GB2100602A - Device for delivering biologically active substances to the digestive tract - Google Patents

Device for delivering biologically active substances to the digestive tract Download PDF

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Publication number
GB2100602A
GB2100602A GB08214240A GB8214240A GB2100602A GB 2100602 A GB2100602 A GB 2100602A GB 08214240 A GB08214240 A GB 08214240A GB 8214240 A GB8214240 A GB 8214240A GB 2100602 A GB2100602 A GB 2100602A
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United Kingdom
Prior art keywords
deposit device
active substance
carrier body
biologically active
body portion
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Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
GB08214240A
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GB2100602B (en
Inventor
Joshua Michael Stuart Lucas
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
May and Baker Ltd
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May and Baker Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
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Priority to GB08214240A priority Critical patent/GB2100602B/en
Publication of GB2100602A publication Critical patent/GB2100602A/en
Application granted granted Critical
Publication of GB2100602B publication Critical patent/GB2100602B/en
Expired legal-status Critical Current

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Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/0012Galenical forms characterised by the site of application
    • A61K9/0053Mouth and digestive tract, i.e. intraoral and peroral administration
    • A61K9/0068Rumen, e.g. rumen bolus
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M31/00Devices for introducing or retaining media, e.g. remedies, in cavities of the body
    • A61M31/002Devices for releasing a drug at a continuous and controlled rate for a prolonged period of time

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Anesthesiology (AREA)
  • Hematology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Biomedical Technology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Nutrition Science (AREA)
  • Physiology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Fodder In General (AREA)
  • Medicinal Preparation (AREA)

Abstract

A device for delivering an active substance to the rumen or reticulum of ruminants comprises a cylindrical body portion (1), having circular flanges (2) of rounded periphery, loaded with an active substance (3). The specific gravity of the loaded device should be at least 2. <IMAGE>

Description

SPECIFICATION Deposit device for delivering biologically active substances to the digestive tract and method of using same 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-rnleasecomposirions to animals is known. For example, it is known to release magnesium 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 flange 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 serves 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. t!7iophanate; 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 order that the present invention may more readily be understood the following description is given, merely by way of example, with reference to the accompanying drawing in which the sole Figure is a side elevational view of a first embodiment of deposit device in accordance with the present invention.
In the drawing, the deposit device comprises a cylindrical elongate body portion 1 having at each end a flange 2 with a rounded radially outer periphery. The body portion 1 and the flanges 2 are made of a bio-compatible 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 orfatty acids, e.g. palmitic acid.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 throughbore 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 throughbore 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 OS 9 2.3 08 8 2.2 1;5 7 2.3 Oil 6 2.0 3X0 5 1.5 4/0 4 1.2 2/0 3 1.2 50 20 2.5 0/3 20 2.0 0/4 20 1.5 1/3 20 1.0 20 In calves 16 2.3-2.8 0 3 9 2.3 0!2 8 1.1 20 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 Device Weight Weight Specific Weight (unloaded) (loaded) Gravity (when (loaded) recovered after 9 days) A A 8.36g 31.72g 2.26 B 8.55g 31.66g 2.4 30.45g TABLE 2 Device Weight Weight Mean daily weight (when (when loss to 59 days recovered recovered after administration after after (grams per day) 28 days 59 days A 29.169 28.58g 0.05 B - 27.86g 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 14to 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 DEVICE Weight (g) Specific Weight after recovery (g) Mean daily weight gravity of loss (mg) Unloaded Laded Loaded (Days after administration) (Days after Carrier Device Device administration) Portion 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 26.56 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.

Claims (15)

1. 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.
2. A deposit device according to claim 1, wherein the elongate carrier body portion is cylindrical.
3. A deposit device according to claim 1 or 2, wherein the flanges are circular when viewed along a direction parallel to the axis of the elongate carrier body portion.
4. A deposit device according to claim 3, wherein the flanges, when viewed in section on a plane extending diametrically of the elongate carrier body portion, have a rounded outer profile.
5. A deposit device according to any one of the preceding claims, and including an axially extending bore centrally of said elongate carrier body portion.
6. A deposit device according to claim 5, and including an X-ray opaque pin received in said axially extending bore.
7. A deposit device according to any one of claims 1 to 6, wherein the bio-compatible material includes mild steel or stainless steel.
8. A deposit device according to any one of claims 1 to 6, wherein the bio-compatible material includes nylon.
9. A deposit device according to claim 8 when appendant to claim 5, and including a pin in said bore, said pin having a specific gravity higher than that of said flanged carrier body.
10. A deposit device according to any one of the preceding claims wherein the specific gravity of the said assembly is at least 2.2.
11. A deposit device substantially as hereinbefore described with reference to, and as illustrated in, the accompanying drawing.
12. A deposit device according to any one of claims 1 to 11 wherein the biologically active substance is a nutrient, a growth-promoting agent, an anti-parasitic agent, and or a therapeutically active substance.
13. A method of delivering a biologically active substance to the rumen or reticulum of a ruminant, comprising introducing into the rumen or reticulum a deposit device according to any one of claims 1 to 12, 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.
14. A method according to claim 13 wherein the biologically active substance is a nutrient, a growth-promoting agent, an anti-parasitic agent, and or a therapeutically active substance.
15. A method for delivering a biologically active substance to the rumen or reticulum of a ruminant, substantially as hereinbefore described with especial reference to Examples I and II.
GB08214240A 1981-06-24 1982-05-17 Device for delivering biologically active substances to the digestive tract. Expired GB2100602B (en)

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GB08214240A GB2100602B (en) 1981-06-24 1982-05-17 Device for delivering biologically active substances to the digestive tract.

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB8119471 1981-06-24
GB08214240A GB2100602B (en) 1981-06-24 1982-05-17 Device for delivering biologically active substances to the digestive tract.

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GB2100602A true GB2100602A (en) 1983-01-06
GB2100602B GB2100602B (en) 1984-11-14

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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2155335A (en) * 1984-03-07 1985-09-25 Crb Virbac Sa Device for sustained release of medicinal substances
GB2196252A (en) * 1986-09-18 1988-04-27 London Pharmacy Innovation Pharmaceutical formulation
EP0609045A2 (en) * 1993-01-27 1994-08-03 Syotaro Nagamari Method and device for improving milk secretion of cattle
USD968646S1 (en) 2021-07-21 2022-11-01 Msg Entertainment Group, Llc Building

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2155335A (en) * 1984-03-07 1985-09-25 Crb Virbac Sa Device for sustained release of medicinal substances
GB2196252A (en) * 1986-09-18 1988-04-27 London Pharmacy Innovation Pharmaceutical formulation
US4938967A (en) * 1986-09-18 1990-07-03 London School Of Pharmacy Innovations Ltd. Pharmaceutical formulations
GB2196252B (en) * 1986-09-18 1990-10-17 London Pharmacy Innovation Gastric controlled-release dosage forms
EP0609045A2 (en) * 1993-01-27 1994-08-03 Syotaro Nagamari Method and device for improving milk secretion of cattle
EP0609045A3 (en) * 1993-01-27 1995-02-22 Syotaro Nagamari Method and device for improving milk secretion of cattle.
USD968646S1 (en) 2021-07-21 2022-11-01 Msg Entertainment Group, Llc Building

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Publication number Publication date
GB2100602B (en) 1984-11-14

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