Abstract: A powder-form composition of 2-acetyl-1-pyrroline incorporated with a support of maltodextrin and/or cyclodextrin. The composition is prepared by hydrolyzing a 2-(1-alkoxyethenyl)-1-pyrroline with an acid to obtain a reaction medium, adding an equimolar amount of a base to the reaction medium to obtain a neutralized reaction medium containing 2-acetyl-1-pyrroline, combining maltodextrin and/or cyclodextrin with the neutralized reaction medium to obtain a support solution and freeze-drying the support solution to obtain the composition.

Abstract: An oral nutritional supplement, i.e., a dietary adjunct, for livestock which includes incompatible live microbial cultures, and vitamin and mineral supplements, each separated from the other via multiple encapsulation. The microbial cultures include gastrointestinal bacteria, yeasts or fungi. A method of delivering incompatible compounds in vivo, a method of preparing shelf-stable compositions of incompatible substances, and a system for delivering oral nutritional supplements to livestock are also provided.

Abstract: A dispenser for use in a fluid environment which is capable of delivery of plurality of drugs in any desired delivery pattern or profile.

Abstract: An article for the controlled delivery of an active substance, comprising a hollow space fully enclosed by a wall and filled in full or in part with one or more active substances, which wall is made using a biodegradable polymeric material permeable to the active substance, wherein the wall is composed mainly of a combination of at least two different polymeric materials in which one polymeric material is permeable to the active substance and is degradable and the other polymeric material is relatively poorly permeable to the active substance and is degradable and the conveyor path for the delivery of the active substance from the hollow space to the surroundings of the article is a continuous distance leading at least through the polymeric material permeable to the active substance.

Abstract: The present invention is directed to an improvement in a delivery system, the system comprising a wall that surrounds an internal lumen or compartment which contains a thermo-responsive beneficial agent formulation, an expandable driving member and an optional density member, and having an exit opening, and wherein the improvement comprises a) a viscosity-inducing amount of an inert viscosity-inducing agent in the thermo-responsive beneficial agent composition for increasing the viscosity of the beneficial agent composition, and/or b) a pressure-inducing exit member in the exit opening in the wall for increasing the pressure inside the lumen.

Abstract: A fluid-activated delivery device is disclosed comprising a housing defining an internal compartment, a beneficial agent formulation in the compartment, exit means in the housing for delivering the beneficial agent formulation from the delivery device, and wherein the formulation comprises an active agent in an amount of 50 wt % or greater blended with a glyceride or a mixture of glycerides of a fatty acid.

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: A device for the controlled delivery of an insoluble or partially aqueous insoluble beneficial agent to an aqueous containing environment. The device comprises a shaped wall that surrounds and defines an internal reservoir. The wall is formed at least in part of a sintered polymer microporous membrane permeable to a beneficial agent-containing hydrophobic medium when the wall is present in the aqueous containing environment. The reservoir contains a mixture of a hydrophilic swellable composition and a beneficial agent-containing hydrophobic medium.

Abstract: The present invention is concerned with improving the delivery of a drug from a ruminal delivery device to give a consistent delivery of drug to the ruminal environment. Thus, the invention is directed to an improved ruminal drug delivery device comprising a semipermeable membrane having an exit orifice and defining a compartment, the compartment containing a swellable osmotic agent expandable member, a drug to be dispensed, a density element and, optionally, a partition layer between the osmotic expandable member and the drug formulation, wherein the improvement comprises an essentially gas-impermeable barrier means that separates the density element from the other components within the delivery device for isolating gases evolved from the density element from the other components within the delivery device. The invention is also directed to methods and articles for providing a consistent delivery of drug from a ruminal drug delivery device.

Abstract: The present invention provides a feed additive composition for ruminants containing a biologically active substance therein. When administered to ruminants, the composition containing the active substance is stably protected in the rumen while efficient release of the active substance is realized in the abomasum and the following digestive tract. Thus, the released active substance is effectively digested and absorbed by ruminants.

Abstract: A density element (12) for use in ruminal delivery devices (10) which is manufactured by partial sintering in such a manner as to fragment upon contact with the many parts in rendering machinery without damage to the blades. The density element (12) has density of at least about 1.5 gm/cm.sup.3 and a transverse rupture strength greater than about 3000 psi no greater than about 30,000 psi. The part is sintered under conditions which do not permit full weld bond strength to be obtained and may thereafter be heat treated or impregnated with an inert hydrophobic material to increase corrosion resistance.

Abstract: Colonic-targeted oral drug dosage forms composed of a drug confined within a crosslinked hydrogel that exhibits pH-dependent swelling and is composed of an ionizable comonomer such as acrylic acid, a nonionizable comonomer such as an acrylamide, and a crosslinking agent that contains an aromatic azobond. Selective drug release in the colon occurs by a combination of pH-dependent swelling of the hydrogel and degradation of the hydrogel by enzymatic cleavage of the azobonds by azoreductases.

Abstract: A feed additive composition is provided having a core which contains a biologically active substance and which is coated with a coating composition which contains components a) and b):a) at least one substance selected from the group consisting of linear or branched saturated or unsaturated aliphatic monocarboxylic acids of 12-22 carbon atoms or salts thereof, hardened vegetable fats and oils, hardened animal fats and oils, and wax; andb) at least one of substances i) and ii):i) one or more linear or branched saturated or unsaturated aliphatic monocarboxylic acids of 11 carbon atoms or less, andii) one or more substances selected from the group consisting of nucleic acids, nucleotides, nucleosides, bases composing nucleic acids and salts thereof.

Abstract: Use of fluid to solid oligomeric esters of lactic acid and/or glycolic acid and dermatologically compatible derivatives thereof as resorbable carriers and/or film formers in preparations for covering undamaged and/or damaged areas of human or animal skin.

Abstract: A preparation for the prevention or treatment of hypocalcemia in ruminants is prepared by forming a homogeneous mixture of CaCl.sub.2.xH.sub.2 O and CaSO.sub.4.yH.sub.2 O, x being a number greater than 0 and lower than 6 and y being a number equal to or greater than zero and lower than or equal to 2, at a weight ratio of 1:0.05 to 1:2.4, adding water to the mixture to convert the ingredients to CaCl.sub.2.6H.sub.2 O and CaSO.sub.4.2H.sub.2 O, introducing the mixture into molds, and heating the molds so that the mixture solidifies.

Abstract: A calcium ion containing composition comprising a water in oil emulsion having a dispersed aqueous phase and a continuous oil phase, which composition is orally administerable and palatable to cows without causing lesions of the stomach and which composition is effective in preventing milk fever, said composition further comprising a calcium salt which is dissolved in the aqueous phase to form a calcium ion containing aqueous phase solution, the calcium in the composition, calculated as free calcium ion, comprising 10 to 20 percent by weight of the composition, said composition further including from 0.5 to 10 percent oil soluble non-ionic emulsifier. The invention also includes the method of orally administering the composition to cows to treat milk fever.

Abstract: A method of treatment for the relieving of the symptoms of colic in horses is disclosed which comprises orally administering an effective amount of a pine tea which is prepared by boiling pine needles in water to the horse. Suitable pine needles include Ponderosa pine needles.

Abstract: An animal premix having improved levels of flowability and dustiness. The premix comprises about 2% to about 10% Semduramicin or its pharmaceutically acceptable cationic salts thereof, about 0.5% to about 50% Semduramicin degradation reducing stabilizer, about 40% to about 80% diluent, about 5% to about 50% density-increasing bulking agent, about 2% to about 10% dust controlling oil and about 0.25% to about 5% flowability enhancing glidant selected from the group consisting of sodium aluminosilicate and silicon dioxide. The invention is also directed to an animal feed containing the above described premix and a method of treating coccidial infections in an animal by administering that animal feed to an animal.

Abstract: Improved animal diets for oral administration are provided which include a quantity of non-hydrolyzed, non-digested, naturally occurring protein supplemented with a minor amount of an additive selected from the group consisting of di- and tripeptides including an essential amino acid residue. The diets commonly include at least about 8% by weight of such intact protein, which may be derived from typical plant or animal sources. The preferred additive includes an essential amino acid residue selected from the group consisting of lysine, methionine, threonine, tryptophan, isoleucine and valine. Use of the di-and tripeptide additives of the invention gives increased nitrogen use by the animal, as compared with feeding of the amino acid constituents of the additives.

Abstract: A density element (12) for use in ruminal delivery devices (10) which is manufactured by partial sintering in such a manner as to fragment upon contact with the many parts in rendering machinery without damage to the blades. The density element (12) has density of at least about 1.5 gm/cm.sup.3 and a transverse rupture strength greater than about 3000 psi no greater than about 30,000 psi. The part is sintered under conditions which do not permit full weld bond strength to be obtained and may thereafter be heat treated or impregnated with an inert hydrophobic material to increase corrosion resistance.

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 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 microgranular preparation having a core of biologically active material that is encapsulated by a water soluble film that is covered by an enteric coating of either an alkali soluble, acid insoluble polymer or a high molecular weight polymer whose structure is substituted with or contains windows of fatty acids or other material capable of being solubilized by intestinal juices. Useful for protecting pH sensitive and other biologically active materials from inactivation or contact with the stomach or rumen, and releasing the same in active form in the intestinal tract, particularly the duodenum.

Abstract: Particulate nedocromil sodium with a mass median diameter of from 5 to 10 .mu.m is useful as a medicament for inhalation.The particulate nedocromil sodium of the invention is particularly advantageous in that its dispersion, i.e. the proportion of particles which are capable of penetrating deep into the lung, is substantially greater than the dispersion of conventional powders having smaller mass median diameters.

Abstract: An oral vaccine formulation is provided for stimulation of an immune response in gut-associated lymphoid tissues. The formulation comprises an enzymatically degradable antigen in a hydrogel matrix. In ruminant species, the vaccine formulation, upon oral administration, is formed to pass through the rumen without substantial hydration and then into the post-ruminal portion of the digestive tract where the antigen is released for contact with the gut-associated lymphoid tissue.

Abstract: The invention relates to a device for the release of at least one active substance (e.g.

Abstract: A sustained release bolus composition, containing a prophylactically effective amount of a compound selected from LL-F28249.alpha., 23-(O-methyloxime)-LL-F28249.alpha. and derivatives thereof provides a method for protecting ruminant animals for a prolonged period of time against infestation by nematodes, acarids and endoand ectoparasitic insects, and which over time can also eliminate the initial population of parasites present at treatment. The invention also relates to a method for the systemic control of ectoparasitic insect infestations of ruminant animals by orally administering to said animals a sustained release bolus containing an insecticidally effective amount of LL-F28249.alpha., 23-(O-methyloxime) LL-F-28249.alpha. or derivative thereof, which continuously releases into the rumen of the treated animal a systemically effective amount of LL-F28249.alpha., 23-(O-methyloxime)LL-F28249.alpha. or derivative thereof.

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 drug delivery capsule from which the delivery of the drug is driven by the osmotic infusion of moisture by the capsule from a physiological environment is provided with a delivery orifice which opens intermittently to achieve a pulsatile delivery effect. The wall in which the orifice is formed is constructed of an elastic material, preferably an elastomer, which stretches under a pressure differential caused by the pressure rise inside the capsule as the osmotic infusion progresses. The orifice is small enough that when the elastic wall is relaxed, the flow rate of drug through the orifice is substantially zero, but that when the elastic wall is stretched due to the pressure differential across the wall exceeding a threshold, the orifice expands sufficiently to allow the release of the drug at a physiologically beneficial rate.

Abstract: An oral nutritional supplement, i.e., a dietary adjunct, for livestock which includes incompatible live microbial cultures, and vitamin and mineral supplements, each separated from the other via multiple encapsulation. A method of delivering incompatible compounds in vivo, a method of preparing shelf-stable compositions of incompatible substances, and a system for delivering oral nutritional supplements to livestock are also provided.

Abstract: The present invention relates to a biologically active substance that is stable in the rumen of ruminants and released in the abomasum and its subsequent digestive tract. The biologically active substance has the additional properties of being digested and absorbed with good efficiency.

Abstract: The present invention relates to new granules, as well as the process for their preparation, obtained by extrusion of a mixture containing a meltable binder in an amount such that it permits the passage of the mixture through a die. The granules obtained are then coated with a polymer permitting their trans-rumen passage without degradation. After coating, these granules are used for animal feeding of ruminants.

Abstract: Improved means for constraining a rumen drug delivery device in a rolled configuration, said means comprising a laminate, which may be perforated, comprising a water-permeable material having a low friction surface in the presence of water, said material being bonded by means of a water-dispersible pressure sensitive adhesive to a repulpable tape, said tape having said water-dispersible pressure sensitive adhesive on both its surfaces; a laminate comprising a flexible, water-permeable polymeric material bonded between the low friction surface material and the repulpable tape; and devices constrained by said means.

Abstract: A large intestinal dissociative hard capsule comprising a capsule mainly composed of chitosan, the viscosity at 20.degree. C. of a solution obtained by dissolving the chitosan in an aqueous 1% by weight acetic acid solution being not higher than 100 cps and the degree of deacetilation of the chitosan being from 60 mol % to 98 mol %, having a coated layer of a polymer soluble in a liquid having pH of at least 5 on the surface of the capsule.

Abstract: A dosage form for administering physiologically active substances to animals, especially ruminant animals. The dosage unit includes a core which contains the active substance and a coating. The coating has selected areas which are thinner than the average thickness of the coating and/or areas which are predetermined rupture sites. These thin areas or predetermined rupture sites are constructed and arranged so as to detach and/or rupture under the conditions which are present after oral administration of the dosage form. As a result, the delayed release of the physiologically-active substance is accelerated. For example, the coating may be formulated to not be affected in the first stomach of a ruminant but to rapidly disintegrate in the animal's second stomach.

Abstract: A sustained release capsule adapted to be inserted into the rumen of a ruminant animal and means for retention of the capsule in the rumen.

Abstract: A dispenser is disclosed for delivering a beneficial agent in a hydrophilic carrier formulation to an animal in a rate-controlled manner. The dispenser comprises (1) a semipermeable housing defining an internal space, (2) at least one composition comprising a beneficial agent and a pharmaceutically acceptable hydrophilic carrier in the space, (3) an expandable hydrophilic driving member in the space, (4) a density member in the space, and (5) one exit passageway or a multiplicity of exit passageways in the housing for delivering the beneficial agent from the dispenser, the diameter of each exit passageway being of a size to maximize release of the beneficial agent by osmotic pumping and to minimize release of the beneficial agent by diffusion or erosion to substantially avoid mechanical agitation-dependent release of the beneficial agent.

Abstract: A device for controllably delivering a material into an aqueous medium, the device comprising a soluble portion which is adapted, in use, to dissolve in an aqueous medium thereby to deliver into the aqueous medium a material which is retained in the device, the soluble portion comprising a soluble phosphate glass having a P.sub.2 O.sub.5 content of from 40 to 50 mole %, and constraining means which are located in the vicinity of the soluble portion and which are arranged, in use, to constrain a stationary liquid layer between the soluble portion and the constraining means. The invention also relates to a method of controllably dissolving a soluble phosphate glass in an aqueous medium.

Abstract: Unit dosage form for delivering drugs into the body in a series of sequential, pulsatle releasing events employs conventional pharmaceutical equipment and processes for optimum economy, reliability, and bioavailability. The system can be used with drugs which cannot be released by diffusion through a porous coating, such as water insoluble drugs. A plurality of populations of pellets is provided within a unit dosage form such as a capsule or tablet. The pellets are composed of a core containing the drug and a swelling agent which expands in volume when exposed to water. The core is enclosed within a membrane or coating which is permeable to water. The membrane is composed of a water insoluble and permeable film forming polymer, a water soluble film forming polymer and a permeability reducing agent. When the unit dose releases the pellets into the digestive tract, water diffuses through the coating and into the core.

Abstract: In one embodiment this invention provides a process for preparing a dietary fatty acid salt supplement composition which contains a combination of additional nutrient or medicament ingredients.The dietary composition can function as a rumen bypass animal feed supplement, and permit a beneficial increase in the nutrient fat content of the feed.

Abstract: A feed additive granule for ruminants comprising a granulated physiologically active substance as the core, a first coating layer placed on the surface of said core, said first coating layer containing a high molecular substance which dissolves or swells in water in an acidic pH region of not greater than 5.5 and is stable in a pH region of 5.6 to 8.0, and a second coating layer placed on said first coating layer, said second coating layer being of a substance which is stable in an acidic pH region of not greater than 5.5, dissolves or swells in water in a pH region of 5.6 to 8.0 and is acceptable to ruminants, and some modifications thereof, as well as feed for ruminants comprising such a novel feed additive.

Abstract: The present invention is directed to a long-term dispensing device for the controlled delivery of a beneficial agent in a hydrophilic carrier, which device quickly and continuously delivers an effective amount of agent followed by a continuous and sustained delivery of agent in a controlled and uniform amount over a prolonged period of time, thus providing for delivery of beneficial agent to an environment of use at two different rates and having a fast startup.

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: In a preferred embodiment this invention provides an animal feed block which has a high content of C.sub.14 -C.sub.22 fatty acid alkaline earth metal salt and nutrient carbohydrate.An invention feed block is suitable for free choice consumption by ruminants and other animals such as horses and house pets.

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: 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: 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 fluidimpermeable, 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: 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 of from about 3 to 25 ug PVA/mm.sup.2 surface area of pellet.

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 present invention relates to a biologically active substance that is stable in the rumen of ruminants and released in the abomasum and its subsequent digestive tract. The biologically active substance has the additional properties of being digested and absorbed with good efficiency.

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.]. .Iadd.tryptophane.Iaddend., protein .[.harmones.]. .Iadd.hormones.Iaddend., 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.