WO1986000519A1 - Drug intermittent release device - Google Patents

Drug intermittent release device Download PDF

Info

Publication number
WO1986000519A1
WO1986000519A1 PCT/GB1985/000297 GB8500297W WO8600519A1 WO 1986000519 A1 WO1986000519 A1 WO 1986000519A1 GB 8500297 W GB8500297 W GB 8500297W WO 8600519 A1 WO8600519 A1 WO 8600519A1
Authority
WO
WIPO (PCT)
Prior art keywords
animal
barrier
compartment
container
tongue
Prior art date
Application number
PCT/GB1985/000297
Other languages
French (fr)
Inventor
Edward Haughey
Robert Francis Crawford Jones
Original Assignee
Norbrook Laboratories Limited
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
Application filed by Norbrook Laboratories Limited filed Critical Norbrook Laboratories Limited
Publication of WO1986000519A1 publication Critical patent/WO1986000519A1/en

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • A61K9/0068—Rumen, e.g. rumen bolus
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61D—VETERINARY INSTRUMENTS, IMPLEMENTS, TOOLS, OR METHODS
    • A61D7/00—Devices or methods for introducing solid, liquid, or gaseous remedies or other materials into or onto the bodies of animals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES 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
    • A61M31/00—Devices for introducing or retaining media, e.g. remedies, in cavities of the body
    • A61M31/002—Devices for releasing a drug at a continuous and controlled rate for a prolonged period of time

Definitions

  • This invention relates to a device for the in vivo intermittent release of medicaments to animals, speci ⁇ fically, but not exclusively, ruminants.
  • compositions are known for the slow or controlled release of materials into the human or animal body. These known compositions rely on the chemistry of a carrier material, normally of a polymeric nature, to degrade or dissolve over a preselected period of time.
  • the material to be delivered to the animal is encap- sulated within" a capsule or entangled within a matrix of the polymeric chains of the degradable or soluble material and is released at a more or less controlled rate determined by the chemistry of the degradable material.
  • Farm animals particularly ruminants such as cattle and sheep, require seasonal dosages of various materials such as pharmaceuticals, vitamin supplements, trace elements and the like. These have to be delivered at the correct time of the year and in the correct order.
  • Drugs are administered to the animals conventiently by oral dosage but this, of course, means that the animals must be herded together to enable the dose of drugs to be given. Each animal has to be individually identified and a record kept of what has been given. This procedure is lengthy and labour-intensive and consequently, when large herds are involved, extremely expensive to operate.
  • An object of this invention is to provide a drug release device providing intermittent release of a sequence of drugs over a prolonged period of time.
  • an intermittent drug release device comprising an orally administrable multi-compartmented container, each compartment of which is separated from the next adjacent compartment by a barrier which is degradable under the conditions prevailing within the animal body, and means for retaining the device in an animal and, within each compartment means for mechanically rupturing the barrier.
  • the container may be formed by a plurality of individual cups having degradable bases and being link ⁇ able one with another to form a chain.
  • the container may be an elongate tube having a series of dividing walls transverse to the longi- tudinal axis of the tube dividing same into a series of compartments, the dividing walls being composed of a material which is degradable in contact with the stomach contents of an animal.
  • the means for mechanically rupturing the barrier comprises a tongue attached to the container wall, the tongue having a spike directed generally toward the barrier to be ruptured, and a dehydrated compressed sponge disposed relative to said tongue so that an absorprtion of moisture passing through the barrier as it degrades the sponge expands urging the tongue and spike through to barrier to rupture same.
  • the container has means for varying the geometry of the container after administra ⁇ tion to the animal so as to prevent regurgitation of the device or passage of the device onwards through the digestive tract of the animal.
  • the container may conveniently be an elongate tube having a series of dividing walls transverse to the longitudinal axis of the tube dividing same into a series of compartments, the dividing walls being composed of a material which degrades in contact with the stomach (rumen of a ruminant animal) contents of the animal.
  • the material may be of any physiologically benign material which has the required ability to degrade.
  • Many suitable materials are available commercially, one such being an ethylene/vinyl acetate based polymer containing starch.
  • the main intended use of the present invention is in the delivery of a seasonal programme of drugs to ruminants such as cattle and sheep.
  • a heavy weight for example a quantity of metal powder or shot may be included in the last compartment to degrade. After the shot or powder has been released it will be relatively easily excreted by the animal. However, it may be inconvenient if some of the shot were to remain in the animal and found after slaughter: iron shot could easily be removed by a magnet but the slaughterhouse may not suspect its presence. However, it is preferred as an alternative or as an addition to the use of a weighted container the container has means for altering its geometry once located in the rumen.
  • the present invention includes the provision on the container of one or more laterally extendable wing members held temporarily in a folded condition against the container during administration and releasable to the extended condition in the rumen.
  • a pair of spring plastic wings may be held against the sides of an elongate container by a simple gummed paper or like band which breaks when moistened allowing the wings to extend.
  • the device comprises a plurality of containers adapted to be joined end to end in snap-fit or nesting fashion to form an elongate chain, the base of each container being formed of degradabl'e material.
  • the container of the device of this invention may be itself composed of degradable material which will disperse after all the drugs have been released, that is, it will degrade over a period of time greater than the time allowed for release of -the drugs.
  • Each compartment may include, in addition to the drug to be released, means for assisting rupture of the compartment to assist drug release.
  • a tablet of effervescent material may be included to release a quantity of gas on contact with moisture.
  • Fig. 1 shows a longitudinal part-section of a tubular device of this invention.
  • Fig. 2 shows a second embodiment of the present invention, also in section.
  • Fig. 3 is an enlarged view of a compartment of the device to illustrate the tongue and sponge arrangement
  • an intermittent drug release device (1) is formed from an elongate tubular container (2) having therein a plurality of internal walls (3) transverse to the longitudinal axis of the container (2) dividing same into a series of compartments indicated in Fig. 1 by 4 to 'n 1 .
  • Attached to the container (2) are a pair of laterally sprung wing members (5) attached y outwardly biassed spring joints (6). As shown in
  • the wing members (5) are held against the spring- biassed joint (6) along the longitudinal sides of the tubular container (2) by means of a securing band (7).
  • the top of the container is closed by a lid (8) and the bottom by closure member (9).
  • the tubular container (2), the wing members (5) and the bottom closure member (9) are made of a material which degrades in contact with the ruminal contents of an animal over a relatively long period of time, characteristically in excess of one year.
  • the dividing internal walls (3) are made of a material which degrades in a much shorter time, typically one month.
  • FIG. 2 A second embodiment of this invention is shown in Fig. 2.
  • An intermittent drug release device is made up of a plurality of cup-shaped members (10) having a tubular wall (11) with a base (12) made of degradable material.
  • the plurality of cups (10) are engageable one with another to form a chain giving in effect the same configuration to the device as in Fig. 1.
  • the engagement of cups (10) may be snap-fit or by the use of a suitable sealing technique to produce a water-tight seal.
  • Top and bottom closures (13) and (14) and wings (15) are equivalent to the parts 8, 9 and 5 in Fig. 1.
  • the wings (15) are shown in the extended position. Referring to Fig.
  • each compartment of the device bounded by degradable internal biodegradable partition walls 3, contains a dosage unit of a drug (20).
  • a tongue member (22) having a terminal spike (23) is attached to the internal wall of container (2).
  • sponge (21) As the biodegradable wall (3) degrades moisture from the animal's stomach leaks through the wall (3) and is absorbed by sponge (21) causing the sponge to expand to several times its original volume. This expansion urges the tongue (22) towards the wall (3) and the spike (23) to rupture the wall. This arrangement assists in the release of the drug (20).
  • a device having the physical structure described above has three main compartments separated by membranes of a polyethylene/ vinyl acetate copolymer containing starch.
  • the first chamber has a closure membrane which is soluble more or less immediately on contact with moisture.
  • Each compart ⁇ ment contains a dosage of anthelmintics.
  • Each membrane takes around three weeks to degrade and thus the device provides a ⁇ thelmintic protection over a period of nine weeks in total. It is convenient to incorporate into the polymers used in construction of the device trace nutrient elements as a convenient method of delivery of these to the animal.

Abstract

An intermittent drug release device (1) comprises an orally administrable multi-compartmented container (2), each compartment of which is separated from the next adjacent compartment by a barrier (3) which is degradable under the conditions prevailing within an animal body, means (5) for retaining the device in the animal and, within each compartment means (22) for mechanically rupturing the barrier.

Description

DRUG INTERMITTENT RELEASE DEVICE
This invention relates to a device for the in vivo intermittent release of medicaments to animals, speci¬ fically, but not exclusively, ruminants.
Compositions are known for the slow or controlled release of materials into the human or animal body. These known compositions rely on the chemistry of a carrier material, normally of a polymeric nature, to degrade or dissolve over a preselected period of time. The material to be delivered to the animal is encap- sulated within" a capsule or entangled within a matrix of the polymeric chains of the degradable or soluble material and is released at a more or less controlled rate determined by the chemistry of the degradable material.. Farm animals, particularly ruminants such as cattle and sheep, require seasonal dosages of various materials such as pharmaceuticals, vitamin supplements, trace elements and the like. These have to be delivered at the correct time of the year and in the correct order. These materials will, for the sake of convenience, be referred to hereinafter simply as "drugs". Drugs are administered to the animals conventiently by oral dosage but this, of course, means that the animals must be herded together to enable the dose of drugs to be given. Each animal has to be individually identified and a record kept of what has been given. This procedure is lengthy and labour-intensive and consequently, when large herds are involved, extremely expensive to operate.
It has been previously proposed to administer to the animals a container in which there is held a succes¬ sion of drugs which are released in the correct sequence by the operation of a spring or a clockwork motor or the like located in the container.
An object of this invention is to provide a drug release device providing intermittent release of a sequence of drugs over a prolonged period of time.
According to this invention there is provided an intermittent drug release device comprising an orally administrable multi-compartmented container, each compartment of which is separated from the next adjacent compartment by a barrier which is degradable under the conditions prevailing within the animal body, and means for retaining the device in an animal and, within each compartment means for mechanically rupturing the barrier. The container may be formed by a plurality of individual cups having degradable bases and being link¬ able one with another to form a chain.
Alternatively the container may be an elongate tube having a series of dividing walls transverse to the longi- tudinal axis of the tube dividing same into a series of compartments, the dividing walls being composed of a material which is degradable in contact with the stomach contents of an animal.
Preferably the means for mechanically rupturing the barrier comprises a tongue attached to the container wall, the tongue having a spike directed generally toward the barrier to be ruptured, and a dehydrated compressed sponge disposed relative to said tongue so that an absorprtion of moisture passing through the barrier as it degrades the sponge expands urging the tongue and spike through to barrier to rupture same.
It is preferred that the container has means for varying the geometry of the container after administra¬ tion to the animal so as to prevent regurgitation of the device or passage of the device onwards through the digestive tract of the animal.
The container may conveniently be an elongate tube having a series of dividing walls transverse to the longitudinal axis of the tube dividing same into a series of compartments, the dividing walls being composed of a material which degrades in contact with the stomach (rumen of a ruminant animal) contents of the animal. The material may be of any physiologically benign material which has the required ability to degrade. Many suitable materials are available commercially, one such being an ethylene/vinyl acetate based polymer containing starch.
The main intended use of the present invention is in the delivery of a seasonal programme of drugs to ruminants such as cattle and sheep.
It is necessary that means be provided to retain the device in the rumen of the animal. This may be achieved by inclusion of a heavy weight, for example a quantity of metal powder or shot may be included in the last compartment to degrade. After the shot or powder has been released it will be relatively easily excreted by the animal. However, it may be inconvenient if some of the shot were to remain in the animal and found after slaughter: iron shot could easily be removed by a magnet but the slaughterhouse may not suspect its presence. However, it is preferred as an alternative or as an addition to the use of a weighted container the container has means for altering its geometry once located in the rumen. Therefore, the present invention includes the provision on the container of one or more laterally extendable wing members held temporarily in a folded condition against the container during administration and releasable to the extended condition in the rumen. in one such configuration a pair of spring plastic wings may be held against the sides of an elongate container by a simple gummed paper or like band which breaks when moistened allowing the wings to extend.
In another embodiment of this invention, the device comprises a plurality of containers adapted to be joined end to end in snap-fit or nesting fashion to form an elongate chain, the base of each container being formed of degradabl'e material.
The container of the device of this invention may be itself composed of degradable material which will disperse after all the drugs have been released, that is, it will degrade over a period of time greater than the time allowed for release of -the drugs.
Each compartment may include, in addition to the drug to be released, means for assisting rupture of the compartment to assist drug release. For example a tablet of effervescent material may be included to release a quantity of gas on contact with moisture.
The present invention will now be described by way of example, with reference to the accompanying drawings, in which:
Fig. 1 shows a longitudinal part-section of a tubular device of this invention.
Fig. 2 shows a second embodiment of the present invention, also in section.
Fig. 3 is an enlarged view of a compartment of the device to illustrate the tongue and sponge arrangement,
Referring to Fig. 1, an intermittent drug release device (1) is formed from an elongate tubular container (2) having therein a plurality of internal walls (3) transverse to the longitudinal axis of the container (2) dividing same into a series of compartments indicated in Fig. 1 by 4 to 'n1. Attached to the container (2) are a pair of laterally sprung wing members (5) attached y outwardly biassed spring joints (6). As shown in
Fig. 1 the wing members (5) are held against the spring- biassed joint (6) along the longitudinal sides of the tubular container (2) by means of a securing band (7). The top of the container is closed by a lid (8) and the bottom by closure member (9). In the embodiment shown in Fig. 1, the tubular container (2), the wing members (5) and the bottom closure member (9) are made of a material which degrades in contact with the ruminal contents of an animal over a relatively long period of time, characteristically in excess of one year. The dividing internal walls (3) are made of a material which degrades in a much shorter time, typically one month.
A second embodiment of this invention is shown in Fig. 2. An intermittent drug release device is made up of a plurality of cup-shaped members (10) having a tubular wall (11) with a base (12) made of degradable material. The plurality of cups (10) are engageable one with another to form a chain giving in effect the same configuration to the device as in Fig. 1. The engagement of cups (10) may be snap-fit or by the use of a suitable sealing technique to produce a water-tight seal. Top and bottom closures (13) and (14) and wings (15) are equivalent to the parts 8, 9 and 5 in Fig. 1. The wings (15) are shown in the extended position. Referring to Fig. 3, each compartment of the device, bounded by degradable internal biodegradable partition walls 3, contains a dosage unit of a drug (20). In each compartment there is disposed a dehydrated, highly compressed sponge (21). A tongue member (22) having a terminal spike (23) is attached to the internal wall of container (2). As the biodegradable wall (3) degrades moisture from the animal's stomach leaks through the wall (3) and is absorbed by sponge (21) causing the sponge to expand to several times its original volume. This expansion urges the tongue (22) towards the wall (3) and the spike (23) to rupture the wall. This arrangement assists in the release of the drug (20).
In an example of this invention, a device having the physical structure described above has three main compartments separated by membranes of a polyethylene/ vinyl acetate copolymer containing starch. The first chamber has a closure membrane which is soluble more or less immediately on contact with moisture. Each compart¬ ment contains a dosage of anthelmintics. Each membrane takes around three weeks to degrade and thus the device provides aήthelmintic protection over a period of nine weeks in total. It is convenient to incorporate into the polymers used in construction of the device trace nutrient elements as a convenient method of delivery of these to the animal.

Claims

1. An intermittent drug release device comprising an orally administrable multi-compartmented container, each compartment of which is separated from the next adjacent compartment by a barrier which is degradable under the conditions prevailing within an animal body, means for retaining the device in the animal and, within each compartment means for mechanically rupturing the barrier.
2. A device as claimedin claim 1, in which the container is formed by a plurality of individual cups having degradable bases and being linkable one with another to form a chain.
3. A device as claimed in claim 1, in which the con¬ tainer is an elongate tube having a series of dividing walls transverse to the longitudinal axis of the tube dividing same into a series of compartments, the divi¬ ding walls being composed of a material which is de¬ gradable in contact with the stomach contents of an animal.
4. A device as claimed in any preceding claim in which the means for mechanically rupturing the barrier com¬ prises a tongue attached to the container wall, the tongue having a spike directed generally toward the barrier to be ruptured, and a dehydrated compressed sponge disposed relative to said tongue so that an absorption of moisture passing through the barrier as it degrades the sponge expands urging the tongue and spike through to barrier to rupture same.
5. A device as claimed in claim 4, wherein the sponge is biodegradable.
6. A device as claimed in any preceding claim in which the means for retaining the device within the animal is a weight sufficient to cause the device to sink into the stomach of the animal.
7. A device as claimed in any preceding claim, in which the means for retaining the device within the animal is one or more laterally extensible wings attached to the device, and means for holding said wings in a temporarily folded position during administration of the device to the animal and being releasable to the extended position in the stomach after administration
8. A drug delivery device as claimed in any preceding claim, in which each compartment of the device contains a dosage unit of a drug.
PCT/GB1985/000297 1984-07-05 1985-07-03 Drug intermittent release device WO1986000519A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB848417202A GB8417202D0 (en) 1984-07-05 1984-07-05 Drug intermittent release device
GB8417202 1984-07-05

Publications (1)

Publication Number Publication Date
WO1986000519A1 true WO1986000519A1 (en) 1986-01-30

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/GB1985/000297 WO1986000519A1 (en) 1984-07-05 1985-07-03 Drug intermittent release device

Country Status (4)

Country Link
EP (1) EP0186697A1 (en)
AU (1) AU4546185A (en)
GB (1) GB8417202D0 (en)
WO (1) WO1986000519A1 (en)

Cited By (23)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0242053A2 (en) * 1986-04-16 1987-10-21 Stc Plc Material dispensers, E.G. for use as rumen boluses
AU579637B2 (en) * 1984-06-02 1988-12-01 Castex Products Limited Release devices
US4874388A (en) * 1987-06-25 1989-10-17 Alza Corporation Multi-layer delivery system
US4883484A (en) * 1986-06-17 1989-11-28 Shepherd Michael T Delivery device
US4957494A (en) * 1987-06-25 1990-09-18 Alza Corporation Multi-layer delivery system
US5017381A (en) * 1990-05-02 1991-05-21 Alza Corporation Multi-unit pulsatile delivery system
US5023088A (en) * 1987-06-25 1991-06-11 Alza Corporation Multi-unit delivery system
US5045082A (en) * 1990-01-10 1991-09-03 Alza Corporation Long-term delivery device including loading dose
US5090903A (en) * 1991-01-18 1992-02-25 Taylor Roy M Dental prosthesis with controlled fluid dispensing means
US5110597A (en) * 1987-06-25 1992-05-05 Alza Corporation Multi-unit delivery system
US5209746A (en) * 1992-02-18 1993-05-11 Alza Corporation Osmotically driven delivery devices with pulsatile effect
US5223266A (en) * 1990-01-24 1993-06-29 Alza Corporation Long-term delivery device with early startup
US5227167A (en) * 1991-06-11 1993-07-13 Alza Corporation Long-term delivery device including hydrophobic loading dose
US5240713A (en) * 1991-09-27 1993-08-31 Alza Corporation Dual rate agent delivery device
US5308348A (en) * 1992-02-18 1994-05-03 Alza Corporation Delivery devices with pulsatile effect
US5366454A (en) * 1993-03-17 1994-11-22 La Corporation De L'ecole Polytechnique Implantable medication dispensing device
US5456679A (en) * 1992-02-18 1995-10-10 Alza Corporation Delivery devices with pulsatile effect
US5499979A (en) * 1987-06-25 1996-03-19 Alza Corporation Delivery system comprising kinetic forces
US5580003A (en) * 1992-01-31 1996-12-03 Svedala Arbra Ab Method for controlling a gyratory crusher
FR2754711A1 (en) * 1996-10-21 1998-04-24 Vandamme Thierry DELAY DEVICE WITH DELAY EFFECT OF AN ACTIVE SUBSTANCE, IN PARTICULAR VETERINARY
WO1998040050A1 (en) * 1997-03-10 1998-09-17 Kemira Kemi Ab Calcium composition
WO2002089767A1 (en) * 2001-05-03 2002-11-14 Massachusetts Eye And Ear Infirmary Implantable drug delivery device and use thereof
US8679093B2 (en) 2010-11-23 2014-03-25 Microchips, Inc. Multi-dose drug delivery device and method

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2137253A1 (en) * 1971-05-17 1972-12-29 Alemany R Placing and retaining device - for vaginal medicaments
EP0062391A1 (en) * 1981-01-19 1982-10-13 Research Corporation Delivery system for the sustained release of a substance in the reticulorumen
EP0079724A2 (en) * 1981-11-09 1983-05-25 Eli Lilly And Company Sustained release capsule for ruminant animals

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2137253A1 (en) * 1971-05-17 1972-12-29 Alemany R Placing and retaining device - for vaginal medicaments
EP0062391A1 (en) * 1981-01-19 1982-10-13 Research Corporation Delivery system for the sustained release of a substance in the reticulorumen
EP0079724A2 (en) * 1981-11-09 1983-05-25 Eli Lilly And Company Sustained release capsule for ruminant animals

Cited By (29)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU579637B2 (en) * 1984-06-02 1988-12-01 Castex Products Limited Release devices
EP0242053A3 (en) * 1986-04-16 1988-06-01 Stc Plc Material dispensers, e.g. for use as rumen boluses
EP0242053A2 (en) * 1986-04-16 1987-10-21 Stc Plc Material dispensers, E.G. for use as rumen boluses
US4883484A (en) * 1986-06-17 1989-11-28 Shepherd Michael T Delivery device
US5110597A (en) * 1987-06-25 1992-05-05 Alza Corporation Multi-unit delivery system
US4874388A (en) * 1987-06-25 1989-10-17 Alza Corporation Multi-layer delivery system
US4957494A (en) * 1987-06-25 1990-09-18 Alza Corporation Multi-layer delivery system
US5499979A (en) * 1987-06-25 1996-03-19 Alza Corporation Delivery system comprising kinetic forces
US5023088A (en) * 1987-06-25 1991-06-11 Alza Corporation Multi-unit delivery system
US5045082A (en) * 1990-01-10 1991-09-03 Alza Corporation Long-term delivery device including loading dose
US5840074A (en) * 1990-01-10 1998-11-24 Alza Corporation Method and apparatus for delivering first agent followed by second agent
US5223266A (en) * 1990-01-24 1993-06-29 Alza Corporation Long-term delivery device with early startup
US5368863A (en) * 1990-01-24 1994-11-29 Alza Corporation Long-term delivery device with early startup
US5017381A (en) * 1990-05-02 1991-05-21 Alza Corporation Multi-unit pulsatile delivery system
US5090903A (en) * 1991-01-18 1992-02-25 Taylor Roy M Dental prosthesis with controlled fluid dispensing means
US5227167A (en) * 1991-06-11 1993-07-13 Alza Corporation Long-term delivery device including hydrophobic loading dose
US5240713A (en) * 1991-09-27 1993-08-31 Alza Corporation Dual rate agent delivery device
US5580003A (en) * 1992-01-31 1996-12-03 Svedala Arbra Ab Method for controlling a gyratory crusher
US5456679A (en) * 1992-02-18 1995-10-10 Alza Corporation Delivery devices with pulsatile effect
US5308348A (en) * 1992-02-18 1994-05-03 Alza Corporation Delivery devices with pulsatile effect
US5209746A (en) * 1992-02-18 1993-05-11 Alza Corporation Osmotically driven delivery devices with pulsatile effect
US5366454A (en) * 1993-03-17 1994-11-22 La Corporation De L'ecole Polytechnique Implantable medication dispensing device
FR2754711A1 (en) * 1996-10-21 1998-04-24 Vandamme Thierry DELAY DEVICE WITH DELAY EFFECT OF AN ACTIVE SUBSTANCE, IN PARTICULAR VETERINARY
WO1998017259A1 (en) * 1996-10-21 1998-04-30 Virbac S.A. Device for releasing with delayed effect an active substance, in particular veterinary
AU737586B2 (en) * 1996-10-21 2001-08-23 Virbac S.A. Device for the delayed release of an active substance, substance, especially a veterinary active substance
US6416781B1 (en) 1996-10-21 2002-07-09 Virbac S.A. Device for releasing with delayed effect an active substance, in particular veterinary
WO1998040050A1 (en) * 1997-03-10 1998-09-17 Kemira Kemi Ab Calcium composition
WO2002089767A1 (en) * 2001-05-03 2002-11-14 Massachusetts Eye And Ear Infirmary Implantable drug delivery device and use thereof
US8679093B2 (en) 2010-11-23 2014-03-25 Microchips, Inc. Multi-dose drug delivery device and method

Also Published As

Publication number Publication date
EP0186697A1 (en) 1986-07-09
GB8417202D0 (en) 1984-08-08
AU4546185A (en) 1986-02-10

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