MXPA97005293A - Method of modification composition of productalimenti - Google Patents

Abstract

The present invention relates to a method for modifying a liquid enteral food product during the flow thereof from a supply container to a feeding tube leading into the gastrointestinal tract of a patient, which steps: to provide an apparatus that comprises: a formulation chamber having an inlet and an outlet, said inlet fluidly connected to a supply container containing a liquid enteral product having a viscosity of at least about 3 centipoise, at least beneficial in at least one unit in the controlled release dosage form in the formulation chamber to be moistened or submerged in the liquid enteral food product in the formulation chamber, each beneficial agent is selected from a group consisting of nutrients, medicaments, probiotics, diagnostic agents and combinations chemically and physiologically compatible thereof, each agent being dis persalbe in the liquid enteral food product; and fluid communication means capable of fluidly connecting to the outlet of the formulation chamber with a device that feeds the liquid enteral food product into the gastrointestinal tract of a patient; liquid enteral from the supply container through the formulation chamber, and into the device that feeds

Description

METHOD OF MODIFICATION COMPOSITION OF FOOD PRODUCT Field of the Invention The invention relates to a method of feeding liquid enteric food products and particularly to the modification of a liquid enteral food product having a viscosity on the scale of 1 to about 300 centipoise (cps.) By adding ingredients. during the feeding thereof into the gastrointestinal tract of a patient.

Background of the Invention It is well known to feed a liquid enteral food product from a hanging container, such as a plastic bag or bottle with a lower outlet that connects to a drip chamber and the latter to a flexible tubing. or lumen, which leads to a nasogastric tube or a feeding tube inserted through a gastrostomy or jejunotomy, by gravity flow or aided by a pump. The liquid enteral food product can be aseptically processed or finally returned and can be supplied in a pre-filled container, ready to be hung or placed in such a container by a health worker. However, the selection of diets, particularly special diets, among the most modest number of liquid enteral food products is limited. This reduces, as a practical matter, the physician's options for dietary modifications, temporary or long-term, that could significantly benefit the patient. In view of the unrecognized importance of providing aseptic food compositions, it can be seen that the modified diets are not readily prepared without observing the strict requirements necessary to deliver an aseptic food composition to the patient. The need to observe such requirements has hitherto militated against the preparation of small amounts of special diets designed for a specific patient. In addition, a number of foods as well as drugs, diagnostic agents and other ingredients such as probiotics, which at a given time may be desirable to administer orally to a patient are not stable during heat sterilization or may not be mutually compatible. with other desired ingredients over a prolonged period, such as days or even months until they are used and, therefore, are not readily sensitive to large scale preparation and consequent storage as the product moves in commerce. Drug delivery systems have been described and claimed in U.S. Patent Nos. 4,511,353, 5,318,558 and 5,324,280 in which the drug component to be delivered is stored in a capsule from which it is expelled for the duration of time. osmotic infusion of the moisture within the capsule, the drug being moved away from the outer surface of the capsule by a suitable liquid in an intravenous, i.e., parenteral or even delivery system, by the device of U.S. Patent 5,318,558 , by means of corporal fluids to the implantation of the capsule. In US Pat. No. 5,069,671 a formulation chamber is described, which may also be a drip chamber, in which various forms of sustained release mechanisms are employed to release a drug or medicament or other physiologically beneficial component such as a food, within the formulation chamber from which the drug or other component is transported by a suitable liquid within a parenteral delivery system. The teachings of U.S. Patents 4,511,353 and 5,069,671 are directed to the intravenous delivery of parenteral compositions and in the case of the last patent, include delivery by infusion through intravenous, intraarterial, intraperitoneal or subcutaneous routes. The osmotic dose system of the United States Patent 5, 324,280 is related to the delivery of the drug formulations over time to a biological environment, such as a tissue or organ implant in a mammal or a stream or tank for marine life. The osmotically driven device of U.S. Patent 5,318,558 is said to be usable to deliver drugs, drugs and foods in a range of environments ranging from veterinary medicine to drug administrations to humans and hobby situations such as fish tanks. Again, in the case of human administration, the delivery appears to be within a tissue or organ implant. Although osmotic delivery devices and other sustained or controlled release dosage forms or containers have been known for some time, to the extent known, there has been no attempt to use that delivery system to add one or more foods, one or more drugs or, a mixture of foods and medicaments, or a probiotic agent, or a diagnostic agent or any of them in combination with a marker dye, up to a liquid enteral food product, with a viscosity of up to 300 cps., during administration of the food product to the gastrointestinal tract of a patient. The liquid inorganic food products currently on the market are described in the reference text "Nutrition In Critical Care", Gary P. Zaloga, of., Mosby - Year Book Inc., St. Louis, MO, 1994, in Chapter 24, by author Barbara Hopkins, Part III, "Feeding", pp. 439-467. This reference indicates that the complete food compositions contain proteins, carbohydrates, fibers, fats, and vitamins and minerals in various proportions in an aqueous or aqueous / fatty medium. Food compositions for special diets may omit one or more of these components.

BRIEF DESCRIPTION OF THE INVENTION A first aspect of the invention relates to an apparatus for adding ingredients to a liquid enteral food product during the delivery of the food product from a supply therefor, such as a hanging container, to a food tube. food that supplies the food product to the gastrointestinal tract of a patient. The apparatus comprises: a formulation chamber, usually in the form of a drip chamber, which is connected to a supply container of a liquid enteral food product, usually an aqueous composition, the formulation chamber having an inlet and an outlet, at least one beneficial agent in the form of controlled release dosage, each unit of controlled release dosage form being placed in the formulation chamber to be moistened by or immersed in the liquid enteral food product passing through the formulation chamber and each beneficial agent being dispersible in the medium of the liquid enteral food product, and fluid communication means connecting the outlet of the formulation chamber to a tube for feeding the modified enteral food product, which contains the at least one beneficial agent thus added, within the gastrointestinal tract of a patient.

Each beneficial agent, at least one, which is to be added in the controlled release dosage form during feeding is added at least a physiologically effective or diagnostically detectable amount and is selected from the group consisting of: a food ingredient; a medicament ingredient, a chemically and physiologically compatible mixture of: a plurality of food ingredients or, a plurality of medicament ingredients or, at least one food ingredient and at least one medicament ingredient; a probiotic; or a diagnostic agent; and any of the above ingredients or mixtures of ingredients in combination with at least one physiologically acceptable and compatible ingredient, the label dye or the dye mixture which is dispersible in the medium of the liquid enteral food product. The formulation chamber can be a conventional drip chamber which here also serves as the formulation or contact chamber. The formulation or contact chamber can be provided, in addition to the controlled release dosage form or forms therein, and whether or not the label dye is employed, with the same or different beneficial agents or agents that are not in dosage form. of controlled release, if desired, in order to add greater amounts of this, or to add a beneficial agent such as a bolus. In addition, the dye or dyes markers can be provided separately from the beneficial agents, in the formulation chamber, in one or more dosage forms of controlled release. If desired, one or more additional contact or formulation chambers may be employed, either in series or in parallel, but feeding into the fluid communication means leading to a patient's feeding tube. Where more than one formulation chamber is used, at least one formulation chamber will have placed thereon a controlled release dosage form containing at least a useful or detectable amount of at least one beneficial agent as defined. before, while each additional formulation chamber may contain one or more beneficial agents in one or both dosage forms of controlled and uncontrolled release. The use of more than one formulation chamber facilitates the addition of ingredients that are not readily available in combination or are not compatible during storage together in a controlled release dosage form. In each formulation chamber the beneficial agent or agents, whether in the form of controlled release doses or not, are placed and sustained or supported, if necessary, so that the liquid enteral food product being modified contacts and moistens or submerges the dosage form of the beneficial agent or agents therein. Preferably, each controlled release dosage form is formed or sustained in such a way as to prevent or prevent the beneficial agent blocking flow of the liquid enteral food product out of the drip chamber or the formulation chamber in which it is placed. The combination of (1) a formulation chamber, ordinarily in the form of a drip chamber and, (2) fluid communication means, accompanied by (3) at least one beneficial agent, as defined in present, in the form of controlled release dosage placed in the formulation chamber or only, accompanying the formulation chamber, in any case when the three parts are supplied together, constitute a useful equipment for expelling a liquid enteral food product from a container of delivery, such as a container that can be hung, and by modifying the liquid enteral food product by the addition of one or more beneficial agents thereto as it flows from the container and the modified product is fed into the gastrointestinal tract of a patient. The equipment formulation chamber may also be loaded with or 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 release dosage form, for example, in uncoated particle form or tablet in a porous carrier cover such as a bag-like package. The dye or markers of the types visible under either white light or ultraviolet light. Preferably, at least one beneficial agent in the form of controlled release dosage and any other additives in uncontrolled release dosage forms supplied as part of an equipment are already placed in the formulation or drip chamber. Otherwise, they are manually placed in the formulation chamber, ordinarily before connecting the apparatus to the supply container from which the liquid enteral food product is to be expelled. In a further aspect of the invention, this relates to a method of preparing a special liquid diet for enterally feeding a tube-fed patient comprising modifying a liquid enteral food product during the flow thereof from a supply container. containing said composition towards a feeding tube leading into 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 to the enteral food product supply container liquid, (b) a physiologically effective or diagnostically detectable amount of at least one beneficial agent in the form of controlled release doses, each beneficial agent being placed in the formulation chamber so that the dosage form thereof is in contact or submerged in the liquid enteral food product that traverses therethrough, each beneficial agent being dispersible in the medium of the liquid enteral food product and each beneficial agent in the form of controlled release dosage being selected from the group comprising: an agent food; an ingredient of medication; a chemical or physiologically compatible combination of: a plurality of food ingredients or, a plurality of food ingredients or, at least one food ingredient and at least one medicament ingredient; or a probiotic ingredient; or a diagnostic agent; and any of the above ingredients or combinations of ingredients together with at least one physiologically acceptable, compatible marker dye that is dispersible in the medium of the liquid enteral food product; and (c) fluid communication means capable of operatively connecting the outlet of the formulation chamber to a tube for feeding a liquid enteral food product into the patient's gastrointestinal tract; B. providing a supply container containing a liquid enteral food product; C. place the apparatus in series of communication in the fluid flow between the supply container and the supply tube; and D. flowing the liquid enteral food product through the apparatus wherein the product is modified within the feeding tube. In a modification of this method which may be especially useful in the proper manufacture of a diet for a patient, one or more beneficial agents that are not in the form of controlled release doses are added to the formulation chamber. The beneficial agent or agents may be the same as or different from the specific beneficial agent or agents provided in the formulation chamber in controlled dosage form. The added beneficial agents that are not in the controlled dosage form are added to achieve a bolus or bolus feeding effect, or simply to add a larger amount of a given beneficial agent. Also, the marker dye in a separate controlled release dosage form, which may have surface coating with the readily soluble dye to impart the initial rapid dye label, may be added to the formulation chamber. In another modification, the fluid communication means are provided with one or more additional formulation or contact chambers, which are not necessarily drip chambers, but each have placed therein either a marker dye or a beneficial agent, as defined herein, in the form of controlled or uncontrolled release, or a combination of label dye and a beneficial agent. The formulation chambers are connected to a supply of the liquid enteral food product and placed to allow the flow of the liquid enteral food product on each dosage form thereof to contact it or even to immerse it dynamically, i.e., immerse it in an amount of liquid that rotates constantly in order to collect the content of the beneficial agent and / or the dye and transport it to the feeding tube of a patient. A pump may be used, if needed or desired, to flow or help flow the modified liquid enteral food product within 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: Fig. 1 is a partially schematic representation of an apparatus for the modification of a liquid enteral food product and nasogastric tube feeding in accordance with the invention; FIG. 2 is a partially schematic representation of an apparatus for the modification of a liquid enteral food product and tube feeding thereof by means of a gastrostomy tube according to the invention; Fig. 3 is a partially schematic representation of an apparatus for the modification of a liquid enteral food product and tube feeding thereof, with the aid of a pump, by means of a jejunotomy tube according to the invention; FIG. 4 is an enlarged fragmentary view in front elevation of a lower portion of a hanging supply container of a liquid enteral food product, such as the container shown in FIGS. 1 to 3, with the bevelled entry tube of a drip chamber inserted through the closure and depending on it and with a beneficial agent in the form of controlled release dose into the drip chamber and immersed in the liquid enteral food product flowing, the lower part of the drip chamber and the controlled release dosage form being partially cut off and in section and, the tube portion of the fluid communication means, ie, mainly the tube leading away from the drip chamber, being truncated for illustration purposes; Fig. 5 is a perspective view of a drip chamber usable in accordance with the invention with a controlled release dosage form in the form of a substantially rectangular solid with slightly rounded corners placed inside the drip chamber, bevelled entry tube of the drip chamber which is the upper end which is traversed in the normal way through the closure of the supply container to communicate with it and receive the liquid enteral food product therefrom; Fig. 6 is a perspective view of the drip chamber of Fig. 5 inverted to show more detail of the construction; FIG. 7 is a perspective, partially exploded and sectional view of a controlled release dosage form of rectangular solid form, of the osmotic pump type, used to deliver a beneficial ingredient or mixture thereof within the formulation chamber in accordance with the invention; FIG. 8 is a front elevational view, partially broken away and in section, of a solid-phase, almost rectangular controlled release dosage form of another type of osmotic device, used to deliver a beneficial ingredient or mixture thereof within the formulation chamber according to the invention; Fig. 8A is a view similar to Fig. 8 of a sustained release dosage form of the same type augh with an outer coating of the marker dye which is readily absorbed immediately in the medium of the liquid enteral food product at the beginning of the flow that begins through the formulation chamber and the use where the dosage form contains the marker dye for sustained release thereof; Fig. 9 is a side elevational view, partially broken away and in section, of an almost rectangular shaped carrier of controlled release dosage forms, microencapsulated particle type or molecular sieve type, used to deliver an ingredient beneficial or mixture thereof within the drip chamber according to the invention; Fig. 9A is a perspective view, partially broken away and in section, of a highly permeable fibrous package, preferably a bag type carrier of the non-spun, suitable for placement in the drip chamber or other formulation chamber and capable of retaining a sustained release dosage form, such as a coated tablet or an osmotic delivery device, or a coated capsule or, a capsule containing an amount of controlled release dosage forms in the form of microencapsulated particles or material of the molecular sieve type or permeable hollow fibers, each form article or dose unit containing at least one beneficial agent or a mixture thereof with a marker dye . A beneficial agent that is not in the form of controlled release dosage, whether in the form of a tablet or loose particle or agglomerate, may also be placed in a measured amount in a porous carrier such as one or more porous packages of the type shown in FIG. 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 at least one formulation camera used with the same communication media. A small amount of marker dye that is not in the form of controlled release dose can also be placed in the fibrous package for rapid initial dye marking; Fig. 10 is a side elevational and partially truncated view of a feeding set or equipment, including a beneficial agent in the form of controlled release dosage to be placed in the formulation chamber by the health worker, the equipment being useful in the modification of a liquid enteral food composition during the feeding thereof in accordance with the invention; Fig. 11 is a view similar to Fig. 4, although with the controlled release dosage forms of any of Figs. 7 to 9A confined within a mesh screen or bag; Fig. 12 is a view similar to Fig. 4, but with the dosage forms of any of Figs. 7 to 9A confined within a foraminated, perforated or fibrous screen or bag; Fig. 13 is a view similar to Fig. 4, but with a plurality of controlled release dosage forms of any of Figs. 7 to 9A supported by a foraminous plate on the lower orifice of the drip chamber; Fig. 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 Fig. 13 instead of the foraminous plate shown for support a controlled release dosage form placed in the drip chamber; Fig. 14 is a side elevational view similar to Fig. 13 showing a drip chamber that depends on a supply container with the liquid enteral food product flowing through the chamber on a beneficial agent in a form of controlled release dose interspersed with the added beneficial agent in an uncontrolled dosage form while the dosage forms are supported on a perforated plate near the bottom of the formulation chamber; Fig. 15 is a side elevational view of a feeding assembly according to the invention, including a drip chamber, loaded with a beneficial agent in the form of controlled release doses and, fluid communication means with the tube feed used to direct the modified liquid enteral food product into a patient's gastrointestinal tract, which includes a removable protective layer for the end connector; Fig. 16 is a side elevational view of a feeding equipment in which a second formulation chamber has been fixed by its input in fluid communication towards the end of the flexible tubing that normally joins an accessory that connects to the patient feeding tube, the outlet tube of the formulation chamber having an accessory for connection to the feeding tube; Fig. 17 is a perspective view of a suitable formulation chamber similar to that shown in Fig. 5 although with a different form of connection for connection to a supply container, the lid here is threadably attached to a container. supply and is formed integrally with the upper part of the formulation chamber; Fig. 18 is a perspective view of the formulation chamber shown in Fig. 17 as viewed in the opposite direction; Fig. 19 is a side elevation view of a feed assembly in which two formulation chambers are connected in series, here in tandem; and Fig. 20 is a side elevation view of part of the apparatus for modifying a liquid enteral food product during enteral feeding wherein two formulation chambers are suspended from respective hanging supply containers, each containing the liquid enteral food product, the outputs of the formulation chambers being connected to segments of pipe that connect to a "Y" fitting that joins the parallel flow of each formulation chamber within a single stream within the communication means, here truncated.

Definitions Used in the Present The following terms and phrases are defined for the purposes of the description and the claims. "Enteric" food products refers to liquid compositions that are commonly understood to be delivered to and used in the gastrointestinal tracts of patients. Such enteric food products have a viscosity in the range of 1 to about 300 cps and more frequently in the range of about 5 to about 150 cps. "Enteral food product medium" refers to the liquid portion of a liquid enteral food product, primarily water, although it often includes smaller or smaller amounts of one or more liquid non-aqueous substances such as lipids, for example, vegetable oil and oil Marine.

The term "gastrointestinal tract" is used herein to refer only to the stomach and small intestine. Feeding into the gastrointestinal tract is done through the use of a nasogastric tube through a nasal passage and the esophagus and from there into the stomach or, through the use of a feeding tube that extends through the abdominal wall towards the stomach or the small intestine. A "physiologically important" or "beneficial" ingredient is an ingredient that is or is considered to be, nutritionally or pharmaceutically important to the patient, or otherwise, medically important as in the case of a probiotic or, a diagnostic agent such as an opaque agent. A "probiotic" is understood to be a live microbial food supplement that beneficially affects the human host by increasing the individual's microbial balance in the gastrointestinal tract, for example, Lactobacillus reuteri. A "beneficial agent or ingredient that is dispersible in the medium of the liquid enteral food product" is an agent or ingredient that is added in a physiologically beneficial or otherwise beneficially added manner, as in the case of a diagnostic agent, to the product. Liquid enteral nutrition during enteral feeding and, is dispersible in the middle of the food product. The beneficial agent (s) or ingredient (s), whether or not supplied in units or devices of controlled release dosage form and used in accordance with the invention, must be dispersible in the medium of the product. Liquid enteral food that is being modified during feeding, in order to be transported along with the food product within the patient's gastrointestinal tract. A "useful amount" of a beneficial ingredient that is dispersible in the medium of the liquid enteral food product is an amount that is physiologically effective or diagnostically detectable "with respect to a patient, i.e., produces, or is reasonably expected to produce, a beneficial effect detectable on the patient either on a short or long term basis when fed as part of a liquid or enteral food product, is detectable in the diagnosis of a condition or disease, generally no more than about 5 grams of beneficial agent will be contained in an individual controlled release dosage unit or device and, a plurality or even a multiplicity of units such as microencapsulated microspheres containing a given desired beneficial agent can be employed to provide a desired level of the beneficial agent in the food product that is being fed, the phrase "at least one ag "beneficial entity dispersible in the medium of the liquid enteral food product" refers to the singular as well as the plural, as may also be decided from the context and includes, combinations of ingredients, agents or factors.

The term "dispersible" as used herein with respect to the beneficial agent (s) is understood to apply to substances that are soluble as well as those that can be suspended sufficient to be readily absorbed and transported through the liquid medium as the liquid enteral food product flows through the formulation chamber containing one or more dosage forms of controlled release. The term "feeding set" refers to the combination of a drip chamber or other formulation chamber and fluid communication means leading to a feeding tube for enteral feeding. The drip chamber or other formulation chamber is loaded with or accompanied by at least a useful amount of at least one beneficial agent in the form of controlled release dosage, the beneficial agent being as defined above or without a label dye in combination and with or without additional benefit agent that is not in the form of controlled release dose. The term also encompasses a feed assembly having at least one additional drip chamber or one or more fluid flow or parallel flow formulation chambers., as a part of the fluid communication means, each feeding set having at least one drip chamber or formulation chamber loaded with at least one beneficial agent in the form of controlled release dosage, each beneficial agent being present in at least a useful amount as identified before. When more than one formulation chamber is used, the additional camera or chambers may contain: (1) one or more beneficial agents in the form of controlled release doses only, with or without marker dye in the controlled release dosage form; or (2) one or more beneficial agents in the form of controlled release dosage interspersed with one or more beneficial agents that are not in the form of controlled release doses and with or without marker dye in the form of controlled release doses, or (3) ) one or more beneficial agents none of which is in the form of controlled release doses and with or without marker dye in the form of controlled release doses. The "infusion" process refers, in the present context, to the process of delivering a soluble enteral beneficial ingredient to the gastrointestinal tract of a patient that extends for at least one minute to about 30 hours, although more usually at least from about 2 hours to about 24 hours. The term "means of supply" generically denotes the means or system for storing and subsequently delivering or releasing a beneficial ingredient or agent or mixture thereof within a formulation chamber such as a drip chamber during and, as a consequence of, the flow through a liquid enteral food product that uses a dosage form of controlled release 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, osmotic delivery device, coated capsule, microencapsulated particles such as microspheres, agglomerated particles, for example , molecular sieve particles, or a fiber of hollow, thin, permeable walls such as a bundle of cut fibers or a spool, each shape containing and storing and subsequently releasing or dispersing in the case of osmotically driven devices, a useful content of a beneficial agent within the medium of a liquid enteral food product at room temperature in a slow, delayed or intermittent manner in comparison to the solubility characteristics normally exhibited by that beneficial agent, when it is in the form of untreated or uncoated particles, in the middle at about room temperature, which any dosage form employing coating, encapsulation, microencapsulation, wrapping in an osmotically driven device, or capture in a structure of the molecular sieve type or in a thin permeable hollow fiber, retarding or postponing the delay or intermittent solubilization of a rapidly soluble beneficial agent so that its dissolution or dispersion with an osmotically driven device takes place during the course of at least 30 minutes and preferably, at least 2 hours, of contact with the flowing enteral liquid food product, or the release is retarded, i.e., not initiated for about 10 minutes after the initial contact in a formulation chamber by the liquid enteral food product, is exhibiting controlled release behavior. For a beneficial agent that is not inherently soluble rapidly in the medium of a liquid enteral food product, any dosage forms that delay or reduce, the delay or intermittent delay solubilization of such beneficial agent by at least 20% of the Normal time for the solubilization or dispersion within the medium of a liquid enteral food product, a given unit amount of the beneficial agent that is not coated or treated to obtain a controlled release is considered for the purpose of the description and the claims that be a form of controlled release dosage. Preferably, the controlled release dosage forms prolong the release of the contents thereof for an appropriate time for the food or drug or other beneficial agent that is being delivered. On the other hand, only by forming in tablet a beneficial agent either not mixed with another material or without combining with a relatively insoluble binder type excipient., for example, as it results in a smaller surface that is exposed to a solvent liquid and a slower dissolution rate than that of the fine particle form of the beneficial agent, it is not considered to make the beneficial agent within a dosage form of controlled release. Clearly, a beneficial agent in the form of a particle that has not been coated with or enclosed in any other material is not in the form of a controlled release dose. There are no tablets or particles not covered by a beneficial agent, clearly neither in the form of controlled release dosage, to be considered as transformed in the controlled release form only by being enclosed in a carrier such as a bag type pack. fibrous or an easily dissolved or disintegrated capsule. The "controlled release dosage forms" useful in accordance with the invention are understood to include the delayed or intermittent release as well as the sustained release dosage forms, some of which constitute the "speed control means" or "the". dosage forms of controlled speed ". Any dosage form that provides, over a period of at least 30 minutes or with a delay of at least 10 minutes, a beneficial agent within the liquid enteral food product flowing through a formulation chamber having a form of dosage therein, is considered to be a controlled release dosage form for the purposes of the invention. Preferably, the controlled release dosage forms prolong the release of the contents thereof for an appropriate time for the food or medicament being delivered. The terms "controlled release dosage form units" or "controlled release dosage form particles" are to be understood as referring to individual coated tablets or coated capsules or devices such as osmotic delivery devices or microcapsule or small particles. thin hollow fiber bundles or small agglomerated groups of molecular screening type material, each capable of sustained or delayed delivery or intermittent delivery of the beneficial agent or dye as defined above. It should also be understood that the phrase "which makes the liquid enteral food product flow through the apparatus, where it is modified and inside the feeding tube" implies that it includes using the gravity flow from a hanging container, as well as using a pump in addition to or without the gravity flow to promote the flow of the modified liquid enteral food product within and through a feeding tube.

Detailed Description of the Invention Referring now to the drawings in which like parts are referenced by similar reference numerals, the apparatus of the invention is shown in Fig. 1 in the form of a feeding assembly, generally indicated by the number 20, which connects the outlet 21 of the hanging supply container 22 to the nasogastric feeding tube 23 which extends through a nasal passage 24 of the patient and down into the esophagus 25 to the stomach 26. The feeding set it consists here of a formulation chamber 27, in the form of a drip chamber which also serves as a formulation or contact chamber and, fluid communication means indicated generally by the number 28. "Fluid communication means" are for it being understood that they include all the fluid communication components used in series give the outlet of the drip chamber 29 to the connection 30 pa the feeding tube, such as the nasogastric feeding tube 23. The components include not only portions of flexible tubing 54 but also any additional drip chambers or other formulation chambers connected in series as seen in Figs. 16 and 19 for serial or parallel flow although soon joined within an individual stream as seen in Fig. 20, for flow of the liquid enteral food product to the patient's feeding tube. The components may also include any portions of special tubing 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 helpful to use two formulation chambers in tandem, 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 also be used in tandem to introduce different respective beneficial ingredients that are not supplied together within the same unit or particle in a controlled release dosage form. The respective ingredients may constitute a poorly used combination, for example, or may not be compatible in storage together within a controlled release container. Two formulation chambers in use sequentially in series are shown in the feed assembly of Fig. 16 where the second formulation chamber 76 is attached to the end of the flexible tubing 54 that is distant from the supply container. This can be found useful in adding a special beneficial ingredient to a ready-made food set. With the formulation chamber 76 at the end of the assembly that is distant from the supply container, it would likewise be placed horizontally as illustrated and is preferably made with a bulbous middle portion 77 or a longitudinal channel portion that is located lower where the Beneficial agent 32 in the form of controlled release dosage will be located on the lower side of the formulation chamber and will be moistened by the flowing liquid enteral food product. If the beneficial agent is not in controlled dosage form it will be located in the same way, for example, on the underside of the bulbous section 77 until it is dispersed. The double training chambers 74 may be used in parallel as indicated in Fig. 20 and, for the same reason as the tandem chambers or, it may be simpler where one wishes to feed a beneficial agent on a bolus basis and another on a sustained basis. It is preferable to hang such chambers from the respective supply vessels, as shown, to avoid control problems in order to obtain adequate flow through both formulation chambers from an individual supply vessel, which would preferably require the use of a splitter valve to distribute the inflow between the two parallel routes. The outlets of each formulation chamber shown in Fig. 20 are connected to segments of flexible tubing 54 leading to a "Y" fitting 75 in which the streams of the liquid enteral food product are joined. Referring again to Fig. 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 is dispersible in the medium of the enteral food product. liquid 33 flowing from the supply container 22 into the formulation chamber 27 where the liquid enteral food product, which is normally based on water, makes contact with the controlled release dosage form unit 32, by wetting or submerging it within of the formulation chamber, causing the release or discharge into the food composition of the dispersible beneficial ingredient or ingredients, in addition to the marker dye if included, stored in the container. The flow of the liquid enteral food product is conveniently initiated or stopped or occasionally regulated by the use of a conventional adjustable compression fastener 34. Turning now to Fig. 2, a hanging supply container 22 is shown supplying the liquid enteral food product 33 to a formulation chamber 27 from which the liquid enteral food product flows through the flexible tubing 54 of the feeding assembly 20a to the gastrostomy feeding tube 33a. The gastrostomy feeding tube shown in Figure 3 is merely illustrative of the wide variety of gastrostomy feeding tubes that are commercially available, it being understood that the apparatus of the present invention is usable with a variety of gastrostomy feeding tubes. Fig. 3 shows a feeding arrangement for a jejunostomy very similar to the apparatus in Fig. 1, except that the feeding assembly 20b is adapted to be used with a pump 35 that provides positive flow within the feeding tube 23b that leads to the small intestine 26a of the patient, considering that in a number of cases the flow of gravity is used. Also, a second formulation chamber 27a is used as part of the feed assembly 20b in order to add additional or different beneficial agent and / or label dye, each dispersible in the medium of the liquid enteral food product 33 flowing from the container. supply 22 to the formulation chamber 27 and thence through the rest of the communication means 28b and the formulation chamber 27a of the feed assembly 20b to the jejunostomy feeding tube 23b. The additional beneficial agent may be in the controlled or uncontrolled release dosage form. If desired, or as needed, as often as the case is when feeding by means of the feeding tube, such as a jejunostomy tube, a pump, such as a peristaltic pump with cam action acting on the tube portion flexible of the media 28 or a positive displacement pump with a disposable fluid infusion pump chamber cartridge such as that described in US Patent 4,927,411 and serially connected in the media, may be used for flowing or helping to flow the modified liquid enteral food product into the feeding tube, for example, when it is not convenient to hang or otherwise locate the supply container in an elevated position relative to the patient or, when the foodstuff It is more viscous and flows slowly by gravity flow. The fluid communication means 28 of the apparatus used will ordinarily 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 formed flexible tubing, said tubing may be replaced by all or part of the communication means that supply the modified liquid enteral food product from the formulation chamber to the tube. of patient feeding. 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 in Fig. 15., while forming the input end of the formulation chamber. In addition to receive the coupling element and, the outlet of the formulation chamber communicates with a short length of the flexible pipe which likewise terminates in a coupling element 30, which is connected to the supply pipe 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 tube. 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 tandem at that end of the assembly. The formulation chamber 27 has been loaded with a beneficial agent in the form of controlled release dose 32, while the second formulation 27a has been provided with the same or different beneficial agent that is not in the form of a controlled release dose. The use of the beneficial agent that is not in the controlled release form is also illustrated in Fig. 14 where a plurality of sustained release dosage form units 32 containing beneficial agent (s) are supported on the plate. cut 53 together with the beneficial agent that is not in the controlled release dosage form as dispersible particles or tablets 80. The formulation chamber 27a may be hung vertically, like a conventional drip chamber, although it will probably be placed more conveniently in the direction of the flow of the liquid enteral food product through it approximately horizontally. Accordingly, the formulation chamber 27a should be provided with means for guiding or channeling the liquid food product into physical contact with the controlled release dosage unit or units therein. Such means may be located inferior to the longitudinal channel in the wall of the body or a bulbous elongation of the chamber body of the type illustrated in Fig. 16 or even a simple lateral depression in the side wall of the lower side of the chamber or, a trap , or pourer or, any other means for retaining the dosage form units where there will be an adequate flow or depth of liquid sufficient to achieve good contact with the units or particles of controlled release dosage form located in the guide means or channel . As seen in Figure 16, a feeding apparatus has been provided with a second formulation chamber 76 with a bulbous body portion 77 in which a controlled release dosage form unit 32 is positioned so that the flow of the control unit is in a controlled manner. Liquid enteral food product will make firm contact with the controlled release dosage unit form unit 32 and absorbs the beneficial agent therefrom. In the enlarged fragmentary view in Fig. 4, a controlled release dosage form unit 32a in the form of an osmotic device capsule is immersed in a liquid enteral food composition 33 within the drip chamber 27. This type of controlled release dosage form having an outer coating or membrane that does not readily disintegrate should preferably have a geometric shape, for example, that of a rectangular solid, which will prevent the flow of blocking of the liquid enteral food product 33 through a circular opening such as that of the channel 40 which serves as the outlet of the lower part 39 of the drip chamber 27, or other means such as a bad sieve can be employed to prevent such blocking. Details of the construction of an example of the conventional drip chamber suitable for use as a formulation chamber in accordance with the invention are illustrated in Figs. 5 and 6 that are seen in perspective enormously elongated. The drip chamber 27 as shown has two parts. The first part is an almost cylindrical camera body, hollow 37 with a first open end 38, which is the upper end when the drip chamber is in its normal operating position and a second end 39, opposite the first end, which tapers or narrows a hole 40 leading to a portion of integrally formed outlet tube 29. Chamber body 37 is preferably formed of a clear material, such as plastic or glass, to allow visibility through the flow of food product. Usually the drip chamber is formed of a self-sterilizable plastic, in some flexible, clear manner, such as clear polyvinyl chloride or polyolefin resin. The second part of the drip chamber 27 shown is of the nature of a plug 42 with a cylindrical body having an inward end portion 43 that closely fits under pressure into the inlet end 38 of the chamber body 37. Preferably the portion end 43 of plug body 37 extending within 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 is slightly raised, being a little larger in diameter and serves as a retainer when assembling the camera body and the cap together. The plug body is provided with an integrally formed fluid communication passage 45 that takes the form of a bore in a solid plug body communicating with an inlet tube portion 46 projecting outwardly in the axial direction from a collar-like flange 47 extending radially from the upper end 48 of the plug body. But, preferably, to provide a cap body with more elasticity for easier insertion into the upper end 38 of the camera body 37, the fluid communication passage 45 is a concentrically located tube axially located in and around as long as the body of plug. The concentric tube 45 is integrally formed with or otherwise operatively connected to the inlet tube portion 46. An integrally formed, peripheral, short flange 50 extending longitudinally from the flange-like flange 47 may be provided if desired. along one side of the plug body 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 can be pigmented, if desired, for visibility as an aid in observing the proper seating in the body chamber. The distal or free end 49 of the inlet pipe portion 46 has a bevelled end sharp enough to facilitate piercing of the seal (not shown) in the closure 21 in the neck of a conventional hanging supply container, such as the container 2. The collar-like flange 47 serves as a retainer for the insertion of the sharpened inlet tube portion 46 into the closure 21 in the neck of the supply container 22. Other construction modes of the forming chamber may be to be employed as long as a suitable connection is provided to the supply container as well as a tubular viewing portion through which the flow velocity of the liquid enteral food product can be observed. For example, see the formulation chamber 82 illustrated in Figs. 17 and 18 wherein the plug end 83 of the formulation chamber is integrally formed with the closure 84 for a conventional supply container to be threadably connected thereto. The apparatus of the invention is not considered to be limited to the inclusion of any of the drip chambers used herein by way of illustration, nor is the method limited to the use thereof.

The drip chamber shown in Figs. 5 and 6 has a controlled release dosage unit 32 placed on the same list for use. The controlled release dosage form unit will be preselected in accordance with the contents thereof to provide the additional food (s) and / or medicament (s) and / or probiotic (s) and / or agent (s). ) Diagnostic and / or other beneficial ingredient (s) selected by the health worker on the load, along with a marker dye if desired. As used herein and in the claims, drugs are understood as substances used in therapy. The formulation chamber, or chambers, selected may contain more than one controlled release container in order to provide a combination of foods or, a combination, of foods and medicaments or other beneficial agents, adjusted to the needs of the patient being fed. . The formulation chamber can also be provided with the same or different beneficial agents or agents in both the controlled and uncontrolled release dosage form to provide, for example, a greater amount, as in the case of a food. A dosage form of uncontrolled release of a beneficial agent can be used to deliver the beneficial agent for a shorter period, as may be desired with a medicament. The controlled release dosage form units employed will preferably be in the form of a coated tablet, an osmotic delivery device, a coated capsule, a microencapsulated microsphere, an agglomerated particle, for example, as the particles of the molecular sieve type or , a bundle of thin hollow permeable fibers or hollow permeable fibers cut, agglomerated or held in a fibrous bundle. To avoid having a unit of dosage form or particle block the flow of the liquid enteral food composition through the outlet orifice 40 of the drip chamber, if the dosage form unit is one that maintains the integrity of the the outer layer of the coating thereof while the ingredients are leached or expressed during contact with the liquid enteral food product, it is preferred that the dosage form unit has a geometric shape, for example, a rectangular solid or a form of star, any of which will not completely block a round passage. If a different type of controlled release dose form is used that dissolves or disintegrates so that the intermediate form is not controllable or leaves an insoluble base structure or debris, it is preferred to confine the controlled release dosage form units in a mesh-type bag within the drip chamber or other formulation chamber such as the mesh screen 51 shown in FIG. 11. A plurality of controlled release dosage form units are also shown in FIG. 11. which may be employed in order to provide additional beneficial ingredients that are dispersible in the medium of the liquid enteral food product in order to obtain a food composition tailored to the patient. This can be especially useful where none of the available controlled release dosage forms can have the exact combination of ingredients that is desired or needed for a patient and the combination can be made to the choice if there are controlled release dosage form units. available that contain the different desired ingredient contents. As seen in Fig. 12, a foraminous sleeve or bag, that is, one with numerous holes therein, can be used to place the controlled release container (s) in the drip chamber or other formulation chamber. Or, returning to Fig. 13, a corrosion resistant ceramic or metal plate 53 which is foraminous or cut out within the body of the lower part of the drip chamber can be placed 37, or another formulation chamber, to support the controlled release dosage form units, 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 screen 41, such as that shown in Fig. 13A and is also preferably formed of a vitrified plastic or ceramic or corrosion resistant metal, such as a stainless steel . The above positioning means, ie, which support the controlled release dosage form units within the drip chamber can also be used in any additional formulation chambers in the feed set employed. The controlled-release dosage form unit illustrated in FIG. 7 is of the osmotic pump type operating in the manner of an osmotically driven delivery device described and claimed in U.S. Patent 5,318,558, the specification and drawings of which are incorporated herein by reference with respect to the structure of the controlled release dosage form units described herein and the method of making them and their mode of operation, although here with different environments and contents and end uses . In controlled release dosage form units of the pump type or delivery devices, the beneficial ingredient (s) in liquid form ie either in the liquid state or in solution in a solvent suitable, is expressed from a cylindrical envelope or cavity 56 within the container through a small hole 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 it confines a hydro-active substance 60 behind the piston 58, which drives the piston firmly toward the side of the container where the ingredient (s) 61 is (are) forced through the orifice 57. The orifice 57 is very small and is preferably perforated by a laser beam. The cylindrical sheath 56 is formed within an external non-permeable membrane or coating 62. The hydro-active substance 60 may 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 polyhydroxyalkyl methacrylate with a molecular weight of 30,000 to 500,000 or a polyvinylpyrrolidone with a molecular weight of 10000 to 360000, an anionic or cationic hydrogel or poly alcohol vinyl that has a lower acetate residue. The controlled release container illustrated in FIG. 8 is another osmotic dose system with a sustained release dosage form that functions in the manner of the osmotically-operated delivery described and claimed in U.S. Patent 5,324,280, the specification and drawings. of which are incorporated herein by reference with respect to the structure of the sustained release dosage form units described therein and the method for doing so and their mode of operation, although here with different environments and contents and end uses. In this type of system, the beneficial ingredient (s) 63 to be fed into the liquid form or solution form is enclosed within a non-permeable coating 64 that is surrounded by a layer 65 of hydro-active material that is entirely confined within a semi-permeable membrane coating 66. The osmotic pressure that develops in the hydro-active layer 65 upon infusion of moisture therein compresses the core 67 containing the (the) beneficial ingredient (s) in liquid form 63 and forces the liquid firmly through a very small passage 68 from the core 67 to the outside of the container. Returning now to Fig. 8A, the controlled release dosage form unit as shown in Figs. 7 and 8 may be coated with an easily soluble coating, such as a coating 69, which may be a marker dye coating or beneficial agent for the purpose of obtaining a rapid initial release of said dye or beneficial agent. In the case of the beneficial agent such as a medicament, this may be desirable in order to raise a blood content, after which a stable sustained release level may be needed. The controlled release container 70 illustrated in FIG. 9 is of the type in which a quantity of microcapsules or particles is provided within a carrier cover 71 that is very rapidly soluble or disintegrable in the medium of the liquid enteral food product. of the type of molecular screening 72. If the microcapsules, the particles 72 are microspheres each individually coated and each containing the same beneficial ingredient or mixture thereof, with a plurality of numerical portions or different fractions thereof each provided with a coating that dissolves or disintegrates in or is infiltrated by the medium of the liquid enteral food product. The different numerical fractions, respectively, each have a coating of a different thickness whereby when making a mixture of the microcapsules with a fraction that is not coated, the mixture shows a sustained release effect when exposed to an aqueous medium, such as the medium of a liquid enteral food product. The cover and coatings must be essentially acceptable for nourishing food or, disintegrable, that is to say that they can be suspended, although not necessarily soluble. If the particles 72 are of a molecular screening type or, a mixture of two or more grades of molecular screening, the particles have been impregnated with a beneficial ingredient or ingredients to be supplied during feeding and the agglomerated particles in granules and groups of the desired size which are usable with or without being coated, to form a controlled release dosage form usable according to the invention, the coating, if applied, being soluble or disintegrable, i.e., can be suspended in or infiltrated towards the medium of the liquid enteral food product to be modified. The molecular screening type material has a porous structure with non-aligned pores where the pore size is critically controlled in manufacturing in order to create the property of retaining molecules of different size or molecular weight characteristics in a selective manner . The holding or storage properties impart sustained release behavior. The carrier of the controlled release dosage form units can take the form shown in Fig. 9 although it contains a fibrous material in which the fibers are hollow and permeable and slowly release substances such as the beneficial ingredients added here to a food product. A measured amount of such fibers, on a reel or in cut-out form, can be used in retention means such as a sleeve or bag or agglomerated with a binder or, coated with a dispersible, disintegrable or permeable coating. Such fibers, which may be formed first of an ether or cellulose ester, are capable of storing and subsequently producing a beneficial ingredient or mixture of ingredients, upon contact with the liquid enteral food product flowing into the drip chamber or other chamber Formulation The fibrous and highly porous bag type carrier cover 79 shown in Fig. 9A can also be used to retain or support, within a formulation chamber, a quantity of microencapsulated myoscospheres or, an amount of material of molecular sieving or, for example, a quantity of thin hollow permeable fibers cut 78, any of which forms retains or contains a quantity of doses of one or more beneficial agents. Said type of cover bag, or a plurality thereof, may also be used to place within a formulation chamber any combination of: (1) one or more beneficial agents in the form of controlled release dosage; (2) one or more beneficial agents in controlled dosage form together with one or more beneficial agents that are not in controlled dosage form, wherein the beneficial agents that are not in controlled dosage form can be the same or different agents that those present in a controlled dose form; and (3) a marker dye or dye mixture in combination with either (1) or (2) and in a controlled release dosage form fixation, as well as in any external coatings of controlled release dosage form units. . 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 the marker dye. Any way of making a sustained release or controlled release coating or binder or coating can be used to make a controlled release dosage form usable according to the invention as the soluble, dispersible or disintegrable components of the release units of the invention. The dosage form used are physiologically acceptable and the controlled release dosage form unit is capable of storing one or more beneficial ingredients as defined above until the use and release thereof within a liquid enteral food product on a scale or manner useful and / or for a useful period of at least 90 minutes and preferably for at least two hours during the course of enteral feeding, or more if necessary for certain drugs and foods. Tablets and capsules and other dosage forms can generally be coated with well-known materials that delay and retard the solubilization or suspension of the beneficial agent, materials such as zein, shellac, polymers and copolymers of methacrylate, and ethers and esters of cellulose that are frequently used for this purpose. Such materials are described in U.S. Patent 5,160,742 and are generally adaptable for the present purpose, although the articles coated in the patent are used in a different manner.

When it is necessary or very important to provide a beneficial ingredient or a mixture of ingredients, as defined herein, for example, one or more medicaments, in accordance with the invention and at an almost uniform rate over time, with preferably no more than about 25% variation above or below the average velocity over a period of two to about 24 hours or more, the osmotic pump and other osmotic delivery systems are preferred. Generally, a wide range of speeds is usable insofar as at least one effective amount is supplied without reaching excessive amounts.

Among the beneficial agents that are most likely added to conventional enteral food compositions are, for example, foods such as glutamine, arginine, vitamins, fermentable diet fibers, non-fermentable diet fibers, enzymes such as lipases, combinations of amino acids, oligosaccharides such as fructo-oligosaccharides, short-chain fatty acids (C3-C4), pyruvate precursors in the form of pyruvamide or, pyruvyl amino acids, such as pyruvam. glycine, pyruvyl-alanine, pyruvyl-leucine, pyruvyl-valine, pyruvyl-sarcosamine and its amides, esters and salts, structural lipids, d-cyclo-nosol, lactoferrin, marine oils and acidulants such as ascorbic acid. An example of a structured lipid that provides excellent food support is a glycerol structure with at least one gamma linoleic acid or linoleic acid residue dihogame in combination with a chain fatty acid residue of medium (C6-C12) and a residue of C18-C22 n-3 fatty acid selected from alpha-linolenic and steardonic acid, eicosapentanoic 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 urinary tract antinfectants; antineoplastic agents; autonomous drugs such as adrenergic and muscle-skeletal relaxing agents; blood formation and coagulation drugs; cardiovascular drugs; agents of the central nervous system; diagnostic agents; electrolytic, caloric and water balance agents; enzymes; antitussives; expectorants and mucolytics; gastrointestinal drugs such as antacids; gold compounds; hormones and synthetic substitutes; gentle muscle relaxants; and unclassified therapeutic agents. Other examples are H2 blockers such as Tagamet®, prokinetic drugs, bioactive peptides, drugs for diabetic condition, chemotherapy agents or any drug intended for oral administration that will not react adversely with the food formulation 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 4,839,281, Lactobacillus reuteri, Lactobacillus animalis and Lactobacillus salivarius, as described in WO 93/02558. Probiotics are live microorganisms that help in the digestion of food or that help control the population of harmful microorganisms in the intestines. If desired, a physiologically acceptable dye marker or 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 food product can be made visible as an aid to the health worker. This can be done by placing in the formulation chamber one or more sustained release dosage form units containing the dye or mixture of the dye and the beneficial ingredient (s), if such dosage form units are present. available. Or, a controlled release dosage form unit containing the dye or dye mixture and a separate controlled release dosage form unit containing the beneficial ingredient (s) can be placed together in the formulation chamber. As indicated before, in order to impart the rapid visibility of the flow of the modified food product as an aid to the health worker, it may be preferred to apply an external, easily soluble coating of the marker dye to a controlled release dosage form unit, in an ordinary manner one that contains the marker dye. The label dye is mixed with a small amount of one or more dispersible tablet coating excipients, such as polyvinylpyrrolidone having a scale average molecular weight of about 35,000 to 500,000, mannitol, magnesium stearate and zein or guar gum, the application of the dye to the dosage form unit during manufacturing. Generally the amount of excipients in total is less than about less than 10 weight percent of the coating. Or, the dosage form unit can be simply immersed in a marker dye solution and dried. A dye label or dye mixture which is useful according to the invention is a dye or a fluorescent dye or a mixture of such dyes which is physiologically acceptable to the patient and compatible with the beneficial agents that are fed therewith. The dye or dye mixture must also be able to be absorbed in the concentration detectable in the liquid medium of the liquid enteral food product while the product flows through a drip chamber or other formulation chamber that is placed therein so minus one unit of sustained release dosage form containing the dye or marker dyes. If the dye is detectable in the drip chamber, it can be expected to be detectable, ordinarily, if it somehow reaches the patient's oral cavity. The marker dye used can be a dye coloring that imparts color that is visible under white light, for example, normal natural light or artificial light found in a hospital or clinic, or the dye marker can be a fluorescent dye that bounces fluorescent light visible under ultraviolet light or, a mixture of a dye dye and a fluorescent dye. A mixture of a dye dye and a fluorescent dye appears to be especially advantageous in that the flow through the formulation chamber is easily perceived under normal lighting conditions with the dye present, while even a small amount of food product outside of the dye is present. Place, for example, in the oral cavity or the nasal passage, be more easily detected with the help of utraviolet light if it contains a fluorescent dye. This is due to the nature of fluorescent dyes that are essentially visible under ultraviolet light even when present at a very low concentration. The dye or mixture of dye used must be physiologically acceptable. Food-grade coloring dyes usually approved according to the provisions of the Food, Drug and Cosmetic Act of the United States are adequate. F.D dyes are preferred. & C. Blue # 1 and F.D. % C. Blue # 2. The dye or dye mixture used should be soluble in the medium of the liquid enteral food product being fed and compatible with the beneficial ingredient (s) that are being added during feeding. Generally, about 0.1 milligram of dye per milliliter of liquid enteral food product is desired to give an easily visible coloration to the food product. When it is important to have the ability to detect the poorly directed liquid enteral food product, the marker dye used may be a fluorescent dye, such as an F.D. & C. Red # 3, which is highly visible at a very low concentration under ultraviolet light and also imparts a visible coloration to the liquid food product under white light conditions. Other suitable fluorescent dyes are: quinine, F.D. & C. Red # 22, F.D. & C. # 28, fluorescin and D 282 UV Blue available from DaGlo of Cincinnati, Ohio and also identified as 16470-24-9 in the "Chemical Abstracts System" with a color index of 220 as a fluorescent brightener. As indicated above, a mixture of dye dye and fluorescent dye can be used, if desired.

Generally, adding the food product in the formulation chamber approximately 0.01 to 0.05 mg / ml of fluorescent dye is suitable for the detection capability under ultraviolet light. A feeding assembly, such as the equipment 20 shown in Fig. 15, is conveniently provided in packaged form ready for use in the feeding of a liquid enteral food product. The equipment includes a controlled release dosage form unit 32, a drip chamber 27 or other formulation chamber, and liquid communication means 28 consisting mainly of a length of flexible tubing attached to one end of the outlet of the device. drip chamber 27 and at the other end to an attachment 30 for mating connection to a feed tube. The accessory 30 is shown with a telescopic cover 55 for purposes of illustration. The cover is simply for protection of the accessory 30 until the feeding set is used. The controlled release dosage form unit 32 has been placed in the drip chamber 27 and contains one or more beneficial ingredients as defined hereinabove for the modification of a liquid enteral food product during feeding thereof and, additionally, , a marker dye, if desired. The equipment may also be provided with a plurality of controlled release dosage form units 32 within the drip chamber 27 if a single dosage form unit does not contain each type of beneficial agent desired for the modification of the food product or if it is desired to add a marker dye and is not present in the controlled release dosage form units for the selected beneficial ingredients. Similar equipment 20c, as shown in Fig. 10, includes the controlled release dosage form unit 32 that has not been placed in the drip chamber 27 prior to boarding the equipment, but accompanies the drip chamber as part of the team. Other kits were prepared with various numbers and varieties of controlled release dosage form units containing various combinations of beneficial agent and marker dye and beneficial agents that are not in the controlled release form, to accompany the release sets. In a preferred embodiment of the apparatus of the invention of the type illustrated in Fig. 2, a controlled release dosage form unit of the type illustrated in Fig. 8A is placed in the formulation chamber. The dosage form unit contains glutamine and dye F. D. & C. Blue # 1 and is coated with a layer of the same blue dye mixed with about 3 weight percent total polyvinylpyrrolidone having an average molecular weight on the scale of about 35000 to 44500. The feeding equipment is connected to a hanging supply container of a liquid enteral food product having a viscosity of about 40 cps., such as PULMOCARE®, a product of Ross Products Division of Abbott Laboratories, Columbus, Ohio and a stable flow of the food product is initiated.

The dye coating provides immediate visible color within the drip chamber in 2 seconds and the controlled release dosage form unit provides the blue dye at a concentration of at least 0.075 mg / ml over a period of 1440 minutes during the flow of approximately 3000 ml of the liquid enteral food product. The dosage form unit also provides glutamine at a concentration of at least 1.25 mg / ml during the flow of the liquid enteral food product, which starts after about 1 ml of flow.

Claims (12)

1. A method for modifying a liquid enteral food product during the flow thereof from a supply container containing the liquid enteral food product to a feeding tube leading into the gastrointestinal tract of a patient, comprising the steps of: ) providing an apparatus comprising: a formulation chamber having an inlet and an outlet and the inlet being connectable to a container for supplying the liquid enteral food product for receiving the contents therefrom; at least one beneficial agent in at least one controlled release dosage form unit and the formulation chamber containing at least one controlled release dosage form unit therein to be moistened or submerged in the food product liquid enteral through it, each beneficial agent being selected from the group comprising foods, medicaments, probiotics and diagnostic agents that are dispersible in the medium of the liquid enteral food product; and fluid communication means capable of operatively connecting the outlet of the formulation chamber to a device for feeding the modified liquid enteral food product into the gastrointestinal tract of a patient; (b) providing a supply container containing a liquid enteral food product; (c) placing the serial communication apparatus in the fluid flow between the supply container and a supply tube; and, (d) flowing the liquid enteral food product through the apparatus and into the feeding tube. The method of claim 1, wherein each beneficial agent provided in the formulation chamber employed is selected from the group consisting of: foods, medicaments, probiotics and diagnostic agents and chemically and physiologically compatible combinations thereof and, any of the above beneficial agents or chemically and physiologically compatible combinations thereof together with a physiologically acceptable dye marker or mixture of dyes, each beneficial agent and dye marker placed in the formulation chamber being dispersible in the medium of the enteral food product. liquid. The method of claim 1, wherein at least one beneficial agent that is not in a controlled release dosage form is further provided in the formulation chamber, said beneficial agent being the same or different than any beneficial agent present in the form of controlled release dosage. The method of claim 2, wherein at least one beneficial agent that is not in the controlled release dosage form, such as a beneficial agent that is the same or different than any other, is additionally provided in the formulation chamber. beneficial agent present in the controlled release dosage form. The method of any one of claims 2, 3 or 4, wherein at least one controlled release dosage form unit provided in the formulation chamber employed is coated with a physiologically acceptable label that is soluble in the medium of the liquid enteral food product. The method of any one of claims 1 to 4, wherein a label dye or mixture of dyes in a controlled release dosage form containing only the dye or mixture of dyes is provided in the formulation chamber employed. The method of claim 1 or claim 2, wherein the apparatus provided includes at least one additional formulation chamber having therein at least one controlled release dosage form unit containing the same or different, at least one, beneficial agent. The method of claim 1, wherein the controlled release dosage form unit provided in the formulation chamber is an osmotically driven device. 9. The method of claim 8, wherein the osmotically-driven device provided in the formulation chamber comprises: an outer capsule formed by an outer wall formed, at least in part, by a semipermeable composition that maintains its integrity in the presence of an aqueous fluid, the outer wall circumscribing a hydro-activated layer comprising a hydro-activated expandable composition or a hydro-activated composition occupying space at a controlled rate and an inner capsule surrounded by the hydro-activated layer and communicating with the outwardly extending lumen of the outer capsule, the inner capsule containing at least a useful amount of at least one beneficial agent soluble or dispersible in the liquid formulation form and the inner capsule wall being substantially non-permeable to the liquid enteral food product. The method of any one of claims 2, 3, 4 or 8, wherein the dye F.D. is provided as the marker dye in the formulation chamber used. & C. Blue # 1 or the dye F.D. & C. Blue # 2 or a mixture thereof. The method of any one of claims 1, 2, 3, 4, 8 or 9, wherein the liquid enteral food product has a scale viscosity of about 1 cps. up to approximately 300 cps. The method of any one of claims 1, 2, 3, 4, 8 or 9, wherein the liquid enteral food product has a viscosity on the scale of about 5 cps. up to approximately 150 cps.