U.S. patent application number 13/963997 was filed with the patent office on 2013-12-12 for stents with radiopaque markers.
This patent application is currently assigned to Abbott Cardiovascular Systems Inc.. The applicant listed for this patent is Abbott Cardiovascular Systems Inc.. Invention is credited to Patrick P. Wu.
Application Number | 20130331926 13/963997 |
Document ID | / |
Family ID | 49668808 |
Filed Date | 2013-12-12 |
United States Patent
Application |
20130331926 |
Kind Code |
A1 |
Wu; Patrick P. |
December 12, 2013 |
Stents With Radiopaque Markers
Abstract
Various embodiments of stents with radiopaque markers arranged
in patterns are described herein.
Inventors: |
Wu; Patrick P.; (San Carlos,
CA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Abbott Cardiovascular Systems Inc. |
Santa Clara |
CA |
US |
|
|
Assignee: |
Abbott Cardiovascular Systems
Inc.
Santa Clara
CA
|
Family ID: |
49668808 |
Appl. No.: |
13/963997 |
Filed: |
August 9, 2013 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
11796226 |
Apr 26, 2007 |
|
|
|
13963997 |
|
|
|
|
60809088 |
May 26, 2006 |
|
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Current U.S.
Class: |
623/1.16 |
Current CPC
Class: |
A61F 2/958 20130101;
Y10T 29/49993 20150115; A61F 2/95 20130101; A61F 2230/0054
20130101; A61L 31/04 20130101; A61B 2090/3966 20160201; Y10T
29/49929 20150115; A61L 31/18 20130101; A61L 31/06 20130101; B29D
23/00 20130101; Y10T 29/49885 20150115; A61F 2002/91516 20130101;
Y10T 29/49927 20150115; A61F 2002/91566 20130101; A61F 2/90
20130101; B29C 65/48 20130101; B29L 2031/7543 20130101; A61F 2/9522
20200501; A61L 31/148 20130101; A61F 2/06 20130101; A61F 2002/91583
20130101; Y10T 156/1034 20150115; A61F 2/82 20130101; A61F 2/844
20130101; A61F 2/915 20130101; Y10T 29/49913 20150115; A61L 29/00
20130101; A61F 2230/0013 20130101; A61F 2250/0098 20130101; A61L
31/06 20130101; C08L 67/04 20130101 |
Class at
Publication: |
623/1.16 |
International
Class: |
A61F 2/06 20060101
A61F002/06 |
Claims
1-20. (canceled)
21. A biodegradable polymeric stent, comprising: (a) a pattern of
rings comprised of struts, such that one ring is connected to its
adjacent ring by at least one connecting element, wherein the
struts and connecting element(s) provide the stent with radial
strength, expansion ratio, and longitudinal flexibility, wherein
the struts and connecting element(s) are generally four sided in
cross-section, and wherein a material from which the struts and
connecting element(s) are made consist of two different
biodegradable polymers, one of the two polymers being a
poly(l-lactide), with the proviso that the struts and connecting
element(s) are made from the poly(l-lactide)-based polymer and no
other polymers; and (b) radiopaque markers supported by the
polymeric stent to provide capability of obtaining images of the
poly(l-lactide)-based polymer with x-ray fluoroscopy during and
after implantation of the stent in a vessel, wherein the stent
consists of two pairs markers, two of the markers being positioned
in an adjacent configuration about a proximal most end ring of the
stent, and the remaining two markers being positioned in an
adjacent configuration about a distal most end ring of the stent,
with the proviso that the stent has no other markers but for the
four markers to allow for imaging of the poly(l-lactide)-based
polymer and with a further proviso that an entire length of the
stent between the first pair and second pair of markers is devoid
of any markers, wherein a center point of a first marker is
positioned at a circumferential distance from a center point of its
adjacent second marker, wherein a center point of a third marker is
positioned at a circumferential distance from a center point of its
adjacent fourth marker, and wherein the pair of markers about the
proximal most end ring of the polymeric stent are circumferentially
off-set from the pair of markers about the distal most end ring of
the polymeric stent.
22. The polymeric stent of claim 21, wherein the markers are
spherical and each are disposed in 4 respective cylindrical depots
laser machined into an element of the polymeric stent.
23. The polymeric stent of claim 21, wherein the depots are
closed-ended.
24. The polymeric stent of claim 21, wherein the depots are open at
both a luminal side and abluminal side.
25. The polymeric stent of claim 21, wherein the makers are
attached to the depots by gluing, welding or through interference
fit.
26. The polymeric stent of claim 21, wherein the markers are
biocompatible so as not to interfere to the treatment of the
patient.
Description
CROSS REFERENCE TO RELATED APPLICATION
[0001] This is a continuation of application Ser. No. 11/796,226,
filed on Apr. 26, 2007 which in turned claims benefit of
provisional application No. 60/809,088, filed on May 26, 2006, both
of which are incorporated herein by reference in their
entirety.
BACKGROUND OF THE INVENTION
[0002] 1. Field of the Invention
[0003] This invention relates to implantable medical devices, such
as stents. In particular, the invention relates to polymeric stents
with radiopaque markers.
[0004] 2. Description of the State of the Art
[0005] This invention relates to radially expandable
endoprostheses, which are adapted to be implanted in a bodily
lumen. An "endoprosthesis" corresponds to an artificial device that
is placed inside the body. A "lumen" refers to a cavity of a
tubular organ such as a blood vessel. A stent is an example of such
an endoprosthesis. Stents are generally cylindrically shaped
devices, which function to hold open and sometimes expand a segment
of a blood vessel or other anatomical lumen such as urinary tracts
and bile ducts. Stents are often used in the treatment of
atherosclerotic stenosis in blood vessels. "Stenosis" refers to a
narrowing or constriction of the diameter of a bodily passage or
orifice. In such treatments, stents reinforce body vessels and
prevent restenosis following angioplasty in the vascular system.
"Restenosis" refers to the reoccurrence of stenosis in a blood
vessel or heart valve after it has been treated (as by balloon
angioplasty, stenting, or valvuloplasty) with apparent success.
[0006] The structure of stents is typically composed of scaffolding
that includes a pattern or network of interconnecting structural
elements or struts. The scaffolding can be formed from wires,
tubes, or sheets of material rolled into a cylindrical shape. In
addition, a medicated stent may be fabricated by coating the
surface of either a metallic or polymeric scaffolding with a
polymeric carrier. The polymeric scaffolding may also serve as a
carrier of an active agent or drug.
[0007] The first step in treatment of a diseased site with a stent
is locating a region that may require treatment such as a suspected
lesion in a vessel, typically by obtaining an x-ray image of the
vessel. To obtain an image, a contrast agent, which contains a
radiopaque substance such as iodine is injected into a vessel.
"Radiopaque" refers to the ability of a substance to absorb x-rays.
The x-ray image depicts the lumen of the vessel from which a
physician can identify a potential treatment region. The treatment
then involves both delivery and deployment of the stent. "Delivery"
refers to introducing and transporting the stent through a bodily
lumen to a region in a vessel that requires treatment. "Deployment"
corresponds to the expanding of the stent within the lumen at the
treatment region. Delivery and deployment of a stent are
accomplished by positioning the stent about one end of a catheter,
inserting the end of the catheter through the skin into a bodily
lumen, advancing the catheter in the bodily lumen to a desired
treatment location, expanding the stent at the treatment location,
and removing the catheter from the lumen. In the case of a balloon
expandable stent, the stent is mounted about a balloon disposed on
the catheter. Mounting the stent typically involves compressing or
crimping the stent onto the balloon. The stent is then expanded by
inflating the balloon. The balloon may then be deflated and the
catheter withdrawn. In the case of a self-expanding stent, the
stent may be secured to the catheter via a retractable sheath or a
sock. When the stent is in a desired bodily location, the sheath
may be withdrawn allowing the stent to self-expand.
[0008] The stent must be able to simultaneously satisfy a number of
mechanical requirements. First, the stent must be capable of
withstanding the structural loads, namely radial compressive
forces, imposed on the stent as it supports the walls of a vessel
lumen. In addition to having adequate radial strength or more
accurately, hoop strength, the stent should be longitudinally
flexible to allow it to be maneuvered through a tortuous vascular
path and to enable it to conform to a deployment site that may not
be linear or may be subject to flexure. The material from which the
stent is constructed must allow the stent to undergo expansion,
which typically requires substantial deformation of localized
portions of the stent's structure. Once expanded, the stent must
maintain its size and shape throughout its service life despite the
various forces that may come to bear thereon, including the cyclic
loading induced by the beating heart. Finally, the stent must be
biocompatible so as not to trigger any adverse vascular
responses.
[0009] In addition to meeting the mechanical requirements described
above, it is desirable for a stent to be radiopaque, or
fluoroscopically visible under x-rays. Accurate stent placement is
facilitated by real time visualization of the delivery of a stent.
A cardiologist or interventional radiologist can track the delivery
catheter through the patient's vasculature and precisely place the
stent at the site of a lesion. This is typically accomplished by
fluoroscopy or similar x-ray visualization procedures. For a stent
to be fluoroscopically visible it must be more absorptive of x-rays
than the surrounding tissue. Radiopaque materials in a stent may
allow for its direct visualization.
[0010] In many treatment applications, the presence of a stent in a
body may be necessary for a limited period of time until its
intended function of, for example, maintaining vascular patency
and/or drug delivery is accomplished. Therefore, stents fabricated
from biodegradable, bioabsorbable, and/or bioerodable materials may
be configured to meet this additional clinical requirement since
they may be designed to completely erode after the clinical need
for them has ended. Stents fabricated from biodegradable polymers
are particularly promising, in part because they may be designed to
completely erode within a desired time frame.
[0011] However, a significant shortcoming of biodegradable polymers
(and polymers generally composed of carbon, hydrogen, oxygen, and
nitrogen) is that they are radiolucent with no radiopacity.
Biodegradable polymers tend to have x-ray absorption similar to
body tissue.
[0012] One way of addressing this problem is to attach or couple
radiopaque markers to a stent. The radiopaque markers allow the
position of the stent to be monitored since the markers are can be
imaged by X-ray imaging techniques. The ability to monitor or
detect a stent visually is limited by the visibility of the
markers.
SUMMARY OF THE INVENTION
[0013] Various embodiments of the present invention include a stent
comprising radiopaque markers disposed on or within the stent,
wherein the radiopaque markers are arranged longitudinally along an
axis of the stent.
[0014] Further embodiments of the present invention include a stent
comprising radiopaque markers disposed on or within the stent,
wherein the radiopaque markers are arranged in a pattern along the
circumference of the stent.
[0015] Additional embodiments of the present invention include a
stent comprising a plurality of radiopaque markers disposed on or
within on the stent, wherein the plurality of radiopaque markers
are selectively arranged in a region of the stent to enhance the
visibility of the stent with an imaging technique.
BRIEF DESCRIPTION OF THE DRAWINGS
[0016] FIG. 1 depicts an exemplary stent.
[0017] FIG. 2 depicts an exemplary embodiment of a radiopaque
marker and a section of a structural element of a stent with a
depot for receiving the marker.
[0018] FIG. 3 depicts a stent pattern with radiopaque markers at
proximal and distal ends.
[0019] FIG. 4 depicts a stent pattern with radiopaque markers
arranged longitudinally along the cylindrical axis.
[0020] FIG. 5 depicts a stent pattern with radiopaque markers
arranged in two longitudinally patterns along the cylindrical
axis.
[0021] FIG. 6 depicts a stent pattern with radiopaque markers
arranged in circumferential patterns.
[0022] FIG. 7 depicts a stent pattern with radiopaque markers
arranged in a diagonal pattern.
[0023] FIG. 8 depicts a stent pattern with radiopaque markers
arranged in circumferential patterns and longitudinal patterns.
[0024] FIG. 9 depicts a stent pattern with radiopaque markers
selectively arranged in the proximal and distal regions of a
stent.
DETAILED DESCRIPTION OF THE INVENTION
[0025] The present invention may be applied to stents and, more
generally, implantable medical devices such as, but not limited to,
self-expandable stents, balloon-expandable stents, stent-grafts,
vascular grafts, cerebrospinal fluid shunts, pacemaker leads,
closure devices for patent foramen ovale, and synthetic heart
valves.
[0026] A stent can have virtually any structural pattern that is
compatible with a bodily lumen in which it is implanted. Typically,
a stent is composed of a pattern or network of circumferential and
longitudinally extending interconnecting structural elements or
struts. In general, the struts are arranged in patterns, which are
designed to contact the lumen walls of a vessel and to maintain
vascular patency. A myriad of strut patterns are known in the art
for achieving particular design goals. A few of the more important
design characteristics of stents are radial or hoop strength,
expansion ratio or coverage area, and longitudinal flexibility. The
present invention is applicable to virtually any stent design and
is, therefore, not limited to any particular stent design or
pattern. One embodiment of a stent pattern may include cylindrical
rings composed of struts. The cylindrical rings may be connected by
connecting struts.
[0027] In some embodiments, a stent of the present invention may be
formed from a tube by laser cutting the pattern of struts in the
tube. The stent may also be formed by laser cutting a polymeric
sheet, rolling the pattern into the shape of the cylindrical stent,
and providing a longitudinal weld to form the stent. Other methods
of forming stents are well known and include chemically etching a
polymeric sheet and rolling and then welding it to form the stent.
A polymeric wire may also be coiled to form the stent. The stent
may be formed by injection molding of a thermoplastic or reaction
injection molding of a thermoset polymeric material. Filaments of
the compounded polymer may be extruded or melt spun. These
filaments can then be cut, formed into ring elements, welded
closed, corrugated to form crowns, and then the crowns welded
together by heat or solvent to form the stent. Lastly, hoops or
rings may be cut from tubing stock, the tube elements stamped to
form crowns, and the crowns connected by welding or laser fusion to
form the stent.
[0028] FIG. 1 depicts an exemplary stent 100 with struts 110 that
form cylindrical rings 115 which are connected by linking struts
120. The cross-section of the struts in stent 100 are
rectangular-shaped. The cross-section of struts is not limited to
what has been illustrated, and therefore, other cross-sectional
shapes are applicable with embodiments of the present invention.
The pattern should not be limited to what has been illustrated as
other stent patterns are easily applicable with embodiments of the
present invention.
[0029] A stent can be made of a biostable and/or biodegradable
polymer. As indicated above, a stent made from a biodegradable
polymer is intended to remain in the body for a duration of time
until its intended function of, for example, maintaining vascular
patency and/or drug delivery is accomplished. After the process of
degradation, erosion, absorption, and/or resorption has been
completed, no portion of the biodegradable stent, or a
biodegradable portion of the stent will remain. In some
embodiments, very negligible traces or residue may be left behind.
The duration can be in a range from about a month to a few years.
However, the duration is typically in a range from about one month
to twelve months, or in some embodiments, six to twelve months. It
is important for the stent to provide mechanical support to a
vessel for at least a portion of the duration. Many biodegradable
polymers have erosion rates that make them suitable for treatments
that require the presence of a device in a vessel for the
above-mentioned time-frames.
[0030] As indicated above, it is desirable to have the capability
of obtaining images of polymeric stents with x-ray fluoroscopy
during and after implantation. Various embodiments of the present
invention include stents with markers arranged in patterns or
selectively arranged on the stent in a manner that facilitates
visualization of the stent.
[0031] Various types of markers can be used in embodiments of the
present invention. Representative types of markers include
constructs made of a radiopaque material that is disposed within
depots or holes in a stent. The construct can be, but is not
limited to a pellet, bead, or slug. The depot or hole can be made
to accommodate the shape of the marker. In an embodiment, the depot
may be formed in a structural element by laser machining. The depot
may extend partially or completely through the portion of the
stent. For example, an opening of a depot may be on an abluminal or
luminal surface and extend partially through the stent or
completely through to an opposing surface. The markers may be
sufficiently radiopaque for imaging the stent. In addition,
embodiments of the stents with markers should be biocompatible and
should not interfere with treatment.
[0032] FIG. 2 illustrates an exemplary embodiment of a spherical
marker 150 and a section 155 of a structural element of a stent
with a cylindrical depot 160. Depot 160 accommodates the shape of
spherical marker 150 so that is can be positioned within depot 160.
Markers can be attached or coupled to a stent using various
techniques, including, but not limited to, gluing, welding, or
through an interference fit.
[0033] The markers and manner of positioning on the stent are
merely representative. Embodiments of the present invention are not
limited to the type of marker or the manner of attachment or
coupling to the stent. The present invention applies to markers
that can be attached or coupled in, on, or around a stent at a
specific locations or positions on the stent structure or
geometry.
[0034] In general, increasing the size of a marker enhances the
visibility of a stent. However, increasing the size of a marker can
have disadvantages. For example, a larger marker can result in an
undesirably large profile of the stent which can interfere with the
flow of blood in a vessel. Complications such as thrombosis can
result from the disturbed blood flow. Additionally, a larger marker
disposed in a structural element can negatively affect its
structural integrity.
[0035] Embodiments of the present invention are directed to
positioning or arranging markers on a stent to facilitate detection
or monitoring the position of the stent. In certain embodiments,
the markers can be arranged in a geometrical pattern that
facilitates visualization of the stent.
[0036] FIG. 3 depicts a stent pattern 180 in a flattened condition
showing an abluminal or luminal surface so that the pattern can be
clearly viewed. When the flattened portion of stent pattern 180 is
in a cylindrical condition, it forms a radially expandable stent.
Line A-A corresponds to the longitudinal axis of a stent made from
stent pattern 180 and line B-B corresponds to the circumferential
direction of a stent made from stent pattern 180.
[0037] Stent pattern 180 includes cylindrically aligned rings 185
and linking structural elements 190. Structural elements at a
proximal end 205 and distal end 210 of stent pattern 180 include
depots with pairs of radiopaque markers 195 and 200, respectively,
disposed within the depots. As shown FIG. 3, the structural
elements are thicker in the vicinity of markers 195 and 200 to
compensate for the presence of the depots. In general, it is
desirable to place radiopaque markers in regions of a stent pattern
that experience relatively low strain during crimping and
expansion. Such low strain regions include straight portions of
structural elements and "spider regions" which are intersections of
three or more structural elements.
[0038] A physician can monitor the position of the stent due to the
presence of the radiopaque markers which are visible using X-ray
imaging. Since markers are located at the distal and proximal ends
of the stent, the positions of the markers allow the physician to
locate the ends of the stent. However, the small size of the
markers can make it difficult to visually detect the individual
markers. As indicated above, the size of markers is limited by a
desired profile of the stent and structural integrity of structural
elements. Since the markers are separated by the length of the
stent, locating the ends of the stent can be difficult.
[0039] Various embodiments of the present invention include a stent
having radiopaque markers arranged in patterns or selectively
arranged in a region in a manner that enhances or facilitates
visualization of the stent. Radiopaque markers arranged in patterns
or selectively arranged in particular region(s) have greater
visibility than one or two localized markers and can substantially
enhance the visibility of a stent.
[0040] FIG. 4 depicts an exemplary stent pattern 220 of the present
invention. Stent pattern 220 is the same as pattern 180 in FIG. 3
except for the number and arrangement of radiopaque markers. Stent
pattern 220 includes radiopaque markers 225 which are arranged
longitudinally along the cylindrical axis of stent pattern 220.
Radiopaque markers 225 can be placed in or on any portion of the
structural elements of stent pattern 220, as long as the mechanical
integrity of the structural element is not undesirably compromised.
As shown in FIG. 4, radiopaque markers 220 are located in the
"spider regions," which are relatively low strain regions of stent
pattern 220. Such a pattern is substantially more visible than one
or two markers localized at either end of the stent, as depicted in
FIG. 3.
[0041] The longitudinal pattern of markers 225 extends from a
proximal end 230 to a distal end 235 of stent pattern 220. In some
embodiments, the pattern does not extend all the way between the
proximal end and distal end. A portion between the proximal and
distal ends can be devoid of markers.
[0042] In other embodiments, the visibility of the stent can be
further enhanced by including additional marker patterns. For
example, FIG. 5 depicts another exemplary stent pattern 250 of the
present invention that is the same as the stent patterns of FIGS. 3
and 4 except for the number and arrangement of radiopaque markers.
Stent pattern 250 includes a longitudinal pattern 255 of markers
265 and another longitudinal pattern 260 of markers 270 at a
different circumferential position. Marker patterns 255 and 260 are
separated by a circumferential distance or arc D. D can be between
0.degree. and 45.degree., 45.degree. and 90.degree., 90.degree. and
135.degree., and between 135 and 180.degree..
[0043] Further embodiments can include marker patterns along at
least a portion of the circumference. Such marker patterns can
include, but are not limited to, a circular pattern, diagonal
pattern, or a spiral pattern. FIG. 6 depicts another exemplary
stent pattern 280 of the present invention that is the same as the
previous stent patterns except for the number and arrangement of
radiopaque markers. Stent pattern 280 includes three
circumferential marker patterns: a marker pattern 285 with markers
287 at a proximal end 300, a marker pattern 290 with markers 292 at
a distal end 305, and a marker pattern 295 with markers 297 between
proximal end 300 and distal end 305. These marker patterns
substantially enhance the visibility of the ends of the stent as
compared to one or two markers at the ends, such as that
illustrated in FIG. 3.
[0044] Each of the circumferential patterns extends all the way
around the circumference of a stent made from stent pattern 280 and
is positioned at a single axial position. Alternatively, the
circumferential patterns can extend partially around the
circumference. Circumferential patterns can also extend diagonally
around the circumference so that the marker pattern is not a single
axial position. For example, FIG. 7 depicts an exemplary stent
pattern 320 that has a diagonal marker pattern with markers 325
extending between a proximal end 330 to a distal end 335.
[0045] In some embodiments, a stent can include both longitudinal
and circumferential marker patters. FIG. 8 depicts an exemplary
stent pattern 350 of the present invention that is the same as the
previous stent patterns except for the number and arrangement of
radiopaque markers. Stent pattern 350 includes two circumferential
marker patterns, 355 and 360, and two longitudinal marker patterns,
365 and 370. Marker patterns 355 and 360 are at proximal end 375
and 380. Such a combination of patterns enhances the visibility of
both the ends of the stent as well as the longitudinal extent of
the stent.
[0046] In certain embodiments, a plurality of radiopaque markers
can be selectively arranged in a region of the stent to enhance the
visibility of the stent with an imaging technique. For example, the
markers can be selectively arranged at a proximal region, distal
region, or both. FIG. 9 depicts an exemplary stent pattern 400 of
the present invention that is the same as the previous stent
patterns except for the number and arrangement of radiopaque
markers. Stent pattern 400 includes a group of markers 405 arranged
at a proximal end 415 and a group of markers 410 arranged at a
distal end 420. The groups of markers tend to increase the
visibility of the respective ends of the stent as compared to the
markers is FIG. 3. The individual markers can be selected and
coupled in a way that there is little or no negative effect on the
structural integrity of the stent and also with a relatively low
profile.
[0047] As indicated above, a stent may have regions with a lower
strain than other higher strain regions when the stent is placed
under an applied stress during use. A depot for a radiopaque marker
may be selectively positioned in a region of lower strain. The
selected region of the structural element may be modified to have a
higher mass or thickness than a region of lower strain without a
marker so as to maintain the load-bearing capability of the region
and to inhibit decoupling of the marker from the stent.
[0048] Furthermore, the markers may be coupled to any desired
location on a stent. In some embodiments, it may be advantageous to
limit the placement of a marker to particular locations or portions
of surfaces of a stent. For example, it may be desirable to couple
a marker at a sidewall face of a structural element to reduce or
eliminate interference with a lumen wall or interference with blood
flow, respectively. To delineate just the margins of the stent so
that the physician may see its full length, markers can be placed
only at the distal and proximal ends of the stent.
[0049] As indicated above, a stent may include a biostable and/or a
biodegradable polymer. The biodegradable polymer may be a pure or
substantially pure biodegradable polymer. Alternatively, the
biodegradable polymer may be a mixture of at least two types of
biodegradable polymers. The stent may be configured to completely
erode away once its function is fulfilled.
[0050] In certain embodiments, the marker may be biodegradable. It
may be desirable for the marker to degrade at the same or
substantially the same rate as the stent. For instance, the marker
may be configured to completely or almost completely erode at the
same time or approximately the same time as the stent. In other
embodiments, the marker may degrade at a faster rate than the
stent. In this case, the marker may completely or almost completely
erode before the body of the stent is completely eroded.
[0051] Furthermore, a radiopaque marker may be composed of a
biodegradable and/or biostable metal. Biodegradable or bioerodable
metals tend to erode or corrode relatively rapidly when exposed to
bodily fluids. Biostable metals refer to metals that are not
biodegradable or bioerodable or have negligible erosion or
corrosion rates when exposed to bodily fluids. Additionally, it is
desirable to use a biocompatible biodegradable metal for a marker.
A biocompatible biodegradable metal forms erosion products that do
not negatively impact bodily functions.
[0052] In one embodiment, a radiopaque marker may be composed of a
pure or substantially pure biodegradable metal. Alternatively, the
marker may be a mixture or alloy of at least two types of metals.
Representative examples of biodegradable metals for use in a marker
may include, but are not limited to, magnesium, zinc, tungsten, and
iron. Representative mixtures or alloys may include magnesium/zinc,
magnesium/iron, zinc/iron, and magnesium/zinc/iron. Radiopaque
compounds such as iodine salts, bismuth salts, or barium salts may
be compounded into the metallic biodegradable marker to further
enhance the radiopacity. Representative examples of biostable
metals can include, but are not limited to, platinum and gold.
[0053] In some embodiments, the composition of the marker may be
modified or tuned to obtain a desired erosion rate and/or degree of
radiopacity. For example, the erosion rate of the marker may be
increased by increasing the fraction of a faster eroding component
in an alloy. Similarly, the degree of radiopacity may be increased
by increasing the fraction of a more radiopaque metal, such as
iron, in an alloy. In one embodiment, a biodegradable marker may be
completely eroded when exposed to bodily fluids, such as blood,
between about a week and about three months, or more narrowly,
between about one month and about two months.
[0054] In other embodiments, a radiopaque marker may be a mixture
of a biodegradable polymer and a radiopaque material. A radiopaque
material may be biodegradable and/or bioabsorbable. Representative
radiopaque materials may include, but are not limited to,
biodegradable metallic particles and particles of biodegradable
metallic compounds such as biodegradable metallic oxides,
biocompatible metallic salts, gadolinium salts, and iodinated
contrast agents.
[0055] In some embodiments, the radiopacity of the marker may be
increased by increasing the composition of the radiopaque material
in the marker. In one embodiment, the radiopaque material may be
between 10% and 80%; 20% and 70%; 30% and 60%; or 40% and 50% by
volume of the marker.
[0056] The biodegradable polymer in the marker may be a pure or
substantially pure biodegradable polymer. Alternatively, the
biodegradable polymer may be a mixture of at least two types of
biodegradable polymers. In one embodiment, the composition of the
biodegradable polymer may be modified to alter the erosion rate of
the marker since different biodegradable polymers have different
erosion rates.
[0057] A biocompatible metallic salt refers to a salt that may be
safely absorbed by a body. Representative biocompatible metallic
salts that may used in a marker include, but are not limited to,
ferrous sulfate, ferrous gluconate, ferrous carbonate, ferrous
chloride, ferrous fumarate, ferrous iodide, ferrous lactate,
ferrous succinate, barium sulfate, bismuth subcarbonate, bismuth
potassium tartrate, bismuth sodium iodide, bismuth sodium tartrate,
bismuth sodium triglycollamate, bismuth subsalicylate, zinc
acetate, zinc carbonate, zinc citrate, zinc iodate, zinc iodide,
zinc lactate, zinc phosphate, zinc salicylate, zinc stearate, zinc
sulfate, and combinations thereof. The concentration of the
metallic salt in the marker may be between 10% and 80%; 20% and
70%; 30% and 60%; or 40% and 50% by volume of the marker.
[0058] In addition, representative iodinated contrast agents may
include, but are not limited to acetriozate, diatriozate, iodimide,
ioglicate, iothalamate, ioxithalamate, selectan, uroselectan,
diodone, metrizoate, metrizamide, iohexol, ioxaglate, iodixanol,
lipidial, ethiodol, and combinations thereof. The concentration of
an iodinated contrast agent in the marker may be between 5% and
80%; 20% and 70%; 30% and 60%; or 40% and 50% by volume of the
marker.
[0059] The composition of metallic particles may include at least
those biodegradable metals discussed above as well as metallic
compounds such as oxides. The concentration of metallic particles
in the marker may be between 10% and 80%; 20% and 70%; 30% and 60%;
or 40% and 50% by volume of the marker. Additionally, individual
metallic particles may be a pure or substantially pure metal or a
metal compound. Alternatively, individual metallic particles may be
a mixture of at least two types of metals or metallic compounds.
Individual metallic particles may also be a mixture or an alloy
composed of at least two types of metals.
[0060] In certain embodiments, the metallic particles may be
metallic nanoparticles. A "nanoparticle" refers to a particle with
a dimension in the range of about 1 nm to about 100 nm. A
significant advantage of nanoparticles over larger particles is
that nanoparticles may disperse more uniformly in a polymeric
matrix, which results in more uniform properties such as
radiopacity and erosion rate. Additionally, nanoparticles may be
more easily absorbed by bodily fluids such as blood without
negative impact to bodily functions. Representative examples of
metallic particles may include, but are not limited to, iron,
magnesium, zinc, platinum, gold, tungsten, and oxides of such
metals.
[0061] In one embodiment, the composition of different types of
metallic particles in the mixture as well as the composition of
individual particles may be modified to alter erosion rates and/or
radiopacity of the marker. In addition, the ratio of polymer to
metallic particles may be modified to alter both the erosion rate,
and radiopacity.
[0062] A marker may be fabricated by methods including, but not
limited to, molding, machining, assembly, or a combination thereof.
All or part of a metallic or polymeric marker may be fabricated in
a mold or machined by a method such as laser machining.
[0063] In general, polymers can be biostable, bioabsorbable,
biodegradable, or bioerodable. Biostable refers to polymers that
are not biodegradable. The terms biodegradable, bioabsorbable, and
bioerodable, as well as degraded, eroded, and absorbed, are used
interchangeably and refer to polymers that are capable of being
completely eroded or absorbed when exposed to bodily fluids such as
blood and can be gradually resorbed, absorbed and/or eliminated by
the body.
[0064] Biodegradation refers generally to changes in physical and
chemical properties that occur in a polymer upon exposure to bodily
fluids as in a vascular environment. The changes in properties may
include a decrease in molecular weight, deterioration of mechanical
properties, and decrease in mass due to erosion or absorption.
Mechanical properties may correspond to strength and modulus of the
polymer. Deterioration of the mechanical properties of the polymer
decreases the ability of a stent, for example, to provide
mechanical support in a vessel. The decrease in molecular weight
may be caused by, for example, hydrolysis, oxidation, enzymolysis,
and/or metabolic processes.
[0065] Representative examples of polymers that may be used to
fabricate embodiments of stents, or more generally, implantable
medical devices include, but are not limited to,
poly(N-acetylglucosamine) (Chitin), Chitosan,
poly(3-hydroxyvalerate), poly(lactide-co-glycolide),
poly(3-hydroxybutyrate), poly(4-hydroxybutyrate),
poly(3-hydroxybutyrate-co-3-hydroxyvalerate), polyorthoester,
polyanhydride, poly(glycolic acid), poly(glycolide), poly(L-lactic
acid), poly(L-lactide), poly(D,L-lactic acid), poly(D,L-lactide),
poly(L-lactide-co-D,L-lactide), poly(caprolactone),
poly(L-lactide-co-caprolactone), poly(D,L-lactide-co-caprolactone),
poly(glycolide-co-caprolactone), poly(trimethylene carbonate),
polyester amide, poly(glycolic acid-co-trimethylene carbonate),
co-poly(ether-esters) (e.g. PEO/PLA), polyphosphazenes,
biomolecules (such as fibrin, fibrinogen, cellulose, starch,
collagen, and hyaluronic acid), polyurethanes, silicones,
polyesters, polyolefins, polyisobutylene and ethylene-alphaolefin
copolymers, acrylic polymers and copolymers, vinyl halide polymers
and copolymers (such as polyvinyl chloride), polyvinyl ethers (such
as polyvinyl methyl ether), polyvinylidene halides (such as
polyvinylidene chloride), polyacrylonitrile, polyvinyl ketones,
polyvinyl aromatics (such as polystyrene), polyvinyl esters (such
as polyvinyl acetate), acrylonitrile-styrene copolymers, ABS
resins, polyamides (such as Nylon 66 and polycaprolactam),
polycarbonates, polyoxymethylenes, polyimides, polyethers,
polyurethanes, rayon, rayon-triacetate, cellulose acetate,
cellulose butyrate, cellulose acetate butyrate, cellophane,
cellulose nitrate, cellulose propionate, cellulose ethers, and
carboxymethyl cellulose. Additional representative examples of
polymers that may be especially well suited for use in fabricating
embodiments of implantable medical devices disclosed herein include
ethylene vinyl alcohol copolymer (commonly known by the generic
name EVOH or by the trade name EVAL), poly(butyl methacrylate),
poly(vinylidene fluoride-co-hexafluoropropene) (e.g., SOLEF 21508,
available from Solvay Solexis PVDF, Thorofare, N.J.),
polyvinylidene fluoride (otherwise known as KYNAR, available from
ATOFINA Chemicals, Philadelphia, Pa.), ethylene-vinyl acetate
copolymers, poly(vinyl acetate), styrene-isobutylene-styrene
triblock copolymers, and polyethylene glycol.
[0066] While particular embodiments of the present invention have
been shown and described, it will be obvious to those skilled in
the art that changes and modifications can be made without
departing from this invention in its broader aspects. Therefore,
the appended claims are to encompass within their scope all such
changes and modifications as fall within the true spirit and scope
of this invention.
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