Abstract: The invention provides a dispensing device comprising a loading dose (first agent delivery means) for short-term and continuous delivery of an agent having a high potency, retained together with a long-term dispensing device (second agent delivery means) capable of a long-term and continuous delivery of agent. The combination of first and second agent delivery means provides a device in which a substantially constant dose of beneficial agent may be delivered to the environment of use over time. A rapid initial delivery of beneficial agent is followed by continuous and prolonged delivery of agent.

Abstract: A method of making cheese with milk obtained from animals which have received feed supplemented or complemented with an amino acid in a protected form. The amino acid is preferably lysine and/or methionine.

Abstract: The present invention is directed to an improvement in a delivery device, the device comprising a wall that surrounds an internal lumen or compartment which contains a beneficial agent or medicament formulation, an expandable driving member and an optional density member, and having an a exit means, and wherein the improvement comprises prehydrating the delivery device as a means for advancing the beginning or startup of agent delivery from the delivery system to give earlier release of beneficial agent to the environment of use. An embodiment of the invention concerns a fluid reservoir in contact with the expandable driving member to provide prehydration of the device.

Abstract: A controlled release delivery device for macromolecular proteins which comprises a water-soluble outer capsule completely surrounding an inner compartment containing a plurality of non-uniform beadlets. The beadlets comprise a rupturable wax shell which completely surrounds a core matrix containing the macromolecular proteins and optional "core agents" such as excipients, stabilizers, binders, surfactants, preservatives, or mixtures thereof, and the like.The water-soluble outer capsule dissolves when the device is administered to an animal and simultaneously exposes substantially all of the beadlets to an aqueous environment. Each beadlet absorbs fluid from the environment and separately ruptures over a prolonged period thus delivering the macromolecular protein to the animal.

Abstract: A dispensing device is disclosed for delivering a beneficial agent. The device comprises (1) a semipermeable housing defining a internal space, (2) an optional and presently preferred in the space, (3) a heat responsive composition comprising a beneficial agent in the space, (4) a space consuming member in the device, (5) a non-toxic compound blended with the heat responsive composition for enhancing its viscosity; (6) an exit port in the wall for increasing the internal pressure of the dispenser and for simultaneously letting the beneficial agent exit through said port from the device, and (7) an embodiment comprising a prehydrating fluid for fastening the start-up of delivery from the delivery system.

Abstract: A dispensing device is disclosed for delivering a beneficial agent. The device comprises (1) a semipermeable housing defining a internal space, (2) an optional and presently preferred in the space, (3) a heat responsive composition comprising a beneficial agent in the space, (4) a space consuming member in the device, (5) a non-toxic compound blended with the heat responsive composition for enhancing its viscosity; (6) an exit port in the wall for increasing the internal pressure of the dispenser and for simultaneously letting the beneficial agent exit through said port from the device, and (7) an embodiment comprising a prehydrating fluid for fastening the start-up of delivery from the delivery system.

Abstract: The invention relates to certain stable microsphere compositions suitable for parenteral administration containing a fat or wax or mixture thereof; a biologically active protein, peptide or polypeptide; and an oil, semi-soft fat, fatty acid derivative or mixture thereof. The invention also relates to a method of making the microsphere compositions.

Abstract: A corrosion resistent density element for use in ruminal delivery devices which fragments upon contact with the blades in grinding machinery without damage to the blades. The density element has density of at least about 1.5 g/ml and a transverse rupture strength no greater than about 30,000 psi.

Abstract: New porous, unitary freeze-dried pharmaceutical form, of homogeneous appearance, consisting of:a) an inclusion compound comprising:one or optionally more active substances,a predetermined quantity of cyclodextrin,optionally an additive facilitating inclusion,b) at least one substance chosen from:diluents,binders; andc) optionally one or more additives.

Abstract: The present invention is directed to a fluid-imbibing drug delivery device having a first, low density such that it floats in the stomach contents for a predetermined prolonged period of time, during which prolonged period of time it dispenses a drug or other active agent to the stomach, and having a second, higher density such that the device exits the stomach at the end of the predetermined prolonged period of time.

Abstract: A time release bolus comprises a tubular member and an end cap secured to each other. The tubular member contains an inner bag which is adapted to receive and contain a nutrient or medicament substance. A capsule is provided in the tubular member, and upon fracture thereof, applies pressure to the inner bag. The end cap includes a plug which fits into an open end of the tubular member and a top portion. A passage is provided which leads from the tubular member to the exterior, such that nutrient or medicament can flow from the inside of the tubular member to the outside of the time release bolus. The bolus further includes in the end cap a mesh in the flow path of the substance, the mesh further restricting and controlling the amount of substance which may pass from the bolus to the exterior.

Abstract: A correlation is established between aflatoxin B1 binding on raw montmorillonite clays and the ratio of their surface acidities divided by their porosities for surface acid sites whose pKa values fall in the range 5.0-6.8 (i.e. weakly acidic) and porosities for pores whose diameters fall in the region 50-600 A. This information provides a method for preselecting clay additives for animal feeds which have enhanced toxin binding capacity.

Abstract: A composition of matter and method for administering a bioactive substance to the post-rumen portion of the digestive system of a ruminant substantially without introducing the substance to the rumen portion of the digestive system is provided. The composition of matter comprises particles which have a specific gravity between about 0.3 and 2.0, preferably between about 1.0 and 2.0. The particles comprises a core comprising bioactive substance; a hydrophobic coating essentially completely encapsulating said core in a quantity sufficient to essentially preclude introduction of bioactive substance into the rumen; and a surfactant applied to the surface of the hydrophobic coating in a quantity sufficient to ensure that said particles do not float on the rumen. The method comprises orally administering this composition of matter to a ruminant.

Abstract: A solid pharmaceutical composition for release of a biologically active substance into a desired aqueous environment, containing a core and an outer layer, said core comprising between 17 and 93% by weight of the biologically active substance, between 0.01 and 7% by weight of a water swellable polymer material and between 0 and 83% of one or more accessory ingredients, relative to the total weight of the core; and the outer layer comprising between 25 and 75% by weight of the biologically active substance, between 25 and 75% by weight of a material for enabling rapid dispersion of the outer layer into the aqueous environment and 0 to 50% by weight of one or more accessory ingredients, relative to the total weight of the outer layer. The composition is preferably formulated as a bolus for veterinary use.

Abstract: A composition which is stable in a medium in which the pH is greater than or equal to 5.5 and which permits the release of an active substance in a medium in which the pH is less than or equal to 3.5, comprising the active substance, which contains inclusions of, or which is completely or partially covered by, a pH sensitive material whose extent and/or rate of swelling is greater in an acidic medium than in a neutral medium, and a coating of a hydrophobic layer.

Abstract: This invention relates to an active agent delivery device. More particularly, the invention relates to a delivery device that includes a sleeve to protect the delivery device from transient mechanical forces. The delivery device of the invention is robust and resistant to transient mechanical forces. The invention provides a fluid-imbibing delivery device comprising a housing enclosing an internal compartment, said housing having a first wall section that substantially restricts the passage of fluid into the delivery device, i.e. is substantially fluid-impermeable, and that contains a beneficial agent; a second wall section that permits the passage of fluid into the delivery device, i.e. is fluid-permeable, and that contains at least one expandable driving member; and exit means; with a protective sleeve means extending from the first wall section of the housing to cover and protect the second wall section of the housing and the junction of the first and second sections.

Abstract: Veterinary delayed release dosage forms which remain in the rumeno-reticular sac of an animal over an extended period of time and in which the therapeutically active substance has a predictable and delayed release pattern. The compositions comprise a dense filler, a disintegrant and a therapeutically active substance. The dosage form has a hydrophobic polymer or co-polymer coating and can deliver a plurality of doses of a medicament intermittently at a preset time interval in the rumen.

Abstract: A filament system for delivery of a medicament in the intestine comprised of a material having the medicament contained therein which is coiled for ease in ingestion and to prevent uncoiling until the filament reaches the intestine. Once the coiled filament reaches the intestine and uncoils, the medicament is released therefrom. The filament is preferably comprised of a material which is water insoluble, semipermeable, enteric, or bioerodible to facilitate release of the medicament, and is provided with or comprised of a bioadhesive for retarding the passage of the filament through the intestine once uncoiled, with the result that therapeutically effective dosage levels are substained for relatively long periods of time.

Abstract: An intraruminal device for controlled release of a drug formulation in the rumen of an animal, comprises an open-ended tube for containing the drug formulation, a piston adapted to travel longitudinally within the tube and biased so as to deliver the drug formulation through the open end of the tube. Travelling with the piston is an associated weight adapted to retain the device within the rumen during delivery of the drug formulation.

Abstract: Solid dosage forms of bioactive materials for parenteral administration such as porcine or bovine somatotropin pellets intended for subcutaneous implantation to improve food production of farm animals are coated with polyvinyl alcohol to extend the release characteristics of the material. The polyvinyl alcohol preferably has a molecular weight of from about 20,000 to 100,000, a degree of hydrolysis of at least about 98%, and is applied from an aqueous solution by spray coating to form a continuous uniform covering having a weight of from about 3 to 25 ug/mm.sup.2.

Abstract: Acid-sensitive antibiotic esters for oral administration to livestock are stabilized by incorporation in premix formulations comprising a carrier, a base, a protective coating, and optionally a sealant film.

Abstract: A delivery system is disclosed for delivering a beneficial agent to an animal. The delivery system comprises a wall that surrounds a lumen, said wall comprising a composition that limits the passage of fluid into the system and a composition that permits the passage of fluid into the system. The lumen comprises a beneficial agent and an expandable member. The delivery system comprises an exit means for delivering the beneficial agent.

Abstract: A dispenser is disclosed for delivering a beneficial ionophore to an animal. The dispenser comprises (1) a semipermeable housing defining an internal space, (2) at least one composition comprising an ionophore and a pharmaceutically acceptable carrier in the space, (3) an expandable hydrophilic composition in the space, (4) a dense member in the space, and (5) at least one exit passageway in the housing for delivering the ionophore from the dispenser.

Abstract: An implantable dispenser is enclosed comprising a wall surrounding a compartment containing a first composition comprising a beneficial agent, an oil, a cosolvent and a polymer gellant, a second expandable composition, a third boundary maintaining composition between the first and second composition, and an exit port.

Abstract: Veterinary delayed release dosage forms which remain in the rumeno-reticular sac of an animal over an extended period of time and in which the therapeutically active substance has a predictable and delayed release pattern. The compositions comprise a dense filler, a disintegrant and a therapeutically active substance. The dosage form a hydrophobic polymer or co-polymer coating and can deliver a plurality of doses of a medicant intermittently at a present time interval in the rumen.

Abstract: A dispenser for use in a fluid environment which is capable of delivery of a plurality of discrete drug-containing units in any desired delivery pattern or profile.

Abstract: A delivery system is disclosed for delivering a beneficial agent to an animal. The delivery system comprises a wall that surrounds a lumen, said wall comprising a composition that limits the passage of fluid into the system and a composition that permits the passage of fluid into the system. The lumen comprises a beneficial agent and an expandable member. The delivery system comprises an exit means for delivering the beneficial agent.

Abstract: This invention relates to devices useful for the controlled delivery of one or more beneficial agents to an environment of use. More specifically, this invention concerns such devices which are powered by lyotropic liquid crystals. This invention also relates to the controlled delivery of one or more beneficial agents to an aqueous environment of use through the use of such lyotropic liquid crystal powered dispensing devices. Also disclosed are methods for the controlled delivery of one or more beneficial agents to an aqueous environment of use which comprise administering to or otherwise placing the devices of this invention in the environment of use.

Abstract: The invention relates to a method of encapsulating biologically active substances by gelling them with intestinal mucus (mucin). The invention is also concerned with a capsule produced by the method, its use as a fodder admixture, and a fodder containing such capsules.

Abstract: A dispensing device is disclosed for delivering a beneficial agent. The device comprises (1) a housing defining an internal space, (2) an expandable composition comprising a dense member in the space, (3) a composition comprising a beneficial agent and a non-toxic heat responsive carrier in the space,and (4) a passageway in the housing for delivering the beneficial agent from the dispensing device.

Abstract: Enzymatically degradable compositions for the coating of feed additives intended for ruminants, including zein, at least one hydrophobic substance, optionally at least one non-water-soluble polymer and at least one inorganic filler. The compositions are used to coat feed additives such as medicinal products, vitamins and amino acids.

Abstract: A stomach chamber bypass nutrient comprises a beadlet fabricated in two steps having two regions, a first region having the desired nutrient and a second region including fats and calcium based compounds. The nutrient includes lysine, methionine, tryptothane, protein harmones, vitamins and other nutrients in amounts of from 36% to 59%. The nutrient is fabricated by forming in a first step the nutrient in a beadlet form, and in a second step coating the nutrient beadlet with the second region.

Abstract: Solid dosage forms of bioactive materials for parenteral administration such as porcine or bovine somatotropin pellets intended for subcutaneous implantation to improve food production of farm animals are coated with polyvinyl alcohol to extend the release characteristics of the material. The polyvinyl alcohol preferably has a molecular weight of from about 20,000 to 100,000, a degree of hydrolysis of at least about 98%, and is applied from an aqueous solution by spray coating to form a continuous uniform covering 3 to 25 .mu.m PVA/mm.sup.2.

Abstract: Novel organosoluble derivatives of chitosan, useful in coating biologically active feedstuff additives intended for ruminants, to provide coatings which are stable at a pH greater than 5 and which release the biologically active substance at a pH below 3.5, consist of a random chain of units represented by the formulae: ##STR1## in which: R.sub.1 represents an alkylcarbonyl radical (2 to 4 carbon atoms), R.sub.2 represents an alkyl radical (2 to 21 carbon atoms) or an optionally substituted phenyl radical, and R.sub.3 and R.sub.4 represent a hydrogen atom or alkylcarbonyl radicals (2 to 4 carbon atoms).

Abstract: A bolus for releasing a biologically active substance into a liquid environment according to this invention comprising an elongate core, at least one end of which is frustoconical and a liquid impervious casing at one end and open at the other disposed about the core, the bolus being so constructed that, in use, the casing is progressively shed as the core retreats, thereby releasing the active substance at a rate which varies over at least one time period, the casing being so structured as to retain its integrity without disintegrating in the absence of any support provided by the core.

Abstract: This invention concerns compositions for zootechnical and veterinary use, characterized in that biologically active substances are incorporated in protective matrices, which have the following properties: 1) controlled release (ruminal by-pass) effect; 2) chemical-physical protection of active principles against degradation induced by technological processes of production, storage and pellettization of fodders for all animal species. The matrices of the invention are characterized by a plastic rheological behaviour due to the presence of lipogelling agents. The obtained products show the following advantages: increased active principle stability in feeds for all animal species; protection of the active principles from attack of Rumen microorganisms in fodder from attack of for ruminants.

Abstract: The device for insertion into a body cavity e.g. the rumen of an animal for example a cattle beast is in the form of a resilient helical coil with bio-degradable portions. The device is deformable to have a smaller dimension to enable insertion through a body passage into the animal cavity. The device carries a drug e.g. progesterone and is retained in the body cavity for a time during which the drug is active. After time has passed the device is broken up by bio-degrading activity into pieces small enough to be discharged naturally by the animal. An applicator is provided.

Abstract: A delivery system is disclosed for delivering a beneficial agent to an animal. The delivery system comprises a wall that surrounds a lumen, said wall comprising a composition that limits the passage of fluid into the system and a composition that permits the passage of fluid into the system. The lumen comprises a beneficial agent and an expandable member. The delivery system comprises an exit means for delivering the beneficial agent.

Abstract: The present invention provides a pharmaceutical granule composition comprising cimetidine and, as a granulating agent and taste-masking agent, an ester of a polyhydroxy compound, and where desired a palatable pharmaceutically acceptable emulsifier. Particular esters are glycerol esters. The granules of the present invention can be used in the preparation of chewable tablets which have good palatability and bioavailability.

Abstract: A delivery system is disclosed for delivering a beneficial agent to an animal. The delivery system comprises a wall that surrounds a lumen, said wall comprising a composition that limits the passage of fluid into the system and a composition that permits the passage of fluid into the system. The lumen comprises a beneficial agent and an expandable member. The delivery system comprises an exit means for delivering the beneficial agent.

Abstract: The invention provides a long-term dispensing device comprising a first agent delivery means for short-term and continuous delivery of agent, retained together with a second agent delivery means capable of long-term and continuous delivery of agent. The combination of first and second agent delivery means provides a device in which a substantially constant dose of beneficial agent is delivered to the environment of use over time. A rapid delivery of beneficial agent is followed by continuous and prolonged delivery of agent.

Abstract: A sustained release, reservoir-type subcutaneous implant device for the sustained administration to a subject of a biologically active compound comprises:an effective amount of a biologically active compound;an amount of a solid hydrophilic polymer sufficient to cause swelling of the device by osmotic pressure after implantation;an effective amount of a solubilizing agent; anda sufficient amount of a non-porous rate-controlling membrane which completely encapsulates said biologically active compound, wherein said rate-controlling membrane is permeable to said biologically active compound, but is impermeable to said solubilizing agent. This device is particularly advantageous for the administration of growth promoting compounds to livestock.

Abstract: A dispenser for use in a fluid environment which is capable of delivery of a plurality of discrete drug-containing units in any desired delivery pattern or profile.

Abstract: The present invention is directed to an active agent dispenser for use in a fluid-containing environment, which dispenser comprises a rigid housing, a plurality of movable active agent units filling a portion of the housing, a fluid-activated driving member for dispensing the active agent units filling the remainder of the housing, and an active agent unit outlet means. In the present invention, each active agent unit is comprised of an active agent dosage or filling contained within a fluid-impermeable cup-shaped member, the cup-shaped members being oriented within the housing with the base of the cup-shaped members facing the outlet means.

Abstract: Ruminants are fed a water-insoluble polymer, which may be swollen (i.e. having absorbed water to form a gel) or unswollen. At least 0.04 kg of (swollen) polymers per day per 100 kg body weight is administered, and the polymer has not necessarily been used as a substrate for the preparation of feedstuff.Such methods are particularly advantageous when the animal is being fed on a diet causing acid conditions in the rumen, such as a diet of silage.A useful polymer is ammonium polyacrylate cross-linked by about 500 ppm methylene bisacrylamide ("MBA").The polymers enhance feed conversion rates and hence lower the effective cost of feeding the animals.

Abstract: An oral drug delivery system having delayed gastrointestinal transit comprising a non-continuous compressible element and an attached controlled release device and which in the expanded form resists gastrointestinal transit; and a modular system for use therein comprising a non-continuous compressible element and an attached receptacle means for receiving and holding a drug-containing orally administrable controlled release device and which in the expanded form resists gastric transit.

Abstract: There are herein disclosed rodent-repellent microcapsules in which a core material is coated with a wall material of the microcapsules, the core material being a solution containing cycloheximide; a rodent-repellent resin composition comprising said microcapsules; a rodent-repellent coating material comprising said microcapsules; and a rodent-repellent adhesive comprising said microcapsules.

Abstract: A dispensing system is disclosed comprising a wall surrounding a lumen. The lumen comprises (1) a thermo responsive composition comprising a beneficial agent, (2) means for occupying space in the lumen for pushing the thermo responsive composition from the dispensing system, and (3) means for enhancing the amount of the beneficial agent dispensed from the system positioned between the thermo responsive composition and the means for occupying space.

Abstract: The invention is an injection molding method for the preparation of sustained release boluses which are useful for administration of insect growth regulators or other veterinary compositions to animals.

Abstract: Device for oral administration of a medicament to a ruminant animal comprises a rilaminate sheet (1) containing the medicament rolled into a tube retained in the rolled configuration by a film (3) of material which disintegrates in the rumen to allow unrolling of the sheet. The tube ends are closed by plugs (2) which keep the tube closed during passage of the device through the oesophagus.