Devices and methods for preparing nutritional formulations

Abstract

To provide a device and method for preparing and / or supplementing nutritional formulations. [Solution] Exemplary embodiments of the present disclosure may relate to a device having an inlet and a chamber. Immobilized lipase, immobilized protease, and immobilized amylase may be contained within the chamber. The device may also include an outlet, and a flow path extends from the inlet through the chamber to the outlet. The chamber may include one or more sections. The lipase, protease, and amylase may be contained within one section of the chamber. The chamber may also include a first section, a second section, and a third section.

Description

[Technical Field]

[0001] Cross-reference of related applications This application claims the benefit of priority to U.S. Provisional Application No. 62 / 556,700, filed September 11, 2017, and U.S. Provisional Application No. 62 / 643,394, filed March 15, 2018, each of which is incorporated herein by reference in its entirety, and also claims the benefit of priority to U.S. Provisional Application No. 16 / 123,712, filed September 6, 2018.

[0002] Areas of disclosure Embodiments of the present disclosure relate to devices and methods for preparing and / or supplementing nutritional formulations, more specifically, to devices and methods for exposing nutritional formulations to lipases, proteases, and / or amylases, and for hydrolyzing fats, proteins, and / or carbohydrates, respectively, prior to administering the nutritional formulations to a subject. [Background technology]

[0003] background Long-chain fatty acids are important for human health and development. Many long-chain fatty acids are consumed as triglycerides, in which three long-chain fatty acids are bonded to a glycerol molecule via ester bonds. The absorption of long-chain triglycerides (LCTs) by the body first requires the enzymatic action of lipases (e.g., pancreatic lipase) and bile salts, which digest the triglycerides through hydrolysis, breaking them down into monoglycerides and two free fatty acids. The digested product, consisting of a mixture of glycerol, tri, di, and monoglycerides, as well as free fatty acids, forms mixed micelles in the watery duodenal contents along with other fat-soluble contents of food (e.g., fat-soluble vitamins and cholesterol) and bile salts. Once broken down, the monoglycerides and free fatty acids can be absorbed by intestinal cells, i.e., the epithelial cells lining the small intestine, for example, within the jejunum. The contents of these micelles (excluding bile salts) enter intestinal cells, where they are resynthesized into triglycerides, encapsulated within chylomicrons, and released into the chyliary tubules (capillaries of the intestinal lymphatic system). Medium-chain triglycerides (MCTs) are absorbed directly into the bloodstream.

[0004] Protein breakdown is a fundamental part of the human digestive system. Proteases are enzymes that break down proteins by hydrolyzing one or more peptide bonds within a protein or peptide. The human digestive tract produces several proteases, including pepsin, trypsin, and chymotrypsin. In the stomach, the inactive enzyme pepsinogen is produced, and when it comes into contact with the acidic environment of the stomach, it reacts to produce pepsin. Pepsin separates from proteins, producing smaller peptides, and begins protein digestion. The pancreas produces trypsin and chymotrypsin, protease enzymes that are released into the small intestine through the pancreatic duct. As partially digested food moves from the stomach into the intestines, trypsin and chymotrypsin produce simple amino acids that complete protein digestion and are absorbed into the bloodstream. Protein breakdown through protease enzymes is essential for a properly functioning digestive system.

[0005] Carbohydrates in food are an important and immediate energy source for the human body. Carbohydrates can be stored in the body as glycogen for future use. When carbohydrates are not properly broken down before being absorbed into the bloodstream, harmful health consequences can occur. Amylase is an enzyme that breaks down carbohydrates such as sugars and starches. Amylase is found in saliva and is secreted by the mouth as soon as a person begins to chew food. The pancreas also produces amylase, which is released into the duodenum of the small intestine. Amylase digests polysaccharides into smaller disaccharide units and finally converts them into monosaccharides such as glucose, completing the digestion of carbohydrates.

[0006] In premature infants, pancreatic exocrine function may not be fully developed at birth, and therefore, premature infants may lack sufficient amounts of the enzymes lipase, protease, and / or amylase, respectively, which are necessary for breaking down triglycerides, proteins, and carbohydrates. Maternal breast milk provides endogenous digestive enzymes that help infants digest triglycerides, proteins, and carbohydrates. For example, at birth, the mother provides the infant through breast milk with an “endogenous lipase” called bile salt-stimulated lipase (BSSL), also known as carboxyester lipase or bile salt-dependent lipase. While this can partially compensate for poor endogenous production, BSSL production may be insufficient to support proper fat absorption, for example, in premature babies. In addition, the majority of fat in mother's breast milk is MCT, in the form of palmitic acid (n-16), and therefore, mother's breast milk may lack sufficient LCT, such as docosahexaenoic acid (DHA, 22:6n-3) and arachidonic acid (ARA20:4n-6), which are important for membrane structure, function, and the development of neurons, the retina, and other tissues. In donor milk, lipases present during the pasteurization process may be inactivated by exposure to high heat, and therefore, LCT fats are not easily broken down. As a result, infants may suffer from feeding intolerance due to their inability to absorb these larger LCTs, which causes inflammation of the intestinal mucosa and localized inflammation.

[0007] Human breast milk may not meet the high daily nutrient requirements of very low birth weight infants and / or may contain nutrients in forms that may be unprocessable by immature or defective glycemic systems. For example, standard fortifications of human breast milk, designed to optimize nutrient intake, often lack sufficient protein, fat, and carbohydrates to meet nutrient requirements. This problem can be exacerbated with the use of donor milk, which is often donated by mothers of full-term infants more than one month postpartum and may have lower protein and fat content than breast milk from premature mothers.

[0008] The fat and protein content of human breast milk is highly variable, with protein levels decreasing over time. Recent studies have shown that premature infants fed fortified human breast milk (mother's milk or donor milk) accept less protein than expected and continue to grow more slowly in the short term, even with standard human breast milk fortification. While some uncertainties exist regarding optimal growth, postnatal growth disorders have not been resolved with standard human breast milk fortification. Therefore, there is a need for improved fortification of human breast milk to better achieve short-term infant growth, particularly associated with improved cognitive and neuroscientific outcomes. The ability to more efficiently process and absorb LCTs, proteins, and carbohydrates can lead to better overall nutrient absorption and, consequently, growth.

[0009] For at least the reasons stated above, current infant nutrition formulas (including mother's breast milk, donor milk, infant formulas, and / or nutritional fortifiers) may lack sufficient nutrient density for premature infants, and / or infants may be unable to absorb the nutrients provided in the formulas. Therefore, methods and devices for increasing the bioavailability of nutrients in formulas and / or increasing the nutrient density in formulas for premature infants are needed. Furthermore, patients with various malabsorption disorders may be unable to properly digest proteins, carbohydrates, and / or fats, LCTs, and other forms of fats through hydrolysis, thus blocking the absorption of proteins, carbohydrates, and / or fatty acids required to maintain health. Exemplary disorders include, but are not limited to, the following: decreased pancreatic juice secretion, acute and chronic pancreatitis, pancreatic cancer, pancreatic failure, cystic fibrosis, cerebral palsy, Crohn's disease, irritable bowel syndrome, chronically abnormal epithelial cells, amyloidosis, celiac disease, ischemia, radiation enteritis, tropical diarrhea, Whipple's disease, inadequate mixing of gastric contents, rapid gastric emptying, or both, Billroth II. Examples of conditions requiring treatment include gastrectomy, gastrocolic fistula, gastrointestinal anastomosis, insufficient digestive agents, bile duct obstruction and cholestasis, cirrhosis, chronic pancreatitis, cholestyramine-induced bile acid loss, cystic fibrosis, lactase deficiency, pancreatic cancer, pancreatectomy, sucrase-isomaltase deficiency, abnormal environment, post-diabetic abnormal motility, sclerosis cutaneously, hypothyroidism or hyperthyroidism, bacterial overgrowth due to blind loop syndrome (bile salt uncoupling), diverticulum in the small intestine, Zollinger-Ellison syndrome (low duodenal pH), acute abnormal epithelial cells, acute intestinal infection, alcohol, neomycin, impaired transport, abetalipoproteinemia, Addison's disease, chyloductal embolism due to lymphoma or tuberculosis, intrinsic factor deficiency (as in pernicious anemia), lymphangiectasia, jejunoileal bypass for obesity, short bowel syndrome, or other conditions. Other patients may also require or desire supplemental dietary support. Further improvements are needed to address these and other known issues. [Overview of the project] [Means for solving the problem]

[0010] Abstract Exemplary embodiments of this disclosure may relate to a device having an inlet and a chamber. Immobilized lipase, immobilized protease, and immobilized amylase may be contained within the chamber. The device may also include an outlet, with a flow path extending from the inlet through the chamber to the outlet.

[0011] Various embodiments of this device may include one or more of the following features: The chamber may include one or more divisions. Lipase, protease, and amylase may be contained within one division of the chamber. The chamber may include a first division, a second division, and a third division. Lipase may be contained within the first division, protease within the second division, and amylase within the third division. The chamber may include a first division and a second division, the first division of which may contain at least two of amylase, protease, or lipase. The device may further include an adjuvant (supplement), the chamber of which includes a first division and a second division, the first division of which contains the adjuvant, the adjuvant may contain at least one of vitamins, minerals, nutrients, or pharmaceuticals. The chamber or at least one of one or more divisions may be removably bonded to the device. The device may further include a first connector connected to the inlet by fluid and a second connector connected to the outlet by fluid, the first and second connectors being sized to connect to a supply pipe. At least one of lipase, protease, or amylase may be immobilized on a plurality of particles contained within the chamber.

[0012] In other exemplary embodiments, the device may include an inlet and a chamber. Lipase, protease, and amylase may be contained within the chamber. The device may also include an outlet, and a flow path extends from the inlet, through the chamber, to the outlet so that the nutritional preparation flowing through the device is exposed to the lipase, protease, and amylase. At least one of the lipase, protease, and amylase may be immobilized on a solid structure within the chamber.

[0013] Various embodiments of this device may include one or more of the following features: The solid structure may include a plurality of particles contained within the chamber, and the device may further include at least one of vitamins, minerals, nutrients, or pharmaceuticals. The chamber may include one or more divisions, and the lipase, protease, and amylase may be contained within one or more divisions. The lipase, protease, and amylase may each be contained within separate divisions of one or more divisions. The chamber or at least one of the one or more divisions may be removably bonded to the device. The lipase, protease, and amylase may each be immobilized within the chamber on one or more solid structures. The device may further include a first connector connected to the inlet by fluid and a second connector connected to the outlet by fluid, the first and second connectors being sized to connect to a supply pipe.

[0014] Both the general description above and the modes for carrying out the invention below are illustrative and descriptive only and do not limit the features claimed. As used herein, the terms “comprises,” “comprising,” “includes,” or other variations thereof are intended to cover non-exclusive inclusions, such that a process, method, article, or apparatus comprising a list of elements may include not only those elements but also other elements not expressly enumerated or specific to such process, method, article, or apparatus. In addition, the term “exemplary” is used herein in the sense of “example,” not “ideal.” Furthermore, the terms “first,” “second,” “third,” etc., are used herein for the purpose of distinguishing features from one another, rather than indicating order. For example, the first category does not necessarily precede the second category, but rather is used to mean that the first and second categories are two different features. It should be noted that all numerical values ​​disclosed or claimed herein (including all disclosed values, limits, and ranges) may have a variation of + / - 10% from the disclosed numerical values ​​(unless otherwise specified). Furthermore, in the claims, values, limits, and / or ranges mean values, limits, and / or ranges of + / - 10%. Furthermore, while some embodiments are discussed in terms of use for infants, it is considered that the methods and devices described herein may be used for subjects of all ages, including the elderly, adults, children, and infants, and for any deficiency, disease, or use not limited to premature birth. The present invention provides, for example, the following items: (Item 1) It is a device, The entrance and Chamber and, The chamber contains immobilized lipase and The chamber contains an immobilized protease, The chamber contains immobilized amylase and An outlet, wherein a flow path extends from the inlet, through the chamber, to the outlet, and the outlet; A device comprising the same. (Item 2) The device according to item 1, wherein the chamber includes one or more compartments. (Item 3) The device according to item 2, wherein the lipase, the protease, and the amylase are contained within one compartment of the chamber. (Item 4) The device according to item 2, wherein the chamber includes a first compartment, a second compartment, and a third compartment. (Item 5) The device according to item 4, wherein the lipase is contained within the first compartment, the protease is contained within the second compartment, and the amylase is contained within the third compartment. (Item 6) The device according to item 2, wherein the chamber includes a first compartment and a second compartment. (Item 7) The device according to item 6, wherein the first compartment contains at least two of the amylase, the protease, or the lipase. (Item 8) The device according to item 2, further comprising an adjuvant, wherein the chamber includes a first compartment and a second compartment, and the first compartment contains the adjuvant. (Item 9) The device according to item 8, wherein the adjuvant includes at least one of vitamins, minerals, nutrients, drugs, probiotics, or prebiotics. (Item 10) The device according to item 2, wherein at least one of the chamber or the one or more compartments is removably coupled to the device. (Item 11) The device according to item 1, further comprising a first connector fluidly connected to the inlet and a second connector fluidly connected to the outlet, wherein the first connector and the second connector are sized to connect to a supply pipe. (Item 12) The device according to item 1, wherein at least one of the lipase, the protease, or the amylase is immobilized on a plurality of particles contained within the chamber. (Item 13) A device comprising: An inlet; A chamber; Lipase contained within the chamber; Protease contained within the chamber; Amylase contained within the chamber; An outlet, wherein a flow path extends from the inlet, through the chamber, to the outlet such that a nutritional preparation flowing through the device is exposed to the lipase, the protease, and the amylase. The device, wherein at least one of the lipase, the protease, and the amylase is immobilized on a solid structure within the chamber. (Item 14) The device according to item 13, wherein the solid structure includes a plurality of particles contained within the chamber. (Item 15) The device according to item 13, further comprising at least one of vitamins, minerals, nutrients, drugs, probiotics, or prebiotics. (Item 16) The device according to item 13, wherein the chamber includes one or more compartments, and the lipase, the protease, and the amylase are contained within the one or more compartments. (Item 17) The device according to item 16, wherein the lipase, the protease, and the amylase are each contained within a separate compartment of the one or more compartments. (Item 18) The device according to item 16, wherein the chamber or at least one of the one or more sections is detachably coupled to the device. (Item 19) The device according to item 13, wherein the lipase, the protease, and the amylase are each immobilized on one or more solid structures within the chamber. (Item 20) The device according to item 13, further comprising a first connector connected to the inlet by fluid and a second connector connected to the outlet by fluid, wherein the first and second connectors are sized to connect to a supply pipe. [Brief explanation of the drawing]

[0015] The accompanying drawings incorporated herein, and constituting part thereof, illustrate the disclosed embodiments and, together with the descriptions, illustrate the principles of the disclosed embodiments. Many aspects and embodiments are described herein. Those skilled in the art will readily recognize that certain aspects or features of embodiments may be used in combination with any or all of the other aspects or embodiments described herein.

[0016] [Figure 1] Figure 1 illustrates an exemplary supply system according to an embodiment of the present disclosure.

[0017] [Figure 2A] Figure 2A illustrates an exemplary device for processing nutritional preparations according to an embodiment of the present disclosure.

[0018] [Figure 2B] Figure 2B illustrates an exemplary device for processing nutritional preparations according to an embodiment of the present disclosure.

[0019] [Figure 2C]Figure 2C illustrates an exemplary device for processing nutritional preparations according to an embodiment of the present disclosure.

[0020] [Figure 3] Figure 3 is a flowchart illustrating an exemplary method of using the device according to an embodiment of the present disclosure. [Modes for carrying out the invention]

[0021] Detailed explanation Hereinafter, exemplary embodiments of the present disclosure, described below and illustrated in the accompanying drawings, are referred to in detail. Wherever possible, the same reference numerals are used throughout the drawings to refer to the same or similar parts.

[0022] Any additional purposes and advantages of the embodiments may become partially apparent from the descriptions partially provided in the following description, or may be acquired through practice of the embodiments. It should be understood that both the above general description and the embodiments for carrying out the invention below are illustrative and descriptive only, and not limitations on the claims.

[0023] Aspects of this disclosure will be described with reference to devices for supplementing nutritional formulations, in particular devices for hydrolyzing lipids, proteins, and / or carbohydrates. Embodiments of this disclosure may generally be described with reference to human breast milk (e.g., pasteurized or unpasteurized mother's milk or donor milk), but it should be understood that embodiments of this disclosure may be used to supplement any nutritional formulation or beverage (e.g., with hydrolyzed lipids, proteins, and / or carbohydrates, or vitamins, minerals, and / or nutrients). For example, embodiments of this disclosure may be used in conjunction with any suitable enteral, infant, or oral formulation.

[0024] As used herein, the term “nutritional preparation” may include, for example, complex mixtures containing proteins, carbohydrates, fats, water, minerals, and / or vitamins. This may include liquid foods specially formulated and processed, liquids used for partial or exclusive delivery to a person using oral ingestion or tube feeding, liquids used for dietary management of a person having a limited or impaired capacity for taking, digesting, absorbing, or metabolizing normal foods or certain nutrients due to therapeutic or medical needs, liquids that meet medically determined nutrient requirements, and liquids designed to deliver nutrients to a subject that cannot be provided to the subject through dietary management and modifications of a normal diet alone. In some embodiments, “nutritional preparation” may include enteral or parenteral preparations, or mixtures of enteral or parenteral preparations.

[0025] In some embodiments, the nutritional preparation may be delivered to a subject under medical supervision, may be intended only for persons under active and continuous medical supervision, or may be delivered to a subject for home use, either under supervision or unsupervised. The nutritional preparation may be packaged as a dry powder and then mixed with a solvent to form a solution, or packaged as a liquid nutritional preparation, beverage, or drink. In some embodiments, the nutritional preparation may be commercially available or prepared by a healthcare professional before supply. In some embodiments, the nutritional preparation may contain a drug and / or at least one drug prescribed for a subject requiring the nutritional preparation, or the nutritional preparation itself may be a prescribed drug. The nutritional preparation may be an infant and / or toddler preparation as a complete or partial substitute for human breast milk, whether pasteurized or unpasteurized, may be donor milk, or may be mother's milk (the infant's own mother or another mother's milk).

[0026] Nutritional formulations may or may not contain at least one fat in triglyceride forms such as short-chain triglycerides (SCTs), MCTs, and LCTs. Nutritional formulation 110 may or may not contain at least one protein and may or may not contain at least one carbohydrate. In some embodiments, the nutritional formulation may further contain water, maltodextrin, protein, amino acids, peptides, SCTs, MCTs, LCTs, diglycerides, monoglycerides, corn starch, fish oil, soybean oil, rapeseed oil, cottonseed oil, sunflower oil, olive oil (the oil may or may not be refined), soluble fiber, lecithin, magnesium chloride, sodium ascorbate, guar gum, calcium phosphate, salt, choline chloride, phosphoric acid, calcium citrate, sodium phosphate, taurine, magnesium oxide, zinc sulfate, potassium chloride, niacin Vitamin A, ferrous sulfate, calcium pantothenate, manganese sulfate, pyridoxine hydrochloride, copper sulfate, thiamine nitrate, beta-carotene, riboflavin, arginine, palmitic acid, other antioxidants, folic acid, biotin, selenium (sodium selenite), chromium chloride, potassium iodide, sodium molybdate, soluble fiber, fructooligosaccharides, prebiotics, citric acid, vitamin A, vitamin D, vitamin E, vitamin K, vitamin B1, vitamin B2, vitamin B3, vitamin B5, vitamin B6, vitamin B7, vitamin B9, and vitamin B 12 It may contain at least one nutrient selected from the following. Exemplary nutritional formulations and systems are described in U.S. Patent Application No. 14 / 378,856, filed on 14 August 2014, which is now U.S. Patent No. 9,668,942 (incorporated herein in whole by reference).

[0027] In some respects, the exemplary nutritional formulations may contain one or more probiotics. As used herein, the term “probiotics” may refer to microorganisms that, when administered in appropriate amounts, can provide health benefits to a host. These health benefits may include those relating to gut health, oral health, and / or immune health. Probiotics may be prepared in a dry form (e.g., powder). In some examples, the dry form of probiotics may be mixed (e.g., dissolved or suspended) with other ingredients in the nutritional formulation.

[0028] The probiotics described herein may include naturally occurring microorganisms. Alternatively, or in addition, the probiotics may include modified microorganisms, such as those produced by selective culture or genetic engineering. Examples of probiotics include, but are not limited to, fungi such as Saccharomyces, Devalomyces, Candida, Pitia, Torlopsis, Aspergillus, Rhizopus, Mucor, Penicillium, and / or Torlopsis, as well as bacteria such as Bifidobacterium, Bacteroides, Clostridium, Fusobacterium, Melisococcus, Propionibacterium, Streptococcus, Enterococcus, Lactococcus, Cochlea, Staphylococcus, Peptostreptococcus, Bacillus, Pediococcus, Micrococcus, Leuconostoc, Weissella, Aerococcus, Oenococcus, and / or Lactobacillus. In some examples, the probiotics in the nutritional preparation include Aspergillus niger, Aspergillus oryzae, Bacillus coagulans, Bacillus lentus, Bacillus licheniformis, Bacillus mecentelicus, Bacillus pumilus, Bacillus subtilis, Bacillus natto, Bacteroides amyrophilus, Bacteroides capillosus, Bacteroides luminicola, Bacteroides swiss, Bifidobacterium adorescentis, Bifidobacterium animalis, Bifidobacterium breve, Bifidobacterium bifidum, Bifidobacterium infantis, Bifidobacterium lactis, Bifidobacterium Bifidobacterium longum, Bifidobacterium pseudolongum, Bifidobacterium thermophyllum, Bacillus tetrasporus, Bacillus evolacticus, Candida pintrepesii, Clostridium butyricum, Enterococcus cremoris, Enterococcus diacetylactis, Enterococcus faecium, Enterococcus intemidium, Enterococcus lactis, Enterococcus muntodi, Enterococcus thermophilus, Escherichia coli, Cleberomyces fragilis, Lactobacillus acidophilus, Lactobacillus alimentarium, Lactobacillus amyroborus, Lactobacillus crispatus,Brevibacillus brevis, Lactobacillus casei, Lactobacillus carbadus, Lactobacillus cellobiosus, Delbrueckii bulgaricus, Lactobacillus farciminis, Lactobacillus fermentum, Lactobacillus gasseri, Lactobacillus helveticus, Lactobacillus, Lactobacillus plantarum, Lactobacillus johnsonii, Lactobacillus reuteri, Lactobacillus rhamnosus, Lactobacillus sakei, Lactobacillus salivarius, Lactobacillus gasseri, Lactobacillus fermentum, Lactobacillus rhamnosus, Lactobacillus salivarius, Leuconostoc mesenteroides, Pediococcus damnosus, Pediococcus acidilactici, Pediococcus pentosaceus, Pediococcus urinae, Propionibacterium freudenreichii, Propionibacterium shermanii, Saccharomyces cerevisiae, spore-forming lactic acid bacteria, Staphylococcus carnosus, Staphylococcus xylosus, Streptococcus infantarius, Streptococcus thermophilus, Streptococcus lactis, and / or derivatives thereof, or any mixture thereof may be included.

[0029] In some aspects, the probiotics may be present in the nutritional composition in an amount sufficient to provide health benefits. In some embodiments, the concentration of probiotics in the nutritional composition is about 10 2 colony forming units (cfu / g) to about 10 12 cfu / g, about 10 2 cfu / g to about 10 6 cfu / g, about 10 4 cfu / g to about 10 8 cfu / g, about 10 6 cfu / g to about 10 10 cfu / g, or about 10 8 cfu / g to about 10 12 cfu / g. As used herein, the term "about" is understood to encompass ±5% of the specified amount or value.

[0030] In some respects, exemplary nutritional formulations may include, in addition to or as an alternative, one or more prebiotics. As used herein, the term “prebiotics” includes, but is not limited to, substances that induce the growth and / or activity of probiotics. Examples of prebiotics include, but are not limited to, non-digestible carbohydrates such as resistant starch, hemicellulose, pectin, gum, galactooligosaccharides, fructooligosaccharides, maltooligosaccharides, lactulose, isomaltoligosaccharides, transgalactooligosaccharides, xylooligosaccharides, soy oligosaccharides, inulin, arabinogalactan, lactitol, and lactulose; fiber sources such as oat gum, bean fiber, apple fiber, pectin, guar gum, psyllium husk, glucomannan, or guar gum hydrolysate; any derivatives thereof; and / or any combination thereof.

[0031] As described above, in some aspects, exemplary nutritional formulations may not contain sufficient amounts of nutrients, such as lipids, proteins, and / or carbohydrates, for the needs of a patient, for example, a premature infant, or the patient may desire further supplementation. In some aspects, the nutrients contained in the nutritional formulations may not be in a form that is digestible or absorbable to the patient. Embodiments of the present disclosure may be used to provide nutritional formulations that deliver increased concentrations of hydrolyzed lipids, proteins, and / or carbohydrates, such as monoglycerides, free fatty acids, glucose, and amino acids, which can be absorbed through the intestines of an infant or other patient as they are fed. As a result, the subject to which the formulation is fed may be provided with, for example, docosahexaenoic acid ("DHA"), eicosapentaenoic acid ("EPA"), arachidonic acid ("ARA" or "AA"), or one or more of other lipids, carbohydrates, or proteins that would otherwise be inaccessible or impossible to digest.

[0032] Embodiments of the present disclosure relate to devices and methods for increasing the amount of total calories, energy, protein, and / or carbohydrates in a nutritional preparation, and / or increasing the bioavailability of nutrients in a nutritional preparation, without significantly increasing the overall volume of the nutritional preparation supplied to a patient (for example, by increasing the nutrient density of the preparation so that a larger portion of the nutrients can be absorbed by the patient, and / or by making the nutrients in the nutritional preparation more readily taken up by the patient). By not substantially increasing the amount of preparation to be supplied to the patient, or by reducing the volume of the nutritional preparation to be supplied to the patient due to the increased concentration and / or bioavailability of nutrients, embodiments of the present disclosure can reduce the inflammatory response found in the patient's (e.g., premature infant) GI duct and / or can modulate the patient's GI duct for improved overall absorption of nutrients, including, but not limited to, proteins and vitamins.

[0033] According to various embodiments, the present disclosure provides devices and methods for preparing nutritional formulations. The devices and methods may be used to expose infant formulations or other nutritional formulations to lipases, proteases, and / or amylases prior to consumption. Lipases, therefore, break down fats and oils, with the subsequent release of free fatty acids and monoglycerides. Proteases, therefore, break down proteins and peptides, with the subsequent release of peptides and amino acids. Amylases, therefore, break down carbohydrates such as sugars and starches into glucose, simple carbohydrates, and oligosaccharides. The devices and methods provide a convenient method for preparing nutritional formulations. In some embodiments, the devices and methods enable infants or others consuming nutritional formulations to avoid consumption of exogenous lipases, proteases, and / or amylases. In some embodiments, the device and method enable the production of formulations containing monoglycerides, free fatty acids, glucose, and / or amino acids, but without any significant amounts of lipase, protease, and / or amylase.

[0034] An exemplary device may include one or more chambers containing immobilized or free (i.e., unimmobilized) lipases, proteases, and / or amylases through which a nutritional preparation can pass to hydrolyze lipids, proteins, and / or carbohydrates in the nutritional preparation. The exemplary device may be fluidly connected to a nutritional preparation source and / or supply system for delivering the nutritional preparation to supplement the nutritional preparation with hydrolyzed lipids, proteins, and / or carbohydrates. Exemplary devices and exemplary systems through which they may be included are described further below.

[0035] Figure 1 illustrates an exemplary dispensing system 100 for dispensing a nutritional preparation 110 to a target, for example, via a dispensing tube. In some embodiments, the system 100 may be an enteral dispensing system, while in other embodiments, the system 100 may be a parenteral dispensing system. As shown in Figure 1, the device of the present disclosure may include a container 115 configured to hold the nutritional preparation 110. The exemplary system 100 may include a pump 120 and a tube 122 that fluidly connects a source of the nutritional preparation 110 to an outlet configured to output the nutritional preparation 110 to a patient for ingestion. The container 115 may include, for example, a dispensing bag, a vial, a syringe, a bottle, or any other suitable container. The nutritional preparation 110 may be dispensed from the source container through the tube 122 to the patient. The tube 122 may be an enteral feeding tube for supplying the nutritional preparation 110 to the target GI tube, for example, through the patient's nose, mouth, stomach, or abdomen, such as a stomach, nasogastrostomy, nasoduodenum, nasajeweria, gastrostomy, gastrojejunostomy, jejunostomy, percutaneous endoscopic gastrostomy (PEG) tube, or jejunal feeding tube. In such embodiments, the system 100 may be used in accordance with standard enteral feeding practices. In some embodiments, the tube 122 may be a parenteral feeding tube for supplying the nutritional preparation 110 to the target bloodstream, for example, through an external or internal jugular vein, subclavian and axillary veins, femoral vein, arm veins, leg veins, or scalp veins. In such embodiments, the system 100 may be used in accordance with standard parenteral feeding processes.

[0036] The flow of the nutritional preparation 110 through the system 100 in Figure 1 may be controlled by a pump 120 of the system 100. In some embodiments, the pump 120 may be a peristaltic pump, but any suitable type of infusion pump, such as an elastomer pump, a multi-channel pump, a syringe pump, and / or a smart pump, may be used. The flow rate of the nutritional preparation 110 through the tube and / or device 200 may be set and / or adjusted by the pump 120. In some embodiments, the pump 120 may include a processor, a display, and / or actuators (e.g., buttons, knobs, touchscreens, etc.) to adjust and control the flow rate of the nutritional preparation 110 in the system 100 and device 200. The pump 120 may be adjusted and set by a healthcare worker and / or the recipient of the nutritional preparation 110. Pump 120 may perform continuous supply, pulsating supply, intermittent supply, bolus supply, and / or jet supply, and the fluid delivery may be set or adjusted automatically, semi-automatically, or manually.

[0037] In other embodiments, the system 100 in Figure 1 may not include the pump 120, and instead, the nutritional preparation 110 may be flowed from the container 115 to the target by gravity. The relative positioning of the source of the nutritional preparation 110 may allow the nutritional preparation 110 to flow through the tubes and device 200 under the influence of gravity alone. For example, the container 115 of the nutritional preparation 110 may be positioned above the tubes to which it is attached, above the device 200, and / or above the patient.

[0038] In other embodiments, the pump 120 of system 100 may be replaced with a syringe. The syringe may be filled with a nutritional preparation 110, and the flow rate of the nutritional preparation 110 in the tube and device 200 may be set and / or adjusted manually, semi-automatically, or automatically by using the syringe. For example, the nutritional preparation 110 may be pre-packaged in a pre-filled syringe mounted inside an automatic injector-like device. The pre-packaged preparation may also contain a pump "engine" (e.g., a spring-loaded piston) and may be used to deliver the preparation to a target through system 100 or in any other supply system.

[0039] In other embodiments, the system 100 may use any suitable means, such as a balloon or other suitable pressure generating device, to generate a pressure drop or flow driving force to drive the nutritional preparation 110 through the tube and / or device 200.

[0040] The system 100 in Figure 1 may include a fat, protein, and / or carbohydrate hydrolysis device 200. A nutritional preparation 110 may be flowed from a container 115 through a first tube 122 to the device 200, where the nutritional preparation 110 is hydrolyzed. The system 100 may also include a second tube 124 having a first end configured to connect to the outlet of the device 200, and a second end opposite the first end, configured to connect to a patient delivery device (e.g., a port, catheter, needle) or directly to the patient, and to deliver the processed nutritional preparation 110 from the device 200 to the patient for administration. The second tube 124 may be an enteral feeding tube for supplying the nutritional preparation 110 to the target GI tube, for example, through the patient's nose, mouth, stomach, or abdomen, such as a stomach, nasogastrostomy, nasoduodenum, nasohiejunum, gastrostomy, gastrojejunostomy, jejunostomy, percutaneous endoscopic gastrostomy (PEG) tube, or jejunal feeding tube. The system 100 may be used in accordance with standard enteral feeding practices. In some embodiments, the tube 124 may be a parenteral feeding tube for supplying the nutritional preparation 110 to the target bloodstream, for example, through an external or internal jugular vein, subclavian and axillary veins, femoral vein, arm veins, leg veins, or scalp veins. In such embodiments, the system 100 may be used in accordance with standard parenteral feeding processes. Exemplary embodiments of the supply system 100 and hydrolysis device 200 are described in U.S. Patent Application No. 15 / 291,530 filed on 12 October 2016, and U.S. Patent Application No. 14 / 378,856 filed on 14 August 2014, which is now U.S. Patent No. 9,668,942 (both incorporated herein by reference as a whole).

[0041] The system 100 in Figure 1 is configured to deliver and process the nutritional preparation 110, for example, at a point of care, so that the device 200 can hydrolyze the fats, proteins, and / or carbohydrates contained in the nutritional preparation 110 prior to administration of the nutritional preparation to a subject. As used herein, “processing” by the device 200 or any other device discussed herein may refer to the hydrolysis of fats, proteins, and / or carbohydrates already contained in the nutritional preparation 110 by exposing the nutritional preparation 110 to lipases, proteases, and / or amylases contained within the device 200. Processing may also refer to supplementing the nutritional preparation 110 with additional nutrients that may be contained within the device 200. As described in detail below, the device 200 may contain one or more lipases, proteases, and / or amylases.

[0042] In some embodiments, one or more of the lipase, protease, and / or amylase may be immobilized such that the nutritional preparation 110, which is supplied to the subject via an enteral or parenteral feeding mechanism or other feeding mechanism (e.g., a baby bottle), does not contain one or more of the lipase, protease, and / or amylase in any perceptible amount. For example, the lipase, protease, and / or amylase may be immobilized along the wall or on or within a structure of the device 200 found elsewhere in the container, so that the lipase, protease, and / or amylase are in fluid contact with the nutritional preparation 110 as it passes through the device 200. Furthermore, as discussed with reference to the various embodiments below, the nutritional preparation 110 may be added to the device 200 in various ways to enable enzymatic treatment of the lipase, protease, and / or amylase within the device 200. System 100 in Figure 1 is provided solely as an embodiment of a supply system in which it may be used in combination with device 200. This disclosure relates to devices and methods for supplying nutritional products and may be used in combination with any other suitable supply system.

[0043] The devices and methods disclosed herein may be used to expose a nutritional preparation 110 to lipase, amylase, and / or protease prior to consumption, and to hydrolyze lipids, proteins, and / or carbohydrates in the nutritional preparation 110. In some embodiments, the devices and methods provide a preparation containing monoglycerides, free fatty acids, amino acids, and / or glucose, or increased concentrations of monoglycerides, free fatty acids, amino acids, and / or glucose, but not containing significant amounts of lipase, protease, and / or amylase, or not containing lipase, protease, and / or amylase.

[0044] Figure 2A illustrates an exemplary device 201 according to an embodiment of the present disclosure. The device 201 may include a body 210 having an inlet 212, a chamber 222, and an outlet 230. The chamber 222 may include three distinct sections 222a, 222b, and 222c. The sections 222a, 222b, and 222c may be spaced apart from each other within the chamber 222, in direct contact with each other within the chamber 222, or formed by partitions dividing parts of the chamber 222. Each section may be uniform in shape and / or size, or one or more sections may vary in shape and / or size. Figure 1 depicts three sections within the chamber 222, but in various embodiments, the chamber 222 may include a single section, two sections, or four or more sections. One or more of sections 222a, 222b, and 222c may be fixed within the chamber 222 and / or the body 210, or may be removable from the chamber 222 and / or the body 210 of the device 201. The chamber 222 may be removable or fixed within the body 210. A chamber 222 containing the sections is described, but it is considered that the body 210 may contain each of the sections, and may not contain separate chambers 222.

[0045] Each section 222a, 222b, and 222c may contain an enzyme. For example, each section may contain a different enzyme or a different combination of enzymes, or some sections may contain the same type of enzyme as another section. In some embodiments, sections 222a, 222b, and 222c may contain one of lipase, amylase, or protease. A section may contain a single type of enzyme (e.g., all lipase, all amylase, or all protease), a single type of lipase, amylase, or protease, or a combination thereof (e.g., multiple types of lipase, multiple types of amylase, or multiple types of protease). The sections may be arranged in any order such that any of the amylase, protease, or lipase sections may be located furthest upstream, furthest downstream, or in the center of chamber 222. The enzymes within the various segments may be free (i.e., not immobilized), immobilized, or a combination thereof. For example, one or more segments may contain one or more structures (e.g., one or more walls of a segment or distinct structure, e.g., multiple particles 300) to which lipases, proteases, and / or amylases can be immobilized, for example, via covalent or ionic bonding, or for example, by absorption.

[0046] The enzymes contained within the various sections can react with the nutritional preparation as it flows from the inlet 212 through the chamber 222 to the outlet 230. For example, a lipase in one section may hydrolyze lipids present in the nutritional preparation as it flows through the lipase section, a protease in one section may hydrolyze proteins present in the nutritional preparation as it flows through the protease section, and an amylase in one section may hydrolyze carbohydrates present in the nutritional preparation as it flows through the amylase section.

[0047] As shown in Figure 2A, sections 222a, 222b, and 222c may be separated by section interfaces 224a and 224b, which may include one or more filters. Section interfaces 224a and 224b may allow nutritional preparations containing one or more of hydrolyzed lipids, hydrolyzed proteins, and / or hydrolyzed carbohydrates to pass, for example, from section 222a to section 222b or from section 222b to section 222c, while preventing lipases, proteases, and / or amylases (and / or structures to which they are bound) from passing through each section interface 224a and 224b. In some aspects, interfaces 224a and 224b may allow some enzymes, such as lipases, proteases, or amylases, to pass through, but may prevent other specific enzymes from flowing through the interface. Interfaces 224a and 224b may be filters and / or made from any suitable material and may have any suitable coating.

[0048] In some embodiments, sections 222a, 222b, and 222c may be separated by one or more valves to control the flow of the nutritional preparation. In some embodiments, one or more sections may include outlets and / or inlets through which the nutritional preparation exits or enters the section. The outlets and / or inlets may have a width less than the width of the chamber 222 or the maximum width of the individual sections, or they may have a width equal to the width of the chamber 222 or the maximum width of the individual sections. In some embodiments, the outlet of one section may be fluidly connected to the inlet of an adjacent section. In some embodiments, the inlets and outlets of different sections may be directly connected, or they may be spaced apart. If they are spaced apart, pipes, funnels, or some other suitable structure may be connected to the outlets and inlets of the sections.

[0049] The separate sections 222a, 222b, and 222c may contain one of lipase, amylase, and / or protease, and the lipase, amylase, and / or protease may or may not be immobilized. In some embodiments, section 222a may contain immobilized lipase, section 222b may contain immobilized protease, and section 222c may contain immobilized amylase. In other embodiments, chamber 222 may contain two sections. Each of the two sections may contain one of lipase, protease, or amylase. In other embodiments, one or both of the two sections may contain two enzymes (e.g., lipase and protease, lipase and amylase, protease and amylase), and / or one of the sections may contain lipase, protease, and / or amylase. In other embodiments, the chamber 222 may include more than three sections, and lipase, protease, and / or amylase (or any combination thereof) may be contained within any number of the more than three sections of the chamber 222.

[0050] The separate sections 222a, 222b, and 222c may be part of a single chamber 222, or they may each be separate chambers arranged in series within the chamber 222 and / or the body 210. The separate sections or chambers may be interchangeable, replaceable, and / or refillable, or they may be fixed within the chamber 222 and / or the body 210. In some embodiments, the chamber 222 may be removable from the body 210, or each section may be removable from the chamber 222 and / or the body 210. In some embodiments, the body 210, the chamber 222, and / or one or more of the sections 222a, 222b, and 222c may be sterilized or sterilizable. In some embodiments, the chamber 222 and / or one or more of the sections 222a, 222b, and 222c may be pre-filled with particles and / or enzymes (e.g., proteases, amylases, and / or lipases).

[0051] In some embodiments, the chamber 222 and / or one or more of the sections 222a, 222b, 222c may be provided in a closed and sealed configuration and may be opened immediately before placement in the device 201. In some embodiments, a user (e.g., a healthcare worker, patient, patient caregiver, pharmacist, or other user) may insert and / or place the chamber 222 and / or one or more of the sections 222a, 222b, 222c into the device 201 prior to use. In some embodiments, the chamber 222 and / or one or more of the sections 222a, 222b, 222c may be pre-filled. In other embodiments, a user may fill the chamber 222 and / or one or more of the sections 222a, 222b, 222c with a desired type and / or amount of enzyme (structure, e.g., whether bound to particles) or a combination thereof. In some embodiments, the chamber 222 and / or one or more of the sections 222a, 222b, 222c may be configured to be cleaned, sterilized, and refilled so that they are removable and disposable after use, and / or reusable. In other embodiments, the chamber 222 and / or one or more of the sections 222a, 222b, 222c may be permanently stored within the device 210. In some embodiments, the chamber 222 and / or one or more of the sections 222a, 222b, 222c may include access ports for refilling the sections or emptying their contents.

[0052] Device 201 may also include an interface 225 through which a nutritional preparation containing unhydrolyzed lipids, proteins, and / or carbohydrates can flow from a source of nutritional preparation into Device 201. In some embodiments, the interface 225 may be configured to fluidly connect to a connector 240 or to a connection from a supply tube (e.g., an enteral or parenteral supply tube), tubing from a breast pump, or another source of nutritional preparation. In some embodiments, Device 201 may not include the interface 225 and may connect directly to tubing or other devices connected to a source of nutritional preparation, or may connect directly to a source of nutritional preparation.

[0053] Device 201 may also include an interface 223 through which a nutritional preparation containing hydrolyzed lipids, proteins, and / or carbohydrates can pass out of Device 210 and be supplied to a subject. In some embodiments, the interface 223 may be configured to fluidly connect to a connector 235 or to an opening in a supply tube (e.g., an enteral or parenteral supply tube) or any other suitable container (e.g., a bottle, cup, bag, vial, etc.) in which the nutritional preparation can be stored or administered. In some embodiments, Device 201 may not include the interface 223 and may connect directly to tubes, a supply device, or a patient, for example.

[0054] In the embodiment shown in Figure 2A, interfaces 223 and 225 are fluidly connected to connectors 235 and 240, respectively. Connectors 235 and 240 may be part of device 201, or they may be separate from device 201 and configured to be removablely connected to device 201 (e.g., via interfaces 223 and 225). In some embodiments, device 201 may not include connectors 235 and 240. Connector 240 may be fluidly coupled to a source of nutritional preparation 110 and configured to receive input of nutritional preparation 110. For example, connector 240 may be fluidly coupled to a supply tube (e.g., enteral or parenteral supply tube), tubing from a breast pump, or a connection from another source of nutritional preparation. Connector 235 may be fluidly coupled to a structure configured to deliver the processed nutritional preparation 111 to a target, such as a supply tube, and may be configured to release the output of the processed nutritional preparation 111. For example, the connector 235 may be configured to connect fluidly to an opening in a supply tube (e.g., an enteral or parenteral supply tube) or any other suitable container in which the nutritional preparation 110 can be stored or administered (e.g., a bottle, cup, bag, vial, etc.).

[0055] In some embodiments, the first connector 240 and / or the second connector 235 may be configured to fluidly connect to, for example, the first tube 122 and one or both of the enteral or parenteral tube 124 of the system 100 (Figure 1) in which the device 200 is located. As the nutritional preparation 110 flows through the system 100 (or any other suitable supply system), the nutritional preparation 110 from the supply source may be received in the connector 240, flow through one or more of the interface 225, chamber 222, sections 222a, 222b, and 222c (or additional sections depending on the sections contained within the device 201), or flow out of the connector 235 through the interface 223. While inside the chamber 222, lipases, proteases, and / or amylases in one or more of the compartments may hydrolyze lipids, proteins, and / or carbohydrates in the nutritional preparation 110, and the processed nutritional preparation 111 may then flow out of the connector 235 through the interface 223 for administration to the subject. The device 201 may be configured to allow the lipases, proteases, and / or amylases to remain inside the chamber 222 and / or its individual compartments, while the nutritional preparation 110 passes through the device 201, and the processed nutritional preparation 111 exiting the device 201 is supplied to the subject.

[0056] Connectors 240 and 235 may include, for example, Luer locking connections, threads, projections, grooves, deformable or expandable structures, and / or any other suitable mechanisms for connecting to one or more tubes or devices for transporting nutritional preparations from a source and / or to a patient. One suitable connector known in the art is the ENFit® connector (GEDSA). In some embodiments, connectors 240 and / or connector 235 may be configured to engage with a baby bottle, baby bottle nipple, or any other structure to facilitate the transport of fluid to another container and / or assist in dispensing or storage. Furthermore, one or both of connectors 240 and 235 may include valves or other fluid flow control mechanisms or filters.

[0057] Interfaces 223, 225 may, in some embodiments, include one or more filters to prevent particles 300 (or other structures to which lipase, protease, and / or amylase may be immobilized) from leaving the chamber 222 of device 201. In addition, or alternatively, filters within device 201 (interfaces 223, 225, 224a, 224b, etc.) may prevent foreign matter from entering the chamber 222 and / or the feed tube 124. One or more of interfaces 223, 225, 224a, 224b may include a semipermeable membrane to prevent or block enzymes (lipase, protease, and / or amylase) from leaking out of device 201 and / or into the processed nutritional preparation 111 exiting device 201, between sections of chamber 222. The particles 300 (or other structures on which lipase, protease, and / or amylase may be immobilized) may be separated by interfaces 225 and 223 (in embodiments where interfaces or filters are used between sections). Interfaces 225 and 223 may retain the particles 300 (or other structures and / or enzymes) within the chamber 222 and / or its own section as the nutritional preparation 110 flows through the device 201.

[0058] In one exemplary embodiment, the chamber 222 of the device 201 may be made of clear plastic or glass so that the multiple particles 300 (or other structures or enzymes) inside the chamber 222 are visible to the user. In some cases, this may allow the user to ensure proper flow through the device 201, for example, by visual inspection. In other embodiments, the chamber 222 may be opaque or made of any suitable material. The particles 300 contained within the device 201 may have lipase, protease, and / or amylase immobilized on their surface, and as the nutritional preparation 110 flows through the chamber 222 and particles 300, the immobilized lipase, protease, and / or amylase hydrolyze the fats (e.g., triglycerides), proteins, and / or carbohydrates in the nutritional preparation 110.

[0059] In some embodiments, the chamber 222 may be filled / refilled with immobilized lipase, protease, and / or amylase, or may be pre-filled, and may not be refillable as described above. In some such embodiments, the user may, prior to use, select between different enzymes (e.g., lipase, protease, amylase), combinations of enzymes, and / or pre-filled devices 201 with a certain volume of enzyme. The chamber 222 may be replaceable, and the device 201 may be separated into its components, allowing for the exchange of the chamber 222, one or more sections, or any other components of the device 201. The refillable chamber 222 and / or refillable sections may be refillable prior to use, in the meantime, and / or thereafter. If the chamber 222 and / or sections are refillable, they may have one or more inlets (not shown), for example, one or more resealable inlets. In some embodiments, a user (e.g., a healthcare professional, patient, patient caregiver, pharmacist, or other user) may assemble the device 201 prior to use. For example, the user may select pre-filled chambers 222 and / or desired individual compartments containing the desired enzyme, and assemble the device 201 with the selected pre-filled chambers 222 and / or pre-filled compartments. In some embodiments, the chambers 222 and / or individual compartments may be pre-filled, and the user may select between different types of enzymes or combinations of enzymes, and / or select different volumes of enzymes, for example, depending on the patient's needs. In such embodiments, the chambers 222 and / or compartments may have sealed openings from which the seals are peeled prior to assembly of the device 201, or the action of assembling the chambers 222 and / or compartments within the device 201 may destroy the seals (e.g., puncture, perforate, displace, or otherwise open the seals).The user may fill the chamber 222 and / or compartment with a desired type of enzyme, combination of enzymes, and / or a desired volume of enzyme prior to and / or during use. In some embodiments, the device 201 may be reusable, while in other embodiments, the device 201 may be disposable.

[0060] In some embodiments, valves, frits, meshes, filters, or other mechanical structures may be used prior to use to maintain the enzymes within the chamber 222 and / or individual compartments, and / or to control the flow of the nutritional preparation 110 through the chamber 222 during use. Valves may be included in connectors 240, 235, inlet 212, outlet 230, between compartments 222a, 222b, 222c, and / or in any one of interfaces 225, 223, 224a, 224b.

[0061] In some embodiments, the enzymes (e.g., lipase, protease, and / or amylase) may be mixed, heated, cooled, stirred, or otherwise prepared before and / or during use. For example, device 201 may include a vibrator to stir device 201 and chamber 222, mixing and / or stirring the enzymes and / or nutritional preparation 110. In some embodiments, a vibrating motor may be included in or attached to device 201 to vibrate device 201, stirring the enzymes, nutritional preparation 110, and / or chamber 222 contained within a section of chamber 222, thereby facilitating the mixing of the enzymes (lipase, protease, and / or amylase) and nutritional preparation 110, assisting the flow of nutritional preparation 110 through chamber 222, and / or assisting the flow of processed nutritional preparation 111 out of outlet 230.

[0062] The nutritional preparation 110 may flow through the device 201 in any preferred manner. In some embodiments, the nutritional preparation 110 may be supplied by gravity through the device 201, where it is processed (e.g., lipids, proteins, and / or carbohydrates are hydrolyzed), and the processed nutritional preparation 111 may then flow out of the device 201 and be supplied to a target or stored, for example, in a blob. In some embodiments, the step of fluidly connecting the device 201 to a supply system (e.g., system 100 in Figure 1) may facilitate the flow of the nutritional preparation through the device 201, including the chamber 222. For example, the flow of the nutritional preparation 110 out of the device 201 may be driven by a pump or other preferred mechanism, as described above.

[0063] Figure 2B shows another exemplary embodiment of a device for processing a processed nutritional preparation. Device 211 may be substantially identical to device 201, but without any divisions separating different compartments of chamber 242. Device 211 may include an inlet 260, an outlet 261, connectors 250, 255, interfaces 245, 243, and particles 300 (or other structures) similar to device 201, which may have any of the aforementioned features and configurations as described with respect to device 201. Lipases, proteases, and / or amylases may be present in chamber 242 or mixed throughout chamber 242. In some embodiments, one or more enzymes (lipases, proteases, amylases) may be immobilized on one or more solid supports, e.g., particles 300, membranes, fibers, or other structures, on any surface of chamber 242 or interfaces 245, 243, or they may be present in chamber 242 without immobilization. Each enzyme may be immobilized on its own structure or multiple structures within chamber 242, or multiple enzymes may be immobilized on the same structure or structures within chamber 242, or a combination thereof. In some embodiments, one or more dry enzymes may not interact with each other when stored in chamber 242, but may interact with the nutritional preparation as the enzymes become wetted as the nutritional preparation flows through it. In some embodiments, one or more dry enzymes may be coated (e.g., with an enteric coating polymer) such that they do not interact with each other when stored in the chamber 242, but interact with the nutritional preparation as the enzymes become wetted when the nutritional preparation flows through it.

[0064] As shown in Figures 2A and 2B, in some embodiments the particles 300 may be formed as substantially spherical beads. In other embodiments the particles 300 may be randomly formed or irregular particles, or may be elliptical, oblong, donut-shaped, prism-shaped, polygonal, elongated, or any other suitable shape or form. The particles 300 may have a smooth or textured surface. The particles 300 may be shaped to increase or decrease their surface area. The particles 300 may be formed from individual particles, each of which may have substantially the same shape and / or surface, or two or more different shape and / or surface combinations. The particles 300 may be formed from any suitable material, and lipases, proteases, and / or amylases may be immobilized on the particles 300 in any suitable manner, for example, by adsorption, ionic bonding, covalent bonding, crosslinking, encapsulation, and / or confinement. The lipase, protease, and / or amylase may be immobilized on or within the particles 300 found in the chamber 222 so that the lipase, protease, and / or amylase come into fluid contact with the nutritional preparation 110 as the nutritional preparation 110 flows through the chamber 222 and / or individual compartments.

[0065] While particle 300 is depicted in the illustrative figure, it should be understood that lipase, protease, and / or amylase may be immobilized within the chamber 222 in any preferred manner. For example, lipase, protease, and / or amylase may be immobilized or contained within a structure located inside the chamber 222, such as beads, rods, projections extending from a portion of the chamber 222, or other preferred structures. In some embodiments, lipase, protease, and / or amylase may be immobilized on or contained within the wall of the chamber 222, and / or immobilized on one or more filters contained within device 200, device 201, and / or device 211. Lipase, protease, and / or amylase may be immobilized on or within any one component of device 200, 201, or 211 so that the nutritional preparation 110 comes into contact with the lipase, protease, and / or amylase as the nutritional preparation 110 flows into the device, such as inside the chamber 222 or individual compartments, and produces the desired enzymatic effect.

[0066] Furthermore, in some embodiments, it has been considered that the lipase, protease, and / or amylase do not need to be immobilized and may simply be contained within the chamber 222 or a section of the chamber 222. In some such embodiments, one or more filters may keep the free (i.e., unimmobilized) lipase, protease, and / or amylase within the chamber 222 and / or device 201. In other embodiments, one or more of the lipase, protease, and / or amylase may be allowed to exit the chamber 222 and / or device 201 and enter the nutritional preparation 110.

[0067] As the nutritional preparation 110 flows through the device 201 and chamber 222, it comes into contact with lipase, protease, and / or amylase contained within the chamber 222, and the lipids, proteins, and / or carbohydrates in the nutritional preparation are hydrolyzed. The lipase, protease, and / or amylase (immobilized or free) may be located along the flow path of the nutritional preparation 110 as it flows through the chamber 222. After the nutritional preparation 110 has come into contact with the lipase, protease, and / or amylase, the processed nutritional preparation 111 may be supplied to a subject or stored.

[0068] The lipase contained within the device herein can cleave two of the three bonds in a triglyceride, namely at the sn-1 and sn-3 positions, leaving the sn-2 monoglyceride. Exemplary lipases may be obtained from animals, plants, natural or genetically modified microorganisms, or combinations thereof. In some embodiments, the lipase is, for example, Chromobacterium viscosum, Pseudomonas The lipase may include one or more of the following: fluorescens, Burcholderia cepacia, or Rhizopus oryzae lipase, or any other suitable wild-type or recombinant lipase, or a combination thereof. In some embodiments, the lipase may include a phospholipase, e.g., phospholipase A, B, C, D, lecithinase, or any other suitable wild-type or recombinant lipase, or a combination thereof. The recombinant lipase may have the same or a different amino acid sequence as the wild-type lipase.

[0069] Exemplary proteases that may be included in the devices herein may include serine, cysteine, threonine, aspartic acid, glutamic acid, asparagine, and metalloproteases, pepsin, chymotrypsin, trypsin, or any other suitable wild-type or recombinant lipase, or a combination thereof, or more than one thereof. Recombinant proteases may have the same or different amino acid sequences as wild-type proteases. Suitable proteases may be derived, for example, from bacterial, fungal, yeast, insect, and / or mammalian sources.

[0070] Exemplary amylases that may be included in the devices of this specification may include α-amylase (calcium metalloenzyme), β-amylase, γ-amylase, or any other suitable wild-type or recombinant lipase, or a combination thereof, or more than one thereof. Recombinant amylases may have the same or different amino acid sequences as wild-type amylases. Suitable amylases may be derived, for example, from bacterial, fungal, yeast, insect, and / or mammalian sources.

[0071] Furthermore, it is considered that devices 200, 201, and 211 may include one or more separate compartments and / or chambers containing one or more nutrients, vitamins, minerals, and / or pharmaceuticals to supplement the nutritional preparation 110. The compartments or chambers may be located upstream, downstream, or interposed within compartments or chambers containing enzymes. As the nutritional preparation 110 passes through one or more compartments or chambers containing the supplements, the supplements may be added to the nutritional preparation.

[0072] In some embodiments, one or more sections or chambers may contain fats, proteins, and / or carbohydrates for addition to the nutritional preparation 110. In such embodiments, the supplement chamber or section may be located upstream of the chamber and / or section and contain enzymes (e.g., lipase, protease, and / or amylase) that hydrolyze the supplement nutrients. For example, a chamber or section containing one or more omega-3 fatty acids may be located upstream of a chamber or section containing lipase so that the nutritional preparation is first supplemented with omega-3 fatty acids and then broken down by lipase within the device. In another embodiment, a supplement chamber or section containing one or more sources of protein may be located upstream of a chamber or section containing protease so that the nutritional preparation is first supplemented with protein and then broken down by protease within the device.

[0073] In some embodiments, a chamber or section containing one or more drugs, such as antacids, proton pump inhibitors, antiemetics, or other drugs, may be located upstream or downstream of one or more enzyme chambers or sections so that the nutritional preparation is supplied with drugs and then delivered to the GI tube.

[0074] Figure 2C schematically depicts an exemplary chamber 222 of the device having several sections 222a, 222b, 222c, and 222d. Sections 222a, 222b, and 222c may contain one or more enzymes, e.g., lipases, proteases, and / or amylases. Chamber 222 may also contain section 222d, which contains an adjuvant to be added to the nutritional preparation, as discussed above. For example, section 222d may contain nutrients, vitamins, minerals, and / or pharmaceuticals. In some embodiments, section 222d may contain one or more enzymes that can assist in the absorption, utilization, storage, and / or excretion of components found in the nutritional preparation. For example, an enzyme that assists in the bioconversion of free fatty acids to phospholipids may be included in section 222d. Phospholipids are more readily incorporated into the cell membrane structures of mammalian cells of various tissues and blood components. Exemplary enzymes that can convert free fatty acids to phospholipids and can be incorporated into section 222d are shown in the chart below. [Table 1]

[0075] Multiple sections 222d may be contained within chamber 222 or may be separate from chamber 222 of the device. One or more sections 222d may be located at any location along the flow path of chamber 222 through which the nutritional preparation progresses. In the embodiment of Figure 2C, the nutritional preparation may enter chamber 222 from the right or left, i.e., section 222d may be located upstream or downstream, and it is also considered that section 222d may be located between one or more of sections 222a, 222b, and 222c. Figure 2C depicts chamber 222d in addition to all three chambers shown in Figure 2A, but as explained with reference to Figure 2A, one or more of sections 222a, 222b, and 222c may be omitted and / or may contain one or more enzymes.

[0076] Furthermore, the chambers 222 may also be arranged as shown in Figure 2B, and it has been considered that, for example, section 222d may be included in addition to the single chamber 242 containing the enzyme mixture.

[0077] As illustrated with reference to Figures 2A and 2B, section 222d may be permanently contained within the device, and / or section 222d may be removable and / or refillable, as described above.

[0078] Devices 200, 201, and 211 may be configured to treat patients suffering from lipase, protease, and / or amylase, or other mineral, vitamin, and / or nutrient deficiencies and / or malabsorption. The devices described herein may be used in place of, or in addition to, other treatments, to provide increased concentrations of hydrolyzed lipids, proteins, and / or carbohydrates in nutritional preparations 110. Device 201 may be used, for example, as a clinical setting device for processing nutritional preparations immediately before ingestion, or for mass production of processed nutritional preparations.

[0079] In some respects, the exemplary devices 200, 201, and 211 may be used in the manner shown in Figure 3. Those skilled in the art will recognize that one or more steps of the method depicted in Figure 3 may be omitted or performed in an order other than that depicted in Figure 3, or other steps may also be performed.

[0080] The first three steps of the method in Figure 3 are optional, and depending on the embodiment of device 200, device 201, or device 211 (collectively referred to as "devices" when referring to Figure 3), any combination of those steps may be performed, or none of the steps may be performed. The first optional step 350 includes the step of preparing one or more enzymes, which may include lipase, protease, and / or amylase. As described above, the step of preparing the enzymes may involve mixing, heating, cooling, stirring, immobilizing, or otherwise preparing the enzymes for use in the device. The preparation may occur with the enzymes already contained within the chamber and / or compartment of the device, the preparation may occur prior to the introduction of the nutritional preparation 110 into the device, or both. In some embodiments, the preparation may include the step of mixing one or more enzymes and / or one or more particles together. In addition, it is noted that step 350 is shown to precede step 352 and step 351, but it should be understood that these steps may be performed in any order.

[0081] Step 351 may include the steps of attaching the chamber and / or one or more sections to the device (in embodiments, the chamber and / or one or more sections are removable from the device) and / or filling the chamber and / or one or more sections with an enzyme which may include lipase, protease, and / or amylase. In some embodiments, both the attaching step and the filling step may occur, while in other embodiments, one of these may occur (or neither may occur). If both actions are performed, the chamber and / or one or more sections may be filled and then attached to the device, while in other embodiments, the chamber and / or one or more sections may be attached to the device and then filled. In some embodiments, multiple chambers and / or multiple sections may be filled and / or attached to the device.

[0082] In step 352, the device may be attached to a feeding system for passing the processed nutritional preparation through the device before it is supplied to the target. For example, the device may be attached to the feeding system shown in Figure 1. In fact, the device may be attached to or otherwise incorporated into any suitable feeding system.

[0083] In step 353, the nutritional preparation 110 may pass through enzymes (lipase, protease, and / or amylase) and / or auxiliary agents (if included) contained within the device, for example, in a chamber or section of one or more of the device. As the nutritional preparation passes through the enzymes in the device, it reacts with the enzymes, and the lipids, proteins, and / or carbohydrates in the nutritional preparation are hydrolyzed. In step 354, the processed nutritional preparation may exit the device. In an optional step 354, the processed nutritional preparation may be supplied to a subject immediately or after a certain period of time. The processed nutritional preparation may be supplied to a subject in any preferred manner, for example, via a supply tube, via a beverage (for example, the processed nutritional preparation may be added to a beverage), or in any other manner. In some embodiments, the devices of the disclosed embodiments may be used to prepare large quantities of processed nutritional preparations, to provide processed nutritional preparations at some time before administration of the processed nutritional preparations to a subject, and / or for industrial or laboratory preparations.

[0084] Many of the embodiments described above with respect to the device include clinical-grade devices for processing nutritional preparations, but it is also being considered that lipase, protease, and / or amylase may be added directly to the nutritional preparation without being contained within the device. For example, lipase, protease, and / or amylase may be added to the nutritional preparation (e.g., individual single doses of the nutritional preparation or a source of the nutritional preparation) immediately before administration to a human, or to a large volume of the nutritional preparation. The large volume of the nutritional preparation may be stored after processing with lipase, protease, and / or amylase, divided and administered to multiple people, and / or divided into multiple doses for a single human.

[0085] The added enzymes (lipases, proteases, amylases) may be immobilized on one or more solid supports, or they may be free. If immobilized, each enzyme type may be immobilized separately from one another (i.e., lipases, proteases, and amylases may each be immobilized on separate structures or subsets of structures without overlap), or multiple enzyme types may be immobilized on the same structure or structure, or a combination thereof. In some such embodiments, one or more of valves, frits, meshes, filters, or other mechanical structures may be used to remove any of the enzymes, i.e., immobilized or free (i.e., unimmobilized) lipases, proteases, and / or amylases, from the nutritional preparation prior to consumption of the preparation. For example, free or immobilized enzymes may be mixed into the oral beverage and then precipitated, or the enzymes may be filtered or otherwise removed prior to consumption of the oral beverage.

[0086] In some embodiments, a container (e.g., a beverage holder) may include a plurality of compartments, i.e., one or more compartments for containing a nutritional preparation and one or more compartments for containing one or more enzymes. For example, a compartment may contain a nutritional preparation, and lipases, proteases, and / or amylases may be stored in separate compartments or dispersed among the plurality of compartments (e.g., lipases, proteases, and / or amylases may be stored separately from each other in their own compartments). The enzymes may be free and / or immobilized in separate compartments. The compartments may be porous to allow the nutritional preparation to interact with the enzymes, or otherwise designed to allow the nutritional preparation to enter the enzyme-containing compartment. Separation of enzymes into compartments can prevent the enzymes from entering the nutritional preparation when the nutritional preparation is removed from the container, for example, for consumption. In an exemplary embodiment, the beverage container may have a porous compartment within it that allows the nutritional preparation to flow through the compartment and mix with the enzymes within the compartment. A person may then tilt the beverage container and drink the nutritional preparation, causing the preparation to flow out of the compartment and out of the beverage container, leaving the enzymes within the compartment.

[0087] In some respects, the beverage container may include a porous compartment containing enzymes, positioned along the opening of the beverage container, such that a nutritional preparation poured into and out of the container can pass through the compartment and thus be exposed to lipase, protease, and / or amylase prior to consumption. Again, a person may tilt the beverage container and drink the nutritional preparation, which may flow out of the beverage container through the compartment, leaving the enzymes within the compartment.

[0088] The principles of this disclosure are described herein with reference to illustrative aspects relating to specific uses, but this disclosure is not limited thereto. Those skilled in the art and those with access to the teachings provided herein will recognize all additional modifications, uses, aspects, and equivalent substitutions that fall within the scope of the aspects described herein. Therefore, this disclosure is not to be considered limited by the foregoing description.

Claims

[Claim 1] The invention as described in the drawings of the present application.

Images