EP2114344A2 - Bouchon de remplissage et de fermeture de récipients contenant des liquides médicaux et procédé de remplissage d'un récipient avec un liquide médical et de fermeture du récipient - Google Patents

Bouchon de remplissage et de fermeture de récipients contenant des liquides médicaux et procédé de remplissage d'un récipient avec un liquide médical et de fermeture du récipient

Info

Publication number
EP2114344A2
EP2114344A2 EP08707179A EP08707179A EP2114344A2 EP 2114344 A2 EP2114344 A2 EP 2114344A2 EP 08707179 A EP08707179 A EP 08707179A EP 08707179 A EP08707179 A EP 08707179A EP 2114344 A2 EP2114344 A2 EP 2114344A2
Authority
EP
European Patent Office
Prior art keywords
closure
piece
container
passage
filling
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.)
Granted
Application number
EP08707179A
Other languages
German (de)
English (en)
Other versions
EP2114344B1 (fr
Inventor
Michael Paul
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.)
Fresenius Medical Care Deutschland GmbH
Original Assignee
Fresenius Medical Care Deutschland GmbH
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 Fresenius Medical Care Deutschland GmbH filed Critical Fresenius Medical Care Deutschland GmbH
Publication of EP2114344A2 publication Critical patent/EP2114344A2/fr
Application granted granted Critical
Publication of EP2114344B1 publication Critical patent/EP2114344B1/fr
Not-in-force legal-status Critical Current
Anticipated expiration legal-status Critical

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
    • A61J1/05Containers specially adapted for medical or pharmaceutical purposes for collecting, storing or administering blood, plasma or medical fluids ; Infusion or perfusion containers
    • A61J1/06Ampoules or carpules
    • 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
    • A61J1/1412Containers with closing means, e.g. caps
    • A61J1/1425Snap-fit type
    • 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
    • A61J1/1475Inlet or outlet ports
    • A61J1/1487Inlet or outlet ports with friction fit, e.g. connecting tubes directly to a protruding port
    • 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
    • A61J1/05Containers specially adapted for medical or pharmaceutical purposes for collecting, storing or administering blood, plasma or medical fluids ; Infusion or perfusion containers
    • A61J1/10Bag-type containers
    • 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
    • A61J1/2096Combination of a vial and a syringe for transferring or mixing their contents

Definitions

  • the invention relates to a closure for filling and closing of containers containing medical fluids. Moreover, the invention relates to a container for receiving a medical fluid with such a closure. Furthermore, the invention relates to a method for filling a container with a medical liquid under aseptic conditions and sealing the container.
  • the aseptic filling of containers is a very important production method in the filling of liquid goods, especially in the medical field, and in the beverage industry.
  • a container to be filled is transferred to a clean room which has been exposed to a special atmosphere and filled with the sterile or aseptically pretreated liquid.
  • different classes of rooms with special atmosphere for the filling are specified.
  • This cleanroom class defines, according to certain specifications, a maximum number of particles and germs. By definition, it is necessary for a class A clean room to be surrounded by a class B clean room that allows for a higher number of particles per volume of atmosphere.
  • the known aseptic filling methods enable a largely germ-free filling of containers with liquids.
  • the aseptic filling methods offer the advantage of obtaining sufficiently germ-free filled liquids without a heat-pressure treatment.
  • the aseptic filling methods are superior to conventional heat sterilization. This becomes especially clear when large volume solution containers, for example pouches of solutions for peritoneal dialysis, to be sterilized by a few liters of volume by a heat / pressure method. In this case, long heating phases are necessary so that the liquid in the bags can assume the appropriate temperature. At the same time, it is necessary to build up an external high pressure acting on the bags, so that the bags do not burst due to the heat-related internal pressure.
  • US 2005/0075613 A1 describes a port for a medical container which has an axially displaceable sealing plug.
  • the sealing plug shifts so that the overpressure can dissipate.
  • the removal or filling of the bag should be done by means of a needle, which is stung by the stopper.
  • a connector with a closure element which serves as a connector for transfer systems.
  • the known connector is not intended for filling containers. When moving the closure element flow openings are exposed.
  • US 4,722,727 describes a port for a bag having a closure body extending into the interior of the bag with a sealing plug. To remove the liquid, the sealing plug located inside the bag is pulled out of the closure body. For this purpose, it is necessary to act on the sealing plug manually from the outside of the bag through the bag wall.
  • An apparatus and a method for filling bottles in which only the bottleneck of the bottles is introduced into a clean room flooded with a special atmosphere, is known from EP 1 514 835 A1.
  • EP 1 230 144 Bl a device and a method for sterile filling of containers is known, in which the containers are introduced into a clean room in which there is a closing station which also touches the containers as sealing caps designated caps. Outside the clean room, the containers are then finally closed, wherein on the cap a closure element is applied, which may be a conventional screw cap.
  • EP 0 352 540 A2 describes a closure cap for dialyzers.
  • a sealing element which, in a first position, allows the passage of a sterilizing fluid and, in a second position, hermetically seals the sterilized dialyzer.
  • the known cap is intended for the so-called in-line sterilization, in which the sterilization takes place in the production line of the dialyzer.
  • the cap is not intended to fill a container to be filled with a medium and to close after filling with the contents, so that the contents are packaged sterile.
  • the invention has for its object to provide a closure for filling and closing of containers containing medical fluids, which reduces the apparatus and energy expenditure in the filling process waiving the known methods of heat sterilization.
  • a further object of the invention is to specify a method with which, dispensing with the known methods of heat sterilization, the apparatus and energy expense during filling and closing containers containing medical fluids is reduced.
  • Another object of the invention is to provide a container with such a closure.
  • the closure according to the invention for filling and closing of containers containing medical fluids has a fastening piece and a connecting piece, wherein a closure body is formed between the fastening piece and the connecting piece.
  • the attachment piece which has a passage, can be attached to the container, while a connection part of a filling device can be connected to the connection piece, which likewise has a passage.
  • the closure body has a recess connecting the passage of the attachment piece and the connection piece, so that after the connection of the filling device to the connection piece, the container can be filled with a medicinal liquid.
  • the closure according to the invention is characterized in that in the recess of the closure body, a closure piece is arranged, which is displaceable between a free passage of the attachment piece or the connector position and a passage of connector or attachment piece closing position.
  • the closure has a removable protective cap.
  • the closure according to the invention is to be understood in connection with the method according to the invention for filling a container with a medical liquid and closing the container.
  • the initially empty but already sterilized container with the closure according to the invention, which has a closure cap is transferred into a clean room which has a predetermined clean room class.
  • the container is transferred with the closure in a clean room of clean room class B.
  • the protective cap of the closure thereby closes the opening of the connector germ-tight.
  • the passage of the connection piece or the attachment piece is not yet closed by the closure piece located in the closure body.
  • the container with the closure in a clean room which has a clean room class, which is higher than the clean room class of the first clean room, preferably in a clean room of clean room class A. It is advantageous if not the entire container, but only the closure in the clean room with the higher Clean room class, preferably the clean room class A is located.
  • the protective cap can be removed in the clean room of cleanroom class B just before it enters the clean room of cleanroom class A, whereby the opening of the connection piece is exposed.
  • the protective cap is removed in the lock section between the clean room of clean room class B and the clean room of clean room class A. In principle, however, the closure can only be removed in the class A clean room.
  • the container After connecting the connection part of the filling device to the connection piece of the closure, the container is filled with the medical liquid in the clean room of cleanroom class A.
  • the closure piece of the closure body After the container has been filled, the closure piece of the closure body is preferably displaced into the position closing the passage of the fastening piece or connecting piece with a pressure stamp of the filling device which can be moved in the axial direction. Thus, the passage of the fitting or attachment piece is sealed. Finally, the filled and sealed container is removed from the clean room.
  • the protective cap has the task of protecting the closure from contamination after the first sterilization process.
  • the protective cap closes the opening of the closure, although the closure piece of the closure body, the passage of the connection or attachment piece releases. Only shortly before entering the cleanroom with the higher cleanroom class, the opening of the closure is released by removing the protective cap. The contamination probability is reduced to a minimum.
  • the protective cap is placed lockably on the connecting piece and the closure body.
  • the protective cap can also be clamped.
  • the decisive factor is that the protective cap is captively secured to the closure.
  • the cap encloses only the connector and the closure body, so that the attachment piece is exposed.
  • the closure piece is arranged latching in the free passage of the attachment piece or the connector free position in the recess of the closure body. This ensures that the closure is open at the beginning of the filling process after removing the protective cap. Instead of a latching connection of the closure piece and closure body, the closure piece can also be inserted by clamping into the closure body.
  • a further preferred embodiment provides an axial guidance of the guide piece in the closure body.
  • the closure piece preferably has a guide piece with openings, which is arranged displaceably in the recess of the closure body.
  • the guide piece of the closure piece has circumferentially distributed ribs, the openings lying between the ribs.
  • the guide piece is pressed by the plunger of the filling device for closing the closure down.
  • the plunger can grip the guide piece better
  • the guide piece preferably has a central recess for receiving the plunger.
  • the closure piece of the closure body preferably has a substantially cylindrical valve piece, with which the passage of the attachment piece can be closed. Alternatively, it is also possible to close the passage of the connecting piece with the cylindrical valve piece.
  • connecting piece and closure body are formed as a substantially hollow cylindrical body, in which the closure piece is inserted, while the attachment piece is preferably formed as a substantially rohrfbrmiger body which is attached to the container.
  • Connecting piece, closure body and attachment piece are in a particularly preferred embodiment, a one-piece injection molded part that can be produced inexpensively in large quantities.
  • the closure according to the invention is intended for filling and closing of medical containers of most diverse design.
  • the container may be a rigid container or flexible bag.
  • FIG. 1 shows an exemplary embodiment of the closure according to the invention for filling and closing of containers containing medicinal liquids in a sectional view
  • FIG. 2 is a perspective view of the closure of FIG. 1 with the protective cap removed
  • Fig. 3 is a section through the closure of Fig. 1 in perspective
  • Fig. 4 is a section through the closure of Fig. 1 in perspective
  • FIG. 6 shows a bag according to the invention with the closure according to the invention
  • Fig. 7 shows a syringe according to the invention with the closure according to the invention
  • FIG. 8 shows an ampoule according to the invention with the closure according to the invention.
  • Fig. 1 shows an embodiment of the closure according to the invention in a sectional view with attached protective cap, while Figure 2 shows a perspective view of the closure with the protective cap removed.
  • the closure according to the invention comprises a closure part 1 and a protective cap 2 which sits on the closure part 1.
  • the closure part 1 has a hollow cylindrical body 3, which serves as a fastening piece for fastening the closure to the connecting piece 4 of a container, not shown in Fig. 1.
  • the connecting piece 4 is seated in the cylindrical attachment piece 3, wherein both parts are glued or welded together.
  • the closure has a connection piece 5, which serves for the connection of a connection part (not shown in FIG. 1) of a filling device.
  • a closure body 6 is formed between the attachment piece 3 and the connector 5, a closure body 6 is formed.
  • Connector 5 and closure body 6 are a substantially hollow cylindrical body having a larger inner and outer diameter than the substantially tubular body of the attachment piece 3.
  • Connector 5 and closure body 6 are made together with the attachment piece 3 as a one-piece injection molded part.
  • FIG. 1 shows the closure with the closure piece in the open position, wherein the passage 10 of the connecting piece 5 is connected via the recess 7 of the closure body with the passage 9 of the attachment piece 3. In the open position, the closure piece 8 is determined latching.
  • the closure piece 8 has a guide piece 11 with openings 13, from which four ribs 12 distributed at equal intervals distributed circumferentially project radially, whose end faces abut the wall 14 of the closure body 6 (FIG. 3).
  • the ribs 12 each have an outwardly projecting shoulder 15, which engages in a circumferential groove 16 in the wall of the closure body 6 snapping.
  • the guide piece 11 of the closure piece 8 has at the top a central cylindrical recess 17 for receiving a plunger, not shown Filling device on.
  • the guide piece 11 further has a substantially cylindrical, preferably hollow cylindrical valve piece 18, with which the passage 9 of the attachment piece 3 can be closed.
  • the guide piece 11 is pressed with a plunger, not shown, in the recess of the closure body down.
  • the latching connection of the valve piece dissolves in the valve body.
  • valve piece 18 of the closure piece 8 being seated in the passage 9 of the attachment piece 3.
  • the ribs 12 lie on a projecting shoulder 20 which extends around the passage 9 of the attachment piece 3.
  • the valve member 18 is sealingly seated in the passage of the attachment piece 3.
  • both parts are conical.
  • the protective cap 2 of the closure shown in FIG. 2 has a cover part 21 and an edge part 22 which encloses the connection piece 5 and the closure body 6 when the protective cap is seated on the closure part 1.
  • a sterile membrane 23 is inserted in the lid part 21 of the protective cap 2.
  • the lower edge 25 of the edge part 22 seals against a projecting shoulder 24, which encloses the closure part 1.
  • a shoulder 29 is formed, on which a sealing ring 30 is fixed, which seals the protective cap 2 against the top of the projecting edge 24 of the closure part 1.
  • Protective cap 2 and closure part 1 can be connected to each other with a bayonet closure 26, which has inwardly projecting locking elements 27 from the lower edge 25 of the edge part 22, which engage in undercut grooves 28 on the outside of the outwardly projecting edge 24 of the closure part 1.
  • FIGS. 5A to 5D show the closure together with a part of the connecting piece 4 of the container.
  • the initially unfilled container as such is not shown in the figures.
  • the container with the closure is fed to a filling station, in which the following process steps are carried out.
  • the container with the closure according to the invention is first introduced into a clean room of cleanroom class B.
  • the protective cap 2 is still on the closure part 1 of the closure.
  • the closure is sealed germ-tight, which has been sterilized together with the container in a previous sterilization process.
  • a sterile membrane 23 is provided in the lid part 21 of the protective cap 2 of the closure, wherein the membrane closes the closure germ-tight after sterilization, but is permeable to water vapor or gas during sterilization.
  • the closure is then transferred from the class B clean room to a class A clean room surrounded by the clean room B. It is not necessary that the entire container with the closure is introduced into a class A clean room. It is crucial that the closure of the container is in the clean room.
  • the limit values for the microbial contaminations and for the permitted particle concentrations are specified in the EC Guide to Good Manufacturing Practice for Class A and B cleanrooms. These limits are known in the art. It is basically irrelevant which specification meets one or the other clean room. It is crucial that the clean room, in which the filling takes place, is so low burdened with germs and / or particles that aseptic filling is possible.
  • the protective cap 2 is removed from the closure part 1 of the closure shortly before the transfer into the clean room of clean room class A.
  • the protective cap is removed in the lock section between the clean room of clean room class B and the clean room of clean room class A.
  • the shutter is still open at this time ( Figure 5A).
  • the bag is now filled in the class A cleanroom.
  • the filling of the bag by means of a filling device, of which only the essential components are shown.
  • the filling device has a filling tube 31, the outer diameter or inner diameter of the outer or inner diameter of the connecting piece 5 of Closure part 1 of the closure corresponds.
  • the filling tube 31 of the filling device is moved in the vertical direction until its end face bears against the end face of the connecting piece 5 of the closure part 1. Both parts seal against each other at the end faces.
  • a plunger 32 which is also movable in the vertical direction.
  • the plunger 32 is moved to close the shutter down.
  • the plunger pushes the closure piece 8 from the latching position downwards, so that the closure piece closes the closure.
  • the filling tube 31 is moved upwards again with the pressure piston 32 (FIG. 5D). After sealing the cap, the cap from the class A clean room is returned to the class B clean room.
  • FIGS. 5A to 5D For gripping the closure during insertion and removal of the closures in or out of the clean rooms, tools, not shown, for example holding jaws or the like are provided in FIGS. 5A to 5D, which are known to the person skilled in the art.
  • the protective cap 2 protects the closure part 1 of the closure, in particular the region of the opening above the closure piece after the preceding heat sterilization from contamination. Since the protective cap in a class B clean room is only removed shortly before entry into a class A clean room for the actual filling process before closing the closure, the probability of contamination is reduced to a minimum.
  • Fig. 6 shows an embodiment of a container according to the invention with the closure according to the invention.
  • the container is a bag 33, in particular for receiving enteral nutrient solution, parenteral nutrient solution, dialysis fluid or infusion solution, which is produced from a film tube 34 or two superimposed films which are welded together at the edges.
  • the connecting piece 4 In the overhead weld 35 of the connecting piece 4 is welded, the connected to the attachment piece 3 of the closure part i, for example glued or welded.
  • Fig. 7 shows a further embodiment of a container with the closure.
  • This container is a syringe 36, which has a syringe barrel 37 with a cone 38, in particular Luer cone, and a piston 39.
  • the closure according to the invention is fastened to the cylinder 37, the cone 38 extending into the attachment piece 3 of the closure part 1.
  • Fig. 8 shows a vial 40 as a container, which also has a cone 41, in particular Luer cone.
  • the closure according to the invention is attached to the ampoule, wherein the cone 41 extends back into the attachment piece 3 of the closure part 1.

Landscapes

  • Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Hematology (AREA)
  • Medical Preparation Storing Or Oral Administration Devices (AREA)
  • Basic Packing Technique (AREA)
  • Closures For Containers (AREA)

Abstract

L'invention concerne un bouchon de remplissage et de fermeture de récipients contenant des liquides médicaux et un procédé de remplissage d'un récipient avec un liquide médical et de fermeture du récipient. Selon l'invention, le bouchon comporte un élément de fixation (3) pouvant être disposé sur le récipient, et un élément de connexion (5) pouvant être connecté à une pièce de connexion d'un dispositif de remplissage. Un corps de fermeture (6) est créé entre l'élément de fixation et l'élément de connexion, un élément de fermeture (8) destiné à fermer le bouchon étant logé dans le corps de fermeture. L'élément de fermeture (8) peut coulisser entre une position de fermeture du bouchon et une position d'ouverture du bouchon. Le bouchon est fermé de façon étanche au moyen d'un capot de protection amovible. Le procédé selon l'invention est caractérisé en ce que le récipient est rempli au moyen du bouchon lorsque le capot de protection est retiré dans une salle blanche, le bouchon étant fermé dans la salle blanche, après remplissage, par compression de l'élément de fermeture dans le bouchon.
EP08707179.1A 2007-01-25 2008-01-22 Procédé de remplissage d'un récipient avec un liquide médical et de fermeture du récipient et bouchon de remplissage et de fermeture de récipients contenant des liquides médicaux Not-in-force EP2114344B1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE200710003835 DE102007003835A1 (de) 2007-01-25 2007-01-25 Verschluss zum Befüllen und Verschließen von medizinische Flüssigkeiten enthaltenen Behältnissen und Verfahren zum Befüllen eines Behältnisses mit einer medizinischen Flüssigkeit und Verschließen des Behältnisses
PCT/EP2008/000446 WO2008089948A2 (fr) 2007-01-25 2008-01-22 Bouchon de remplissage et de fermeture de récipients contenant des liquides médicaux et procédé de remplissage d'un récipient avec un liquide médical et de fermeture du récipient

Publications (2)

Publication Number Publication Date
EP2114344A2 true EP2114344A2 (fr) 2009-11-11
EP2114344B1 EP2114344B1 (fr) 2016-03-23

Family

ID=39327160

Family Applications (1)

Application Number Title Priority Date Filing Date
EP08707179.1A Not-in-force EP2114344B1 (fr) 2007-01-25 2008-01-22 Procédé de remplissage d'un récipient avec un liquide médical et de fermeture du récipient et bouchon de remplissage et de fermeture de récipients contenant des liquides médicaux

Country Status (6)

Country Link
US (1) US8763798B2 (fr)
EP (1) EP2114344B1 (fr)
JP (1) JP5461195B2 (fr)
CN (1) CN101588781B (fr)
DE (1) DE102007003835A1 (fr)
WO (1) WO2008089948A2 (fr)

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EP3383343A4 (fr) 2015-12-04 2019-07-10 ICU Medical, Inc. Systèmes, procédés et composants pour le transfert de fluides médicaux
USD851745S1 (en) 2016-07-19 2019-06-18 Icu Medical, Inc. Medical fluid transfer system
JP7046051B2 (ja) 2016-07-25 2022-04-01 アイシーユー・メディカル・インコーポレーテッド 医療用流体移送モジュールおよびシステムの中の空気バブルをトラップするためのシステムおよびコンポーネント
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CN101588781B (zh) 2013-10-16
DE102007003835A1 (de) 2008-07-31
JP5461195B2 (ja) 2014-04-02
JP2010516360A (ja) 2010-05-20
US8763798B2 (en) 2014-07-01
US20090314781A1 (en) 2009-12-24
CN101588781A (zh) 2009-11-25
WO2008089948A2 (fr) 2008-07-31
WO2008089948A3 (fr) 2008-10-30
EP2114344B1 (fr) 2016-03-23

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