WO1995032015A1 - Device for the preparation of a solution, a suspension or an emulsion of a medicinal substance - Google Patents
Device for the preparation of a solution, a suspension or an emulsion of a medicinal substanceInfo
- Publication number
- WO1995032015A1 WO1995032015A1 PCT/CH1994/000097 CH9400097W WO9532015A1 WO 1995032015 A1 WO1995032015 A1 WO 1995032015A1 CH 9400097 W CH9400097 W CH 9400097W WO 9532015 A1 WO9532015 A1 WO 9532015A1
- Authority
- WO
- Grant status
- Application
- Patent type
- Prior art keywords
- container
- device
- piston
- figure
- valve
- Prior art date
Links
Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61J—CONTAINERS 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
- A61J1/00—Containers specially adapted for medical or pharmaceutical purposes
- A61J1/05—Containers specially adapted for medical or pharmaceutical purposes for collecting, storing or administering blood, plasma or medical fluids ; Infusion or perfusion containers
- A61J1/14—Details, e.g. provisions for hanging or shape retaining means; Accessories therefor, e.g. inlet or outlet ports, filters or caps
- A61J1/20—Arrangements for transferring or mixing fluids, e.g. from vial to syringe
- A61J1/2093—Containers having several compartments for products to be mixed
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
- A61M5/178—Syringes
- A61M5/24—Ampoule syringes, i.e. syringes with needle for use in combination with replaceable ampoules or carpules, e.g. automatic
- A61M5/2422—Ampoule syringes, i.e. syringes with needle for use in combination with replaceable ampoules or carpules, e.g. automatic using emptying means to expel or eject media, e.g. pistons, deformation of the ampoule, or telescoping of the ampoule
- A61M5/2429—Ampoule syringes, i.e. syringes with needle for use in combination with replaceable ampoules or carpules, e.g. automatic using emptying means to expel or eject media, e.g. pistons, deformation of the ampoule, or telescoping of the ampoule by telescoping of ampoules or carpules with the syringe body
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
- A61M5/178—Syringes
- A61M5/24—Ampoule syringes, i.e. syringes with needle for use in combination with replaceable ampoules or carpules, e.g. automatic
- A61M5/2448—Ampoule syringes, i.e. syringes with needle for use in combination with replaceable ampoules or carpules, e.g. automatic comprising means for injection of two or more media, e.g. by mixing
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
- A61M5/50—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests having means for preventing re-use, or for indicating if defective, used, tampered with or unsterile
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61J—CONTAINERS 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
- A61J1/00—Containers specially adapted for medical or pharmaceutical purposes
- A61J1/05—Containers specially adapted for medical or pharmaceutical purposes for collecting, storing or administering blood, plasma or medical fluids ; Infusion or perfusion containers
- A61J1/14—Details, e.g. provisions for hanging or shape retaining means; Accessories therefor, e.g. inlet or outlet ports, filters or caps
- A61J1/20—Arrangements for transferring or mixing fluids, e.g. from vial to syringe
- A61J1/2003—Accessories used in combination with means for transfer or mixing of fluids, e.g. for activating fluid flow, separating fluids, filtering fluid or venting
- A61J1/2006—Piercing means
- A61J1/201—Piercing means having one piercing end
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61J—CONTAINERS 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
- A61J1/00—Containers specially adapted for medical or pharmaceutical purposes
- A61J1/05—Containers specially adapted for medical or pharmaceutical purposes for collecting, storing or administering blood, plasma or medical fluids ; Infusion or perfusion containers
- A61J1/14—Details, e.g. provisions for hanging or shape retaining means; Accessories therefor, e.g. inlet or outlet ports, filters or caps
- A61J1/20—Arrangements for transferring or mixing fluids, e.g. from vial to syringe
- A61J1/2003—Accessories used in combination with means for transfer or mixing of fluids, e.g. for activating fluid flow, separating fluids, filtering fluid or venting
- A61J1/2006—Piercing means
- A61J1/2013—Piercing means having two piercing ends
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61J—CONTAINERS 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
- A61J1/00—Containers specially adapted for medical or pharmaceutical purposes
- A61J1/05—Containers specially adapted for medical or pharmaceutical purposes for collecting, storing or administering blood, plasma or medical fluids ; Infusion or perfusion containers
- A61J1/14—Details, e.g. provisions for hanging or shape retaining means; Accessories therefor, e.g. inlet or outlet ports, filters or caps
- A61J1/20—Arrangements for transferring or mixing fluids, e.g. from vial to syringe
- A61J1/2003—Accessories used in combination with means for transfer or mixing of fluids, e.g. for activating fluid flow, separating fluids, filtering fluid or venting
- A61J1/202—Separating means
- A61J1/2031—Separating means having openings brought into alignment
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61J—CONTAINERS 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
- A61J1/00—Containers specially adapted for medical or pharmaceutical purposes
- A61J1/05—Containers specially adapted for medical or pharmaceutical purposes for collecting, storing or administering blood, plasma or medical fluids ; Infusion or perfusion containers
- A61J1/14—Details, e.g. provisions for hanging or shape retaining means; Accessories therefor, e.g. inlet or outlet ports, filters or caps
- A61J1/20—Arrangements for transferring or mixing fluids, e.g. from vial to syringe
- A61J1/2003—Accessories used in combination with means for transfer or mixing of fluids, e.g. for activating fluid flow, separating fluids, filtering fluid or venting
- A61J1/202—Separating means
- A61J1/2044—Separating means having slits
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61J—CONTAINERS 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
- A61J1/00—Containers specially adapted for medical or pharmaceutical purposes
- A61J1/05—Containers specially adapted for medical or pharmaceutical purposes for collecting, storing or administering blood, plasma or medical fluids ; Infusion or perfusion containers
- A61J1/14—Details, e.g. provisions for hanging or shape retaining means; Accessories therefor, e.g. inlet or outlet ports, filters or caps
- A61J1/20—Arrangements for transferring or mixing fluids, e.g. from vial to syringe
- A61J1/2003—Accessories used in combination with means for transfer or mixing of fluids, e.g. for activating fluid flow, separating fluids, filtering fluid or venting
- A61J1/2048—Connecting means
- A61J1/2051—Connecting means having tap means, e.g. tap means activated by sliding
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61J—CONTAINERS 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
- A61J1/00—Containers specially adapted for medical or pharmaceutical purposes
- A61J1/05—Containers specially adapted for medical or pharmaceutical purposes for collecting, storing or administering blood, plasma or medical fluids ; Infusion or perfusion containers
- A61J1/14—Details, e.g. provisions for hanging or shape retaining means; Accessories therefor, e.g. inlet or outlet ports, filters or caps
- A61J1/20—Arrangements for transferring or mixing fluids, e.g. from vial to syringe
- A61J1/2003—Accessories used in combination with means for transfer or mixing of fluids, e.g. for activating fluid flow, separating fluids, filtering fluid or venting
- A61J1/2079—Filtering means
- A61J1/2086—Filtering means for fluid filtration
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
- A61M5/178—Syringes
- A61M5/31—Details
- A61M2005/3123—Details having air entrapping or venting means, e.g. purging channels in pistons
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M39/00—Tubes, tube connectors, tube couplings, valves, access sites or the like, specially adapted for medical use
- A61M39/02—Access sites
- A61M39/04—Access sites having pierceable self-sealing members
- A61M2039/042—Shrouds encircling the access needle preventing accidental needle-stick
Abstract
Description
DEVICE FOR PREPARING A SOLUTION OF SUSPENSION OR EMULSION OF A MEDICINAL SUBSTANCE
The present invention relates to a device for preparing a solution, suspension or emulsion from an active medicinal substance, from at least two components at least one is in the liquid state .
Reconstitution before use of a drug from one or more components stored in the same set sealed and intended to be mixed in this set, without the introduction of external elements, pose several problems. Many bottles two component has been developed for this purpose. These bottles generally include a single container separated into two compartments by a movable sealing member. The two compartments are hermetically sealed during storage. Prior to use of the reconstituted drug, the system activation step allows to mix the substances of which at least one is in the liquid state. For this purpose the movable sealing member which separates the two compartments is pushed so as to penetrate in an enlarged area, or provided with a bypass, allowing the flow of liquid or solvent to the other component which may be liquid, solid, paste, etc. .
The manufacture of these double containers is not always easy and does not always meet the pharmaceutical industry requirements for a particular application. A two-component syringe of the aforementioned type has been the subject of US Patent 2 / "014 330 which discloses a syringe for two components respectively contained in two closed compartments by two shutters also having a piston function. This device is built in two parts that must be assembled before use. The establishment of the bottle, which defines the distal compartment, necessarily correspond with the activation of the system. The reconstruction and the transfer can not be done in a closed environment, where significant risks of contamination of nursing staff by the product, and loss of sterility of the mixture. In addition, the active product is contained in the front container open at both ends and provided with fins. This poses particular production problems during the packaging of a lyophilisate, a powder or a liquid.
Indeed, it is imperative to condition these active products in a cylindrical vial flat sealed bottom for the flame to meet the specific requirements of packaging of these substances with equipment known per se, when the vacuum preparation (washing, siliconizing, fixing of the silicone film, depyrogenation and sterilizing said bottle), fill (liquid, powder, lyophilizate), closing (capping) and transfer towards an assembly unit with the component having the chamber containing the diluent.
The system as described in US Patent 4,014,330 can not meet these requirements because the active product should be packaged in the rear container and, in these conditions, because of its construction, reconstruction is no longer possible .
One problem that arises in particular, and which can hardly be solved by systems where components are contained in a single container with two compartments, is that of the individual packaging of the two components. In other words, the conditions of preparation and sterilization of the components are not necessarily those suitable for the preparation of the other. A solvent can not be treated in the same way as a freeze-dried or certain powders. The lyophilisate does not withstand the heat needed to sterilize a solvent by autoclaving. In a single container, the lyophilisate is separated from the solvent by an elastomer mobile shutter. The solvent is in permanent contact with the movable shutter so that the steam partial pressure is constant at its maximum. Steam penetration risk through this movable shutter is large and the freeze-dried product shelf life can be compromised or limited in time. Accordingly the choice of elastomers is limited to that which the sealing barrier ability is highest. This latter constraint requires the establishment of evidence in real time stability and compatibility which is very costly and time and handicaps the pharmaceutical companies when they have to take a decision on the packaging of their products in systems with two bedrooms.
To these disadvantages, there is the increased risk of loss of sterility because of the wet container. In monocompact packaging conditions, a dry product, otherwise not autoclavable, is less likely to let grow germs it is in a dry environment. This lack of risk disappears from the moment, in the same container, packaged liquid. The addition of preservatives is not desired, and even forbidden in some cases, especially for disposable products.
multi-purpose products, in successive doses, are packaged with preservatives, not to limit the growth of bacteria during storage, but to maintain the sterile state after reconstitution throughout the period of use that may last several days .
Another problem that arises and that can hardly be solved by the existing systems is the control flow when the replenishment without external mixing action by such a screw method described in the European patent N 2 0298067 Bl .
The present invention proposes to overcome these disadvantages by providing a simple and effective device in which the risk of contamination of components are removed by the other, in which the basic components necessary for the preparation of a mixture of treatment can be subjected to different operations for their preparation and their packaging, and wherein the replenishment rate is controlled in sealed and sterile without external work environment.
This object is achieved by the device of the invention as defined by claim 1. In a preferred embodiment, the device may comprise a sleeve in which is located the front container and at least partially the rear container.
This sleeve may be associated with a push cap and a metering mechanism for applying multiple doses.
According to another embodiment, said sleeve can be made in one piece by molding with the front container.
Depending on the application to which the device is intended, said sleeve is provided with an endpiece constituting an ophthalmic drops applicator or a nasal spray, integrated in the front container.
In the preferred embodiment, said sleeve comprises a first tubular element and a second tubular element can be nested into one another, the first tubular element containing said front container and said second sub-element containing said rear container .
Preferably, said first tubular member comprises notches and said second tubular member comprises at least two tabs arranged to cooperate with said notches.
Said stopper-piston-valve of the apparatus of the invention each comprise a central recess and said transfer rod has a tight and sterile coupling means with said stopper-piston-valves.
Advantageously, said transfer rod has end stops arranged to abut against the facing surfaces of the corresponding stopper-piston-valves when the device is in the use position. When the device is in the storage position, said piston-obturateurs- are arranged to ensure a tight and sterile closure of the corresponding containers, by bearing against the inner walls of these containers, so that these containers can be stored and processed independently .
In all embodiments, said transfer rod is arranged to ensure a rigid coupling, said watertight and sterile rendered stopper-piston-valves integral with said distal and proximal containers.
In the device according to the invention, said front container is arranged to be able to receive various nozzles and applicators depending on the intended therapeutic uses.
The invention will be better understood by reference to the description of preferred embodiments and accompanying drawings in which:
Figures 1 to 4 show an advantageous embodiment of the device according to the invention successively during the storage phases, activation and use,
Figure 5 illustrates a particular embodiment of the device for use as eye drop dispenser,
Figures 6 to 9 show another embodiment of the device of the invention successively storing, activating, at the beginning and the end of use,
Figures 10 to 13 show a variant constituting an improvement of the device as shown in Figures 1 to,
FIGS 14 to 18 illustrate another embodiment of the device used as a syringe associated with a metering mechanism for applying multiple doses, Figures 19 to 22 illustrate the device of the invention suitable for ophthalmic field,
Figures 23 and 24 show enlarged views of the stopper-piston-valves in the rest position,
Figures 25 and 26 show enlarged views of the stopper-piston-valves in the position of activation and use,
Figures 27-30 show enlarged views of suitable accessories to the device according to the intended uses, and
Figures 31-62 show schematically the different phases of preparation and assembly of the constituent components of the device according to the invention in the different uses of the device and with the various basic components corresponding to such uses.
Figures 1 to 4 show an advantageous embodiment of the device 10 for carrying out the preparation of a medical solution, for example an injectable solution, from two basic components. In particular Figure 1 shows the device during the storage phase. It comprises a first container 11 in which is stored a lyophilisate 12, a second container 13 containing a solvent in this case 14, and a transfer rod 15 provided with a hollow conduit 16. The container 11, hereinafter called the rear container has a closed bottom 17 and an open end 18 through which is engaged a stopper-piston-valve 19 which delimits, inside the rear container, a chamber 20 containing the lyophilisate 12. Note that this lyophilisate 12 may be replaced by another active ingredient such as for example a liquid, a powder or a pasty substance of greater or lesser viscosity. The container 13, referred to hereinafter as the front container, is open at both ends. In the example shown, the open end 21 is closed by a capsule 22 secured by crimping. This capsule, known per se, is used on many vials containing drug substances and may be in the form of a compound of plastic material for sealing and aluminum ensuring the mechanical strength and forming an antiseptic barrier.• The other open end 23 of container 13 is closed by a stopper-piston-valve 24. The two stopper-piston-valves 19 and 24 are each provided with a central recess 25- respectively 26 in which are engaged the two end pieces respectively 27 and 28 integral with the transfer pin 15. the stopper-piston-valve 24 defines with the walls of container 13 and the cap 22 a chamber 29 containing the solvent 14. According to the drug substance contained in the chamber 20 of the rear container 11, the solvent 14 may be replaced by a diluent. Whatever the nature of the active substance of the rear container, the substance accommodated in the front container is always in the liquid state and is intended to achieve with the process medium a solution, suspension or emulsion reconstituted from two and basic components to be subsequently used in the framework of a therapeutic treatment in an injectable form can be administered externally or internally by means of any applicator, including a needle, a trocar, a gob distributor, a spray, etc. .
The stopper-piston-valve 24 comprises, in the extension of the central recess 26, a small clearance 30 in which is engaged the front end of the transfer rod 15. In the extension of the clearance 30, the shutter -piston-valve includes a precut slit 31 which precisely allows this member to act as valve closed for storage and opened during the other phases, that is to say during activation and use. The elastomer walls of the stopper-piston-valve
24 which surround the lips of the slots 31, are thick, and this slot is provided in an area ensuring a high compression of said lip of said slot when the stopper-piston-valve is in compression inside the front container of so that the shutter storage is effected in a perfectly efficient way to guarantee both the tightness and sterility of the chamber and the contents of the front container.
In a similar way, the stopper-piston-valve 19 comprises a central recess 32 in which is engaged the other end of the transfer rod 15. In an extension of this clearance, the stopper-piston-valve comprises a slot 33 which ensures the valve function closed for storage and opened during other system operating phases, that is to say the activation and use. Again, the thickness of the material surrounding the lips of the slot 33, pre-cut, is sufficient if the stopper-piston-valve is in place within the rear container to ensure a relatively large compression of said lips to ensure both the tightness and sterility of the chamber 20 of the rear container 11.
In the embodiment shown, the inner diameter of the rear container is substantially equal to the outer diameter of the proximal part so that they can be nested at least partly one inside the other, at the time of use. For obvious reasons of simplicity of manufacture and production cost, the two containers are cylindrical general elongated shape with circular section. Due to the differences in diameter of the two containers, the stopper-piston-valve 19 has a diameter greater than that of the stopper-piston-valve 24. At the time of activation, the first phase is shown in Figure 2, initiated by the exercise of a pressure exerted axially, preferably on the bottom 17 of the rear container, the front container being held in position, the ends of the transfer rod respectively engage the slots 31 and 33 of obturateurs--valve pistons 24 and 19, which has the effect of placing the chambers 20 and 29 into communication and allow the flow of solvent 14 through the conduit 16 into the chamber 20 containing the lyophilisate 12. the diameter and the length of conduit 16 are dimensioned so as to obtain a controlled flow when the flow of solvent 14 through the conduit 16. it will be noted in passing that the ends of the transfer rod are constituted by bevels since their function is not to pierce a membrane, but by a flat section disposed along planes perpendicular to the axis of the transfer rod, and optionally extended by a slightly frustoconical zone. This geometry allows for easy introduction into the slots sealed and sterile, the end being adapted to separate the lips of the slots to open the valve of the stopper-piston-valve, unlike many known systems where a rod transfer presents a beveled end whose function consists in perforating a membrane. The seal between the membrane and the bevelled end can only be ensured if the thickness of the membrane is substantially greater than the length of the bevel, which is incompatible with a compact construction and ease of puncturing the membrane. Moreover, it is also noted that the transfer rod is provided with a first stop 34 and second stop 35 which, except for storage, respectively bearing against the facing faces of the valves obtùrateurs--pistons 24 and 19 . These stops serve to define precisely the degree of penetration of the ends of the transfer rod in the corresponding chambers of the proximal and distal containers.
When the user continues to press the bottom 17 while the solvent contained in the front container 13 flows into the chamber 20, comes into contact with the freeze-dried product 12 to form a solution 12 + 14 constituting the reconstituted medicinal substance.
By finding the pressures and differences between surfaces of the two stopper-piston-valves, the stopper-piston-valve 24 is housed at the front end of the front container 13 and the obturateur- piston valve 19 is put in a position such that it becomes possible to ensure the degassing, the flask having been equipped with a suitable tip depending on the intended use of the medicinal solution. If this solution is to be injected, the nozzle will be a needle. If this solution is intended to be transferred to a transfusion bag, the endpiece can be a trocar. If the solution is intended for another use, the tip will be selected accordingly. Whatever the nozzle, the solution is transferred through the conduit 16. To this end, the user presses on the bottom of the rear container 11 which fits on the front container 13. The stopper-piston-valve 19 gradually sinks inside the rear container 11 until it touches the bottom 17. to prevent reuse of the device, particularly in the case where it is used as a syringe, the coupling means of the end pieces
27 and 28 of the transfer pin 15 respectively with the piston--shutters 19 and 24 are low enough to distance themselves said stopper-piston-valves when a user attempt to remove the container proximal the rear container , making any re-suction of a possible liquid inside the device.
Figure 5 shows the device according to the invention adapted for application to ophthalmic treatment. In this case, the two containers, respectively proximal and distal, 11 and 13 are nested pré¬. The rear container 11, which contains a lyophilisate 12 is completely empty of air, the stopper-piston-valve 19 being engaged inside said container, in tight abutment against the material contained therein. The advantage of this embodiment is that it allows to completely remove any purging operation or de-airing and to avoid oxidation of the mixture after reconstitution, that is to say at the time of device activation.
The front container 13 which, recall, is open at both ends, is closed at one of its ends by obturateur- piston valve 24 and at its other end by a plug 50. A capsule cap 51 and the plug a filter 52 and a silver pellet having an oligodynamic function are interposed between the capsule and the stopper. The pellet of silver may be replaced by another material such as for example silver oxide or a compound containing substances having similar properties. A protective cap 53 closes this set. A cannula tip 54 to spiral 55, team end of the capsule 51. In this case, the transfer rod 15 is advantageously made of a rigid synthetic material molded part in one piece. Note that the plug 50 has a geometry which is substantially identical to that of the stopper-piston-valve 24 and it operates on the same principles, at least as regards its central opening making an incorporated valve a pre-slit to be opened by the end of the transfer rod, in the phase of use of the device. In this embodiment also, the cap 51 has a skirt long enough to cover a portion of the rear container near its open end. It turns out that this rear container 11 is itself housed within a cap 56 of synthetic material, molded which ensures its protection. The cap 56 is pre-fitted in the skirt of the capsule 51. For other uses, the cap 56 could be omitted and the rear container could be directly engaged around its open top, inside of the skirt of the capsule 51.
Figures 6 to 9 illustrate another embodiment of the device for use as a syringe for injection of the reconstituted medicinal substance. 6 shows the storage, Figure 7 activation, Figures 8 and 9 for use in the context of a mechanical system with multidose. As before, the device 10 comprises a rear container 11 containing for example a lyophilisate 12 and a proximal container 13 containing for example a solvent 14, and a transfer rod 15 for allowing the communication between the two containers through a conduit 16. the distal tubular container 11 has a closed bottom 17 and has an opening 18 at its end opposite the base 17. 11 is closed off by a valve shutter -piston 19 defining a chamber 20 containing the lyophilisate 12. the front container 13 has an upper opening 21 closed by a crimped cap 22. As the container is open at both ends, its other end 23 is closed by a stopper-piston-valve 24. The stopper-piston-valve 19 comprises a central recess 25 and the stopper-piston-valve 24 has a central recess 26, these two seals being intended to receive respectively two end caps 27 and 28 of the a transfer rod 15. obturàteur- piston valve 24 has a precut slit 31 which serves as valve and which is intended to receive the end of the transfer rod 15 and the stopper-piston-valve 19 also comprises a precut slit 33 serving as a valve which is designed to be traversed by the other end of the transfer rod 15.
We herewith that some construction details, the above-described elements are identical to those described with reference to Figures 1 to 4. However, it is noted that the front container 13 is housed within a first element tube 40 whose proximal end is capped with a protective cap 41 and the rear container 11 is housed within a second tubular member 42 partially engaged inside the first tubular element 40.
In the storage position shown in Figure 6, the two tubular elements 40 and 42 define a substantially cylindrical box inside of which is housed the device 10 as shown in Figure 1. In order to enabling this device, the second element 42 has a series of notches 43 which can be arranged over the entire periphery of the element or only on a specific area of the periphery. These notches are intended to cooperate with at least one flexible tongue 44 formed within the side wall of the element 4-0 for generating predetermined braking forces for regulating the relative axial displacement of the two elements 40 and 42 and to define non-return abutments preventing the decrease or removal of the second member 42 when engaged within the first member 40.
7 shows the activation phase and preparing the mixture of the two components. In this phase, the tubular element 42 has been pushed inside the tubular element 40, which has the effect of moving the rear container towards the front container. 11 result on the one hand the penetration of both ends of the transfer rod in the slots constituting the valves corresponding obturators-pistons-valves, the movement of the stopper-piston-valve 24 axially inside the front container and solvent flow into the chamber 20 where the lyophilisate 12. at the end of this activation phase, the mixture of the two base substances or constituents of the medicinal substance has been completed and this substance is ready for employment. 8 illustrates the final phase of preparation that is to be degassed or debubble the device which, in this case, is equipped with a needle 45 for injection of the reconstituted medicinal substance. The second tubular member 42 has been completely pushed inside the first tubular member 40, the rear container in which is carried out dissolving the lyophilized t was fully degassed, and a thrust exerted on the bottom 17 of said rear container by means a suitable pusher 46 makes it possible to penetrate the stopper-piston-valve 19 bearing against the solution contained in said rear container. Thereafter, this obturateur- piston valve has a piston function and delivers the solution through the conduit 16 of the transfer pin 15 in the direction of the injection needle 45.
At the end of the utilization phase illustrated by Figure 9, the pusher
46 has fully pushed the rear container in the direction of the proximal end of the device such that the obturateur- piston valve 19 has been pushed completely inside the rear container and that almost all of the injectable substance consisting of the reconstituted medicinal substance solution was evacuated.
Furthermore, it is noted that the second cylindrical member 42 is completely fitted into the first cylindrical member 40 and the one or more notches 43 cooperate with the flexible tongue 44 to lock the two elements relative to each other and prevent return of the second element to its initial position. Through these bodies, the device is not reusable guaranteed.
Figures 10 to 13 show a variant which can be considered as an improvement of the device as shown in Figures 1 to 4 and corresponding in fact to what might be called the primary tank. The device as shown in Figure 10 to the stored state substantially corresponds to the combination of said primary reservoir as shown in Figure 1 with its rear container 11, the front container 13 and the transfer rod 15, housed at least partially, at least during storage, within a cylindrical body or sleeve 60. This sleeve is preferably made of molded synthetic material. It comprises at its front end a zone of lesser thickness 61 that can be easily punctured by a needle reported as shown in Figure 12. Furthermore, it is noted that the transfer rod contains the inner duct 16 which is preferably constituted by a cannula hollow metal that is overmolded.
Figure 11 shows the device 10 terminal activation, the solvent 14 having been transferred through the transfer shaft 15 into the chamber 20 of the rear container 11 to dissolve the lyophilisate 12.
12 illustrates the degassing phase of the syringe provided by the addition of a needle 62 pre-assembled on a base 63 and protected by a protective cap 64. Note that the rear container 11 a. been pushed toward the proximal end of the device to evacuate the air contained in the chamber 20 distal of said tank after completion of mixing.
Figure 13 shows the device after use. It will be noted that the cap 64 has been repositioned to the end of the device to hide the needle and prevent the caregiver accidental injury by this pricking tool. Finally, both distal and proximal containers are nested one inside the other and completely housed within the sleeve 60, which prevents any reuse of the syringe as it is impossible, without breaking the sleeve, of pull the rear container rearwardly. Even if this could be accomplished, security achieved through effective separation of the stopper-piston-valves and the transfer rod is forfeited, as has been explained with reference to the description of Figures 1 to 4.
Figures 14 to 18 illustrate another embodiment derived from the preceding embodiment, wherein the sleeve 60 has been replaced by a sleeve 60 'longer than the sleeve 60. This sleeve 60 is associated a pusher cap 70 as well as a dosing mechanism 71, known per se and commercially available for example under the name "PEN" or similar. The device 10 comprises as before the following main elements which are the rear container 11, the front container 13 and the transfer rod 15. It is shown by Figure 14 to the state of storage. Figure 15 shows the activated state. Figure 16 shows the activated device and equipped with the metering mechanism 71. Figure 17 shows the activated device with the dosing mechanism and provided with an injection syringe 72. Figure 18 shows the device at the end of use.
Figures 19 to 22 show the device adapted for application to ophthalmic field. Note that in this embodiment the front container 13 is made of molded synthetic material in one piece with the sleeve 60 which integrally contains said proximal and partially container, at least during storage, the rear container 11. The sleeve 60 is extended by a ophthalmic drops applicator consisting of a cap 54 substantially identical, at least in function, to that described with reference to Figure 5. This tip may also be in the form of a nasal spray. A protective cap 53 provides a tight and sterile closure of the device during the storage phase shown in Figure 19 and the activation phase represented by Figure 20. The use phase is represented by Figure 21. The end of use is shown in FIG 22. Note that the rear container 11 is fully pressed into the sleeve 60, which guarantees the non-reuse of the device.
23 shows an enlarged view of the stopper-piston-valve 24 and the corresponding end of the transfer rod fitted to its central duct in the storage position. In this position the end 15a of the actual transfer rod is engaged in a first area 24a of the stopper-piston-valve 24, this engagement being formed so as to guarantee a perfect seal and a sterile barrier due to elastic compression which is exerted at the surface 15b. In this position also, the end 16a of the duct 16 which is delimited by a flat section substantially perpendicular to the axis of the conduit, is in abutment against the inlet of the slot 31 constitutes the valve of the obturateur- piston valve 24. As mentioned previously, this valve is kept sealed by the compression of the relatively large material surrounding his lips. The opening of this valve does not take place, as in many prior art systems, under the effect of the pressure of a liquid substance which is forced through the conduit 16 but under the mechanical pressure of introduction of the end 16a of the duct. Therefore, the sealing between the walls of the duct 16 and the lips of the slot 31 remains preserved and the central recess 26 of the stopper-piston-valve
24 never comes into contact with the components of the two containers nor with the reconstituted substance.
Figure 24 shows an enlarged view similar to Figure 23, but on the stopper-piston-valve 19 to the storage state. As before, the other end 15c of the transfer rod 15 is engaged in a central recess 32 of the stopper-piston-valve 19 and the end 16c of the pipe is in abutment against the inlet of the slot 33 acting valve. Tightness and sterility are guaranteed at the surface 15d due to the compression exerted by the material of the stopper-piston-valve 19 of the end 15c of the transfer rod in the area concerned. Similarly, sealing between the end 16c of the duct 16 and the lips of the slot 33 is assured when this end is engaged in said slot.
Note also that for the two obturators-pistons-valves 19 and 24, respectively shown in FIGS 24 and 23, the ends 15a on the one hand and 15c on the other hand of the transfer rod 15 have a shape of harpoon provided with stops to ensure a relatively firm connection of the transfer rod and stopper-piston-valves during the storage phase. With this harpoon-shaped, the ends 15a and 15c define end stops and connecting means for defining a highly accurate position of the said stopper-piston-valves within the device. 25 shows the stopper-piston-valve 24 of Figure 23 in the device activation position. The end 15a of the transfer pin has been pushed inside the central recess 26 and the end 16a of the conduit 16 has been pushed through the pre-slit 31. This figure clearly shows that the zones of sealing and sterility mentioned above are preserved in this phase.
26 shows the stopper-piston-valve 19 shown in FIG 24, the activation phase. Again, the end 15c of the transfer rod 15 has been pushed inside the central recess 32 and the end 16c of the pipe 16 has been pushed through the pre-slit 33. As before, the zones sealing and sterility barriers are preserved in this phase.
Figures 27 to 30 illustrate various accessories or devices intended to be associated to the device 10 for specific uses of this device. In particular, Figure 27 is an enlarged view of the end of the device 10 as shown in FIG 12, the needle 62 mounted on a base 63 is protected by a protective cap 64.
28 shows another embodiment wherein a 62a transfer needle is protected by a rigid plastic guard 80, this needle being 62a also covered with a flexible sleeve 81. The sleeve 81 has a function to avoid a nebulisation of the reconstituted substance within the device 10 at the time of connecting this device to another container such as eg a transfusion bag, through the transfer needle 62a. Indeed, because of a slight overpressure inside the device 10, it may be an nebulization of the medicinal substance, which can be dangerous for the caregiver. This fogging is prevented by the protection afforded by the sleeve 81 which is flexible and folds upon itself as and as the transfer needle is pressed in a suitable tip of the transfusion bag and unfolds when removing and disconnecting block for the device 10. Figure 29 shows the device 10 provided with a sleeve 60a having substantially the same functions as the sleeve 60 shown in Figure 10. At the end of this sleeve there is fitted a nozzle 60b having the shape of a female Luer cone for ensuring the connection of accessories such as a needle holder support, a male Luer connection tip, etc. .
Figure 30 is similar to Figure 29 but the tip 60b has been replaced by a nozzle 60c shaped male Luer cone.
The following figures show schematically the kinematic assembly and construction phases of the device 10 and its components in different scenarios, that is to say when the rear container is intended to contain a lyophilisate, a liquid or less pasty and powder. Figure 31 shows the rear container 11 stored in a cassette 90. Note that this tight storage is made possible by the cylindrical shape of that container. Figure 32 illustrates the filling of the rear container 11 by means of a solution to be lyophilized.
Figure 33 illustrates a prepositioning phase obturateur- the piston-valve 19.
Figure 34 illustrates the lyophilization step during which the steam and gases can escape through the grooves 91 formed on the lower zone of the stopper-piston-valve 19. The transmission of energy is noted that is easy thanks to the bottom flat bottle which promotes uniform formation of ice crystals and the almost complete drying of the lyophilized product.
Figure 35 illustrates the sealing phase of the rear container. This closure is effected by depressing the obturateur- the piston-valve 19 by a pusher 92 which can be constituted by the ceiling of the freeze drying chamber within which is effected the operation . Figure 36 illustrates a positioning phase of the obturateur- piston-valve 19, which positioning is done automatically by suction of this organ within the rear container in which there is vacuum, then mechanically to adjust the final position.
Figure 37 illustrates the return of the filled containers in the magazine 90.
Note that all these operations are performed with standard means widely used in the pharmaceutical industry.
In the case where the active substance contained in the container 11 is a liquid and not a lyophilisate, the process is simplified since it contains only the filling stages shown in Figure 32, pre-positioning of the stopper-piston-valve shown in Figure 33 and final positioning of the stopper-piston-valve, possibly by means of a suitable pusher which allows degassing inside the container.
Figures 4-4 illustrate 38 to fill the rear container 11 by means of a powder. In particular, Figure 38 shows the container 11 accommodated in a cassette 90. Figure 39 illustrates the filling of container 11 by means of a powder dose, such doses being contained in the buckets 93 mounted on a feed system type wheel 94, used in the pharmaceutical industry.
Figure 40 illustrates a prepositioning phase obturateur- the piston valve 19, accompanied by a degassing phase by means of a suction nozzle 95 of appropriate shape. This piece comprises for this purpose a cannula 96 which is engaged through the slot 33 of said stopper-piston-valve. After removal of the instrument, the distal containers are introduced in bulk in a transfer tray 97 from which they emerge in an arrangement ordrée for further processing as shown in Figure 41. Figure 42 shows the container 11 with its distal stopper-piston-valve 19 pre-positioned as shown by the transfer tray 97 of Figure
41. This powder vibration phase is necessary to ensure its settling bottom of the container. The precise positioning of the stopper-piston-valve 19 within the rear container 11 is accompanied, as shown in Figure 43, a suction gas surmounting the powder through the cannula 96 described with reference to 4-0 figure. Figure 44 illustrates the rear container 11 with the stopper-piston-valve positioned properly.
The powder is scraped off the walls of the container during the introduction of the stopper-piston-valve due to the pressure it exerts on these walls. However, a decontamination phase of discharging powder residues on the inner and outer walls of the rear container is still required.
FIGS 45-54 illustrate assembly of the device 10 more specifically for an ophthalmic application. Figure 45 illustrates the front container 13 housed in a cassette 100. This container corresponds to those particularly described above with reference to Figure 5 and Figures 19 to 22. Figure 46 illustrates the filling phase of the container 13 by means of a liquid 14 which may be a solvent or diluent, as was previously mentioned. Figure 47 illustrates the implementation phase of the stopper-piston-valve 24 within the container 13.
After these operations, the containers 13 are replaced in cassette 100 (see Figure 48). As before, this tight storage cassette is only possible thanks to the fact that these containers have a cylindrical shape and free of roughness in particular protruding fins.
The containers 13 arranged in cassette can be stored for a shorter or longer duration and possibly subjected to treatment such as eg sterilization. This phase is illustrated in Figure 49. Figure 50 shows a cassette 90 in which are placed the distal containers 11. Figure 51 illustrates the implementation of the transfer pin 15 in the front container 13.
Figure 52 illustrates the phase terminal assembly which comprises bringing up the rear container 11 of the transfer pin 15 previously positioned inside the front container 13. Figure 53 illustrates a visual control phase of device 10 preassembled . Figure 54 shows the fully assembled device 10 and controlled following the various procedures set forth above.
Note that all these operations can be performed in standard equipment widely used in the pharmaceutical industry and require no special machine for assembling the various components of the device. To facilitate the assembly and reduce the cost, the number of storage modes changes, including the number of times an ordered arrangement to a disordered arrangement and vice versa, is limited to a minimum.
Figures 55-62 illustrate the method of preparing the front container 13 and the establishment of the transfer rod 15. The vacuum container 13 is, as shown in Figure 55, housed in the cassettes 100. Figure 56 illustrates the positioning phase of the stopper-piston-valve 24 within the container 13. Figure 57 shows the filling phase of the solvent or diluent 14. Figure 58 illustrates the encapsulation of the container is -to say, the establishment of the capsule 22. Figure 59 illustrates the return of the containers 13 in the cassette 100 for their temporary storage or later processing such as for example sterilization. Figure 60 illustrates the placement of containers 13 as they are stored in the cassette 100 after any sterilization treatment or the like, within a sleeve 60 as shown in Figure 10. These sleeves 60 are themselves collected within cassette 110 where they have been stored for this assembly. Figure 61 shows the implementation of the transfer pin 15 of the front container 13 previously mounted within the sleeve 60. Figure 62 shows the establishment of the rear container 11 on the other end of the rod transfer 15 pre-assembled as shown in Figure 61.
Again we can say that the assembly is done with standard means which are commonly used in the pharmaceutical industry and that do not require special equipment. In addition, most components including the distal and proximal containers and the sleeve in which is disposed the proximal container are housed in cassettes which reduces or eliminates the number of passages of an ordered state to a disordered state.
Claims
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
PCT/CH1994/000097 WO1995032015A1 (en) | 1994-05-25 | 1994-05-25 | Device for the preparation of a solution, a suspension or an emulsion of a medicinal substance |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
PCT/CH1994/000097 WO1995032015A1 (en) | 1994-05-25 | 1994-05-25 | Device for the preparation of a solution, a suspension or an emulsion of a medicinal substance |
FI960320A FI960320A (en) | 1994-05-25 | 1996-01-24 | Device manufactures of the drug solution, suspension or emulsion |
Publications (1)
Publication Number | Publication Date |
---|---|
WO1995032015A1 true true WO1995032015A1 (en) | 1995-11-30 |
Family
ID=4549348
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/CH1994/000097 WO1995032015A1 (en) | 1994-05-25 | 1994-05-25 | Device for the preparation of a solution, a suspension or an emulsion of a medicinal substance |
Country Status (2)
Country | Link |
---|---|
FI (1) | FI960320A (en) |
WO (1) | WO1995032015A1 (en) |
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WO1998013084A1 (en) * | 1996-09-25 | 1998-04-02 | Abbott Laboratories | Pharmaceutical ampul |
WO2000013723A3 (en) * | 1998-09-04 | 2000-07-06 | Owen Mumford Ltd | Improvements relating to fluid tranfer assemblies |
WO2001026718A1 (en) * | 1999-10-13 | 2001-04-19 | Societe De Conseils De Recherches Et D'applications Scientifiques (S.C.R.A.S.) | Device for reconstituting a therapeutic solution, suspension or dispersion |
FR2799643A1 (en) * | 2000-01-28 | 2001-04-20 | Sod Conseils Rech Applic | Syringe for preparing solutions, suspensions or dispersions, has separate compartments for solid and liquid components prior to injection |
WO2002076373A1 (en) * | 2001-03-27 | 2002-10-03 | Allen Beaumont Hall | Twin chamber dispenser with twist valve |
WO2007020239A1 (en) * | 2005-08-13 | 2007-02-22 | Boehringer Ingelheim International Gmbh | Twin-chamber receptacle and method for filling the same |
WO2009134282A1 (en) * | 2008-04-29 | 2009-11-05 | Medtronic Minimed, Inc. | Systems and methods allowing for reservoir air bubble management |
US7678333B2 (en) | 2003-01-22 | 2010-03-16 | Duoject Medical Systems Inc. | Fluid transfer assembly for pharmaceutical delivery system and method for using same |
US7736353B2 (en) | 2003-01-22 | 2010-06-15 | Duoject Medical Systems Inc. | Pharmaceutical delivery systems and methods for using same |
WO2011064160A1 (en) * | 2009-11-25 | 2011-06-03 | Boehringer Ingelheim International Gmbh | Nebulizer |
US8096971B2 (en) | 2005-08-13 | 2012-01-17 | Boehringer Ingelheim International Gmbh | Dual chamber container for lyophilization, process for the filling up and use thereof |
WO2012059449A1 (en) * | 2010-11-03 | 2012-05-10 | Sanofi-Aventis Deutschland Gmbh | Method and system for preventing leakage of a medicament |
CN104001241A (en) * | 2013-02-21 | 2014-08-27 | 无锡星创生物技术有限公司 | Piston device of retractable safety syringe |
US9089641B2 (en) | 2007-04-30 | 2015-07-28 | Medtronic Minimed, Inc. | Automated filling systems and methods |
US9199030B2 (en) | 2005-05-06 | 2015-12-01 | Medtronic Minimed, Inc. | Infusion medium delivery device and method with drive device for driving plunger in reservoir |
US9522225B2 (en) | 2007-04-30 | 2016-12-20 | Medtronic Minimed, Inc. | Adhesive patch systems and methods |
US9545487B2 (en) | 2012-04-13 | 2017-01-17 | Boehringer Ingelheim International Gmbh | Dispenser with encoding means |
US9682202B2 (en) | 2009-05-18 | 2017-06-20 | Boehringer Ingelheim International Gmbh | Adapter, inhalation device, and atomizer |
US9724482B2 (en) | 2009-11-25 | 2017-08-08 | Boehringer Ingelheim International Gmbh | Nebulizer |
US9744313B2 (en) | 2013-08-09 | 2017-08-29 | Boehringer Ingelheim International Gmbh | Nebulizer |
US9757750B2 (en) | 2011-04-01 | 2017-09-12 | Boehringer Ingelheim International Gmbh | Medicinal device with container |
US9827384B2 (en) | 2011-05-23 | 2017-11-28 | Boehringer Ingelheim International Gmbh | Nebulizer |
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WO1998013084A1 (en) * | 1996-09-25 | 1998-04-02 | Abbott Laboratories | Pharmaceutical ampul |
WO2000013723A3 (en) * | 1998-09-04 | 2000-07-06 | Owen Mumford Ltd | Improvements relating to fluid tranfer assemblies |
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FR2799654A1 (en) * | 1999-10-13 | 2001-04-20 | Sod Conseils Rech Applic | Device for reconstituting a solution, suspension or dispersion and a therapeutic method of preparing and packaging in said device |
WO2001026718A1 (en) * | 1999-10-13 | 2001-04-19 | Societe De Conseils De Recherches Et D'applications Scientifiques (S.C.R.A.S.) | Device for reconstituting a therapeutic solution, suspension or dispersion |
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WO2002076373A1 (en) * | 2001-03-27 | 2002-10-03 | Allen Beaumont Hall | Twin chamber dispenser with twist valve |
US7736353B2 (en) | 2003-01-22 | 2010-06-15 | Duoject Medical Systems Inc. | Pharmaceutical delivery systems and methods for using same |
US7678333B2 (en) | 2003-01-22 | 2010-03-16 | Duoject Medical Systems Inc. | Fluid transfer assembly for pharmaceutical delivery system and method for using same |
US9199030B2 (en) | 2005-05-06 | 2015-12-01 | Medtronic Minimed, Inc. | Infusion medium delivery device and method with drive device for driving plunger in reservoir |
US8096971B2 (en) | 2005-08-13 | 2012-01-17 | Boehringer Ingelheim International Gmbh | Dual chamber container for lyophilization, process for the filling up and use thereof |
WO2007020239A1 (en) * | 2005-08-13 | 2007-02-22 | Boehringer Ingelheim International Gmbh | Twin-chamber receptacle and method for filling the same |
US8002734B2 (en) | 2005-08-13 | 2011-08-23 | Boehringer Ingelheim International Gmbh | Dual chamber container and process for its filling up |
US9522225B2 (en) | 2007-04-30 | 2016-12-20 | Medtronic Minimed, Inc. | Adhesive patch systems and methods |
US9205191B2 (en) | 2007-04-30 | 2015-12-08 | Medtronic Minimed, Inc. | Automated filling systems and methods |
US9089641B2 (en) | 2007-04-30 | 2015-07-28 | Medtronic Minimed, Inc. | Automated filling systems and methods |
US9901514B2 (en) | 2007-04-30 | 2018-02-27 | Medtronic Minimed, Inc. | Automated filling systems and methods |
WO2009134282A1 (en) * | 2008-04-29 | 2009-11-05 | Medtronic Minimed, Inc. | Systems and methods allowing for reservoir air bubble management |
US9682202B2 (en) | 2009-05-18 | 2017-06-20 | Boehringer Ingelheim International Gmbh | Adapter, inhalation device, and atomizer |
KR101725106B1 (en) * | 2009-11-25 | 2017-04-10 | 베링거 인겔하임 인터내셔날 게엠베하 | Nebulizer |
US9724482B2 (en) | 2009-11-25 | 2017-08-08 | Boehringer Ingelheim International Gmbh | Nebulizer |
JP2013511366A (en) * | 2009-11-25 | 2013-04-04 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | Nebulizer |
WO2011064160A1 (en) * | 2009-11-25 | 2011-06-03 | Boehringer Ingelheim International Gmbh | Nebulizer |
KR20120096524A (en) * | 2009-11-25 | 2012-08-30 | 베링거 인겔하임 인터내셔날 게엠베하 | Nebulizer |
JP2013542021A (en) * | 2010-11-03 | 2013-11-21 | サノフィ−アベンティス・ドイチュラント・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツング | Method and system for preventing leakage of the drug |
WO2012059449A1 (en) * | 2010-11-03 | 2012-05-10 | Sanofi-Aventis Deutschland Gmbh | Method and system for preventing leakage of a medicament |
US9757750B2 (en) | 2011-04-01 | 2017-09-12 | Boehringer Ingelheim International Gmbh | Medicinal device with container |
US9827384B2 (en) | 2011-05-23 | 2017-11-28 | Boehringer Ingelheim International Gmbh | Nebulizer |
US9545487B2 (en) | 2012-04-13 | 2017-01-17 | Boehringer Ingelheim International Gmbh | Dispenser with encoding means |
CN104001241A (en) * | 2013-02-21 | 2014-08-27 | 无锡星创生物技术有限公司 | Piston device of retractable safety syringe |
US9744313B2 (en) | 2013-08-09 | 2017-08-29 | Boehringer Ingelheim International Gmbh | Nebulizer |
Also Published As
Publication number | Publication date | Type |
---|---|---|
FI960320D0 (en) | grant | |
FI960320A (en) | 1996-03-11 | application |
FI960320A0 (en) | 1996-01-24 | application |
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