Deposit device for delivering biologically active substances to the digestive tract and method of using same

A deposit device for delivering a biologically active substance to the rumen or reticulum of a ruminant comprises a cylindrical body portion, having circular flanges of rounded periphery, loaded with an active substance. The specific gravity of the loaded device should be at least 2 for retention in the stomach.

The present invention relates to a deposit device for delivering a 
biologically active substance, for example a nutrient substance, a 
growth-promoting agent, an antiparasitic agent or a therapeutic substance, 
to the digestive tract, and also relates to a method of administering an 
active substance to a ruminant. 
The administration of slow-release compositions to animals is known. For 
example, it is known to release magmesium from a magnesium alloy "bullet" 
deposited in the rumen of cattle in order to allow the cattle to benefit 
from the activity of the magnesium. 
The present invention provides a deposit device formed of a bio-compatible 
material, for delivering a biologically active substance to the digestive 
tract, comprising an elongate carrier body portion having respective 
flanges near its ends to define a flanged carrier body with, between the 
flanges, an annular space to receive a said biologically active substance; 
and, carried by the flanged carrier body between the said flanges, a load 
in the form of a mass of a biologically active substance, mounted on and 
around the elongate carrier body portion, the overall specific gravity of 
the assembly of the flanged carrier body together with its load being at 
least 2, and the assembly being free of sharp edges likely to cause trauma 
in the digestive tract of an animal. 
The present invention also provides a method of delivering a biologically 
active substance to the rumen or reticulum of a ruminant, comprising 
introducing into the rumen or reticulum the above defined deposit device, 
and allowing the deposit device to remain in the rumen or reticulum at 
least until the required amount of the biologically active substance has 
been absorbed from the load of the deposit device. 
For example, the deposit device may be intended to be retained in the rumen 
or reticulum of a ruminant. 
The flanges not only serve to define an annular space to be occupied by the 
load of biologically active substance, thereby facilitating the loading of 
the desired amount of load onto the elongate carrier body portion, 
particularly when the load fills completely the annular space so-defined, 
but also serve, to protect the ends of the load from physical damage 
during handling and administration to an animal and to maintain a more 
constant surface area for the load during erosion of the load in the 
digestive tract of an animal, e.g. in the rumen or reticulum, than would 
be the case in the absence of the flanges. 
Generally, the biologically active substance may for example comprise: a 
nutrient, a growth-promoting agent, an anti-parasitic agent and/or a 
therapeutically active substance. 
More specific examples of biologically active substances include: vitamins; 
minerals; aminoacids; anthelmintics, e.g. thiophanate; anticoccidial 
agents, e.g. decoquinate; anti-microbial agents, e.g. antibiotics; 
hormones; antibloat agents; antihistaminics; systemic insecticides; and 
trace elements, e.g. cobalt, copper, manganese, molybdenum, iron, iodine, 
boron, vanadium and selenium.

In the drawing, the deposit device comprises a substantially solid 
cylindrical elongate body portion 1 having at each end a radially 
outwardly projecting external flange 2 having a diameter at least about 3 
times the diameter of the body portion 1 and with a rounded radially outer 
periphery. The body portion 1 and the flanges 2 are made of a 
biocompatible composition, for example nylon or a non-toxic metal, e.g. 
mild or stainless steel, so as to avoid damage to the deposit device by 
chemical action in the rumen or reticulum, and so as also to avoid 
contaminating the rumen or reticulum. The flanges 2 are non-releasably 
attached to the body portion 1 so as to define therebetween an annular 
space which, in the drawing, is occupied by a load 3 comprising a suitable 
active substance, either alone or in a bio-compatible carrier composition, 
for example a wax, e.g. paraffin wax or fatty acids, e.g. palmitic acid. 
The load is carried solely by the flanges and the carrier body. 
Preferably, the cylindrical elongate body portion 1 is made of a non-toxic 
metal and the flanges 2 are made of nylon or the cylindrical elongate body 
portion 1 is made of nylon and the flanges 2 are made of a non-toxic 
metal, but more particularly both the cylindrical body portion 1 and the 
flanges 2 are made of a non-toxic metal. 
As indicated above, the active substance may be a nutrient substance, or a 
growth-promoting substance, or a therapeutically active composition to 
treat some disorder of the beast. 
In the embodiment of the deposit device illustrated in the drawing an 
axially extending through-bore 4 is formed in the cylindrical elongate 
body portion 1, for the purposes of receiving a supplementary component 
such as a pin which may be of X-ray opaque material or of a high density 
composition to adjust the density of the deposit device. However, the 
axial through-bore 4 is an optional aspect as one example of means of 
ensuring that the deposit has the required density, to be discussed below. 
The rounded outer periphery of the flanges 2 serves to eliminate trauma in 
the beast when the deposit device is entering the rumen or reticulum or is 
at rest in the rumen or reticulum. 
The deposit device illustrated in the drawing can be of various sizes. 
Generally the length of the device may be from 45 mm to 80 mm and the 
flange diameter may be from 15 to 26 mm. 
One preferred form of the device, which has been used successfully in 
sheep, is 5 cm in overall length and has a diameter of 4 mm for the 
elongate body portion 1 and of 15 mm for the flanges 2, the flanges 2 each 
having an axial extent (thickness) of 5 mm. The empty weight of the device 
was approximately 11 g. and the volume approximately 2.25 ml empty. 
For cattle, a successful embodiment has an overall length of 6 cm with a 
diameter of 4 mm for the elongate body portion 1, a thickness of 5 mm for 
the flanges 2, but a diameter of 22 mm for the flanges. In each case the 
flanged carrier body of the successful deposit device has been made of 
nylon and a non-toxic metal (mild or stainless steel), or of metal (mild 
or stainless steel) alone. An X-ray opaque pin (5 in the drawing) was 
inserted in certain of these flanged carrier bodies in order to identify 
the device when more than one had been administered to a single animal, 
and to observe the placement and retention of the device. 
A device of the form described above intended for sheep has been used 
successfully in cattle, subject to the overall specific gravity of the 
device falling within a particular range. 
In each case, the device was administered by being placed, by hand or using 
a balling gun, on the back of the tongue of the beast with the 
longitudinal axis of the elongate body portion 1 coaxial with the throat. 
In tests carried out with the devices just described the following results 
were obtained: 
______________________________________ 
Device 
Illustrated 
(empty) Control Bolus 
Wt. (g) S.G. Lost/Retained 
Lost/Retained 
______________________________________ 
In sheep 
11 7.3 0/20 
10 2.7 0/5 
9 2.3 0/8 
8 2.2 1/5 
7 2.3 0/1 
6 2.0 3/0 
5 1.5 4/0 
4 1.2 2/0 
3 1.2 5/0 
20 2.5 0/3 
20 2.0 0/4 
20 1.5 1/3 
20 1.0 2/0 
In calves 
16 2.3-2.8 0/3 
9 2.3 0/2 
8 1.1 2/0 
4 2.0 4/0 
______________________________________ 
The column headed "control bolus" relates to a body having a known density 
and a shape similar to that of the device illustrated (when loaded), and 
served to evaluate the density values required of the loaded device, 
whereas the column "device illustrated" gives the number of unloaded 
flanged carrier bodies lost and the number retained, respectively, for the 
configuration of flanged carrier body illustrated in the drawing. 
From the above results, we conclude that the specific gravity of the 
unloaded flanged carrier body must be at least 2, preferably at least 2.2 
for it to remain in the rumen. When the composition to be applied as the 
load 3 has a specific gravity of less than 2, added ballast may be 
required if the specific gravity of the flanged carrier body itself is not 
high enough to ensure that when initially loaded with a low specific 
gravity composition the overall specific gravity will still be in the 
required range. The specific gravities of the flanged carrier body, the 
load and any ballast must be such that the overall specific gravity of the 
device at the time of administration to the animal is at least 2, and 
preferably at least 2.2, and remains at least 2, and preferably at least 
2.2, during the progressive erosion of the load by physical or chemical 
action in the rumen or reticulum. 
Other tests have revealed that with exactly the same shape of deposit 
device, an all-nylon flanged carrier body having a relatively low specific 
gravity may be lost whereas a similar device having a weightening pin in 
its bore 4 will be retained, by virtue of the higher specific gravity of 
the flanged carrier body. 
The flanged carrier body may be formed of any suitable material provided it 
is not toxic to the ruminant in which it is to be placed. 
It is envisaged that any bio-compatible active substance can be 
administered as biologically active substance using the flanged carrier 
body illustrated in the drawing. 
EXAMPLE I 
Tests were carried out with two devices, according to the present 
invention, which devices had the form illustrated in the drawing. The 
overall length was 4.9 cm, the diameter of the cylindrical body portion 1 
was 4.5 mm. The diameter of the flanges 2 was 19 mm, the flanges 2 each 
having an axial extent (thickness) of 3.5 mm. The body portion 1 was of 
steel and the flanges of nylon. The results for these devices, 
(hereinafter identified as Devices A and B) are given in Tables 1 and 2 
below. The devices were loaded (load 3 of the drawing) with a mixture of 2 
parts by weight of paraffin wax, 5 parts by weight of iron filings and 1 
part by weight of the anthelmintic thiophanate 
[1,2-bis-(3-ethoxycarbonyl-2-thioureido)benzene], and were administered by 
mouth to sheep and recovered from the rumen or reticulum 9, 28 and 59 days 
after administration. 
TABLE 1 
______________________________________ 
Weight 
(when 
Specific 
recovered 
Weight Weight Gravity 
after 
Device (unloaded) 
(loaded) (loaded) 
9 days) 
______________________________________ 
A 8.36 g 31.72 g 2.26 -- 
B 8.55 g 31.66 g 2.4 30.45 g 
______________________________________ 
TABLE 2 
______________________________________ 
Weight Weight 
(when (when Mean daily weight 
recovered recovered loss to 59 days 
after after after administration 
Device 28 days) 59 days) (grams per day) 
______________________________________ 
A 29.16 g 28.58 g 0.05 
B -- 27.86 g 0.06 
______________________________________ 
As can be seen from the above Tables 1 and 2, in these tests, the devices A 
and B of the form illustrated in the drawing were retained in the rumen or 
reticulum of the sheep for 59 days after administration, during which time 
there was a slow and sustained release of the load composition at a rate 
of between 50 and 70 mg per day into the digestive tract of the sheep, 
thereby producing a sustained administration of the anthelmintic 
thiophanate at a rate of between about 12 and about 17 mg per day. 
EXAMPLE II 
Tests were carried out on nine devices (hereinafter identified as Devices C 
to K) according to the present invention, which devices had the form 
illustrated in the drawing. The overall length was 4.9 cm, the diameter of 
the cylindrical body portion 1 was 4.5 mm. The diameter of the flanges 2 
was 19 mm, the flanges 2 each having an axial extent (thickness) of 3.5 
mm. The materials of the devices were: 
______________________________________ 
Device Body Portion Flanges Load 
______________________________________ 
C and D Steel Nylon 1 
E and F Nylon Steel 2 
G to K Steel Steel 2 
______________________________________ 
the Loads indicated above were: 
______________________________________ 
Load 1: a mixture of 2 parts by weight of 
paraffin wax, 5 parts by weight of 
iron powder and 1 part by weight of 
thiophanate. 
Load 2: 2 parts by weight of paraffin wax, 
3 parts by weight of iron powder and 
5 parts by weight of thiophanate. 
______________________________________ 
The devices were administered by mouth to sheep, and subsequently recovered 
from the rumen or reticulum 14 to 35 days later, weighed, returned to the 
animal, and recovered and weighed 47 to 74 days from initial 
administration, as indicated in Table 3 below, in which the results of 
this test are given. 
TABLE 3 
__________________________________________________________________________ 
Weight (g) Specific Mean daily weight 
Unloaded gravity of loss (mg) 
Carrier 
Loaded 
Loaded 
Weight after recovery (g) 
(Days after 
DEVICE 
Portion 
Device 
Device 
(Days after administration) 
administration) 
__________________________________________________________________________ 
C 9.0 30.73 
2.3 29.26 27.93 105 59.6 
(14) (47) (0-14) 
(0-47) 
D 8.5 30.32 
2.3 28.56 26.42 125.7 
63.9 
(14) (61) (0-14) 
(0-61) 
E 12.84 
31.12 
2.4 27.77 24.75 95.7 86.1 
(35) (74) (0-35) 
(0-74) 
F 12.7 29.05 
2.2 26.16 21.94 82.6 96.08 
(35) (74) (0-35) 
(0-74) 
G 18.3 35.04 
2.7 31.9 29.5 94.8 79.1 
(33) (70) (0-33) 
(0-70) 
H 18.5 35.38 
2.7 32.11 29.52 99.1 83.7 
(33) (70) (0-33) 
(0-70) 
I 18.0 33.9 
2.6 30.77 27.92 95.1 85.57 
(33) (70) (0-33) 
(0-70) 
J 18.14 
34.04 
2.6 30.85 28.04 96.7 85.7 
(33) (70) (0-33) 
(0-70) 
K 18.12 
34.37 
2.5 31.4 28.85 90.0 78.8 
(33) (70) (0-33) 
(0-70) 
__________________________________________________________________________ 
As can be seen from the above Table 3, in these tests, Devices C to K, of 
the form illustrated in the drawing, were retained in the rumen of the 
sheep for up to 74 days after administration, during which time there was 
a slow and sustained release of the load composition at a rate of between 
about 60 and about 125 mg per day into the digestive tract of the sheep, 
thereby producing a sustained administration of the anthelmintic 
thiophanate at a rate between about 7.5 and about 50 mg per day.