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Publication numberUS3844285 A
Publication typeGrant
Publication dateOct 29, 1974
Filing dateDec 14, 1972
Priority dateAug 28, 1969
Also published asCA947157A1
Publication numberUS 3844285 A, US 3844285A, US-A-3844285, US3844285 A, US3844285A
InventorsLaby R
Original AssigneeCommw Scient Ind Res Org
Export CitationBiBTeX, EndNote, RefMan
External Links: USPTO, USPTO Assignment, Espacenet
Device for administration to ruminants
US 3844285 A
Abstract
A device for administering a therapeutic or nutrient substance to a ruminant over an extended period of time, comprising at least one body portion containing or comprising said substance and having a first configuration or being adapted to be arranged in a first configuration, whereby it is adapted to be administered per os so as to pass into the rumen and being adapted to change in the rumen into a second configuration which will prevent or at least hinder regurgitation of the device, whereby the device is retained in the rumen.
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United States Datent [191 Laby [ DEVICE FOR ADMINISTRATION TO RUMINANTS [75] Inventor: Ralph Henry Laby, Victoria,

Australia [73] Assignee: Commonwealth Scientific and Industrial Research Organization, Campbell, Australia [22] Filed: Dec. 14, 1972 [21] Appl. No.: 315,013

Related US. Application Data [63] Continuation of Ser. No. 67,955, Aug. 28, 1970,

abandoned.

[52] US. Cl. 128/260 [51] Int. Cl A6lm 31/00 [58] Field of Search 128/260, 272, 130, 213,

[56] References Cited UNlTED STATES PATENTS 462,990 11/1891 Oppenheimer 128/272 X 1,957,564 5/1934 West 128/272 2,580,414 1/1952 Duffey 206/84 3,118,439 1/1964 Perrenoud 128/260 X 3,136,695 6/1964 Tansey 424/22 3,247,066 4/1966 Milosovich, .lr. 424/37 X 3,315,660 4/1967 Abella 128/260 X 3,463,745 8/1969 Hofrichter 128/127 X 3,507,952 4/1970 Rednick et a1 424/22 3,545,439 12/1970 128/260 3,577,513 5/1971 Roebuck et a1 424/22 Primary ExaminerRichard A. Gaudet Assistant Examiner-J. C. McGowan Attorney, Agent, or Firm-Bacon & Thomas [57] ABSTRACT The device is especially useful in the treatment of bovine bloat by extended release in the rumen of surface active substances.

18 Claims, 13 Drawing Figures PAIENTEMMQ m4 3.844.285 sum 2 0F 3 Rr 6 mB/Ww E w W MW M H m6 av R5 PAIENIEDums m4 3l844l285 am an 3 nvvew r02 Rem HEN/er Mar TTORNEYS 1 DEVICE FOR ADMINISTRATKON TO RUMINANTS This is a continuation, of application Ser. No. 67,955, filed Aug. 28, i970, now abandoned.

, This invention relates to devices suitable for administering to ruminants. More particularly, it relates to devices useful for preventing bloat in bovines, and for preventing other disorder of ruminants for which reticulorumen (hereinafter abbreviated to rumen) infusion of an effective curative or control agent over an extended period of time would be an advantage. Whilst particular reference is made hereinafter to devices for the prevention of bloat, it will be understood that these devices are equally applicable to the prevention of these other disorders. Thus, for example, the devices described herein provide a means for the perfusion into the rumen of the therapeutic substances, metal salts for the correction of deficiency diseases, or nutrients or other agents which may be of advantage for healthy stock.

Bovine bloat is characterized by distension of the animals rumen and results from the formation of a stable foam above the rumen liquor which prevents the escape of gases produced by the micro-organisms in the rumen. Cattle feeding on fresh clover are particularly prone to bloat as stable foams are rapidly produced from certain clover proteins.

At the present time bloat may be prevented by daily administration of a surfactant to the animal, for example, in the form of a drench.

That method of prevention, however, is only truly practicable with dairy cattle since the cattle are brought in daily for milking; even here there is considerable farmer resistance to drenching because of the additional handling of the animals.

ln general, that method is not feasible for beef cattle and thus there is a need for a prophylactic which can be administered to beef cattle at the commencementof the bloat season in order to allow the cattle to take advantage of lush pastures.

It is known to employ a variety of heavy pellets for prophylaxis in ruminant animals, for example, for correcting cobalt deficiency. These pellets rely upon their size and density so that they will remain within the rumen and upon their chemical composition for gradual dissipation of the active agent. It is difficult to apply this principle to the prevention of bloat since surfactants have a relatively low density and must be incorporated as a minor constituent in a large pellet weighted by a suitable inert material. The result is that very large quantities (3kg) of such pellets must be employed in order to furnish bloat protection for about 3 months the period of the normal bloat season. If the weighting material is not used so that a high concentration of agent can be employed, it is found that such pellets can be readily regurgitated.

According to this invention there is provided a device for administering a therapeutic or nutrient substance to a ruminant over an extended period of time, said device comprising a body portion containing or comprising said substance and having a first configuration or being adapted to be arranged in a first configuration, whereby it is adapted to be administered per os so as to pass into the rumen and being adapted to change in the rumen into a second configuration which will prevent or at least hinder regurgitation of the device, whereby the device is retained in the rumen.

In one aspect, the device comprises a body portion which, by virtue of its nature, construction or composition, is adapted to be arranged in a first configuration whereby the device can be administered to a ruminant per os so as to pass into the rumen and, in the rumen environment, to change into a second configuration as above mentioned.

In this aspect of the device, the body portion may comprise for example a substantially insoluble, resilient matrix material which contains or comprises a material to be released in the rumen. Such a material may be retained in the matrix material in the form of a suspension, solid solution or the like. Alternatively it may be weakly chemically bonded to the matrix material.

ln a particular example of this aspect of the device, the body portion may consist of a gel comprising a material to be released in the rumen.

Such a gel may be moulded or otherwise formed into a body portion of a suitable shape whereby it is adapted to be arranged in said first configuration and, in the rumen environment, to change into said second configuration as above mentioned. The gel may contain gelling agents and other components required to obtain the desired mechanical properties.

Suitable shapes into which the body portion may be formed include, for example, shapes which may be termed doughnut-shaped" (i.e. toroidal) and boomerang-shaped" (i.e. angular) and other similar shapes. Preferably the device is "doughnut-shaped."

In this particular aspect, the material to be released in the rumen may be one or more non-ionic surfactant compounds.

The preferred surfactants are block copolymers of polyoxypropylene and polyoxyethylene, such as those manufactured under the trade name Pluronic, especially types L62, L62 and L64 thereof. Other polyoxyalkylenes and copolymers thereof are also suitable, as are polyoxyethylene alcohols (sometimes called polyoxyethylene alkyl ethers), i.e., consisting of straight or branched long chain alcohols condensed with ethylene oxide with or without end groups formed by condensation with propylene oxide. The condensation products of dodecanol with'6, 8, 10 or 12 moles of ethylene oxide are preferred members of this class.

Another type of surfactants which may be used is the polyoxyethylene alkylphenyl ethers, for example the condensation products of nonylor octyl-phenol with 8 or 9 moles of ehtylene oxide, or with 9 to ll moles of ethylene oxide followed by 9 to l 1 moles of propylene oxide.

The preparation and properties of the abovedescribed substances are well known in the art and will not be described herein.

The gelling agent may be of any suitable known type; ethyl cellulose is one example but the art discloses many other suitable substances.

In order to obtain a matrix material having the desired properties, the gel suitably contains at least 3 percent by weight, and preferably 6 to 15 percent by weight, of the gelling agent.

In another aspect, the device comprises at least one container portion and at least one obstructing means associated therewith, said obstructing means being arranged in a first position relative to the container portion to allow the device to be administered to a ruminant per os so as to pass into the rumen but which, in the rumen environment, moves or is caused to move relative to the container portion to a second position thereby to change the device into a second configuration as mentioned above.

The obstructing means may comprise for example one or more protruding or protusible structures attached to or formed integrally with the container portion and arranged so that (a) it may be positioned adjacent to the container portion, preferably more or less in conformity with the shape of the container portion, for passage of the device into the rumen, and (1)) once in the rumen it can be caused or allowed to extend or protrude from the container portion and thereby obstruct or at least hinder passage of the device out of the rumen.

Thus the obstructing means may comprise one or more flaps, tabs, flanges or like projections, or loops, bubbles, blisters or like protuberances.

In an extension of the latter aspect, the obstructing means may comprise one or more further container portions. Thus in yet another aspect of the invention, the device comprises at least two inter-connected container portions which" are arranged relative to one another in a first configuration to allow the device to be administered to a ruminant per os so as to pass into the rumen thereof, and which, in the rumen environment, may be caused or allowed to move relative to one another to change the device into a second configuration as above mentioned. In this form of the device the container portions generally will be connected together by some connecting means which may take the form either of a simple hinge or like member==-which permits the container portions to move relative to one another but to remain essentially adjacent or it might comprise a member such as a web, string or rod which permits the container portions to separate from one another whilst still remaining connected. In the latter case, it is preferred that the connecting member is at least semirigid and capable of holding the container portions in the separated configuration.

Means may also be provided to positively assist or bring about the change in configuration of the device within the rumen environment. Such means may com prise the obstructing means or connecting means broadly described above or may consist of additional biasing means. For example, the obstructing or connecting means may be made of a suitable resilient material and arranged so that normally the obstructing or connecting means is biased towards its extended or protuberant position by virtue of its resilience. Alternatively the same function may be achieved by attaching the obstructing or connecting means to its respective container portion by a hinge of resilient material or by a passive hinge provided or associated with biasing means.

The biasing means may be any suitable elastic or resilient material such as natural or synthetic elastomers or resilient synthetic resins, for example, natural or synthetic rubber, semi synthetic plastic materials such as cellulose esters, synthetic plastic materials such as the polyamides including nylon, polyethylene terephthalate, polyethylene and other similarly resilient materials or an elasticized cloth.

The means provided to assist or bring about the change in configuration of the device in the rumen environment may also be a strip comprised of a length or hydrophobic material and a length of hydrophobic material bonded or otherwise connected together. In the presence of moisture, such strips will deform as a result of expansion or contraction of the hydrophilic material. Such strips will hereinafter be referred to as "hydrophilic/hydrophobic strips. Alternatively, the means may be a strip or piece of a material which shrinks in the rumen environment.

Hydrophilic materials suitable for use in the hydrophilic/hydrophobic strips described above include cross-linked polydextrans, gelatin treated with formalin and cross-linked polyvinylalcohols. Suitable hydrophobic materials include water-insoluble polymers such as P.V.C., polyethylene and nylon.

A suitable material which shrinks in the rumen environment is cross-linked polyvinal alcohol. This material, if stretched when fully swollen with water and allowed to dry in the stretched state, will shrink when placed in the rumen environment.

Generally on administration the device will be held in the first configuration, by the throat of the animal but, if desired, restraining means may be provided which, in the rumen environment, are released to allow the device to move or be caused to move into the second configuration which will prevent or at least hinder passage of the device out of the rumen.

The restraining means may be or comprise any material which is dissolved, destroyed, ruptured or broken in the rumen environment. Suitable materials from which the restraining means may be made include gelatin string, gelatin tape and water-soluble adhesives.

As it is sometimes desirable to provide for the regurgitation of the device (if indigestible) by the animal, it is also preferred that the connecting means or hinge of the previously described embodiments comprise at least one soluble, corrodible or frangible element, which, after the device has ended its functional life, will dissolve, disintegrate or fracture to allow the device to fragment into smaller sections which are more readily regurgitated by the animal. For example, the hinge may be provided with a soluble or corrodible pin or secured to the container portion by a clip, button, link or trigger made of a corrodible or slowly soluble material. Suitable materials for this purpose will be obvious but by way of example there may be mentioned poly (vinyl alcohol), proteinaceous materials, e.g. casein, magnesuim and its alloys, iron, steel and other corrodible metals.

In a further aspect of the device, the actual containers by solid or semi-solid blocks comprising or consisting of the active substance. Where the substance to be released in the rumen is contained in one or more con tainer portions, the device is normally constructed so that the material contained therein is released over an extended period of time. This may be achieved in a number of ways. For example, this material may be enclosed in a number of capsules having differing solubility in rumen liquor. Tablets of the material may be coated with other materials having differing solubility in rumen liquor. The container portions of the device may be permeable in whole or in part to the material or to rumen liquor, the permeability and amount of permeable material being such that the material contained in the container portions will be released into the rumen at the desired rate. Sustained release of a solid material may be achieved by using the material in the form ofa sparingly soluble solid, the rate of dissolution of which gives the required rate of release of the material. The solid may be contained in the device behind an insoluble gauze, for example, of nylon, or a perforated or slotted plate of the container materials. Where the material to be released is a corrodible solid (for example magnesium metal for the control of grass tenany, as described hereinafter), it is preferred that the material is in the form of a hollow half-cylinder. This has the advantage that reduction in the surface area by corrosion from the outside or inside cylindrical surfaces is kept to a minumum throughout the lifetime of the device.

When liquid surfactants are to be administered by use of a device according to the invention having one or more container portions, it is preferred that sustained release is obtained by using the surfactant in the form of a gel, as has already been described. Other methods include encasing the surfactant in a permeable, water-insoluble materials having capillaries or interconnecting pores extehding through them and paper or cloth partially impregnated with water-insoluble polymers such as cellulose acetate or polystyrene to reduce the permeability. Such permeable materials may be protected by water-destructable coatings. Films comprising water-soluble and water insoluble materials in which the water-soluble material will dissolve away in the rumen environment to make the film permeable, may also be used. Examples of such films are films of ethyl and methyl cellulose, the latter being soluble, and films of cellulose esters such as the acetone and poly (dimethylaminoethyl methacrylate) or poly (tertbutylaminoethyl methacrylate) the latter materials being soluble in acids.

Materials which may be administered by use of the device according to the invention include not only liquid surfactants as mentioned above, but also other medicaments, dietary suppliments or concentrated nutrients, or combinations of any two or more of these materials. Examples of medicaments which may be administered include antibiotics, sulpha drugs, sedatives, anthelmintics, antipyretics, hormones, hypoglycemic agents, antispasmodics and hematics. Furthermore, the device may be used to release rumen-by-pass" materials. These materials comprise an active material which has a coating of, or is incorporated in a matrix of, a polymeric material which is unaffected in the rumen environment, but which is attacked and dissolved as the materials pass further down the digestive tract of the ruminant.

Suitable polymeric materials include polymers of formaldehyde or its condensation product, with amines and/or amides, polymers and copolymcrs of certain of the N-alkyl amino aIkyl-acrylates, -methacrylates, -acrylamides and -methacrylamides and cyclic imides of copolymers of maleic anhydride and styrene, which are insoluble in the rumen environment.

As indicated above, the device may be used to prevent disorders of ruminants other than bloat. Such disorders include hypomagnesemia (grass tetany), hypocalcaemia (milk fever) and acetonaemia (ketosis, grass fever).

Hypomagnesemia and grass tetany are both manifestations of magnesium deficiency. They can occur in cattle, particularly during the early stages of lactation, when the daily intake of magnesium with their diet is less than the demands imposed by milk production. Administration of sufficient magnesium to prevent hypomagnesemia (l to 3 g/day) generally elliminates the more severe milk fever. Both disorders may be manifest over the whole of the lactation period, but treatment with a magnesium supplement during the first 8 to 12 weeks is generally considered to be adequate in most cases. The use of the devices herein described for supplying supplementary magnesium is not restricted by the requirement of a high density as are the known pellets for preventing these disorders. Consequently, a wider selection of magnesium compounds as potential prophylactics may be made. For example, magnesium oxide (periclase), hydroxide (brucite) laurate, oxalate, and other compounds or mixtures of compounds may be used to provide the required daily supplement of magnesium.

It will be appreciated that while passage of the presently known pellets form the rumen further down the digestive tract does not appear to be likely, the configuration to which a device according to the invention is changed in the rumen environment will also prevent or hinder passage of this device further down the digestive tract.

The present invention also extends to methods of treating ruminants which comprise the steps of administering to the ruminant, per 0s, a device according to the invention or a plurality of such devices.

Several examples of devices in accordance with this invention will now be described with reference to the accompanying drawings in which:

FIG. 1 is an exploded perspective view of one half of a preferred form of the device;

FIG. 2 is an end elevation and FIG. 3 is a sectional view of the device of FIG. 1, in the first and second configurations respectively;

FIGS. 4 and 5, 6 and 7, 8 and 9 are sectional views of other devices in the first and second configurations respectively;

FIGS. 10 and ll, 12 and 13 are plan and sectional views of another embodiment in the first and second configurations, respectively.

The first configuration of the devices refers to that configuration in which they are adapted to be passed via the oesophagus of a ruminant into the rumen, and the second confuguration to that adopted once in the rumen.

The device shown in FIGS. I to 3 comprises a body position formed of two boat-like semi-cylinders 1 which are 6 inches to 7 inches long and have semihemispherical ends. When placed together they form a 1 /2 inch diameter cylinder with rounded ends, and having two filling spouts 2.

The semi-cylinders are made of an impermeable and water-insoluble polymer, such as cellulose acetate, polypropylene or polyethylene. They may, if desired, be reinforced with paper or other fibers, or cloth.

The flat face of each semi-cylinder l, is comprised by a plate 3 having a half-inch slot 4 therein, provided with a curved inwardly directed lip 5.

The plate 3 also has a projecting tab 6 provided with a slot 7. A male hinge member 8 and a female hinge member 9 are attached to or moulded integrally with the edge of the plate 3 carrying the tab 6. The male hinge member 8 comprises an outwardly projecting spigot 8A carrying a short pin 88. The female hinge member 9 comprises a spaced pair of spigots 9A having pin-receiving slots 9B in their outer ends.

As shown in FIG. 3, the device is also provided with a trigger mechanism comprising corrodible metal washer 10 attached to the outside wall of each semicylinder I by an expanded spigot 11. A circumferential groove 12 runs from the spigot 11 around the semicylindrical face of each semi-cylinder 1. A hinge link 13 (FIGS. 1 and 3) is provided to secure the two semicylinders I together. The link 13 consists of a strip of flexible plastics material having thickened end portions 13A with a hole 13B therein. If desired a narrow slit 13C may be provided between the hole 138 and and edge of the strip to facilitate assembly of the device as described hereinafter. In an alternative form of the link shown as 113 two holes 1138 are provided, each with a slit 13C, communicating with edges of the strip. In use two semi-cylinders I are secured together as shown in FIG. 3 by inserting the male hinge members 8 in the female hinge members 9. The link 13 is bent to a U- shape and one end portion is passed through the slot 7 in each semi-cylinder 1. One end of a band 14 of an elastic material, e.g. rubber, is looped around the spigot 11 and under the washer on one of the semicylinders 1. The band 14 is passed along the groove 12 through the holes 1313 in each end of the link 13 and then along the groove 12 of the other semi-cylinder and the other end of the band is looped around the spigot 11 of the other semi-cylinder.

Each of the semi-cylinders contains about 100 ml. of gelled Pluronic L62 (see Example 1). Other suitable antifoaming agents include polypropylene glycols, Pluronic" L61 and L64, and products produced by condensing long chain alcohols with ethylene oxide, e.g., lauryl alcohol condensed with 6 to 12 moles of ethylene oxide.

As shown in FIG. 2 the cylinders may be folded together to form an essentially cylindrical structure against the tension of the band 14. The device may be retained in this configuration by means ofa band of soluble material e.g., a gelatin tape, or alternatively the constriction of the oesophahus in the animal may be sufficient to provide the necessary restraint during administration. Once in the rumen the device opens to the configuration shown in FIG. 3 thus allowing the contents of the rumen to Contact the material contained in the semi-cylinders through the slot 4.

The washers 10 are made of magnesium or any similar corrodible metal and are proportioned so that at some time after the contents of the device have been released the pins will corrode to such an extent that they will release the ends of the band 14 from the spigots II. The band 14 can then pull free of the link 13 which in turn can become detached from the slots by the natural movement of the device within the rumen.

The hinge members 8, 9 can then detach and the animal can regurgitate the individual semi-cylinders.

In an alternative arrangement the semi-cylinders I are filled with liquid Pluronic L62 or the like, and the flat faces are closed by a sheet of porous paper impregnated with cellulose acetate to reduce its permeability. Other permeable materials or materials adapted to become permeable which could be used have previously been listed.

The device shown in FIGS. 4 and 5 is similar to the one shown in FIGS. 1 to 3, except that it has a body portion formed of hemi-cylinders 21 which are closed on their straight sides and are made of permeable material or material adapted to become permeable. In lieu of hinges and elastic bands, the hemi-cylinders 21 are connected to two hydrophilic/ hydrophobic strips 22 and as shown in FIG. 4 are secured together by means of a gelatin tape 23. In the rumen, the gelatin tape 23 dissolves and the strips deform to the configuration shown in FIG. 5, thereby to prevent or hinder regurgitation of the device.

A similar device can be constructed with three lobes which together make up a cylinder. In a further modification, elastic hinges, which have a rest position similar to that shown in FIG. 5, and are deformed to a configuration similar to that shown in FIG. 4 to allow the device to pass via the oesophagus into the rumen, may replace the hydrophilic/hydrophobic strips.

The device shown in FIGS. 6 and 7 is particularly suitable for administering solid substances such as magnesium metal or gelled Pluronic surfactants. The two hemi-cylinders 31 are joined by an elastic hinge member 32 made out of nylon. The rest position of the hinge is as shown in FIG. 7, but it is deformed into the configuration shown in FIG. 6 to allow the device to pass via the oesophagus into the rumen. A gelatin tape 33 may be positioned as shown to secure the device in the configuration.

The devices shown in FIGS. 8 and 9 consist ofa body portion formed of a cylinder 41 having two substantially rigid, hemicylindrical wings" 42, 43 respectively attached to the cylinder 41. Preferably, both the cylinder 41 and the wings 42, 43 have rounded ends. The cylinder 41 is made of permeable material or has slots to allow release of the active material. The wings 42, 43 are initially folded so as to fit closely around the cylinder 41, as shown in FIG. 8, to allow the devices to pass via the oesophagus into the rumen. There, the gelatin tape 44 dissolves and the devices are changed to the configuration shown in FIG. 9, thereby to prevent or hinder regurgitation.

The device shown in plan in FIGS. 10 and 12 and in cross section in FIGS. 11 and 13, comprises a body portion 51 of a substantially insoluble resilient matrix material incorporating a material to be released in the rumen, moulded or otherwise formed into a doughnutshape as shown in FIGS. 12 and 13. The body portion 51 may for example have an overall diameter of 4 inches, the diameter of the inside cutaway portion being 2.8 inches and the maximum thickness 0.6 inches. This device, before administration to the ruminant is deformed to the configuration shown in FIGS. 10 and 11 and held in that configuration by gelatin tapes 52. When the device in this configuration is passed into the rumen, the rumen liquor causes the gel atin tape 52 to dissolve and the device, because of the resilience of the body portion, reverts to the configuration shown in FIGS. 12 and 18 thereby to prevent or hinder regurgitation of the device.

A suitable material from which the body portion 51 may be formed may be prepared by heating a liquid surfactant with 8 percent by weight of ethyl cellulose to a temperature of C. to form a clear solution. This clear solution is poured into a suitable mould and cooled to form a rubber-like solid. A body portion formed in this way releases the surfactant slowly from the matrix material into the rumen environment. Liquid surfactants which may be incorporated into a matrix material in this way include the Pluronics L62 and L64 and the product formed by condensing 1 mol. of nonyl phenol with 11 mols. of ethylene oxide and further condensing the thus produced product with 11 mols. of propylene oxide.

The following examples show the use of some of the above described devices.

EXAMPLE 1 Plastic cylindrical capsules 150 mm long and 30 mm diameter, made up of two half-cylinders hinged along one edge, were constructed. The hinges were of rubber and were biased so that two half-cylinders would spring apart in the rumen and thus expose fiat surfaces of the half-cylinders through which the agent in the capsule could diffuse into the rumen. The hinges were constructed so that, under the rumen conditions, they would pull away from the half-cylinders after effective release of the agent, thereby facilitating regurgitation of the fragmented devices.

The capsules were filled with a gel of Pluronic L62 (90 percent) and ethyl cellulose percent). Release of the surfactant from the gel was restricted by 90 X 130 mm slots in the flat face of the capsules.

A commercial herd of 46 milking cows, predominantly Jersey, were treated with two capsules each. Thirty further cows of the same herd were drenched at the evening milking with 7.5 ml ofPluronic" L64. The cows grazed on irrigated pasture, predominantly white clover (Trifolium repens). Bloat was assessed visually, scores 1 to 3 being (1) left flank distended, (2) both flanks distended, and (3) in need of immediate treatment. The trial lasted for 28 days.

Preliminary experiments showed that half-cylinders and un-opened capsules of the quoted dimensions were regurgitated less than 48 hours after administration. The rate of release of surfactant from the capsules was approximately proportional to the amount remaining in the capsule, the half-life being 42 days. The mean release was og/cow/day.

No bloat was observed in the animals treated with the capsules during the first four days of the trial, whilefive cases of bloat were recorded for the drenched cows. Over the trial period 76 percent of the animals treated with the capsules and 47 percent of those drenched had bloated. Of the total number of bloated cases observed in the treated animals, 6 percent occurred during the first 9 days, 24 percent during the next fifteen days and 70% during the final four days. The corresponding proportions in the drenched animals were 31 percent, 48 percent and 2| percent.

Regurgitated fragments of capsules were recovered in the fields from the first day after treatment; 34 halfcylinders and 9 smaller fragments were found. One intact capsule was found after the experiment concluded.

While these trials indicate some degree of success it was considered that the hinges of the capsules failed too quickly leading to premature regurgitation. However, it was clear that release of the surfactant from the retained capsules continued for about 25 days.

EXAMPLE 2 The experiment of Example l was repeated using capsules with strengthened hinges.

In this case 50 cows of the same herd as in Example 1 were treated with two of the devices and 16 further cows of the same herd were kept overnight in pastures sprayed with anti-bloat oil. The conditions of the experiment were similar to those of Example 1 and the trial lasted 36 days.

In the animals treated with the capsules, no bloat occurred during the first l 1 days while 30 cases were recorded for the animals on the sprayed pasture. Over the trial period percent of the treated animals and 88 percent of those on spray pasture bloated.

The incidence of severe bloat (i.e. that requiring treatment of drenching with oil) per 1,000 cow-days, in the animals treated with the capsules was reduced to 1 percent of that for the control animals over the first 32 days. The surfactant in the capsules was exhausted by the 36th day.

Five complete capsules and 3 fragments were recovered in the field over the trial period.

These results show that with a correctly constructed capsule substantial protection of cows against bloat can be achieved for extensive periods, and no treatment is required other than the initial administration of the capsules.

It is to be realised that modifications and adaptions may be made to the constructions specifically described above. For instance, use may be made of semipermeable materials to cause configuration changes by osmotic swelling. Accordingly, all such modifications and adaptions are to be considered as falling within the spirit and scope of this invention which includes every novel feature and combination of features disclosed herein.

The claims defining the invention are as follows:

1. A device for insertion into the rumen of a ruminant through the esophagus and adapted to be retained within the rumen for free movement therein over an extended period of time, said device comprising a body containing an effective amount of a therapeutic or nutrient substance of a type normally administered to a ruminant per os, a major proportion of said body consisting of said substance, said body having a compressed configuration and an expanded configuration, the compressed configuration permitting the passage of the device through the esophagus into the rumen and the expanded configuration being one which will substantially retard passage of the device through the esophagus but will still permit substantially free movement of the device within the rumen, means for resiliently urging said body from said compressed configuration to said expanded configuration, restraining means dissolvable in the rumen holding said body in said compressed configuration until it is received within the rumen whereby said device in compressed configuration may be administered per os so as to pass into the rumen and will expand in the rumen so as to hinder regurgitation during the period of treatment, and means for holding said substance in said body and for slowly releasing said substance from said body when said body is in the rumen.

2. A device as claimed in claim 1 wherein said substance is a bloat control agent.

3. A device as claimed in claim 2 wherein a major proportion of said body consists of a bloat control agent.

4. A device as claimed in claim 2 wherein said body contains a gel formed from said bloat control agent and a gelling agent.

5. A device as claimed in claim 4 wherein said bloat control agent is a polyoxyalkylene surfactant and said gelling agent is ethyl cellulose.

6. A device as claimed in claim 4 wherein said gel contains from about 3 to 15 percent by weight of the gelling agent and the remainder of the gel consists es sentially of the bloat control agent.

7. A device as claimed in claim 2 wherein said bloat control agent is a polyoxyalkylene surfactant.

8.,A device as claimed in claim 2 wherein said bloat control agent is selected from the group consisting of block copolymers of polyoxypropylene and polyoxyethylene and condensation products of dodecanol with 6 to l2 moles of ethylene oxide.

9. A device as claimed in claim 1 wherein said substance is a magnesium supplement.

10. A device for administering a therapeutic or nutrient substance to a ruminant over an extended period of time, said device comprising a resilient, permeable body which will allow passage of the substance to be administered and which is of essentially toroidal form having a compressed configuration which will permit passage of the device into the rumen through the esophagus of the ruminant and an expanded configuration toward which it is resiliently urged which will retard passage of the device from the rumen but will still permit substantially free movement of the device in the rumen, and restraining means dissolvable in the rumen holding said body in said compressed configuration whereby said device may be administered per os for expansion and retention in the rumen during the period of treatment.

11. A method for the administration of a therapeutic or nutrient substance to a ruminant over an extended period of time comprising incorporating said substance in a device from which it is releasable in the rumen of a ruminant, said device having a first configuration in which it is held by restraining means and a second configuration into which it is resiliently urged, said restraining means being rendered ineffective in and by the rumen environment to hold said device in the first configuration in the rumen, the first configuration permitting passage of the container into the rumen through the esophagus of the ruminant and the second configuration being one which will hinder passage of the container from the rumen but will still permit substantially free movement of the container within the rumen, holding said container in said first configuration by said restraining means and administering it to the ruminant per os so as to pass into the rumen where the restraining means is rendered ineffective to hold the device in the first configuration and the device assumes the second configuration for retention in the rumen during the period of treatment.

12. A device for administering a therapeutic or nutrient substance to a ruminant over an extended period of time, said device comprising a body portionof which a major proportion comprises said substance, said body portion having a first configuration into which it may be urged for administration per os so as to pass into the rumen and a second configuration which it will assume in the rumen and which will hinder regurgitation of the device but will still permit substantially free movement in the rumen, and restraining means for holding said body portion in said first configuration until it passes into the rumen, said restraining means being rendered ineffective in and by the rumen environment to hold said body portion in the first configuration in the rumen and to permit said body portion to assume said second configuration in the rumen.

13. A device for administering a therapeutic or nutrient substance to a ruminant over an extended period of time, said device comprising a body portion of which a major proportion comprises said substance, said body portion having first configuration into which it may be urged for administration per 05 so as to pass into the rumen and a second configuration which it will assume in the rumen and which will hinder regurgitation of the device but will still permit substantially free movement in the rumen, and restraining means for holding said body portion in said first configuration until it passes into the rumen, said restraining means being destroyed in the rumen environment to permit said body portion to assume said second configuration in the rumen.

14. A device as claimed in claim 13 wherein said body portion comprises at least one container portion and at least one obstructing means associated therewith, said obstructing means being movable into a first position relative to said container portion to provide said first configuration to allow the device to be administered to a ruminant per os so as to pass into the rumen and, in the rumen environment, movable relative to the container portion to a second position thereby to change said body into said second configuration.

15. A device as claimed in claim 14, wherein the obstructing means comprises at least one protruding structure attached to the container portion.

16. A device as claimed in claim 14 wherein the obstructing means comprises at least one further container portion.

17. A device as claimed in claim 14, wherein the obstructing means is attached to the container portion by a corrodible element which is susceptible to eventual destruction in the rumen environment, whereby after the device has ended its functional life the destruction of the element will allow fragmentation of the device.

18. A device as claimed in claim 13, wherein said body portion comprises at least two inter-connected body portions which are movable relative to one another into said first configuration to allow the device to be administered to a ruminant per os as to pass into the rumen thereof, and which, in the rumen environment, move relative to one another to change the device into said second configuration.

Patent Citations
Cited PatentFiling datePublication dateApplicantTitle
US462990 *Sep 23, 1891Nov 10, 1891 William oppenheimek
US1957564 *Nov 23, 1932May 8, 1934West Aubra TExpanding capsule body
US2580414 *Mar 1, 1948Jan 1, 1952Duffey Thomas EdwardCapsule
US3118439 *Mar 19, 1958Jan 21, 1964Jean-Pierre PerrenoudDiagnostic and medicating capsule and the method of use
US3136695 *Mar 10, 1961Jun 9, 1964Strong Cobb Arner IncAnhydrous thixotropic gel sustained release therapeutic compositions and method of preparation
US3247066 *Sep 12, 1962Apr 19, 1966Parke Davis & CoControlled release dosage form containing water-swellable beadlet
US3315660 *Aug 8, 1963Apr 25, 1967Abella Carlos ACapsule for insertion in the digestive track
US3463745 *Dec 29, 1966Aug 26, 1969Olin MathiesonPolyurethane sponge and process therefor
US3507952 *Dec 20, 1968Apr 21, 1970Smithkline CorpSustained release bolus for animal husbandry
US3545439 *Jan 4, 1968Dec 8, 1970Upjohn CoMedicated devices and methods
US3577513 *Dec 20, 1967May 4, 1971PfizerPellets for supplying biologically active substance to ruminants containing magnesium and coated iron particles
Referenced by
Citing PatentFiling datePublication dateApplicantTitle
US3998211 *Dec 20, 1974Dec 21, 1976Louis BucaloStructures for growing cultures within human and animal bodies
US4055178 *Mar 10, 1976Oct 25, 1977Harrigan Roy MajorDrug delivery device for preventing contact of undissolved drug with the stomach lining
US4172446 *Dec 30, 1975Oct 30, 1979Louis BucaloApparatus for collecting body fluids
US4186730 *Dec 2, 1976Feb 5, 1980Louis BucaloMethods for collecting body fluids
US4239040 *Oct 13, 1977Dec 16, 1980Kabushiki Kaisha Daini SeikoshaCapsule for medical use
US4257427 *Sep 13, 1979Mar 24, 1981Louis BucaloMethod for collecting body fluids
US4268497 *Nov 7, 1979May 19, 1981Beecham Group LimitedSustained drug release device
US4293539 *Sep 12, 1979Oct 6, 1981Eli Lilly And CompanyControlled release formulations and method of treatment
US4308250 *Dec 9, 1980Dec 29, 1981Beecham Group LimitedFor oral administration to ruminants
US4326522 *Jun 9, 1980Apr 27, 1982Pitman-Moore, Inc.Mesh-covered bolus
US4333919 *Dec 15, 1980Jun 8, 1982Eli Lilly And CompanyGrowth promotant controlled release formulations and method of treatment
US4595583 *Mar 19, 1984Jun 17, 1986Alza CorporationDelivery system controlled administration of beneficial agent to ruminants
US4601893 *Dec 6, 1984Jul 22, 1986Pfizer Inc.Anthelminics for ruminants
US4612186 *Sep 27, 1985Sep 16, 1986Alza CorporationAvermectin
US4623345 *Apr 17, 1984Nov 18, 1986Laby Ralph HCapsule for administration to ruminants
US4717566 *Jun 23, 1986Jan 5, 1988Alza CorporationDosage system and method of using same
US4717568 *Aug 11, 1986Jan 5, 1988Alza CorporationThermo-responsive device for administering drugs at a controlled rate
US4717718 *Aug 11, 1986Jan 5, 1988Alza CorporationAvermectin layer, heat sensitive layer for pushing, veterinary medicine
US4729793 *Sep 2, 1986Mar 8, 1988Alza CorporationCellulose acetates and trialkyl citrates
US4735804 *May 7, 1987Apr 5, 1988Merck & Co., Inc.Sustained release from polymer rod
US4758436 *May 7, 1987Jul 19, 1988Merck & Co., Inc.Drug delivery device which can be retained in the stomach for a controlled period of time
US4767627 *May 1, 1987Aug 30, 1988Merck & Co., Inc.Drug delivery device which can be retained in the stomach for a controlled period of time
US4844984 *Mar 24, 1988Jul 4, 1989Alza CorporationFor ruminants, semipermeable walls
US4871544 *Nov 27, 1987Oct 3, 1989Alza CorporationRuminant dispensing device
US4883484 *Dec 2, 1987Nov 28, 1989Shepherd Michael TDelivery device
US4883667 *Nov 27, 1987Nov 28, 1989Alza CorporationThermosensitive for drug delivery, ruminants
US4927633 *Jun 24, 1987May 22, 1990Alza CorporationDispenser for delivering drug to livestock
US4955881 *Jul 25, 1989Sep 11, 1990Alza CorporationRuminant dispensing device
US4966767 *Mar 23, 1989Oct 30, 1990Alza CorporationA housing containing a beneficial agent and means for urging it through exit for delivery and a density member; drugs paracitides
US5000957 *Mar 28, 1989Mar 19, 1991Alza CorporationDispenser comprising hydrophilic osmopolymer
US5002772 *May 31, 1988Mar 26, 1991Pfizer Inc.Gastric retention system for controlled drug release
US5167962 *Aug 8, 1991Dec 1, 1992Southwest Research InstituteRelease at desired location in intestine
US5181505 *Jun 28, 1991Jan 26, 1993Lew Chel WMethod and apparatus for delivery of a medicament in the oral cavity
US5198222 *Aug 31, 1990Mar 30, 1993Agribiotech, Inc.Time release bolus
US5206024 *Dec 24, 1991Apr 27, 1993Alza CorporationDensity element for ruminal delivery device
US5270048 *Sep 3, 1992Dec 14, 1993Borden (Uk) LimitedControlled delivery devices
US5284658 *Jun 9, 1992Feb 8, 1994Pfizer Inc.Means for constraining a rumen drug delivery device in a rolled configuration
US5372776 *Mar 2, 1994Dec 13, 1994Alza CorporationDensity element and method of manufacture thereof to achieve a particular transverse rupture strength
US5417976 *Mar 10, 1994May 23, 1995AlzaDrug delivery for ruminants
US5443843 *Dec 24, 1990Aug 22, 1995Pfizer Inc.Gastric retention system for controlled drug release
US5792470 *Aug 8, 1996Aug 11, 1998Baumgardner, Sr.; Merwyn J.Edible container for administering medication to animals
US5922340 *Sep 16, 1996Jul 13, 1999Children's Medical Center CorporationAdministering with glucocorticoid; sustained release
US5942241 *Jun 7, 1996Aug 24, 1999Euro-Celtique, S.A.A sustained release drug containing a substrate comprising a local anesthetic and a biocompatible, biodegradable, controlled release polymer selected from polyanhydrides, lactic acid and glycolic acid homo-or/and copolymers
US6046187 *Sep 16, 1996Apr 4, 2000Children's Medical Center CorporationUse of glucocorticosteroids in methods and formulations for prolonging and/or reactivating local anesthesia or local anesthesia previously induced by a local anesthetic agent
US6238702Jul 12, 1999May 29, 2001Children's Medical Center Corp.High load formulations and methods for providing prolonged local anesthesia
US6248345Jul 2, 1998Jun 19, 2001Euro-Celtique, S.A.Prolonged anesthesia in joints and body spaces
US6426339Apr 3, 2000Jul 30, 2002Children's Medical Center CorporationIn situ; sustained release; preadministering glucocorticosteroid
US6514516Jun 29, 1999Feb 4, 2003Euro-Celtique, S.A.Local anesthetic and a biocompatible controlled release material consisting of polyanhydrides, copolymers of lactic acid and glycolic acid, poly(lactic) acid, poly(glycolic) acid, polyesters, polyorthoesters, proteins, polysaccharides
US6521259Mar 10, 2000Feb 18, 2003Euro-Celtique S.A.Controlled release material comprising polyanhydrides, copolymers of lactic acid and glycolic acid, polylactic acid, polyglycolic acid, polyesters, polyorthoesters, proteins, polysaccharides; ouabain, digoxin
US6534081Apr 2, 2001Mar 18, 2003Euro-Celtique S.A.Administration of microparticles in a form suitable for injection and containing active agents suitable for treating or diagonising a disease or painful condition in joints in a patient in need, safe and effective procedure; sustained
US6699908Sep 26, 2001Mar 2, 2004Euro-Celtique, S.A.Methods for providing safe local anesthesia
US6921541Sep 9, 2002Jul 26, 2005Euro-Celtique S.A.Formulations and methods for providing prolonged local anesthesia
US8795721 *Dec 18, 2007Aug 5, 2014Eatlittle Inc.Device for delivery of a substance
US20090292173 *Jul 30, 2009Nov 26, 2009Olympus Medical Systems Corp.Lumen passability checking device and method of manufacturing lumen passability checking device
US20100145316 *Dec 18, 2007Jun 10, 2010Electronic Dietary Foods Inc.Device for delivery of a substance
EP0202159A2 *May 6, 1986Nov 20, 1986Merck & Co., Inc.Drug delivery device which can be retained in the stomach for a controlled period of time
EP0936904A1 *Oct 20, 1997Aug 25, 1999Virbac S.A.Device for releasing with delayed effect an active substance, in particular veterinary
EP2106732A1 *Jan 21, 2008Oct 7, 2009Olympus Medical Systems Corp.Device for checking for lumen passage and method of producing device for checking for lumen passage
EP2106732A4 *Jan 21, 2008Jun 19, 2013Olympus Medical Systems CorpDevice for checking for lumen passage and method of producing device for checking for lumen passage
WO2003024355A1 *Sep 20, 2002Mar 27, 2003Anderson Jason WilliamIntraruminal device
Classifications
U.S. Classification424/438, 604/890.1
International ClassificationA61K9/00, A61D7/00, A61M31/00, A23K1/18
Cooperative ClassificationA61M31/002, A61D7/00, A61K9/0068, A23K1/1813
European ClassificationA61K9/00M18G, A61M31/00D, A61D7/00, A23K1/18K