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
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B65—CONVEYING; PACKING; STORING; HANDLING THIN OR FILAMENTARY MATERIAL
  • B65D—CONTAINERS FOR STORAGE OR TRANSPORT OF ARTICLES OR MATERIALS, e.g. BAGS, BARRELS, BOTTLES, BOXES, CANS, CARTONS, CRATES, DRUMS, JARS, TANKS, HOPPERS, FORWARDING CONTAINERS; ACCESSORIES, CLOSURES, OR FITTINGS THEREFOR; PACKAGING ELEMENTS; PACKAGES
  • B65D33/00—Details of, or accessories for, sacks or bags
  • B65D33/16—End- or aperture-closing arrangements or devices
  • B65D33/1658—Elements for flattening or folding the mouth portion
  • B65D33/1675—Hinged clips
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B65—CONVEYING; PACKING; STORING; HANDLING THIN OR FILAMENTARY MATERIAL
  • B65D—CONTAINERS FOR STORAGE OR TRANSPORT OF ARTICLES OR MATERIALS, e.g. BAGS, BARRELS, BOTTLES, BOXES, CANS, CARTONS, CRATES, DRUMS, JARS, TANKS, HOPPERS, FORWARDING CONTAINERS; ACCESSORIES, CLOSURES, OR FITTINGS THEREFOR; PACKAGING ELEMENTS; PACKAGES
  • B65D65/00—Wrappers or flexible covers; Packaging materials of special type or form
  • B65D65/38—Packaging materials of special type or form
  • B65D65/46—Applications of disintegrable, dissolvable or edible materials
  • B65D65/466—Bio- or photodegradable packaging materials
• • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
  • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
  • Y02W—CLIMATE CHANGE MITIGATION TECHNOLOGIES RELATED TO WASTEWATER TREATMENT OR WASTE MANAGEMENT
  • Y02W90/00—Enabling technologies or technologies with a potential or indirect contribution to greenhouse gas [GHG] emissions mitigation
  • Y02W90/10—Bio-packaging, e.g. packing containers made from renewable resources or bio-plastics

Definitions

• the invention relates to a device for releasing, with a delayed effect, an active substance, in particular a veterinary substance.
• One of the main lines of research aims to develop anthelmintic compounds intended for the treatment of verminosis of ruminants (cattle, goats, etc.).
• the most common formulations use granules or medicated premixes containing anthelmintic agents. More sophisticated formulations have also been designed for the oral route. These allow a release of the active ingredient for a longer period of time and thereby avoid having to regularly reprocess the animals and go looking for them in the pasture to care for them.
• These devices for prolonged release of active principle also called intraruminal diffusers or boli
• the early release of the active ingredient also has the disadvantage of avoiding contact between the host and the infestant at a stage where this contact would allow the ruminant to acquire immune protection against these parasites.
• There is therefore a need for a device which would allow, on the one hand, a lag time after the ingestion of the device by the animal, before any release of active principle at the time of grazing, and on the other hand, would ensure the release of an active agent, in particular anthelmintic continuously or preferably by impulse, in an increasing amount as a function of time during the months of July and August.
• the invention relates to a device for distributing an active substance, intended for use in a biological medium, in particular the rumen of an animal, comprising: - a sealed container intended to contain said substance, said container having at least one opening;
• the container is a flexible waterproof bag or a waterproof bag having a certain rigidity and capable of being rolled up and unwound. Any waterproof and non-biodegradable material may be suitable. Mention may be made of a non-biodegradable polymer, in particular a polypropylene, polyester, polyvinyl, etc.
• the closure means comprises a member formed of two elements which apply to one another.
• biodegradable element can be held together at each of their ends by the biodegradable element. They can also be interconnected by a hinge portion and held together at one end by said biodegradable element.
• these two elements comprise on their internal face of the complementary longitudinal ribs, so that when the two elements are applied one on the other the ribs interpenetrate and ensure the complete sealing of the closure means.
• the closure means comprises a clamp normally open and maintained in the closed state by means of the biodegradable element, said clamp preferably having branches comprising ribs which interpenetrate.
• the container is formed by a rigid cup of cylindrical shape, closed at one of its ends and open at the other of said ends and the means for temporarily closing said open end comprises a washer pierced d '' a central orifice, a plug of complementary shape to this central orifice and held on said central orifice by the biodegradable element supported by a ring, and by a ring, intended to be fixed on the cup to hold the washer and the ring applied against the open end of said cup.
• the receptacle is formed by a cylinder comprising at one of its ends a ballast element and at the other of these ends a plug provided with perforations and this cylinder comprises several superimposed compartments and each containing a active substance, said compartments communicating with each other and being closed each by said temporary closure means.
• Each compartment is formed by a sleeve provided at one of its ends with an external thread and at the other of its ends with an internal thread.
• the means for temporarily closing each compartment comprises a washer pierced with a central orifice, a plug of a shape complementary to this central orifice and held on said central orifice by the biodegradable element supported by a ring applied to said washer by the socket of the adjacent compartment.
• the receptacle is formed by an envelope of elongated shape made of impermeable and biologically non-degradable material, comprising at least at one of its ends an opening and containing a matrix formed of a resin in which are distributed. particles of a material of high density, particles of said active substance, said opening being maintained in the closed state by said biodegradable element.
• the envelope has at each of its ends an opening and the matrix has a passage extending over the entire length of said matrix and disposed in the axis of said openings, these openings being each closed by a plug made of non-biodegradable material and said plugs being connected by said biodegradable element.
• the receptacle is formed by a cylindrical container comprising two half-shells connected to each other at one of their ends by a portion forming a hinge and at the other of said ends by said biodegradable element to temporarily maintain the container in the closed state.
• the half-shells are provided to contain a form with delayed release of an active principle of the type comprising a matrix in which an active principle is dispersed and a central recess being provided in said matrix to allow a gradual release of the active principle based on the differences in the migration path of the active principle from the matrix to the central recess.
• the biodegradable element consists of a wire or a strip of a biologically degradable polymeric material.
• Any biodegradable polymer material is suitable. Mention may be made of polyglycolic acid (PGA), polylactic acid (PLA) or a copolymer of polyglycolic acid and polylactic acid (PLGA), poly ( ⁇ -caprolactone) (PCL), poly (p- dioxanone), polyanhydrides, polyorthoesters, etc.
• the biodegradable element consists of a surgical suture thread, in particular a monofilament or braided surgical suture thread.
• Yarns of this type which may be suitable are in particular polyamides, such as those described in US Pat. No. 5,068,220, polymers of polyglycolic acid, for example that sold under the brand
• the diameter of the wire or strip is variable and depends on the size of the device, the nature of the material used and the time after which its degradation is desired. A person skilled in the art is able, using routine calculations, to determine the size thereof. Preferred suture sizes correspond to the numbers: 0; 1/0 and 2/0.
• the closure of the strip or of the suture is ensured by maintaining traction on the ends of the strip or of the thread, by any appropriate means, in particular using a knot or any external device enabling the free ends of the wire or strip, such as glue, wax, a non-degradable polymer, a crimping ring, etc.
• a bioresorbable screw is also used in a material resorbable by hydrolysis, such as a high molecular weight polymer of polylactic acid or polycaprolactone type.
• the biologically active substance advantageously consists of a medicament, in particular an anthelmintic, a growth-promoting agent, etc., the device then being intended to be introduced into the stomach of a ruminant.
• the release of the active substance when the suture has lost its mechanical properties, can be facilitated by formulating the active principle in an effervescent dosage form or by adding to the sachet next to the diffuser.
• an effervescent mixture without pharmacological properties.
• the mixture can consist of citric acid and sodium bicarbonate or other mixtures whose hydration produces a gas.
• the device according to the invention in particular in the form of the first mode of realization of the invention, can be inserted in a bag provided with perforations or allowing an easy diffusion of the active ingredient, or the sachet of the device will contain either a rolled up sheet which, after unwinding, will prevent regurgitation of the device, or will be made denser by adding an element of density increase.
• the device then comprises a flexible or deformable sachet containing a support sheet in which an active ingredient is dispersed, said support sheet being designed so as to be able to be brought positively by deformation to a first wound form and to take a second rumen. form by which the device is retained in the rumen.
• the invention therefore also relates to a device as described for the first embodiment of the invention, comprising a flexible or deformable sachet containing a support sheet of the aforementioned type, the sachet and the support sheet being in a wound form with the closure means disposed inside the winding, and the assembly being held in this wound form by means of positive deformation which can be eliminated quickly in the rumen.
• the sheet perforated or provided with perforations can also be wrapped around the device and the assembly included in a bag as described above.
• Regurgitation phenomena can also be avoided by providing the device of the invention, in particular in the second, third and fourth embodiments of the invention in an elongated cylindrical shape, provided with a ballasting element.
• the invention also relates to a system for distributing a substance or several active substances, intended for use in a biological medium, in particular the rumen of an animal, comprising at least two devices arranged one inside the other, each container possibly containing said active substance in addition to at least one other similar container, or the ones contiguous to the others.
• the system comprises a first external device as described above in relation to the first embodiment of the invention, preferably containing an active substance and containing in turn at least one other similar device containing a biologically active substance, preferably different from that contained by the external device or the device (s) - arranged in the external device.
• a biologically active substance of different nature, in particular substances having an incompatibility in terms of chemical and / or physical stability or an incompatibility in pharmacological terms.
• the devices are arranged in a nesting arrangement.
• the system comprises a first external device, containing in addition to an active substance, a device of reduced dimensions, which, in addition to a second active substance containing a third device, of dimensions smaller than that of the second device, etc.
• L either of the systems described above can be designed to provide a sequential release according to the pharmacological, chemical and physical properties of several different active ingredients.
• the active substances can be of different nature, or of the same nature and different dosages. It is thus possible to provide a system of devices arranged one inside the other in a nesting fashion, in which the receptacles of the respective devices contain the same active substance, but in increasing doses, when moving from the outermost system to the most interior. In this way, a release over time of the biological substance will be obtained, so that, when the latter is an anthelmintic, the maximum dose will be released at a selected time, for example at the end of the grazing season
• Nonlimiting examples of active principles with pharmacological activity which can be administered by means of a device and / or a system according to the invention are anthelmintics such as ivermectin, morantel tartrate, levamisole hydrochloride, oxfendazole, etc, douvicides, including rafoxanide, antibiotics and vaccines
• FIG. 1 represents an exploded perspective view of a first embodiment of a device according to the invention representing a container as well as its closing means
• FIG. 2 represents a perspective view of the container according to the first embodiment of the invention kept closed by means of pliers,
• FIG. 3 shows a variant of the closure mode of the clamp of the device according to the first embodiment of the invention
• FIG. 4 shows a system composed of several devices according to the first embodiment of the invention arranged into each other
• FIG. 5 represents a system composed of several devices according to the first embodiment of the invention arranged in a pull-out arrangement
• FIG. 6 represents a perspective view of a second embodiment of a device according to the invention in a form particularly suitable for administration to a ruminant
• FIG. 7 represents an exploded perspective view of a device according to the invention representing a container as well as its method of closing
• - Figure 8 shows a longitudinal view of a third embodiment of a device according to the invention
• FIG. 9 shows an exploded perspective view of part of the device according to the third embodiment
• FIG. 10 shows a biodegradable element in the form of a biodegradable screw
• FIG. 11 shows a longitudinal sectional view of a fourth embodiment of a device according to the invention.
• FIG. 12 shows an elevational view of a fifth embodiment of a device according to the invention, in the closed position
• FIG. 13 shows an elevational view of the device according to the fifth embodiment, in the open position.
• the device 1 shown in Figure 1 comprises a container 2 formed of a flexible waterproof bag, three sides are welded, the fourth 3 being kept open.
• the device also includes a means for temporarily closing the open end 3 of the bag 2.
• This closing means is constituted in this embodiment, by a clamp 4 comprising two branches 5 and 6 connected to one of their ends by a connecting portion 4a forming a hinge to hold the arms 5 and 6 of the clamp in the open position in the absence of an external force.
• Each branch 5 and 6 has on its internal face longitudinal ribs 7.
• a groove 8 extends over the external faces 9 of said branches.
• the open end 3 of the flexible waterproof bag 2 in which the active principle has been placed here a tablet 12, is placed between the open branches 5,6 of the clamp 4. These branches are then tightened one against the other as shown in Figure 2, the ribs 7 'interpenetrating, and held in this configuration by means of a wire of biodegradable suture 13 placed in the groove 8, the two ends of which are connected by means of a knot 14.
• the device is in this form, or after introduction into a perforated bag comprising a rolled up unwound sheet as described above, introduced into the rumen of a bovine in a known manner, using a pistol commonly used for the introduction of boli in the digestive tract of a ruminant.
• the device can also be wound on itself as described below.
• the biodegradable suture 13 In contact with the gastric fluid of the rumen, the biodegradable suture 13 will gradually degrade until it breaks, favored by the tension exerted on the branches 5,6 of the clamp 4, at the desired moment of release of the active principle .
• FIG. 3 represents a variant of the method of fixing the wire of suture 13 on the branches 5,6 of the clamp 4.
• the branches 5,6 each have a bore 15.
• the biodegradable suture thread 13 is introduced into these bores and its ends connected by any means, in particular a knot.
• the arms of the clamp may have a ring at their end, in which case they are held together by means of a wire passing through the two rings, the ends of the wire being connected to one another. by an appropriate means, for example a knot.
• the durations at the end of which a device as described above releases the active principle which it contains will be given below.
• the wires used are all No. 2/0 wires, with a diameter of between 0.30 and
• FIG. 4 represents a distribution system according to the invention comprising a first device 21 as described above, but with a closure member 22 comprising two elements applying one to the other in a sealed manner, both elements being held against each other at each of their ends by a biodegradable thread 23 inserted in a groove 24, and the two ends of which are linked together by means of a biodegradable suture thread 23 as described above.
• This first external device comprises a flexible bag 26 containing an anthelmintic active principle in the form of a tablet 27 as well as two other identical devices 31, 32 and of reduced dimensions compared to the first external device 21.
• the flexible bag 33 of the device 31 comprises for example a tablet 34 of an anthelmintic active principle and the flexible sachet 35 of the device 32, a capsule 36 containing a vaccine in the form of a lyophilisate, these two compounds having an incompatibility on the pharmacological and possibly chemical level.
• one of the devices may contain an acidic anthelmintic, for example levamisole hydrochloride, or strongly basic; another device then containing for example an antibiotic decomposable in an acidic or strongly basic medium.
• an acidic anthelmintic for example levamisole hydrochloride, or strongly basic
• another device then containing for example an antibiotic decomposable in an acidic or strongly basic medium.
• one of the devices may contain an active ingredient in the form of an anion, and another device, an active ingredient in the form of a cation, so as to avoid the formation of a pair. ions.
• FIG. 5 shows another distribution system according to the invention.
• the flexible bag 43 of the device 41 contains a tablet 44 of an anthelmintic active principle to a first dose x 1 and another device 51 identical to the first but of reduced dimensions relative to the latter.
• the flexible bag 52 of this second device 51 contains a tablet 53 of the same anthelmintic active ingredient at a dose x 2 as well as a device 61 identical to the first two and of dimensions even smaller compared to the second device 51 and of which the flexible bag 62 contains a tablet 63 of the same active ingredient at a dose x 3 .
• the biodegradable threads 45, 55, 65 of the various "nesting" devices 41, 51, 61 are preferably designed so as to release their active ingredients respectively in June, preferably at the end of June, July and August.
• the dose x 1 released in June is the lowest; the proliferation of parasites being at its minimum, while the doses x 2 and x 3 are released at the end of July and at the end of August and adapted to the increasing quantities of worms which one finds in the pastures at these times and also to the increase in weight of the animal.
• FIG. 6 represents a device according to the invention in a form particularly suitable for administration to a ruminant, in particular a bovine.
• This device 71 comprises a deformable sachet 72 enclosing a support sheet 73 of a polymer material insoluble in water in which a drug is dispersed.
• the support sheet is designed so that it can be brought positively by deformation to a first wound form.
• the dimensions of the support sheet 73 are slightly smaller than those of the deformable bag 72.
• the device also comprises a clamp 74, the arms 75 and 76 of which enclose the open end 77 of the deformable bag 72 and are held one against the other using a suture thread 78 closed using 'a node 79.
• the support sheet 73 in which the active ingredient is dispersed is introduced into the bag 72 and the open end of the latter closed by means of the clamp 74; the assembly is then brought by positive deformation, for example by heating the support sheet to a temperature sufficient to soften the polymer, but not to decompose the medicament, in the wound form shown in FIG. 6, so that the clamp 74 is located inside the rolled form.
• the assembly can be kept in this position, by an appropriate means, for example one or two strips of gummed paper 81, 82 carrying a water-soluble adhesive or one or two strips of a water-soluble polymer, in particular gelatin.
• an appropriate means for example one or two strips of gummed paper 81, 82 carrying a water-soluble adhesive or one or two strips of a water-soluble polymer, in particular gelatin.
• the paper strips peel off or the gelatin dissolves and the device is unwound to leave its first form under the influence of the elasticity of the support sheet and take a second, substantially planar form, by which the device is retained in the bovine stomach.
• the polymeric support sheet in which the medicament is dispersed is, for example, of the type described in patent EP-010 967.
• FIG 7 a second embodiment is shown 'embodiment of a dispensing device according to the invention.
• This device comprises a container designated as a whole by the reference 81 and formed by a rigid cup 82 of cylindrical shape, one end 82a of which is closed and the other end of which 82b is open.
• the cup 82 comprises at its open end 82b and on its external face a thread 83.
• the container 81 also includes a means for temporarily closing the open opening 82b of the cup 82.
• This temporary closing means consists of a thin washer 84 having an external diameter substantially equal to that of the cup 82 and pierced with a central orifice 85, preferably of frustoconical shape.
• the top of the truncated cone delimited by the central orifice 85 is directed towards the interior of the cup 82.
• the temporary closure means further comprises a plug 86 of a shape complementary to the central orifice 85 of the washer.
• the temporary closing means also comprises a ring 87 whose external diameter is substantially equal to the external diameter of the cup 82.
• This ring 87 has a central bore 88 inside which is fixed the biodegradable element 89 which maintains the plug 86 in the central opening 85 when the container 81 is closed, as will be seen later.
• the biodegradable element 89 is formed by a biodegradable wire, the ends of which are fixed to two diametrically opposite points of the bore 88 of said ring 87.
• the temporary closure means comprises a ring 90 provided at one of its ends with an orifice 91 and comprising on its internal face a thread, not shown, intended to cooperate with the external thread 83 of the cup 82.
• the assembly formed by the washer 84, the plug 86 and the ring 87 holding said plug 86 on the central orifice 85 is positioned on the open end 82b of the cup 82 and this assembly is held on said open end 82b by the ring 90 which is screwed onto the cup 82.
• a tablet 92 containing an active ingredient is placed in the cup 82, on which the washer are successively placed
• biodegradable wire 89 The choice of the nature and the dimensions of the biodegradable wire 89 are determined by the time after which it is desired to degrade said wire 89 and release the active ingredient from the tablet.
• the plug 86 following the movements of the medium in which it is placed, for example, the movements of the animal, then release the orifice 85, into which the surrounding liquid medium penetrates by causing the release therein of active ingredient in container 81.
• this container 81 Preferably, the various elements constituting this container 81 are made of a plastic or metallic material.
• the container of the dispensing device is formed by a cylinder designated as a whole by the reference 100 comprising at one of its ends a ballast element 101 and at the other of its ends a plug 102 provided with perforations 103.
• the free end of the ballast element 101 has a frustoconical shape.
• the cylinder 100 has several compartments, respectively A, B, .... N which may each contain an active substance. These compartments A, B, ... N communicate with each other and are each closed by means of temporary closure. With particular reference to FIG. 9, a compartment of the cylinder 100 will be described, the other compartments being identical.
• Each compartment is formed by a sleeve 104 provided at one of its ends with an external thread 104a and at the other of its ends with an internal thread 104b.
• the sleeve 104 has internally, substantially in its middle part, an internal rim 104c intended to receive the means for temporarily closing the corresponding compartment.
• This means of temporarily closing each compartment comprises a washer 105 pierced with a central orifice 106 of frustoconical shape and a plug 107 of form complementary to said central orifice 106.
• the temporary closing means also comprises a ring 108 comprising a biodegradable wire 109 intended to hold the plug 107 in the orifice 106 of the corresponding washer 105.
• the washer 105 and the ring 108 are kept applied to the rim 104c of the corresponding socket 104 by the lower edge of the threaded end 104a of the adjacent socket 104
• a seal 1 10 and a ring 1 1 1 are interposed between the ring 108 and the lower edge of the threaded end 104a of the corresponding sleeve 104.
• the threaded end 1 04a of the sleeve 104 of the lower compartment N is intended to be screwed into the ballast element 101 and the upper threaded end 104b of the sleeve
• the various elements making up the cylinder 100 of the dispensing receptacle are preferably made of plastic or metallic material.
• the perforations 103 of the cover 102 allow the passage of the biological liquid medium in which the release system is disposed and these perforations 103 are of sufficiently small dimensions not to allow fibers or other solid elements which are found in the surrounding medium to pass through and which could hinder the release of the active substance in each compartment.
• the upper compartment A of the device does not contain tablets containing an active principle, so that, if necessary, the animal has time to acquire a certain protective immunity before the quantity of parasitic worms becomes too important.
• the liquid biological medium enters the first compartment A via the perforations 103 and this biological medium will, at the end of the scheduled time, degrade the biodegradable wire 109 of said first compartment A so as to cause the release of the plug 107 closing the orifice 106 for communication with the second compartment B of the device.
• the biological fluid from the surrounding medium can then penetrate inside the next compartment B and cause the disintegration of the tablet 1 12 disposed inside this compartment B and cause the release into the surrounding biological medium of the active ingredient contained in this tablet 1 12.
• each compartment can take place at regular or irregular intervals depending on the nature and thickness of the biodegradable wire or wires 109.
• Each compartment may contain the same active ingredient at identical or different doses, for example progressively higher or else contain active ingredients depending on the pharmacological activity or the pharmacological kinetics sought.
• each compartment can be closed by a plug having the shape of a screw 1 13 as shown in FIG. 10
• the container is formed by an envelope 120 of elongated shape made of impermeable material and biologically non-degradable and comprising at at least one of its ends an opening
• the envelope 120 contains a matrix 121 of shape complementary to said envelope 120
• This matrix 121 is formed of a resin in which are distributed particles of a material of high density and particles of the active substance.
• the opening of the envelope 120 is maintained in the closed state by a biodegradable element
• the envelope 120 has at each of its ends an opening 122 and the matrix 120 has a passage 123 extending over the entire length of said matrix 121 and is arranged in the axis of said openings 122.
• each opening 122 is temporarily closed by a plug 124 comprising a first cylindrical portion 124a of diameter slightly greater than the diameter of the opening 122 and a second cylindrical portion 124b of diameter slightly less than the diameter of l opening 122
• the second part 124b is designed to fit into the corresponding opening 122 and temporarily close it
• the plugs 124 are held in place in the openings 122 by the tension exerted by the biodegradable element which is, in this case, constituted by a wire 125 having the shape of a loop.
• This biodegradable wire 125 extends over the entire length of the recess 123 and passes through the plugs 124 at two different points by forming a rounded end 125a protruding from each plug 124 and accessible to degradation by the surrounding biological medium.
• the biodegradable wire 125 is designed to break at one or its two rounded ends 125a, after a predetermined time under the action of the surrounding biological liquid medium. The tension exerted by the wire 125 is then released and the plugs 124 released from the openings 122.
• the biological liquid can then enter the passage 123 formed in the matrix 121 and the particles of active principle be released at a speed which is a function of the distance at which they are located with respect to the central longitudinal axis of the passage 123.
• the plugs 124 are made, for example, of rubber or silicone.
• the biodegradable wire can form a loop along the external contour of the envelope 120.
• the biodegradable wire 123 connects each plug 124 by passing through it transversely.
• the casing 120 comprises at least one opening 122 temporarily closed by a biodegradable screw 1 13 as shown in Figure 10.
• the corresponding orifice 122 comprises internal thread.
• Figures 12 and 13 show a fifth embodiment of the dispensing device according to the invention.
• the container is formed by a cylindrical casing 130 comprising two half-shells, respectively 131 and 132.
• 131 and 132 extends along the longitudinal axis of the envelope 130.
• the half-shells 131 and 132 are articulated at one of their ends by a portion 133 forming a hinge and each have at its end opposite to that comprising the portion 133, an eyelet 134.
• the half-shells 131 and 132 are held in the closed position by a biodegradable wire 135 passing through the eyelets 134.
• the envelope 130 contains a delay form, comprising a matrix in which an active ingredient is placed, the matrix being provided for a prolonged release of the active ingredient.
• Such a delay form may consist of the delay form 121 described in relation to FIG. 11.
• the devices and systems according to the invention can be used in the rumen of ruminants as described above, in particular cattle, sheep, goats.
• the biological environment can be an aquatic environment such as a river, a pond, an aquarium, a water trough.
• the devices and systems according to the invention also have sanitary applications, in particular for the delayed release over time of disinfectants, bacteria, etc.

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• Health & Medical Sciences (AREA)
• Engineering & Computer Science (AREA)
• Mechanical Engineering (AREA)
• Life Sciences & Earth Sciences (AREA)
• Epidemiology (AREA)
• Chemical & Material Sciences (AREA)
• Medicinal Chemistry (AREA)
• Pharmacology & Pharmacy (AREA)
• Physiology (AREA)
• Nutrition Science (AREA)
• Animal Behavior & Ethology (AREA)
• General Health & Medical Sciences (AREA)
• Public Health (AREA)
• Veterinary Medicine (AREA)
• Biodiversity & Conservation Biology (AREA)
• Medicinal Preparation (AREA)

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• 1996
  • 1996-10-21 FR FR9612761A patent/FR2754711B1/fr not_active Expired - Lifetime
• 1997
  • 1997-10-20 US US09/284,838 patent/US6416781B1/en not_active Expired - Fee Related
  • 1997-10-20 EP EP97911305A patent/EP0936904A1/de not_active Withdrawn
  • 1997-10-20 JP JP51904298A patent/JP2001508325A/ja active Pending
  • 1997-10-20 AU AU48729/97A patent/AU737586B2/en not_active Expired
  • 1997-10-20 WO PCT/FR1997/001880 patent/WO1998017259A1/fr not_active Application Discontinuation

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