[go: up one dir, main page]
More Web Proxy on the site http://driver.im/

EP0827419A1 - Device and process for mixing a pharmaceutical composition with another agent and method for oral administration of the pharmaceutical preparation - Google Patents

Device and process for mixing a pharmaceutical composition with another agent and method for oral administration of the pharmaceutical preparation

Info

Publication number
EP0827419A1
EP0827419A1 EP96912371A EP96912371A EP0827419A1 EP 0827419 A1 EP0827419 A1 EP 0827419A1 EP 96912371 A EP96912371 A EP 96912371A EP 96912371 A EP96912371 A EP 96912371A EP 0827419 A1 EP0827419 A1 EP 0827419A1
Authority
EP
European Patent Office
Prior art keywords
chamber
rod
hollow body
plunger
agent
Prior art date
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.)
Withdrawn
Application number
EP96912371A
Other languages
German (de)
French (fr)
Inventor
Seppo Arento
Hakan Glad
Tore Kers
Mats Ruden
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.)
AstraZeneca AB
Original Assignee
Astra AB
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 Astra AB filed Critical Astra AB
Publication of EP0827419A1 publication Critical patent/EP0827419A1/en
Withdrawn legal-status Critical Current

Links

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61JCONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
    • A61J1/00Containers specially adapted for medical or pharmaceutical purposes
    • A61J1/14Details; Accessories therefor
    • A61J1/20Arrangements for transferring or mixing fluids, e.g. from vial to syringe
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61JCONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
    • A61J7/00Devices for administering medicines orally, e.g. spoons; Pill counting devices; Arrangements for time indication or reminder for taking medicine
    • A61J7/0015Devices specially adapted for taking medicines
    • A61J7/0038Straws
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01FMIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F33/00Other mixers; Mixing plants; Combinations of mixers
    • B01F33/50Movable or transportable mixing devices or plants
    • B01F33/501Movable mixing devices, i.e. readily shifted or displaced from one place to another, e.g. portable during use
    • B01F33/5011Movable mixing devices, i.e. readily shifted or displaced from one place to another, e.g. portable during use portable during use, e.g. hand-held
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01FMIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F33/00Other mixers; Mixing plants; Combinations of mixers
    • B01F33/50Movable or transportable mixing devices or plants
    • B01F33/501Movable mixing devices, i.e. readily shifted or displaced from one place to another, e.g. portable during use
    • B01F33/5011Movable mixing devices, i.e. readily shifted or displaced from one place to another, e.g. portable during use portable during use, e.g. hand-held
    • B01F33/50112Movable mixing devices, i.e. readily shifted or displaced from one place to another, e.g. portable during use portable during use, e.g. hand-held of the syringe or cartridge type
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01FMIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F35/00Accessories for mixers; Auxiliary operations or auxiliary devices; Parts or details of general application
    • B01F35/71Feed mechanisms
    • B01F35/713Feed mechanisms comprising breaking packages or parts thereof, e.g. piercing or opening sealing elements between compartments or cartridges
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01FMIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F2101/00Mixing characterised by the nature of the mixed materials or by the application field
    • B01F2101/22Mixing of ingredients for pharmaceutical or medical compositions

Definitions

  • the invention relates to a device for mixing a pharmaceutical, preferably dry and granular, composition, with another, preferably fluid, agent to a preparation, preferably a gel, in accor ance with the preamble of claim 1.
  • the major problem forming the basis for the present invention relates to the handling, the storage and the administration of a pharmaceutical composition to be mixed with another agent, that may adversely affect the stability of the composition to form a preparation suited for administration to a living being, especially an animal.
  • such preparations e.g. comprising a mixture of a pharmaceutical composition and a consistency forming agent
  • a consistency forming agent will have a sho ⁇ storage stability. Therefore, the components comprised in those preparations must be kept isolated from each other until a short time before use, when they are mixed with each other to form the desired preparation.
  • the most common prior solution is a syringe of the kind disclosed in the US-A-3 340 873, having a plunger, slidably accommodated in a cylindrical body.
  • the two components to be mixed are contained in two different compartments, isolated from each other by a thin diaphragm. Shortly before the preparation is to be used, the diaphragm is ruptured or pierced, so that a communication is established between the two compartments.
  • the syringe, with the mixture is then shaken to form a homogenous preparation. After this operation a cap is removed to open a passage and the content is expelled through a needle by depressing the plunger.
  • compositions comprising a proton pump inhibitor, such as omeprazole, which degrades during long term storage in the presence of moisture.
  • a proton pump inhibitor such as omeprazole
  • DK Patent Specification 112 893 filed July 25, 1966 discloses an injection syringe for the injection of a pharmaceutical composition, that can not be stored in solution for a longer period of time without detrimental effects.
  • the syringe basically corresponds to a standard syringe, the main difference being that the opening in the needle fitting is sealed by a diaphragm.
  • the composition is contained in the syringe in dry form.
  • a double ended injection needle is mounted on the needle fitting, one end of the needle piercing the diaphragm. Solvent is aspirated into the syringe through the needle. Then the syringe is shaken and the resulting solution is injected through the needle.
  • a drawback with this type of syringe is that the filling operation is rather complex, it requires the mounting of a double-ended injection needle for piercing the diaphragm. Furth ⁇ ermore, after the rupture of the diaphragm, the rnixing chamber will be open to the air, so that care must be taken during the shaking operation to prevent the mixture from leaking out through the needle. Further, because of the .ligh flow resistance of the syringe due to the narrow passages therein, in particular in the needle, it could not be used for viscous, pasty or gel-like preparations. Moreover, this known apparatus is not suited for oral admini ⁇ stration because of the needle. Furthermore, the manufacturing costs for the syringe will be relatively high.
  • An object of the invention is to obviate the disadvantages of the prior art by providing a mixing device, in which a pharmaceutical composition may be stored for a longer period of time and to which a desired agent easily and rapidly can be added immediately before the administration of the preparation. After addition of the agent the device also should be capable of being vigorously shaken without leaking. Furthermore, the manufacturing cost for the device of the invention should be relatively low.
  • a package or a seal which protects the prefilled chamber against moisture during storage first has to be removed. Then the agent to be mixed with the composition contained in the chamber is supplied, the fluid agent being separated from the chamber by the flexible sealing member. Then the plunger is displaced in opposite direction to the expel direction causing an expansion of the closed chamber defined by the plunger, the side wall portion and the closure, thereby creating a vacuum in the chamber. Initially, the pressure differential over the sealing member will be too low to flex it, but when the plunger continues to be displaced the vacuum in the chamber gradually increases so that the sealing member deforms and looses its contact with the wall, thereby establishing a communication into the chamber. Th agent will then be aspirated into the chamber.
  • the device When the required amount of agent has been drawn into the chamber and the flexible sealing member has flexed back to its rest position, the device is shaken until the preparation is ready for administration. Just before the administration is to be carried out, the closure to the chamber is removed and the device is inserted in for example the mouth of a horse. The content of the device is now expelled by depressing the plunger.
  • Fig. 1 is an axial section of a first preferred embodiment of the invention.
  • Fig. 2 shows the encircled portion in Fig. 1 at a larger scale
  • Fig. 3 is a cross- section along the line HI- HI in Fig. 1,
  • Fig. 4 is an axial section of a further embodimenL which is slightly modified in relation to that of Figs 1-3,
  • Fig. 5 shows the encircled portion of Fig. 4 at a larger scale
  • Fig. 6 is a section along the line VI- VI of Fig. 4,
  • Fig. 7 shows a part of a slight modification of the embodiment of Fig. 4 at a larger scale
  • Fig. 8 is an axial section of still another embodiment of the invention.
  • Fig. 9 is a section along the line D -IX of Fig. 8,
  • Fig. 10 shows the encircled portion of Fig. 8 at a larger scale
  • Fig. 11 discloses a slight modification of the embodiment of Figs 8-10.
  • the syringe- like device of the first preferred embodiment of the in- vention comprises a tubular, elongated, cylindrical hollow body 2, which is open at both ends.
  • the lower end in Fig. 1 is the outlet end 4.
  • a plunger 6 is inserted through the open upper end 10.
  • a flange portion or a finger grip portion 13 extends substantially per ⁇ pendicular to the longitudinal direction of the hollow body 2 around the upper end thereof.
  • the outlet end 4 is closed by a removable lid 12, which has a groove 14, having a diameter corresponding to that of the side wall 8 of the hollow body 2.
  • the groove 14 is constructed with a depth to provide an airtight seal with the lower end 4 of the cylindrical body into the interior of the hollow body 2.
  • the lid 12 has a radially extending lug 16 to facilitate the removal of the lid 12 when the preparation is to be expelled.
  • the plunger 6 is comprised by two parts 18, 20.
  • a support means 18 in the form of a flat web, which extends diametrically, perpendicularly to the axis of the hollow body 2 and a sealing member 20 in the shape of a thin, flexible disc, which when unloaded is sized to sealingly contact the inner wall 8 of the hollow body 2, thereby isolating the spaces on each side of the sealing member 20 from each other.
  • the disc 20 is at the centre provided with a peg 22, having a compressible bulged end portion 24, while the web 18 has a centre aperture 26 having a diameter less than that of the bulge portion 24.
  • the shank 28 of the peg 22 is adapted to the thickness of the web 18, so that the peg 22 may be snapped into the aperture 26, so that the disc 20 will lie close to the web 18.
  • a rod 30 is made integral with the plunger 6. Its external diameter is somewhat smaller than the internal diameter of the hollow body 2, so that the rod 30 is slidably guided therein.
  • the rod 30 is tubular, and its annular end portion 32 is made in one piece with the web 18. The end face ⁇ f said portion 32 flushes with the end face (the lower face in Fig. 1) of the web 18.
  • a radially extending finger grip 23 is provided at the open end 40 of the rod 30 .
  • the flexible disc 20 is made of a resilient material and will deflect, when subjected to a sufficiently large force and return to its original position upon the removal of said force.
  • a closed chamber 38 is defined by the lid 12 or other seal, the flexible disc 20 and the inner wall 8 of the hollow body, the volume of said chamber being variable due to the axially displaceable plunger 6.
  • the unloaded disc 20 rests against the web 18 and the annular end portion of the rod 30.
  • the edge portion 34 of the disc 20 is prevented from flexing upwards by the web 18 and the annular end portion 32.
  • the edge portion 34 is allowed to flex downwardly. If this occurs the edge portion 34 will loose its sealing contact with the inner wall 8 of the hollow body 2, thereby opening a communication at the wall 8 between the upper and lower sides of the flexible disc 20.
  • the disc 20 thus functions as a non-return valve.
  • any method for fixing the resilient disc 20 to the rod 30 may be used.
  • a keyhole connection could be used.
  • a keyhold aperture is then provided at the bottom end of the rod 30 and, the peg 22 of the sealing disc 20 then being introduced through the wider opening of the keyhole and then being pushed into the narrower slit of the keyhole.
  • the flexible disc 20 may be provided with a shank portion at the center thereof which portion then is introduced in an aperture provided at the lower end of the rod 30. The end of shank is then heatened to a softening temperature and thereupon flattened to form a rivet joint- like connection.
  • the rod 30 is tubular and has an open bottom and, which normally is sealed by the flexible disc 20.
  • the interior 36 of the rod 30 and the disc 20 form a filling compartment for the agent to be mixed with a composition contained in the chamber.
  • composition for the device is described in WO/SE94/25070.
  • the pharmaceutical composition is constituted by beads of an active substance, such as enteric coating layered omeprazole pellets mixed with a gelforming agent such as xanthan gum, guar gum, locust bean gum. tragacanth, modified cellulose derivates or similar, to which mixture of dry components a fluid agent such as for instance water later is added for forming a viscous gel.
  • a gelforming agent such as xanthan gum, guar gum, locust bean gum.
  • tragacanth modified cellulose derivates or similar, to which mixture of dry components a fluid agent such as for instance water later is added for forming a viscous gel.
  • a fluid agent such as for instance water later is added for forming a viscous gel.
  • a suitable dosage of a dry mixture of enteric coating layered omeprazole pellets and a gelforming agent is filled into the chamber 38.
  • a buffering or pH-adjusting agent such as citric acid may optionally be added to prevent premature dissolution of the enteric coated beads when water later is added to the composition.
  • This operation could be carried out in two ways, either the plunger 6 is placed in a suitable position in the hollow body 2 with the lid 12 removed, the filling then taking place through the lower end 4, or the lid 12 is applied on the lower end 4 with the plunger 6 removed, the filling then taking place via the upper opening 10.
  • the quantity or the volume of the mixture is optional within certain limits, since the volume of the chamber 38 is variable because of the axially displaceable plunger 6.
  • the hollow rod 30 in an advantageous manner serves as a metering device for the agent to be added to the chamber 38. It is transparent and preferably provided with gradation lines, so that the agent to be added precisely could be measured with the device. Superfluous agent may be poured off from the rod 30 before the rod 30 has been displaced to open a communication into the chamber 38.
  • a very precise measuring of the agent to be added can be made without the need of any additional means than the syringe itself.
  • the content in the chamber must be protected against penetrating moisture, which else would accumulate in the gelfo ⁇ riing agent to sooner or later cause degradation of the omeprazole during long-term storage. Therefore, after the filling operation, the device is enclosed in a moisture tight envelope, preferably having a moisture barrier made of aluminium, but other materials fulfilling the same purpose are of course also conceivable.
  • a siccative preferably in a small bag, is enclosed in the envelope as a further protection against moisture.
  • the device When to be used, the device is taken out from the moisture tight package or the seal on top of the tubular rod 30 is removed. A suitable quantity of water to be added to the mixture within the chamber 38 is then filled into the tubular compartment of the rod 30 up to a desired level (marked by a gradation line or level mark). The plunger 6 is then displaced upwardly, thus creating a vacuum in the chamber 38. After a sufficient displacement, the vacuum will be so strong therein, that the flexible disc 20 will flex downwards, the circumferential edge 34 of the flexible disc 20 loosing its sealing contact with the inner wall 8, so that a communication is established from the compartment 36 into the chamber 38, so that the water in the compartment 36 of the rod 30 will be aspirated into the chamber 38.
  • the disc 20 When the water has been transferred thereto, the disc 20 will flex back to its rest position and the device is then shaken until a viscous gel containing the omeprazole pellets has been formed. During the shaking operation, the mixture is prevented by the flexible disc 20 to leak into the compartment 36.
  • the mixture could be stored in the device for a short period of time before administration. Just before administration the lid 12 is removed and the device is placed, where the preparation is to be administered. The preparation is then expelled by depressing the rod 30.
  • the rod 30 has such an axial length, that when fully depressed, all of the preparation is expelled from the device.
  • the flexible disc 20 has an even surface to expel the composition completely, thereby avoiding the risk for any residues, pellets or gel, being left in openings or slits, which could happen with a slitted disc.
  • a tear-off or a rupturable seal could be provided to seal the chamber 38.
  • Fig. 4 demonstrates a slight modification of the embodiment of Figs 1-3.
  • the tubular rod 30a has two opposed longitudinal slits 42, which extend from the bottom portion of the rod 30a up to about half the height of the rod 30a, thereby providing a communication between the interior 36a of the rod 30a and the upper side of the disc 20a.
  • the bottom portion comprises an aperture 26a in the centre, which functions in a similar way as the aperture 26 in the embodiment of Fig. 1.
  • the bottom portion of the rod 30 is circular and provides a support for the middle portion of the flexible disc 20a.
  • the sealing member 20'a is integral with the rod 30'a and consists of an annular flexible ring, see Fig. 7.
  • the advantage of this embodiment is that it only requires a single operation in the manufacture of the rod 30'a and the sealing member 20'a.
  • the upper part of the rod 30b is tubular, while the lower part 46 thereof has a section in the shape of a cross, as clearly could be seen in Fig. 9.
  • the lower part consists of two longitudinally extending, pe ⁇ endicular wall portions 48, 50, which extend from the bottom portion of the rod 30b up to about half the height of the rod 30b.
  • the cross-shaped portion 46 includes a first part having a constant section to provide sufficient stiffness and guidance against the inner wall 8.
  • the following part 56 tapers downwards towards the bottom portion, which in turn comprises an annular rim 60 to support the flexible disc 20b and prevent it from being flexed upwardly.
  • the bottom portion also includes an aperture 62, into which the bulge 24b of the flexible disc 20b is snapped (cf. Fig. 10).
  • FIG. 11 A modification of the Figs. 8-10 embodiment is shown in Fig. 11.
  • the flexible sealing member 34'b is integral with the rod 30b. which has a radially protruding annular rim 60', which is prolonged by a thinner flexible annular edge 34'b in sealing contact with the inner wall 8 of the hollow body 2.
  • the water to be added is introduced as before through the open end 40 of the rod 30b but in opposition to the previously described embodiments the water will not be contained in a lower tubular portion of the rod. but will rise along the cross-shaped portion up to a desired level.
  • the cross-shaped portion could be provided with coloured lines to indicate the volume levels.
  • the rod must not be transparent but can be made in an appropriate colour.
  • a fluid agent preferably water
  • water is filled into the upper end 40 of the rod 30, which water then flows through the opening provided in the rod and subsequently reaches the upper side of the flexible sealing member.
  • the sealing member prevents the water from reaching the chamber 38.
  • the rod will then be displaced backwards, thereby creating a vacuum in the chamber 38.
  • the combined action of the weight of the water and the vacuum will flex the sealing member downwards, so that water will be aspirated into the chamber 38.
  • said member will flex back to its original rest position and seal off the chamber 38.
  • the sealing member is a separate constructional detail, it offers a great freedom in the choice of material.
  • the material in the sealing mem er can be chosen to have optimal sealing and elastic properties, w hue the material in the rod can be chosen to provide sufficient stiffness and support for the sealing member. If the rod and the sealing member are made integral, the choice of material must be a compromise between required stiffness of the rod and needed flexibility and elasticity of the sealing member. However, this latter solution offers advantages as regards manufacturing costs.
  • all the elements can be made of polymeric materials, such as for instance polyethylene, polypropylene, polyester, elastomer, polycarbonate, rubber or silicone, and manufactured by conventional and cheap methods, such as injection moulding. Moreover, all the details have a simple construction and are easy to assemble. Consequently, the devices can be produced at a low cost
  • the lid 12 is provided with an radially protruding lug 16, which extends around a part of the circumference of the lid 12 and forms a grip portion for facilitating the removal of said element
  • the grip portion may have any suitable configuration. For example, it could be oval, or it could be constituted by a protruding flange extending over the whole circumference of the lid.
  • the devices are in particular suited for oral administration to an animal, especially a horse, in particular of an aqueous gel containing a formulation of a proton pump inhibitor e.g. omeprazole or a similar composition.
  • a proton pump inhibitor e.g. omeprazole or a similar composition.
  • the use of the device is not restricted to this field, since it can be used for rnixing various kinds of pharmaceutical compositions with other agents, and for oral, rectal or any other suitable administration to many different kinds of living beings, including humans.
  • compositions in the sense of this application does not solely mean a drug, also other kinds of beneficial agents, for instance essential nut ⁇ rients are intended to be included by this expression.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Infusion, Injection, And Reservoir Apparatuses (AREA)
  • Medical Preparation Storing Or Oral Administration Devices (AREA)
  • Package Specialized In Special Use (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Device for mixing a pharmaceutical composition stored in a chamber (38) in said device with an agent to be added shortly before administration to form a preparation to be administered. The device should be capable of being shaken without leaking. It comprises a hollow body (2) having an outlet (4), sealed by a removably closure (12) and a plunger (6), which includes a flexible sealing member (20) having a circumferential edge in sealing contact with the inner wall (8) of the hollow body. The plunger (6), the hollow body (2) and the removable closure (12) define said chamber (38). A hollow rod (30) is connected to the plunger (6) for displacing the same in the hollow body (2) and includes at least one opening, which communicates with the interior of the rod (30) with the upper side of the flexible member (20). The flexible member (20) is supported on the plunger (6), so that it can only flex downwards. At a predetermined pressure differential over the upper side and the lower side of the flexible member (20) the flexible member will flex downwards to open a communication at the inner wall (8) of the hollow body into the chamber (38), so that said agent flows into the chamber (38).

Description

Device and process for mixing a pharmaceutical composition with another agent and method for oral administration of the pharmaceutical preparation.
Technical Field
The invention relates to a device for mixing a pharmaceutical, preferably dry and granular, composition, with another, preferably fluid, agent to a preparation, preferably a gel, in accor ance with the preamble of claim 1.
Background of the Invention
The major problem forming the basis for the present invention relates to the handling, the storage and the administration of a pharmaceutical composition to be mixed with another agent, that may adversely affect the stability of the composition to form a preparation suited for administration to a living being, especially an animal.
It is well known in the veterinary art to administer pharmaceutical compositions in the form of paste-like preparations to horses by means of a syringe-like device. The syringe is then inserted into the mouth of the horse and the preparation is expelled onto the root of the tongue. The viscous nature of the preparation and the placing thereof in the back of the mouth makes it difficult for the horse to spit out the preparation.
In some cases such preparations, e.g. comprising a mixture of a pharmaceutical composition and a consistency forming agent, will have a shoπ storage stability. Therefore, the components comprised in those preparations must be kept isolated from each other until a short time before use, when they are mixed with each other to form the desired preparation.
There exists a plurality of solutions to the problem of storing and mixing two components to a preparation, which can not be stored for a longer period of time after mixing. The most common prior solution is a syringe of the kind disclosed in the US-A-3 340 873, having a plunger, slidably accommodated in a cylindrical body. The two components to be mixed are contained in two different compartments, isolated from each other by a thin diaphragm. Shortly before the preparation is to be used, the diaphragm is ruptured or pierced, so that a communication is established between the two compartments. The syringe, with the mixture is then shaken to form a homogenous preparation. After this operation a cap is removed to open a passage and the content is expelled through a needle by depressing the plunger.
This kind of prior art has in most cases proved satisfactory and reliable and is moreover relatively easy to manufacture, e.g. by plastics injection moulding, at a low cost
However, the above syringe is not suitable for the administration of a gel, primarily because of the presence of the needle. But apart from this, generally, mixing devices having two compartments isolated from each other by a thin diaphragm of rubber or plastics could not be used for certain kinds of moisture sensitive pharmaceutical compositions. An example of such a composition is compositions comprising a proton pump inhibitor, such as omeprazole, which degrades during long term storage in the presence of moisture. The always present molecular migration through a rubber or a plastics diaphragm would be sufficient to cause degradation of such sensitive compositions during long term storage.
Thus, conventional two compartments mixing devices are unsuitable for such compositions.
DK Patent Specification 112 893 filed July 25, 1966, discloses an injection syringe for the injection of a pharmaceutical composition, that can not be stored in solution for a longer period of time without detrimental effects. The syringe basically corresponds to a standard syringe, the main difference being that the opening in the needle fitting is sealed by a diaphragm. The composition is contained in the syringe in dry form. When the syringe is to be used, a double ended injection needle is mounted on the needle fitting, one end of the needle piercing the diaphragm. Solvent is aspirated into the syringe through the needle. Then the syringe is shaken and the resulting solution is injected through the needle.
A drawback with this type of syringe is that the filling operation is rather complex, it requires the mounting of a double-ended injection needle for piercing the diaphragm. Furth¬ ermore, after the rupture of the diaphragm, the rnixing chamber will be open to the air, so that care must be taken during the shaking operation to prevent the mixture from leaking out through the needle. Further, because of the .ligh flow resistance of the syringe due to the narrow passages therein, in particular in the needle, it could not be used for viscous, pasty or gel-like preparations. Moreover, this known apparatus is not suited for oral admini¬ stration because of the needle. Furthermore, the manufacturing costs for the syringe will be relatively high.
Object of the Invention
An object of the invention is to obviate the disadvantages of the prior art by providing a mixing device, in which a pharmaceutical composition may be stored for a longer period of time and to which a desired agent easily and rapidly can be added immediately before the administration of the preparation. After addition of the agent the device also should be capable of being vigorously shaken without leaking. Furthermore, the manufacturing cost for the device of the invention should be relatively low.
This object of the invention is attained at by a device in accordance with the preamble of claim 1, which includes the features of the characterizing part of claim 1.
Further independent claims define processes using the device for rnixing a pharmaceutical preparation and methods for administration of a mixed preparation by means of the device.
When to be used for administration of the preparation, a package or a seal which protects the prefilled chamber against moisture during storage first has to be removed. Then the agent to be mixed with the composition contained in the chamber is supplied, the fluid agent being separated from the chamber by the flexible sealing member. Then the plunger is displaced in opposite direction to the expel direction causing an expansion of the closed chamber defined by the plunger, the side wall portion and the closure, thereby creating a vacuum in the chamber. Initially, the pressure differential over the sealing member will be too low to flex it, but when the plunger continues to be displaced the vacuum in the chamber gradually increases so that the sealing member deforms and looses its contact with the wall, thereby establishing a communication into the chamber. Th agent will then be aspirated into the chamber. When the required amount of agent has been drawn into the chamber and the flexible sealing member has flexed back to its rest position, the device is shaken until the preparation is ready for administration. Just before the administration is to be carried out, the closure to the chamber is removed and the device is inserted in for example the mouth of a horse. The content of the device is now expelled by depressing the plunger.
Description of preferred embodiments
Preferred embodiments of the invention will now be described by way of example with reference to the drawings, in which:
Fig. 1 is an axial section of a first preferred embodiment of the invention.
Fig. 2 shows the encircled portion in Fig. 1 at a larger scale,
Fig. 3 is a cross- section along the line HI- HI in Fig. 1,
Fig. 4 is an axial section of a further embodimenL which is slightly modified in relation to that of Figs 1-3,
Fig. 5 shows the encircled portion of Fig. 4 at a larger scale, Fig. 6 is a section along the line VI- VI of Fig. 4,
Fig. 7 shows a part of a slight modification of the embodiment of Fig. 4 at a larger scale,
Fig. 8 is an axial section of still another embodiment of the invention,
Fig. 9 is a section along the line D -IX of Fig. 8,
Fig. 10 shows the encircled portion of Fig. 8 at a larger scale, and
Fig. 11 discloses a slight modification of the embodiment of Figs 8-10.
As shown in Fig. 1. the syringe- like device of the first preferred embodiment of the in- vention, comprises a tubular, elongated, cylindrical hollow body 2, which is open at both ends. The lower end in Fig. 1 is the outlet end 4. A plunger 6 is inserted through the open upper end 10. A flange portion or a finger grip portion 13 extends substantially per¬ pendicular to the longitudinal direction of the hollow body 2 around the upper end thereof. The outlet end 4 is closed by a removable lid 12, which has a groove 14, having a diameter corresponding to that of the side wall 8 of the hollow body 2. The groove 14 is constructed with a depth to provide an airtight seal with the lower end 4 of the cylindrical body into the interior of the hollow body 2. The lid 12 has a radially extending lug 16 to facilitate the removal of the lid 12 when the preparation is to be expelled.
As best can be seen in Fig. 2, the plunger 6 is comprised by two parts 18, 20. a support means 18 in the form of a flat web, which extends diametrically, perpendicularly to the axis of the hollow body 2 and a sealing member 20 in the shape of a thin, flexible disc, which when unloaded is sized to sealingly contact the inner wall 8 of the hollow body 2, thereby isolating the spaces on each side of the sealing member 20 from each other. The disc 20 is at the centre provided with a peg 22, having a compressible bulged end portion 24, while the web 18 has a centre aperture 26 having a diameter less than that of the bulge portion 24. The shank 28 of the peg 22 is adapted to the thickness of the web 18, so that the peg 22 may be snapped into the aperture 26, so that the disc 20 will lie close to the web 18.
A rod 30 is made integral with the plunger 6. Its external diameter is somewhat smaller than the internal diameter of the hollow body 2, so that the rod 30 is slidably guided therein. The rod 30 is tubular, and its annular end portion 32 is made in one piece with the web 18. The end face υf said portion 32 flushes with the end face (the lower face in Fig. 1) of the web 18. At the open end 40 of the rod 30 a radially extending finger grip 23 is provided.
The flexible disc 20 is made of a resilient material and will deflect, when subjected to a sufficiently large force and return to its original position upon the removal of said force. When the lid 12 or other seal is placed on the outlet end 4, a closed chamber 38 is defined by the lid 12 or other seal, the flexible disc 20 and the inner wall 8 of the hollow body, the volume of said chamber being variable due to the axially displaceable plunger 6. When snapped into the hole 26, the unloaded disc 20 rests against the web 18 and the annular end portion of the rod 30. Thus, the circumferential edge portion 34 of the disc 20 is prevented from flexing upwards by the web 18 and the annular end portion 32. On the other hand the edge portion 34 is allowed to flex downwardly. If this occurs the edge portion 34 will loose its sealing contact with the inner wall 8 of the hollow body 2, thereby opening a communication at the wall 8 between the upper and lower sides of the flexible disc 20. The disc 20 thus functions as a non-return valve.
It should be noted that any method for fixing the resilient disc 20 to the rod 30 may be used. For example a keyhole connection could be used. A keyhold aperture is then provided at the bottom end of the rod 30 and, the peg 22 of the sealing disc 20 then being introduced through the wider opening of the keyhole and then being pushed into the narrower slit of the keyhole. In still a further fixing method the flexible disc 20 may be provided with a shank portion at the center thereof which portion then is introduced in an aperture provided at the lower end of the rod 30. The end of shank is then heatened to a softening temperature and thereupon flattened to form a rivet joint- like connection.
As mentioned above and as can be seen in the Figs 1-3, the rod 30 is tubular and has an open bottom and, which normally is sealed by the flexible disc 20. The interior 36 of the rod 30 and the disc 20 form a filling compartment for the agent to be mixed with a composition contained in the chamber.
The function of this first embodiment of the device will now be described by way of an example. Suitable composition for the device is described in WO/SE94/25070. In the following example the pharmaceutical composition is constituted by beads of an active substance, such as enteric coating layered omeprazole pellets mixed with a gelforming agent such as xanthan gum, guar gum, locust bean gum. tragacanth, modified cellulose derivates or similar, to which mixture of dry components a fluid agent such as for instance water later is added for forming a viscous gel. The use of the device defined by the present invention will not be restricted to use in connection to an omeprazole preparation.
A suitable dosage of a dry mixture of enteric coating layered omeprazole pellets and a gelforming agent is filled into the chamber 38. A buffering or pH-adjusting agent such as citric acid may optionally be added to prevent premature dissolution of the enteric coated beads when water later is added to the composition. This operation could be carried out in two ways, either the plunger 6 is placed in a suitable position in the hollow body 2 with the lid 12 removed, the filling then taking place through the lower end 4, or the lid 12 is applied on the lower end 4 with the plunger 6 removed, the filling then taking place via the upper opening 10. The quantity or the volume of the mixture is optional within certain limits, since the volume of the chamber 38 is variable because of the axially displaceable plunger 6. When the filling is completed, the lid 12 or other seal is applied onto the end 4 or the plung¬ er 6 inserted into the hollow body 2, respectively. It should be noted that the hollow rod 30 in an advantageous manner serves as a metering device for the agent to be added to the chamber 38. It is transparent and preferably provided with gradation lines, so that the agent to be added precisely could be measured with the device. Superfluous agent may be poured off from the rod 30 before the rod 30 has been displaced to open a communication into the chamber 38. Thus, due to the incorporated metering means provided by the particular design of the rod 20 a very precise measuring of the agent to be added, can be made without the need of any additional means than the syringe itself.
In view of the hygroscopic nature of the gelforming agent, and a required durability of several years, for the pharmaceutical composition, the content in the chamber must be protected against penetrating moisture, which else would accumulate in the gelfoπriing agent to sooner or later cause degradation of the omeprazole during long-term storage. Therefore, after the filling operation, the device is enclosed in a moisture tight envelope, preferably having a moisture barrier made of aluminium, but other materials fulfilling the same purpose are of course also conceivable. Suitably a siccative, preferably in a small bag, is enclosed in the envelope as a further protection against moisture. As an alternative to the above package, it might be sufficient providing an impermeable seal or lid of a similar material on top of the open end 40 of the rod 30. A siccative could then be incorporated in the seal or the lid to absorb any penetrating damp. The device could now be stored for several years until use.
When to be used, the device is taken out from the moisture tight package or the seal on top of the tubular rod 30 is removed. A suitable quantity of water to be added to the mixture within the chamber 38 is then filled into the tubular compartment of the rod 30 up to a desired level (marked by a gradation line or level mark). The plunger 6 is then displaced upwardly, thus creating a vacuum in the chamber 38. After a sufficient displacement, the vacuum will be so strong therein, that the flexible disc 20 will flex downwards, the circumferential edge 34 of the flexible disc 20 loosing its sealing contact with the inner wall 8, so that a communication is established from the compartment 36 into the chamber 38, so that the water in the compartment 36 of the rod 30 will be aspirated into the chamber 38. When the water has been transferred thereto, the disc 20 will flex back to its rest position and the device is then shaken until a viscous gel containing the omeprazole pellets has been formed. During the shaking operation, the mixture is prevented by the flexible disc 20 to leak into the compartment 36. The mixture could be stored in the device for a short period of time before administration. Just before administration the lid 12 is removed and the device is placed, where the preparation is to be administered. The preparation is then expelled by depressing the rod 30.
Conveniently, the rod 30 has such an axial length, that when fully depressed, all of the preparation is expelled from the device. Preferably the flexible disc 20 has an even surface to expel the composition completely, thereby avoiding the risk for any residues, pellets or gel, being left in openings or slits, which could happen with a slitted disc.
Instead of the plastic lid 12, a tear-off or a rupturable seal could be provided to seal the chamber 38.
Fig. 4 demonstrates a slight modification of the embodiment of Figs 1-3. Instead of being open at the bottom end the tubular rod 30a has two opposed longitudinal slits 42, which extend from the bottom portion of the rod 30a up to about half the height of the rod 30a, thereby providing a communication between the interior 36a of the rod 30a and the upper side of the disc 20a. The bottom portion comprises an aperture 26a in the centre, which functions in a similar way as the aperture 26 in the embodiment of Fig. 1. The bottom portion of the rod 30 is circular and provides a support for the middle portion of the flexible disc 20a.
In a further modification of the Fig. 4 embodiment, the sealing member 20'a is integral with the rod 30'a and consists of an annular flexible ring, see Fig. 7. The advantage of this embodiment is that it only requires a single operation in the manufacture of the rod 30'a and the sealing member 20'a. In still a further modification (Figs. 8-10) of the previously described embodiments the upper part of the rod 30b is tubular, while the lower part 46 thereof has a section in the shape of a cross, as clearly could be seen in Fig. 9. Thus, the lower part consists of two longitudinally extending, peφendicular wall portions 48, 50, which extend from the bottom portion of the rod 30b up to about half the height of the rod 30b. From the tubular portion 44 and extending downwards the cross-shaped portion 46 includes a first part having a constant section to provide sufficient stiffness and guidance against the inner wall 8. The following part 56 tapers downwards towards the bottom portion, which in turn comprises an annular rim 60 to support the flexible disc 20b and prevent it from being flexed upwardly. The bottom portion also includes an aperture 62, into which the bulge 24b of the flexible disc 20b is snapped (cf. Fig. 10).
A modification of the Figs. 8-10 embodiment is shown in Fig. 11. As in Fig. 7 the flexible sealing member 34'b is integral with the rod 30b. which has a radially protruding annular rim 60', which is prolonged by a thinner flexible annular edge 34'b in sealing contact with the inner wall 8 of the hollow body 2.
In the embodiment of Figs. 8-11 the water to be added is introduced as before through the open end 40 of the rod 30b but in opposition to the previously described embodiments the water will not be contained in a lower tubular portion of the rod. but will rise along the cross-shaped portion up to a desired level. In this case the cross-shaped portion could be provided with coloured lines to indicate the volume levels. In these embodiments the rod must not be transparent but can be made in an appropriate colour.
As should be understood all the embodiments function in a similar manner. A fluid agent, preferably water, is filled into the upper end 40 of the rod 30, which water then flows through the opening provided in the rod and subsequently reaches the upper side of the flexible sealing member. The sealing member prevents the water from reaching the chamber 38. The rod will then be displaced backwards, thereby creating a vacuum in the chamber 38. The combined action of the weight of the water and the vacuum will flex the sealing member downwards, so that water will be aspirated into the chamber 38. When the water has disappeared from above the flexible sealing member into the chamber, said member will flex back to its original rest position and seal off the chamber 38.
The described solutions offer different advantages. If the sealing member is a separate constructional detail, it offers a great freedom in the choice of material. The material in the sealing mem er can be chosen to have optimal sealing and elastic properties, w hue the material in the rod can be chosen to provide sufficient stiffness and support for the sealing member. If the rod and the sealing member are made integral, the choice of material must be a compromise between required stiffness of the rod and needed flexibility and elasticity of the sealing member. However, this latter solution offers advantages as regards manufacturing costs.
It should further be noted that in the two embodiments all the elements can be made of polymeric materials, such as for instance polyethylene, polypropylene, polyester, elastomer, polycarbonate, rubber or silicone, and manufactured by conventional and cheap methods, such as injection moulding. Moreover, all the details have a simple construction and are easy to assemble. Consequently, the devices can be produced at a low cost
In the above described embodiments of the invention the lid 12 is provided with an radially protruding lug 16, which extends around a part of the circumference of the lid 12 and forms a grip portion for facilitating the removal of said element It should be realized that the grip portion may have any suitable configuration. For example, it could be oval, or it could be constituted by a protruding flange extending over the whole circumference of the lid.
The devices are in particular suited for oral administration to an animal, especially a horse, in particular of an aqueous gel containing a formulation of a proton pump inhibitor e.g. omeprazole or a similar composition. However, it should be evident to the man skilled in the art that the use of the device is not restricted to this field, since it can be used for rnixing various kinds of pharmaceutical compositions with other agents, and for oral, rectal or any other suitable administration to many different kinds of living beings, including humans.
It should also be noted that a pharmaceutical composition in the sense of this application does not solely mean a drug, also other kinds of beneficial agents, for instance essential nut¬ rients are intended to be included by this expression.

Claims

1. Device for rnixing a pharmaceutical, preferably dry and granular, composition with a, preferably fluid, agent to a preparation, preferably a gel or the like, and subsequently ad- ministering said preparation to a living being, e g an animal or a human being, the device comprises a hollow body (2) having an outlet (4) sealed by a removable closure (12) a plunger (6, 6a, 6'a, 6b, 6'b) being displaceably accommodated in said hollow body (2) and in sealing contact with an inner wall of said hollow bocy (8), an actuating means (30, 30a, 30b) being connected to said plunger (6.6a.6'a.6b, 6'b), for displacing the same in said hollow body (2), said plunger, characterized in said hollow body and said removable closure defining a chamber for said composition, that said plunger (6, 6a, 6'a, 6b, 6'b) comprises a sealing member (20.20a.20'a, 20b.20'b) having a flexible edge portion (34, 34a, 34'a, 34b, 34'b) in sealing contact with said inner wall f S) of said hollow body (2). one side of said edge portion facing said chamber (38). thus separating said chamber from the opposite side of said flexible edge portion, said edge portion being supported to be able to flex in a sufficient degree in one direction only to loose its sealing contact with said inner wall (8) of said hollow body (2) in order to establish a communication between said chamber (38) and said opposite side of said edge portion, when said plunger is displaced in a direction away from said chamber (38).
2. Device according to claim 1, characterized in that said actuating means is a tubular rod (30, 30a, 30b), provided with at least one opening at a bottom portion thereof.
3. Device according to claim 2. characterized in that said rod (30, 30a, 30b) has a diametrically extending web (18). openings being defined between the side edges of said web (18) and the inner wall of said tubular rod (30).
4. Device according to claim 3, characterized in that said web (18) has a centre aperture (26) adapted for detachably connecting said flexible sealing member (20) to said rod (30) said sealing member being circular and extending at least to the outer wall of said tubular rod.
5. Device according to claim 2, characterized in that said tubular rod (30a) has a closed bottom portion and axial slits (42) extending from said bottom portion.
6. Device according to claim 5, characterized in that said flexible sealing member is a circular disc (20a), detachably fixed to said bottom portion.
7. Device according to claim 6, characterized in that said flexible sealing member is integral with said tubular rod (30'a) and consists of a flexible annular ring (34'a) extending radially from said bottom portion to said inner wall (8) of said hollow body (2).
8. Device according to any of claims 2-7. characterized in that said tubular rod (30,30a,30a') includes a volume measurement means for said agent to be added.
9. Device according to claim 8, characterized in that said tubular rod (30,30a,30a') has level gradations for said agent to be added.
10. Device according to claim 8 or 9, characterized in that said tubular rod (30,30a,30a') is transparent.
11. Device according to claim 2, characterized in that said rod (30b) includes a tubular first part (44) connected to a second part (46) having a cτoss-shaped section.
12. Device according to claim 11, characterized in that said second part (46) tapers towards the bottom portion of said rod (30b).
13. Device according to claim 11 or 12, characterized in that said rod has a plate- formed bottom portion having a centre aperture (62) adapted for detachably connecting said flexible sealing member (20b) to said rod (30b), said sealing member being circular and extending to the inner wall of said hollow body (2).
14. Device according to claim 11 or 12, characterized in that said flexible sealing member is integral with said rod (30b) and consists of a flexible annular ring (34'b) extending radially from said bottom portion to said inner wall (8) of said hollow body (2).
15. Device according to any of claims 11-14, characterized in that said cross- shaped second part (46) includes a volume measurement means for said agent to be added.
16. Device according to claim 15, characterized in that said second part (46) has level gradation for said agent to be added.
17. Device according to claim 16, characterized in that said level gradations are coloured lines.
18. Device according to any of claims 11-17, characterized in that said second pan (46) is coloured.
19. Device according to any of claims 2-18, characterized in that said tubular rod (30, 30a, 30b) includes an open end (40) remote from said plunger (6), which is closed by a moisture proof seal.
20. Device according to any of claims 1-19, characterized in that said closure is a removable lid (12).
21. Device according to any of claims 1-19, characterized in that said removable closure (12) is a rupturable or a tear-off closure.
22. Device according to any preceding claim, c h a r a c t e r i z e d in that said chamber (38) is prefilled with said pharmaceutical composition and said device is enclosed in a moisture proof envelope, comprising at least one moisture barrier.
23. Device according to claim 22, c h a r a c t e r i z e d in that said at least one moisture barrier is comprised by an aluminium layer.
24. Device ac ;oording to claims 22 or 23, c h a r a c t e r i z e d in that a siccative is contained in said envelope.
1"
25. Device according to any preceding claim, c h a r a c t e r i z e d in that said pharmaceutical composition is constituted by enteric coating layered pellets comprising a proton pump inhibitor e.g. omeprazole pellets, mixed with a dry gelforming agent
if
26. Process for preparing a pharmaceutical preparation by mixing a pharmaceutical, preferably dry and granular, composition with a. preferably fluid, agent shortly before the administration thereof to a living being, comprising the following steps:
a) filling said composition into a chamber 38 of a device comprising a hollow body 20 (2;) and a plunger (6;) displaceable therein in sealing engagement with an inner wall portion of said hollow body (2:), thereby defining a movable end wall of said chamber (38), the plunger (6) comprises a sealing member (20) having a flexible edge portion (34) in sealing contact with the inner wall (8) of the hollow- body (2), separating the chamber(38) from the opposite side of the edge ;5 portion, the edge portion (34) is able to flex to permit a communication between the chamber (38) and the opposite side of the edge portion (34), b) closing said chamber with a closure (12) c) providing a moisture tight seal to said filled chamber (38), d) storing said device until time of use,
?o e) removing said moisture tight seal to said chamber (38), f) expanding said chamber (38) by displacing said plunger (6) thereby establish communication between the (38) causing the opening of said edge portion (34), thereby transferring fluid agent to said chamber (38) g) if required, shaking said device until said preparation is formed, h) providing an opening to said chamber (38) by removing said closure (12) when said preparation is to be administered, allowing said preparation to be expelled from said device by displacing said plunger (6) towards said opening.
27. Process according to claim 26, characterized in that said moisture tight seal in step c) to said chamber (38) is accomplished by enclosing said device in a moisture proof envelope, which comprises at least one moisture barrier.
28. Process according to claim 27, characterized in that said at least one moisture proof barrier is an aluminium layer.
29. Process according to any of claims 26-28, characterized in that said pharmaceutical composition is constituted by enteric coated pellets of a proton pump inhibitor e.g. omeprazole pellets, mixed with a dry gelforming agent and that said preferably fluid agent is water.
30. Method for oral administration to a living being of a pharmaceutical preparation, which is achieved by mixing a preferably dry and granular, composition with a preferably fluid agent by using a device according to any of claims 1-25.
31. Method according to claim 30, characterized in that said living being is an animal, e.g. a horse.
32. Method according to claim 31, characterized in that said device is inserted into the mouth of the horse just in front of the first pre-molar tooth, said preparation being deposited onto the root of the tongue.
EP96912371A 1995-05-03 1996-04-23 Device and process for mixing a pharmaceutical composition with another agent and method for oral administration of the pharmaceutical preparation Withdrawn EP0827419A1 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
SE9501631 1995-05-03
SE9501631A SE504683C2 (en) 1995-05-03 1995-05-03 Device for mixing a pharmaceutical composition with another agent
PCT/SE1996/000527 WO1996034681A1 (en) 1995-05-03 1996-04-23 Device and process for mixing a pharmaceutical composition with another agent and method for oral administration of the pharmaceutical preparation

Publications (1)

Publication Number Publication Date
EP0827419A1 true EP0827419A1 (en) 1998-03-11

Family

ID=20398172

Family Applications (1)

Application Number Title Priority Date Filing Date
EP96912371A Withdrawn EP0827419A1 (en) 1995-05-03 1996-04-23 Device and process for mixing a pharmaceutical composition with another agent and method for oral administration of the pharmaceutical preparation

Country Status (21)

Country Link
EP (1) EP0827419A1 (en)
JP (1) JPH11504245A (en)
KR (1) KR19990008268A (en)
CN (1) CN1183057A (en)
AR (1) AR001841A1 (en)
AU (1) AU700156B2 (en)
BR (1) BR9608271A (en)
CA (1) CA2218739A1 (en)
CZ (1) CZ345697A3 (en)
EE (1) EE9700265A (en)
HU (1) HUP9801947A3 (en)
IS (1) IS4595A (en)
NO (1) NO975019D0 (en)
NZ (1) NZ306603A (en)
PL (1) PL323157A1 (en)
SE (1) SE504683C2 (en)
SK (1) SK142897A3 (en)
TR (1) TR199701288T1 (en)
TW (1) TW341520B (en)
WO (1) WO1996034681A1 (en)
ZA (1) ZA963190B (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6036935A (en) * 1995-09-18 2000-03-14 Delta Chemical Corporation Polyaluminum chlorides and polyaluminum chlorosulfates methods and compositions

Families Citing this family (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE60029301T2 (en) * 1999-12-03 2007-07-05 Baxter International Inc., Deerfield Method and apparatus for controlling the strategy of compounding pharmaceutical mixtures
PL2136764T3 (en) 2007-04-10 2017-07-31 Sandoz Ag Device for the oral application of a substance
USD962471S1 (en) 2013-03-13 2022-08-30 Abbott Laboratories Reagent container
US9535082B2 (en) 2013-03-13 2017-01-03 Abbott Laboratories Methods and apparatus to agitate a liquid
USD978375S1 (en) 2013-03-13 2023-02-14 Abbott Laboratories Reagent container
US10058866B2 (en) 2013-03-13 2018-08-28 Abbott Laboratories Methods and apparatus to mitigate bubble formation in a liquid

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
SE462315B (en) * 1989-05-03 1990-06-11 Surgitec Ab DEVICE FOR MANUFACTURING BENCEMENT
DK235589D0 (en) * 1989-05-12 1989-05-12 Wolff & Kaaber METHOD AND APPARATUS FOR MIXING A SOLID AND LIQUID COMPONENT

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO9634681A1 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6036935A (en) * 1995-09-18 2000-03-14 Delta Chemical Corporation Polyaluminum chlorides and polyaluminum chlorosulfates methods and compositions

Also Published As

Publication number Publication date
BR9608271A (en) 1999-05-11
CA2218739A1 (en) 1996-11-07
AU700156B2 (en) 1998-12-24
JPH11504245A (en) 1999-04-20
HUP9801947A2 (en) 1998-12-28
PL323157A1 (en) 1998-03-16
NO975019L (en) 1997-10-31
AR001841A1 (en) 1997-12-10
KR19990008268A (en) 1999-01-25
CZ345697A3 (en) 1998-07-15
WO1996034681A1 (en) 1996-11-07
TW341520B (en) 1998-10-01
ZA963190B (en) 1996-11-04
SE9501631D0 (en) 1995-05-03
SE9501631L (en) 1996-11-04
NO975019D0 (en) 1997-10-31
TR199701288T1 (en) 1998-02-21
SE504683C2 (en) 1997-04-07
SK142897A3 (en) 1998-07-08
AU5520396A (en) 1996-11-21
CN1183057A (en) 1998-05-27
EE9700265A (en) 1998-04-15
IS4595A (en) 1997-10-20
HUP9801947A3 (en) 1999-04-28
NZ306603A (en) 1998-05-27

Similar Documents

Publication Publication Date Title
AU680959B2 (en) Device for mixing a pharmaceutical compositiion with another agent
US7779609B2 (en) Method of filling a device
US4693706A (en) Two compartment mixing syringe
US5871355A (en) Dental mixing capsule for dispensing a multiple component dental material
US4331146A (en) Syringe assembly
US4551135A (en) Syringe for extrusion of semi-plastic material
US4412836A (en) Syringe assembly
US6543612B2 (en) Container for compositions made of two or more components
CA1221063A (en) Single barrel two-compartment medicament container assembly
US3255752A (en) Hypodermic syringe
US20070015106A1 (en) Delivery system for dental materials
JPS6039043B2 (en) Osmotic fluid dosing device
AU2002356671B2 (en) Device for storing, mixing and dispensing a free-flowing material
AU700156B2 (en) Device and process for mixing a pharmaceutical composition with another agent and method for oral administration of the pharmaceutical preparation
MXPA97008366A (en) Device and process for mixing a pharmaceutical composition with another agent and method for the oral administration of farmaceut preparation
US20120017412A1 (en) Package and dispensing system
US5746313A (en) Mixing capsule and method of manufacturing same
CA1222424A (en) Syringe for extrusion of semi-plastic material

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 19971203

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): AT BE CH DE DK ES FI FR GB GR IE IT LI LU MC NL PT SE

RAX Requested extension states of the european patent have changed

Free format text: LT PAYMENT 971203;LV PAYMENT 971203;SI PAYMENT 971203

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE APPLICATION HAS BEEN WITHDRAWN

18W Application withdrawn

Withdrawal date: 19990701

REG Reference to a national code

Ref country code: HK

Ref legal event code: WD

Ref document number: 1006084

Country of ref document: HK