WO2006004496A1 - An inhalation device and a method for assembling said inhalation device - Google Patents

An inhalation device and a method for assembling said inhalation device Download PDF

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Publication number
WO2006004496A1
WO2006004496A1 PCT/SE2005/000994 SE2005000994W WO2006004496A1 WO 2006004496 A1 WO2006004496 A1 WO 2006004496A1 SE 2005000994 W SE2005000994 W SE 2005000994W WO 2006004496 A1 WO2006004496 A1 WO 2006004496A1
Authority
WO
WIPO (PCT)
Prior art keywords
canister
counter
inhalation device
count
predetermined amount
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.)
Ceased
Application number
PCT/SE2005/000994
Other languages
English (en)
French (fr)
Inventor
Darren Hodson
William Treneman
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
AstraZeneca AB
Original Assignee
AstraZeneca AB
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority to AU2005260193A priority Critical patent/AU2005260193B2/en
Priority to PL05754148T priority patent/PL1768727T3/pl
Priority to MXPA06014659A priority patent/MXPA06014659A/es
Priority to DE602005026526T priority patent/DE602005026526D1/de
Priority to US11/571,389 priority patent/US8616196B2/en
Priority to NZ552105A priority patent/NZ552105A/en
Priority to CA2569923A priority patent/CA2569923C/en
Priority to HK07109885.2A priority patent/HK1101895B/en
Priority to AT05754148T priority patent/ATE499132T1/de
Application filed by AstraZeneca AB filed Critical AstraZeneca AB
Priority to BRPI0512848A priority patent/BRPI0512848B8/pt
Priority to EP05754148A priority patent/EP1768727B1/en
Priority to JP2007520260A priority patent/JP4869226B2/ja
Publication of WO2006004496A1 publication Critical patent/WO2006004496A1/en
Priority to IL179971A priority patent/IL179971A/en
Priority to KR1020067027821A priority patent/KR101267923B1/ko
Anticipated expiration legal-status Critical
Priority to NO20070495A priority patent/NO20070495L/no
Ceased legal-status Critical Current

Links

Classifications

    • 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
    • A61M15/00—Inhalators
    • 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
    • A61M15/00—Inhalators
    • A61M15/009—Inhalators using medicine packages with incorporated spraying means, e.g. aerosol cans
    • 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
    • A61M15/00—Inhalators
    • A61M15/0065—Inhalators with dosage or measuring devices
    • 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
    • A61M15/00—Inhalators
    • A61M15/0065—Inhalators with dosage or measuring devices
    • A61M15/0068—Indicating or counting the number of dispensed doses or of remaining doses
    • A61M15/007—Mechanical counters
    • 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
    • A61M15/00—Inhalators
    • A61M15/0065—Inhalators with dosage or measuring devices
    • A61M15/0068—Indicating or counting the number of dispensed doses or of remaining doses
    • A61M15/007—Mechanical counters
    • A61M15/0071—Mechanical counters having a display or indicator
    • A61M15/0075—Mechanical counters having a display or indicator on a disc
    • G—PHYSICS
    • G06—COMPUTING OR CALCULATING; COUNTING
    • G06M—COUNTING MECHANISMS; COUNTING OF OBJECTS NOT OTHERWISE PROVIDED FOR
    • G06M1/00—Design features of general application
    • G06M1/02—Housing
    • G06M1/026—Connecting or supporting parts

Definitions

  • the present invention relates to an inhalation device for delivery of a medicament by inhalation according to the preamble of claim 1. It further relates to a canister and a counter assembly according to the preamble of claim 15 adapted to be positioned in an inhalation device and to a method for assembling said canister and said counter according to the preamble of claim 8.
  • Inhalers are commonly used for delivery of a wide range of medicaments.
  • the inhaler holds a canister of medicament, the canister being actuated by compression to deliver a dose of medicament through a mouthpiece to a user.
  • Canisters for holding a suspension or solution of a pharmaceutical substance in a propellant under pressure are well known.
  • One such known canister to be used in an inhalation device comprises a can coupled with a valve.
  • the valve consists of a body comprising a chamber, a valve stem (which extends from a head of the body) and a metering chamber, selectively communicable by the valve stem to the atmosphere via an L-shaped conduit within the valve body.
  • the valve stem is axially displaceable between a first, extended position in which the metering chamber, and hence the canister, is closed to the atmosphere (since the L-shaped conduit is disposed wholly outside the metering chamber), and a second, depressed position, in which the metering chamber is in open communication with the outlet provided by the L-shaped conduit in the valve stem and through which a metered dose of propellant containing pharmaceutical substance is delivered.
  • the valve stem is inserted into a stem body component, which is part of the mouthpiece and housing of the device. The patient applies a compressive force between the base of the canister, held in an inverted position in the housing, and the stem body which forces the valve stem into the canister.
  • An inhaler traditionally contains from 120 to 200 doses (shots) so any counter must be reliable, accurate and easy to read.
  • dose counters in the prior art, some located near the valve region of the canister and some attached to the base of the canister which due to the fact that the canister is in an inverted position in the inhaler mouthpiece means that the counter is on the top of the assembled inhaler and can be easily viewed.
  • US 6446627 a dose counter attached to the base of the actuator is described.
  • the counter measures the displacement of the top of the canister relative to the valve stem.
  • the counter is not attached to the canister and therefore a problem is that the user can swap canisters between actuators and that would cause the indicator of the counter to display the incorrect number of doses remaining in the canister.
  • a problem with the inhalation device according to US 6446627 is that the actuator and counter assembly are difficult to clean and are vulnerable to damage with water and cleaning products.
  • a counter attached to the base of the canister i.e. on the top of the inhalation device.
  • One embodiment of this inhalation device measures the displacement of the canister base relative to the actuator body.
  • a problem with the counter disclosed in US 4817822 is miscounting since the counter relies on the displacement of the canister and the canister length due to manufacturing variables is a length with a variable tolerance. A large tolerance of the canister length has the potential to cause miscounting.
  • a counter attached to the base of the canister where the counter counts when a certain force is reached.
  • the counter is attached to the canister but does not require alignment with the actuator body since it relies on the force of the spring in the counter mechanism being less than the force of the spring in the metering valve, such that the counting occurs before firing.
  • a problem with such a counter is that the force of the counting spring and the metering valve need to be accurately controlled, and may vary with use.
  • An object of the invention is to provide an inhalation device with a dose counter counting the delivered doses of medicament in a secure and reliable way.
  • a further object of the invention is to provide an inhalation device where a counter is securely fixed to the canister.
  • the counter is securely fixed to the canister and the length tolerance of the canister and counter is limited by the controlled fixing of the counter to the base of the canister.
  • the counter on the base of the canister (i.e. the top of the inhalation device) and keep the count point close to the fire point and avoid miscounting.
  • Fig. 1 shows one embodiment of an inhalation device according to the invention.
  • Fig. 2a shows schematically a diagram of the relation between displacement of the canister and the fire and count points in an inhalation device not using the assembly process according to the invention.
  • FIG. 2b shows schematically the same as figure 2a but for an inhalation device using the assembly process according to the invention.
  • Fig. 3 shows schematically one embodiment of the canister and the positioning of a roughened surface on the canister base.
  • Fig 4 shows how the counter is attached to the canister.
  • Fig. 5a shows schematically a cross section of one embodiment of the counter and deformable ribs provided on the inside of the counter base before assembly to the canister.
  • Fig. 5b shows schematically the deformable ribs of Fig. 5a when the counter is assembled to the canister.
  • an inhalation device 1 according to one embodiment of the invention is shown. It comprises a housing 3, which encloses a canister 5 holding the medicament.
  • the canister comprises a base end 6a and a valve end 6b.
  • the medicament is delivered to the user through a valve stem 7 connected to the valve end 6b of the canister (lower part of the canister in the figure due to the invert position of the canister in the inhalation device).
  • the medicament is inhaled by the user through a mouth piece 13 that is a part of the housing 3.
  • the mouthpiece is in connection with the valve stem 7 for receiving the medicament to be delivered.
  • a dose counter 15 is provided on the base end 6a of the canister, i.e. in the opposite end to the valve stem 7.
  • the dose counter 15 is attached to the canister and will be pressed down together with the canister. The counting is related to the downward motion of the canister and counter. See more detailed description below.
  • the dose counter 15 should increase the number of counted doses by one every time a dose has been delivered.
  • the counter Since undercounting is not to recommend due to the risk that the user believes that there is medicament left in the canister when it actually is empty, the counter usually is affected to count one count only when the canister has been pressed down a distance less than is needed for delivering the dose of medicament.
  • the position to where the canister is needed to be pressed down for affecting the counter to count one dose is called the count point and the position to where the canister is needed to be pressed down to deliver one dose is called fire point.
  • the counter is provided onto the base of the canister 5.
  • the counter 15 is attached to the canister 5 in an assembling process and it can be attached to the canister 5 at any one of numerous points along the base part of the canister, i.e. the part of the canister opposite from the valve stem, from the outermost edge of the counter to its inside base giving ranges of variation of positions and varying lengths of canister tolerances.
  • the counter can be attached anywhere on the base of the canister.
  • the contact areas between the counter and the canister, i.e. the inside of the counter 18 and/or the outside surfaces of the base of the canister 20 (see fig 5a), are provided with means for enhancing the friction and ensuring that the counter is fixedly attached to the counter.
  • the counter 15 is pressed down onto the canister 5 and at the same time the length of the canister together with the counter is measured. The counter 15 is pressed down until a predefined length of the canister and counter together is achieved and this length should also be within a predefined tolerance interval.
  • an inhalation device 1 having a counter securely fixed to the canister and the canister and counter together having a predefined length within a predefined tolerance interval. This is preferred since this allows the control of the distance the canister needs to be depressed before a dose of medicament is delivered and thus also how much the canister needs to be depressed before the counter counts a dose.
  • Fig. 2a shows schematically how the fire point 21 (dose delivering) and the count point 22 are related to the compression of the canister in an inhaler device where the counter is attached to the base of the canister but the method according to the invention for assembling the counter and canister to achieve a small length tolerance is not used.
  • the length tolerance of the canister and counter is large.
  • This large length tolerance results in a range of possible counting points 24.
  • the range of fire points is only dependent on the valve tolerances and not on the canister length tolerance.
  • the given lengths in fig. 2a and b for input displacement of the canister are only examples. In reality these could vary for different products.
  • the whole tolerances need to be considered when the position of the count point 22 is decided.
  • the count point 22 needs to be positioned relatively far away from the fire point 21 and in reality this means that the dose counter will count one dose when the canister is pressed down much less than is needed for delivering a dose. This in turn results in a tendency for the counter to overcount the doses and there will actually be medicine remaining when the counter says the canister is empty.
  • Fig. 2b shows schematically the same as Fig. 2a but for an inhalation device according to the invention.
  • the length tolerance of the canister and counter together is much smaller giving a smaller range of possible count points 28. Therefore the count point 26 can be positioned closer to the fire point 25. Hereby there is less tendency for overcounting.
  • the counter should be a displacement counter, i.e. a counter that is affected by the displacement of the canister and counts one count each time the canister is pressed down for delivering a dose.
  • a displacement counter i.e. a counter that is affected by the displacement of the canister and counts one count each time the canister is pressed down for delivering a dose.
  • a counter that could be positioned onto the base of the canister according to the invention comprises a mechanism to convert longitudinal compression of the canister to a rotational, horizontal movement of an indicating mechanism of the counter.
  • WO 01/37909 Displacement counters with other kinds of indicating mechanisms are also possible.
  • one or more of the contact surfaces between the counter and canister are provided with means for increasing the friction.
  • the means for increasing the friction can be for example roughened areas or deformable means or both. Preferably roughened areas are provided onto the base of the canister.
  • Deformable means can in one embodiment be provided on the inside base of the counter.
  • Fig. 3 shows schematically where roughened areas 37 on the base end 6a of the canister 5 can be provided.
  • the outer side wall at the base of the canister and more preferably the widest part of the wall nearest the base is roughened and the inside of the counter is smooth plastic that deforms into the roughened surface and thereby provides a secure grip.
  • the counter is securely fixed onto the base of the canister and furthermore the counter may, during the assembly process when the counter is fitted onto the canister, be pressed onto the canister to fit in a range of different positions.
  • the area that should be provided with a roughened surface can vary between different types of canisters but should preferably be provided on the widest part of the base.
  • the inside of the counter i.e.
  • the contact surface of the counter (18 in Fig. 5) could also be provided with some kind of roughened surface for increasing the friction.
  • a roughened surface could be produced by for example mechanical working of the surface, knurling the surface, forming grooves into the surface, chemically etching the surface or by laser marked hatching of the surface.
  • the roughened surface is in one embodiment positioned on the outer wall of the canister at the base end and circumvents the canister, ie it is all the way around the canister side at the widest point of the canister length, see Fig. 3.
  • the friction between said canister and said counter could also be further increased by means of adhesive.
  • the inner surface of the counter could be co-moulded with a high friction coefficient material.
  • Another possible way of attaching the counter to the base of the canister fixedly to a predefined position is to melt the plastic into a close fit to the canister.
  • An example of this is to use ultra sonic welding or other heating process.
  • Fig. 4 shows how the counter 15 is attached to the canister 5.
  • Fig. 5a shows schematically a cross section of one embodiment of a counter 15 according to the invention before assembly to the canister 5.
  • deformable means 52 in the form of ribs are provided around the inside of the counter base.
  • Fig. 5b shows schematically the deformable ribs of Fig. 5a when the counter 15 is assembled to the canister.
  • the deformable ribs 52 are provided for improving the possibility to control the position of the counter on the base of the canister in a range of different positions.
  • the deformable ribs are deformed (can be seen in Fig. 5b) until the predefined length of the counter and canister together is achieved and then the pressing process is stopped.
  • the force to deform the ribs is higher than the maximum force a patient can apply to the device therefore the canister remains in a fixed position.
  • the deformable means could be shaped differently and also be positioned in other positions along the inside of the counter than what is shown in Fig. 5.
  • the deformable means could for example be spike shaped features, foam material etc.
  • the deformable means should deform in a controlled manner.
  • the deformable means could for example be of a rubber material or a polymer material. They could also be co-moulded from two or more materials.
  • Another method for preventing movement of the counter and canister when assembled is to use a quick setting polymer to deform and fill the space between the counter and canister during the assembly process.
  • correct depth alignment of the canister into the counter is achieved by controlling the distance the canister travels into the counter during the assembly process and thereby controlling the overall length tolerances. This is vital to the correct firing and count ratios of the device, encompassing the strict requirements of the regulatory bodies for under and over counting of said counting devices when used in conjunction with a metered dose inhaler system.

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  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Biomedical Technology (AREA)
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  • Infusion, Injection, And Reservoir Apparatuses (AREA)
  • Containers And Packaging Bodies Having A Special Means To Remove Contents (AREA)
  • Medical Preparation Storing Or Oral Administration Devices (AREA)
  • Medicinal Preparation (AREA)
  • Respiratory Apparatuses And Protective Means (AREA)
PCT/SE2005/000994 2004-07-02 2005-06-23 An inhalation device and a method for assembling said inhalation device Ceased WO2006004496A1 (en)

Priority Applications (15)

Application Number Priority Date Filing Date Title
AT05754148T ATE499132T1 (de) 2004-07-02 2005-06-23 Inhalationsvorrichtung und verfahren zum zusammenbauen dieser inhalationsvorrichtung
MXPA06014659A MXPA06014659A (es) 2004-07-02 2005-06-23 Dispositivo de inhalacion y metodo para ensamblar el dispositivo de inhalacion.
BRPI0512848A BRPI0512848B8 (pt) 2004-07-02 2005-06-23 dispositivo de inalação, método para montagem de um recipiente e um contador em um dispositivo de inalação, e, conjunto de recipiente e elemento contador adaptado para ser usado no dito dispositivo de inalação
US11/571,389 US8616196B2 (en) 2004-07-02 2005-06-23 Inhalation device and a method for assembling said inhalation device
NZ552105A NZ552105A (en) 2004-07-02 2005-06-23 An inhalation device and a method for assembling said inhalation device
CA2569923A CA2569923C (en) 2004-07-02 2005-06-23 An inhalation device and a method for assembling said inhalation device
HK07109885.2A HK1101895B (en) 2004-07-02 2005-06-23 An inhalation device and a method for assembling said inhalation device
AU2005260193A AU2005260193B2 (en) 2004-07-02 2005-06-23 An inhalation device and a method for assembling said inhalation device
DE602005026526T DE602005026526D1 (de) 2004-07-02 2005-06-23 Inhalationsvorrichtung und verfahren zum zusammenbauen dieser inhalationsvorrichtung
PL05754148T PL1768727T3 (pl) 2004-07-02 2005-06-23 Urządzenie inhalacyjne oraz sposób montażu wspomnianego urządzenia inhalacyjnego
EP05754148A EP1768727B1 (en) 2004-07-02 2005-06-23 An inhalation device and a method for assembling said inhalation device
JP2007520260A JP4869226B2 (ja) 2004-07-02 2005-06-23 吸入装置および該吸入装置を組み立てる方法
IL179971A IL179971A (en) 2004-07-02 2006-12-11 Inhalation device and method for assembling said inhalation device
KR1020067027821A KR101267923B1 (ko) 2004-07-02 2006-12-29 흡입 장치 및 상기 흡입 장치를 조립하는 방법
NO20070495A NO20070495L (no) 2004-07-02 2007-01-25 Inhalatoranordning og fremgangsmate for sammensetning av inhaleringsanordningen

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
SE0401773-7 2004-07-02
SE0401773A SE0401773D0 (sv) 2004-07-02 2004-07-02 An inhalation and a method for assemnling said inhalation device

Publications (1)

Publication Number Publication Date
WO2006004496A1 true WO2006004496A1 (en) 2006-01-12

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/SE2005/000994 Ceased WO2006004496A1 (en) 2004-07-02 2005-06-23 An inhalation device and a method for assembling said inhalation device

Country Status (22)

Country Link
US (1) US8616196B2 (enExample)
EP (1) EP1768727B1 (enExample)
JP (1) JP4869226B2 (enExample)
KR (1) KR101267923B1 (enExample)
CN (1) CN100563743C (enExample)
AR (1) AR054294A1 (enExample)
AT (1) ATE499132T1 (enExample)
AU (1) AU2005260193B2 (enExample)
BR (1) BRPI0512848B8 (enExample)
CA (1) CA2569923C (enExample)
DE (1) DE602005026526D1 (enExample)
ES (1) ES2359251T3 (enExample)
IL (1) IL179971A (enExample)
MX (1) MXPA06014659A (enExample)
NO (1) NO20070495L (enExample)
NZ (1) NZ552105A (enExample)
PL (1) PL1768727T3 (enExample)
SE (1) SE0401773D0 (enExample)
TW (1) TW200616602A (enExample)
UY (1) UY28991A1 (enExample)
WO (1) WO2006004496A1 (enExample)
ZA (1) ZA200610414B (enExample)

Cited By (3)

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WO2006126965A1 (en) * 2005-05-24 2006-11-30 Shl Medical Ab Dose counter device for inhaler
US8528545B2 (en) 2004-07-05 2013-09-10 Astrazeneca Ab Inhaler device that reduces the risk for miscounting a dosage
US9168343B2 (en) 1998-05-05 2015-10-27 Trudell Medical International Dispensing device

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SE0401787D0 (sv) * 2004-07-05 2004-07-05 Astrazeneca Ab Inhaler device counter
EP2077132A1 (en) 2008-01-02 2009-07-08 Boehringer Ingelheim Pharma GmbH & Co. KG Dispensing device, storage device and method for dispensing a formulation
US10011906B2 (en) 2009-03-31 2018-07-03 Beohringer Ingelheim International Gmbh Method for coating a surface of a component
US9265910B2 (en) 2009-05-18 2016-02-23 Boehringer Ingelheim International Gmbh Adapter, inhalation device, and nebulizer
US10016568B2 (en) 2009-11-25 2018-07-10 Boehringer Ingelheim International Gmbh Nebulizer
AP3141A (en) * 2009-11-25 2015-02-28 Boehringer Ingelheim Int Nebulizer
WO2011064163A1 (en) 2009-11-25 2011-06-03 Boehringer Ingelheim International Gmbh Nebulizer
BR112012019878A2 (pt) * 2010-02-10 2017-10-10 Astrazeneca Uk Ltd processo para fornecimento de um receptáculo cheio para um inalador
US9943654B2 (en) 2010-06-24 2018-04-17 Boehringer Ingelheim International Gmbh Nebulizer
WO2012130757A1 (de) 2011-04-01 2012-10-04 Boehringer Ingelheim International Gmbh Medizinisches gerät mit behälter
US9827384B2 (en) 2011-05-23 2017-11-28 Boehringer Ingelheim International Gmbh Nebulizer
WO2013152894A1 (de) 2012-04-13 2013-10-17 Boehringer Ingelheim International Gmbh Zerstäuber mit kodiermitteln
JP6643231B2 (ja) 2013-08-09 2020-02-12 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 ネブライザ
EP2835146B1 (en) 2013-08-09 2020-09-30 Boehringer Ingelheim International GmbH Nebulizer
CN106456913B (zh) 2014-05-07 2019-08-30 勃林格殷格翰国际有限公司 喷雾器和容器
DK3139979T3 (da) 2014-05-07 2023-10-09 Boehringer Ingelheim Int Enhed, forstøver og fremgangsmåde
EP3139984B1 (en) 2014-05-07 2021-04-28 Boehringer Ingelheim International GmbH Nebulizer
CA3073195A1 (en) 2017-08-15 2019-02-21 Nephron Pharmaceuticals Corporation Aqueous nebulization composition
US20240382701A1 (en) * 2021-07-20 2024-11-21 Invox Belgium Nv Inhalation device system with a counting and blocking assembly

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HK1101895A1 (en) 2007-11-02
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BRPI0512848B8 (pt) 2021-06-22
NZ552105A (en) 2010-04-30
CA2569923C (en) 2013-10-01
IL179971A (en) 2010-06-16
UY28991A1 (es) 2006-01-31
KR20070027652A (ko) 2007-03-09
JP4869226B2 (ja) 2012-02-08
PL1768727T3 (pl) 2011-06-30
SE0401773D0 (sv) 2004-07-02
AU2005260193B2 (en) 2009-04-23
AU2005260193A1 (en) 2006-01-12
MXPA06014659A (es) 2007-02-12
JP2008504923A (ja) 2008-02-21
TW200616602A (en) 2006-06-01
CN100563743C (zh) 2009-12-02
EP1768727B1 (en) 2011-02-23
CN1997417A (zh) 2007-07-11
DE602005026526D1 (de) 2011-04-07
ES2359251T3 (es) 2011-05-19
IL179971A0 (en) 2007-05-15
US20080083408A1 (en) 2008-04-10
BRPI0512848A (pt) 2008-04-08
EP1768727A1 (en) 2007-04-04
NO20070495L (no) 2007-03-20
KR101267923B1 (ko) 2013-05-27
ATE499132T1 (de) 2011-03-15
AR054294A1 (es) 2007-06-20
ZA200610414B (en) 2008-02-27
US8616196B2 (en) 2013-12-31

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