ES2353733T3 - Sistema de anclaje para prótesis implantables de válvula cardiaca. - Google Patents

Sistema de anclaje para prótesis implantables de válvula cardiaca. Download PDF

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Publication number
ES2353733T3
ES2353733T3 ES01916903T ES01916903T ES2353733T3 ES 2353733 T3 ES2353733 T3 ES 2353733T3 ES 01916903 T ES01916903 T ES 01916903T ES 01916903 T ES01916903 T ES 01916903T ES 2353733 T3 ES2353733 T3 ES 2353733T3
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Prior art keywords
heart valve
valve prosthesis
hook
shaped elements
prosthesis according
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Inventor
Markus Ferrari
Klaus Lang
Hans-Reiner Figulla
Christoph Damm
Carsten Weber
Stefan Risse
Volker Guyenot
Matthias Mohaupt
Gerd Harnisch
Peggy DÖRRER
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Jenavalve Technology Inc
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Jenavalve Technology Inc
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02—Prostheses implantable into the body
    • A61F2/24—Heart valves ; Vascular valves, e.g. venous valves; Heart implants, e.g. passive devices for improving the function of the native valve or the heart muscle; Transmyocardial revascularisation [TMR] devices; Valves implantable in the body
    • A61F2/2412—Heart valves ; Vascular valves, e.g. venous valves; Heart implants, e.g. passive devices for improving the function of the native valve or the heart muscle; Transmyocardial revascularisation [TMR] devices; Valves implantable in the body with soft flexible valve members, e.g. tissue valves shaped like natural valves
    • A61F2/2418—Scaffolds therefor, e.g. support stents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2220/00—Fixations or connections for prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
    • A61F2220/0008—Fixation appliances for connecting prostheses to the body
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2220/00—Fixations or connections for prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
    • A61F2220/0008—Fixation appliances for connecting prostheses to the body
    • A61F2220/0016—Fixation appliances for connecting prostheses to the body with sharp anchoring protrusions, e.g. barbs, pins, spikes

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  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Cardiology (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Transplantation (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Vascular Medicine (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Prostheses (AREA)
  • Materials For Medical Uses (AREA)

Abstract

Prótesis de válvula cardíaca implantable con un anclaje presentando el anclaje varios elementos en forma de gacho (2) o elementos en forma de gancho (2) con garfios, y por lo menos un elemento base o puente (3) mediante el cual van sujetos los elementos en forma de gancho (2) o los elementos en forma de gancho (2) con garfio, estando fijados los elementos en forma de gancho (2) o los elementos en forma de gancho (2) con garfio en por lo menos una comisura de la prótesis de válvula cardíaca (1), estando conducidos los elementos en forma de gancho (2) hacia el exterior a través del material de la válvula cardíaca, siendo los elementos en forma de gancho (2) o los elementos en forma de gancho (2) con garfio de un metal con memoria de forma, estando diseñados para que asienten planos durante la fase de inserción durante la implantación de la prótesis de válvula cardíaca (1) y se levanten al alcanzar o rebasar la temperatura de salto característica del metal con memoria de forma.

Description

La invención se refiere a un anclaje para prótesis de válvulas cardíacas que se puedan implantar sin gran intervención operativa, mediante inserción a través de la aorta, para la que de forma convencional se requería la apertura completa del tórax. 5
En el pasado se han efectuado los intentos más diversos y se han ofrecido también soluciones mediante las cuales se pudieran conducir las prótesis de válvulas cardíacas a través de la aorta hasta el corazón, y que allí se implantaran firmemente después de un proceso de desplegado o de fijación.
10
Así p.ej. se describe entre otros en el documento US 5.855.601 lo que se denomina un stent, en el que se puede fijar una prótesis de válvula cardíaca. El stent se forma esencialmente de un metal filiforme con memoria de forma, que en una estructura reticular representa una formación de forma cilíndrica. El material con memoria de forma se puede plegar a temperaturas inferiores a 37°C, y en estado plegado se pretende conducir mediante un catéter a través de la aorta hasta el corazón, donde al desconectar una refrigeración y alcanzar la temperatura de 15 unos 37°C, adopta la forma inculcada y en el correspondiente estado desplegado asienta en la pared interior de la aorta.
Debido a las limitaciones que presenta el metal con memoria de forma, un stent de esta clase solamente con dificultad se puede miniaturizar y plegar lo suficiente para poderlo conducir sin problemas a través de la aorta, y 20 tener además en estado desplegado unas dimensiones tales que asiente en la pared interior de la aorta y también quede allí sujeto con seguridad.
La fabricación de un soporte de anclaje con esta estructura y diseño, a base de un material con memoria de forma convencional y adecuado dentro de la gama de temperatura requerida (p.ej. Nitinol), crea además problemas 25 y entraña un correspondiente elevado coste de fabricación, ya que un cuerpo de esta clase por lo general se recorta mediante corte por rayo láser a partir de un material macizo.
En el estado de la técnica se dan a conocer en el artículo 54 (3) EPÜ unos elementos en forma de gancho de ELGILOY. 30
Constituye por lo tanto el objetivo de la invención proponer una posibilidad mediante la cual se puedan conducir prótesis de válvula cardíaca al corazón a través de la aorta, y se puedan fijar allí.
De acuerdo con la invención se resuelve este objetivo por las características de la reivindicación 1. Unas 35 formas de realización ventajosas y perfeccionamientos de la invención se obtienen con las características citadas en las reivindicaciones subordinadas.
De acuerdo con la invención se fijan unos elementos en forma de gancho directamente en las comisuras de una prótesis de válvula cardíaca biológica, que puede estar obtenida p.ej. de un corazón de cerdo, o de otra prótesis 40 de válvula cardíaca artificial, cuyos ganchos pasan a través del material de la prótesis de válvula cardíaca y van clavados en estado implantado en la pared de la aorta o atraviesan la pared de la aorta, de modo que la prótesis de válvula cardíaca se pueda fijar con seguridad en la pared de la aorta.
Además puede haber otros elementos adicionales en forma de gancho fijados en el anillo exterior de la 45 prótesis de válvula cardíaca.
Los elementos en forma de gancho pueden estar cosidos a la prótesis de válvula cardíaca.
Sin embargo es más sencillo y entraña un gasto menor introducir los elementos en forma de gancho desde 50 el interior en la prótesis de válvula cardíaca, y atravesar por lo menos los ganchos a través del material de la prótesis de válvula cardíaca, siendo conveniente disponer los elementos en forma de gancho sobre un puente o realizarlos con un elemento base, con lo cual se tiene la seguridad de que únicamente sobresalen de la prótesis de válvula cardíaca los ganchos de los elementos en forma de gancho, y la parte restante quede asegurada en el interior de la prótesis de válvula cardíaca debido a su tamaño respectivo. 55
El puente puede presentar p.ej. la forma de una varilla plana o de una placa alargada, en la que están dispuestos por lo menos dos elementos en forma de gancho.
Un elemento base puede estar realizado p.ej. en forma de placa de forma circular, en cuyo caso la 60 superficie de la sección del círculo puede impedir que se atraviese el material de la prótesis de válvula cardíaca.
Los elementos de gancho dispuestos en los puentes o sobre los elementos base pueden estar realizados esencialmente en forma de espiga. En este caso, en la parte en forma de espiga están realizados uno o más garfios para el anclaje en la pared de la aorta, que después de introducir a presión se enganchan en o detrás de la pared de la aorta.
5
La forma de los garfios se puede inculcar en un material con memoria de forma, de modo que los garfios solamente estén orientados hacia el exterior por encima de las temperaturas de salto, facilitándose de este modo el clavado y atravesamiento de la pared de la aorta.
Si se emplean puentes en los que estén realizados los elementos en forma de gancho o si están fijados en 10 éstos, se pueden fijar entonces en las comisuras de una prótesis de válvula cardíaca de tal modo que en estado implantado queden orientados en la dirección longitudinal de la aorta.
Pero también puede ser sumamente ventajoso formar los puentes con forma espiral, de modo que gracias a la forma espiral se adapten al contorno interior de la aorta y asienten directamente en ésta después de efectuado el 15 anclaje mediante los ganchos, donde debido a la forma espiral hay una zona mayor de la pared interior de la aorta que queda cubierta y por lo tanto se puede conseguir un mayor grado de estanqueidad.
Si se emplean elementos en forma de gancho que por lo demás están separados entre sí, con elementos base, entonces éstos también deben estar distribuidos a lo largo de las comisuras, siendo posible también realizar 20 una disposición que siga una forma espiral o una disposición a base de dos espirales enrolladas en sentido contrario.
Si se emplean puentes con elementos en forma de gancho, estos puentes deben presentar una longitud que sea por lo menos tan grande como la longitud de las comisuras de la prótesis de válvula cardíaca. 25
Los puentes fijados en las diversas comisuras no están unidos entre sí.
Para efectuar la inserción de la prótesis de válvula cardíaca con el anclaje fijado en ella, es además conveniente si elementos en forma de gancho son de un metal con memoria de forma que asegure que los 30 elementos en forma de gancho asientan planos durante la fase de inserción y ofrezcan solo escasa resistencia a la inserción y permitan alcanzar un volumen reducido, y solamente se produzca la forma deseada y el levantamiento de los ganchos para su anclaje en la pared de la aorta, después de haber desconectado el enfriamiento.
La altura eficaz de los elementos en forma de gancho debería ser entonces por lo menos de 2 mm, de 35 modo que sobresalgan con esta altura de la prótesis de la válvula cardíaca y penetren o atraviesen la pared de la aorta.
También es ventajoso que los ganchos de los diferentes elementos en forma de gancho estén acodados en diferentes direcciones, de modo que se pueda conseguir una fijación segura del anclaje objeto de la invención, 40 teniendo también en cuenta las condiciones existentes en la aorta, las condiciones de presión y flujo que existen en las proximidades del corazón.
Los elementos en forma de gancho próximos entre sí pueden estar acodados ventajosamente y orientados de modo enfrentado entre sí, o se les puede inculcar esta posición al utilizar un metal con memoria de forma. Esto 45 da lugar a que al alcanzar o rebasar la temperatura de salto se produzca en la pared de la aorta un engrapado de los elementos en forma de gancho contiguos.
En el interior de la prótesis de válvula cardíaca, en la zona de su anillo exterior, puede estar fijado además un elemento adicional de forma anular, que en la fase de inserción a través de la aorta también se pueda plegar 50 ocupando un volumen menor. Para ello se puede emplear un material elástico, tal como p.ej., un plástico o caucho adecuados, dotados eventualmente de un muelle helicoidal, o también un muelle helicoidal solo o un metal con memoria de forma.
La prótesis de válvula cardíaca dotada del anclaje conforme a la invención se puede insertar en la aorta 55 mediante un catéter en el que esté dispuesto un mecanismo adecuado, donde el mecanismo debe asegurar el despliegue de la prótesis de válvula cardíaca y el soltar la prótesis de válvula cardíaca una vez colocada en la posición deseada.
Pero también se puede utilizar un catéter de globo, en cuyo caso la prótesis de válvula cardíaca dotada del 60 anclaje conforme a la invención se puede insertar en la aorta, en posición vuelta. Una vez que se alcance el lugar de la implantación se aplica presión al globo y se comprime la prótesis de válvula cardíaca con los elementos en forma de gancho contra la pared de la aorta, pudiendo entonces anclarse los ganchos en la pared de la aorta, en cuyo caso al emplear un metal con memoria de forma se puede emplear el catéter de globo también para obtener la refrigeración necesaria.
La superficie del globo de un catéter de este tipo puede presentar el contorno correspondiente, de modo 5 que debido a la elasticidad del globo y al contorno realizado de forma correspondiente, los elementos base o los puentes sujeten con seguridad los puentes o los elementos base durante la fase de paso a través de la aorta, y esta sujeción se pueda liberar al inflar el globo.
Pero también se puede emplear un catéter con un mecanismo que se despliegue automáticamente, que 10 nuevamente consiste también de un metal con memoria de forma, con el fin de asegurar la fijación de la prótesis de válvula cardíaca con el anclaje conforme a la invención.
En cualquier caso es conveniente sin embargo que durante la fase de paso a través de la aorta se envuelva la prótesis de válvula cardíaca con el fin de evitar lesiones indeseables de la pared de la aorta antes de alcanzar el 15 lugar de la implantación, y asegurar además el correspondiente aislamiento térmico, cuando se requiera refrigeración. Una vez alcanzado el lugar de la implantación se puede abrir esta envoltura o activar un mecanismo de desbloqueo, que se vuelve a retirar junto con el catéter fuera de la aorta.
Si se emplea un mecanismo de despliegue a base de un metal con memoria de forma éste se puede 20 realizar, tal como ya se ha mencionado, como elemento en forma de anillo, que en la zona del anillo exterior de la prótesis de válvula cardíaca va fijada en ésta. Un elemento de forma anular de esta clase puede asegurar entonces la estabilidad de la prótesis de válvula cardíaca implantada, así como una superior función de sellado.
A continuación se trata de explicar la invención con mayor detalle sirviéndose de un ejemplo de realización. 25
Las Figuras muestran:
Figura 1 un ejemplo de un anclaje conforme a la invención en una prótesis de válvula cardíaca.
30
En el ejemplo de un anclaje conforme a la invención para una prótesis de válvula cardíaca 1, mostrado en la Figura 1, se han formado en los puentes 3 unos elementos en forma de gancho, y se ha dispuesto y fijado cada uno de tales puentes 3 en una comisura de la prótesis de válvula cardíaca 1.
En este ejemplo, tanto los puentes 3 como los elementos en forma de gancho 2 son de un metal con 35 memoria de forma, tal como se puede obtener p.ej. con la denominación Nitinol. Para realizar la fijación se introducen los puentes 3 desde el interior en la prótesis de la válvula cardíaca 1, y se comprimen simplemente a través de las comisuras de la prótesis de válvula cardíaca 1, de modo que ésta queda atravesada.
Al metal con memoria de forma empleado se le puede inculcar la forma representada en la Figura 1, que se 40 adopta después de rebasar la temperatura de salto de 37°C. Durante la fase de inserción de la prótesis de la válvula cardíaca 1 sin embargo los elementos en forma de gancho 2 deben estar inclinados a ser posible casi 90° en dirección hacia el eje longitudinal de los puentes 3, con el fin de que requieran un volumen relativamente pequeño y sobresalgan sólo ligeramente, de modo que se pueda facilitar la inserción y evitar lesiones de la pared de la aorta.
45
En el ejemplo que aquí está representado hay cinco elementos en forma de gancho realizados en cada uno de los puentes 3. En total se deberían emplear como mínimo 15 elementos en forma de gancho.
El número de los elementos en forma de gancho 2 se puede variar sin embargo sin problemas, existiendo además la posibilidad de fijar en una comisura de la prótesis de la válvula cardíaca 1 varios de tales puentes 50 dotados de elementos en forma de gancho 2.
Los puentes 3 pueden estar orientados inclinados un ángulo, a diferencia de lo aquí representado, en cuyo caso dos de tales puentes 3 pueden presentar también una inclinación opuesta entre ellos.
55
En una forma no representada puede haber un elemento adicional de forma anular fijado en la prótesis de válvula cardíaca 1 en la zona del anillo exterior 4 de ésta.
Para mejorar la fijación puede haber también unos garfios realizados en los elementos en forma de gancho 12 o en sus ganchos. 60

Claims (13)

  1. REIVINDICACIONES
    1. Prótesis de válvula cardíaca implantable con un anclaje presentando el anclaje varios elementos en forma de gacho (2) o elementos en forma de gancho (2) con garfios, y por lo menos un elemento base o puente (3) mediante el cual van sujetos los elementos en forma de gancho (2) o los elementos en forma de gancho 5 (2) con garfio, estando fijados los elementos en forma de gancho (2) o los elementos en forma de gancho (2) con garfio en por lo menos una comisura de la prótesis de válvula cardíaca (1), estando conducidos los elementos en forma de gancho (2) hacia el exterior a través del material de la válvula cardíaca, siendo los elementos en forma de gancho (2) o los elementos en forma de gancho (2) con garfio de un metal con memoria de forma, estando diseñados para que asienten planos durante la fase de inserción durante la 10 implantación de la prótesis de válvula cardíaca (1) y se levanten al alcanzar o rebasar la temperatura de salto característica del metal con memoria de forma.
  2. 2. Prótesis de válvula cardíaca según la reivindicación 1, en la que los elementos en forma de gancho (2) van cosidos a la prótesis de válvula cardíaca (1). 15
  3. 3. Prótesis de válvula cardíaca según la reivindicación 1 ó 2, en la que hay por lo menos dos elementos en forma de gancho (2) dispuestos sobre un elemento base o puente (3).
  4. 4. Prótesis de válvula cardíaca según la reivindicación 1 ó 2, en la que hay varios elementos base o puentes 20 (3) orientados en la dirección longitudinal de la prótesis de válvula cardíaca.
  5. 5. Prótesis de válvula cardíaca según la reivindicación 1, en la que los elementos en forma de gancho (2) presentan en estado desplegado una altura efectiva mínima de 2 mm, en la que sobresalen de la prótesis de válvula cardíaca, para efectuar el anclaje en la pared de la aorta. 25
  6. 6. Prótesis de válvula cardíaca según la reivindicación 1, en la que los elementos en forma de gancho (2) están realizados en forma de espiga y están dotados de garfios.
  7. 7. Prótesis de válvula cardíaca según la reivindicación 1, en la que los garfios de los elementos en forma de 30 gancho (2) están acodados en distintas direcciones.
  8. 8. Prótesis de válvula cardíaca según la reivindicación 1, en la que los elementos en forma de gancho (2) van sujetos en el interior de la prótesis de válvula cardíaca (1) mediante por lo menos un elemento base.
    35
  9. 9. Prótesis de válvula cardíaca según la reivindicación 3, en la que hay varios elementos base orientados en la dirección longitudinal de la prótesis de válvula cardíaca.
  10. 10. Prótesis de válvula cardíaca según la reivindicación 3, en la que hay varios elementos base realizados con forma espiral. 40
  11. 11. Prótesis de válvula cardíaca según la reivindicación 3, en la que varios elementos base tienen una longitud por lo menos igual a la de las comisuras.
  12. 12. Prótesis de válvula cardíaca según una de las reivindicaciones anteriores, en la que en el interior de la 45 prótesis de válvula cardíaca (1) y en la zona del anillo exterior, va fijado un elemento de forma anular.
  13. 13. Prótesis de válvula cardíaca según la reivindicación 12, en la que el elemento de forma anular es de un material elástico o de un metal con memoria de forma.
ES01916903T 2000-02-28 2001-02-28 Sistema de anclaje para prótesis implantables de válvula cardiaca. Expired - Lifetime ES2353733T3 (es)

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Application Number Priority Date Filing Date Title
DE10010073A DE10010073B4 (de) 2000-02-28 2000-02-28 Verankerung für implantierbare Herzklappenprothesen
DE10010073 2000-02-28

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ES2353733T3 true ES2353733T3 (es) 2011-03-04

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US (2) US20030149476A1 (es)
EP (1) EP1259193B1 (es)
JP (1) JP4246433B2 (es)
AT (1) ATE488199T1 (es)
CY (1) CY1111106T1 (es)
DE (2) DE10010073B4 (es)
DK (1) DK1259193T3 (es)
ES (1) ES2353733T3 (es)
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US8579965B2 (en) 2001-08-03 2013-11-12 Jenavalve Technology, Inc. Methods of implanting an implantation device
US11185405B2 (en) 2013-08-30 2021-11-30 Jenavalve Technology, Inc. Radially collapsible frame for a prosthetic valve and method for manufacturing such a frame
US11357624B2 (en) 2007-04-13 2022-06-14 Jenavalve Technology, Inc. Medical device for treating a heart valve insufficiency
US11589981B2 (en) 2010-05-25 2023-02-28 Jenavalve Technology, Inc. Prosthetic heart valve and transcatheter delivered endoprosthesis comprising a prosthetic heart valve and a stent

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US6006134A (en) * 1998-04-30 1999-12-21 Medtronic, Inc. Method and device for electronically controlling the beating of a heart using venous electrical stimulation of nerve fibers
EP0850607A1 (en) 1996-12-31 1998-07-01 Cordis Corporation Valve prosthesis for implantation in body channels
US20070043435A1 (en) * 1999-11-17 2007-02-22 Jacques Seguin Non-cylindrical prosthetic valve system for transluminal delivery
US8579966B2 (en) 1999-11-17 2013-11-12 Medtronic Corevalve Llc Prosthetic valve for transluminal delivery
US8016877B2 (en) 1999-11-17 2011-09-13 Medtronic Corevalve Llc Prosthetic valve for transluminal delivery
US7018406B2 (en) 1999-11-17 2006-03-28 Corevalve Sa Prosthetic valve for transluminal delivery
US8241274B2 (en) 2000-01-19 2012-08-14 Medtronic, Inc. Method for guiding a medical device
US7749245B2 (en) 2000-01-27 2010-07-06 Medtronic, Inc. Cardiac valve procedure methods and devices
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US8579965B2 (en) 2001-08-03 2013-11-12 Jenavalve Technology, Inc. Methods of implanting an implantation device
US8585756B2 (en) 2001-08-03 2013-11-19 Jenavalve Technology, Inc. Methods of treating valves
US9889002B2 (en) 2001-08-03 2018-02-13 Jenavalve Technology, Inc. Devices useful for implantation at a heart valve
US9949824B2 (en) 2001-08-03 2018-04-24 Jenavalve Technology, Inc. Devices useful for implantation at a heart valve
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US11589981B2 (en) 2010-05-25 2023-02-28 Jenavalve Technology, Inc. Prosthetic heart valve and transcatheter delivered endoprosthesis comprising a prosthetic heart valve and a stent
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EP1259193B1 (de) 2010-11-17
PT1259193E (pt) 2011-01-13
JP2003524504A (ja) 2003-08-19
WO2001064137A1 (de) 2001-09-07
JP4246433B2 (ja) 2009-04-02
ATE488199T1 (de) 2010-12-15
CY1111106T1 (el) 2015-06-11
US7896913B2 (en) 2011-03-01
US20030149476A1 (en) 2003-08-07
DE10010073B4 (de) 2005-12-22
DE50115708D1 (de) 2010-12-30
DK1259193T3 (da) 2011-01-31
US20070005129A1 (en) 2007-01-04
DE10010073A1 (de) 2001-09-27
EP1259193A1 (de) 2002-11-27

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