U.S. patent number 3,844,285 [Application Number 05/315,013] was granted by the patent office on 1974-10-29 for device for administration to ruminants.
This patent grant is currently assigned to Commonwealth Scientific and Industrial Research Organization. Invention is credited to Ralph Henry Laby.
United States Patent |
3,844,285 |
Laby |
October 29, 1974 |
DEVICE FOR ADMINISTRATION TO RUMINANTS
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. The device is especially useful in the treatment of bovine
bloat by extended release in the rumen of surface active
substances.
Inventors: |
Laby; Ralph Henry (Victoria,
AU) |
Assignee: |
Commonwealth Scientific and
Industrial Research Organization (Campbell, AU)
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Family
ID: |
3745317 |
Appl.
No.: |
05/315,013 |
Filed: |
December 14, 1972 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
Issue Date |
|
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67955 |
Aug 28, 1970 |
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Current U.S.
Class: |
424/438;
604/890.1 |
Current CPC
Class: |
A23K
50/10 (20160501); A61D 7/00 (20130101); A61K
9/0068 (20130101); A61M 31/002 (20130101) |
Current International
Class: |
A23K
1/18 (20060101); A61D 7/00 (20060101); A61K
9/00 (20060101); A61M 31/00 (20060101); A61m
031/00 () |
Field of
Search: |
;128/260,272,130,213,217,261,223,264,271,1.1,1.2,127-129
;424/19,22,37,14-18,20,21,6 ;206/63.2R,47A,84 |
References Cited
[Referenced By]
U.S. Patent Documents
Primary Examiner: Gaudet; Richard A.
Assistant Examiner: McGowan; J. C.
Attorney, Agent or Firm: Bacon & Thomas
Parent Case Text
This is a continuation, of application Ser. No. 67,955, filed Aug.
28, 1970, now abandoned.
Claims
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 essentially 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 12 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 portion of 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 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 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.
Description
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 animal's 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.
In 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 commencement of 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.
In 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 nonyl- or octyl-phenol with 8 or 9 moles of ehtylene
oxide, or with 9 to 11 moles of ethylene oxide followed by 9 to 11
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 (b) 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 semi-rigid 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 comprise 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 container 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 of
a 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 extending 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
copolymers of certain of the N-alkyl amino alkyl-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 (1 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 os,
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 11, 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. 1 to 3 comprises a body position formed
of two boat-like semi-cylinders 1 which are 6 inches to 7 inches
long and have semi-hemispherical ends. When placed together they
form a 11/2 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 1, 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 8B. 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 1 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 semi-cylinders 1
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 13B
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 113B are provided, each with a slit 13C,
communicating with edges of the strip. In use two semi-cylinders 1
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 10 on
one of the semi-cylinders 1. The band 14 is passed along the groove
12 through the holes 13B 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 of a
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 11. 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 1 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 of a 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
"doughnut"-shape 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 gelatin tape 52 to dissolve and the device, because of
the resilience of the body portion, reverts to the configuration
shown in FIGS. 12 and 1B 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 160.degree.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 flat
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 (10 percent). Release of the surfactant from
the gel was restricted by 90 .times. 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 of "Pluronic"
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
6g/cow/day.
No bloat was observed in the animals treated with the capsules
during the first four days of the trial, while five 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 21 percent.
Regurgitated fragments of capsules were recovered in the fields
from the first day after treatment; 34 half-cylinders 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 1 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 11 days while 30 cases were recorded for the animals on
the sprayed pasture. Over the trial period 65 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 semi-permeable 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.
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