Micronutrient compositions and systems for treating malnutrition and preventing refeeding syndrome

Abstract

Provided herein are kits, compositions, systems, and methods for treating a subject that is at risk for refeeding syndrome (e.g., a human subject that is starving and about to receive caloric support, or at risk of malnutrition or refeeding syndrome). In some embodiments, the system and kits herein provide a container (e.g., pouch for attaching to a feeding tube, or part of a syringe for feeding) that contains a micronutrient composition that contains thiamine, phosphorous, magnesium, and potassium, wherein the micronutrient composition is optionally substantially free from calories. In particular embodiments, methods herein rapidly replace micronutrients commonly depleted in the malnourished patient (e.g., that are important for tube feeding tolerance).

Description

[0001] MICRONUTRIENT COMPOSITIONS AND SYSTEMS FOR TREATING MALNUTRITION AND PREVENTING REFEEDING SYNDROME

[0002] The present application claims priority to U.S. provisional application serial number 63 / 607,664, filed December 8, 2023, which is herein incorporated by reference in its entirety.

[0003] FIELD OF THE INVENTION

[0004] Provided herein are kits, compositions, systems, and methods for treating a subject that is at risk for refeeding syndrome (e.g., a human subject that is starving and about to receive caloric support, or at risk of malnutrition or refeeding syndrome). In some embodiments, the system and kits herein provide a container (e.g., pouch for attaching to a feeding tube, or part of a syringe for feeding) that contains a micronutrient composition that contains thiamine, phosphorous, magnesium, and potassium, wherein the micronutrient composition is optionally substantially free from calories. In particular embodiments, methods herein rapidly replace micronutrients commonly depleted in the malnourished patient (e.g., that are important for tube feeding tolerance).

[0005] BACKGROUND OF THE INVENTION

[0006] There are currently more than 1 million people receiving new tube feeding in the US each year (Bloom, 2022). With the start of enteral nutrition (“EN”, aka “tube feeding”), there is an unmet need during the first 14 days of feeding the patient. Initiation of EN should be done gradually over the first few weeks. In this period, there is a micronutrient deficiency that commonly occurs. This deficiency can be prevented if the patient supplements these micronutrients. However, current supplementation is difficult and provides a risk of clogging the patients newly placed tube. Additionally, the prevalence of Home Enteral Nutrition (“HEN”) has grown significantly over the past few decades (Mundi, 2023) with patients preferring to initiate enteral nutrition at home. This change in the prevalence of HEN alongside the ongoing home healthcare shortages (USnews 2023), presents a challenging environment for those starting on EN in which Refeeding Syndrome risk is left unacknowledged and unmonitored. In a 2023 research article about HEN, it is noted that “despite knowledge that tube-related complications, EFI (enteral feeding intolerance), and electrolyte changes are common with initiation of EN in the inpatient setting, there remains a paucity of data regarding the prevalence of such complications in the HEN population” (Mundi, 2023). Refeeding Syndrome (“RFS”), a condition that occurs in patients initiating EN, can occur when a person goes from a starved state to a fed state. It is the result of a micronutrient deficiency in which intracellular ions shift out of the blood and into the cell during feeding. The clinical manifestations of Refeeding Syndrome range from mild to moderate symptoms of tachycardia, tachypnea and edema. More serious manifestations of RFS may result in irreversible neurological disorders, organ dysfunction or death. (Krutkyte 2022). Patients at high risk for RFS include those having reduced absorption (e.g. IBS, celiac), reduced intake from physical or psychosocial issues (e.g. dysphagia, alcoholism, anorexia nervosa, depression), increased metabolic demands (e.g. cancer, surgery) and anyone with “negligible food intake for more than 5 days” or chronic malnourishment (Mehanna et al). When applying the ASPEN Consensus Guidelines for RFS in 3854 enterally fed hospitalized patients, 90% were found to have at least mild RFS, 65% were found to have at least moderate RFS and 25% were found to have Severe RFS. (Adika, 2022). It is unknown how many patients suffer from this disorder in the home setting.

[0007] The ASPEN Consensus Guidelines for Refeeding Syndrome, which is our national standard for prevention and treating refeeding syndrome suggests that a minimum of lOOmg thiamine and a multivitamin be included for 7-10 days when starting enteral nutrition in patients at risk for refeeding syndrome (daSilva 2020). Patients who have home enteral nutrition initiation have a unique risk of developing refeeding syndrome.

[0008] The unique challenges of patients starting HEN include needing to crush extra tablets of vitamins to make up their nutrition needs in an environment where caregivers are “over extended.” With multi-step procedures to learn with EN, patients often omit purchasing and administering the extra vitamins, which furthers their risk for electrolyte derangements. Patients at home are typically already weak or frail and it is difficult to monitor adherence to the daily changing regimen of starting EN slowly and adding in additional nutrients and hydration. Once electrolyte derangements become more severe, they can be difficult to correct without hospitalization

[0009] SUMMARY OF THE INVENTION

[0010] Provided herein are kits, compositions, systems, and methods for treating a subject that is at risk for refeeding syndrome (e.g., a human subject that is starving and about to receive caloric support, or at risk of malnutrition or refeeding syndrome). In some embodiments, the system and kits herein provide a container (e.g., pouch for attaching to a feeding tube, or part of a syringe for feeding, or a tear-off packet) that contains a micronutrient composition that contains thiamine, phosphorous, magnesium, and potassium, wherein the micronutrient composition is optionally substantially free from calories. In particular embodiments, methods herein rapidly replace micronutrients commonly depleted in the malnourished patient (e.g., that are important for tube feeding tolerance).

[0011] In some embodiments, provided herein are systems and kits comprising: a) a container, and b) at least one of the following: i) a connector (e.g., spout) for attaching to an enteral feeding tube system, wherein the connector is integral or attached to the container, and ii) a propulsion component that is integral with, attached to, or fitted to, the container, optionally wherein the propulsion component comprises a plunger that pushes material through the container, and c) a micronutrient composition optionally present in the container, wherein the micronutrient container comprises: i) at least 10 mg of thiamine; ii) at least 20 mg of phosphorous, hi) at least 21 mg of magnesium, iv) at least 75 mg of potassium, wherein the micronutrient composition is present in the form of a rehydratable powder or in the form of a liquid solution (or some powder and some liquid, separated by a physical barrier in the container), and wherein the micronutrient composition is optionally substantially free from calories, and wherein the micronutrient composition is optionally free of: caffeine, is detectably free of sugar or has less than . 150 g (or less than 75 mg, or less than 35 mg) of sugar, or less than 5 grams of sugar, is delectably free of sodium or has less than 2000 mg of sodium (e.g., less than 1000 mg or less than 500 mg of sodium). In particular embodiments, the containers and connectors are shown, for example, in U.S. Patent 11,918,540, which is herein incorporated by reference in its entirety.

[0012] In particular embodiments, provided herein are methods of treating a patient comprising: performing at least one of the following: a) connecting the system or kit of any of those described above and herein with an enteral feeding tube system or a food syringe system, wherein said micronutrient composition is in the form of said liquid solution and wherein said connecting causes or allows said liquid solution to flow in said enteral feeding tube system or in said food syringe system; b) administering the micronutrient composition is any of those described above and herein to the patient, wherein said administering is optionally orally or via a feeding tube; and / or c) mixing water or a beverage with the any of the micronutrient compositions described above or herein to generate a liquid composition, wherein said micronutrient composition is initially present in the form of said rehydratable powder, wherein said water or beverage is optionally 125 - 250 mL or 50-12 mL, and wherein said liquid composition is administered to said subject which is optionally performed with a syringe.

[0013] In particular embodiments, provided herein are micronutrient compositions comprising: a) at least 10 mg of thiamine, b) at least 20 mg of phosphorous, c) at least 21 mg of magnesium, d) at least 75 mg of potassium, wherein said micronutrient composition is present in the form of a rehydratable powder or in the form of a liquid solution, and wherein said micronutrient composition is optionally substantially free from calories, and wherein said micronutrient composition is optionally free of: caffeine, is delectably free of sugar or has less than 150 mg of sugar, is delectably free of sodium or has less than 2000 mg of sodium. In some embodiments, the at least 10 mg of thiamine is at least 25 mg or at least 50 mg of thiamine. In other embodiments, the at least 10 mg of thiamine is at least 75 mg or at least 100 mg of thiamine. In further embodiments, the at least 10 mg of thiamine is at least 150 mg or at least 200 mg of thiamine. In additional embodiments, the at least 10 mg of thiamine is 50-200 mg of thiamine.

[0014] In certain embodiments, the liquid solution has a viscosity of between 1 centipoise and 20 centipoise (e.g., about 5-10, or about 1 1-20, or about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 centipoise), or between 1 and 50 centipoise, or between 1 and 200 centipoise. In further embodiments, the at least 10 mg of thiamine is at least 30 mg, 49 mg, 50 mg, 88 mg, 127 mg, 166 mg, 205 mg, 244 mg, 283 mg, 322 mg, 361 mg, or 400 mg, or 30-400 mg or 50 - 300 mg. In particular embodiments, the at least 10 mg of thiamine is at least 25, 30 mg, 49 mg, 50 mg, 75 mg, 88 mg, 127 mg, 166 mg, 205 mg, 244 mg, 283 mg, 322 mg, 361 mg, or 400 mg, or between 100-200 mg or between 150-250 mg.

[0015] In other embodiments, the at least 20 mg of phosphorous is 144 mg, 268 mg, 312.5 mg, 516 mg, 764 mg, 1012 mg, 1260 mg, 1508 mg, 1756 mg, 2004 mg, 2252 mg, or 2500 mg, or 20-2500 mg, or 100-1500 mg, or 200-100 mg. In other embodiments, the at least 21 mg of magnesium is 62 mg, 103 mg, 105 mg, 185 mg, 267 nm, 349 mg, 431 mg, 512 mg, 594 mg, 676 mg, 758 mg, 840 mg or 21-840 mg, or 100-700 mg or 200-600 mg. In additional embodiments, the at least 75 mg of potassium is 541 mg, 1008 mg, 1175 mg, 1940 mg, 2873 mg, 3805 mg, 4738 mg, 5670 mg, 6603 mg, 7535 mg, 8468 mg, 9400 mg or 75- 9400 mg or 150 - 500 mg, or 200-400 mg. In further embodiments, the micronutrient composition is present in the container (e.g., squeezable pouch or syringe or tear off packet), or is separate from the container.

[0016] In additional embodiments, the micronutrient composition further comprises at least one of (e.g., one of, or five of, or 10 of, or 12 of) or all of, the following: i) riboflavin (B2), optionally present at about 0.06 - 20 mg (e.g., 0.1 - 10 mg), ii) niacin (B3), optionally present at about 0.75 - 30 mg range (e.g., 1.0 - 20 mg), iii) calcium, optionally present at about 5 - 2600 mg (e.g., 20 - 1000 mg); iv) glucose, optionally present at about 1-15 grams (e.g., 5-10 grams); v) Vitamin D, optionally present at about 1-150 IUS (e.g., 10-100 IUS); vi) Zinc, optionally present at about 0.3 - 3 mgs (e.g., 1.0-2.0 mgs); vii) Folic acid, optionally present at about 20-100 mcg (e.g., 40-80 mcg); viii) B5, optionally present at about 0.1 - 1.5 mg (e.g., 1.0 - 1.3 mg); ix) B6, optionally present at about 0.04 - 0.5 mg (e.g., 0.1-0.3 mg); x) B8, optionally present at about 2.5 - 12.5 mcg (e.g., 4.0 - 10.0 mcg); xi) B9 folate, optionally present at about 20-100 mcg (e.g., 40-80 mcg); xii) B12 Cobalamin, optionally present at about 0.1 - 0.5 mcg (e.g., 0.2 - 0.4 mcg); xiii) Vitamin C, optionally present at about 4.5 - 22.5 mg (e.g., 5.0 - 15.0 mg); and / or xiv) Sodium, optionally present at about 60-625 mg (e.g., 100 - 500 mg).

[0017] In some embodiments, the micronutrient composition further comprises at least one of (e.g., one of, or five of, or nine of), or all of, the following: i) Thiamine (Bl), ii) Riboflavin (B2), iii) Niacin (B3), iv) Pantothenic acid (B5), v) Pyridoxine (B6), vi) Biotin (B7), vii) Folate (B9), viii) Cobalamin (B 12), ix) Vitamin C, and / or x) Zinc. In additional embodiments, the micronutrient composition further comprises at least one of (e.g., one of, or five of, or nine of), or all of, the following: i) Thiamine (Bl) present as Thiamine hydrochloride, ii) Riboflavin (B2) present as Riboflavin-5'-phosphate, iii) Niacin (B3) present as Nicotinic acid, iv) Pantothenic acid (B5) present as Calcium pantothenate, v) Pyridoxine (B6) present as Pyridoxine hydrochloride, vi) Biotin (B7) present as D-Biotin, vii) Folate (B9) present as Folic acid, viii) Cobalamin (B 12) present as Cyanocobalamin, ix) Vitamin C present as Ascorbic acid, and / or x) Zinc present as Zinc Chloride.

[0018] In particular embodiments, the container comprises a squeezable pouch or the body of a syringe or a hanging gravity bag. In certain embodiments, comprises a material selected from: plastic film, aluminum foil, polyethylene, polypropylene, polyethylene terephthalate (PET), and / or Linear low-density polyethylene (LLDPE). In further embodiments, the systems and kits further comprise: d) the enteral feeding tube system. In additional embodiments, the enteral feeding tube system is connected to the container via the connector. In other embodiments, the connector is selected from ENFit or Legacy connectors, or an adapter, which is optionally from Bolink.

[0019] In additional embodiments, the container has a volume of about 120 ml or about 125 mL, or about 100-150 mL. In further embodiments, the container has a volume of about 250 mL, or about 200-300 mL. In other embodiments, the container has a volume of about 500 mL, or about 400-600 mL. In additional embodiments, the container has a volume of about

[0020] 1000 mL, or about 800-1200 mL. In further embodiments, the container has a volume of about 125 ml, or about 120 ml, or about 100-150 mL, or holds up to 3, 5, or 10 or 25 grams of powdered material, and optionally has a volume to hold such up to 3, 5, or 10, or 25 grams of powdered material that has been reconstituted with water or a beverage. In certain embodiments, the micronutrient composition provides less than 5, 10, 20, 25, 50, 100, 200, or 500 calories when administered to a patient, or between 0 and 500 calories, or between 10 and 150 calories, or between 20 and 100 calories. In other embodiments, the thiamin is present at about 50 mg or about 40-60 mg, the phosphorous is present at about 312.5 mg, or about 290-330 mg, the magnesium is present at about 105 mg or about 80-120 mg, and the potassium is present at about 1175 mg or about 1000-1350 mg. In additional embodiments, the micronutrient composition provides about 25-50 calories when administered to a patient.

[0021] In other embodiments, provided herein are methods of treating a patient comprising: connecting the system or kit as described above and herein with an enteral feeding tube system or a food syringe system, wherein the micronutrient composition is in the form of the liquid solution, and wherein the connecting causes, and / or allows, the liquid solution to flow in the enteral feeding tube system or in the food syringe system. In certain embodiments, the enteral feeding tube system is present in a subject at risk for Refeeding Syndrome (RFS), wherein the subject is optionally a human subject. In particular embodiments, the subject has one of the following characteristics: subject has one of the following characteristics: undergoing enteral nutrition as a result of surgery, chemotherapy, oncology treatment, malnutrition, sarcopenia, cachexia, a treatment or condition requiring placement of a feeding tube, having reduced absorption, inflammatory bowel disease, Celiac disease, reduced intake from physical or psychosocial issues, dysphagia, alcoholism, bulimia, anorexia nervosa, depression, increased metabolic demands, GI disorders, an individual at risk for malnutrition, an individual needing assistance to meet their caloric and protein needs, cancer, post-surgery, and anyone with negligible food intake for more than 5 days, chronic malnourishment, in post-surgical recovery, in critical care, receiving chemotherapy, receiving oncology treatments, is malnourished, has sarcopenia, has cachexia, has reduced absorption of nutrients due to a gastrointestinal disorder, has physical or psychosocial issues affecting food intake, has dysphagia, has depression, has an eating disorder, has disordered eating, has anorexia nervosa, has bulimia, is fasting for medical or religious reasons, is fasting for hospital procedures, has increased metabolic demands, has trauma, has an infection, or has a severe illness, is an individual needing assistance to meet their nutritional needs, which is optionally adequate caloric and protein intake.

[0022] In certain embodiments, a syringe is used to add water or other liquid to the container (e.g., squeezable pouch) to reconstitute the powder components that may be contained in the container. After such reconstitution, the container is connected to the tube feed via a connector. In other embodiments, a syringe is used to add water or other liquid to the container (e.g., squeezable pouch) to reconstitute the powder components, and then used to withdraw the contents of the container into the syringe. Then the syringe is connected to the tube feed (with or without a connector).

[0023] In some embodiments, provided herein are methods comprising: administering the micronutrient compositions described above and herein, wherein the subject is at risk for Refeeding Syndrome (RFS). In further embodiments, the subject is at risk for RFS as they are in a starved state. In some embodiments, the methods are performed in a hospital, skilled nursing facility, a long term care facility, or a home.

[0024] DESCRIPTION OF THE FIGURES

[0025] Figure 1 shows an exemplary container (squeezable pouch) for providing the micronutrient compositions herein. The container is attached to a connector that can connect to an enteral feeding tube system or feeding syringe.

[0026] Figure 2A shows an exemplary container (pouch is shown) connected to a feeding tube directly. In such exemplary embodiments, the pouch may have an ENFit or legacy compatible spout, or similar spout. Figure 2B shows a close up an ENFit connector that can screw on the connector (spout) of the pouch shown

[0027] Figure 3A shows a container (pouch is shown) connected to a feeding tube using an adaptor (such as Bolink) between the pouch connector (spout) and the feeding tube. In such embodiments, the pouch may have, for example, a standard spout that the Bolink adaptor connects to and bridges this to the feeding tube. Figure 3B shows a close up of a Bolink adaptor.

[0028] Figure 4A shows a container (pouch is shown) that has powder / dry material that needs to be rehydrated. A syringe is connected to the pouch to transfer fluid to rehydrate the material and then the pouch will either (fig 4B) be connected to the feeding tube using a Bolink adapter, or (fig 4C) the syringe will be used to withdraw the rehydrated material and the syringe itself connected to the feeding tube to deliver the product.

[0029] DESCRIPTION OF THE INVENTION

[0030] Provided herein are kits, compositions, systems, and methods for treating a subject that is at risk for refeeding syndrome (e.g., a human subject that is starving and about to receive caloric support, or at risk of malnutrition or refeeding syndrome). In some embodiments, the system and kits herein provide a container (e.g., pouch for attaching to a feeding tube, or part of a syringe for feeding) that contains a micronutrient composition that contains thiamine, phosphorous, magnesium, and potassium, wherein the micronutrient composition is optionally substantially free from calories. In particular embodiments, methods herein rapidly replace micronutrients commonly depleted in the malnourished patient (e.g., that are important for tube feeding tolerance).

[0031] In some embodiments, the micronutrient composition contains all of, or most of, the nutrients in the left side of Table 1 below. In certain embodiments, the micronutrients are in the form shown on the right side of Table 1. In particular embodiments, the micronutrients are in the form shown in bold on the right side of Table 1.

[0032] TABLE 1

[0033] In certain embodiments, certain of the micronutrients herein are fat soluble (e.g., vitamin D3, and are mixed with co-solvents (e.g., such as transcutol (Diethylene glycol monoethyl ether, DEGEE), ethanol, 2-propanol (IP A), 1-butanol, 2-butanol, propylene glycol (PG), polyethylene glycol-400 (PEG-400), ethyl acetate (EA), and oils such as MCT oil), in order to make them soluble. In some embodiments, the containers herein (e.g., squeezable pouch) has one compartment for aqueous micronutrients and one compartment for nonaqueous micronutrients. Examples of aqueous components include, for example, those listed in Table 1. Examples of non-aqueous components include, for example, vitamin D.

[0034] In certain embodiments, the refeeding compositions herein (e.g., in a pouch type container) is a calorie free (or nearly calorie free) supplement that provides ready-to-use hydration and electrolyte flush, and is a companion to enteral formula for those starting and receiving enteral nutrition. In particular embodiments, the dose of multivitamins and thiamine is optimized to prevent re-feeding syndrome. In particular embodiments, the containers with enclosed micronutrient composition is a single-use medical food product that replaces multiple medications with one product (e.g., being simple, cost-effective, and safe). Exemplary features include: easy connection to standard enteral feeding (EN) tubes; convenient single-serving package (e.g., 4 x 4 ounce squeezable pouches per day for 14-28 days); shelf stable with no mixing needed; a thin formula that won't clog tubes and functions as flush. In certain embodiments, the medical food product herein allows tube-feeding patients to safely start enteral nutrition at home by providing an easy-to-administer medical food product specifically formulated to prevent refeeding syndrome. In particular embodiments, the medical food product herein does not clog the feeding tube system a patient is on or is starting.

[0035] In certain embodiments, an advantage of the systems and kits herein is that a single container (e.g., squeezable container, such as in Figure 1) is provided which replaces the use of syringes, multiple pills, pill crushing, etc. In certain embodiments, the container is squeezable and connectable to a feeding tube system. When used daily as a packet of four, it provides 200 mg (Bl) thiamine, a multivitamin blend, and 16 ounces of fluid. This can be performed, for example, over 2-4 weeks (e.g., at home or in a hospital or medical clinic). In particular embodiments, the container (e.g., squeezable packaging, such as in Figure 1) is lightweight, easy to self-administer, and comes ready to use.

[0036] In certain embodiments, the micronutrients are administered by connecting the container directly to an enteral feeding tube (e.g., figure 2) that has been placed in the individual in need of care. This tube can be any enteric tube, such as a nasogastric (NG) tube, a gastric (G) tube, a jejunostomy (J) tube, a nasojejunal (NJ) tube, a nasoduodenal (ND) tube, a nasoenteric tube. The connector on the feeding tube is attached directly to a compatible connector (e.g., ENFit compatible) incorporated into the container. This allows the micronutrient solution to be transferred from the container directly into the enteral feeding tube. This approach removes the need to transfer the contents of the container to an intermediate vessel, avoiding potential loss of product in the process and is amenable to selfadministration in the home or other settings.

[0037] In certain embodiments, the micronutrients are administered by connecting the container to an enteral feeding tube (all types of compatible feeding tube system) that has been placed in the individual in need of care using an intermediate adapter (e.g., figure 3). The connector on the feeding tube, and the container are both attached to an intermediate transfer device (e.g., Bolink small cap adapter) to facilitate the administration of the micronutrient solution to the individual. This simple process is amenable to selfadministration in the home or other settings.

[0038] In certain embodiments, the micronutrients within the container are in powder form and need to be rehydrated prior to administration to the individual in need of care. This is accomplished by connecting a syringe containing water or another liquid or beverage to the spout on the container and transferring said liquid to the container and reconstituted the micronutrients by mixing (e.g., figure 4a). The reconstituted micronutrients can then be administered to the patient by using an adapter (e.g., Bolink small cap adapter) to bridge between the container holding the reconstituted micronutrients and the individuals feeding tube (figure 4b). The reconstituted micronutrient can also be administered to the patient by drawing the liquid back in to the syringe and administering this directly to the individual via their feeding tube (e.g., figure 4c).

[0039] The kits, system, containers, and compositions herein (such as shown in figure 1), target the need profile for those starting EN. It is designed as a companion to enteral formula. For example, one packet (e.g., Figure 1) could be designed with a recommended serving of 4 packets per day. It is, in some embodiments, a calorie-free supplement that provides ready-to-use hydration and electrolyte flush with multivitamin and thiamine blend dose-optimized to prevent refeeding syndrome. In certain embodiments, the single use medical food product in a small size (e.g. four-ounce packet) is appropriate for all EN patients and replaces multiple medications with one product. Other design features may include, for example: i) easy connection to EN port with ENFit compatible; ii) delivered alongside prescribed formula from home infusion pharmacy; and / or iii) reduced risk for clogging when compared to crushed pill administration due to thin formula that will not clog feeding tube.

[0040] In some embodiments, the kits, system, containers, and compositions herein are designed for at-home use, though they can also be applied to inpatient or outpatient settings. In particular embodiments, the kits, system, containers, and compositions herein are designed to partner with an enteral nutrition formula to overcome micronutrient deficiency during early feeding and prevent refeeding syndrome. For example, an exemplary product may contain about 50 mg thiamine per 4 oz package, with 4 packages / day allowing one to surpass the ASPEN-recommended minimum dose. In certain embodiments, the micronutrient compositions are delivered by intravenous administration (IV).

[0041] A exemplary feeding protocol is generally as follows. A patient receiving consultation for a feeding tube is often in a transition from a fed state to a starved state. The patient comes into an outpatient setting and has anesthesia while the tube is placed. When they wake up, they may have education provided on how to use the tube. In many cases, the patient has a gap in their teaching, but is also in an altered mental state from the starvation, underlying nutrient deficiencies and anesthesia. Once they go home, they will have supplies and enteral nutrition formula shipped to them. They will need to go to the pharmacy to purchase additional supplements which is a barrier to correct the underlying nutrient deficiencies and the gap in nutrients during the gradual titration up to EN.

[0042] It is known in the art (reference 8) that there are adherence issues when using multiple medications. The current standard of care for the prevention of refeeding syndrome (use of multivitamin and thiamine) goes unrecognized by many providers and if the education is provided to the patient, follow through is difficult. The kits, system, containers, and compositions herein provide a fist- line prevention for an at-risk population. In some embodiments, it is a one size fits all approach that partners with the patient’s enteral nutrition formula and fills in the gap of micronutrient needs during the first two weeks of EN.

[0043] Further advantages provided by the kits, system, containers, and compositions herein include at least one of the following: i) improves treatment for an at risk population; ii) easier than current practice as delivery of vitamins via enteral feeding tube must be crushed, requiring strength and dexterity, mixed with water and provided via tube; iii) easily provided in the home setting; iv) use are already taught to this population and would not require additional skill; v) patients are already providing water flushes to themselves; i.e. this is not an additional step; vi) decrease risk of tube clogging resulting in tube malfunction and possible need for ER, tube replacement and delay in delivery of enteral nutrition if tube is unable to be used; vi) provide the recommended dosage of thiamine in a simple and easy way; and vii) can be prescribed by dietitian

[0044] Other standard of care options are resource and time consuming (intravenous supplements) and cannot be self-administered. They may also require transportation, additional appointments (increased clinical burden), and extra monitoring. Other advantages provides by the kits, system, containers, and compositions herein include, in certain embodiments: i) an ENFit compatible connection; ready to use formulation; iii) ingredients, in some embodiments, target needs of 90% of the adult EN population at home packaged in a 4 oz (or similar size) disposable container; iv) does not require patient manual manipulation to provide the needed vitamins (e.g. crushing of vitamins to appropriate dosage and reconstituting with water prior to administration); vi) able to provide targeted nutrients known to prevent / minimize refeeding syndrome; vii) light weight; vii) soft squeezable pouch; viii) no mixing needed; ix) easy to dispense; and / or shelf stable

[0045] REFERENCES:

[0046] 1. https: / / my.clevelandclinic.org / health / diseases / 23228-refeeding-syndrome

[0047] 2. Adika, et al., (2022b). Evaluation of the ASPEN guidelines for refeeding syndrome among hospitalized patients receiving enteral nutrition: A retrospective cohort study. Journal of Parenteral and Enteral Nutrition, 46(8), 1859-1866.

[0048] 3. Brown, et al. Home Initiated Parenteral Nutrition is a Safe and Cost-Effective Approach to Nutrition Support, https: / / nhia.org / nhif / nhif-supporting-home-infusion /

[0049] 4. Bloom, L., & Seckel, M. A. (2022). Placement of Nasogastric Feeding Tube and Postinsertion Care Review. AACN advanced critical care, 33(1), 68-84.

[0050] 5. da Silva et al., Parenteral Nutrition Safety and Clinical Practice Committees, American Society for Parenteral and Enteral Nutrition (2020). ASPEN Consensus Recommendations for Refeeding Syndrome. Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition, 35(2), 178-195.

[0051] 6. lolanda et al, The incidence of the refeeding syndrome. A systematic review and metaanalyses of literature, Clinical Nutrition 2021, 40(6), 3688-3701.

[0052] 7. Kraaijenbrink et al., (2016). Incidence of refeeding syndrome in internal medicine patients. The Netherlands journal of medicine, 74(3), 116-121.

[0053] 8. Krutkyte et al. (2022). Refeeding Syndrome: A Critical Reality in Patients with Chronic Disease. Nutrients, 14(14), 2859.

[0054] 9. McCray & Parrish. Refeeding the malnourished patient: Lessons learned. https : / / med. virginia.edu / ginutrition / wp-content / uploads / sites / 199 / 2014 / 06 / Parrish- September- 16.pdf 10. Mundi et al. Home enteral nutrition: A descriptive study. J Parenter Enteral Nutr. 2023; 47: 550-562.

[0055] 11. Rio et al. Occurrence of refeeding syndrome in adults started on artificial nutrition support: prospective cohort study. BMJ Open 2013;3:e002173. 12. https: / / www.usnews.eom / news / health-news / articles / 2023-04-26 / in-an-aging-america-a- looming-shortage-of-home -health-care-workers

[0056] 13. Mehanna HM, Moledina J, Travis J. Refeeding syndrome: what it is, and how to prevent and treat it. BMJ. 2008 Jun 28;336(7659): 1495-8. All publications and patents mentioned in the above specification are herein incorporated by reference. Various modifications and variations of the described method and system of the invention will be apparent to those skilled in the art without departing from the scope and spirit of the invention. Although the invention has been described in connection with specific preferred embodiments, it should be understood that the invention as claimed should not be unduly limited to such specific embodiments. Indeed, various modifications of the described modes for carrying out the invention which are obvious to those skilled in chemistry, medicine, and molecular biology or related fields are intended to be within the scope of the following claims.

Claims

CLAIMS:We claim:

1. A system or kit comprising: a) a container, and b) at least one of the following: i) a connector for attaching to an enteral feeding tube system, wherein said connector is integral or attached to said container, and ii) a propulsion component that is integral with, attached to, or fitted to, said container, optionally wherein said propulsion component comprises a plunger that pushes material through said container, and c) a micronutrient composition optionally present in said container, wherein said micronutrient container comprises: i) at least 10 mg of thiamine, ii) at least 20 mg of phosphorous, iii) at least 21 mg of magnesium, iv) at least 75 mg of potassium, wherein said micronutrient composition is present in the form of a rehydratable powder or in the form of a liquid solution, and wherein said micronutrient composition is optionally substantially free from calories, and wherein said micronutrient composition is optionally free of: caffeine, is detectably free of sugar or has less than . 150 g of sugar, or less than 5 grams of sugar, is delectably free of sodium or has less than 2000 mg of sodium.

2. The system or kit of claim 1 , wherein said liquid solution has a viscosity of between 1 centipoise and 20 centipoise, or between 1 and 50 centipoise, or between 1 and 200 centipoise.

3. The system or kit of claim 1 , wherein said at least 10 mg of thiamine is at least 25, 30 mg, 49 mg, 50 mg, 75 mg, 88 mg, 127 mg, 166 mg, 205 mg, 244 mg, 283 mg, 322 mg, 361 mg, or 400 mg, or between 100-200 mg or between 150-250 mg.

4. The system or kit of claim 1 , wherein said at least 20 mg of phosphorous is 144 mg, 268 mg, 312.5 mg, 516 mg, 764 mg, 1012 mg, 1260 mg, 1508 mg, 1756 mg, 2004 mg, 2252 mg, or 2500 mg.

5. The system or kit of claim 1, wherein said at least 21 mg of magnesium is 62 mg, 103 mg, 105 mg, 185 mg, 267 mg, 349 mg, 431 mg, 512 mg, 594 mg, 676 mg, 758 mg, 840 mg.

6. The system or kit of claim 1 , wherein said at least 75mg of potassium is 541 mg, 1008 mg, 1175 mg, 1940 mg, 2873 mg, 3805 mg, 4738 mg, 5670 mg, 6603 mg, 7535 mg, 8468 mg, 9400 mg.

7. The system or kit of claim 1 , wherein said micronutrient composition is present in said container.

8. The system or kit of claim 1 , wherein micronutrient composition further comprises at least one of, or all of, the following: i) riboflavin (B2), optionally present at about 0.06 - 20 mg, ii) niacin (B3), optionally present at about 0.75 - 30 mg range, iii) calcium, optionally present at about 5 - 2600 mg; iv) glucose, optionally present at about 1-15 grams; v) Vitamin D, optionally present at about 1-150 IUS; vi) Zinc, optionally present at about 0.3 - 3 mgs; vii) Folic acid, optionally present at about 20-100 mcg; viii) B5, optionally present at about 0.1 - 1.5 mg; ix) B6, optionally present at about 0.04 - 0.5 mg; x) B8, optionally present at about 2.5 - 12.5 mcg; xi) B9 folate, optionally present at about 20-100 mcg; xii) B 12 Cobalamin, optionally present at about 0.1 - 0.5 mcg; xiii) Vitamin C, optionally present at about 4.5 - 22.5 mg; and / or xiv) Sodium, optionally present at about 60-625 mg.

9. The system or kit of claim 1 , wherein micronutrient composition further comprises at least one of, or all of, the following: i) Thiamine (Bl), ii) Riboflavin (B2),iii) Niacin (B3), iv) Pantothenic acid (B5), v) Pyridoxine (B6), vi) Biotin (B7), vii) Folate (B9), viii) Cobalamin (Bl 2), ix) Vitamin C, and / or x) Zinc.

10. The system or kit of claim 1 , wherein micronutrient composition further comprises at least one of, or all of, the following: i) Thiamine (B 1 ) present as Thiamine hydrochloride, ii) Riboflavin (B2) present as Riboflavin-5 '-phosphate, iii) Niacin (B3) present as Nicotinic acid, iv) Pantothenic acid (B5) present as Calcium pantothenate, v) Pyridoxine (B6) present as Pyridoxine hydrochloride, vi) Biotin (B7) present as D-Biotin, vii) Folate (B9) present as Folic acid, viii) Cobalamin (B12) present as Cyanocobalamin, ix) Vitamin C present as Ascorbic acid, and / or x) Zinc present as Zinc Chloride.

11. The system or kit of claim 1 , wherein said container comprises a squeezable pouch or the body of a syringe or a hanging gravity bag.

12. The system or kit of claim 1, further comprising: d) said enteral feeding tube system.

13. The system or kit of claim 12, wherein said enteral feeding tube system is connected to said container via said connector.

14. The system or kit of claim 1 , wherein said connector is selected from ENFit or Legacy connectors, or an adapter, which is optionally from Bolink.

15. The system or kit of claim 1, wherein said container has a volume of about 125 ml, or about 120 ml, or about 100-150 mL, or holds up to 5, or 10 or 25 grams of powderedmaterial, and optionally has a volume to hold such up to 5, or 10, or 25 grams of powdered material that has been reconstituted with water or a beverage.

16. The system or kit of claim 1 , wherein said container has a volume of about 250 mL, or about 200-300 mL.

17. The system or kit of claim 1 , wherein said container has a volume of about 500 mL, or about 400-600 mL.

18. The system or kit of claim 1, wherein said container has a volume of about 1000 mL, or about 800-1200 mL.

19. The system or kit of claim 1 , wherein said micronutrient composition provides less than 5, 10, 20, 25, 50, 100, 200, or 500 calories when administered to a patient.

20. The system or kit of claim 1 , wherein said thiamin is present at about 50 mg or about 40-60 mg, said phosphorous is present at about 312.5 mg, or about 290-330 mg, said magnesium is present at about 105 mg or about 80-120 mg, and said potassium is present at about 1175 mg or about 1000-1350 mg.

21. The system or kit of claim 1 , wherein said micronutrient composition provides about 25-50 calories when administered to a patient.

22. A method of treating a patient comprising: performing at least one of the following: a) connecting the system or kit of any one of claims 1-21 with an enteral feeding tube system or a food syringe system, wherein said micronutrient composition is in the form of said liquid solution and wherein said connecting causes or allows said liquid solution to flow in said enteral feeding tube system or in said food syringe system; b) administering said micronutrient composition of any of claims 1-21 to said patient, wherein said administering is optionally orally or via a feeding tube; and / or c) mixing water or a beverage with said micronutrient composition of any of claims 1-21 to generate a liquid composition, wherein said micronutrient composition is initially present in the form of said rehydratable powder, wherein said water or beverage is optionally 125 - 250 mL, and wherein said liquid composition is administered to said subject which is optionally performed with a syringe.

23. The method of claim 22, wherein said enteral feeding tube system is present in a subject at risk for Refeeding Syndrome (RFS), wherein said subject is optionally a human subject.

24. The method of claim 23, wherein said subject has one of the following characteristics: undergoing enteral nutrition as a result of surgery, chemotherapy, oncology treatment, malnutrition, sarcopenia, cachexia, a treatment or condition requiring placement of a feeding tube, having reduced absorption, inflammatory bowel disease, Celiac disease, reduced intake from physical or psychosocial issues, dysphagia, alcoholism, bulimia, anorexia nervosa, depression, increased metabolic demands, GI disorders, an individual at risk for malnutrition, an individual needing assistance to meet their caloric and protein needs, cancer, post-surgery, and anyone with negligible food intake for more than 5 days, chronic malnourishment, in post-surgical recovery, in critical care, receiving chemotherapy, receiving oncology treatments, is malnourished, has sarcopenia, has cachexia, has reduced absorption of nutrients due to a gastrointestinal disorder, has physical or psychosocial issues affecting food intake, has dysphagia, has depression, has an eating disorder, has disordered eating, has anorexia nervosa, has bulimia, is fasting for medical or religious reasons, is fasting for hospital procedures, has increased metabolic demands, has trauma, has an infection, or has a severe illness, is an individual needing assistance to meet their nutritional needs, which is optionally adequate caloric and protein intake.

25. The method of claim 23, wherein said food syringe system is used to administer said micronutrient composition to a subject, such as a human.

26. The method of claim 23, wherein the method is performed within a home.

27. A method comprising: administering the micronutrient composition of any of claims 1-21 to a subject, wherein said subject is at risk for Refeeding Syndrome (RFS).

28. The method of claim 27, wherein said subject is at risk for RFS as they are in a starved state.

29. The method of claim 27, wherein the method is performed in a hospital, skilled nursing facility, a long term care facility, or a home.

30. A micronutrient composition comprising: a) at least 10 mg of thiamine, b) at least 20 mg of phosphorous, c) at least 21 mg of magnesium, d) at least 75 mg of potassium, wherein said micronutrient composition is present in the form of a rehydratable powder or in the form of a liquid solution, and wherein said micronutrient composition is optionally substantially free from calories, and wherein said micronutrient composition is optionally free of: caffeine, is detectably free of sugar or has less than 150 mg of sugar, is delectably free of sodium or has less than 2000 mg of sodium.

31. The micronutrient composition of claim 30, wherein said at least 10 mg of thiamine is at least 25 mg or at least 50 mg of thiamine.

32. The micronutrient composition of claim 30, wherein said at least 10 mg of thiamine is at least 75 mg or at least 100 mg of thiamine.

33. The micronutrient composition of claim 30, wherein said at least 10 mg of thiamine is at least 150 mg or at least 200 mg of thiamine.

34. The micronutrient composition of claim 30, wherein said at least 10 mg of thiamine is 50-200 mg of thiamine.

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