (EU) and European Free Trade Association (EFTA). An example of a Copper Chlorophyllin colorant for use in the present invention is the trisodium salt identified by the C.l. No. 75815 or CAS-No. 11006-34-1.

[0012] Carbon Black as used herein refers to a colorant comprising a dispersion of micronized vegetable carbon, C.l. No. 77266, CAS-No. 7440-44-0. Carbon Black is commercially available for instance from Sensient Colors Europe GmbH, Geesthachter Str. 103, 21502 Geesthacht, Germany, Product number 409208. Carbon Black refers to E153 in the E-number codes for substances used as food additives for use within the European Union (EU) and European Free Trade Association (EFTA).

[0013] Anthocyanin as used herein refers to an Anthocyanin extract. Anthocyanin is commercially available for instance from Sensient Colors Europe GmbH, Geesthachter Str. 103, 21502 Geesthacht, Germany, Product number 409291. Anthocyanin refers to E163 in the E-number codes for substances used as food additives for use within the European Union (EU) and European Free Trade Association (EFTA). [0014] Marine Blue as used herein refers to a water-soluble preparations of spirulina concentrate made from Spirulina Platensis. Marine blue is for instance commercially available from Sensient Colors Europe GmbH, Geesthachter Str. 103, 21502 Geesthacht, Germany, Product number 419174.

[0015] Group II colorants as used herein refers to food colors authorized at quantum satis (group II) pursuant to the regulation No. 1333/2008 of the European Parliament of 16. Dec 2008 to be used in food for special medical purposes defined in directive 1999/21/EC. [0016] E-numbers as used herein refer to the E-number codes for substances used as food additives for use within the European Union (EU) and European Free Trade Association (EFTA).

[0017] Vol.% (v/v) as used herein refers to volume percent (volume per volume) based on the volume of the colored tube feed composition.

[0018] Caloric density as used herein refers to the calorie content relative to its volume.

[0019] Dietary fiber as used herein refers to indigestible carbohydrates, such as fructooligosaccharides, fructanes, e.g. inulin, galactooligosaccharides, pectin, gums, such as guar gum, loctus bean gum and gum acacia, cocoa, xanthan, carrageenan, cellulose, such as microcristalline cellulose, dextrins, such as wheat dextrin, fruit purees, and mixtures thereof.

[0020] Protein component as used herein refers to the entirety of ingredients of the nutritional composition declarable as protein, such as total milk protein, milk protein concentrate, milk protein isolate, casein, caseinate, such as sodium caseinate, potassium caseinate, calcium caseinate, whey protein, vegetable proteins, such as pea protein and soy protein, animal proteins, such as collagen, and mixtures thereof. The protein component may comprise protein that is essentially non-hydrolyzed, partially hydrolyzed protein, or in amino acid form, as well as mixtures thereof. The protein may be present in native or denatured form or mixtures of both.

[0021] Fat component as used herein refers to the entirety of ingredients of the nutritional composition declarable as fat, such as fish oil, rapeseed oil, safflower oil, sunflower oil, linseed oil, canola oil, tributyrin, medium chain triglycerides (MCT), and mixtures thereof.

[0022] Carbohydrate component as used herein refers to the entirety of ingredients of the nutritional composition declarable as carbohydrate, such as starch, maltodextrin, glucose syrup, mono- and disaccharides, such as sucrose, maltose, isomaltulose, lactose, glucose, fructose, galactose, and mixtures thereof.

[0023] Amino acid as used herein includes the free amino acid, salts of the amino acid, chemically modified amino acids and metabolites of amino acids, such as alpha-ketoisocaproic acid (KIC), 3-Hydroxy- 3-methyl-butyric acid (HMB) and (R)-3-Hydroxybutyl-(R)-3-hydroxybutyrate, and mixtures thereof.

[0024] Nutritionally complete as used herein refers to nutritional compositions suitable as sole source of nutrition. To be nutritionally complete, it is required that a nutritional composition comprises - in addition to the fat, carbohydrate and protein components - minerals and vitamins. In order to be nutritionally complete, vitamins and minerals should be present in amounts in accordance with established nutritional guidelines. The recommended nutrient requirements, particularly with respect to minerals and vitamins, can be found in standard nutritional guidelines, such as EU commission directive 1999/21/EC (see table 1 herein below). Suitable nutritional compositions according to the present disclosure fulfil the requirements of / are listed in REGULATION (EU) No 609/2013.

[0025] Caseinate as used herein refers to caseinate salts with alkali and earth-alkali metals, e.g. sodium caseinate, potassium caseinates, calcium caseinate, acid casein, rennet casein, and mixtures thereof. [0026] Tube feed or tube feeds as used herein refers to food, which is provided to the gastro-intestinal tract, e.g. stomach or small intestine, of a patient via a tube, e.g. a tube inserted through the nose or abdomen of the patient.

[0027] Co-polymers as used herein include random- and block-copolymers.

[0028] Transferable from the second compartment to the first compartment as used herein refers to a complete or partial transfer of the colorant from the second compartment to the first compartment comprising the tube feed composition or vice versa or a mixture of both.

[0029] Mixing of the at least one colorant with the tube feed composition as used herein refers to a complete or partial mixing of the at least one colorant and the tube feed composition in the first compartment. Depending on the means by which the transfer of colorant into the tube feed composition is accomplished, mixing of partial amounts of the at least one colorant and the tube feed composition may also take place in other compartments of the kit as well as in the coupling links or the connectors comprised in the kit.

[0030] Secondary packaging as used herein refers to a packaging, which is neither in contact with the tube feed composition comprised in the first compartment, nor with the at least one colorant comprised in the second compartment.

[0031] ENPlus system as used herein refers to a connecting system for tube feed containers and administration systems for tube feeds comprising a plus (+) shaped connector on the feed containers as well as a plus (+) shaped spike on the administration system. The ENPlus connection system ensures that only enteral nutrition feed containers can be attached to enteral feed administration systems and that enteral nutrition administration sets cannot be connected to IV solution containers. ENPlus connection systems are routinely used in commercially available tube feed products and are described in the ISO Norm 18250. One example of a tube feed container comprising an ENplus connecting system is the EasyBag^® system by Fresenius Kabi.

The kit

[0032] The kit of the present invention comprises at least a first and a second compartment, wherein the first compartment comprises a tube feed composition, the second compartment comprises at least one colorant selected from the group consisting of copper complexes of chlorophyllins, copper complexes of chlorophylls, vegetable charcoal, anthocyanins, spirulina, and mixtures thereof; and wherein the at least one colorant is transferable from the second compartment to the first compartment to allow a mixing of the at least one colorant with the tube feed composition.

[0033] In a preferred embodiment the colorant is selected from the group consisting of Copper Chlorophyllin (E141(ii)), Carbon Black (E153), Anthocyanin (E163), Marine Blue, and mixtures thereof, more preferably from Copper Chlorophyllin (E141(ii)), Carbon Black (E153), Anthocyanin (E163), and mixtures thereof. Most preferably, the colorant is Copper Chlorophyllin (E141(ii)).

[0034] Substances to enhance the storage stability of the at least one colorant, such as emulsifiers and / or antioxidants may also be comprised in the second compartment of the kit.

[0035] Preferably, the kit of the present invention comprises handling instructions. Handling instructions allow for a safe and convenient handling of the kit of the present invention as well as a safe and convenient preparation of colored tube feed compositions by mixing the at least one colorant comprised in the second compartment and the tube feed composition comprised in the first compartment.

[0036] The kit of the present invention may comprise a secondary packaging. Preferably the second packaging encloses at least the first and the second compartment, and, optionally the handling instructions and auxiliary means comprised in the kit. The secondary packaging may be selected from the group consisting of bags, blisters, and flow-packs. The secondary packaging may be impermeable for oxygen. It may further be partially or fully transparent for light. Additionally, it may protect the kit of the present invention from contamination, e.g. dust.

[0037] The kit may comprise auxiliary means for the administration of the at least one colorant from the second compartment to the tube feed composition comprised in the first compartment, such as coupling links, syringes or needles. In case the kit comprises a needle, the needle is packaged prior to the administration of the colorant from the second compartment to the tube feed composition comprised in the first compartment in order to keep it sterile. Preferably, the needle is included in a protecting cap. The use of packaged, protected needles allows for a safe and convenient handling of the kit as well as for a sterile administration of the colorant from the second compartment to the tube feed in the first compartment.

[0038] In one embodiment the first compartment is a container, for example a bottle, a bag or a pouch, such as a stand-up pouch. [0039] Preferably the, first compartment is a plastic container. Preferably, the plastic container comprises polymers selected form the group consisting of polyethylene, polypropylene, polybutylene, polyisoprene, polystyrene, polyamide, polyvinylchloride, and mixtures thereof, more preferably polyethylene, polypropylene, polyamide, and mixtures thereof. The polymers may be present in the form of homo polymers or co-polymers.

[0040] In case the first compartment is a plastic container, the plastic container may comprise one or more layers, preferably 1 to 4 layers, more preferably 3 to 4 layers. In the case the plastic container comprises more layers the layers may be identical of different regarding their polymer composition. The one or more layer may be coated independently from each other. Preferred coatings comprise ceramics. Coating leads to improved properties of the container, e.g. improved mechanical properties. One example for a plastic container according to the present invention is a container as disclosed in W02015/052209. [0041] In a preferred embodiment the first compartment comprises a connector. The connector may comprise a break-up part and/or a septum. In a particularly preferred embodiment, the connector comprises a break-up part and a septum and is connectable to an administration system comprising a spike by injection of the spike through the septum comprised in the connector. Most preferably the administration system is connected to the connector by an ENPlus system.

[0042] Optionally, the first compartment may comprise a suspension arrangement, such as a hanger, an aperture or an orifice. Preferably the suspension arrangement is placed at the opposite side to the connector comprised in the first compartment. This arrangement allows for a flow out of the contents through the connector comprised in the first compartment by means of gravity, i.e. without the need to apply additional force.

[0043] The tube feed composition comprised in the first compartment may be sterilized. Alternatively, the colorant comprised in the second compartment as well as at least one of the additional parts, optionally comprised in the kit, such as coupling links, auxiliary means or the secondary packaging, may be sterilized as well. In one embodiment all parts of the kit are sterilized.

[0044] The second compartment may be a container, wherein the container is selected from the group consisting of syringes, bottles, ampules, bags, pouches, such as stand-up pouches, vials, tubes and capsules, preferably from syringes, bottles, bags, and pouches, such a stand-up pouches, more preferably the second compartment is a syringe.

[0045] In case the second compartment is a plastic container, the plastic container comprises polymers selected form the group consisting of polyethylene, polypropylene, polybutylene, polyisoprene, polystyrene, polyamide, polyvinylchloride, and mixtures thereof, more preferably polyethylene, polypropylene, polyamide, and mixtures thereof. The polymers may be present in the form of homo polymers or co-polymers.

[0046] The plastic container may comprise one or more layers, preferably 1 to 4 layers, more preferably 3 to 4 layers. In the case the plastic container comprises more layers the layers may be identical of different regarding their polymer composition. The one or more layer may be coated independently from each other. Preferred coatings comprise ceramics. Coating leads to improved properties of the container, e.g. improved mechanical properties.

[0047] In one embodiment the second compartment is a device for the administration of the at least one colorant into the tube feed composition comprised in the first compartment, optionally via a coupling link. One example for the device for the administration of the at least one colorant into the tube feed composition comprised in the first compartment is a syringe.

[0048] The second compartment can alternatively be connected to the first compartment to administer the colorant to the tube feed composition in the first compartment, optionally via a coupling link.

[0049] In a preferred embodiment the coupling link comprises a least a first and a second connector, wherein the first connector fits to a connector comprised in the first compartment and wherein the second connector fits to a connector comprised in the second compartment. This allows for the mixing of colorant and tube feed composition under sterile conditions and avoids the contamination of the tube feed composition prior to its administration to the patient. The first and/or the second connector comprised in the coupling link may comprise a spike that are connectable to the first and/or the second compartment by injecting the spike through the septum comprised in the connector comprised in the first and/or the second compartment. Most preferably the connectors comprised in the coupling link are connected to the connectors in the first and/or the second compartment by an ENPlus system.

[0050] The coupling link may comprise at least one branching point, such as a Y-conjunction or a T- conjunction, for the simultaneous addition of at least the at least one colorant comprised in the second compartment and the tube feed composition comprised in the first compartment to a patient.

[0051] Alternatively, the colorant and the tube feed composition may be mixed in a third compartment prior to the administration to a patient.

[0052] In an alternative embodiment the coupling link comprises more than one branching point. By means of a second or more branching points additional substances other than the at least one colorant and the tube feed composition can be added.

[0053] In one embodiment the coupling link comprises a shut-off device, preferably a stopcock, such as a two-way stopcock or a three-way stopcock. Thereby, the controlled mixing of the tube feed composition comprised in the first compartment and the at least one colorant comprised in the second compartment as well as a controlled administration of the colored tube feed to patients can be achieved.

[0054] In a preferred embodiment the coupling link is a tube, more preferably a plastic tube, Preferably, the plastic tube comprises polymers selected form the group consisting of polyethylene, polypropylene, polybutylene, polyisoprene, polystyrene, polyamide, polyvinylchloride, and mixtures thereof. The plastic tube may be coated in an alternative embodiment.

[0055] In another embodiment the second compartment comprises a connector that fits to a connector comprised in the first compartment. This allows for the mixing of the at least one colorant and the tube feed composition comprised in the first compartment without the need to use a coupling link under sterile conditions and avoids the contamination of the colored tube feed composition prior to its administration to the patient.

[0056] The at least one colorant may be transferred from the second compartment to the tube feed composition comprised in the first compartment by the application of force. In case the second compartment is a syringe, the force is applied to the piston of the syringe to transfer the at least one colorant comprised in the syringe to the first compartment comprising the tube feed composition, preferably through a needle. In case the second compartment is separated from the first compartment by a seal, the force is applied to the first compartment, the second compartment or to both, to break the seal and allow for a mixing of the colorant comprised in the second compartment and the tube feed composition comprised in the first compartment. The force may be applied to both compartments stepwise or simultaneously.

[0057] Preferably, the at least one colorant is transferred from the second compartment to the tube feed composition comprised in the first compartment through a needle, preferably through a septum comprised in the first compartment. The septum is preferably comprised in a connector comprised in the first compartment.

[0058] In a preferred embodiment, the second compartment is a syringe and the at least one colorant is transferred from the second compartment to the tube feed composition comprised in the first compartment through a needle, preferably through a septum comprised in the first compartment. The septum is preferably comprised in a connector comprised in the first compartment.

[0059] In a further preferred embodiment, the first compartment is a pouch, such as a stand-up pouch, or a bottle, the second compartment is a syringe and the at least one colorant is transferred from the syringe to the pouch through a needle by injecting the needle through the septum comprised in a connector comprised in the first compartment. [0060] In another preferred embodiment the kit comprises a third compartment for transferring the at least one colorant from the second compartment to the tube feed composition comprised in the first compartment. Preferably, the third compartment is comprised in a syringe and the at least one colorant is transferred in a first step from the second compartment to the third compartment comprised in the syringe through a needle by injecting the needle through a septum comprised in a connector comprised in in the second compartment. In a second step the at least one colorant is transferred from the third compartment comprised in the syringe to the tube feed composition comprised in the first compartment through the needle by injecting the needle through a septum comprised in the first compartment.

[0061] The first and the second compartment may be placed inside one container. In one embodiment the container is equal to the fist compartment.

[0062] In a preferred embodiment the second compartment placed inside the first compartment, is a capsule or a small bag, wherein the capsule or the small bag releases the colorant after the application of force.

[0063] More preferably, the second compartment is a capsule or a small bag placed in the first compartment and the first compartment comprises a connector comprising a septum, the connector is connectable to an administration system comprising a spike by injecting the spike through the septum comprised in the connector, and a suspension arrangement placed at the opposite side to the connector in the second compartment. Most preferably the administration system is connected to the connector by an ENPlus system.

[0064] Alternatively, the first and the second compartment placed in one container are separated by a peelable seal or a permanent seal having a frangible valve. In one embodiment, the container comprising the first and the second compartment separated by a peelable seal or a permanent seal having a frangible valve is a multi-chamber bag, such as at two- or a three-chamber bag. Multi-chamber bags according to this invention are for example disclosed in EP1773277B1.

[0065] In another particularly preferred embodiment the container is a two-chamber bag, wherein the two chamber bag comprises a first chamber comprising the first compartment and a second chamber comprising the second compartment, wherein the first and the second compartment are separated by a seal, and wherein the at least one colorant comprised in the second compartment is transferred to the tube feed composition comprised in the first compartment by the application of force, and wherein the first compartment comprises a connector comprising a septum, the connector is connectable to an administration system comprising a spike by injecting the spike through the septum comprised in the connector, and a suspension arrangement placed at the opposite side to the connector comprised in the first compartment. Most preferably the administration system is connected to the connector by an ENPlus system.

[0066] The tube feed composition of the present invention may have a caloric density of at least 0.3 kcal/ml, preferably of at least 0.8 kcal/ml, more preferably of at least 1.0 kcal/ml, such as 1.0 kcal/ml, 2.0 kcal/ml, 2.4 kcal/ml, 3.2 kcal/ml or 5.0 kcal ml.

[0067] In one embodiment, the tube feed composition of the present invention comprises a protein component. The protein component may comprise at least one protein selected from non-hydrolyzed protein, partially hydrolyzed protein, or amino acids, and mixtures thereof. The protein component may comprise one or more proteins selected from milk proteins, such as total milk protein, milk protein concentrate, milk protein isolate, casein, caseinate, such as sodium caseinate, potassium caseinate, calcium caseinate, whey protein, vegetable proteins, such as pea protein and soy protein, animal proteins, such as collagen, and mixtures thereof. The proteins in the protein component may be essentially non- hydrolyzed protein or partially hydrolyzed protein, such as casein hydrolysate, hydrolyzed caseinate, whey hydrolysate, pea protein hydrolysate and collagen hydrolysate, and mixtures thereof. Furthermore, the protein component may comprise amino acids. Preferably, the protein component comprises one or more proteins selected from casein, caseinate, whey protein, and mixtures thereof. In one embodiment the protein component comprises one or more protein hydrolysates, such as casein hydrolysate, hydrolyzed caseinate, whey hydrolysate, pea protein hydrolysate, collagen hydrolysate or mixtures thereof.

[0068] The tube feed composition of the present invention may comprise a carbohydrate component. The carbohydrate component may comprise at least one carbohydrate selected from digestible polysaccharides, mono- and disaccharides, and mixtures thereof. The carbohydrate component may comprise one or more digestible polysaccharides, such as starch, maltodextrin, or glucose syrup, and mixtures thereof. The carbohydrate component may comprise one or more mono- and disaccharides, such as sucrose, maltose, isomaltulose, lactose, glucose, fructose, or galactose, and mixtures thereof. Preferably, the carbohydrate component comprises one or more carbohydrates selected from starch, maltodextrin, glucose syrup, fructose, isomaltulose, or sucrose, and mixtures thereof.

[0069] Optionally, the tube feed composition of the present invention comprises a fat component. Preferably, the fat component may comprise one or more oils selected from the group consisting of fish oil, rapeseed oil, safflower oil, sunflower oil, linseed oil, canola oil, tributyrin, or medium chain triglycerides (MCT), and mixtures thereof.

[0070] In a preferred embodiment the tube feed of the present invention comprises a protein component, preferably at least one protein selected from casein, caseinate, or whey protein, and mixtures thereof, a carbohydrate component, preferably at least one carbohydrate selected from starch, maltodextrin, glucose syrup, fructose, isomaltulose, or sucrose, and mixtures thereof, and a fat component, preferably at least one oil selected from fish oil, rapeseed oil, safflower oil, sunflower oil, linseed oil, canola oil, tributyrin, or medium chain triglycerides (MCT), and mixtures thereof.

[0071] In one embodiment the tube feed composition of the present invention comprises at least one dietary fiber, selected from fructooligosaccharides or fructanes, e.g. inulin, galactooligosaccharides, pectin, gums, such as guar gum, loctus bean gum and gum acacia, cocoa, xanthan, carrageenan, cellulose, such as microcristalline cellulose, wheat dextrin fibre, soyapolysaccharide, and mixtures thereof.

[0072] Optionally, the tube feed composition of the present invention may comprise additional ingredients, such as, vitamins, minerals, and mixtures thereof, required to adapt the nutritional profile of the tube feed composition to address the nutritional requirements of the patients in need thereof.

[0073] Preferably, the tube feed composition of the present invention is a food for special medical purposes (FSMP). The food for special medical purposes may be nutritionally complete or in the form of a nutritional supplement.

[0074] In one embodiment the tube feed composition of the present invention is nutritionally complete. [0075] Substances to enhance the storage stability of the compositions, such as emulsifiers and / or antioxidants may also be comprised in the tube feed composition of the present invention.

[0076] The tube feed composition of the present invention may preferably comprise a protein component, a carbohydrate component, a fat component, dietary fibers, vitamins, minerals and substances to enhance the storage stability of the composition such as emulsifier and / or antioxidants and mixtures thereof.

The device

[0077] The present invention also relates to a device for the administration of at least one colorant into a tube feed composition (the device), wherein the device is connectable to a compartment comprising a tube feed composition, the device comprises at least one colorant, and, wherein the at least one colorant is selected from the group consisting of copper complexes of chlorophyllins, copper complexes of chlorophylls, vegetable charcoal, anthocyanins, spirulina, and mixtures thereof.

[0078] In a preferred embodiment the at least one colorant is selected from the group consisting of Copper Chlorophyllin (E141(ii)), Carbon Black (E153), Anthocyanin (E163), Marine Blue, and mixtures thereof, more preferably from Copper Chlorophyllin (E141(ii)), Carbon Black (E153), Anthocyanin (E163), and mixtures thereof. Most preferably, the colorant is Copper Chlorophyllin (E141(ii)). [0079] Substances to enhance the storage stability of the at least one colorant, such as emulsifiers and / or antioxidants may also be comprised in the device.

[0080] In one embodiment the device is selected from the group consisting of syringes, bottles, ampules, bags, pouches, such as stand-up pouches, vials, tubes and capsules, preferably from syringes, bottles, bags, and pouches, such as stand-up pouches, more preferably the device is a syringe.

[0081] In one embodiment the device comprises a connector that fits to a connector of the compartment comprising a tube feed composition. This allows for the mixing of colorant and tube feed composition under sterile conditions and avoids the contamination of the tube feed composition prior to its administration to the patient. [0082] In one embodiment the device comprises a coupling link.

[0083] Alternatively, the colorant may be transferred from the device to the tube feed composition by the application of force. In case the device is a syringe, the force is applied to the piston of the syringe to transfer the colorant comprised in the syringe to the compartment comprising the tube feed composition, preferably through a needle. The force may also be applied to the devise, for example in case the device is a pouch, a bag or a capsule, to transfer the at least one colorant comprised in the device to the tube feed composition comprised in the compartment, optionally through a connector or a coupling link. The force may also be applied to the compartment, the device or to both, to allow for a mixing of the colorant comprised in the device and the tube feed composition comprised in the compartment. The force may be applied to the compartment and the device stepwise or simultaneously. [0084] Preferably, the at least one colorant is transferred from the device to the tube feed composition through a needle, preferably through a septum comprised in the compartment. The septum is preferably comprised in a connector comprised in the compartment.

[0085] In a particularly preferred embodiment, the device is a syringe and the colorant is transferred from the device to the tube feed composition through a needle, preferably through a septum comprised in the compartment. The septum is preferably comprised in a connector comprised in the compartment.

[0086] Additionally, reference is made to the embodiments as under the first aspect of the present invention, which are disclosed in the section "The kit". They are in their entirety explicitly incorporated as embodiments of the second aspect of the present invention, i.e. a device for the administration of at least one colorant into a tube feed composition as described under this section. Preparation of a colored tube feed.

[0087] The present invention also relates to a method for preparing a colored tube feed composition comprising the steps of a) providing a first compartment comprising a tube feed composition, b) providing a second compartment comprising at least one colorant selected from the group consisting of copper complexes of chlorophyllins, copper complexes of chlorophylls, vegetable charcoal, anthocyanins, spirulina, and mixtures thereof, c) transferring the at least one colorant from the second compartment to the first compartment, optionally by means of a third compartment, to allow a mixing of the at least one colorant with the tube feed composition to obtain a colored tube feed composition, optionally, the colored tube feed composition obtained in step c) is administered to a patient.

[0088] In a preferred method the second compartment is a syringe and the at least one colorant is transferred from the second compartment to the tube feed composition comprised in the first compartment through a needle, preferably through a septum comprised in the first compartment. The septum is preferably comprised in a connector comprised in the first compartment.

[0089] In an alternatively method the at least one colorant comprised in the second compartment is transferred in a first step from the second compartment to a third compartment comprised in a syringe through a needle injected in a septum comprised in a connector comprised in the second compartment. In a second step the colorant is transferred from the third compartment to the first compartment through a needle injected in a septum comprised in a connector comprised in the first compartment.

[0090] In another method the colorant comprised in the second compartment is transferred to the tube feed composition comprised in the first compartment through a seal by the application of force, wherein the first and the second compartment are positioned within a multi chamber bag.

[0091] Additionally, reference is made to the embodiments as disclosed under the first aspect of the present invention, which are disclosed in the section "The kit". They are in their entirety explicitly incorporated as embodiments of the third aspect of the present invention, i.e. a method for preparing a colored tube feed composition. DESCRIPTION OF THE FIGURES

[0092] Figure 1 shows a first embodiment of the present invention. The kit comprises a first compartment 1 comprising a tube feed composition and a connector 11, a syringe 40 comprising the second compartment 2 comprising at least one colorant. The at least one colorant can be transferred from the second compartment 2 to the first compartment 1 comprising the tube feed composition through a needle 41 by injecting the needle 41 through the connector 11. The kit is included in a secondary packaging 100.

[0093] Figure 2 shows another embodiment of the present invention. The kit comprises a first compartment 1 comprising a connector 11 and a tube feed composition, a second compartment 2 comprising a connector 21 and at least one colorant, and a syringe 40 comprising a third compartment 3. The at least one colorant can be transferred in a first step from the second compartment 2 to the third compartment 3 through the needle 41 by injecting the needle 41 through the connector 21. After removal of the syringe 40 from the first compartment 1, the at least one colorant can be transferred in a second step from the third compartment 3 to the first compartment 1 comprising the tube feed composition through the needle 41, by injecting the needle 41 through the connector 11. The kit is included in a secondary packaging 100.

[0094] Figures 3a) and 3b) show kits, in which the first compartment 1 comprising the tube feed composition and the second compartment 2 comprising the at least one colorant are placed inside one container 60. The first 1 and the second compartment 2 are separated by a seal 50. The at least one colorant comprised in the second compartment 2 can be transferred to the first compartment 1 comprising the tube feed composition by the application of force. The force is applied to the first compartment 1, the second compartment 2 or to both, to break the seal 50 and allow for a mixing of the at least one colorant comprised in the second compartment 2 and the tube feed composition comprised in the first compartment 1. The force may be applied to both compartments stepwise or simultaneously. The kits are included in a secondary packaging 100.

EXAMPLES

[0095] A set of colorants was investigated for coloring properties, pH-stability and stability in the presence of secretions from the Gl tract.

Colorants

[0096] The following colorants were used in the experiments: Copper Chlorophyllin (E141(ii)):

Copper Chlorophyllin (E141(ii)) 3% AS L-WS solution (SENSIENT Colors Europe GmbH, Product number 503523).

Marine Blue: Marine Blue L-WS (SENSIENT Colors Europe GmbH, Product number 419174.

Carbon Black (E153):

Carbon Black L-WS (E153) (SENSIENT Colors Europe GmbH, Product number 409208).

Anthocyanin (E163):

Anthocyanin L-WS (E163) (SENSIENT Colors Europe GmbH, Product number 409291). Green Plant Extract (E140) (SENSIENT Colors Europe GmbH, Product number 409290).

Riboflavin 10% P-WS (E101) (SENSIENT Colors Europe GmbH, Product number 503051).

Tube Feeds

[0097] The coloring of the following commercially available tube feed compositions was investigated: Reconvan^®, Diben^®, Fresubin Energy Fibre^®- all available from Fresenius Kabi Deutschland GmbH, 61346 Bad Homburg, Germany

All tube feed compositions were tested in tube feed container containing 500 ml of the tube feed compositions. Example 1: Coloring and pH-stability

[0098] The coloring properties and pH-stability under stomach conditions of the colorants were tested

Example la: Coloring of Reconvan^®:

[0099] Colorants tested: Copper Chlorophyllin (E141(ii)), Marine Blue

3 ml of the colorants were injected through the septum of the bag containing 500 ml of Reconvan^®. The bag was shaken until a complete distribution of the colorant, samples were taken through the septum of the port using a syringe and the color was inspected visually and by colorimetric analysis.

Stability under stomach conditions: The stability of the samples obtained in the previous step under stomach conditions was tested by acidification of the samples to pH = 2.2 with hydrochloric acid followed by visible inspection.

The results are outlined in table Ela.

Table Ela: Results coloring and pH-stability testing of Reconvan®:

Example lb: Coloring of Diben^®:

[0100] Colorants tested: Copper Chlorophyllin (E141(ii)), Marine Blue, Carbon Black (E153), Green Plant Extract (E140), Anthocyanin (E163), Riboflavin (E101).

Five ml of the colorants were injected through the septum of the bag containing 500 ml of Diben^®.The bag was shaken until a complete distribution of the colorant, samples were taken through the septum of the port using a syringe, diluted 1:5 (v/v) with water and the color of all samples was inspected visually. Copper Chlorophyllin (E141(ii)) and Marine Blue were additionally investigated by colorimetric analysis. Stability under stomach conditions:

The stability of Carbon Black (E153) and Anthocyanin (E163) under stomach conditions was tested by acidification of the samples to pH = 2.2 with hydrochloric acid followed by visible inspection.

The results of both examples are summarized in table Elb. Table Elb: Results coloring and pH-stability testing of Diben^®:

¹¹ other than the color of the tube feed n.a. means colorant not tested Results:

Copper Chlorophyllin (E141(ii)), Marine Blue, Carbon Black (E153) and Anthocyanin (E163) show coloring of the different tube feeds. Additionally, the colors obtained with those colorants is stable under stomach conditions, i.e. pH=2.2.

Example 2: Stability against Gl secretions [0101] Copper Chlorophyllin(E141(ii)), Marine Blue, Carbon Black (E153) and Anthocyanin (E163) were investigated for stability against secretions from the Gl tract. Riboflavin (E1011) and Green Plant Extract were not further investigated due to their insufficient coloring properties as demonstrated in example lb. The following secretions were used:

Gastric enzymes:

Gastric enzyme solution consisting of:

- 1.5g Acetate buffer; 87.1 g Sodium acetate (Sigma-Aldrich (S1304)) 21,6 g Acetic acid (Sigma-Aldrich (A6283))

Final volume 1 1 in demineralized water

- 151g GELS: Gastric electrolyte solution:

- 310 g NaCI (Honeywell S9888 or comparable)

- 110 g KCI (Sigma-Aldrich P5405 or comparable) - 8 g CaCI2(H20)2 (Applichem A0775 or comparable)

- Total volume: 5 L in demineralized water, dilute 53g in 450g of demineralized water prior to use.

- 1.5g Pepsin: Pepsin from porcine gastric mucosa (Sigma-Aldrich P7012), 60000000 U = 24 g in 100 ml demineralized water. Bile:

Bile bovine (Sigma-Aldrich B3883), 70 mM = 18,2 g in 231,8 g demineralized water.

Pancreatic enzymes:

Pancreatic enzyme solution consisting of:

- Pancreatin (Nordmark N0066397),2900 U/ml - lipase activity - Alpha-amylase from porcine pancreas (Sigma-Aldrich A3176), 1200 U/ml - total amylase activity

- Trypsin from bovine pancreas (Sigma-Aldrich T9201), 400 U/ml - total trypsin activity

- Solvent: demineralized water SIES:

Small intestine electrolyte concentrate (25 x concentrated SIES) - 1250 g NaCI (Honeywell S9888 or comparable)

- 150 g KCI (Sigma-Aldrich P5405 or comparable)

- 25 g CaCI2(H20)2 (Applichem A0775 or comparable)

- Adjust to pH 7 - Total volume: 10 L, dilute 88g in 1920g of demineralized water prior to use.

Five ml of the colorants were injected through the septum of a bag containing 500 ml of Diben^®. The bag was shaken until a complete distribution of the colorant, samples were taken through the septum of the port using a syringe, diluted 1:5 (v/v) with water. The samples obtained after dilution were diluted 1:1 (v/v) with the secretions from the Gl tract and the color was tested visually for all samples.

Copper Chlorophyllin (E141(ii)) and Marine Blue were additionally investigated by colorimetric analysis.

The results are summarized in table E2.

Table E2: Results stability test with Gl secretions:

Result:

Copper Chlorophyllin, Carbon Black and Anthocyanin are stable against all the tested secretions from the Gl tract, whereas Marine Blue is not stable against Bile and pancreatic enzymes.

Example 3: Stability in a dynamic in vitro test (TIM-1 model)

[0102] Copper Chlorophyllin ( E141(ii )) was tested for its stability against secretion from the Gl tract during the digestion process in the dynamic in vitro test.

The TIM-1 model is an established model for the in vitro investigation of the stability of samples against Gl secretions, which is in detail described in the following publications:

Dickinson et al.; The AAPS Journal 14(2): 196-205, Feb 2012 (DOI: 10.1208/sl2248-012-9333-x),

Minekus M. et al., „The TNO Gastro-lntestinal Model (TIM)" in: Verhoeckx K.et al. (editors); "The Impact of Food Bio-Actives on Gut Hea Ith - In vitro and Ex Vivo Models", part I, chapter 5, p. 37-46. Springer Cham Fleidelberg, New York, Dordrecht, London 2015 (DOI: 10.1007/978-3-319-16104-4_5).

5 ml of Copper Chlorophyllin (E141(ii)) were injected through the septum of a bag containing 500 ml of Fresubin Energy Fibre^®. The bag was shaken until a complete distribution of the colorant. An aliquot of 100ml was taken through the septum of the port using a syringe and used for the experiment. The in-vitro digestion was performed by means of the artificial intestinal dynamic apparatus (AIDA) TIM-1 with the advanced gastric compartment. The experiment was run under stomach bolus - water fed conditions.

The starting volume of the gastric compartment comprises a total of 300 g, whereof 100 g were the colored tube feed.

From the dialyzed jejunum and ileum fraction, samples were taken during the run at 2 h time intervals as well as at the end (300 min). At 150 min run-time, a lumen sample was taken from the duodenum compartment and the entire ileum efflux sample was taken. At the end of the experiment (300 min), all remaining liquids were collected individually for all 4 compartments (stomach, duodenum, jejunum and ileum) as well as the remaining ileum efflux sample (150-300 min).

The samples were visually inspected for color appearance. Furthermore, the dialyzed samples of jejunum and ilieum were analyzed for color absorbance by means of a UV-spectrometer (Biospectrometer kinetic, Eppendorf). The samples were scanned in the wavelength range of 250-700 nm. Additionally, all samples were analyzed by using a colorimeter (Hunterlab). Copper-Chlorophyllin showed an absorption maximum in a wavelength range between 530-560 nm.

Results: The color was visually stable over the full time of the experiment (300 min) and independent of the compartments of the AIDA model. The visual impression was confirmed by the analytical results of spectrometer (transparent dialyzed samples) and colorimeter (turbid lumen samples). However, in presence of the brown secretion fluid "bile", the green color is partially overlaid. On the other hand, it can still be seen that the pure "bile" color is affected when the green color is present in the duodenum compartment. The studied color can be stated as fully stable towards human digestive fluids and furthermore the distinct color can be visually and analytical differentiated in the specific samples.

Claims

1. A kit for coloring tube feed compositions comprising at least a first (1) and a second (2) compartment, and, optionally, handling instructions; wherein the first compartment (1) comprises a tube feed composition, the second compartment (2) comprises at least one colorant selected from the group consisting of copper complexes of chlorophyllins, copper complexes of chlorophylls, vegetable charcoal, anthocyanins, spirulina, and mixtures thereof; and wherein the at least one colorant is transferable from the second compartment to the first compartment to allow a mixing of the at least one colorant with the tube feed composition.

2. The kit according to claim 1, wherein the at least one colorant is selected from the group consisting of Copper Chlorophyllin (E141(ii)), Carbon Black (E153), Anthocyanin (E163), Marine Blue, and mixtures thereof.

3. The kit according to claim 1 or 2, wherein the at least one colorant is selected from the group consisting of Copper Chlorophyllin (E141(ii)), Carbon Black (E153), Anthocyanin (E163), and mixtures thereof, preferably Copper Chlorophyllin (E141(ii)).

4. The kit according to any of the preceding claims, wherein the second compartment (2) is a container selected from the group consisting of syringes, bottles, ampules, bags, pouches, such as a stand-up pouches, vials, tubes, and capsules, preferably from syringes, bottles, bags, pouches, such as a stand-up pouches, more preferably the second compartment is a syringe.

5. The kit according to any of the preceding claims, wherein the second compartment (2) is a device for the administration of the at least one colorant into the tube feed composition, optionally via a coupling link.

6. The kit according to any of the preceding claims, wherein the second compartment (2) is connectable to the first compartment (1) to administer the at least one colorant to the tube feed composition comprised in the first compartment (1), optionally via a coupling link.

7. The kit according to any of the preceding claims, wherein the at least one colorant is transferred from the second compartment (2) to the tube feed composition comprised in the first compartment (1) by the application of force.

8. The kit according to any of the preceding claims, wherein the kit comprises a third compartment (3) for transferring the at least one colorant from the second compartment (2) to the tube feed composition comprised in the first compartment (1).

9. The kit according to any of the preceding claims, wherein the at least one colorant is transferred from the second compartment (2) to the tube feed composition comprised in the first compartment (1) through a needle (41), preferably through a septum comprised in the first compartment (1).

10. The kit according to claim 1 to 3 or 7. wherein the first (1) and the second (2) compartment are positioned inside one container (60).

11. The kit according to claim 10, wherein the first (1) and the second compartment (2) are separated by a peelable seal (50) or a permanent seal having a frangible valve (50).

12. A device for the administration of a colorant into a tube feed composition, wherein the device is connectable to a compartment comprising a tube feed composition, optionally via a coupling link, the device comprises at least one colorant, and, wherein the at least one colorant is selected from the group consisting of copper complexes of chlorophyllins, copper complexes of chlorophylls, vegetable charcoal, anthocyanins, spirulina, and mixtures thereof.

13. The device for the administration of a colorant into a tube feed composition according to claim 11, wherein the at least one colorant is selected from the group consisting of Copper Chlorophyllin (E141(ii)), Carbon Black (E153), Anthocyanin (E163), Marine Blue, and mixtures thereof.

14. The device for the administration of a colorant into a tube feed composition according to claim 11 or 12, wherein the at least one colorant is selected from the group consisting of Copper Chlorophyllin (E141(ii)), Carbon Black (E153), Anthocyanin (E163), and mixtures thereof, preferably Copper Chlorophyllin (E141(ii)).

15. A method for preparing a colored tube feed composition comprising the steps of a) providing a first compartment (1) comprising a tube feed composition, b) providing a second compartment (2) comprising at least one colorant selected from the group consisting of copper complexes of chlorophyllins, copper complexes of chlorophylls, vegetable charcoal, anthocyanins, spirulina, and mixtures thereof, c) transferring the at least one colorant from the second compartment (2) to the first compartment (1), optionally by means of a third compartment (3), to allow a mixing of the at least one colorant with the tube feed composition to obtain a colored tube feed composition.