US20070102393A1 - Specimen enclosure apparatus and containers and closure devices for the same - Google Patents

Specimen enclosure apparatus and containers and closure devices for the same Download PDF

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Publication number
US20070102393A1
US20070102393A1 US11/523,306 US52330606A US2007102393A1 US 20070102393 A1 US20070102393 A1 US 20070102393A1 US 52330606 A US52330606 A US 52330606A US 2007102393 A1 US2007102393 A1 US 2007102393A1
Authority
US
United States
Prior art keywords
closure device
seal
neck
flange
cavity
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.)
Abandoned
Application number
US11/523,306
Other languages
English (en)
Inventor
Bruno Colin
Sylvain Baeyaert
Chris Ronsick
Mark Wilson
Ron Robinson
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.)
Biomerieux SA
Biomerieux Inc
Original Assignee
Biomerieux SA
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 Biomerieux SA filed Critical Biomerieux SA
Priority to US11/523,306 priority Critical patent/US20070102393A1/en
Assigned to BIOMERIEUX, INC. reassignment BIOMERIEUX, INC. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: ROBINSON, RON, RONSICK, CHRIS, WILSON, MARK, BAEYAERT, SYLVAIN, COLIN, BRUNO
Publication of US20070102393A1 publication Critical patent/US20070102393A1/en
Abandoned legal-status Critical Current

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Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B65—CONVEYING; PACKING; STORING; HANDLING THIN OR FILAMENTARY MATERIAL
    • B65D—CONTAINERS FOR STORAGE OR TRANSPORT OF ARTICLES OR MATERIALS, e.g. BAGS, BARRELS, BOTTLES, BOXES, CANS, CARTONS, CRATES, DRUMS, JARS, TANKS, HOPPERS, FORWARDING CONTAINERS; ACCESSORIES, CLOSURES, OR FITTINGS THEREFOR; PACKAGING ELEMENTS; PACKAGES
    • B65D51/00—Closures not otherwise provided for
    • B65D51/24—Closures not otherwise provided for combined or co-operating with auxiliary devices for non-closing purposes
    • B65D51/241—Closures not otherwise provided for combined or co-operating with auxiliary devices for non-closing purposes provided with freeze-drying means
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/508—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above
    • B01L3/5082—Test tubes per se
    • B01L3/50825—Closing or opening means, corks, bungs
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B65—CONVEYING; PACKING; STORING; HANDLING THIN OR FILAMENTARY MATERIAL
    • B65D—CONTAINERS FOR STORAGE OR TRANSPORT OF ARTICLES OR MATERIALS, e.g. BAGS, BARRELS, BOTTLES, BOXES, CANS, CARTONS, CRATES, DRUMS, JARS, TANKS, HOPPERS, FORWARDING CONTAINERS; ACCESSORIES, CLOSURES, OR FITTINGS THEREFOR; PACKAGING ELEMENTS; PACKAGES
    • B65D39/00—Closures arranged within necks or pouring openings or in discharge apertures, e.g. stoppers
    • B65D39/0005—Closures arranged within necks or pouring openings or in discharge apertures, e.g. stoppers made in one piece
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B65—CONVEYING; PACKING; STORING; HANDLING THIN OR FILAMENTARY MATERIAL
    • B65D—CONTAINERS FOR STORAGE OR TRANSPORT OF ARTICLES OR MATERIALS, e.g. BAGS, BARRELS, BOTTLES, BOXES, CANS, CARTONS, CRATES, DRUMS, JARS, TANKS, HOPPERS, FORWARDING CONTAINERS; ACCESSORIES, CLOSURES, OR FITTINGS THEREFOR; PACKAGING ELEMENTS; PACKAGES
    • B65D41/00—Caps, e.g. crown caps or crown seals, i.e. members having parts arranged for engagement with the external periphery of a neck or wall defining a pouring opening or discharge aperture; Protective cap-like covers for closure members, e.g. decorative covers of metal foil or paper
    • B65D41/02—Caps or cap-like covers without lines of weakness, tearing strips, tags, or like opening or removal devices
    • B65D41/16—Snap-on caps or cap-like covers
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B65—CONVEYING; PACKING; STORING; HANDLING THIN OR FILAMENTARY MATERIAL
    • B65D—CONTAINERS FOR STORAGE OR TRANSPORT OF ARTICLES OR MATERIALS, e.g. BAGS, BARRELS, BOTTLES, BOXES, CANS, CARTONS, CRATES, DRUMS, JARS, TANKS, HOPPERS, FORWARDING CONTAINERS; ACCESSORIES, CLOSURES, OR FITTINGS THEREFOR; PACKAGING ELEMENTS; PACKAGES
    • B65D45/00—Clamping or other pressure-applying devices for securing or retaining closure members
    • B65D45/32—Clamping or other pressure-applying devices for securing or retaining closure members for applying radial or radial and axial pressure, e.g. contractible bands encircling closure member
    • B65D45/322—Clamping or other pressure-applying devices for securing or retaining closure members for applying radial or radial and axial pressure, e.g. contractible bands encircling closure member the clamping device being an annular member moved axially to clamp the closure by using radial pressure
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/04—Closures and closing means
    • B01L2300/041—Connecting closures to device or container
    • B01L2300/042—Caps; Plugs
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/04—Closures and closing means
    • B01L2300/046—Function or devices integrated in the closure
    • B01L2300/048—Function or devices integrated in the closure enabling gas exchange, e.g. vents
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/04—Closures and closing means
    • B01L2300/046—Function or devices integrated in the closure
    • B01L2300/049—Valves integrated in closure

Definitions

  • the present invention relates to apparatus for enclosing a specimen, reagants and components thereof.
  • the present invention relates to an apparatus for enclosing a specimen that can be used in a microbial detection and/or characterization system.
  • FIGS. 1A and 1B show a simple plug stopper 100 where the plug seal 106 is defined by contact between the cylindrical surface of the stopper 100 and the neck 108 of the bottle 102 . The closure holding the stopper in the bottle is not shown in FIGS.
  • the stopper 100 may be sealed in the neck 108 of the bottle 102 by radial R compression. This compression may be induced by the interference of the stopper 100 with the bottle neck 108 .
  • the stopper plug 100 may, therefore, have an outer diameter greater than the inner diameter of the neck 108 of the bottle to cause the stopper 100 to be compressed.
  • This plug seal 106 may also be referred to as a valve seal.
  • a flange seal 104 may be created by contact between a flange 104 a , which is the horizontal surface of the stopper, and a top horizontal surface 104 b of the bottle 102 .
  • the compression where these two surfaces mate may be provided by a closure member, which may be applied over the stopper 100 and onto the bottle 102 .
  • these closures may be a crimp seal, a screw cap or a tear-off seal.
  • the stopper 100 may seal to the top surface 104 b of the bottle 102 by being compressed by the closure.
  • a flange seal is generally compressed by the closure and this sealing force (compression) can generally be controlled by the equipment that applies the stopper.
  • Lyophilization stoppers are another known type of stopper used in the pharmaceutical industry. Typically, these stoppers 110 contain a slot 114 in the stopper legs 116 as seen in FIGS. 2A through 2C . The stopper 110 may be held above the vial 112 by protruding nibs 118 , which position ( FIG. 2C ) allows gas to be evacuated from the vial 112 through the slots 114 in the stopper 110 . At the end of the degassing process, the stopper 110 may be pressed into the vial (bottle) 112 and seal the bottle 112 through a flange and/or a plug seal ( FIG. 2A ). A plug seal and flange seal have been described above.
  • the limitations of a standard lyophilization stopper depend on the applications of the product.
  • the standard lyophilization stopper typically has two legs 116 that deflect in towards the bottle 112 due to the compression of the stopper 110 into the bottle 112 . This can be seen in a finite element analysis model shown in FIG. 3 . Due to the plug seal and the geometric interference, the legs 116 of the stopper 110 generally deflect in towards the center of the vial. The vial is not shown for clarity.
  • the stopper and crimp shown above are modeled in a cross section in FIG. 3 , because the boundary and load conditions in FIG. 3 are symmetric about the center plane.
  • the movement of the surface contact (interface) between the stopper and bottle or vial can make it difficult to sterilize this interface.
  • the product In an autoclave process, the product is typically placed into an autoclave and steam heats the product for at least 15 minutes at 121° C. The steam outside the product transfers heat to the interior contents of the vial, which heat vaporizes moisture in the vial. This moist heat is then transferred to the inner surfaces of the bottle, which kill microorganisms and spores. The rate of kill for microorganisms (bacteria, molds etc) depends on the amount of time exposed to this moist heat.
  • FIG. 4 illustrates two zones where moist and dry heat may be transferred to the stopper/vial interface.
  • steam from the heated moisture inside the vial does not penetrate into first zone 124 , as the stopper 120 is compressed against the bottle 122 in the first zone 124 .
  • Dry heat may still be transferred to this area 124 and this area 124 may still reach the temperature of the autoclave (standard cycle temperature 121° C.).
  • standard cycle temperature 121° C. standard cycle temperature 121° C.
  • dry heat is generally not as effective at killing microorganisms as moist heat.
  • the second zone 126 is exposed directly with moist heat due to clearance between the stopper 120 and the bottle (vial) 122 .
  • septums may also be used to seal a vial.
  • This type of stopper/seal may be a circular elastomeric material.
  • An advantage of a septum (flange) seal is that there is no plug seal. The plug seal may move away from the bottle neck during shipping or rough handling.
  • the contact area of a plug seal may change with pressure inside the bottle or vary with the crimping pressure on the stopper. If the contact area changes after the product is terminally sterilized in an autoclave, microorganisms trapped in the plug seal may come into contact with the product.
  • a septum stopper may eliminate the problems with a plug seal as no plug seal is provided. However, a plug seal may be beneficial to retaining the seal integrity of the product. In addition, a plug seal may be more stable in the vial than the flange only seal of a septum stopper. A septum stopper generally may move radially, as there is no plug seal preventing this radial movement. This radial movement may break the integrity of the flange seal between the septum and vial. Secondly, the plug seal may be more stable in the bottle during the assembly of the stopper to the vial. A crimp seal placed over the septum may move the septum and compromise the seal integrity. FIG.
  • FIG. 5 shows the cross-section of a septum 130 forming a flange seal with a bottle (vial) 132 .
  • the illustrated flange seal is between the flat surface of the septum 130 and the top surface 134 of the vial 132 .
  • a closure (not shown) compresses the septum 130 on top of the vial 132 .
  • Embodiments of the present invention include a specimen enclosure apparatus.
  • the specimen enclosure apparatus includes a container having a cavity configured to receive the specimen and an opening extending through a neck of the container to the cavity.
  • An internal flange is positioned intermediate the neck of the container.
  • the specimen enclosure apparatus further includes a closure device configured to be received in the opening.
  • the closure device has a flange seal portion configured to contact the internal flange to form a flange seal proximate the cavity and further has a radial travel limiter integrally formed with the closure device that is configured to contact the container in the opening to limit radial movement of the flange seal portion relative to the internal flange.
  • the neck further includes a plug sealing cylindrical surface extending from proximate the internal flange away from the cavity.
  • the radial travel limiter is a mating plug sealing cylindrical surface configured to form a plug seal with the plug sealing cylindrical surface of the neck.
  • the flange seal is positioned between the plug seal and the cavity.
  • the flange seal is an internal flange seal and the container further includes an external flange positioned at an end of the neck away from the cavity.
  • the closure device further includes an external flange seal portion configured to contact the external flange to form an external flange seal at the end of the neck.
  • the plug seal is positioned between the external flange seal and the internal flange seal.
  • the closure device is positioned in the opening and the apparatus further includes a closure member extending over the closure device and coupled to the container that retains the closure device in the opening and compresses the flange seal.
  • the closure member may be a crimp seal, a screw cap and/or a tear-off seal.
  • An edge of the flange seal adjacent the cavity may be positioned to be directly exposed to moist heat during sterilization of the apparatus.
  • the closure device further includes a degassing extension member extending from the flange seal portion into the cavity that is configured to retain the closure device in a degassing position in the opening defining a passage from the cavity through the opening through which a gas may be moved into and out of the cavity.
  • the degassing extension member may include a plurality of tabs extending from an exterior surface thereof configured to engage the neck in the opening to retain the closure device in the degassing position and to displace the exterior surface of the degassing extension member from the neck to define the passage from the cavity through the opening.
  • specimen enclosure apparatus include a container having a cavity configured to receive the specimen and an opening extending through a neck of the container to the cavity and a closure device.
  • the closure device covers the opening and has a flange seal portion configured to contact an external flange seal portion on an end of the neck of the container displaced from the cavity to form a flange seal closing the opening.
  • the closure device further has a radial travel limiter integrally formed with the closure device that contacts an exterior surface of the neck to limit radial movement of the flange seal portion of the closure device relative to the external flange seal portion of the container.
  • the apparatus may further include a closure member coupled to the container that retains the closure device covering the opening and compresses the flange seal.
  • the closure device further includes a degassing extension member extending from the flange seal portion along an exterior surface of the neck that is configured to retain the closure device in a degassing position defining a passage from the cavity through the opening through which a gas may be moved into and out of the cavity.
  • the degassing extension member may include a tab extending from a surface thereof configured to engage the exterior surface of the neck to retain the closure device in the degassing position.
  • the tab may be a circumferentially extending ridge and the degassing extension member may further include a slot extending past the ridge to define the passage along the exterior surface of the neck.
  • the neck further includes a plug sealing cylindrical surface defined by the exterior surface of the neck and the radial travel limiter is a mating plug sealing cylindrical surface configured to form a radial seal with the plug sealing cylindrical surface of the neck, the flange seal being positioned between the radial seal and the cavity.
  • the apparatus may further include a closure member coupled to the container that retains the closure device covering the opening and compresses the flange seal. The closure member may further compress the radial seal.
  • the neck may further include a narrowed portion and an intermediate portion extending from the narrowed portion to the plug sealing cylindrical surface and the closure member may engage the intermediate portion to retain the closure device.
  • containers for a specimen enclosure apparatus include a main portion including a cavity configured to receive the specimen and a neck extending from the main portion. An opening extends through the neck to the cavity.
  • An internal flange is positioned intermediate the neck of the container that is configured to contact a flange seal portion of a closure device to form a flange seal proximate the cavity.
  • a radial travel limiting contact surface is provided in the opening that is configured to contact the closure device to limit radial movement of the flange seal.
  • the radial travel limiting contact surface may be a plug sealing cylindrical surface extending from proximate to the internal flange away from the cavity that is configured to form a plug seal with the closure device.
  • the container may further include an external flange positioned at an end of the neck away from the cavity that is configured to contact the closure device to form an external flange seal, the plug seal being positioned between the flange seal formed by the internal flange and the external flange seal.
  • closure devices for a specimen enclosure apparatus include a flange seal portion configured to contact an internal flange positioned intermediate a neck of a container configured to receive the specimen to form a flange seal proximate the cavity and further include a radial travel limiter.
  • the radial travel limiter is integrally formed with the flange seal portion and is configured to contact the container in an opening extending through the neck to the cavity to limit radial movement of the flange seal portion relative to the internal flange.
  • the radial travel limiter may be a mating plug sealing cylindrical surface extending from the flange seal portion that is configured to form a plug seal with a plug sealing cylindrical surface extending from the internal flange of the container away from the cavity of the container.
  • the closure device may further include an external flange seal portion configured to form a further flange seal with an external flange of the container positioned at an end of the neck away from the cavity, the plug seal being positioned between the flange seal and the further flange seal.
  • the closure device further includes a degassing extension member extending from the flange seal portion and away from the radial travel limiter that is configured to retain the closure device in a degassing position in the opening defining a passage from the cavity through which a gas may be moved into and out of the cavity.
  • the degassing extension member may include a plurality of tabs extending from an exterior surface thereof configured to engage the neck in the opening to retain the closure device in the degassing position and to displace the exterior surface of the degassing extension member from the neck to define the passage.
  • FIG. 1A is a cross-sectional view illustrating the flange and plug areas of a conventional stopper in a specimen bottle.
  • FIG. 1B is a bottom perspective view of the stopper of FIG. 1A .
  • FIG. 2A is a perspective view illustrating a conventional lyophilization stopper insert to a sealed position in a specimen bottle according to the prior art.
  • FIG. 2B is a bottom perspective view illustrating the lyophilization stopper of FIG. 2A .
  • FIG. 2C is a perspective view illustrating of the arrangement of FIG. 2A with the stopper in a degassing position.
  • FIG. 3 illustrates a finite element analysis of the lyophilization stopper shown in FIG. 2A .
  • FIG. 4 is a cross-sectional view illustrating the interface between a stopper and a vial including two areas of the interface of a plug seal therebetween according to the prior art.
  • FIG. 5 is a cross-sectional view of a conventional septum forming a flange seal with a vial according to the prior art.
  • FIGS. 6A through 6D illustrate a closure device for a specimen container according to some embodiments of the present invention.
  • FIGS. 6E through 6F illustrate a closure device for a specimen container according to other embodiments of the present invention.
  • FIG. 6G is a perspective view of a closure device for a specimen container according to further embodiments of the present invention.
  • FIGS. 7A through 7D illustrate a closure device for a specimen container according to yet further embodiments of the present invention.
  • FIG. 8 is a perspective view of a specimen container according to some embodiments of the present invention.
  • FIG. 9A is a cross-sectional view of the neck of the specimen container of FIG. 8 .
  • FIG. 9B is a cross-sectional view of the neck of conventional specimen container.
  • FIG. 10 is a front elevational view of the specimen container shown in FIG. 8 .
  • FIG. 11 is a cross-sectional view of the specimen container shown in FIG. 8 .
  • FIG. 12 is a cross-sectional view of the closure device shown in FIG. 6A placed in the specimen container shown in FIG. 8 .
  • FIGS. 13A and 14A are cross-sectional views illustrating the closure devices of FIGS. 6A and 7A , respectively, in the degassing position in the specimen container shown in FIG. 8 .
  • FIGS. 13B and 14B are cross-sectional views illustrating the closure devices of FIGS. 6A and 7A , respectively, in the sealing/closed position in the specimen container shown in FIG. 8 .
  • FIG. 15 is a perspective view illustrating a closure device according to further embodiments of the present invention.
  • FIG. 16A is a cross-sectional view illustrating the neck area of a specimen enclosure apparatus in a degassing position according to further embodiments of the present invention.
  • FIG. 16B is a front perspective view illustrating the neck area of a specimen enclosure apparatus of FIG. 16A in a sealed/closed position.
  • FIG. 16C is a cross-sectional view illustrating the neck area of the specimen enclosure apparatus FIG. 16B .
  • first, second, etc. may be used herein to describe various elements, components, regions, layers and/or sections, these elements, components, regions, layers and/or sections should not be limited by these terms. These terms are only used to distinguish one element, component, region, layer or section from another region, layer or section. Thus, a first element, component, region, layer or section discussed below could be termed a second element, component, region, layer or section without departing from the teachings of the present invention.
  • spatially relative terms such as “beneath”, “below”, “lower”, “above”, “upper” and the like, may be used herein for ease of description to describe one element or feature's relationship to another element(s) or feature(s) as illustrated in the figures. It will be understood that the spatially relative terms are intended to encompass different orientations of the device in use or operation in addition to the orientation depicted in the figures. For example, if the device in the figures is turned over, elements described as “below” or “beneath” other elements or features would then be oriented “above” the other elements or features. Thus, the exemplary term “below” can encompass both an orientation of above and below. The device may be otherwise oriented (rotated 90° or at other orientations) and the spatially relative descriptors used herein interpreted accordingly.
  • FIG. 6A is a perspective view of a closure device 200 a .
  • FIG. 6B is a top plan view
  • FIG. 6C is a front view
  • FIG. 6D is a bottom plan view of the closure device 200 a of FIG. 6A .
  • FIGS. 6E and 6 F show a closure device 200 b that differs in the number of tabs provided relative to the closure device 200 a of FIGS. 6A through 6D (three versus four).
  • the closure device 200 c shown in FIG. 6G differs in that a depression 204 is not included in a top surface 202 of the closure device.
  • the closure devices (stoppers) shown in FIGS. 6A-6G may be inserted into a container of a specimen enclosure apparatus (see FIG. 8 ) to provide two flange seals and one plug seal.
  • the closure device 200 a is illustrated as an elastomeric stopper extending along a central axis A.
  • references to longitudinal will refer to a direction extending along the central axis A
  • circumferential will refer to extending around the central axis A
  • radial will refer to a radial direction as illustrated by the arrow R in FIG. 6A .
  • the closure device 200 a is configured to be received in an opening to a specimen container, such as illustrated in FIG. 8 .
  • the illustrated closure device 200 a includes an internal flange seal portion 206 and an external flange seal portion 210 .
  • the internal flange seal portion 206 is configured to contact an internal flange of a specimen container to form a flange seal proximate the specimen cavity of the container.
  • the external flange seal portion 210 is configured to contact an external flange of the container to form an external flange seal at the end of a neck of the enclosure.
  • the flange seal formed by the internal flange seal portion 206 has an edge positioned adjacent to the cavity, which is positioned to be directly exposed to moist heat during sterilization of the specimen in the container.
  • the closure device further includes a radial travel limiter 208 , integrally formed with the closure device 200 a , that is configured to contact the specimen container in an opening to the container to limit radial movement of the flange seal portion 206 relative to the internal flange of the container.
  • the radial travel limiter is a mating plug sealing cylindrical surface 208 configured to form a plug seal with a plug sealing cylindrical surface in the neck of the container.
  • the internal flange seal formed using the internal flange seal portion 206 is positioned between the plug seal formed by the mating plug sealing cylindrical surface 208 and the specimen-containing cavity of the container when the closure device 200 a is inserted in the container.
  • the closure device 200 a may be pressed into the opening in the neck of the container 400 to position an internal flange seal 450 between a cavity 402 and a plug seal 452 .
  • the plug seal 452 is positioned between the internal flange seal 450 and an external flange seal 454 .
  • the closure device 200 a includes a degassing extension member 212 .
  • the degassing extension member 212 extends longitudinally towards the cavity 402 as best seen in FIG. 12 .
  • the degassing extension member 212 is configured to retain the closure device 200 a in a degassing position in the opening of the container and to define a passage 460 ( FIG. 13A ) from the cavity 402 through the opening through which a gas may be moved into and out of the cavity 402 .
  • the degassing extension member 212 includes a plurality of tabs 214 extending from an exterior surface thereof. The tabs 214 are configured to engage the neck of the container to retain the closure device 200 a in a degassing position and to displace the exterior surface of the degassing extension member 212 from the neck to define a passage from the cavity through the opening.
  • a top surface 202 of the closure device 200 a includes a depression 204 in a central region thereof.
  • the depression 204 may be used, for example, for insertion of a needle or the like through the closure device 200 a to withdraw a specimen from the cavity 402 .
  • the mating plug sealing cylindrical surface 208 may be used to form a plug seal. Accordingly, a diameter of the mating plug sealing surface 208 may be selected to provide an interference fit with a smaller diameter opening in the neck of the container to provide a desired compression of the closure device 200 a in forming the plug seal.
  • a closure member 407 FIG.
  • 13B may extend over the closure device 200 a and may be coupled to a container to retain the closure device 200 a and to compress the closure device 200 a longitudinally to form flange seals with the respective flange seal portions 206 , 210 .
  • the degassing extension member 212 may include a longitudinally extending hollow core 220 . However, it will be understood that the degassing extension member 212 may be a solid elastomeric member and need not include the hollow core 220 .
  • FIGS. 6E through 6G Further embodiments of a closure device 200 b are illustrated in FIGS. 6E through 6G . As shown in the embodiments of FIGS. 6E and 6F , three tabs 214 are provided, each uniformally displaced from the other tabs by an angle ⁇ 2 , shown as 120° in FIG. 6F . Note that, as with the description of FIG. 6D above, a uniform spacing of the tabs 214 may not be provided in other embodiments of the present invention.
  • the closure device 200 b shown in FIGS. 6E and 6F may operate otherwise substantially as described with reference to the embodiments of FIGS. 6A through 6D .
  • the closure device 200 c illustrated in FIG. 6G differs in that a top surface 202 ′ thereof does not include the depression 204 shown in FIG. 6A .
  • Various like numbered elements in FIG. 6G may otherwise be described substantially as previously described with reference to FIGS. 6A through 6F .
  • FIG. 7A is a perspective view of a closure device 300 .
  • FIG. 7B is a top plan view
  • FIG. 7C is a front view
  • FIG. 7D is a bottom plan view of the closure device 300 of FIG. 7A .
  • the closure device (stopper) 300 shown in FIGS. 7A-7D may be inserted into a container of a specimen enclosure apparatus (see FIG. 8 ) to provide one flange seal and one plug seal.
  • the closure device 300 shown in FIGS. 7A through 7D eliminates the top (external) flange seal, i.e., the flange seal that mates with the top surface of the vial.
  • the closure device 300 extends longitudinally along a central axis A.
  • the closure device 300 is shown as an elastomeric stopper for closing a specimen enclosure apparatus.
  • a top surface 302 of the closure device 300 includes a depression 304 that may be used substantially as described with reference to the depression 204 of FIG. 6A .
  • a flange seal portion 306 is configured to contact the internal flange positioned intermediate a neck of a container configured to receive the specimen to form a flange seal proximate a cavity containing the specimen in the container.
  • a radial travel limiter 308 is integrally formed with the flange seal portion 306 .
  • the radial travel limiter 308 is configured to contact the container in an opening extending through a neck of the container to the cavity to limit radial movement of the flange seal portion 306 relative to an internal flange of the container.
  • the radial travel limiter is a mating plug sealing cylindrical surface 308 extending from the flange seal portion 306 that is configured to form a plug seal with a plug sealing cylindrical surface extending from the internal flange of the container away from the cavity. This arrangement can be seen, for example, in FIG. 14B where the closure device 300 is shown inserted in a neck 406 of the container of the specimen and closure apparatus.
  • a degassing extension member 312 extending from the flange seal portion 306 and away from the radial travel limiting mating plug sealing cylindrical surface 308 .
  • the degassing extension member 312 is configured to retain the closure device 300 in a degassing position in the opening of the container to define a passage 460 ′ from the cavity 402 through which a gas may be moved into and out of the cavity as seen in FIG. 14A .
  • the degassing extension member 312 includes a plurality of tabs 314 extending from an exterior surface thereof configured to engage the neck in the opening to retain the closure device 300 in the degassing position and to displace the exterior surface of the degassing extension member 312 from the neck to define the passage 460 ′.
  • the illustrated embodiments of FIGS. 7A through 7D include a total of four uniformly circumferentially placed tabs 314 and the degassing extension member 312 includes a longitudinally extending hollow core 320 .
  • the degassing extension member 312 may be solid without the hollow core 320 in some embodiments.
  • FIG. 8 illustrates a specimen container 400 or vial according to some embodiments of the present invention.
  • the neck 406 of the container 400 of FIG. 8 includes an internal step, which forms a flange seal with a closure device as described with reference to FIGS. 6A-6G and 7 A- 7 D.
  • FIG. 8 is a perspective view of the container 400
  • FIG. 10 is a front plan view
  • FIG. 11 is a cross-sectional view of the container 400 .
  • the container 400 includes a main portion 408 including a cavity 402 configured to receive the specimen.
  • a neck 406 extends upwardly longitudinally from the main portion 408 .
  • An opening 404 extends through the neck 406 to the cavity 402 defined by the main portion 408 .
  • An internal flange 410 is positioned intermediate the neck 406 of the container 400 .
  • the internal flange 410 is configured to contact the flange seal portion 206 , 306 of the closure device 200 a , 200 b , 200 c , 300 to form a flange seal proximate the cavity 402 .
  • a radial travel limiting contact surface 412 in the opening 404 is shown in the embodiments of FIGS. 8, 10 and 11 .
  • the radial travel limiting contact surface 412 is configured to contact the closure device 200 a , 200 b , 200 c , 300 to limit radial movement of the flange seal 450 ( FIG. 12 ). More particularly, as shown in FIGS. 8, 10 and 11 , the radial travel limiting contact surface is a plug sealing cylindrical surface 412 extending from proximate to the internal flange 410 away from the cavity 402 that is configured to form a plug seal with a closure device 200 a , 200 b , 200 c , 300 .
  • the container 400 illustrated in FIGS. 8, 10 and 11 further includes an external flange 414 including a raised portion 416 positioned at an end of the neck 406 away from the cavity 402 .
  • the external flange 414 is configured to contact the closure device 200 a , 200 b , 200 c , 300 to form an external flange seal 454 ( FIG. 12 ).
  • the plug seal 452 is positioned between the internal flange seal 450 formed by the internal flange 410 and the external flange seal 454 .
  • the internal flange seal 450 is positioned between the plug seal 452 and the cavity 402 .
  • the container 400 is configured to mate with a closure member retaining a closure device 200 a , 200 b , 200 c , 300 in the opening 404 .
  • the neck 406 includes a narrowed portion 430 and an intermediate portion 432 extending from the narrowed portion 430 to the longitudinally extending member 420 defining the plug sealing cylindrical surface 412 .
  • a closure member may, thus, be crimped or the like around the neck portion 406 to engage an intermediate portion 432 to retain the closure device 200 a , 200 b , 200 c , 300 in the opening 404 and to apply longitudinal forces for forming respective flange seals 450 , 454 .
  • the narrowed portion 430 is further shown as having an internal surface 418 configured to engage the tabs 214 , 314 to hold a closure device 200 a , 200 b , 200 c , 300 in the degassing position as seen in FIGS. 13A and 14A , respectively.
  • a standard vial 140 generally contains straight sides 144 in the neck of the bottle as shown in FIG. 9B .
  • a neck 356 of a container 350 includes an internal step 360 .
  • An opening 354 extends through the neck 356 to a cavity 352 defined by a main body 358 of the container 350 .
  • FIG. 9A and 9B differ in that the neck of the container 350 shown in FIG. 9A has a flange seal between the vial contents and the plug seal, whereas the neck of standard vial 140 as shown in FIG. 9B does not have such a flange seal, although the sides 144 may provide a plug seal and an external flange seal may be provided by the surface 142 .
  • FIG. 12 shows the placement of the closure device 200 a of FIG. 6A in the container (vial) of FIG. 8 , including a main body 408 defining a cavity 402 for receiving a specimen.
  • the vial has an internal flange which mates with the stopper flange to form an internal flange seal 450 .
  • An external flange seal 454 is also shown with a plug seal 452 between the flange seals 450 , 454 .
  • the crimp seal or closure is not shown for clarity.
  • an edge of the internal flange seal 450 may be placed in direct contact with the product (specimen) contents.
  • the plug seal 452 On top of the internal flange seal 450 is the plug seal 452 . This is the reverse of most standard stoppers, in which a plug seal is in direct contact with the product contents and a flange seal is behind this plug seal.
  • the internal flange seal 450 is in direct contact with the product contents, which may allow for moist heat to penetrate the product contact surfaces.
  • the flange seal 450 between the stopper and specimen container or vial may be a more controlled surface and may be less variable in contact than a plug seal.
  • the stopper compression at this flange seal may be set by the closure force, which is in contrast to a plug seal that relies on the geometric interference to maintain compression.
  • the seal integrity of the product may be more robust than if the flange seal were used alone.
  • the plug seal is isolated from the vial contents. This may result in a higher rate of lethality of microorganisms during a terminal sterilization process.
  • the illustrated closure devices (stoppers) 200 a , 300 include four tabs (nibs) 214 , 314 at the end of the stopper 200 a , 300 , although fewer or more nibs can be used. These nibs 214 , 314 have a geometrical interference with the neck 406 of a bottle. Further, these nibs 214 , 314 are compressed into the inner neck 418 of a bottle and hold the stopper 200 a , 300 above the surface of the bottle.
  • Gases can be evacuated or added to the bottle through a passage 460 , 460 ′ defined by the annulus between the stopper and the inner neck of the bottle, up between the stopper nibs 214 , 314 .
  • the stopper 200 a , 300 may be pressed into the bottle and the sealing surfaces of the stopper seals the contents as seen in FIGS. 13B and 14B , respectively.
  • FIG. 15 is a perspective view illustrating a closure device (stopper) 500 according to yet further embodiments of the present invention.
  • the stopper 500 of FIG. 15 does not have a large plug seal.
  • the illustrated stopper 500 includes a cap part 507 defining a flange seal surface 506 and an extension part 512 .
  • the extension part 512 includes 6 tabs (nibs) 508 defining a radial travel limiter. However, more or less tabs 508 may be provided.
  • the cap part 507 may define a plug seal exterior circumferential surface that forms a plug seal with a mating surface of a receiving container, where a flange seal formed by the flange seal surface 506 will be positioned between the contents of the container and the plug seal.
  • FIG. 16A is a cross-sectional view illustrating a degassing position while FIG. 16C is a cross-sectional view illustrating a closed or sealed position.
  • FIG. 16B is a perspective view illustrating the closed position of FIG. 16C .
  • a container 408 ′ has a cavity 402 ′ configured to receive the specimen.
  • An opening 404 ′ extends through a neck 406 ′ of the container 408 ′ to the cavity 402 ′.
  • a closure device 601 covers the opening 404 ′.
  • the closure device 601 has a flange seal portion 606 that is configured to contact an external flange seal portion 414 ′ on an end of the neck 406 ′ of the container 408 ′ displaced from the cavity 402 ′ to form a flange seal 450 ′ ( FIG. 16C ).
  • the flange seal 450 ′ closes the opening 404 ′.
  • the closure device further includes a radial travel limiter 608 integrally formed with the closure device 601 that contacts an exterior surface 420 ′ of the neck 406 ′ to limit radial movement of the flange seal portion 606 of the closure device 601 relative to the external flange seal portion 414 ′ of the container 408 ′.
  • a closure member 407 , 407 ′, 407 ′′ is coupled to the container 408 ′ that retains the closure device 601 covering the opening 404 ′ and compresses the flange seal 450 ′.
  • the closure member 407 , 407 ′, 407 ′′ may be a crimp seal, a screw cap, a tear-off seal and/or the like with a septum liner.
  • the closure member 407 , 407 ′, 407 ′′ may be metal and/or plastic.
  • an edge 620 of the flange seal 450 ′ adjacent the opening 404 ′ is positioned to be directly exposed to moist heat during sterilization.
  • the illustrated closure device 601 of FIGS. 16A through 16C further includes a degassing extension member 612 extending from the flange seal portion 606 along an exterior surface of the neck 406 ′ that is configured to retain the closure device 601 in degassing position ( FIG. 16A ) defining a passage from the cavity 402 ′ through the opening 404 ′ through which a gas may be moved into and out of the cavity 402 ′.
  • the degassing extension member 612 includes a tab 614 extending from a surface thereof configured to engage the exterior surface 420 ′of the neck 406 ′ to retain the closure device 601 in the degassing position shown in FIG. 16A .
  • the illustrated tab 614 is a circumferentially extending ridge 614 and the degassing extension member 612 further includes a plurality of slots 615 extending past the ridge 614 to define the passage along the exterior surface of the neck.
  • the neck 406 ′ includes a plug sealing cylindrical surface defined by the exterior surface 420 ′ of the neck 406 ′.
  • the radial travel limiter is formed by a mating plug sealing cylindrical surface 608 of the closure device 601 that is configured to form a radial seal 652 ( FIG. 16C ) with a plug sealing cylindrical surface 420 ′ of the neck 406 ′.
  • the flange seal 450 ′ is positioned between the radial seal 652 and the cavity 402 ′ as seen in FIG. 16 C.
  • the closure member 407 , 407 ′, 407 ′′ may serve to compress both the flange seal 450 ′ and the radial seal 652 .
  • references to a radial seal herein refer to the radial direction in which the seal forming forces are imparted by the closure member 407 , 407 ′, 407 ′′.
  • a plug seal as discussed above, is formed by geometric interference of the fit of the closure device into an opening in the neck of the container.
  • a flange seal is positioned with an edge in direct contact to the cavity so as to be exposed to moist heat, while the radial seal is positioned outside the container 408 ′ forming a seal with an exterior surface thereof with a flange seal 450 ′ positioned between the radial seal 652 and the specimen contents of the cavity 402 ′.
  • Some embodiments of the present invention can be used in products other than those which require terminal sterilization, such as lyophilized products including pharmaceuticals.
  • the process of degassing described above with various stoppers of the present invention is similar to that in a lyophilization process. Lyophilized products generally require that ambient moisture does not penetrate into the vial and cause melt-back of the lyophilized product.
  • Some embodiments of the present invention provide stoppers having three sealing surfaces that may have a high level of seal integrity.
  • injectable pharmaceutical products generally must be sterile as the contents are injected into a patient.
  • the flange seal in proximity to the sample contents may prevent specimens, such as microorganisms, on the plug seal surface from entering the vial contents.
  • the flat surface of the stopper in some embodiments can typically be easily sterilized with UV or other sterilization, whereas the cylindrical plug surface may be more difficult.
  • Example stoppers such as illustrated in FIGS. 6A and 7A and a vial as illustrate in FIG. 8 may be made from stereolithography models and cast into polyurethane models.
  • the final polyurethane models may have 50 Shore A hardness that is a typical durometer of elastomer stoppers.
  • a prototype model of the vial may be made by stereolithography and may be tested with the stopper prototypes for fit.

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  • Mechanical Engineering (AREA)
  • Engineering & Computer Science (AREA)
  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Clinical Laboratory Science (AREA)
  • Hematology (AREA)
  • General Health & Medical Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Closures For Containers (AREA)
  • Sampling And Sample Adjustment (AREA)
  • Medical Preparation Storing Or Oral Administration Devices (AREA)
  • Automatic Analysis And Handling Materials Therefor (AREA)
  • Devices For Use In Laboratory Experiments (AREA)
US11/523,306 2005-09-20 2006-09-19 Specimen enclosure apparatus and containers and closure devices for the same Abandoned US20070102393A1 (en)

Priority Applications (1)

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US11/523,306 US20070102393A1 (en) 2005-09-20 2006-09-19 Specimen enclosure apparatus and containers and closure devices for the same

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US71865505P 2005-09-20 2005-09-20
US11/523,306 US20070102393A1 (en) 2005-09-20 2006-09-19 Specimen enclosure apparatus and containers and closure devices for the same

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US (1) US20070102393A1 (fr)
EP (1) EP1926556A2 (fr)
JP (1) JP2009508781A (fr)
CN (1) CN101287553B (fr)
AU (1) AU2006292280A1 (fr)
CA (1) CA2622752A1 (fr)
WO (1) WO2007035746A2 (fr)

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US20080000870A1 (en) * 2006-06-19 2008-01-03 Grifols, S.A. Stopper for flasks of sterile products and use of said stopper in sterile measured filling
US20090036866A1 (en) * 2007-08-01 2009-02-05 Hospira, Inc. Medicament admixing system
US20110184373A1 (en) * 2008-05-24 2011-07-28 Ulrich Moser Ampoule comprising an ampoule holder
US20110224640A1 (en) * 2008-08-30 2011-09-15 Sanofi-Aventis Deutschland Gmbh Cartridge and needle system therefor
WO2013087763A1 (fr) * 2011-12-14 2013-06-20 Nucomat Dispositif de bouchon pour reflux
US20130312373A1 (en) * 2011-04-04 2013-11-28 Genesis Packaging Technologies Methods for sealing pharmaceutical vials
US8684204B2 (en) 2009-10-01 2014-04-01 A. Raymond Et Cie Locking cover for a vessel having a neck, including a cap having attachment tabs
US8684225B2 (en) 2009-09-15 2014-04-01 A. Raymond Et Cie Locking cap for a vessel having a neck
US8721612B2 (en) 2010-12-17 2014-05-13 Hospira, Inc. System and method for intermixing the contents of two containers
US8834444B2 (en) 2011-10-03 2014-09-16 Hospira, Inc. System and method for mixing the contents of two containers
US20140271408A1 (en) * 2013-03-13 2014-09-18 Dale Singh Taunk Microtube cap
US20150290645A1 (en) * 2012-10-30 2015-10-15 Hitachi High-Technologies Corporation Reagent container and automatic analysis apparatus
US20150353225A1 (en) * 2014-06-06 2015-12-10 The Procter & Gamble Company Faceted container
US9382044B2 (en) 2012-02-13 2016-07-05 A. Raymond Et Cie Locking device for a cap
US10219983B2 (en) 2016-08-03 2019-03-05 Genesis Packaging Technologies Cap systems with piercing member for pharmaceutical vials
USD931107S1 (en) 2017-09-08 2021-09-21 The Procter & Gamble Company Bottle
USD981854S1 (en) 2015-12-04 2023-03-28 The Procter & Gamble Company Bottle
USD996220S1 (en) 2020-08-14 2023-08-22 The Procter & Gamble Company Bottle

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EP2517791A1 (fr) 2011-04-18 2012-10-31 Vibod GmbH Tube d'échantillon doté d'un bouchon amélioré
CN102743287B (zh) * 2011-04-20 2014-03-12 江苏博生医用新材料股份有限公司 一种新型镀膜药物瓶塞及其制造方法
CN102743291B (zh) * 2011-04-20 2014-03-12 江苏博生医用新材料股份有限公司 无硅化高弹性镀膜药物瓶塞及其制造方法
JP5988768B2 (ja) * 2012-08-17 2016-09-07 株式会社積水化成品山口 容器
KR200475233Y1 (ko) 2013-04-12 2014-11-17 롯데칠성음료주식회사 주류 용기
EP3688392B1 (fr) 2017-09-28 2023-12-06 F. Hoffmann-La Roche AG Kit de lyophilisation et procédé de fermeture d'un flacon de lyophilisation
EP3689396A4 (fr) * 2017-10-31 2020-08-19 Terumo Kabushiki Kaisha Seringue et seringue pré-remplie
JP6952614B2 (ja) * 2018-01-23 2021-10-20 ミツボシプロダクトプラニング株式会社 採精容器
CN110068673A (zh) * 2019-06-04 2019-07-30 深圳麦科田生物医疗技术有限公司 反应容器
US20220296470A1 (en) * 2019-08-21 2022-09-22 Sanofi Closure for Medicament Container
CN112744444A (zh) * 2020-11-30 2021-05-04 安徽华能集团电器有限公司 一种医用覆膜橡胶塞
DE202022104567U1 (de) 2022-08-11 2023-11-16 M L S Mikrowellen - Labor - Systeme GmbH Probenbehältersystem

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Publication number Priority date Publication date Assignee Title
US20080000870A1 (en) * 2006-06-19 2008-01-03 Grifols, S.A. Stopper for flasks of sterile products and use of said stopper in sterile measured filling
US8801689B2 (en) 2007-08-01 2014-08-12 Hospira, Inc. Medicament admixing system
US9205026B2 (en) 2007-08-01 2015-12-08 Hospira, Inc. Medicament admixing system
US20090036864A1 (en) * 2007-08-01 2009-02-05 Hospira, Inc. Medicament admixing system
US20090036865A1 (en) * 2007-08-01 2009-02-05 Hospira, Inc. Medicament admixing system
WO2009029390A1 (fr) * 2007-08-01 2009-03-05 Hospira, Inc. Système de mélange de médicaments
US20090036866A1 (en) * 2007-08-01 2009-02-05 Hospira, Inc. Medicament admixing system
US20090032489A1 (en) * 2007-08-01 2009-02-05 Hospira, Inc. Medicament admixing system
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US9205025B2 (en) 2007-08-01 2015-12-08 Hospira, Inc. Medicament admixing system
US9198832B2 (en) 2007-08-01 2015-12-01 Hospira, Inc. Medicament admixing system
US20110184373A1 (en) * 2008-05-24 2011-07-28 Ulrich Moser Ampoule comprising an ampoule holder
US8721615B2 (en) * 2008-05-24 2014-05-13 Tecpharma Licensing Ag Ampoule comprising an ampoule holder
US20110224640A1 (en) * 2008-08-30 2011-09-15 Sanofi-Aventis Deutschland Gmbh Cartridge and needle system therefor
US8574214B2 (en) * 2008-08-30 2013-11-05 Sanofi-Aventis Deutschland Gmbh Cartridge and needle system therefor
US8684225B2 (en) 2009-09-15 2014-04-01 A. Raymond Et Cie Locking cap for a vessel having a neck
US8684204B2 (en) 2009-10-01 2014-04-01 A. Raymond Et Cie Locking cover for a vessel having a neck, including a cap having attachment tabs
US9610223B2 (en) 2010-12-17 2017-04-04 Hospira, Inc. System and method for intermixing the contents of two containers
US8721612B2 (en) 2010-12-17 2014-05-13 Hospira, Inc. System and method for intermixing the contents of two containers
US8726619B2 (en) * 2011-04-04 2014-05-20 Genesis Packaging Technologies Methods for sealing pharmaceutical vials
US20130312373A1 (en) * 2011-04-04 2013-11-28 Genesis Packaging Technologies Methods for sealing pharmaceutical vials
US8882739B2 (en) 2011-10-03 2014-11-11 Hospira, Inc. System and method for mixing the contents of two containers
US8911421B2 (en) 2011-10-03 2014-12-16 Hospira, Inc. System and method for mixing the contents of two containers
US9079686B2 (en) 2011-10-03 2015-07-14 Hospira, Inc. Port assembly for mixing the contents of two containers
US8834444B2 (en) 2011-10-03 2014-09-16 Hospira, Inc. System and method for mixing the contents of two containers
WO2013087763A1 (fr) * 2011-12-14 2013-06-20 Nucomat Dispositif de bouchon pour reflux
US9382044B2 (en) 2012-02-13 2016-07-05 A. Raymond Et Cie Locking device for a cap
US20150290645A1 (en) * 2012-10-30 2015-10-15 Hitachi High-Technologies Corporation Reagent container and automatic analysis apparatus
US9776185B2 (en) * 2012-10-30 2017-10-03 Hitachi High-Technologies Corporation Reagent container and automatic analysis apparatus
US9289767B2 (en) * 2013-03-13 2016-03-22 Alphagem Bio Inc. Microtube cap
US20140271408A1 (en) * 2013-03-13 2014-09-18 Dale Singh Taunk Microtube cap
US20150353225A1 (en) * 2014-06-06 2015-12-10 The Procter & Gamble Company Faceted container
USD981854S1 (en) 2015-12-04 2023-03-28 The Procter & Gamble Company Bottle
US11039983B2 (en) 2016-08-03 2021-06-22 Genesis Packaging Technologies Cap systems with piercing member for pharmaceutical vials
US10219983B2 (en) 2016-08-03 2019-03-05 Genesis Packaging Technologies Cap systems with piercing member for pharmaceutical vials
USD931107S1 (en) 2017-09-08 2021-09-21 The Procter & Gamble Company Bottle
USD1028732S1 (en) 2020-08-14 2024-05-28 The Procter & Gamble Company Bottle
USD996220S1 (en) 2020-08-14 2023-08-22 The Procter & Gamble Company Bottle

Also Published As

Publication number Publication date
EP1926556A2 (fr) 2008-06-04
CN101287553B (zh) 2011-09-14
CN101287553A (zh) 2008-10-15
JP2009508781A (ja) 2009-03-05
WO2007035746A2 (fr) 2007-03-29
WO2007035746A3 (fr) 2007-06-14
CA2622752A1 (fr) 2007-03-29
AU2006292280A1 (en) 2007-03-29

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