CA2490174A1 - Gas separation devices - Google Patents

Gas separation devices Download PDF

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Publication number
CA2490174A1
CA2490174A1 CA002490174A CA2490174A CA2490174A1 CA 2490174 A1 CA2490174 A1 CA 2490174A1 CA 002490174 A CA002490174 A CA 002490174A CA 2490174 A CA2490174 A CA 2490174A CA 2490174 A1 CA2490174 A1 CA 2490174A1
Authority
CA
Canada
Prior art keywords
chamber
containing body
fluid
aperture
guide element
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
CA002490174A
Other languages
French (fr)
Other versions
CA2490174C (en
Inventor
Jacques Chevallet
Francesco Ribolzi
Alain Frugier
Nicolas Semenzato
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.)
Gambro Lundia AB
Original Assignee
Individual
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 claimed from IT2002MI001389A external-priority patent/ITMI20021389A1/en
Priority claimed from IT2002MI001390A external-priority patent/ITMI20021390A1/en
Application filed by Individual filed Critical Individual
Priority to CA2729519A priority Critical patent/CA2729519C/en
Publication of CA2490174A1 publication Critical patent/CA2490174A1/en
Application granted granted Critical
Publication of CA2490174C publication Critical patent/CA2490174C/en
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

Links

Classifications

    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01DSEPARATION
    • B01D19/00Degasification of liquids
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01DSEPARATION
    • B01D19/00Degasification of liquids
    • B01D19/0042Degasification of liquids modifying the liquid flow
    • B01D19/0052Degasification of liquids modifying the liquid flow in rotating vessels, vessels containing movable parts or in which centrifugal movement is caused
    • B01D19/0057Degasification of liquids modifying the liquid flow in rotating vessels, vessels containing movable parts or in which centrifugal movement is caused the centrifugal movement being caused by a vortex, e.g. using a cyclone, or by a tangential inlet
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES 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
    • A61M1/00Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
    • A61M1/34Filtering material out of the blood by passing it through a membrane, i.e. hemofiltration or diafiltration
    • A61M1/342Adding solutions to the blood, e.g. substitution solutions
    • A61M1/3424Substitution fluid path
    • A61M1/3437Substitution fluid path downstream of the filter, e.g. post-dilution with filtrate
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES 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
    • A61M1/00Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
    • A61M1/36Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits
    • A61M1/3621Extra-corporeal blood circuits
    • A61M1/3627Degassing devices; Buffer reservoirs; Drip chambers; Blood filters
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES 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
    • A61M1/00Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
    • A61M1/36Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits
    • A61M1/3621Extra-corporeal blood circuits
    • A61M1/3639Blood pressure control, pressure transducers specially adapted therefor
    • A61M1/3641Pressure isolators
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES 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
    • A61M1/00Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
    • A61M1/36Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits
    • A61M1/3672Means preventing coagulation
    • A61M1/3676Means preventing coagulation by interposing a liquid layer between blood and air
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01FMIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F25/00Flow mixers; Mixers for falling materials, e.g. solid particles
    • B01F25/10Mixing by creating a vortex flow, e.g. by tangential introduction of flow components
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B04CENTRIFUGAL APPARATUS OR MACHINES FOR CARRYING-OUT PHYSICAL OR CHEMICAL PROCESSES
    • B04CAPPARATUS USING FREE VORTEX FLOW, e.g. CYCLONES
    • B04C5/00Apparatus in which the axial direction of the vortex is reversed
    • B04C5/08Vortex chamber constructions
    • B04C5/103Bodies or members, e.g. bulkheads, guides, in the vortex chamber
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES 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
    • A61M1/00Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
    • A61M1/36Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits
    • A61M1/3621Extra-corporeal blood circuits
    • A61M1/3639Blood pressure control, pressure transducers specially adapted therefor
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES 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
    • A61M2205/00General characteristics of the apparatus
    • A61M2205/33Controlling, regulating or measuring
    • A61M2205/3379Masses, volumes, levels of fluids in reservoirs, flow rates
    • A61M2205/3382Upper level detectors
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES 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
    • A61M2206/00Characteristics of a physical parameter; associated device therefor
    • A61M2206/10Flow characteristics
    • A61M2206/16Rotating swirling helical flow, e.g. by tangential inflows

Abstract

A description is given of a gas separation device for a physiological fluid, comprising a containing body (6) having at least a first inlet aperture (7) for a physiological fluid, positioned with a tangential direction of access, at least one outlet aperture (9) for the said fluid, spaced apart from the said inlet aperture, and a guide element (17) housed within the said body. T he guide element (17) has a continuous active surface (15) designed to contact and guide the said fluid and delimits, together with the containing body (6) , a first annular chamber (20) into which the first inlet aperture (7) opens directly.

Claims (66)

1. Gas separation device for a physiological fluid, comprising:
- a containing body having an internal active surface and having at least a first inlet aperture for a physiological fluid, positioned with a tangential direction of access, and at least one outlet aperture for the said fluid, spaced apart from the said inlet aperture; characterized in that it comprises:
- a guide element housed at least partially within the said body and having a continuous active surface designed to contact and guide the said fluid;
- a first annular chamber formed between the active surface of the said guide element and the internal active surface of the said containing body.
2. Device according to claim 1, characterized in that the said inlet aperture opens directly into the said first chamber.
3. Device according to claim 1, characterized in that the said guide element is wholly housed within the containing body, extends coaxially with the latter and is spaced axially apart from the said outlet aperture.
4. Device according to claim 3, characterized in that the active surfaces of the said containing body and of the said guide element face each other and are shaped in the form of surfaces of revolution about a common axis of symmetry which is transverse with respect to the tangential direction of access of the said flow.
5. Device according to claim 1, characterized in that the said outlet aperture is positioned in a lower end of the said containing body, the said guide element and the said first chamber extending above the said outlet aperture.
6. Device according to claim 1, characterized in that the said guide element is a solid or internally hollow solid of rotation, designed to reduce the volume of at least the said first chamber.
7. Device according to claim 1, characterized in that the said guide element comprises:
- a central portion;
- a first terminal portion, facing towards the said outlet aperture; and - a second terminal portion, axially opposed to the first terminal portion and facing towards a second chamber extending above the said guide element.
8. Device according to claim 7, characterized in that the first terminal portion has a cross section whose radial dimension is reduced progressively towards the said outlet aperture.
9. Device according to Claim 8, characterized in that the said first terminal portion has a conical shape with its vertex facing towards the outlet aperture.
10. Device according to Claim 7, characterized in that the second terminal portion has a cross section whose radial dimension is reduced progressively away from the said outlet aperture.
11. Device according to Claim 10, characterized in that the said second terminal portion has a conical shape with its vertex opposed to the outlet aperture.
12. Device according to Claim 7, characterized in that the central portion has a cross section with a radial dimension which is reduced progressively away from the said terminal portions, to form an intermediate area having a minimum radial dimension.
13. Device according to Claim 12, characterized in that the central portion has a curved profile in longitudinal section.
14. Device according to Claim 7, characterized in that the said active surface of the containing body has:
- a first area, of maximum radial dimension, extending around the central portion of the guide element;
- a second area, whose radial dimension is reduced progressively towards the outlet aperture, the second area extending consecutively to the first area and essentially around the first terminal portion of the guide element;
- a third area, whose radial dimension is reduced progressively away from the outlet aperture, the third area extending consecutively to the first area and essentially around the second terminal portion of the guide element.
15. Device according to Claim 14, characterized in that the first inlet aperture opens into the said first chamber, in the said intermediate first area of the active surface of the containing body.
16. Device according to Claim 14, characterized in that the first area of the active surface has a constant radius.
17. Device according to Claim 1, characterized in that the said containing body comprises a second inlet aperture located above the said first inlet aperture and designed to convey a second fluid into the containing body.
18. Device according to Claim 17, characterized in that it comprises a second chamber extending above the said
19 guide element, in an axially consecutive position and in fluid communication with the said first chamber and with the said second inlet aperture.

19. Device according to Claim 18, characterized in that the said second inlet aperture opens directly into the said second chamber, preferably in a direction parallel to, and staggered with respect to, that of the said first inlet aperture.
20. Device according to Claim 18, characterized in that the said containing body includes a third chamber, which is axially consecutive to the said second chamber and which is designed to contain the gas separated from the said fluids, the said third chamber extending in the top of the said containing body.
21. Device according to Claim 20, characterized in that it comprises at least one service line having a first end which is brought into fluid communication with the said third chamber by means of a fourth aperture formed in the said containing body.
22. Device according to Claim 21, characterized in that it comprises at least one pressure sensor element associated for operation with the said service line.
23. Device according to Claim 2l, characterized in that it comprises at least one hydrophobic membrane associated for operation with an intermediate area of the service line.
24. Device according to Claim 21, characterized in that the third chamber has a nominal volume V c delimited below by a theoretical maximum level line BL and above by the said fourth aperture.
25. Device according to Claim 21, comprising a pneumatic circuit operating in the said service line, for selectively sending gas to the service line and drawing gas from it.
26. Device according to Claim 25, comprising a liquid level sensor LLS located above a level BL, and a control unit connected to the sensor LLS and designed to control the said pneumatic circuit to maintain the liquid level in the vicinity of the said level BL.
27. Device according to Claim 26, in which the level sensor LLS operates in a section of the service line and in which the said control unit is designed to cause the execution of the following steps:
- determining whether LLS is signalling the presence of liquid, and, if so, executing the following sub-steps in sequence:
a) activation of the pneumatic circuit to drive towards the third chamber a volume V1, equal to the volume between the section in which LLS operates and the fourth aperture, b) activation of the pneumatic circuit to draw gas from the third chamber while LLS continues to signal the presence of liquid, c) activation of the pneumatic circuit to drive towards the third chamber a volume of liquid V2, equal to V1 + V c, where V c is the volume of the third chamber;
- if, on the other hand, LLS is not signalling the presence of liquid, executing the aforementioned three steps a), b) and c) at specified time intervals.
28. Device according to Claim 21, characterized in that it comprises at least one access site located in the said service line for manually drawing fluid from the said line or sending fluid into it.
29. Device according to Claim 26, characterized in that the level sensor LLS can operate on the said containing body.
30. Device according to Claim 1, characterized in that it comprises:
- a first line for sending the physiological fluid into the said containing body through the first inlet aperture, - a second line for sending a second fluid into the said containing body through a second inlet aperture, - a pump operating to create a flow along the first line, - a pump operating to create a flow along the second line, - a control unit programmed to control the pumps operating in the first and second lines and to ensure the constant presence in the containing body of a layer of the said second fluid whose thickness lies within. a specified range, this layer being located above the physiological fluid.
31. Fluid mixing device with gas separation, comprising a containing body having an internal active surface and having at least one first inlet aperture for a physiological fluid, and at least one fluid outlet aperture, spaced apart from the said first inlet aperture, characterized in that the containing body has at least one second inlet aperture located above the said first inlet aperture and designed to convey a second fluid into the containing body to form a layer of the said second fluid above the said physiological fluid.
32. Device according to Claim 31, characterized in that the said containing body includes:

- at least a first chamber extending in a lower area of the containing body and in fluid communication with the said outlet aperture;
- at least a second chamber, extending in an axially consecutive upper area and in fluid communication with the said first chamber.
33. Device according to Claim 32, characterized in that the said containing body includes a third chamber, which is axially consecutive to the said second chamber and which is designed to contain the gas separated from the said fluids, the said third chamber extending in the top of the said containing body and having a fourth aperture.
34. Device according to Claim 33, characterized in that it comprises at least one service line having a first end which is brought into fluid communication with the said third chamber by means of the fourth aperture formed in the said containing body.
35. Device according to Claim 34, characterized in that it comprises at least one pressure sensor element associated for operation with the said service line.
36. Device according to Claim 35, characterized in that it comprises at least one hydrophobic membrane associated for operation with an intermediate area of the service line, between the fourth aperture and the pressure sensor element.
37. Device according to Claim 33, characterized in that the third chamber has a nominal volume V c delimited below by a theoretical maximum level line BL and above by the said fourth aperture.
38. Device according to Claim 34, comprising a pneumatic circuit for selectively sending gas to the service line and drawing gas from the line.
39. Device according to Claim 38, comprising a liquid level sensor LLS located above a level BL, and a control unit connected to the sensor LLS and designed to control the said pneumatic circuit to maintain the liquid level in the vicinity of the said level BL.
40. Device according to Claim 39, in which the said level sensor is located in the said service line and the said control unit is designed to cause the execution of the following steps:
- determining whether LLS is signalling the presence of liquid, and, if so, executing the following sub-steps in sequence:
a) activation of the pneumatic circuit to drive towards the third chamber a volume V 1, equal to the volume between the section in which LSS operates and the fourth aperture, b) activation of the pneumatic circuit to draw gas from the third chamber while LSS continues to signal the presence of liquid, c) activation of the pneumatic circuit to drive towards the third chamber a volume of liquid V2, equal to V1 + V c, where V c is the volume of the third chamber;
- if, on the other hand, LLS is not signalling the presence of liquid, executing the aforementioned three steps a), b) and c) at specified time intervals.
41. Device according to Claim 34, characterized in that it comprises at least one access site located in the said service line for manually drawing fluid from the line or sending fluid to it.
42. Device according to Claim 39, characterized in that the level sensor LLS operates on the said containing body.
43. Device according to Claim 31, characterized in that it comprises:
- a first line for sending the physiological fluid into the said containing body through the first inlet aperture, - a second line for sending the second fluid into the said containing body through the second inlet aperture, - a pump operating to create a flow along the first line, - a pump operating to create a flow along the second line, - a programmable control unit for controlling the pumps operating in the first and second lines and for ensuring the constant presence in the containing body of a layer whose thickness lies within a specified range, this layer being located above the physiological fluid.
44. Device according to Claim 43, characterized in that the control unit activates the pump operating in the said second line in a continuous or intermittent mode, to provide a specified flow rate at every specified time interval.
45. Device according to Claim 43, characterized in that it comprises a means for sensing the actual flow in the second line, this sensor means sending corresponding signals to the said control unit.
46. Device according to Claim 43, in which the thickness of the said layer is smaller than the maximum diameter of the internal surface of the containing body.
47. Device according to Claim 32, in which the said first inlet aperture opens directly into the said first chamber in a tangential direction of access, and in which the said second inlet aperture opens directly towards the said second chamber in a direction of access parallel to that of the said first aperture.
48. Device according to Claim 47, comprising a guide element housed at least partially within the said body and having a continuous active surface designed to contact and guide the said fluid, the said first chamber having an annular configuration and being formed between the active surface of the said element and the active surface of the containing body.
49. Device according to Claim 48, characterized in that the said guide element is wholly housed within the containing body, extends coaxially with the latter and is spaced axially apart from the said outlet aperture.
50. Device according to Claim 48, characterized in that the active surfaces of the said containing body and of the said guide element face each other and are shaped in the form of surfaces of revolution about a common axis of symmetry which is transverse with respect to the tangential direction of access of the said flow.
51. Device according to Claim 48, characterized in that the said outlet aperture is positioned in a lower end of the said containing body, the said guide element and the said first chamber extending above the said outlet aperture.
52. Device according to Claim 50, characterized in that the said guide element is a solid or internally hollow solid of rotation, designed to reduce the volume of at least the said first chamber.
53. Device according to Claim 48, characterized in that the said guide element comprises:
- a central portion;

- a first terminal portion, facing towards the said outlet aperture; and - a second terminal portion, axially opposed to the first terminal portion and facing towards the said second chamber.
54. Device according to Claim 53, characterized in that the first terminal portion has a cross section whose radial dimension is reduced progressively towards the said outlet aperture.
55. Device according to Claim 54, characterized in that the said first terminal portion has a conical shape with its vertex facing towards the outlet aperture.
56. Device according to Claim 53, characterized in that the second terminal portion has a cross section whose radial dimension is reduced progressively away from the said outlet aperture.
57. Device according to Claim 56, characterized in that the said second terminal portion has a conical shape with its vertex opposed to the outlet aperture.
58. Device according to Claim 53, characterized in that the central portion has a cross section with a radial dimension which is reduced progressively away from the said terminal portions, to form an intermediate area having a minimum radial dimension.
59. Device according to Claim 58, characterized in that the central portion has a curved profile in longitudinal section.
60. Device according to Claim 53, characterized in that the said active surface of the containing body has:
- a first area, of maximum radial dimension, extending around the central portion of the guide element;

- a second area, whose radial dimension is reduced progressively towards the outlet aperture, the second area extending consecutively to the first area and essentially around the first terminal portion of the guide element;
- a third area, whose radial dimension is reduced progressively away from the outlet aperture, the third area extending consecutively to the first area and essentially around the second terminal portion of the guide element.
61. Device according to Claim 60, characterized in that the first inlet aperture opens into the said first chamber, in the said intermediate first area.
62. Device according to Claim 60, characterized in that the first area of the active surface has a constant radius.
63. Fluid mixing method with gas separation, comprising the following steps:
- providing a containing body having an internal active surface and having at least a first inlet aperture, at least one fluid outlet aperture spaced apart from the said first inlet aperture, and at least a second inlet aperture located above the said first inlet aperture;
- sending a first physiological fluid into the containing body through the said first aperture;
- conveying a second fluid into the containing body through the said second aperture to form a layer of the said second fluid above the said physiological fluid;
- conveying a separated gas from the said first and second fluids above the said layer.
64. Method according to Claim 63, characterized in that it comprises the steps of:

- measuring the flow rate of the said first fluid;
- measuring the flow rate of the said second fluid;
- regulating the flow rate of the said first and the said second fluid to provide a layer of the said second fluid with a thickness lying within a specified range.
65. Method according to Claim 64, characterized in that the said second fluid is sent, in continuous or intermittent mode, in a direction of access to the containing body parallel to that of the said first fluid.
66. Method according to Claim 64, characterized in that the thickness of the said layer is kept below the maximum diameter of the internal surface of the containing body.
CA2490174A 2002-06-24 2003-05-26 Gas separation devices Expired - Lifetime CA2490174C (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CA2729519A CA2729519C (en) 2002-06-24 2003-05-26 Gas separation devices

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
IT2002MI001389A ITMI20021389A1 (en) 2002-06-24 2002-06-24 MIXING DEVICE FOR FLUIDS WITH GAS SEPARATION
ITMI2002A001390 2002-06-24
IT2002MI001390A ITMI20021390A1 (en) 2002-06-24 2002-06-24 GAS SEPARATION DEVICE FOR PHYSIOLOGICAL FLUIDS
ITMI2002A001389 2002-06-24
PCT/IB2003/002281 WO2004000391A1 (en) 2002-06-24 2003-05-26 Gas separation devices

Related Child Applications (1)

Application Number Title Priority Date Filing Date
CA2729519A Division CA2729519C (en) 2002-06-24 2003-05-26 Gas separation devices

Publications (2)

Publication Number Publication Date
CA2490174A1 true CA2490174A1 (en) 2003-12-31
CA2490174C CA2490174C (en) 2011-04-19

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CA2729519A Expired - Lifetime CA2729519C (en) 2002-06-24 2003-05-26 Gas separation devices
CA2490174A Expired - Lifetime CA2490174C (en) 2002-06-24 2003-05-26 Gas separation devices

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CA2729519A Expired - Lifetime CA2729519C (en) 2002-06-24 2003-05-26 Gas separation devices

Country Status (10)

Country Link
US (1) US7517387B2 (en)
EP (2) EP2055331B1 (en)
JP (1) JP4358736B2 (en)
KR (1) KR100947006B1 (en)
AT (1) ATE426420T1 (en)
AU (1) AU2003233023B2 (en)
CA (2) CA2729519C (en)
DE (1) DE60326847D1 (en)
ES (2) ES2473627T3 (en)
WO (1) WO2004000391A1 (en)

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