CA2119358C - Self-curving cochlear electrode array - Google Patents
Self-curving cochlear electrode array Download PDFInfo
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- CA2119358C CA2119358C CA002119358A CA2119358A CA2119358C CA 2119358 C CA2119358 C CA 2119358C CA 002119358 A CA002119358 A CA 002119358A CA 2119358 A CA2119358 A CA 2119358A CA 2119358 C CA2119358 C CA 2119358C
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- Canada
- Prior art keywords
- array
- portions
- longitudinal axis
- volume
- electrodes
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- 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.)
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N1/00—Electrotherapy; Circuits therefor
- A61N1/02—Details
- A61N1/04—Electrodes
- A61N1/05—Electrodes for implantation or insertion into the body, e.g. heart electrode
- A61N1/0526—Head electrodes
- A61N1/0541—Cochlear electrodes
Abstract
An electrode array (12) for cochlear (30) implant is formed by two layers, wherein the first layer (10, 20) is formed from a bio-compatible material and contains electrode contacts and connecting leads and the second layer (11, 21) is formed from a bio-compatible material having a property of a controlled rate of expansion when exposed to the water contained in body fluids. This material expands in use and curves the implanted array and enables more effective stimulation.
Description
WO 93/06698 ~ ~ ~ ~ ~ ~ ~ PCT/AU92/00517 Self-curving Cochlear Electrode Array Technical Field This invention relates to electrode arrays for cochlear implants.
Background Art Electrode arrays for insertion into the cochlea are known in various forms in the prior art . They are generally manufactured in a straight form from a resilient material. When they are inserted into the cochlea, they flexibly curve into the spiral form of the scala tympani. However, the electrode array is resilient and hence tends to 1 0 "remember" its straight form, and accordingly engages the outer (radially) wall of the scala tympani. For optimum electrical stimulation to occur, it is preferred that the electrodes engage the inner wall , near the modiolus.
One solution which has been proposed is to manufacture the electrode in a spiral shape. This type of arrangement is shown in US patent No 4284085 to Hansen et al, and in the device developed by the University of Catifomia at San Francisco. However, these devices are difficult to insert in a surgical procedure, and require specialised equipment and skills to approach satisfactory performance. Moreover, they use a curve for the array which is an estimate of average shape, not the actual shape of each patient's cochlea. These devices also require very careful manufacturing techniques to produce a 2 0 reliable product.
Disclosure of Invention It is accordingly an objective of the present invention to provide an electrode which combines the manufacturing and insertion advantages of the straight form of electrode, while providing engagement in use with the inner wall of the canal.
2 5 The present invention accordingly provides an electrode array which after insertion curves from its original substantially linear form into a curved shape.
Preferably,. the electrode array is constructed from a ,first portion which is flexible but stable which contains the electrodes, and a second portion which is formed from material which wilt expand after insertion so as to curve the overall electrode into a spiral shape.
Background Art Electrode arrays for insertion into the cochlea are known in various forms in the prior art . They are generally manufactured in a straight form from a resilient material. When they are inserted into the cochlea, they flexibly curve into the spiral form of the scala tympani. However, the electrode array is resilient and hence tends to 1 0 "remember" its straight form, and accordingly engages the outer (radially) wall of the scala tympani. For optimum electrical stimulation to occur, it is preferred that the electrodes engage the inner wall , near the modiolus.
One solution which has been proposed is to manufacture the electrode in a spiral shape. This type of arrangement is shown in US patent No 4284085 to Hansen et al, and in the device developed by the University of Catifomia at San Francisco. However, these devices are difficult to insert in a surgical procedure, and require specialised equipment and skills to approach satisfactory performance. Moreover, they use a curve for the array which is an estimate of average shape, not the actual shape of each patient's cochlea. These devices also require very careful manufacturing techniques to produce a 2 0 reliable product.
Disclosure of Invention It is accordingly an objective of the present invention to provide an electrode which combines the manufacturing and insertion advantages of the straight form of electrode, while providing engagement in use with the inner wall of the canal.
2 5 The present invention accordingly provides an electrode array which after insertion curves from its original substantially linear form into a curved shape.
Preferably,. the electrode array is constructed from a ,first portion which is flexible but stable which contains the electrodes, and a second portion which is formed from material which wilt expand after insertion so as to curve the overall electrode into a spiral shape.
3 0 Preferably, this is achieved by utilising a material which expands slowly when in contact with water, so that over a period of hours or days after insertion the electrode slowly curves inwardly so as to engage the inner wall of the canal. Hence, the optimal stimulation arrangement whereby the electrodes engage the inner wall of the canal is likely to be achieved.
3 5 Brief Description of Drawings WO 93/06698 , . ~ ' PCT/AU92/00517 ;"",, One embodiment of the invention will now be described with reference to the accompanying figures, in which:
Figure 1 is a schematic cross-sectional illustration through the plane of the cochlea showing insertion of the electrode ;
Figures 2 and 3 are crosssectional views along line A-A of alternative constructions of the electrode array;
Figure 4 is a similar view to Figure 1 showing the positionat change of the electrode array after curving;
Figure 5 is a lateral section across Figure 4;
Figure 6 shows the preferred mechanical properties required of the electrode array according to the present invention;
Figure 7 is a detailed illustration of one construction of the electrode array according to the present invention;
Figure 8 is a detailed illustration of another construction of the electrode array according to the present invention; and Figure 9 shows one method for electrically connecting the electrodes according to the embodiment of Figure 8.
iDescriptio~ of Preferred Embodiment One embodiment of the invention will now be described, however, it is noted 2 0 that the present invention is of wide scope and that many possible embodiments fall within the general inventive concept.
Referring to Figure 1, the electrode array 12 is initially preferably formed in a generally straight cylindrical or semi-cylindrical shape. The materials are selected such that this shape will generally be maintained outside of the human body at nomnal 2 5 conditions of temperature and humidity. In this form, it is relatwety s~mpie to control the insertion of the electrode into the cochlea 30. It will be appreciated that the illustration of the oochlear is purely schematic and is .not intended to be anatomically accurate. immediately after insertion, the electrode generally rests against the radially outer wall of the scala tympani 31, as can be seen in Figures 4 and 5, at position 1.
a l 3 0 The electrode is preferably constructed in essentially two layers.
Referring to Figures 2 and 3, the first layer (10, 20) is formed from a suitable bio-compatible .
material, such as a silicone polymer, and contains the electrode contacts and connecting leads in the form of a long strip structure. It is preferably constructed from a material which is flexible for bending in at feast one direction, and stable in its dimensions both 3 5 outside and inside the living body. In this fashion, the correct spacings between WO 93/06698 ~ ~ ~ ~ ~ ~,~j ~ PCT/AU92/OOS17 electrodes can be maintained, and the proper electrical functioning predicted accurately in use.
The second layer (11, 21) is formed from a bio-compatible material which is adhered, co-extruded or moulded to the first layer. This material has the important property of a controlled rate of expansion when exposed to the water contained in body fluids.
Any suitable water-expanding material which fulfils the above criteria may be utilised in the invention. A suitable material may be a plymer which swells in response to contact with a fluid such as water. A first preferred material ,is Silastic A
( Trade Mark) silicone polymer mixed with a certain amount of finely ground NaCI. The exact proportion of NaCI depends on the geometry chosen and can be readily determined by those skilled in the art. A second preferred material is Silastic A mixed with polyacrylic acid to form a hygroscopic layer in the electrode structure. Both these materials will slowly expand in contact with water, thereby deforming the electrode structure from its original straight shape to a generally spiral shape with a curvature equal to or smaller than the scala tympani 31.
It will be appreciated that in its broadest form the invention encompasses alteration of shape in situ by any means, including polymers or other materials which alter their volume in response to other stimuli, such as heat or electrical stimuli, or 2 0 materials which merely alter their shape so as to deform the array. It is the post insertion curving which is at the core of the present invention.
Thus, after a suitable period of time, typically hours or days, the electrode array 12 gradually moves ,into substantially position 2 shown in figures 4 and 5. The electrodes are always positioned on their correct side because of the expansion geometry 2 5 involved, so that they are in close proximity to the modiolus. It will be appreciated that the insertion is a surgical procedure and so will not always result in theoretical results, owing to differences in human anatomy, the skill and experience of the surgeon, and other factors.
Figure 7 illustrates one structure incorporating the features of the present 3 0 invention. A first layer 10 is constructed from a mechanically stable and bio-compatible a polymer strip, with metal electrodes 13 deposited on one side and leads 14 on the other side. Any suitable material may be used for the first layer 10, although polyamide foil is preferred. The electrodes 13 and leads 14 may be formed from any suitable material, for instance sputtered platinum.
3 5 The other side of the electrode 11 is formed from a generally semi-WO 93/>~ ~ ~ '~ ~ PGT/AU92/0051~~
3 5 Brief Description of Drawings WO 93/06698 , . ~ ' PCT/AU92/00517 ;"",, One embodiment of the invention will now be described with reference to the accompanying figures, in which:
Figure 1 is a schematic cross-sectional illustration through the plane of the cochlea showing insertion of the electrode ;
Figures 2 and 3 are crosssectional views along line A-A of alternative constructions of the electrode array;
Figure 4 is a similar view to Figure 1 showing the positionat change of the electrode array after curving;
Figure 5 is a lateral section across Figure 4;
Figure 6 shows the preferred mechanical properties required of the electrode array according to the present invention;
Figure 7 is a detailed illustration of one construction of the electrode array according to the present invention;
Figure 8 is a detailed illustration of another construction of the electrode array according to the present invention; and Figure 9 shows one method for electrically connecting the electrodes according to the embodiment of Figure 8.
iDescriptio~ of Preferred Embodiment One embodiment of the invention will now be described, however, it is noted 2 0 that the present invention is of wide scope and that many possible embodiments fall within the general inventive concept.
Referring to Figure 1, the electrode array 12 is initially preferably formed in a generally straight cylindrical or semi-cylindrical shape. The materials are selected such that this shape will generally be maintained outside of the human body at nomnal 2 5 conditions of temperature and humidity. In this form, it is relatwety s~mpie to control the insertion of the electrode into the cochlea 30. It will be appreciated that the illustration of the oochlear is purely schematic and is .not intended to be anatomically accurate. immediately after insertion, the electrode generally rests against the radially outer wall of the scala tympani 31, as can be seen in Figures 4 and 5, at position 1.
a l 3 0 The electrode is preferably constructed in essentially two layers.
Referring to Figures 2 and 3, the first layer (10, 20) is formed from a suitable bio-compatible .
material, such as a silicone polymer, and contains the electrode contacts and connecting leads in the form of a long strip structure. It is preferably constructed from a material which is flexible for bending in at feast one direction, and stable in its dimensions both 3 5 outside and inside the living body. In this fashion, the correct spacings between WO 93/06698 ~ ~ ~ ~ ~ ~,~j ~ PCT/AU92/OOS17 electrodes can be maintained, and the proper electrical functioning predicted accurately in use.
The second layer (11, 21) is formed from a bio-compatible material which is adhered, co-extruded or moulded to the first layer. This material has the important property of a controlled rate of expansion when exposed to the water contained in body fluids.
Any suitable water-expanding material which fulfils the above criteria may be utilised in the invention. A suitable material may be a plymer which swells in response to contact with a fluid such as water. A first preferred material ,is Silastic A
( Trade Mark) silicone polymer mixed with a certain amount of finely ground NaCI. The exact proportion of NaCI depends on the geometry chosen and can be readily determined by those skilled in the art. A second preferred material is Silastic A mixed with polyacrylic acid to form a hygroscopic layer in the electrode structure. Both these materials will slowly expand in contact with water, thereby deforming the electrode structure from its original straight shape to a generally spiral shape with a curvature equal to or smaller than the scala tympani 31.
It will be appreciated that in its broadest form the invention encompasses alteration of shape in situ by any means, including polymers or other materials which alter their volume in response to other stimuli, such as heat or electrical stimuli, or 2 0 materials which merely alter their shape so as to deform the array. It is the post insertion curving which is at the core of the present invention.
Thus, after a suitable period of time, typically hours or days, the electrode array 12 gradually moves ,into substantially position 2 shown in figures 4 and 5. The electrodes are always positioned on their correct side because of the expansion geometry 2 5 involved, so that they are in close proximity to the modiolus. It will be appreciated that the insertion is a surgical procedure and so will not always result in theoretical results, owing to differences in human anatomy, the skill and experience of the surgeon, and other factors.
Figure 7 illustrates one structure incorporating the features of the present 3 0 invention. A first layer 10 is constructed from a mechanically stable and bio-compatible a polymer strip, with metal electrodes 13 deposited on one side and leads 14 on the other side. Any suitable material may be used for the first layer 10, although polyamide foil is preferred. The electrodes 13 and leads 14 may be formed from any suitable material, for instance sputtered platinum.
3 5 The other side of the electrode 11 is formed from a generally semi-WO 93/>~ ~ ~ '~ ~ PGT/AU92/0051~~
cylindrical portion of water absorbing polymer. Preferably, the strip 10 is adhered to the material 11 during the moulding process.
Figure 8 illustrates an alternative embodiment of the inventive structure.
The first layer 20 is formed from a number of wires 23 placed side by side to form a flat ribbon connected to the platinum disk electrodes 22. This complete structure 20 is then moulded into the water absorbing polymer 21. Figure 9 shows the connection of the discs 22 by lead wires 23.
The electrode is preferably formed with mechanical characteristics as shown in Figure 6. The electrode (in its straight form) should be flexible in a direction which is perpendicular to the plane of the electrodes, or in other words in the radial direction in the inserted structure, shown in Figure 6 as direction 0. It should, however, be stable along the plane of the electrodes, and relatively stiff, across the plane of the electrodes, or in other words in directions perpendicular to the radial and coming out of the page in the illustration of Figure 6, shown as directions B and C.
it will be appreciated that suitable polymer selection and the exact volumes of the various portions of the array will enable a suitable degree of curvature to be provided. Other differential expansion or contraction mechanisms using the same or other material properties, or other arrangements of water expanding polymer, for instance in shaped sections, are encompassed within the present invention. The array 2 0 need not be precisely straight when manufactured - it may incorporate a small curve at the end to aid insertion. It will also be appreciated that embodiments are possible which do not have unifomn characteristics at all points in the array.
It will be appreciated that the present invention relates to a principle of general application and the particular embodiments disclosed herein are not to be 2 5 considered as limitative. Variations and additions will be apparent to those skilled in the art and are encompassed within the general scope of the invention.
Figure 8 illustrates an alternative embodiment of the inventive structure.
The first layer 20 is formed from a number of wires 23 placed side by side to form a flat ribbon connected to the platinum disk electrodes 22. This complete structure 20 is then moulded into the water absorbing polymer 21. Figure 9 shows the connection of the discs 22 by lead wires 23.
The electrode is preferably formed with mechanical characteristics as shown in Figure 6. The electrode (in its straight form) should be flexible in a direction which is perpendicular to the plane of the electrodes, or in other words in the radial direction in the inserted structure, shown in Figure 6 as direction 0. It should, however, be stable along the plane of the electrodes, and relatively stiff, across the plane of the electrodes, or in other words in directions perpendicular to the radial and coming out of the page in the illustration of Figure 6, shown as directions B and C.
it will be appreciated that suitable polymer selection and the exact volumes of the various portions of the array will enable a suitable degree of curvature to be provided. Other differential expansion or contraction mechanisms using the same or other material properties, or other arrangements of water expanding polymer, for instance in shaped sections, are encompassed within the present invention. The array 2 0 need not be precisely straight when manufactured - it may incorporate a small curve at the end to aid insertion. It will also be appreciated that embodiments are possible which do not have unifomn characteristics at all points in the array.
It will be appreciated that the present invention relates to a principle of general application and the particular embodiments disclosed herein are not to be 2 5 considered as limitative. Variations and additions will be apparent to those skilled in the art and are encompassed within the general scope of the invention.
Claims (19)
1. An electrode array for a cochlear implant device, said array having a longitudinal axis and comprising a first portion including a plurality of electrodes at predetermined spacings from each other and a second portion which is longitudinally interconnected and at least partly coextensive with said first portion, said first and second portions having respective initial volumes, said second portion being adopted to undergo a change of volume relative to the first portion in a direction along said longitudinal axis, characterised by said first and second portions being disposed relatively to each other so that when the volume of the second portion changes relative to the first portion longitudinally, at least that part of said array which includes the coextensive parts of said first and second portions inherently curves while the spacings between said electrodes borne by said first portion remain substantially constant along said longitudinal axis.
2. An array according to claim 1, wherein said first portion of said array is adapted to retain a substantially constant volume.
3. An array according to claim 1 or 2, wherein said second portion of said array comprises a biocompatible expanding material.
4. An array according to claim 3, wherein said biocompatible expanding material of said second portion is adapted to expand when exposed to water.
5. An array according to claim 1, wherein said second portion is adapted to undergo a change of volume in a relatively slow, controlled manner.
6. An array according to claim 1, wherein prior to implantation of the device into the cochlea said array is adapted to remain substantially stable in volume under normal conditions of temperature and humidity.
7. An array according to claim 1, wherein said first and second portions are arranged longitudinally on both sides of said longitudinal axis.
8. An array according to claim 1, Wherein said array is most flexible in a plane, said plane intersecting the plurality of electrodes when said array is operatively curved
9. A cochlear implant device including an electrode array adapted to be inserted in the cochlear of a patient's ear, said array having a longitudinal axis and comprising a first portion including a plurality of electrodes at predetermined spacings from each other and a second portion which is longitudinally interconnected and at least partly coextensive with said first portion, said first and second portions having respective initial volumes, said second portion being adopted to undergo a change of volume relative to the first portion in a direction along said longitudinal axis, characterised by said first and second portions being disposed relatively to each other so that when the volume of the second portion changes relative to the first portion longitudinally, at least that part of said array which includes the coextensive parts of said first and second portions inherently curves while the spacings between said electrodes borne by said first portion remain substantially constant along said longitudinal axis.
10. A device according to claim 9, wherein said first portion of said array is adapted to retain a substantially constant volume.
11. A device according to claim 9 or 10, wherein said second portion of said array comprises a biocompatible expanding material.
12. A device according to claim 11, wherein said biocompatible expanding material of said second portion is adapted to expand when exposed to water in the patient's ear.
13. A device according to claim 9, wherein prior to implantation of the device into the cochlea, said array is adapted to remain substantially stable in volume under normal conditions of temperature and humidity.
14. A device according to claim 9, wherein said array is most flexible in a plane, said plane intersecting the plurality of electrodes when said array is operatively curved.
15. A device according to claim 9, wherein the interconnection between said first and second portions of said array is such that, upon said second portion undergoing a change in volume, the curvature assumed by said array as a whole is concave towards said first portion.
16. A device according to claim 15, wherein the curvature assumed by said array as a whole, after implantation of the device into the cochlea, is such that said electrodes are disposed adjacent the radially inner wall of the cochlea within the scala tympani thereof.
17. A device according to claim 9, wherein said first and second portions are arranged longitudinally on both sides of said longitudinal axis
18. An electrode array for a cochlear implant device, said array having a longitudinal axis and comprising:
a first portion comprising a strip extending axially along one surface of said electrode array including a plurality of electrodes at predetermined spacings from each other; and a second portion which is longitudinally interconnected and at least partly coextensive with said first portion, said first and second portions having respective initial volumes, said second portion being adopted to undergo a change of volume relative to the first portion in a direction along said longitudinal axis, characterised by said first and second portions being disposed relatively to each other so that when the volume of the second portion changes relative to the first portion longitudinally, at least that part of said array which includes the coextensive parts of said first and second portions inherently curves while the spacings between said electrodes borne by said first portion remain substantially constant along said longitudinal axis.
a first portion comprising a strip extending axially along one surface of said electrode array including a plurality of electrodes at predetermined spacings from each other; and a second portion which is longitudinally interconnected and at least partly coextensive with said first portion, said first and second portions having respective initial volumes, said second portion being adopted to undergo a change of volume relative to the first portion in a direction along said longitudinal axis, characterised by said first and second portions being disposed relatively to each other so that when the volume of the second portion changes relative to the first portion longitudinally, at least that part of said array which includes the coextensive parts of said first and second portions inherently curves while the spacings between said electrodes borne by said first portion remain substantially constant along said longitudinal axis.
19. An electrode array for a cochlear implant device, said array having a longitudinal axis and comprising:
a first portion comprising a ribbon formed from a plurality of wires and including a plurality of electrodes at predetermined spacings from each other, wherein each of said wires is connected to a respective electrode; and a second portion which is longitudinally interconnected and at least partly coextensive with said first portion, said first and second portions having respective initial volumes, said second portion being adopted to undergo a change of volume relative to the first portion in a direction along said longitudinal axis, characterised by said first and second portions being disposed relatively to each other so that when the volume of the second portion changes relative to the first portion longitudinally, at least that part of said array which includes the coextensive parts of said first and second portions inherently curves while the spacings between said electrodes borne by said first portion remain substantially constant along said longitudinal axis.
a first portion comprising a ribbon formed from a plurality of wires and including a plurality of electrodes at predetermined spacings from each other, wherein each of said wires is connected to a respective electrode; and a second portion which is longitudinally interconnected and at least partly coextensive with said first portion, said first and second portions having respective initial volumes, said second portion being adopted to undergo a change of volume relative to the first portion in a direction along said longitudinal axis, characterised by said first and second portions being disposed relatively to each other so that when the volume of the second portion changes relative to the first portion longitudinally, at least that part of said array which includes the coextensive parts of said first and second portions inherently curves while the spacings between said electrodes borne by said first portion remain substantially constant along said longitudinal axis.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AUPK8653 | 1991-09-27 | ||
| AUPK865391 | 1991-09-27 | ||
| PCT/AU1992/000517 WO1993006698A1 (en) | 1991-09-27 | 1992-09-25 | Self-curving cochlear electrode array |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2119358A1 CA2119358A1 (en) | 1993-04-01 |
| CA2119358C true CA2119358C (en) | 2002-12-17 |
Family
ID=3775723
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002119358A Expired - Fee Related CA2119358C (en) | 1991-09-27 | 1992-09-25 | Self-curving cochlear electrode array |
Country Status (8)
| Country | Link |
|---|---|
| US (1) | US5578084A (en) |
| EP (1) | EP0724819B1 (en) |
| JP (1) | JP3522749B2 (en) |
| AT (1) | ATE176568T1 (en) |
| AU (1) | AU675411B2 (en) |
| CA (1) | CA2119358C (en) |
| DE (1) | DE69228397T2 (en) |
| WO (1) | WO1993006698A1 (en) |
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|---|---|---|---|---|
| CN103932842A (en) * | 2014-05-14 | 2014-07-23 | 重庆大学 | Pre-bent type artificial cochlea electrode |
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1992
- 1992-09-25 US US08/211,269 patent/US5578084A/en not_active Expired - Lifetime
- 1992-09-25 CA CA002119358A patent/CA2119358C/en not_active Expired - Fee Related
- 1992-09-25 AT AT92920267T patent/ATE176568T1/en active
- 1992-09-25 EP EP92920267A patent/EP0724819B1/en not_active Expired - Lifetime
- 1992-09-25 WO PCT/AU1992/000517 patent/WO1993006698A1/en active IP Right Grant
- 1992-09-25 JP JP50172193A patent/JP3522749B2/en not_active Expired - Lifetime
- 1992-09-25 AU AU26864/92A patent/AU675411B2/en not_active Ceased
- 1992-09-25 DE DE69228397T patent/DE69228397T2/en not_active Expired - Fee Related
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103932842A (en) * | 2014-05-14 | 2014-07-23 | 重庆大学 | Pre-bent type artificial cochlea electrode |
Also Published As
| Publication number | Publication date |
|---|---|
| US5578084A (en) | 1996-11-26 |
| AU675411B2 (en) | 1997-02-06 |
| EP0724819B1 (en) | 1999-02-03 |
| ATE176568T1 (en) | 1999-02-15 |
| AU2686492A (en) | 1993-04-27 |
| CA2119358A1 (en) | 1993-04-01 |
| DE69228397T2 (en) | 1999-08-26 |
| WO1993006698A1 (en) | 1993-04-01 |
| DE69228397D1 (en) | 1999-03-18 |
| JP3522749B2 (en) | 2004-04-26 |
| JPH07501951A (en) | 1995-03-02 |
| EP0724819A4 (en) | 1994-11-11 |
| EP0724819A1 (en) | 1996-08-07 |
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