MXPA97005135A

MXPA97005135A - Apparatus to alter the composition of a nutrit product

Info

Publication number: MXPA97005135A
Application number: MXPA/A/1997/005135A
Authority: MX
Inventors: Bruce Mazer Terrence; Edward Walton Joseph; Kay Geckle Ronita; Anthony Mccamish Mark; Joseph Pionteck Carl; Beth Duel Susan; Daabkrzykoswki Andre; Louis Joseph Robert; Guy Pierson William
Original assignee: Abbott Laboratories
Priority date: 1995-01-13
Filing date: 1997-07-08
Publication date: 1998-07-03

Abstract

The present invention relates to an apparatus for modifying a liquid enteral nutrient product during the feeding thereof comprising: a formulation chamber, the formulation chamber has an inlet and an outlet and the inlet is connected with a container with an enteral nutritive product liquid having a viscosity in the range of about 5 to about 300 centipoises in order to receive the product therefrom, the formulation chamber further comprising at least one beneficial agent in at least one dosage form unit controlled release and the formulation chamber contains the at least one unit in controlled release dosage form, each of the beneficial agents are selected from the group consisting of: nutrients, drugs, probiotics, and diagnostic agents that are dispersed in the liquid enteral nutrition product, the unit in dosage form of continuous release Rolled is able to supply each beneficial agent in the liquid enteral nutrient product in a period of time in the range of at least 30 minutes approximately during the feeding of the same to a patient.

Description

APPARATUS TO ALTER THE COMPOSITION OF A NUTRITIVE PRODUCT Field of the Invention The invention relates to an apparatus for feeding liquid enteric nutritive products, and particularly to the modification of a liquid enteral nutrient product having a viscosity on the scale of approximately 300 centipoise (cps), by adding ingredients. , during feeding, to the gastrointestinal tract of a patient.

Background of the Invention Feeding a liquid enteral nutrient product from a collapsible container, such as a bottle or a plastic bag with an outlet at the bottom that connects with a drip chamber, and the latter with a flexible tubing, or lumen, which leads to a nasogastric tube or a feeding tube inserted through a gastronomy or jejunostomy, by gravity flow or auxiliary by a pump, is well known. The liquid enteral nutrient product can be processed aseptically or terminally distilled, and can be supplied in a pre-filled container, ready to be hung, or it can be placed in this container by an assistant. However, the selection of diets, particularly special diets, from the rather modest number of liquid enteral nutrient products typically available, is limited. As a practical matter, this narrows the physician's choices regarding diet modifications, temporary or long-term, that could significantly benefit the patient. In view of the now recognized importance of providing aseptic nutritive compositions, it can be seen that modified diets are not easily prepared without observing the strict requirements, necessary to deliver an aseptic nutritive composition to the patient. Until now, the need to observe these requirements has militated against the preparation of small amounts of special diets designed for a specific patient. Furthermore, a number of nutrients, as well as drugs, diagnostic agents, and other ingredients such as probiotics, which at any given time might be desirable to orally administer to a patient, are not stable during heat styling, or may not be mutually compatible with other desired ingredients over an extended period of time, such as days or even months until used, and therefore, are not easily susceptible to large-scale preparation and consequent storage as the product moves through trade. Drug delivery systems have been described and claimed in U.S. Patent Nos. 4,511,353; 5,318,558; and 5,324,280, wherein the drug component to be delivered is stored in a capsule from which it is expelled over time on the osmotic infusion of moisture into the capsule, the drug being carried from the outer surface of the capsule by a suitable liquid in an intravenous delivery system, ie, parenteral, or even by the device of US Pat. No. 5,318,558, by the body fluids when implanting the capsule. In US Pat. No. 5,069,671 a formulation chamber is described, which may also be a drip chamber, wherein different forms of sustained release mechanisms are employed to release a drug or medicament, or other physiologically beneficial component. such as a nutrient, within the formulation chamber from which the drug or other component is carried by a suitable liquid to a parenteral application system. The teachings of U.S. Patent Nos. 4,511,353 and 5,069,671 relate to the intravenous application of parenteral compositions, and in the case of the latter patent, includes the application by infusion through the intravenous lines., intraarterial, intraperitoneal, or subcutaneous. The osmotic dosage system of U.S. Patent No. 5,324,280 relates to the application of drug formulations over time to a biological environment, such as an implant of tissue or organ in a mammal, or a current. or tank for marine life. The osmotically driven device of U.S. Patent No. 5,318,558 is said to be used to apply drugs, medications, and nutrients in a range of environments ranging from veterinary medicine to drug administrations to humans , and recreational situations such as fish tanks. Again, in the case of administration to humans, the application appears to be within a tissue or organ implant. Although osmotic application devices and other dosage forms or reservoirs of sustained or controlled release have been known for some time, as far as is known, there has been no attempt to use this application system to add one or more nutrients, or one or more medications, or a mixture of nutrients and medications, or a probiotic, or a diagnostic agent, or any of these mixed with a marker dye, to a liquid enteral nutrient product, with a viscosity up to 300 cps, during administration from the nutritive product to the gastrointestinal tract of a patient. The liquid inorganic nutrient products currently on the market are described in the reference text "Nutrition In Critical Care", Gary P. Zaloga, ed. , Mosby - Year Book Inc., St. Louis, MO, 1994, in Chapter 24, authored by Barbara Hopkins, Part III, "Feeding", page 439-467. This reference indicates that the complete nutrient compositions contain proteins, carbohydrates, fibers, fats, and vitamins and minerals in different proportions in an aqueous or aqueous / fatty medium. Nutrient compositions for special diets may omit one or more kinds of these components.

SUMMARY OF THE INVENTION A first aspect of the invention relates to an apparatus for adding ingredients to a liquid enteral nutrient product during the application of the nutritive product from a supply thereof, such as a collapsible container, to a feeding tube that delivers the nutritious product to the gastrointestinal tract of a patient. The apparatus comprises: a formulation chamber, usually in the form of a drip chamber, which can be connected to a supply container of a liquid enteral nutrient product, normally an aqueous composition, the formulation chamber having an inlet and an outlet , at least one beneficial agent in a controlled release dosage form, each unit being provided with a controlled release dosage form in the formulation chamber to be moistened by, or immersed in, the liquid enteral nutrient product passing through the formulation chamber. , and each beneficial agent can be dispersed in the medium of the liquid enteral nutrient product, and a fluid communication element that connects the outlet of the formulation chamber with a tube for feeding the modified enteral nutrient product, which contains the at least one agent beneficial thus added, to the gastrointestinal tract of a patient. Each at least one beneficial agent to be added in a controlled release dosage form during feeding is added in at least one physiologically effective or diagnostically detectable amount, and is selected from the group consisting of: a nutritional ingredient; an ingredient of medication; a chemically and physiologically compatible mixture of: a plurality of nutritive ingredients, or a plurality of medicament ingredients, or at least one nutritional ingredient and at least one medicament ingredient; a probiotic; or a diagnostic agent; and any of the ingredients or mixtures of the above ingredients, mixed with at least one physiologically acceptable dye or mixture of dye marker compatible with the ingredients, that can be dispersed in the medium of the liquid enteral nutrient product. The formulation chamber can be a conventional drip chamber which here also serves as the formulation or contact chamber. The formulation chamber can be provided, in addition to the controlled release dosage form or forms thereof, and whether or not a label dye is employed, with the same or different beneficial agents or agents, other than in a controlled release dosage form, if desired, in order to add larger amounts of these, or to add a beneficial agent such as a bolus. In addition, the dye or label dyes can be provided separately from the beneficial agents, in the formulation chamber, in one or more controlled release dosage forms. If desired, one or more additional contact or formulation chambers can be employed, either in series or in parallel, but feeding into a fluid communication element leading to the patient feeding tube. Where more than one formulation chamber is used, at least one formulation chamber will have placed thereon at least one controlled release dosage form containing at least one useful or detectable amount of at least one beneficial agent as defined above. , while each additional formulation chamber may contain one or more beneficial agents in either or both controlled and uncontrolled release dosage forms. The use of more than one formulation chamber facilitates the addition of ingredients that are not readily available in combination, or that are not compatible during storage together in a controlled release dosage form. In each formulation chamber, the beneficial agent or agents, either in a controlled release dosage form or not, are placed, and stopped or supported, if necessary, in such a manner that the liquid enteral nutrient product being modified contacts and moistens or immerses the form of dosage of the beneficial agent or agents therein. Preferably, each controlled release dosage form is configured or stopped in such a manner as to prevent the beneficial agent from blocking the flow of the liquid enteral nutrient product out of the drip chamber or the formulation chamber where it is placed. The combination of: (1) a formulation chamber, ordinarily in the form of a drip chamber, and (2) a fluid communication element, accompanied by: (3) at least one beneficial agent, as defined in present, in a controlled release dosage form disposed in the formulation chamber, or merely accompanying the formulation chamber, in any case when the three parts are supplied together, constitutes a useful case for evacuating a liquid enteral nutrient product from a delivery container, such as a collapsible container, and modifying the liquid enteral nutrient product by the addition of one or more beneficial agents thereto as it flows from the container, and feeding the modified product into the gastrointestinal tract of a patient. The kit formulation chamber may also be loaded with, or may be accompanied by, a dye or marker dyes in a separate controlled release dosage form, and / or one or more beneficial agents in an uncontrolled dosage release form. suitable, for example, in form, of uncoated particles or of tablet in a porous carrier wrap, such as a package in the form of a tea bag. The dye or dyes markers may be of the types visible under either or both of white light or ultraviolet light. Preferably, the at least one beneficial agent in a controlled release dosage form and any other additives in uncontrolled release dosage forms supplied as part of a kit, are already placed in the formulation or drip chamber. If not, they are easily placed in a manual manner in the formulation chamber, ordinarily before connecting the apparatus with the supply container from which the liquid enteral nutrient product is to be evacuated. In a further aspect of the invention, the invention relates to a method for preparing a special liquid diet for enterally feeding a tube-fed patient, which comprises modifying a liquid enteral nutrient product during its flow from a supply container containing This composition, up to a feeding tube that leads to the patient's gastrointestinal tract. More specifically, the method comprises the steps of: A. Providing an apparatus comprising: (a) a formulation chamber having an inlet and an outlet, the inlet being connected in fluid communication with the product supply container liquid enteral nutrient, (b) a physiologically effective or diagnostically detectable amount of at least one beneficial agent in a controlled release dosage form, with each beneficial agent being arranged in the formulation chamber, such that its dosage form is contacted by or submerged in the liquid enteral nutrient product passing through it, each beneficial agent can be dispersed in the medium of the liquid enteral nutrient product, and each beneficial agent can be selected in a controlled release dosage form from the group that consists of: a nutritious ingredient; an ingredient of medication; a chemically and physiologically compatible combination of: a plurality of nutritive ingredients, or a plurality of medicament ingredients, or at least one nutritional ingredient and at least one medicament ingredient; or a probiotic ingredient; or a diagnostic agent; and any of the ingredients or combinations of ingredients above together with at least one compatible physiologically acceptable marker dye that can be dispersed in the medium of the liquid enteral nutrient product, and (c) a fluid communication element capable of operatively connecting the exit from the formulation chamber with a tube to feed a liquid enteral nutrient product into the patient's gastrointestinal tract; B. Provide a supply container that contains a liquid enteral nutrient product; C. Place the apparatus in a communicative series in the fluid flow between the supply container and the supply tube; and D. Flowing the liquid enteral nutrient product through the apparatus, where the product becomes modified, and into the feeding tube. In a modification of this method, which may be especially useful for customizing a diet for a patient, one or more beneficial agents are added that are not in a controlled release dosage form to the formulation chamber. The added agent or beneficial agents may be the same or different from the specific beneficial agent or agents provided in the formulation chamber in a controlled release dosage form. The added beneficial agents that are not in a controlled dosage form are added to perform a bolus feed or a bolus effect, or simply to add a greater amount of a given beneficial agent. Also, the label dye in a separate controlled release dosage form, which may be surface coated with an easily soluble dye to impart a rapid initial dye label, may be added to the formulation chamber. In another modification, the fluid communication element is provided with one or more additional formulation or contact chambers, which are not necessarily drip chambers, but each having either a marker dye or a beneficial agent thereon. , as defined herein, in a controlled or uncontrolled release form, or a combination of marker dye and beneficial agent. The formulation chambers are connected with a supply of liquid enteral nutritive product, and are placed to allow the flow of the liquid enteral nutrient product on each dosage form thereof, to put it in contact or even to immerse it dynamically, that is, to immerse it in a amount of liquid that changes constantly, in order to recover the beneficial agent and / or dye content, and transport it to a patient's feeding tube. If necessary or desired, a pump may be used to make flow or to aid the flow of the modified liquid enteral nutrient product to the feeding device or tube.

BRIEF DESCRIPTION OF THE DRAWINGS The present invention will be better understood with reference to the accompanying drawings, in which: Figure 1 is a partially schematic representation of an apparatus for modifying a liquid enteral nutrient product, and feeding it by nasogastric tube in accordance with invention. Figure 2 is a partially schematic representation of an apparatus for modifying a liquid enteral nutrient product, and feeding it by tube by means of a gastronomy tube according to the invention. Figure 3 is a partially schematic representation of an apparatus for modifying a liquid enteral nutrient product, and feeding it by tube, with the aid of a pump, by means of a jejunostomy tube according to the invention. Figure 4 is an enlarged fragmentary view in front elevation of the lower portion of a hanging supply container of a liquid enteral nutrient product, such as the container shown in Figures 1 to 3, with the inlet tube bevelled from a chamber drip inserted through the closure, and depending on it, and with a beneficial agent in a controlled release dosage form disposed inside the drip chamber and immersed in the liquid enteral nutrient product that flows, the lower part of the chamber being of drip and dosage form of controlled release from inside, partially separated into parts and in section, and driving the pipe portion of the fluid communication element, ie, primarily the pipe leading away from the drip chamber, truncated for purposes of illustration. Figure 5 is a perspective view of a drip chamber that can be used according to the invention, with a controlled release dosage form in the form of a substantially rectangular solid with slightly rounded corners, disposed within the chamber of dripping, the end of the bevelled inlet tube of the drip chamber being the upper end which is pushed in the normal way through the closure of the supply container to communicate with it and to receive the liquid enteral nutrient product therefrom. . Figure 6 is a perspective view of the drip chamber of Figure 5 inverted to show more detail of the construction. Figure 7 is a perspective view, partially broken away in parts and in section, of a controlled release dosage form in the form of a rectangular solid, of the osmotic pump type, used to deliver a beneficial ingredient or a mixture thereof within the formulation chamber according to the invention. Figure 8 is a front elevational view, partially broken away in parts and in section, of a controlled-release dosage form in the form of an almost rectangular solid, of another type of osmotic device, used to deliver a beneficial ingredient or a mixture of same within the formulation chamber according to the invention. Figure 8A is a view similar to Figure 8, of a sustained release dosage form of the same type, but with an outer coating of marker dye that is already immediately recovered in the medium of the liquid enteral nutrient product at the beginning of the beginning of the flow through the formulation chamber, and used where the dosage form contains the marker dye for sustained release. Figure 9 is a front elevational view, partially broken away in parts and in section, of a carrier in the form of an almost rectangular solid of controlled release dosage forms, of the microencapsulated particle type or of the molecular sieve type, used to supply a beneficial ingredient or a mixture thereof within the drip chamber according to the invention. Figure 9A is a perspective view, partially separated in sections and in section, of a highly permeable fibrous packet, preferably of the non-spun tea bag carrier type, suitable for being placed in a drip chamber, or in another formulation chamber, and capable of sustaining a sustained release dosage form. , such as a coated tablet, or an osmotic application device, or a coated capsule, or a capsule containing a quantity of controlled release dosage forms in the form of microencapsulated particles or a material of the type of molecular sieve or hollow fibers permeable, each article or unit of dosage form containing at least one beneficial agent or a mixture thereof with label dye. A beneficial agent that is not in a controlled release dosage form, either in tablets or agglomerate or in loose particles, may also be placed in an amount measured in a porous carrier such as one or more fibrous packets of the kind shown in Figure 9A, and used in a formulation chamber in addition to one or more controlled release dosage form units, or separately if there is at least one controlled release dosage form placed in the same formulation chamber, or in at least one formulation chamber used with the same communication element. A small amount of marker dye that is not in a controlled release dosage form can also be placed in the fibrous pack for a rapid initial dye mark. Figure 10 is a side elevational and partially truncated view of a feeding set or package, including a beneficial agent in a controlled release dosage form for placement in the formulation chamber by the health care assistant , the kit being useful for modifying a liquid enteral nutritional composition during its feeding according to the invention. Figure 11 is a view similar to Figure 4, but with the controlled release dosage forms of any of Figures 7 to 9A confined within a shirt or mesh bag. Figure 12 is a view similar to Figure 4, but with the controlled release dosage forms of any of Figures 7 to 9A confined within a foraminate, perforated, or fibrous liner or bag. Figure 13 is a view similar to Figure 4, but with a plurality of the controlled release dosage forms of any of Figures 7 to 9A, supported by a foraminous plate above the bottom orifice of the drip chamber. Figure 13A is a cross-sectional view of a formulation chamber taken at the level just above a grid that has been placed in the drip chamber of Figure 13 in place of the foraminous plate shown therein, for the support of a controlled release dosage form placed in the drip chamber. Figure 14 is a side elevation view similar to Figure 13, showing a drip chamber that depends on a supply container with liquid enteral nutrient product flowing through the chamber on a beneficial agent in a release dosage form Controlled intermixed with added beneficial agent that is not in controlled dosage form, while the dosage forms are supported on a perforated plate near the bottom of the formulation chamber. Figure 15 is a side elevation of a feeding assembly according to the invention, including a drip chamber, loaded with a beneficial agent in the controlled release dosage form, and a fluid communication element for connecting the chamber drip with the feeding tube used to direct the modified liquid enteral nutrient product to a patient's gastrointestinal tract, which includes a removable protective cap for the end connector. Figure 16 is a side elevational view of a feeding case in which a second formulation chamber has been connected by its input in fluid communication with the end of the flexible tubing that is normally connected to a connection that connects to the patient feeding tube, the outlet tube of the formulation chamber having a connection to connect to the feeding tube. Figure 17 is a perspective view of a suitable formulation chamber similar to that shown in Figure 5, but with a different form of connection for connecting to a supply container, the lid here being threadably attached to a supply container, and forming integrally with the upper part of the formulation chamber. Figure 18 is a perspective view of the formulation chamber shown in Figure 17, as viewed in the opposite direction. Figure 19 is a side elevation of a feed assembly where two formulation chambers are connected in series, here in a row. Figure 20 is a side elevational view of part of the apparatus for modifying a liquid enteral nutrient product during enteral feeding, wherein two formulation chambers are suspended from respective hanging supply vessels, each containing liquid enteral nutrient product, connecting the outputs of the formulation chambers with pipe segments that are connected to a "Y" connection that joins the parallel flow from each formulation chamber in a single stream within the communication element, truncated here.

Definitions used in the Present The following terms and phrases are defined for the purposes of the description and the claims. "Enteral" nutritional product refers to liquid compositions commonly understood to be supplied to, and used in, the gastrointestinal tracts of patients. These enteric nutritive products have a viscosity in the range of one to about 300 cps, and more frequently in the range of about 5 to about 150 cps. "Enteral nutrient product medium" refers to the liquid portion of a liquid enteral nutrient product, primarily water, but often including minor amounts of one or more non-aqueous liquid substances, such as lipids, for example vegetable oil and marine oil. The term "gastrointestinal tract," as used herein, refers only to the stomach and small intestine. Feeding to the gastrointestinal tract is done by using a nasogastric tube that extends through a nasal passage and esophagus, and from there to the stomach, or by using a feeding tube that extends through the stomach. abdominal wall to the stomach or small intestine. A "physiologically significant" or "beneficial" ingredient is an ingredient that is, or is believed to be, nutritionally or pharmaceutically important to the patient, or is otherwise medically important as in the case of a probiotic or an agent of diagnosis such as an opaque agent. A "probiotic" is understood as a food supplement of living microbes that beneficially affects the human host by improving the individual's microbial balance in the gastrointestinal tract, for example, Lactobacillus reuteri. A "beneficial agent or ingredient that can be dispersed in the medium of the liquid enteral nutrient product" is an agent or ingredient that is beneficially added in a physiological manner, or that is beneficially added in another useful way, as in the case of an agent of diagnosis, to the liquid nutritional product during enteral feeding, and it can be dispersed in the middle of the nutritional product. The beneficial agent (s) or ingredient (s), whether or not supplied by, ie, from units or devices in controlled release dosage form, and used in accordance with the invention, should be dispersible in the medium of the liquid enteral nutrient product that is being modified during feeding, in order to be taken along with the nutritive product to the patient's gastrointestinal tract. A "useful amount" of a beneficial ingredient that can be dispersed in the medium of the liquid enteral nutrient product is an amount that is "physiologically effective or diagnostically detectable" with respect to a patient, that is, it produces, or reasonably is expected to produces a detectable beneficial effect on the patient, either on a short-term or long-term basis, when it is fed as part of a liquid enteral nutrient product, or it can be detected in the diagnosis of a condition or disease. In general, there will be no more than about 5 grams of beneficial agent contained in a single unit or device in controlled release dosage form, and a plurality or even a multiplicity of units such as microencapsulated microspheres containing a given beneficial agent to provide a desired level of the beneficial agent in the nutrient product being fed. The phrase "at least one beneficial agent that can be dispersed in the middle of the liquid enteral nutrient product" refers to both the singular and the plural, as may be judged from the context, and includes combinations of ingredients, agents, or factors. The term "dispersible" as used herein with respect to beneficial agents or ingredients, must be understood to apply to substances that are soluble., as well as those that can be suspended sufficiently to be easily recovered and carried by the liquid medium as the liquid enteral nutrient product flows through the formulation chamber containing the one or more controlled release dosage forms. The term "feeding set" refers to the combination of a drip chamber, or other formulation chamber, and the fluid communication element leading to a feeding tube for enteral feeding. The drip chamber or other formulation chamber is loaded with, or is accompanied by, at least a useful amount of at least one beneficial agent in a controlled release dosage form, the beneficial agent being as defined above, with or without a marker dye in combination, and with or without additional beneficial agent that is not in a controlled release dosage form. The term also encompasses a feeding assembly having at least one additional drip chamber or one or more additional formulation chambers in fluid flow or in parallel series, as a part of the fluid communication element, each feeding assembly having at least one drip chamber or a formulation chamber loaded with at least one beneficial agent in a controlled release dosage form, each beneficial agent being present in at least one useful amount as defined above. Where more than one formulation chamber is employed, the additional chamber or chambers may contain: (1) one or more beneficial agents in a controlled release dosage form only, with or without label dye in a controlled release dosage form; or (2) one or more beneficial agents in a controlled release dosage form interspersed with one or more beneficial agents that are not in a controlled release dosage form, and with or without label dye in a controlled release dosage form; (3) one or more beneficial agents, none of which is in a controlled release dosage form, and with or without a label dye in a controlled release dosage form. The process of "infusion" refers, in the present context, to the process of delivering an enterally soluble beneficial ingredient to the gastrointestinal tract of a patient that extends over time from at least 1 minute to about 30 hours, but more usually from at least about 2 hours to about 24 hours. The term "application element" generically denotes an element or system for storing and subsequently applying or releasing a beneficial ingredient or agent or a mixture thereof within a formulation chamber, or a drip chamber, during, and as a consequence of, the flow through it of a liquid enteral nutrient product, using a controlled release dosage form of the beneficial ingredient or agent. The term "a controlled release dosage form" refers to any of the well known conventional controlled release forms, such as a coated tablet, an osmotic application device, a coated capsule, microencapsulated particles such as microspheres, agglomerated particles, for example molecular sieve particles, or a thin, hollow, permeable wall fiber, such as a bundle of crushed fibers or a coil, and each of these forms contains and subsequently stores and releases, or disperses in the case of devices osmotically driven, a useful content of; a beneficial agent towards the medium of a liquid enteral nutrient product at room temperature, in a slow manner, or delayed or intermittent, comparing with the solubility characteristics normally exhibited by that beneficial agent when it is in a non-coated particle form or not treated, in said medium, at about »room temperature. Any dosage form that employs coating, encapsulation, microencapsulation, closure in an osmotically driven device, or capture in a molecular sieve type structure, or in a thin permeable hollow fiber, to slow or slow down, delay or delay a intermittently, the solubilization of an immediately soluble beneficial agent, such that its dissolution or dispersion, as with an osmotically driven device, takes place during the course of at least 30 minutes, and preferably at least two hours, of its contact with the liquid enteral nutrient product that flows, or delays the release, that is, does not start, for at least 10 minutes after the initial contact in a formulation chamber with the liquid enteral nutrient product, is exhibiting a controlled release behavior. With respect to a beneficial agent that is inherently not immediately soluble in the medium of a liquid enteral nutrient product, any of these dosage forms that retards or slows, delays or intermittently delays the solubilization of this beneficial agent by when less than 20 percent of the normal time for the solubilization or dispersion in the medium of a liquid enteral nutrient product, of a given unit amount of the beneficial agent that is not coated or treated to obtain a controlled release, is considered, for the purposes of the description and claims, as a controlled release dosage form. Preferably, the controlled release dosage forms prolong the release of their content for an appropriate time so that the nutrient or drug or other beneficial agent is delivered. On the other hand, the mere formation of a beneficial agent tablet, either not mixed with another material, or not mixed with a relatively insoluble binder type excipient, for example, as long as it results in a smaller surface area being exposed to a liquid solvent, and a slower dissolution rate than that of a fine particle form of the beneficial agent, is not to be considered as converting the beneficial agent into a controlled release dosage form. Clearly, a beneficial agent in a form of particles that have not been coated with, or encased in, any other material, is not in a controlled release dosage form. Neither the tablets or particles not coated with a beneficial agent, which are clearly not in a controlled release dosage form, will be considered transformed to a controlled release form merely by being enclosed in a carrier, such as a type of package. of fibrous tea bag, or a capsule that dissolves or disintegrates easily. The "controlled release dosage forms" useful in accordance with the invention are understood to include delayed or intermittent release, as well as sustained release dosage forms, some of which constitute "a speed control element". or "controlled rate dosage forms". Preferably, the controlled release dosage forms prolong the release of their content for an appropriate time for the nutrient or medicament being delivered. The terms "controlled release dosage form units" or "controlled release dosage form particles" are to be understood to refer to individual coated tablets or coated capsules or devices such as osmotic application devices, or particles in microcapsules. or small bundles of fine hollow fibers, or small agglomerated lumps of molecular sieve type material, each capable of applying in a sustained manner, or applying in a delayed or intermittent manner, the beneficial agent or the marker dye as defined It should also be understood that the phrase "to make the liquid enteral nutrient product flow through the apparatus, where it becomes modified, and into the feeding tube", includes using gravity flow from a hanging container, as well as use a pump in addition to, or without, flow by gravity, to promote the flow of the enteral nutrient product modified liquid to and through a feeding tube.

Detailed Description of the Invention Referring now to the drawings, in which like parts are referred by like reference numerals, the apparatus of the invention is shown in Figure 1 in the form of a feeding set, indicated generally by numeral 20, which connects the outlet 21 of the hanging supply container 22, with the nasogastric feeding tube 23 that extends through a nasal passage 24 of the patient, and down the esophagus 25 to the stomach 26. Here the assembly The feed consists of a formulation chamber 27, in the form of a drip chamber that also serves as a containment or formulation chamber, and a fluid communication element indicated generally by 28. "Fluid communication element" "is understood to include all fluid communication components used in series from the outlet of the drip chamber 29 to the connection 30 and up to the feeding tube, such as the nasogastric feeding tube 23. The components include not only portions of flexible tubing 54, but also any drip chambers or other additional formulation chambers connected in series, as seen in Figures 16 and 19 for the flow in series, or in parallel but soon joined in a single stream as seen in Figure 20, for the flow of the liquid enteral nutrient product to the patient's feeding tube. The components may also include any special pipe portions necessary for the use of a pump, and connecting elements, respectively, among all other components, such as the connector elements 31 or adapters 30. It may be useful to use two row formulation chambers. , such as drip chambers 27 and 73, as seen in Figure 19, to introduce a higher concentration or amount of a given ingredient. The formulation chambers can be used in a row to introduce also different respective beneficial ingredients that are not supplied together within the same unit or particle of the controlled release dosage form. The respective ingredients may constitute a combination of little use, for example, or they may not be compatible in storage together in a controlled release tank. Two formulation chambers are shown in sequential series use in the power assembly of Figure 16, wherein the second formulation chamber 76 is connected, at the end of the flexible tubing 54 that is distal to the supply container. This can be useful for adding a special beneficial ingredient to an already formed feeding set. With the formulation chamber 76 at the end of the assembly that is distal of the supply container, more possibly it will be positioned horizontally as illustrated, and preferably made with a bulbous middle portion 77, or a longitudinal channel portion that remains low, wherein the beneficial agent 32 in the controlled release dosage form will be on the lower side of the formulation chamber, and will be moistened by the flowing liquid enteral nutrient product. If the beneficial agent is not in a controlled dosage form, it will likewise remain, for example, on the underside of the bulbous section 77 until it is dispersed.

Double formulation chambers 74 can be used in parallel as indicated in Figure 20, and for the same reason as the chambers in a row, or it can be simpler where one wants to feed a beneficial agent on a bolus basis, and another on a sustained basis. It is preferable to hang these chambers from respective supply containers, as shown, to avoid control problems, in order to obtain an adequate flow through both formulation chambers from a single supply container, which would preferably require the use of a divider valve to divide the intake flow between the two parallel tracks. The outputs of each formulation chamber shown in Figure 20, they are connected with flexible pipe segments 54 leading to a "Y" shaped connection 75, where the liquid enteral nutrient product streams are joined. Referring again to Figure 1, the formulation chamber 27 has placed therein a controlled release dosage form unit 32 containing at least a physiologically effective or diagnostically detectable amount of at least one beneficial ingredient that can be dispersed in the liquid enteral nutrient product medium 33 flowing from the supply container 22 to the formulation chamber 27, wherein the liquid enteral nutrient product, which is normally water based, contacts the controlled release dosage form unit 32, moistening or immersing it within the formulation chamber 27, causing the release or discharge into the nutrient composition of the dispersible beneficial ingredient or ingredients, in addition to the label dye, if included, stored in the reservoir. The flow of the liquid enteral nutrient product is conveniently activated or deactivated, or is sometimes regressed by the use of a conventional adjustable compression fastener 34. Turning now to Figure 2, a hanging supply container 22 is shown to supply the product. liquid enteral nutrient 33 to a formulation chamber 27 from which the liquid enteral nutrient product flows through flexible tubing 54 of feeding assembly 20a to gastronomy feeding tube 23a. The geystronomy feeding tube shown in Figure 3 is merely an example of the wide variety of gastronomy feeding tubes that are commercially available, it being understood that the apparatus of the present invention can be used with a variety of feeding tubes. gastronomy. A feeding configuration for a jejunostomy very similar to that of the apparatus of Figure 1 is shown in Figure 3, with the exception that the feeding assembly 20b is adapted to be used with a pump 35 that provides a positive flow to a tube of feeding 23b leading to the small intestine 26a of the patient, while in a number of cases, flow by gravity is used. Also, a second formulation chamber 27a is used as part of the feed assembly 20b for the purpose of adding an additional or different beneficial agent and / or marker dye, each dispersible in the medium of the liquid enteral nutrient product 33 flowing from the supply container 22 to the formulation chamber 27, and thence through the remainder of the communication element 28b and the formulation chamber 27a of the feed assembly 20b to the jejunostomy feeding tube 23b. The additional benefit agent may be in a controlled or non-controlled dosage form. If desired or necessary, as often as the case when fed by a feeding tube, such as a jejunostomy tube, a pump, such as a peristaltic pump with camming action, can be used acting on the portion of flexible tube 54 of the communication element 28, or a positive displacement pump with a disposable fluid infusion pump chamber cartridge such as described in United States Patent Number 4,927,411, and connected in series in the element of communication, for flowing or assisting the flow of the modified liquid enteral nutrition product to the feeding tube, for example, when it is not convenient to hang or otherwise locate the delivery container in an elevated position relative to the patient, or when the nutritive product is rather viscous and flows slowly by gravity flow. The fluid communication element 28 of the ordinarily used apparatus will include a portion of flexible tubing 54 connectable to, or usable with, a conventional pump. If the pump used, for example, is a peristaltic pump that requires specially configured flexible tubing, this tubing can be used to replace all or a part of the communication element that applies the modified nutrient product from the formulation chamber to the tube. feeding the patient. The end of the flexible tubing 54 connected to the inlet end of the second formulation chamber 27a is preferably provided with a coupling element 30, such as that shown in the feeding assembly of Figure 15, while the Inlet end of the formulation chamber is further configured to receive the coupling element,, and the outlet of the formulation chamber communicates with a short length of flexible tubing which likewise terminates in a coupling element 30, which it is connected to the feeding tube 23b. It can be seen that it is convenient to add the second formulation chamber 27a, when the need arises, without having to disconnect the parts of the feeding assembly. Here, for example, the flexible tubing 54 would have to be disconnected from the drip chamber 27 to add the formulation chamber 27a directly in a row at that end of the assembly. The formulation chamber 27 has been charged with a beneficial agent in a controlled release dosage form 32, while the second formulation chamber 27a has been provided with the same beneficial agent or a different one, not in a release dosage form. controlled The use of the beneficial agent that is not in a controlled release dosage form is also illustrated in Figure L4, where a plurality of sustained release dosage form units 32 containing beneficial agent are supported, above the perforated plate. 53, together with beneficial agent that is not in a controlled release dosage form, such as dispersible particles or tablets 80. The formulation chamber 27a can be hung vertically, like a conventional drip chamber, but will probably be placed more conveniently with the flow direction of the liquid enteral nutrient product through it approximately horizontally. Accordingly, the formulation chamber 27a must be provided with elements to guide or channel the liquid nutritional product, to physically contact the controlled release dosage unit or units therein. These elements can be a longitudinal channel that is low in the wall of the body, or a bulbous enlargement of the chamber body of the class illustrated in Figure 16, or even a simple lateral depression in the side wall of the lower side of the chamber , or a trap, or spillway, or any other element for retaining dosage unit units where there is adequate flow or sufficient liquid depth to provide good contact with the units or particles in controlled release dosage form located at this guide element or channel. As seen in Figure 16, a feeding box has been provided with a second formulation chamber 76 with a bulbous body portion 77 where a controlled release dosage form 32 is placed, such that the flow of the liquid enteral nutrient product will continuously contact the controlled release dosage form unit 32, and recover the beneficial agent therefrom. In the amplified fragmentary view of Figure 4, a controlled release dosage form unit 32a is seen in the form of an osmotic device capsule immersed in a liquid enteral nutrient composition 33 inside the drip chamber 27. This class of controlled release dosage form unit 32a, having an outer coating or membrane that does not disintegrate easily, preferably, it must have a geometric shape, for example, that of a rectangular solid, which prevents blocking of the flow of the liquid enteral nutrient product 33 through a circular opening such as that of the channel 40 that serves as the outlet for the lower part 39 of the drip chamber 27, or another element such as a mesh jacket that can be used to prevent such blocking. Details of the construction of an example of a conventional drip chamber suitable for use as a formulation chamber in accordance with the invention are illustrated in Figures 5 and 6, which are highly amplified perspective views. The drip chamber 27 as shown, has two parts. The first part is a hollow, almost cylindrical chamber body 37, with a first open end 38, which is the upper end when the drip chamber is in its normal operative position, and a second end 39, opposite the first end, which it is thinned or narrowed to form a hole 40 which leads to an integrally formed outlet tube portion 29. The body 37 of the chamber is preferably formed of a transparent material, such as plastic or glass, to allow visibility of the flow of the nutritive product. Typically, the drip chamber is formed of a transparent, somewhat flexible plastic that can be autoclaved, such as a polyvinyl chloride or a transparent polyolefin resin. The second part of the drip chamber 27 shown is in the nature of a plug 42 with a cylindrical body having an inward end portion 43 that fits comfortably at the inlet end 38 of the body 37 of the chamber. Preferably, the end portion 43 of the plug body 37 that extends into the body of the chamber has a slightly reduced diameter. The edge 44 of this end portion 43, remote from the end face of the cap, rises slightly, being of a slightly larger diameter, and serves as a stop when assembling the body of the chamber and the cap to each other. The body of the plug is provided with an integrally formed fluid communication passage 45, which may take the form of an axial bore in a solid plug body communicating with a portion 46 of the inlet tube, which projects outwardly in the axial direction from a flange-shaped flange 47 radially extending from the upper end 48 of the plug body. But preferably, in order to provide a plug body with more elasticity for easier insertion into the upper end 38 of the body 37 of the chamber, the fluid communication passage 45 is a concentric tube axially located in and around the body of the stopper. The concentric tube 45 is integrally formed with, or otherwise operatively connected to, the inlet tube portion 46. A short, integrally formed peripheral flange 50, extending longitudinally from the collar-shaped flange 47 may be provided. along one side of the plug body, if desired, to assist in holding the plug body when the drip chamber is assembled. The plug can be molded from a plastic such as a polyvinyl chloride resin, which may be pigmented, if desired, for visibility, as an aid in observing the proper seating in the body of the chamber. The distal or free end 49 of the inlet pipe portion 46 has a bevelled end sufficiently sharp to facilitate perforation of the seal (not shown) in the closure 21 of the neck of the conventional hanging supply vessel, such as the supply container 22. The collar-shaped flange 47 serves as a stop to the insertion of the sharpened entry tube portion 46 into the closure 21 in the neck of the supply container 22. Other modes of construction of the chamber can be employed. formulation, provided that a suitable connection is provided with the supply container, as well as a transparent tubular portion, where the flow velocity of the liquid enteral nutrient product can be observed. For example, see the formulation chamber 82 illustrated in Figures 17 and 18, wherein the plug end 83 of the formulation chamber is formed integrally with the closure 84 so that a conventional supply container is threadably connected thereto. The apparatus of the invention should not be considered limited to the inclusion of any of the drip chambers used herein by way of illustration, nor is the method limited to its use. The drip chamber shown in Figures 5 and 6 has a controlled release dosage form unit 32 disposed on the same list for use. The controlled release dosage form unit will be pre-sorted according to its content, to provide the nutrients and / or drugs and / or probiotics, and / or diagnostic agents and / or other additional beneficial ingredients selected by the assistant for the Charge for health care, along with a marker dye, if desired. As used herein and in the claims, medicaments are understood as substances used in therapy. The selected formulation chamber or chambers may contain more than one controlled release reservoir in order to provide a combination of nutrients, or a combination, such as nutrients and drugs or other beneficial agents, tailored to the needs of the patient. patient who is feeding. The formulation chamber can also be provided with the same or different beneficial agents or agents, both in a controlled and uncontrolled release dosage form, in order to provide, for example, a greater amount, as in the case of a nutrient An uncontrolled dosage form of a beneficial agent can be used to deliver the beneficial agent for a shorter period of time, as might be desired with a medicament. The units in controlled release dosage form employed preferably will be in the form of a coated tablet, an osmotic application device, a coated capsule, a microencapsulated microsphere, an agglomerated particle, for example, as a molecular sieve type particle. , or a bundle of thin, hollow, permeable fibers, or hollow permeable fibers crushed, agglomerated or held in a fibrous package. To prevent a dosage form unit or particle from blocking the flow of the liquid enteral nutrient composition through the exit orifice 40 of the drip chamber, if the dosage form unit is one that maintains the integrity of the outer layer or its coating while the ingredients are leached out or squeezed out during contact with the liquid enteral nutrition product, it is preferred that the dosage form unit have a geometric shape, eg, a rectangular solid, or a shape star, any of which will not completely block a round passage. If a different type of controlled release dosage form is used that dissolves or disintegrates, so that the internal form can not be controlled, or if it leaves an insoluble skeletal structure or waste, it is preferred to confine the units in dosage form controlled release in a mesh bag inside the drip chamber or other formulation chamber, such as the mesh sleeve 51 shown in Figure 11. A plurality of units in dosage form are also shown in Figure 11. of controlled release that can be used for the purpose of providing additional beneficial ingredients that can be dispersed in the medium of the liquid enteral nutrient product, in order to obtain a nutrient composition tailored for the patient. This can be especially useful where none of the controlled release dosage forms at hand can have the exact combination of ingredients that is desired or necessary for a patient, and the combination can be formed on demand if there are on hand controlled release dosage units containing the different desired ingredient contents. As seen in Figure 12, a foraminous liner, or a bag, i.e., one with numerous holes, can be used to place the controlled release tanks in the drip chamber or other formulation chamber. 0, going now to Figure 13, a metal plate of plastic or ceramic or corrosion resistant 53 that is foraminous or that is perforated, can be placed inside the body of the lower part of the drip chamber 37, or another formulation chamber, to support the units in controlled release dosage form, in this case, a very large number where the desired ingredient is needed in a relatively large amount. If desired, the foraminous plate 53 can be replaced by a grid or mesh 41, as shown in Figure 13a, and is also preferably formed of a vitrified plastic or ceramic or corrosion-resistant metal, such as stainless steel . The above means for arranging, ie supporting, the units in controlled release dosage form inside the drip chamber, can also be used in any additional formulation chambers in the feed set employed. The unit in controlled release dosage form illustrated in Figure 7 is of the osmotic pump type which operates in the manner of the osmotically driven application device described and claimed in U.S. Patent No. 5,318,558, the specification and drawings of which they are incorporated herein by reference with respect to the structure of the units in controlled release dosage form described therein, and the method for manufacturing them and their mode of operation, although different environments and contents are used here and end uses. In the pump type, the units in controlled release dosage form, or application devices, the beneficial ingredients in liquid form, ie, either in the liquid state or in solution in a suitable solvent, are squeezed out from an enclosure or cylindrical cavity 56 inside the reservoir, through a small orifice 57, by the action of a piston 58 driven by the pressure developed by the osmotic infusion of moisture through a semi-permeable membrane 59, which confines a hydroactive substance 60 behind the piston 58, urging the piston continuously towards the side of the reservoir where the ingredients 61 are forced out through the hole 57. The orifice 57 is very small and preferably pierced with a laser beam. The cylindrical enclosure 56 is formed inside an external non-permeable membrane or coating 62. The hydroactive substance 60 can be a water soluble salt such as magnesium sulfate, magnesium chloride, potassium sulfate, sodium chloride, sorbitol, inositol, urea , or a saccharide such as glucose or fructose or dextran, or a hydrophilic polymer such as a poly (hydroxyalkyl methacrylate) with a molecular weight of 30,000 to 5,000,000, or a poly (vinyl pyrrolidine) with a molecular weight of 10,000 to 360,000, an anionic or cationic hydrogel, or a polyvinyl alcohol having low acetate residue. The controlled release reservoir illustrated in Figure 8 is another osmotic dosing system with a sustained release dosage form that functions in the manner of the osmotically operated delivery device described and claimed in U.S. Patent No. 5,324,280, whose specification and drawings are incorporated herein by reference with respect to the structure of the units in sustained release dosage form described therein, and the method for making them and their mode of operation, despite the fact that here we have different environments and contents and end uses. In this type of system, the beneficial ingredients 63 to be fed in a liquid state or in a solution form, are enclosed within a non-permeable coating 64 which is surrounded by a layer 65 of hydroactive material that is entirely confined within. a semipermeable membrane coating 66. The osmotic pressure that develops in the hydroactive layer 65 on the infusion of moisture towards it, compresses the core 67 that contains the beneficial ingredients in liquid form 63, and forces that liquid outwardly. continuously through a very small passage 68 from number 67 and to the outside of the reservoir. Turning now to Figure 8A, the unit in controlled release dosage form as shown in Figures 7 and 8, may be coated with an easily soluble coating, such as coating 69, which may be a dye coating marker or beneficial agent for the purpose of obtaining a rapid initial release of this dye or beneficial agent. In the case of a beneficial agent, such as a medicament, this may be desirable in order to obtain a leveling of the blood content rapidly, after which a level of sustained sustained release may be required. The controlled release reservoir 70 illustrated in Figure 9 is of the type wherein a quantity of microcapsules or particles of type is provided within a carrier envelope 71 that is very readily soluble or disintegrable in the medium of the liquid enteral nutrient product. molecular sieve 72. If they are microcapsules, the particles 72 are microspheres, each individually coated, and each containing the same beneficial ingredient or a mixture thereof, with a plurality of portions or different numerical fractions thereof, provided each with a coating that dissolves or disintegrates in, or is permeated by, the medium of the liquid enteral nutrient product. The different numerical fractions, respectively, each have a coating of a different thickness, whereby, by forming a mixture of the microcapsules with a fraction that is not coated, the mixture shows a sustained release effect when exposed to a aqueous medium, such as the medium of a liquid enteral nutrient product. The wrapping and the coatings must be essentially acceptable for nourishing food, or disintegrable, that is, suspendable, but not necessarily soluble. If the particles 72 are of a type of molecular sieve, or a mixture of two or more grades of molecular sieve, the particles have been impregnated with a beneficial ingredient or ingredients to be supplied during feeding, and the particles have been agglomerated to obtain granules or lumps of the desired size, which may be used with or without coating, to form a controlled release dosage form useful in accordance with the invention, the coating, if applied, is soluble or disintegrable, i.e., suspendable in, or permeable to, the medium of the liquid enteral nutrient product to be modified. The molecular sieve type material has a porous structure with non-aligned pores, where the size of the pores is critically controlled in manufacturing, in order to create the property of containing the molecules of different size or molecular weight characteristics. a selective way The containment or storage properties impart a sustained release behavior. The carrier for the units in controlled release dosage form can also take the form shown in Figure 9, but containing a fibrous material in which the fibers are hollow and permeable, and slowly release substances such as the beneficial ingredients added herein to a nutritious product. A measured amount of these fibers can be used, either in a coil or in crushed form, to a retention element such as a shirt or bag, or they may be agglomerated with a binder, or they may be coated with a dispersible, disintegrable, or permeable coating. These fibers, which can be formed primarily from an ether or cellulose ester, can store and subsequently release a beneficial ingredient or mixture of ingredients, upon contact with the liquid enteral nutrient product flowing into the drip chamber or other formulation chamber . The fibrous and highly porous carrier bag type of carrier wrap 79 shown in FIG. 9A, can also be used to contain or support, within a formulation chamber, a quantity of microencapsulated microspheres, or a quantity of material of the type. molecular sieve, or, for example, a quantity of crushed hollow and fine permeable fibers 78, any of which forms contain a dosage amount of one or more beneficial agents. This type of tea bag wrap, or a plurality thereof, can also be used to place inside a formulation chamber, any combination of: (1) one or more beneficial agents in a controlled release dosage form; (2) one or more beneficial agents in a controlled dosage form, together with one or more beneficial agents that are not in a controlled dosage form, wherein the beneficial agents that are not in a controlled dosage form can be the same or different agents to those present in a controlled dosage form; and (3) a marker dye or a dye mixture in combination with any of (1) or (2), and in a controlled release dosage form, as well as in any external coatings of units in controlled release dosage form. . Where more than one formulation chamber is used, the additional formulation chamber may have placed therein, for example, a fibrous carrier bag having thereon only the uncontrolled beneficial agent, together with or without marker dye. Any mode of manufacture of a controlled-release storage, coating or binder coating can be employed to manufacture a unit in controlled release dosage form that can be used in accordance with the invention, provided that the soluble, dispersible components. or disintegrables of the dosage form units used are physiologically acceptable, and that the unit in controlled release dosage form can store one or more beneficial ingredients as defined above, up to the use and release thereof to a nutritional product. enteral liquid, at a speed or in a useful manner, and / or over a useful period of time of at least half an hour, and preferably of more than at least two hours during enteral feeding, or longer if necessary for certain medicines and nutrients. Tablets and capsules and other dosage forms can be generally coated with well-known materials which slow down and delay the solubilization or suspension of the beneficial agent, with materials such as zein, shellac, methacrylate polymers and copolymers, and ethers and esters of cellulose those that are frequently used for the purpose. These materials are described in U.S. Patent No. 5,160,742, and may be adapted in general for the present purpose, although the coated articles described in the patent are used in a different manner. Where it is necessary or very important to provide a beneficial ingredient, or a mixture of ingredients, as defined herein, for example, one or more drugs, in accordance with the invention, and at a uniform rate over time, with a variation of preference not greater than about 25 percent above or below the average velocity over a period of 2 to about 24 hours or more, the osmotic pump and other osmotic application systems will be preferred. In general, a wide range of speeds can be used, provided that at least one effective amount is supplied without reaching excessive amounts. Among the beneficial agents that are more likely to be added to conventional enteral nutritional compositions are, for example, nutrients, such as glutamine, arginine, dietary fibers fermentabl.es, non-fermentable dietary fibers, enzymes such as lipases, combinations of amino acids, oligosaccharides such as fructo-oligosaccharides, vitamins, short-chain fatty acids (of 3 to 4 carbon atoms), pyruvate precursors in the form of pyruvamide, or pyruvam-amino acids, such as pyruvyl-glycine, pyruvyl-alanine, pyruvyl-leucine , piruvil-valine, piruvil-sarcosamine and its amides, esters, and salts, lipid structures, d-ciroinositol, lactoferrin, marine oils and acidulants such as ascorbic acid. An example of a structured lipid that provides excellent nutritional support is a glycerol base structure with at least one gamma-linolenic acid or dihomogamma-linolenic acid residue in combination with a medium chain fatty acid residue (6 to 12 atoms) carbon) and an n-3 fatty acid residue of 18 to 22 carbon atoms selected from alpha-linolenic and stearodonic acid, eicosapentaenoic acid and docosahexaenoic acid. Medications that can be usefully administered in this manner include, for example, antihistamine drugs; anti-infective agents, such as antibiotics, antivirals, and anti-infectives of the urinary tract; antineoplastic agents; autonomic drugs such as adrenergic and relaxing agents of the skeletal muscles; blood formation and coagulation drugs; cardiovascular drugs; agents for the central nervous system; diagnostic agents; electrolytic, caloric, and water balance agents; enzymes; antitussive, expectorant, and mucolytic agents; gastrointestinal drugs such as antacids; gold compounds; hormones and synthetic substitutes; smooth muscle relaxants; and unclassified therapeutic agents. Other examples are H2 blockers such as Tagamet®, prokinetic drugs; bioactive peptides; medications for the diabetic condition, agents for chemotherapy, or any medication intended for oral administration that does not react adversely with the nutritional formulation that is being fed into the gastrointestinal tract. Probiotics that can be usefully administered in this manner include, for example, Lactobacillus acidophilus GG, as described in U.S. Patent No. 4,839,281, Lactobacillus reuteri, Lactobacillus animalis, and Lactobacillus salivarius, as described in US Pat. Patent Number WO 93/02558. Probiotics are live microorganisms that help the digestion of food or help control the population of harmful microorganisms in the intestines. If desired, a marker dye or a physiologically acceptable dye mixture can be provided in the formulation chamber or chambers in addition to one or more of the beneficial ingredients described above, so that the flow of the modified liquid nutritional product is can make it visible as an aid for the health care assistant. This can be done by placing in the formulation chamber one or more units in sustained release dosage form containing both the dye or the dye mixture and the beneficial ingredients, if these dosage form units are available. A unit may be placed in controlled release dosage form containing the dye or dye mixture and a unit in separate controlled release dosage form containing the beneficial ingredients, together in the formulation chamber. As indicated above, in order to impart an immediate visibility to the flow of the modified nutritional product as an aid to the health care assistant, it may be preferred to apply an easily soluble outer coating of the marker dye to a unit in dosage form. controlled release, ordinarily one containing marker dye. The label dye is mixed with a small amount of one or more conventional easily dispersible tablet coating excipients, such as, polyvinyl pyrrolidone having a scale average molecular weight of about 35,000 to 50,000, mannitol, magnesium stearate, and zein or guar gum, in the application of the dye to the dosage form unit during manufacture. In general, the amount of excipients in total of excipients in total is less than about 10 weight percent of the coating. Or the dosage form unit can simply be dipped into a marker dye solution and dried. A label dye or a dye mixture which is useful according to the invention is a dye or a fluorescent dye or a mixture of these dyes which is physiologically acceptable to the patient and compatible with the beneficial agents that are being fed with the dye. the same. The dye or dye mixture must also be capable of recovering at a detectable concentration in the liquid medium of the liquid enteral nutrition product as long as the product flows through a drip chamber or other formulation chamber that is placed therein when minus one unit in a sustained release dosage form containing the dye or marker dyes. If the dye can be detected in the drip chamber, it can be expected that it can be detected, ordinarily, if it reaches in any way the oral cavity of the patient. The marker dye used can be a dye coloring that imparts color that is visible under white light, for example, normal daylight, or artificial light found in the hospital or clinic, or the dye marker can be a fluorescent dye that fluoresces visibly under ultraviolet light, or a mixture of dye dye and a fluorescent dye. A mixture of a dye dye and a fluorescent dye seems to be especially convenient, because the flow through the formulation chamber is easily perceived under normal lighting conditions with the dye present, while even a small amount of nutritive product outside of the dye is present. its place, for example, in the oral cavity or in the nasal passage, will be more easily detected with the help of ultraviolet light if it contains a fluorescent dye. This is due to the nature of the fluorescent dyes, which are especially visible under ultraviolet light, even when they are present in a very low concentration.

The dye or dye mixture used must be physiologically acceptable. Normally food coloring dyes approved under the provisions of the Food, Drug, and Cosmetic Act of the United States are suitable. F.D dyes are preferred. & C. Blue # 1 and F.D. & C Blue # 2. The dye or mixture of dye used must be soluble in the medium of the liquid enteral nutrient product being fed, and must be compatible with the beneficial ingredients that are being added during feeding. In general, approximately 0.1 milligrams of dye per milliliter of liquid enteral nutrient is desired to give an easily visible coloration to the nutritional product. Where it is important to detect the poorly directed liquid enteral nutrient product, the marker dye used can be a fluorescent dye, such as F.D. & C Red # 3, which is highly visible in a very low concentration of ultraviolet light, and also imparts a visible coloration to the liquid nutritional product under white light conditions. Other suitable fluorescent dyes are: quinine, F.D. & C. Red # 22, F.D. & C. # 28, Fluorescein, and D 282 UV Blue, available from DaGlo of Cincinnati, Ohio, and also identified as 16470-24-9 on the Chemical Abstracts System with a color index of 220 as a fluorescent brightener. As indicated above, if desired, a mixture of dye dye and fluorescent dye can be used. In general, addition to the nutrient in the formulation chamber of about 0.01 to 0.05 milligrams / milliliter of fluorescent dye is adequate for detectability under ultraviolet light. A feeding assembly, such as the kit shown in Figure 15, is conveniently provided in a packaged form ready for use in the feeding of a liquid enteral nutrient product. The case includes a unit in controlled release dosage form 32, a drip chamber 27 or another formulation chamber, and a liquid communication element 28 consisting mainly of a length of flexible tubing connected at one end to the outlet of the other. the drip chamber 27, and at the other end with a connection 30 for coupling to a feed tube. The connection 30 is shown with a cover 55 in telescope for illustration purposes. The lid is simply to protect the connection 30 until the power pack is used. The unit in controlled release dosage form 32 has already been placed in the drip chamber 27, and contains one or more beneficial ingredients as defined hereinabove, for the modification of a liquid enteral nutrient product during its feeding, and additionally a marker dye, if desired. The kit can also be provided with a plurality of units in controlled release dosage form 32 inside the drip chamber 27, if a single dosage form unit does not contain each type of beneficial ingredient desired for the modification of the nutritional product, or if it is desired to add a marker dye and is not present in the units in controlled release dosage form for the selected beneficial ingredients. A similar case 20c, as shown in Figure 10, includes the unit in controlled release dosage form 32 that has not been placed in the drip chamber 27 before shipping the case, but accompanies the drip chamber as part of the case. Other kits are prepared with different numbers and varieties of units in controlled release dosage form containing different combinations of beneficial agent and label dye, and beneficial agents that are not in a controlled release form, to accompany the feeding sets. In a preferred embodiment of the apparatus of the invention of the type illustrated in Figure 2, a unit in controlled release dosage form of the type illustrated in Figure 8A is placed in the formulation chamber. The dosage form unit contains glutamine and dye F.D. & C. Blue # 1, and coated with a layer of the same blue dye mixed with about 3 weight percent total of polyvinyl pyrrolidine having an average molecular weight on the scale of about 35,000 to 44,500. The feeding kit is connected to a hanging supply container of a liquid enteral nutrient product having a viscosity of about 40 cps, such as PULMOCARER, a product of the Ross Products Division of Abbott Laboratories, Columbus, Ohio, and a continuous flow of the nutritious product. The dye coating provides an immediate visible color inside the drip chamber within 2 seconds, and the unit in controlled release dosage form provides the blue dye at a concentration of at least 0.075 milligrams / milliliter, over a period of more of 1,440 minutes during the flow of approximately 3,000 milliliters of the liquid enteral nutrient product. The dosage form unit also provides glutamine at a concentration of at least 1.25 milligrams / milliliter during the flow of the liquid enteral nutrient product, beginning after approximately 1 milliliter of flow.

Claims

1. An apparatus for modifying a liquid enteral nutrient product during its feeding, which comprises: a formulation chamber, the formulation chamber having an inlet and an outlet, and the inlet can be connected to a container of the liquid enteral nutrient product, to receive the contained therein, at least one beneficial agent in at least one unit in controlled release dosage form, and the formulation chamber containing at least one unit in controlled release dosage form, each beneficial agent being selected from group consisting of nutrients, drugs, probiotics, and diagnostic agents, which are each dispersible in the middle of the liquid enteral nutrient product.

2. The apparatus of claim 1, wherein; The formulation chamber is a drip chamber.

The apparatus of claim 1 or claim 2, wherein the formulation chamber additionally contains at least one beneficial agent that is not in a controlled release dosage form.

The apparatus of claim 1 or claim 2, wherein the formulation chamber additionally contains at least one label dye in a unit in controlled release dosage form.

The apparatus of claim 4, wherein the unit in controlled release dosage form containing the label dye is coated with a fast release label dye layer.

The apparatus of claim 1 or claim 2, wherein the formulation chamber additionally contains both a label dye in a unit in controlled release dosage form, and at least one beneficial agent that is not in a unit in controlled release dosage form.

The apparatus of claim 2, wherein the drip chamber has in fluid connection with its outlet, at least one formulation chamber, and at least one of the drip chamber and each formulation chamber, contains at least one char agent in a controlled release dosage form, and the other chamber or chambers contain at least one member of the group consisting of beneficial agents in a controlled release dosage form, beneficial agents that are not in a dosage dosage form controlled, and marker dyes in a controlled release dosage form.

8. The apparatus of claim 1, wherein; the outlet of the formulation chamber is connected to a fluid communication element that can be connected to a feeding tube communicating with the gastrointestinal tract of a patient.

9. The apparatus of claim 1, wherein the at least one beneficial agent is glutamine.

10. The apparatus of claim 1, wherein the at least one beneficial agent is a probiotic.

The apparatus of claim 1, wherein, the at least one beneficial agent is a pyruvate precursor.

12. The apparatus of claim 1, wherein the at least one beneficial agent is a structured lipid.

13. An apparatus for feeding a liquid enteral nutrient product, which comprises: a formulation chamber having an inlet and an outlet, and which can be connected to a supply container of a liquid enteral nutrient product, at least one beneficial agent in a controlled release dosage formci, each beneficial agent being provided in a controlled release dosage form within the formulation chamber, such that it is moistened by, or immersed in, the liquid enteral nutrient product that passes through the body. the same, and each beneficial agent being selected from the group consisting of: nutrients, medicaments, probiotics, and diagnostic agents, and chemically and physiologically competing combinations thereof, and any of the above beneficial agents or chemically or physiologically compatible combinations of them together with a physiologically acceptable dye marker le, each beneficial agent and marker dye disposed in the formulation chamber dispersible in the medium of the liquid enteral nutrient product; and a fluid communication element capable of operatively connecting the outlet of the drip chamber with a tube for feeding, to the gastrointestinal tract of a patient, the modified liquid enteral nutrient product.

The apparatus of claim 13, wherein the formulation chamber is a drip chamber.

15. The apparatus of claim 13, wherein the formulation chamber contains a plurality of units in controlled release dosage form, each containing at least one beneficial agent, or a different one.

The apparatus of claim 13, for use in the application of an aqueous liquid enteral nutrient product, wherein the at least one beneficial agent is soluble or dispersible in water, and the unit in controlled release dosage form is a device application of a water soluble or dispersible ingredient containing at least one beneficial agent soluble or dispersible in water, the device comprising: at least one internal mass transfer conductor; wherein the at least one beneficial agent is soluble or dispersible in water present in a physiologically useful or diagnostically detectable amount, the at least one beneficial agent being soluble or dispersible in water in the at least one internal mass transfer conductor, the at least one being an internal mass transfer conductor permeable to the passage of at least one beneficial agent soluble or dispersible in water; and a membrane surrounding the at least one internal mass transfer conductor, which membrane releases at least a useful amount of the at least one beneficial agent soluble or dispersible in water to the liquid enteral nutrient product used when the product is gradually passed over the body. membrane and enterally administered to a patient.

The apparatus of claim 13, for use in the application of an aqueous liquid enteral nutrient product, wherein the at least one beneficial agent is soluble or dispersible in water, and the unit in controlled release dosage form is a device Osmotically driven, the device comprising: a capsule formed by an outer wall made, at least in part, of a semipermeable composition that maintains its integrity in the presence of an aqueous fluid, surrounding the outer wall to a hydroactivated layer comprising a swellable composition hydroactivated or a hydroactivated composition occupying space at a controlled rate, and an inner capsule surrounded by the hydroactivated layer and communicating with a lumen extending to the outside of the outer capsule, the inner capsule containing at least a useful amount of at least one beneficial agent soluble or dispersible in water in a form of formula liquid ion, and the wall of the internal capsule being substantially not permeable to the liquid enteral nutrient product.

The apparatus of claim 13, wherein the controlled release dosage form is a particulate controlled release composition comprising microencapsulated particles that contain at least a useful amount of the at least one beneficial agent, the particles having a plurality of coating thicknesses that dissolve or disintegrate gradually, and release the at least one beneficial agent into the particle when the liquid enteral nutrient product makes contact with it over time.

19. The apparatus of claim 13, wherein the controlled release dosage form is a molecular sieve-type dosage formci impregnated with at least a useful amount of the at least one beneficial agent, releasing the molecular sieve dosage form step by step. at least one beneficial agent towards the middle of the liquid enteral nutrient product when it makes contact, through time, with the liquid enteral nutritive product.

The apparatus of claim 13, wherein the controlled release dosage form contains as the beneficial agent at least one nutrient selected from the group consisting of glutamine, vitamins, arginine, oligosaccharides, short chain fatty acids, enzymes , fermentable dietary fibers, non-fermentable dietary fibers, pyruvamide, pyruvam-amino acids and their amides, esters, and salts, structured lipids, d-ciroinositol, lactoferrin, marine oils and acidulants.

The apparatus of claim 20, wherein the controlled release dosage form contains as the beneficial agent at least one nutrient selected from the group consisting of glutamine, ascorbic acid, and a pyruvate.

22. The apparatus of claim 13, wherein the controlled release dosage form contains as the beneficial agent at least one medicament selected from the group consisting of antacids, antibiotics, probiotic drugs, prokinetic drugs, bioactive peptides, drugs for the diabetic condition, agents for chemotherapy, and any other medication intended for oral administration that does not react adversely with the nutritional formulation that is being fed into the gastrointestinal tract.

23. The apparatus of claim 13, wherein the controlled release reservoir contains as the beneficial agent a probiotic selected from the group consisting of Lactobacil lus reuteri, Lactobacillus acidophilus, Lactobacillus animal is, and Lactobacillus salivarius.

The apparatus of claim 13, wherein the formulation chamber contains at least one beneficial agent selected from the group consisting of a label dye in a controlled release dosage form, and a beneficial agent which is not in a controlled release dosage form in addition to the unit in controlled release dosage form containing the beneficial agent.

25. The apparatus of claim 13, wherein each unit in controlled release dosage form contains a physiologically acceptable label dye in addition to at least one beneficial agent.

26. The apparatus of claim 13, wherein the unit in controlled release dosage form is provided with an outer layer that substantially maintains its integrity for at least the shelf life of the dosage form unit during a feeding, while being exposed to the liquid enteral nutrient composition, and the dosage form unit is in the form of a rectangular solid.

27. The apparatus of claim 13, wherein; The controlled release reservoir is confined inside a mesh bag inside the drip chamber.

28. The apparatus of claim 13, wherein the unit in controlled release dosage form is confined within a foraminous bag inside the drip chamber.

29. The apparatus of claim 13, wherein the fluid communication element includes a section of flexible tubing suitable for use with a pump.

30. The apparatus of claim 13, wherein the drip chamber contains a plurality of units in controlled release dosage form.

31. The apparatus of claim 13, wherein; the fluid communication element further includes as a component thereof, at least one additional formulation chamber having therein at least one unit in controlled release dosage form containing therein at least one beneficial agent or a different one.

32. The apparatus of claim 31wherein the at least one drip chamber and the at least one additional formulation chamber contain a plurality of units in controlled release dosage form containing at least one beneficial agent.

The apparatus of claim 31, wherein the at least one additional formulation chamber contains a unit in controlled release dosage form that contains only a physiologically acceptable dye marker.

34. A drip chamber having therein disposed a sustained release dosage form containing at least a useful amount of at least one beneficial agent selected from the group consisting of nutrients, medicaments, probiotics, and diagnostic agents. , and chemically and physiologically compatible combinations thereof, and any of the above beneficial agents or combinations of beneficial agents together with a dye marker or mixture of physiologically acceptable dyes.

35. The drip chamber of claim 34, having at least one additional sustained release dosage unit disposed therein, each unit containing at least one useful amount of at least one of the beneficial agents.

36. A case for feeding a liquid enteral nutrient product to a patient's gastrointestinal tract, which comprises: a formulation chamber having an inlet and an outlet, and which can be connected to an enteral nutrient product supply container liquid; at least one unit in controlled release dosage form containing at least one beneficial agent and up to a plurality of labeling dyes, each at least one unit being provided in controlled release dosage form within the formulation chamber to be moistened by, or submerged in, the liquid enteral nutrient product that passes through it; and a fluid communication element having first, and second ends, the first end being operatively connected to the outlet of the formulation chamber, and the second end being operably connected to a tube to feed a liquid enteral nutrient product into the gastrointestinal tract of a patient.

37. A case for feeding a liquid enteral nutrient product to a patient's gastrointestinal tract, which comprises: a formulation chamber having an inlet and an outlet, and which can be connected to an enteral nutrient supply container liquid; at least one unit in controlled release dosage form containing at least one beneficial agent and up to a plurality of labeling dyes, each unit accompanying in dosage form controlled release to the formulation chamber, and being outside thereof; and a fluid communication element having first and second ends, the first end being operatively connected to the outlet of the formulation chamber, and the second end being operably connected to a tube for feeding a liquid enteral nutrient product to the gastrointestinal tract of a patient.