U.S. patent application number 11/425546 was filed with the patent office on 2007-12-27 for embolic coils and related components, systems, and methods.
This patent application is currently assigned to BOSTON SCIENTIFIC SCIMED, INC.. Invention is credited to Christopher J. Elliott.
Application Number | 20070299461 11/425546 |
Document ID | / |
Family ID | 38705059 |
Filed Date | 2007-12-27 |
United States Patent
Application |
20070299461 |
Kind Code |
A1 |
Elliott; Christopher J. |
December 27, 2007 |
EMBOLIC COILS AND RELATED COMPONENTS, SYSTEMS, AND METHODS
Abstract
Embolic coils, and related components, systems, and methods, are
disclosed.
Inventors: |
Elliott; Christopher J.;
(Hopkinton, MA) |
Correspondence
Address: |
FISH & RICHARDSON PC
P.O. BOX 1022
MINNEAPOLIS
MN
55440-1022
US
|
Assignee: |
BOSTON SCIENTIFIC SCIMED,
INC.
Maple Grove
MN
|
Family ID: |
38705059 |
Appl. No.: |
11/425546 |
Filed: |
June 21, 2006 |
Current U.S.
Class: |
606/191 |
Current CPC
Class: |
A61B 2017/00004
20130101; A61B 17/1215 20130101; A61B 90/37 20160201; A61B 17/12113
20130101; A61B 17/12131 20130101; A61B 2017/00526 20130101; A61B
2017/12054 20130101; A61B 17/12022 20130101; A61B 2017/00867
20130101; A61B 17/1214 20130101; A61B 17/12145 20130101; A61B 90/39
20160201 |
Class at
Publication: |
606/191 |
International
Class: |
A61M 29/00 20060101
A61M029/00 |
Claims
1. An article, comprising: an embolic coil; and a non-hook-shaped
head attached to the embolic coil.
2. The article of claim 1, wherein the head has a longitudinal
axis, and the head is rotationally symmetric about the longitudinal
axis.
3. The article of claim 1, wherein the head is peanut-shaped.
4. The article of claim 1, wherein the head defines a lumen.
5. The article of claim 1, wherein the head defines a groove.
6. An embolic coil delivery wire having a non-hook-shaped head.
7. The embolic coil delivery wire of claim 6, wherein the head has
a longitudinal axis, and the head is rotationally symmetric about
the longitudinal axis.
8. The embolic coil delivery wire of claim 6, wherein the head is
peanut-shaped.
9. An article, comprising: an embolic coil delivery wire; and at
least two arms extending from the embolic coil delivery wire.
10. The article of claim 9, wherein the at least two arms are
attached to a distal portion of the embolic coil delivery wire.
11. The article of claim 9, wherein the at least two arms are
adapted to flex.
12. The article of claim 9, wherein the embolic coil delivery wire
and the at least two arms are formed of a same material.
13. An article, comprising: an embolic coil; and at least two arms
extending from the embolic coil.
14. The article of claim 13, wherein the at least two arms are
adapted to flex.
15. An article, comprising: a first coiled wire; and a second
coiled wire that is co-wound with the first coiled wire, wherein
the article is an embolic coil.
16. The article of claim 15, wherein the article has a first end
and a second end, and the first end of the article comprises a
first arm formed from the first coiled wire and a second arm formed
from the second coiled wire.
17. An embolic coil system, comprising: a catheter defining a
lumen; and a first article disposed in the lumen of the catheter,
the first article comprising: an embolic coil, and a
non-hook-shaped head attached to the embolic coil.
18. The embolic coil system of claim 17, wherein the embolic coil
system further comprises a second article comprising an embolic
coil delivery wire that is detachably engaged with the
non-hook-shaped head.
19. The embolic coil system of claim 18, wherein the second article
further comprises at least two arms extending from the embolic coil
delivery wire, and at least one of the at least two arms is
detachably engaged with the head of the embolic coil.
20. An embolic coil system, comprising: a catheter defining a
lumen; and an embolic coil delivery wire disposed in the lumen of
the catheter, wherein the embolic coil delivery wire has a
non-hook-shaped head.
21. The embolic coil system of claim 20, wherein the embolic coil
system further comprises an article comprising an embolic coil, and
the article is detachably engaged with the head of the embolic coil
delivery wire.
22. The embolic coil system of claim 21, wherein the article
further comprises at least two arms extending from the embolic
coil, and at least one of the at least two arms is detachably
engaged with the head of the embolic coil delivery wire.
23. An embolic coil system, comprising: a catheter defining a
lumen; an embolic coil delivery wire disposed in the lumen of the
catheter, the embolic coil delivery wire having an end; and at
least two arms extending from the end of the embolic coil delivery
wire.
24. The embolic coil system of claim 23, further comprising an
embolic coil, wherein the at least two arms are detachably engaged
with the embolic coil.
25. The embolic coil system of claim 23, wherein the at least two
arms are adapted to flex.
26. The embolic coil system of claim 23, wherein the at least two
arms form an interference fit within the lumen of the catheter.
27. An embolic coil system, comprising: a catheter defining a
lumen; and an article disposed in the lumen of the catheter,
wherein the article comprises: an embolic coil, and at least two
arms extending from the embolic coil.
28. An article, comprising: an embolic coil delivery wire; and a
tubular mesh member attached to the embolic coil delivery wire.
29. The article of claim 28, further comprising an embolic coil,
wherein the tubular mesh member defines a lumen and the embolic
coil is at least partially disposed in the lumen.
30. The article of claim 29, wherein the embolic coil has a
non-hook-shaped head that is disposed in the lumen.
Description
TECHNICAL FIELD
[0001] The invention relates to embolic coils, and related
components, systems, and methods.
BACKGROUND
[0002] Therapeutic vascular occlusions (embolizations) are used to
prevent or treat pathological conditions in situ. Embolic coils can
be used to occlude vessels in a variety of medical applications.
Delivery of embolic coils (e.g., through a catheter) can depend on
the size and/or shape of the coils. Some embolic coils include
fibers that can, for example, enhance thrombosis at a treatment
site.
SUMMARY
[0003] In one aspect, the invention features an article that
includes an embolic coil and a non-hook-shaped head attached to the
embolic coil.
[0004] In another aspect, the invention features an embolic coil
delivery wire having a non-hook-shaped head.
[0005] In an additional aspect, the invention features an article
that includes an embolic coil delivery wire and at least two arms
extending from the embolic coil delivery wire.
[0006] In a further aspect, the invention features an article that
includes an embolic coil and at least two arms extending from the
embolic coil.
[0007] In another aspect, the invention features an article that
includes a first coiled wire and a second coiled wire that is
co-wound with the first coiled wire. The article is an embolic
coil.
[0008] In an additional aspect, the invention features an embolic
coil system that includes a catheter having a lumen and an article
disposed in the lumen of the catheter. The article includes an
embolic coil and a non-hook-shaped head attached to the embolic
coil.
[0009] In a further aspect, the invention features an embolic coil
system that includes a catheter having a lumen and an embolic coil
delivery wire disposed in the lumen of the catheter. The embolic
coil delivery wire has a non-hook-shaped head.
[0010] In another aspect, the invention features an embolic coil
system that includes a catheter having a lumen, an embolic coil
delivery wire disposed in the lumen of the catheter, and at least
two arms extending from an end of the embolic coil delivery
wire.
[0011] In an additional aspect, the invention features an embolic
coil system that includes a catheter having a lumen and an article
disposed in the lumen of the catheter. The article includes an
embolic coil and at least two arms extending from the embolic
coil.
[0012] In a further aspect, the invention features an article that
includes an embolic coil delivery wire and a tubular mesh member
attached to the embolic coil delivery wire.
[0013] In another aspect, the invention features a method that
includes delivering an embolic coil system into a body of a
subject. The embolic coil system includes a catheter having a lumen
and an article disposed in the lumen of the catheter. The article
includes an embolic coil and a non-hook-shaped head attached to the
embolic coil.
[0014] In an additional aspect, the invention features a method
that includes delivering an embolic coil system into a body of a
subject. The embolic coil system includes a catheter having a lumen
and an embolic coil delivery wire disposed in the lumen of the
catheter. The embolic coil delivery wire has a non-hook-shaped
head.
[0015] In a further aspect, the invention features a method that
includes delivering an embolic coil system into a body of a
subject. The embolic coil system includes a catheter having a
lumen, an embolic coil delivery wire disposed in the lumen of the
catheter, and at least two arms extending from an end of the
embolic coil delivery wire.
[0016] In another aspect, the invention features a method that
includes delivering an embolic coil system into a body of a
subject. The embolic coil system includes a catheter having a lumen
and an article disposed in the lumen of the catheter. The article
includes an embolic coil and at least two arms extending from the
embolic coil.
[0017] In an additional aspect, the invention features a method
that includes delivering an embolic coil system into a body of a
subject. The embolic coil system includes an embolic coil delivery
wire, at least two arms extending from the embolic coil delivery
wire, and an embolic coil that is detachably engaged with the arms.
The method also includes detaching the embolic coil from the arms
of the embolic coil system.
[0018] In a further aspect, the invention features a method that
includes delivering an embolic coil system into a body of a
subject. The embolic coil system includes an embolic coil delivery
wire having a non-hook-shaped head, and an embolic coil that is
detachably engaged with the non-hook-shaped head. The method also
includes detaching the embolic coil from the non-hook-shaped
head.
[0019] In another aspect, the invention features a method that
includes delivering an embolic coil system into a body of a
subject. The embolic coil system includes a catheter including a
sheath having a lumen, an embolic coil delivery wire disposed in
the lumen of the sheath, a tubular mesh member attached to the
embolic coil delivery wire, and an embolic coil that is at least
partially disposed in a lumen of the tubular mesh member. The
method also includes retracting the sheath so that the sheath
releases the embolic coil.
[0020] Embodiments can also include one or more of the
following.
[0021] The head can have a longitudinal axis, and can be
rotationally symmetric about the longitudinal axis. In some
embodiments, the head can be peanut-shaped. The head can have a
lumen and/or a groove. The embolic coil delivery wire can include a
body, and the head can be attached to the body or can be integrally
formed with the body.
[0022] The arms can be attached to a distal portion of the embolic
coil delivery wire. The arms can be adapted to flex. The arms can
form an interference fit within the lumen of the catheter. The arms
can be formed of the same material as the embolic coil delivery
wire. The article can have an end that includes an arm formed from
the first coiled wire and an arm formed from the second coiled
wire.
[0023] The embolic coil system can include an article including an
embolic coil delivery wire that is detachably engaged with the
non-hook-shaped head. The article can also include at least two
arms extending from the embolic coil delivery wire. At least one of
the arms can be detachably engaged with the head of the embolic
coil.
[0024] The embolic coil system can include an article including an
embolic coil, and the article can be detachably engaged with the
head of the embolic coil delivery wire. The article can also
include at least two arms extending from the embolic coil. At least
one of the arms can be detachably engaged with the head of the
embolic coil delivery wire.
[0025] The embolic coil system can include an embolic coil, and the
arms can be detachably engaged with the embolic coil.
[0026] The article can include an embolic coil. The tubular mesh
member can have a lumen, and the embolic coil can be at least
partially disposed in the lumen of the tubular mesh member. In
certain embodiments, the embolic coil can have a non-hook-shaped
head that is disposed in the lumen of the tubular mesh member.
[0027] Embodiments can include one or more of the following
advantages.
[0028] In some embodiments, an embolic coil or an embolic coil
delivery wire can be adapted for use in delivery devices of
different sizes. For example, in certain embodiments, an embolic
coil delivery wire with multiple arms extending from it can be
adapted for use in microcatheters having different inner diameters.
In some embodiments, the arms can flex to allow the embolic coil
delivery wire or the embolic coil to fit within a lumen of a
delivery device (e.g., a catheter).
[0029] In certain embodiments, an embolic coil delivery wire with
multiple arms extending from it can have enhanced rotational and/or
axial flexibility relative to an embolic coil delivery wire that
does not have multiple arms extending from it. This enhanced
rotational and/or axial flexibility can, for example, allow the
embolic coil delivery wire to relatively easily and/or precisely
deliver an embolic coil to a target site. In some embodiments, the
embolic coil delivery wire can be used to manipulate an embolic
coil into a desired position (e.g., by rotating the arms) prior to
releasing the embolic coil into a target site.
[0030] In certain embodiments, an embolic coil having a
non-hook-shaped head can be relatively easy to maneuver and/or to
deliver to a target site. As an example, the embolic coil can be
detachably engaged with an embolic coil delivery wire (e.g., an
embolic coil delivery wire with multiple arms extending from it),
which can be used to precisely place the embolic coil at a target
site. In some embodiments, after the embolic coil is delivered to a
first site, the embolic coil delivery wire can be used to withdraw
the embolic coil from the site and to re-position the embolic coil
at a second site. The maneuverability of the embolic coil can, for
example, allow the embolic coil to be relatively easily packed into
a target site.
[0031] In certain embodiments, an embolic coil system including a
catheter and an embolic coil delivery wire having arms that are
engaged with a head of an embolic coil can be used to deliver the
embolic coil to a target site relatively easily and/or efficiently.
As an example, in some embodiments, the embolic coil system can
experience relatively little friction between the embolic coil and
the walls of the catheter during delivery of the embolic coil to a
target site. As another example, in certain embodiments, the
embolic coil system can be used to deliver the embolic coil to a
target site without resulting in significant deformation of the
shape of the embolic coil. As an additional example, in some
embodiments, the embolic coil can assume its secondary shape
relatively easily as the embolic coil is being delivered from the
catheter.
[0032] In some embodiments, an embolic coil having a
non-hook-shaped head can be sufficiently radiopaque to be viewed
(e.g., by a physician and/or a technician), for example, using
X-ray fluoroscopy without using a radiopaque contrast agent. Such
an embolic coil may be viewed using a non-invasive technique,
and/or may be monitored to determine the progress of a procedure.
In certain embodiments, such an embolic coil can be monitored to
determine whether the embolic coil is migrating to a site that is
not targeted for treatment.
[0033] Features and advantages are in the description, drawings,
and claims.
DESCRIPTION OF DRAWINGS
[0034] FIG. 1 is a side view in partial cross-section of an
embodiment of an embolic coil system.
[0035] FIGS. 2A and 2B illustrate the delivery of an embodiment of
an embolic coil to the site of an aneurysm.
[0036] FIG. 3A is a side view of an embodiment of an embolic coil
delivery wire.
[0037] FIG. 3B is a cross-sectional view of the embolic coil
delivery wire of FIG. 3A, taken along line 3B-3B.
[0038] FIG. 4 is a side view of an embodiment of an embolic coil
delivery wire.
[0039] FIG. 5A is a side view of an embodiment of an embolic
coil.
[0040] FIG. 5B is a cross-sectional view of the embolic coil of
FIG. 5A, taken along line 5B-5B.
[0041] FIG. 6 is a perspective view of an embodiment of an embolic
coil.
[0042] FIG. 7 is a perspective view of an embodiment of an embolic
coil.
[0043] FIG. 8 is a perspective view of an embodiment of an embolic
coil.
[0044] FIG. 9 is a perspective view of an embodiment of an embolic
coil.
[0045] FIG. 10A is a front view of an embodiment of an embolic
coil.
[0046] FIG. 10B is a side view of the embolic coil of FIG. 10A.
[0047] FIG. 11A is a front view of an embodiment of an embolic
coil.
[0048] FIG. 11B is a side view of the embolic coil of FIG. 11A.
[0049] FIG. 12 is a side view of an embodiment of an embolic
coil.
[0050] FIG. 13 is a side view of an embodiment of a process for
forming an embolic coil.
[0051] FIG. 14A is a side view of an embodiment of a mandrel.
[0052] FIGS. 14B and 14C are illustrations of an embodiment of a
process for forming an embolic coil using the mandrel of FIG.
14A.
[0053] FIG. 15A is a side view in partial cross-section of an
embodiment of an embolic coil system.
[0054] FIG. 15B is a side view of an embolic coil delivery wire of
the embolic coil system of FIG. 15A.
[0055] FIG. 15C is a cross-sectional view of the embolic coil
delivery wire of FIG. 15B, taken along line 15C-15C.
[0056] FIG. 15D is a side view of an embolic coil from the embolic
coil system of FIG. 15A.
[0057] FIG. 15E is a cross-sectional view of the embolic coil of
FIG. 15D, taken along line 15E-15E.
[0058] FIG. 16 is a side view of an embodiment of an embolic coil
system.
[0059] FIG. 17 is a side view in partial cross-section of an
embodiment of an embolic coil system.
[0060] FIGS. 18A-18C illustrate the delivery of an embodiment of an
embolic coil from an embodiment of an embolic coil system.
[0061] FIG. 19 is a side view of an embodiment of an embolic
coil.
[0062] FIG. 20 is a side view in partial cross-section of an
embodiment of an embolic coil system.
[0063] FIG. 21 is a side view of an embodiment of an embolic coil
system.
[0064] FIG. 22 illustrates the delivery of an embodiment of an
embolic coil from an introducer sheath into a delivery device.
DETAILED DESCRIPTION
[0065] FIG. 1 shows an embolic coil system 10, which includes a
catheter 12 with a lumen 14. An embolic coil delivery wire 16 and
an embolic coil 18 that is detachably engaged with embolic coil
delivery wire 16 are both disposed within lumen 14. Embolic coil 18
includes an embolic coil body 20 that is formed out of windings
(e.g., windings 22, 23, 24, and 26) of a wire 28. Embolic coil body
20 has a proximal end 30 and a distal end 32. Embolic coil 18 also
includes a non-hook-shaped head (as shown, a peanut-shaped head 34)
that is attached to proximal end 30 of embolic coil body 20. Two
arms 36 and 38 extend from the distal end 40 of embolic coil
delivery wire 16. Arms 36 and 38, which are detachably engaged with
head 34 of embolic coil 18, form an interference fit within lumen
14 of catheter 12. In some embodiments, when embolic coil delivery
wire 16 and embolic coil 18 are disposed within lumen 14 of
catheter 12, a fluid (e.g., a saline solution, a contrast agent, a
heparin solution) can also be disposed within lumen 14.
[0066] Arms 36 and 38 are capable of flexing, such that they can
fit within the lumens of catheters having a range of different
inner diameters. As shown in FIG. 1, catheter 12 has an inner
diameter ID1 and an outer diameter OD1. In some embodiments, inner
diameter ID1 can be at least 0.018 inch (e.g., at least 0.021 inch,
at least 0.027 inch, at least 0.03 inch) and/or at most 0.035 inch
(e.g., at most 0.03 inch, at most 0.027 inch, at most 0.021 inch).
As an example, in certain embodiments, inner diameter ID1 can be
0.021 inch. An example of a catheter having an inner diameter of
0.021 inch is the Renegade.RTM. 18 Microcatheter (from Boston
Scientific Corp.). As another example, in some embodiments, inner
diameter ID1 can be 0.027 inch. An example of a catheter having an
inner diameter of 0.027 inch is the Renegade.RTM. Hi-Flo.TM.
Microcatheter (from Boston Scientific Corp.). In certain
embodiments, outer diameter OD1 can be at least about 0.024 inch
and/or at most about 0.05 inch.
[0067] FIGS. 2A and 2B show the use of embolic coil 18 to fill and
occlude an aneurysmal sac 52 formed in a wall 54 of a lumen 50 of a
subject. As shown in FIG. 2A, embolic coil system 10 is delivered
into lumen 50 of the subject. As shown in FIG. 2B, embolic coil
delivery wire 16 and arms 36 and 38 are used to push embolic coil
18 out of catheter 12. When arms 36 and 38 are released from
catheter 12, they open up, thereby releasing embolic coil 18 into
aneurysmal sac 52. Embolic coil 18 partially fills aneurysmal sac
52 after embolic coil 18 has been pushed out of catheter 12 by
embolic coil delivery wire 16 and arms 36 and 38. By partially
filling aneurysmal sac 52, embolic coil 18 helps to occlude
aneurysmal sac 52. In some embodiments, after embolic coil 18 has
been delivered into aneurysmal sac 52, one or more additional
embolic coils can be delivered into aneurysmal sac 52.
[0068] Embolic coils can generally be used in a number of different
applications, such as neurological applications and/or peripheral
applications. In some embodiments, embolic coils can be used to
embolize a lumen of a subject (e.g., to occlude a vessel), and/or
to treat an aneurysm (e.g., an intercranial aneurysm), an
arteriovenous malformation (AVM), a traumatic fistula, uterine
fibroids, and/or cancer (e.g., cervical cancer). In certain
embodiments, embolic coils can be used in an AAA (abdominal aortic
aneurysm) application. In some embodiments, embolic coils can be
used to embolize a tumor (e.g., a liver tumor), and/or can be used
in transarterial chemoembolization (TACE). In certain embodiments,
embolic coils can be used to occlude a lumbar artery and/or to
embolize a spleen (e.g., after a portion of the spleen has
ruptured). In some embodiments, embolic coils can be used in a
portal vein embolization (PVE) procedure.
[0069] FIGS. 3A and 3B provide enlarged views of embolic coil
delivery wire 16 and arms 36 and 38. As shown in FIG. 3B, embolic
coil delivery wire 16 includes a wire portion 70 and a sheath 72
surrounding wire portion 70. Wire portion 70 is attached to arms 36
and 38 at the distal end 40 of embolic coil delivery wire 16. In
certain embodiments, wire portion 70 can be soldered (e.g., gold
soldered) to arm 36 and/or arm 38. In some embodiments, wire
portion 70 can be resistance welded to arm 36 and/or arm 38.
[0070] Wire portion 70 and arms 36 and/or 38 can be formed of the
same material or different materials, such as metals (e.g.,
platinum) and/or metal alloys (e.g., stainless steel). In some
embodiments, wire portion 70 and arms 36 and/or 38 can be formed of
an iridium-platinum alloy (e.g., 10 percent iridium/90 percent
platinum).
[0071] In certain embodiments, sheath 72 can be formed of
tetrafluoroethylene (TFE). This can, for example, cause sheath 72
to be relatively lubricious. In some embodiments, as the lubricity
of sheath 72 increases, the maneuverability of embolic coil
delivery wire 16 within lumen 14 of catheter 12 can also increase.
Embolic coil delivery wire 16 can be relatively flexible, which can
reduce the likelihood of perforation of a delivery device wall
and/or a body lumen wall.
[0072] While embolic coil delivery wire 16 includes a wire portion
70 surrounded by a sheath 72, in some embodiments, an embolic coil
delivery wire may not include a sheath. Additionally, while embolic
coil delivery wire 16 includes arms 36 and 38 that are attached to
wire portion 70 at distal end 40 of embolic coil delivery wire 16,
in certain embodiments, one or more arms can be attached to an
embolic coil delivery wire in a different location. As an example,
FIG. 4 shows an embolic coil delivery wire 82 including a wire
portion 83 having a distal end 84, and two arms 86 and 88 extending
from wire portion 83 at a location that is proximal to distal end
84. Arms 86 and 88 are directly bonded to wire portion 83. Embolic
coil delivery wire 82 does not include a sheath.
[0073] FIGS. 5A and 5B show enlarged views of embolic coil 18. As
shown in FIGS. 5A and 5B, peanut-shaped head 34 is rotationally
symmetric about a longitudinal axis LA1 of head 34. As shown in
FIG. 5B, head 34 includes an attachment region 90 to which embolic
coil body 20 is attached (e.g., welded). Head 34 and embolic coil
body 20 can be formed of the same material or of different
materials, such as metals, metal alloys, and/or polymers. In
certain embodiments in which head 34 and embolic coil body 20 are
formed of the same metals and/or metal alloys, head 34 and embolic
coil body 20 can be relatively corrosion-resistant.
[0074] Examples of metals include platinum, tungsten, tantalum,
palladium, lead, gold, titanium, and silver. Examples of metal
alloys include stainless steel, alloys of tungsten, alloys of
tantalum, alloys of platinum (e.g., platinum-tungsten alloys such
as 92 percent platinum/eight percent tungsten, platinum-iridium
alloys such as 92 percent platinum/eight percent iridium), alloys
of palladium, alloys of lead, alloys of gold, alloys of titanium,
alloys of silver, and cobalt-chromium alloys (e.g., Elgiloy.RTM.
alloy, from Elgiloy Specialty Materials). Examples of polymers
include polyolefins, polyurethanes, block copolymers, polyethers,
and polyimides. Other examples of polymers are disclosed, for
example, in Buiser et al., U.S. patent application Ser. No.
11/311,617, filed on Dec. 19, 2005, and entitled "Coils", which is
incorporated herein by reference.
[0075] In some embodiments, it may be desirable to observe embolic
coil 18 using X-ray fluoroscopy. In some such embodiments, head 34
and/or embolic coil body 20 can include one or more radiopaque
materials that can enhance the visibility of head 34 and/or embolic
coil body 20 under X-ray fluoroscopy. As an example, embolic coil
body 20 may be formed of a radiopaque material. As another example,
peanut-shaped head 34 may be formed of a material (e.g., a metal, a
polymer) that encapsulates a radiopaque material, and/or may be
formed of a material (e.g., a metal, a polymer) within which a
radiopaque material is disposed. As an additional example,
peanut-shaped head 34 may include a coating of a radiopaque
material.
[0076] As used herein, a radiopaque material refers to a material
having a density of about ten grams per cubic centimeter or greater
(e.g., about 25 grams per cubic centimeter or greater, about 50
grams per cubic centimeter or greater). A radiopaque material can
be, for example, a metal, a metal alloy, a metal oxide (e.g.,
titanium dioxide, zirconium oxide, aluminum oxide), bismuth
subcarbonate, or barium sulfate. In some embodiments, a radiopaque
material is a radiopaque contrast agent. Examples of radiopaque
contrast agents include Omnipaque.TM., Renocal.RTM., iodiamide
meglumine, diatrizoate meglumine, ipodate calcium, ipodate sodium,
iodamide sodium, iothalamate sodium, iopamidol, and metrizamide.
Radiopaque contrast agents are commercially available from, for
example, Bracco Diagnostic. Radiopaque materials are described, for
example, in Rioux et al., U.S. Patent Application Publication No.
US 2004/0101564 A1, published on May 27, 2004, and entitled
"Embolization", which is incorporated herein by reference.
[0077] In some embodiments, head 34 and/or embolic coil body 20 can
be formed out of one or more shape-memory materials, such as
shape-memory metal alloys and/or shape-memory polymers. An example
of a shape-memory metal alloy is Nitinol. Examples of shape-memory
polymers include shape-memory polyurethanes and the Veriflex.TM.
two-part thermoset shape-memory polymer resin system (from CRG
Industries, Dayton, Ohio).
[0078] In certain embodiments, head 34 and/or embolic coil body 20
can be formed of one or more bioerodible materials. Examples of
bioerodible materials include polylactic acid (PLA), polyglycolic
acid (PGA), polysaccharides (e.g., alginate), water soluble
polymers (e.g., polyvinyl alcohol, such as polyvinyl alcohol that
has not been cross-linked), biodegradable poly DL-lactide-poly
ethylene glycol (PELA), hydrogels (e.g., polyacrylic acid,
hyaluronic acid, gelatin such as gelatin foam, carboxymethyl
cellulose), polyethylene glycol (PEG), chitosan, polyesters (e.g.,
polycaprolactones), poly(lactic-co-glycolic) acid (e.g., a
poly(d-lactic-co-glycolic) acid), polyamino acids, polynucleic
acids, polyhydroxyalkanoates, polyanhydrides, and combinations
thereof.
[0079] As shown in FIGS. 5A and 5B, embolic coil 18 in its primary
shape has a length L1. In some embodiments, length L1 can be at
least about two millimeters (e.g., at least about 10 millimeters,
at least about 50 millimeters, at least about 100 millimeters, at
least about 250 millimeters) and/or at most about 500 millimeters
(e.g., at most about 250 millimeters, at most about 100
millimeters, at most about 50 millimeters, at most about 10
millimeters).
[0080] As shown in FIG. 5B, embolic coil body 20 has an inner
diameter ID2 and an outer diameter OD2. In some embodiments, inner
diameter ID2 can be at least 0.006 inch (e.g., at least 0.01 inch,
at least 0.02 inch) and/or at most 0.028 inch (e.g., at most 0.02
inch, at most 0.01 inch). In certain embodiments, outer diameter
OD1 can be at least 0.01 inch (e.g., at least 0.02 inch, at least
0.03 inch) and/or at most 0.038 inch (e.g., at most 0.03 inch, at
most 0.02 inch).
[0081] The pitch of an embolic coil body is the sum of the
thickness of one winding of wire (e.g., winding 22 of wire 28) and
the amount of space between that winding and a consecutive winding
of wire (e.g., winding 23 of wire 28). FIG. 5A shows the pitch P1
of embolic coil body 20. Because the windings of embolic coil body
20 are flush with each other, pitch P1 of embolic coil body 20 is
equal to the thickness of one winding of embolic coil body 20. In
some embodiments, pitch P1 can be at most 0.004 inch and/or at
least 0.002 inch.
[0082] In general, embolic coil 18 has a primary shape and a
secondary shape. Embolic coil 18 exhibits only its primary shape
when embolic coil 18 is extended within lumen 14 of catheter 12 (as
shown in FIG. 1). As embolic coil 18 exits catheter 12, however,
embolic coil 18 further assumes its secondary shape, which can, for
example, allow embolic coil 18 to fill a target site (e.g., an
aneurysmal sac). Typically, the primary shape of embolic coil 18
can be selected for deliverability, and the secondary shape of
embolic coil 18 can be selected for application (e.g., embolization
of an aneurysm).
[0083] As FIGS. 6-12 illustrate, an embolic coil can have any of a
number of different secondary shapes, which can depend on the
particular application for the embolic coil.
[0084] For example, FIG. 6 shows an embolic coil 100 with a spiral
secondary shape, which can be used, for example, to provide a
supportive framework along a vessel wall. Alternatively or
additionally, an embolic coil with a spiral secondary shape can be
used to hold other embolic coils that are subsequently delivered to
the target site.
[0085] FIG. 7 shows an embolic coil 110 with a single apex vortex
secondary shape, which can be used, for example, to close the
center of a target site (e.g., a vessel, an aneurysm) that is to be
occluded, and/or to occlude a target site in conjunction with an
embolic coil such as embolic coil 100 (FIG. 6). An embolic coil
with a single apex vortex secondary shape can be used to occlude a
vessel having low flow, intermediate flow, or high flow. In some
embodiments, multiple embolic coils with single apex vortex
secondary shapes can be used to occlude a vessel. In certain
embodiments, an embolic coil with a single apex vortex secondary
shape can be used as a packing coil, such that the coil can be
packed into a vessel that is slightly smaller than the diameter of
the coil. As an example, a six-millimeter diameter coil can be
packed into a vessel having a five-millimeter diameter. In some
embodiments, an embolic coil with a single apex vortex secondary
shape can be used to embolize a tumor and/or to treat
gastrointestinal bleeding.
[0086] As shown in FIG. 8, an embolic coil 120 can have a dual apex
vortex secondary shape (also known as a diamond secondary shape),
which, like the single apex vortex secondary shape, can used, for
example, to close the center of a target site (e.g., a vessel, an
aneurysm) that is to be occluded, and/or to occlude a target site
in conjunction with an embolic coil such as embolic coil 100 (FIG.
6). An embolic coil with a dual apex vortex secondary shape can be
used to occlude a vessel having low flow, intermediate flow, or
high flow, and can be used alone or in combination with other
embolic coils (e.g., other embolic coils having dual apex vortex
secondary shapes). In certain embodiments, an embolic coil with a
dual apex vortex secondary shape can be used as a packing coil. In
some embodiments, an embolic coil with a dual apex vortex secondary
shape can be used to embolize a tumor and/or to treat
gastrointestinal bleeding.
[0087] FIG. 9 shows an embolic coil 130 with a secondary shape in
the form of a J, which can be used, for example, to fill remaining
space in an aneurysm that was not filled by other coils. In some
embodiments, an operator (e.g., a physician) can hook the curved
portion of embolic coil 130 into a coil or coil mass that has
already been deployed at a target site, and then shape the
straighter portion of coil 130 to fill the target site.
[0088] FIGS. 10A and 10B show an embolic coil 140 having a complex
helical secondary shape. An embolic coil with a complex helical
secondary shape can be used, for example, to frame a target site.
In certain embodiments, an embolic coil with a complex helical
secondary shape can be used as an anchoring coil that helps to hold
other embolic coils in place at a target site (e.g., thereby
allowing additional embolic coils to be packed into the target
site).
[0089] FIGS. 11A and 11B show an embolic coil 150 having a helical
secondary shape. An embolic coil with a helical secondary shape can
be used, for example, as a packing coil.
[0090] FIG. 12 shows an embolic coil 160 having a straight
secondary shape. An embolic coil with a straight secondary shape
can be used, for example, in a relatively small vessel (e.g., to
block blood flow to a tumor).
[0091] FIG. 13 illustrates a process for forming an embolic coil
(e.g., embolic coil 18) in its primary shape, and FIGS. 14A-14C
show a process for forming the secondary shape of the embolic
coil.
[0092] As shown in FIG. 13, a coil-forming apparatus 200 includes a
mandrel 210 held by two rotatable chucks 220 and 230. A spool 240
of wire 28 is disposed above mandrel 210, and is attached to a
linear drive 260. To form an embolic coil in its primary shape,
chucks 220 and 230 are activated so that they rotate in the
direction of arrows A2 and A3, thereby rotating mandrel 210. Linear
drive 260 also is activated, and moves spool 240 in the direction
of arrow A1. The rotation of mandrel 210 pulls wire 28 from spool
240 at a predetermined pull-off angle, and causes wire 28 to wrap
around mandrel 210, forming a coil 270.
[0093] As FIG. 13 shows, the pull-off angle (a) is the angle
between axis PA1, which is perpendicular to longitudinal axis LA2
of mandrel 210, and the portion 280 of wire 28 between spool 240
and coil 270. In some embodiments, a can be from about one degree
to about six degrees (e.g., from about 1.5 degrees to about five
degrees, from about 1.5 degrees to about 2.5 degrees, about two
degrees). In certain embodiments, a controller (e.g., a
programmable logic controller) can be used to maintain the pull-off
angle in coil-forming apparatus 200. Because mandrel 210 is
rotating as it is pulling wire 28 from spool 240, and because
linear drive 260 is moving spool 240 in the direction of arrow A1,
wire 28 forms coil 270 in a primary shape around mandrel 210. Coil
270 can be formed, for example, at room temperature (25.degree.
C.).
[0094] After coil 270 has been formed, chucks 220 and 230, and
linear drive 260, are deactivated, and portion 280 of wire 28 is
cut. Mandrel 210 is then released from chuck 220, and coil 270 is
pulled off of mandrel 210. While coil 270 might lose some of its
primary shape as it is pulled off of mandrel 210, coil 270 can
generally return to its primary shape shortly thereafter, because
of memory imparted to coil 270 during formation. In some
embodiments, after coil 270 has been removed from mandrel 210, one
or both of the ends of coil 270 can be heated and melted to form
rounder, more biocompatible (e.g., atraumatic) ends.
[0095] Mandrel 210 can be formed of, for example, a metal or a
metal alloy, such as stainless steel. In some embodiments, mandrel
210 can be formed of one or more polymers, such as Teflon.RTM.
(polytetrafluoroethylene) or Delrin.RTM. (polyoxymethylene). In
certain embodiments, mandrel 210 can be formed of a shape-memory
material, such as Nitinol.
[0096] The tension of mandrel 210 as it is held between chucks 220
and 230 preferably is sufficiently high to avoid vibration of
mandrel 210 during the winding process, and sufficiently low to
avoid stretching of mandrel 210 during the winding process. In some
instances, significant stretching of mandrel 210 during the winding
process could cause coil 270 to have a smaller primary shape than
desired, and/or could make it relatively difficult to remove coil
270 from mandrel 210. In certain embodiments, the tension of
mandrel 210 can be from about 100 grams to about 1,000 grams (e.g.,
from about 300 grams to about 600 grams, from about 400 grams to
about 500 grams). For example, the tension of mandrel 210 can be
about 506 grams.
[0097] In some embodiments, wire 28 can be wound around mandrel 210
at a tension of at least about four grams (e.g., at least about
five grams, at least about six grams, at least about 10 grams, at
least about 22 grams, at least about 27 grams, at least about 32
grams, at least about 40 grams, at least about 60 grams, at least
about 65 grams, at least about 85 grams) and/or at most about 100
grams (e.g., at most about 85 grams, at most about 65 grams, at
most about 60 grams, at most about 40 grams, at most about 32
grams, at most about 27 grams, at most about 22 grams, at most
about 10 grams, at most about six grams, at most about five
grams).
[0098] In certain embodiments, the length of coil 270 in its
primary shape and while under tension on mandrel 210 can be from
about 10 centimeters to about 250 centimeters (e.g., from about 50
centimeters to about 200 centimeters, from about 130 centimeters to
about 170 centimeters, from about 144 centimeters to about 153
centimeters, from about 147 centimeters to about 153 centimeters).
For example, the length of coil 270 in its primary shape and while
under tension on mandrel 210 can be about 132 centimeters or about
147 centimeters. Coil 270 may recoil to some extent (e.g., by at
most about five centimeters) when portion 280 of wire 28 is
severed, such that coil 270 will be somewhat smaller once it has
been removed from mandrel 210. In some embodiments, coil 270 can
have a length of from about five centimeters to about 225
centimeters (e.g., from about 25 centimeters to about 170
centimeters, from about 120 centimeters to about 140 centimeters,
from about 137 centimeters to about 140 centimeters) after being
removed from mandrel 210. After coil 270 has been removed from
mandrel 210, coil 270 can be cut into smaller coils.
[0099] Once coil 270 has been formed in its primary shape, coil 270
can be further shaped into a secondary shape, as shown in FIGS.
14A-14C.
[0100] FIG. 14A shows a mandrel 310 used to form the secondary
shape of coil 270. While mandrel 310 is shaped to form a diamond,
other types of mandrels can be used to form other secondary shapes.
Mandrel 310 is formed of a diamond-shaped block 320 with grooves
330 cut into its surface. As shown in FIGS. 14B and 14C, coil 270
in its primary shape is wrapped around mandrel 310, such that coil
270 fills grooves 330, creating the secondary shape. The ends of
coil 270 are then attached (e.g., pinned) to mandrel 310, and coil
270 is heat-treated to impart memory to coil 270. In some
embodiments, coil 270 can be heat-treated at a temperature of at
least about 1000.degree. F. (e.g., at least about 1050.degree. F.,
at least about 1100.degree. F., at least about 1150.degree. F.),
and/or at most about 1200.degree. F. (e.g., at most about
1150.degree. F., at most about 1100.degree. F., at most about
1050.degree. F.). In certain embodiments, the heat treatment of
coil 270 can last for a period of from about 10 minutes to about 40
minutes (e.g., about 25 minutes). After being heat-treated, coil
270 is unwrapped from mandrel 310. The removal of coil 270 from
mandrel 310 allows coil 270 to reassume its secondary shape. In
some embodiments, after coil 270 has been removed from mandrel 310,
one or both of the ends of coil 270 can be heated and melted to
form rounder, more biocompatible (e.g., atraumatic) ends.
[0101] Mandrel 310 can be formed of, for example, a metal or a
metal alloy (e.g., stainless steel). In some embodiments, mandrel
310 can be formed of a plated metal or a plated metal alloy (e.g.,
chrome-plated stainless steel).
[0102] Before, during, or after the formation of the secondary
shape of coil 270, a head can be attached (e.g., welded) to coil
270. The head can be formed, for example, using a micromachining
process and/or an etching process.
[0103] Embolic coils and methods of making embolic coils are
described, for example, in Elliott et al., U.S. Patent Application
Publication No. US 2006/0116711 A1, published on Jun. 1, 2006, and
entitled "Embolic Coils", which is incorporated herein by
reference.
[0104] In some embodiments, an embolic coil such as embolic coil 18
can include one or more therapeutic agents (e.g., drugs). For
example, wire 28 can include one or more therapeutic agents (e.g.,
dispersed within and/or encapsulated by the material of wire 28),
can be coated with one or more therapeutic agents, and/or can be
coated with one or more coatings including one or more therapeutic
agents. In some embodiments, the therapeutic agents can be
dispersed within, and/or encapsulated by, the coatings. Embolic
coil 18 can, for example, be used to deliver the therapeutic agents
to a target site.
[0105] In certain embodiments in which embolic coil 18 is coated by
one or more coatings including one or more therapeutic agents, the
coatings can include one or more bioerodible and/or bioabsorbable
materials. When the coatings are eroded and/or absorbed, they can
release the therapeutic agents into the body of a subject (e.g.,
during delivery and/or at a target site).
[0106] In some embodiments, a therapeutic agent-coated embolic coil
can include a coating (e.g., a bioerodible and/or bioabsorbable
polymer coating) over the surface of the therapeutic agent. The
coating can assist in controlling the rate at which therapeutic
agent is released from the embolic coil. For example, the coating
can be in the form of a porous membrane. The coating can delay an
initial burst of therapeutic agent release. The coating can be
applied by dipping or spraying the embolic coil. The coating can
include therapeutic agent or can be substantially free of
therapeutic agent. The therapeutic agent in the coating can be the
same as or different from a therapeutic agent on a surface layer of
the embolic coil and/or within the embolic coil (e.g., within a
wire forming the embolic coil). A polymer coating (e.g., that is
bioerodible and/or bioabsorbable) can be applied to an embolic coil
surface and/or to a coated embolic coil surface in embodiments in
which a high concentration of therapeutic agent has not been
applied to the embolic coil surface or to the coated embolic coil
surface.
[0107] Coatings are described, for example, in Buiser et al., U.S.
patent application Ser. No. 11/311,617, filed on Dec. 19, 2005, and
entitled "Coils", and in DiMatteo et al., U.S. Patent Application
Publication No. US 2004/0076582 A1, published on Apr. 22, 2004, and
entitled "Agent Delivery Particle", both of which are incorporated
herein by reference.
[0108] In some embodiments, one or more embolic coils can be
disposed in one or more liquid therapeutic agents.
[0109] Therapeutic agents include genetic therapeutic agents,
non-genetic therapeutic agents, and cells, and can be negatively
charged, positively charged, amphoteric, or neutral. Therapeutic
agents can be, for example, materials that are biologically active
to treat physiological conditions; pharmaceutically active
compounds; gene therapies; nucleic acids with and without carrier
vectors (e.g., recombinant nucleic acids, DNA (e.g., naked DNA),
cDNA, RNA, genomic DNA, cDNA or RNA in a non-infectious vector or
in a viral vector which may have attached peptide targeting
sequences, antisense nucleic acids (RNA, DNA)); peptides (e.g.,
growth factor peptides, such as basic fibroblast growth factor
(bFGF)); oligonucleotides; gene/vector systems (e.g., anything that
allows for the uptake and expression of nucleic acids); DNA
chimeras (e.g., DNA chimeras which include gene sequences and
encoding for ferry proteins such as membrane translocating
sequences ("MTS") and herpes simplex virus-1 ("VP22")); compacting
agents (e.g., DNA compacting agents); viruses; polymers; hyaluronic
acid; proteins (e.g., enzymes such as ribozymes, asparaginase);
immunologic species; nonsteroidal anti-inflammatory medications;
chemoagents; pain management therapeutics; oral contraceptives;
progestins; gonadotrophin-releasing hormone agonists;
chemotherapeutic agents; and radioactive species (e.g.,
radioisotopes, radioactive molecules). Non-limiting examples of
therapeutic agents include anti-thrombogenic agents; antioxidants;
angiogenic and anti-angiogenic agents and factors;
anti-proliferative agents (e.g., agents capable of blocking smooth
muscle cell proliferation); calcium entry blockers; and survival
genes which protect against cell death (e.g., anti-apoptotic Bcl-2
family factors and Akt kinase).
[0110] Exemplary non-genetic therapeutic agents include:
anti-thrombotic agents such as heparin, heparin derivatives,
urokinase, and PPack (dextrophenylalanine proline arginine
chloromethylketone); anti-inflammatory agents such as
dexamethasone, prednisolone, corticosterone, budesonide, estrogen,
acetyl salicylic acid, sulfasalazine and mesalamine;
antineoplastic/antiproliferative/anti-mitotic agents such as
paclitaxel, 5-fluorouracil, cisplatin, methotrexate, doxorubicin,
vinblastine, vincristine, epothilones, endostatin, angiostatin,
angiopeptin, monoclonal antibodies capable of blocking smooth
muscle cell proliferation, and thymidine kinase inhibitors;
anesthetic agents such as lidocaine, bupivacaine and ropivacaine;
anti-coagulants such as D-Phe-Pro-Arg chloromethyl ketone, an RGD
peptide-containing compound, heparin, hirudin, antithrombin
compounds, platelet receptor antagonists, anti-thrombin antibodies,
anti-platelet receptor antibodies, aspirin, prostaglandin
inhibitors, platelet inhibitors and tick antiplatelet factors or
peptides; vascular cell growth promoters such as growth factors,
transcriptional activators, and translational promoters; vascular
cell growth inhibitors such as growth factor inhibitors (e.g., PDGF
inhibitor-Trapidil), growth factor receptor antagonists,
transcriptional repressors, translational repressors, replication
inhibitors, inhibitory antibodies, antibodies directed against
growth factors, bifunctional molecules consisting of a growth
factor and a cytotoxin, bifunctional molecules consisting of an
antibody and a cytotoxin; protein kinase and tyrosine kinase
inhibitors (e.g., tyrphostins, genistein, quinoxalines);
prostacyclin analogs; cholesterol-lowering agents; angiopoietins;
antimicrobial agents such as triclosan, cephalosporins,
aminoglycosides and nitrofurantoin; cytotoxic agents, cytostatic
agents and cell proliferation affectors; vasodilating agents; and
agents that interfere with endogenous vasoactive mechanisms.
[0111] Exemplary genetic therapeutic agents include: anti-sense DNA
and RNA; DNA coding for anti-sense RNA, tRNA or rRNA to replace
defective or deficient endogenous molecules, angiogenic factors
including growth factors such as acidic and basic fibroblast growth
factors, vascular endothelial growth factor, epidermal growth
factor, transforming growth factor .alpha. and .beta.,
platelet-derived endothelial growth factor, platelet-derived growth
factor, tumor necrosis factor a, hepatocyte growth factor, and
insulin like growth factor, cell cycle inhibitors including CD
inhibitors, thymidine kinase ("TK") and other agents useful for
interfering with cell proliferation, and the family of bone
morphogenic proteins ("BMP's"), including BMP2, BMP3, BMP4, BMP5,
BMP6 (Vgr1), BMP7 (OP1), BMP8, BMP9, BMP10, BM11, BMP12, BMP13,
BMP14, BMP15, and BMP16. Currently preferred BMP's are any of BMP2,
BMP3, BMP4, BMP5, BMP6 and BMP7. These dimeric proteins can be
provided as homodimers, heterodimers, or combinations thereof,
alone or together with other molecules. Alternatively or
additionally, molecules capable of inducing an upstream or
downstream effect of a BMP can be provided. Such molecules include
any of the "hedgehog" proteins, or the DNA's encoding them. Vectors
of interest for delivery of genetic therapeutic agents include:
plasmids; viral vectors such as adenovirus (AV), adenoassociated
virus (AAV) and lentivirus; and non-viral vectors such as lipids,
liposomes and cationic lipids.
[0112] Cells include cells of human origin (autologous or
allogeneic), including stem cells, or from an animal source
(xenogeneic), which can be genetically engineered if desired to
deliver proteins of interest.
[0113] Several of the above and numerous additional therapeutic
agents appropriate for the practice of the present invention are
disclosed in Kunz et al., U.S. Pat. No. 5,733,925, assigned to
NeoRx Corporation, which is incorporated herein by reference.
Therapeutic agents disclosed in this patent include the
following:
[0114] "Cytostatic agents" (i.e., agents that prevent or delay cell
division in proliferating cells, for example, by inhibiting
replication of DNA or by inhibiting spindle fiber formation).
Representative examples of cytostatic agents include modified
toxins, methotrexate, adriamycin, radionuclides (e.g., such as
disclosed in Fritzberg et al., U.S. Pat. No. 4,897,255), protein
kinase inhibitors, including staurosporin, a protein kinase C
inhibitor of the following formula:
##STR00001##
[0115] as well as diindoloalkaloids having one of the following
general structures:
##STR00002##
as well as stimulators of the production or activation of TGF-beta,
including Tamoxifen and derivatives of functional equivalents
(e.g., plasmin, heparin, compounds capable of reducing the level or
inactivating the lipoprotein Lp(a) or the glycoprotein
apolipoprotein(a)) thereof, TGF-beta or functional equivalents,
derivatives or analogs thereof, suramin, nitric oxide releasing
compounds (e.g., nitroglycerin) or analogs or functional
equivalents thereof, paclitaxel or analogs thereof (e.g.,
taxotere), inhibitors of specific enzymes (such as the nuclear
enzyme DNA topoisomerase II and DNA polymerase, RNA polymerase,
adenyl guanyl cyclase), superoxide dismutase inhibitors, terminal
deoxynucleotidyl-transferase, reverse transcriptase, antisense
oligonucleotides that suppress smooth muscle cell proliferation and
the like. Other examples of "cytostatic agents" include peptidic or
mimetic inhibitors (i.e., antagonists, agonists, or competitive or
non-competitive inhibitors) of cellular factors that may (e.g., in
the presence of extracellular matrix) trigger proliferation of
smooth muscle cells or pericytes: e.g., cytokines (e.g.,
interleukins such as IL-1), growth factors (e.g., PDGF, TGF-alpha
or -beta, tumor necrosis factor, smooth muscle- and
endothelial-derived growth factors, i.e., endothelin, FGF), homing
receptors (e.g., for platelets or leukocytes), and extracellular
matrix receptors (e.g., integrins). Representative examples of
useful therapeutic agents in this category of cytostatic agents
addressing smooth muscle proliferation include: subfragments of
heparin, triazolopyrimidine (trapidil; a PDGF antagonist),
lovastatin, and prostaglandins E1 or I2.
[0116] Agents that inhibit the intracellular increase in cell
volume (i.e., the tissue volume occupied by a cell), such as
cytoskeletal inhibitors or metabolic inhibitors. Representative
examples of cytoskeletal inhibitors include colchicine, vinblastin,
cytochalasins, paclitaxel and the like, which act on microtubule
and microfilament networks within a cell. Representative examples
of metabolic inhibitors include staurosporin, trichothecenes, and
modified diphtheria and ricin toxins, Pseudomonas exotoxin and the
like. Trichothecenes include simple trichothecenes (i.e., those
that have only a central sesquiterpenoid structure) and macrocyclic
trichothecenes (i.e., those that have an additional macrocyclic
ring), e.g., a verrucarins or roridins, including Verrucarin A,
Verrucarin B, Verrucarin J (Satratoxin C), Roridin A, Roridin C,
Roridin D, Roridin E (Satratoxin D), Roridin H.
[0117] Agents acting as an inhibitor that blocks cellular protein
synthesis and/or secretion or organization of extracellular matrix
(i.e., an "anti-matrix agent"). Representative examples of
"anti-matrix agents" include inhibitors (i.e., agonists and
antagonists and competitive and non-competitive inhibitors) of
matrix synthesis, secretion and assembly, organizational
cross-linking (e.g., transglutaminases cross-linking collagen), and
matrix remodeling (e.g., following wound healing). A representative
example of a useful therapeutic agent in this category of
anti-matrix agents is colchicine, an inhibitor of secretion of
extracellular matrix. Another example is tamoxifen for which
evidence exists regarding its capability to organize and/or
stabilize as well as diminish smooth muscle cell proliferation
following angioplasty. The organization or stabilization may stem
from the blockage of vascular smooth muscle cell maturation in to a
pathologically proliferating form.
[0118] Agents that are cytotoxic to cells, particularly cancer
cells. Preferred agents are Roridin A, Pseudomonas exotoxin and the
like or analogs or functional equivalents thereof. A plethora of
such therapeutic agents, including radioisotopes and the like, have
been identified and are known in the art. In addition, protocols
for the identification of cytotoxic moieties are known and employed
routinely in the art.
[0119] A number of the above therapeutic agents and several others
have also been identified as candidates for vascular treatment
regimens, for example, as agents targeting restenosis. Such agents
include one or more of the following: calcium-channel blockers,
including benzothiazapines (e.g., diltiazem, clentiazem);
dihydropyridines (e.g., nifedipine, amlodipine, nicardapine);
phenylalkylamines (e.g., verapamil); serotonin pathway modulators,
including 5-HT antagonists (e.g., ketanserin, naftidrofuryl) and
5-HT uptake inhibitors (e.g., fluoxetine); cyclic nucleotide
pathway agents, including phosphodiesterase inhibitors (e.g.,
cilostazole, dipyridamole), adenylate/guanylate cyclase stimulants
(e.g., forskolin), and adenosine analogs; catecholamine modulators,
including .alpha.-antagonists (e.g., prazosin, bunazosine),
.beta.-antagonists (e.g., propranolol), and
.alpha./.beta.-antagonists (e.g., labetalol, carvedilol);
endothelin receptor antagonists; nitric oxide donors/releasing
molecules, including organic nitrates/nitrites (e.g.,
nitroglycerin, isosorbide dinitrate, amyl nitrite), inorganic
nitroso compounds (e.g., sodium nitroprusside), sydnonimines (e.g.,
molsidomine, linsidomine), nonoates (e.g., diazenium diolates, NO
adducts of alkanediamines), S-nitroso compounds, including low
molecular weight compounds (e.g., S-nitroso derivatives of
captopril, glutathione and N-acetyl penicillamine) and high
molecular weight compounds (e.g., S-nitroso derivatives of
proteins, peptides, oligosaccharides, polysaccharides, synthetic
polymers/oligomers and natural polymers/oligomers), C-nitroso-,
O-nitroso- and N-nitroso-compounds, and L-arginine; ACE inhibitors
(e.g., cilazapril, fosinopril, enalapril); ATII-receptor
antagonists (e.g., saralasin, losartin); platelet adhesion
inhibitors (e.g., albumin, polyethylene oxide); platelet
aggregation inhibitors, including aspirin and thienopyridine
(ticlopidine, clopidogrel) and GP IIb/IIIa inhibitors (e.g.,
abciximab, epitifibatide, tirofiban, intergrilin); coagulation
pathway modulators, including heparinoids (e.g., heparin, low
molecular weight heparin, dextran sulfate, .beta.-cyclodextrin
tetradecasulfate), thrombin inhibitors (e.g., hirudin, hirulog,
PPACK (D-phe-L-propyl-L-arg-chloromethylketone), argatroban), FXa
inhibitors (e.g., antistatin, TAP (tick anticoagulant peptide)),
vitamin K inhibitors (e.g., warfarin), and activated protein C;
cyclooxygenase pathway inhibitors (e.g., aspirin, ibuprofen,
flurbiprofen, indomethacin, sulfinpyrazone); natural and synthetic
corticosteroids (e.g., dexamethasone, prednisolone,
methprednisolone, hydrocortisone); lipoxygenase pathway inhibitors
(e.g., nordihydroguairetic acid, caffeic acid; leukotriene receptor
antagonists; antagonists of E- and P-selectins; inhibitors of
VCAM-1 and ICAM-1 interactions; prostaglandins and analogs thereof,
including prostaglandins such as PGE1 and PGI2; prostacyclin
analogs (e.g., ciprostene, epoprostenol, carbacyclin, iloprost,
beraprost); macrophage activation preventers (e.g.,
bisphosphonates); HMG-CoA reductase inhibitors (e.g., lovastatin,
pravastatin, fluvastatin, simvastatin, cerivastatin); fish oils and
omega-3-fatty acids; free-radical scavengers/antioxidants (e.g.,
probucol, vitamins C and E, ebselen, retinoic acid (e.g.,
trans-retinoic acid), SOD mimics); agents affecting various growth
factors including FGF pathway agents (e.g., bFGF antibodies,
chimeric fusion proteins), PDGF receptor antagonists (e.g.,
trapidil), IGF pathway agents (e.g., somatostatin analogs such as
angiopeptin and ocreotide), TGF-.beta. pathway agents such as
polyanionic agents (heparin, fucoidin), decorin, and TGF-.beta.
antibodies, EGF pathway agents (e.g., EGF antibodies, receptor
antagonists, chimeric fusion proteins), TNF-.alpha. pathway agents
(e.g., thalidomide and analogs thereof), thromboxane A2 (TXA2)
pathway modulators (e.g., sulotroban, vapiprost, dazoxiben,
ridogrel), protein tyrosine kinase inhibitors (e.g., tyrphostin,
genistein, and quinoxaline derivatives); MMP pathway inhibitors
(e.g., marimastat, ilomastat, metastat), and cell motility
inhibitors (e.g., cytochalasin B); antiproliferative/antineoplastic
agents including antimetabolites such as purine analogs (e.g.,
6-mercaptopurine), pyrimidine analogs (e.g., cytarabine and
5-fluorouracil) and methotrexate, nitrogen mustards, alkyl
sulfonates, ethylenimines, antibiotics (e.g., daunorubicin,
doxorubicin, daunomycin, bleomycin, mitomycin, penicillins,
cephalosporins, ciprofalxin, vancomycins, aminoglycosides,
quinolones, polymyxins, erythromycins, tertacyclines,
chloramphenicols, clindamycins, linomycins, sulfonamides, and their
homologs, analogs, fragments, derivatives, and pharmaceutical
salts), nitrosoureas (e.g., carmustine, lomustine) and cisplatin,
agents affecting microtubule dynamics (e.g., vinblastine,
vincristine, colchicine, paclitaxel, epothilone), caspase
activators, proteasome inhibitors, angiogenesis inhibitors (e.g.,
endostatin, angiostatin and squalamine), and rapamycin,
cerivastatin, flavopiridol and suramin; matrix
deposition/organization pathway inhibitors (e.g., halofuginone or
other quinazolinone derivatives, tranilast); endothelialization
facilitators (e.g., VEGF and RGD peptide); and blood rheology
modulators (e.g., pentoxifylline).
[0120] Other examples of therapeutic agents include anti-tumor
agents, such as docetaxel, alkylating agents (e.g.,
mechlorethamine, chlorambucil, cyclophosphamide, melphalan,
ifosfamide), plant alkaloids (e.g., etoposide), inorganic ions
(e.g., cisplatin), biological response modifiers (e.g.,
interferon), and hormones (e.g., tamoxifen, flutamide), as well as
their homologs, analogs, fragments, derivatives, and pharmaceutical
salts.
[0121] Additional examples of therapeutic agents include
organic-soluble therapeutic agents, such as mithramycin,
cyclosporine, and plicamycin. Further examples of therapeutic
agents include pharmaceutically active compounds, anti-sense genes,
viral, liposomes and cationic polymers (e.g., selected based on the
application), biologically active solutes (e.g., heparin),
prostaglandins, prostcyclins, L-arginine, nitric oxide (NO) donors
(e.g., lisidomine, molsidomine, NO-protein adducts,
NO-polysaccharide adducts, polymeric or oligomeric NO adducts or
chemical complexes), enoxaparin, Warafin sodium, dicumarol,
interferons, chymase inhibitors (e.g., Tranilast), ACE inhibitors
(e.g., Enalapril), serotonin antagonists, 5-HT uptake inhibitors,
and beta blockers, and other antitumor and/or chemotherapy drugs,
such as BiCNU, busulfan, carboplatinum, cisplatinum, cytoxan, DTIC,
fludarabine, mitoxantrone, velban, VP-16, herceptin, leustatin,
navelbine, rituxan, and taxotere.
[0122] Therapeutic agents are described, for example, in Buiser et
al., U.S. patent application Ser. No. 11/311,617, filed on Dec. 19,
2005, and entitled "Coils"; DiMatteo et al., U.S. Patent
Application Publication No. US 2004/0076582 A1, published on Apr.
22, 2004, and entitled "Agent Delivery Particle"; Pinchuk et al.,
U.S. Pat. No. 6,545,097; and Schwarz et al., U.S. Pat. No.
6,368,658, all of which are incorporated herein by reference.
[0123] While certain embodiments have been described, other
embodiments are possible.
[0124] As an example, in some embodiments, an embolic coil can have
at least two arms extending from it, and in certain embodiments, an
embolic coil delivery wire can have a non-hook-shaped head (e.g., a
peanut-shaped head). For example, FIG. 15A shows an embolic coil
system 350 including a catheter 352 with a lumen 354. Embolic coil
system 350 also includes an embolic coil delivery wire 356 and an
embolic coil 362 disposed within lumen 354. Embolic coil delivery
wire 356 includes a peanut-shaped head 360, and embolic coil 362
includes arms 364 and 366 extending from it. Arms 364 and 366 are
detachably engaged with head 360 of embolic coil delivery wire
356.
[0125] FIGS. 15B and 15C show enlarged views of embolic coil
delivery wire 356. As shown in FIG. 15C, embolic coil delivery wire
356 includes a wire portion 368 surrounded by a sheath 370. Wire
portion 368 is connected to head 360. However, in some embodiments,
a wire portion can be integrally formed with a non-hook-shaped
head.
[0126] FIGS. 15D and 15E show enlarged views of embolic coil 362.
As shown in FIG. 15E, arms 364 and 366 are integrally formed with
an attachment portion 372 that is attached to embolic coil body 361
of embolic coil 362.
[0127] As another example, while embolic coils and embolic coil
delivery wires with two arms extending from them have been
described, in some embodiments, more than two arms (e.g., three
arms, four arms, five arms, 10 arms, 16 arms) can extend from an
embolic coil or an embolic coil delivery wire.
[0128] As a further example, while embolic coils and embolic coil
delivery wires with peanut-shaped heads have been described, in
some embodiments, an embolic coil or an embolic coil delivery wire
can have a head that is not peanut-shaped. For example, in certain
embodiments, an embolic coil or an embolic coil delivery wire can
have a conical head.
[0129] As an additional example, while embolic coils and embolic
coil delivery wires with heads that are rotationally symmetric
about a longitudinal axis have been described, in some embodiments,
an embolic coil or an embolic coil delivery wire can have a head
that is not rotationally symmetric about a longitudinal axis. In
certain embodiments, an embolic coil or an embolic coil delivery
wire can have a head that is not rotationally symmetric about any
axis.
[0130] As another example, in some embodiments, an embolic coil or
an embolic coil delivery wire can have a head including a lumen.
This can, for example, allow fluids (e.g., contrast agent, saline
solution) to flow through the head during delivery and/or use of
the embolic coil or embolic coil delivery wire.
[0131] As an additional example, in certain embodiments, an embolic
coil or an embolic coil delivery wire can include a head having one
or more grooves in it. For example, FIG. 16 shows an embolic coil
system 400 including an embolic coil delivery wire 402 with arms
404 and 406 extending from it, and an embolic coil 408 having a
head 410. Head 410 includes a helical groove 412 on its surface
414. The tip 416 of arm 404 and the tip 418 of arm 406 each are
disposed within groove 412. The presence of groove 412 on head 410
can, for example, enhance the engagement of arms 404 and 406 with
head 410.
[0132] As a further example, in some embodiments, an embolic coil
can include an embolic coil body and one or more arms that are
integrally formed with the embolic coil body. For example, FIG. 17
shows an embolic coil system 450 including a catheter 452 having a
lumen 454, an embolic coil delivery wire 456 having a head 458, and
an embolic coil 460 including two arms 462 and 464 that are
detachably engaged with head 458. Embolic coil 460 is formed of two
coiled wires 466 and 468 that are co-wound with each other. Arm 462
is formed from an end of coiled wire 466, and arm 464 is formed
from an end of coiled wire 468.
[0133] As another example, while arms have been described as being
used to engage an embolic coil with an embolic coil delivery wire,
in certain embodiments, one or more other devices can be used to
engage an embolic coil with an embolic coil delivery wire. For
example, FIG. 18A shows an embolic coil system 500 including a
catheter 501 having a lumen 502, and an embolic coil delivery wire
504 and an embolic coil 506 disposed in lumen 502. Embolic coil
delivery wire 504 has a tubular mesh member 508 in its distal
section 510. Tubular mesh member 508 is engaged with a head 512 of
an embolic coil 506. Catheter 501 helps to restrain tubular mesh
member 508. As shown in FIG. 18B, when embolic coil delivery wire
504 is pushed in the direction of arrow A4, tubular mesh member 508
exits catheter 501 and opens up. As shown in FIG. 18C, when tubular
mesh member 508 has opened up sufficiently, tubular mesh member 508
releases embolic coil 506. Tubular mesh member 508 can be formed
of, for example, one or more metals (e.g., platinum) and/or metal
alloys (e.g., stainless steel, cobalt-chromium alloys such as
Elgiloy.RTM.). In certain embodiments, tubular mesh member 508 can
be formed of tantalum-cored wire. This can, for example, result in
tubular mesh member 508 being sufficiently radiopaque to be viewed
using X-ray fluoroscopy.
[0134] In some embodiments, an embolic coil delivery wire including
a tubular mesh member can be disposed within a lumen of a sheath
that, in turn, is disposed within a lumen of a catheter. The
embolic coil delivery wire can be used to deliver an embolic coil
by pushing the embolic coil delivery wire distally and withdrawing
the sheath proximally, thereby exposing the tubular mesh member and
releasing the embolic coil.
[0135] In certain embodiments, an embolic coil delivery wire can
include a tubular mesh member that is engaged with an embolic coil
(e.g., a head of an embolic coil), and when the tubular mesh member
and the embolic coil are unconstrained by a delivery device, the
tubular mesh member can have a retention strength that is less than
the flexural spring strength of the embolic coil. The result can be
that the tubular mesh member disengages from the embolic coil,
thereby deploying the embolic coil.
[0136] As an additional example, in certain embodiments, an embolic
coil can include fibers. For example, FIG. 19 shows embolic coil
600 including a peanut-shaped head 602, an embolic coil body 604,
and fibers 606 tightly fitted between consecutive windings (e.g.,
windings 608 and 610) of embolic coil body 604. In some embodiments
in which an embolic coil includes fibers, the occlusion of a target
site by the embolic coil can be accelerated by the fibers, which
can enhance thrombosis at the target site. An accelerated
embolization procedure can benefit the subject by, for example,
reducing exposure time to fluoroscopy.
[0137] Fibers 606 typically can be made of one or more materials
that can enhance thrombosis (e.g., at a target site). In some
embodiments, fibers 606 can be made of one or more polyesters
and/or polyamides. Examples of materials from which fibers 606 can
be made include polyethylene terephthalate (e.g., Dacron.RTM.),
nylon, and collagen. In certain embodiments, fibers 606 can have a
length of from about 0.5 millimeter to about five millimeters
(e.g., about 2.5 millimeters).
[0138] While FIG. 19 shows bunches of fibers 606 that are all
separated from their neighboring bunches of fibers 606 by the same
number of windings, in some embodiments, an embolic coil can have a
different configuration of fibers. For example, in certain
embodiments, an embolic coil can have only one bunch of fibers, or
can have bunches of fibers that are separated from their
neighboring bunches of fibers by different numbers of windings. As
an example, one bunch of fibers on an embolic coil may be separated
from a neighboring bunch of fibers by three windings, while another
bunch of fibers on the embolic coil is separated from a neighboring
bunch of fibers by five windings.
[0139] In some embodiments, a fibered embolic coil such as embolic
coil 600 can be formed as follows. After the embolic coil has been
formed into its secondary shape, fibers can be attached to the
embolic coil. In some embodiments, an embolic coil can be stretched
prior to attaching fibers to the embolic coil, so that the embolic
coil is in its extended primary shape, and can then be loaded onto
a fibering mandrel (e.g., a fibering mandrel from Sematool Mold and
Die Co., Santa Clara, Calif.). In certain embodiments, fibers can
be snapped between windings of an embolic coil. In some
embodiments, fibers can be tied to windings of an embolic coil
and/or wrapped around windings of an embolic coil. In certain
embodiments, fibers can be bonded (e.g., adhesive bonded) to
windings of an embolic coil. In some embodiments, one portion
(e.g., one end) of a bunch of fibers can be snapped in between
windings in one region of an embolic coil, and another portion
(e.g., the other end) of the same bunch of fibers can be wrapped
around part of the embolic coil and snapped in between windings in
another region of the embolic coil.
[0140] As a further example, in some embodiments, an embolic coil
can have at least two regions (e.g., three, four, five, 10, 15, 20)
with different outer diameters. Embolic coils including regions
with different outer diameters are described, for example, in
Elliott et al., U.S. Patent Application Publication No. US
2006/0116711 A1, published on Jun. 1, 2006, and entitled "Embolic
Coils", and Buiser et al., U.S. patent application Ser. No.
11/430,602, filed on May 9, 2006, and entitled "Embolic Coils",
both of which are incorporated herein by reference.
[0141] As another example, while embodiments have been shown in
which the pitch of an embolic coil is substantially the same in
different regions of the embolic coil, in certain embodiments, the
pitch of an embolic coil can differ in different regions of the
embolic coil. For example, some regions of an embolic coil can have
a pitch of 0.002 inch, while other regions of an embolic coil can
have a pitch of 0.004 inch.
[0142] As an additional example, in some embodiments, an embolic
coil delivery wire can be temporarily attached to an embolic coil
by one or more bioerodible connectors. For example, in certain
embodiments, an embolic coil delivery wire can have one or more
arms extending from it, and the arms can be connected to an embolic
coil (e.g., a head of an embolic coil) by one or more bioerodible
connectors.
[0143] As a further example, in some embodiments, an embolic coil
can be delivered to a target site by electrolytically detaching the
embolic coil from an embolic coil delivery wire. For example, FIG.
20 shows an embolic coil system 700 including a catheter 702 having
a lumen 704, and an embolic coil delivery wire 706 and an embolic
coil 708 disposed in lumen 704. Embolic coil delivery wire 706
includes two arms 710 and 712 that are detachably engaged with a
head 714 of embolic coil 708. Arms 710 and 712 include insulated
portions 716 and 718, and metal portions 720 and 722 that are
welded to head 714. Metal portions 720 and 722 are electrolytically
detachable from head 714. Electrolytic detachment is described, for
example, in Guglielmi et al., U.S. Pat. No. 5,895,385, which is
incorporated herein by reference.
[0144] As an additional example, in some embodiments, an embolic
coil delivery wire can include arms that are connected directly to
an embolic coil body of an embolic coil. For example, FIG. 21 shows
an embolic coil system 750 including an embolic coil delivery wire
752 having arms 754 and 756, and an embolic coil 758 including an
embolic coil body 760. Arms 754 and 756 are connected directly to
embolic coil body 760. In certain embodiments, embolic coil 758 can
be delivered to a target site by electrolytically detaching embolic
coil body 760 from arms 754 and 756.
[0145] As another example, in some embodiments, multiple (e.g.,
two, three, four) embolic coils can be delivered using one delivery
device.
[0146] As an additional example, in certain embodiments, a
treatment site can be occluded by using embolic coils in
conjunction with other occlusive devices. For example, embolic
coils can be used with embolic particles such as those described in
Buiser et al., U.S. Patent Application Publication No. US
2003/0185896 A1, published on Oct. 2, 2003, and entitled
"Embolization", and in Lanphere et al., U.S. Patent Application
Publication No. US 2004/0096662 A1, published on May 20, 2004, and
entitled "Embolization", both of which are incorporated herein by
reference. In some embodiments, embolic coils can be used in
conjunction with one or more embolic gels. Embolic gels are
described, for example, in Richard et al., U.S. Patent Application
Publication No. US 2006/0045900 A1, published on Mar. 2, 2006, and
entitled "Embolization", which is incorporated herein by
reference.
[0147] As another example, in certain embodiments, an embolic coil
can be loaded into a delivery device using an introducer sheath.
For example, FIG. 22 illustrates the transfer of an embolic coil
800 from an introducer sheath 810 into a catheter 820. A hub 830
located at the proximal end 840 of catheter 820 directs the
placement of introducer sheath 810. After introducer sheath 810 has
been placed in hub 830, an embolic coil delivery wire 850, having
two arms 860 and 870 that are detachably engaged with a head 880 of
embolic coil 800, is used to push embolic coil 800 out of
introducer sheath 810 and into catheter 820.
[0148] As an additional example, in some embodiments, an embolic
coil can include one or more radiopaque markers. The radiopaque
markers can, for example, be attached to one or more windings of
the embolic coil.
[0149] As a further example, in certain embodiments, an end of an
embolic coil can be heated and melted to make the end rounder
and/or more biocompatible (e.g., atraumatic).
[0150] As another example, in some embodiments, an embolic coil can
be formed of windings of a ribbon. Embolic coils that are formed of
windings of a ribbon are described, for example, in Buiser et al.,
U.S. patent application Ser. No. 11/430,602, filed on May 9, 2006,
and entitled "Embolic Coils", which is incorporated herein by
reference.
[0151] Other embodiments are in the claims.
* * * * *