U.S. patent application number 12/282710 was filed with the patent office on 2009-03-19 for method of monitoring positioning of polymer stents.
Invention is credited to Patrick Sabaria.
Application Number | 20090076594 12/282710 |
Document ID | / |
Family ID | 38308646 |
Filed Date | 2009-03-19 |
United States Patent
Application |
20090076594 |
Kind Code |
A1 |
Sabaria; Patrick |
March 19, 2009 |
METHOD OF MONITORING POSITIONING OF POLYMER STENTS
Abstract
The invention is directed to a polymer stent with one or more
markers such that when the stent is placed within a lumen, the
markers can be detected external to the body. The markers can also
be used to monitor the stent position after placement and
absorption of bioabsorbable stents. Further, the stent may comprise
two markers used to determine the diameter of the stent in real
time. It is also contemplated that the stent may comprise at least
three markers. The use of at least three markers enables the three
dimensional orientation of the stent to be determined at any time.
The stent may also comprise markers such that the markers are
located in regions with different in vivo lifetimes. It is also
contemplated that the pattern and material type of markers on the
stent may be used to determine the type of stent within a lumen or
box.
Inventors: |
Sabaria; Patrick; (Saint Nom
La Breteche, FR) |
Correspondence
Address: |
TAROLLI, SUNDHEIM, COVELL & TUMMINO L.L.P.
1300 EAST NINTH STREET, SUITE 1700
CLEVEVLAND
OH
44114
US
|
Family ID: |
38308646 |
Appl. No.: |
12/282710 |
Filed: |
March 12, 2007 |
PCT Filed: |
March 12, 2007 |
PCT NO: |
PCT/IB2007/000588 |
371 Date: |
September 12, 2008 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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60781748 |
Mar 14, 2006 |
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60781747 |
Mar 14, 2006 |
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60781741 |
Mar 14, 2006 |
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60791220 |
Apr 12, 2006 |
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60814533 |
Jun 19, 2006 |
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60854075 |
Oct 25, 2006 |
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Current U.S.
Class: |
623/1.34 ;
128/898; 623/1.15; 623/1.32 |
Current CPC
Class: |
A61B 90/39 20160201;
A61F 2/91 20130101; A61F 2002/91541 20130101; A61L 31/18 20130101;
A61F 2250/0098 20130101; A61F 2210/0004 20130101; A61F 2250/003
20130101; A61L 31/148 20130101; A61F 2/915 20130101; A61F 2/82
20130101; A61F 2002/91558 20130101 |
Class at
Publication: |
623/1.34 ;
623/1.15; 623/1.32; 128/898 |
International
Class: |
A61F 2/06 20060101
A61F002/06; A61B 19/00 20060101 A61B019/00 |
Claims
1-30. (canceled)
31. A polymer stent for implantation within a body lumen of a
patient, said stent comprising: a plurality of struts, a first
predetermined inner diameter in a production state and a second
predetermined diameter in an expanded state; and at least one
marker that is imagable external to the body.
32. The stent of claim 31, wherein the marker is a metal or metal
alloy.
33. The stent of claim 32, wherein the metal or metal alloy
comprises gold.
34. The stent of claim 33, wherein said marker is colloidal
gold.
35. The stent of claim 31, wherein the marker has a thickness in
the range of 1 micron to 20 microns.
36. The stent of claim 31, wherein said marker is deposited onto
the stent by a heated filament under a vacuum or reduced air
pressure.
37. The stent of claim 31, wherein the marker is attached to the
stent by a means selected from the group consisting of: crimping,
folding, tying, melting, use of a knitted mesh, binding by use of a
glue compound, and winding around the polymer in a helical or
zig-zag design.
38. The stent of claim 37, wherein the marker is crimped onto the
stent.
39. The stent of claim 31, wherein the stent is self-expanding.
40. The stent of claim 31, wherein the stent comprises at least two
markers.
41. The stent of claim 40, wherein the at least two markers are
placed such that the length of the stent can be determined.
42. The stent of claim 31, wherein the stent comprises at least
three markers for allowing spatial placement of an unhomogenous
shape of stent.
43. The stent of claim 42, wherein the at least three markers are
placed such that the three-dimensional orientation of the stent can
be determined.
44. The stent of claim 31, wherein the stent comprises at least one
in vivo degradation region.
45. The stent of claim 44, wherein the stent comprises at least two
in vivo degradation regions.
46. The stent of claim 45, wherein the markers are placed upon
stent regions having at least two different in vivo degradation
rates.
47. A method of determining the length of stent placed within a
body lumen of a patient, said method comprising: crimping a first
and second markers upon a stent so that the markers are spatially
oriented such that the markers lie on a line with a component
vector parallel to the longitudinal axis of the stent; placing a
polymer stent having a plurality of struts within a body lumen of a
patient; generating a signal from the first and second markers by
use of a machine external to the body lumen of the patient;
determining the location of the first and second marker relative to
one another; calculating the distance between the first and second
marker by use of a software program.
48. A method of determining the diameter of stent placed within a
body lumen of a patient, said method comprising: crimping a first
and second marker upon a stent so that the markers are spatially
oriented such that the markers lie on a line with a component
vector perpendicular to the longitudinal axis of the stent; placing
a polymer stent having a plurality of struts within a body lumen of
a patient; generating a signal from the two markers by use of a
machine external to the body lumen of the patient; determining the
location of the first and second marker relative to one another;
calculating the distance between the first and second marker by use
of a software program.
49. The method of claim 48, wherein the signal generated is by an
x-ray.
50. The method of claim 48, whereby the distance between the first
and second marker is compared to an ideal distance to find if there
was an error with stent deployment.
51. A method of determining the three dimensional orientation of
stent placed within a body lumen of a patient, said method
comprising: crimping a first and second marker upon a stent so that
the markers are spatially oriented such that the markers lie on a
line with a component vector perpendicular to the longitudinal axis
of the stent; crimping a third marker upon the stent so that the
third marker is spatially oriented such that the third marker lies
on a line with a component vector parallel to the longitudinal axis
of the stent; placing a polymer stent having a plurality of struts
within a body lumen of a patient; generating a signal from the
three markers by use of a machine external to the body lumen of the
patient; determining the location of the first, second and third
marker relative to one another; calculating the distance between
any of the first, second marker and third by use of a software
program.
52. The method of claim 51, whereby the distance between any of the
first, second and third marker is compared to an ideal distance to
find if there was an error with stent deployment.
53. The method of claim 51, whereby the movement of the first,
second and third marker within a body lumen of a patient may be
tracked to determine if the stent is rotating within the lumen.
54. The method of claim 47, wherein said markers are a metal or
metal alloy.
55. The method of claim 54, wherein the metal or metal alloy
comprises gold.
56. The method of claim 47, wherein the marker has a thickness in
the range of 1 micron to 20 microns.
57. The method of claim 47, wherein the stent is
self-expanding.
58. The method of claim 47, wherein the stent has at least one in
vivo degradation region.
59. The method of claim 58, wherein the stent has at least two in
vivo degradation regions.
Description
BACKGROUND OF THE INVENTION
[0001] The use of stents in various surgical, interventional
cardiology, and radiology procedures has quickly become accepted as
experience with stent devices accumulates and as the advantages of
stents become more widely recognized. Stents are often used in body
lumens to maintain open passageways such as in the prostatic
urethra, the esophagus, the biliary tract, intestines, and various
coronary arteries and veins, as well as more remote cardiovascular
vessels such as the femoral artery.
[0002] Stents are often used to treat atherosclerosis, a disease in
which vascular lesions or plaques consisting of cholesterol
crystals, necrotic cells, lipid pools, excess fiber elements and
calcium deposits accumulate in the walls of an artery. One of the
most successful procedures for treating atherosclerosis is
insertion of a deflated balloon within the lumen, adjacent the site
of the plaque or atherosclerotic lesion. The balloon is then
inflated to put pressure on and "crack" the plaque. This procedure
increases the cross-sectional area of the lumen of the artery.
Unfortunately, the pressure exerted also traumatizes the artery,
and in 30-40% of the cases, the vessel either gradually renarrows
or recloses at the locus of the original stenotic lesion. This
renarrowing is sometimes referred to as restenosis.
[0003] A common approach to prevent restenosis is to deploy a
metallic tube or stent to the site of the stenotic lesion. Although
metallic stents have the mechanical strength necessary to prevent
the retractile form of restenosis, their presence in the artery can
lead to biological problems including vasospasm, compliance
mismatch, and even occlusion. Moreover, there are inherent,
significant risks from having a metal stent permanently implanted
in the artery, including erosion of the vessel wall. The stents may
also migrate on occasion from their initial insertion location
raising the potential for stent induced blockage. Metal stents,
especially if migration occurs, cause irritation to the surrounding
tissues in a lumen. Also, since metals are typically much harder
and stiffer than the surrounding tissues in a lumen, this may
result in an anatomical or physiological compliance mismatch,
thereby damaging tissue or eliciting unwanted biologic responses.
In addition, the constant exposure of the stent to the blood can
lead to thrombus formation within the blood vessel. Stents also
allow the cellular proliferation of the injured arterial wall to
migrate through the stent mesh, where the cells continue to
proliferate and eventually lead to the narrowing of the vessel.
Further, metal stents typically have some degree of negative
recoil. Finally, metallic stents actually prevent or inhibit the
natural vascular remodeling that can occur in the organism by
rigidly tethering the vessel to a fixed, maximum diameter.
[0004] Because of the problems of using a metallic stent, others
have recently explored use of bioabsorbable and biodegradable
materials stents. The conventional bioabsorbable or bioresorbable
materials from which such stents are made can be selected to absorb
or degrade over time. This degradation enables subsequent
interventional procedures such as restenting or arterial surgery to
be performed. It is also known that some bioabsorbable and
biodegradable materials tend to have excellent biocompatibility
characteristics, especially in comparison to most conventionally
used biocompatible metals. Another advantage of bioabsorbable and
biodegradable stents is that the mechanical properties can be
designed to substantially eliminate or reduce the stiffness and
hardness that is often associated with metal stents. This is
beneficial because the metal stent stiffness and hardness can
contribute to the propensity of a stent to damage a vessel or
lumen. Examples of novel biodegradable stents include those found
in U.S. Pat. No. 5,957,975 and U.S. application Ser. No.
10/508,739, which is herein incorporated by reference in its
entirety.
[0005] For both metal and polymer stents, however, it is important
to accurately place the stent into the vasculature. To visualize
the stent placement, a metal stent can be coated with a radiopaque
metal to allow real time visualization of the stent by the
cardiologist or interventional radiologist. See, for example, U.S.
Pat. Nos. 5,824,045 and 6,099,561. This allows the medical
professional to track the delivery catheter through the patient's
vasculature and precisely place the stent at the site of a lesion.
Gold can be used as the radiopaque metal because gold is
non-irritating and substantially non-allergic. Further, gold offers
high fluoroscopic visibility in a very thin layer. Use of gold on a
metal stent, however, may also result in an increase in corrosion
where the two metals meet, thus further increasing thrombosis.
[0006] Conventional radiopaque metals, however, have a number of
limitations. Completely coating a stent with the radiopaque metal
may change the size of the stent, resulting in a less than ideal
stent profile. Further, stents are often crimped to a smaller
diameter to allow the stent to be easily inserted into the lumen.
Once the stent is properly placed in the lumen, an inflatable
device expands the stent. In this case, completely coating the
stent with a radiopaque metal creates the risk of cracking the
metal coating, thereby causing portions of the coating to separate
from the underlying substrate. This can create jagged edges on the
stent that inflicts increased physical trauma on the lumen wall
tissue. Further, this may also induce thrombus formation because of
increased turbulence in the blood flow. Finally, any material
released can provide blockage and damage at sites distant from the
initial stent positioning.
[0007] Because polymeric stents are not radiopaque, there is no an
ideal solution for determining the location, three-dimensional
orientation and expansion of the stent in real time.
SUMMARY OF THE INVENTION
[0008] The present invention is directed to a polymer stent that
comprises one or more markers such that when the stent is placed
within a lumen, the markers can be detected external to the body.
Examples of methods to detect the marker may include, but is not
limited to, x-ray or other electromagnetic radiation detection
method, magnetic resonance imaging (MRI), and ultrasound.
[0009] The markers may be used to track the location of the stent
as it travels through the body. This greatly assists the physicians
in determining if the stent is traveling the correct path through
the vasculature. This further assists the physician in placing the
stent at the correct site within the lumen. In some embodiments,
these markers can also be used to monitor the stent position after
placement and to monitor absorption of bioabsorbable stents.
[0010] In certain embodiments, it is contemplated that the stent
may comprise at least two markers placed such that the diameter of
the stent may be determined in real time. This feature helps to
determine if a crimped stent has been properly expanded. The
placement of such markers may also determine at any time if the
diameter of the stent has increased or decreased.
[0011] In certain embodiments, it is also contemplated that the
stent may comprise at least three markers. The use of at least
three markers enables the three dimensional location of the stent
to be determined at any time. This feature can be used to determine
if the stent has a rotational motion within the lumen. Rotational
motion of the stent within the lumen is disfavored because it
increases blood flow turbidity, which increases thrombus
formation.
[0012] In certain embodiments, it is also contemplated that the
stent may comprise markers such that the markers are located in
regions with different in vivo lifetimes. Stent regions with
different in vivo lifetimes means that the in vivo lifetime of the
region is predetermined and found to be different from the in vivo
lifetime of a different region. This feature enables one to
determine the degradation pattern of the stent in real time.
[0013] In certain embodiments, it is contemplated that the pattern
and material type of markers on the stent may be such that one can
determine the type of stent inserted within a lumen or within a
box. This feature may greatly assist in determining and monitoring
what type of stents is located within a package as the packages
travel through the supply chain. This feature may also assist in
determining what type of stent is located within a person
post-implantation.
[0014] The marker may be any material that is visible within the
body by an external means, including but limited to x-ray and MRI.
In one embodiment, the stent of the present invention achieves MRI
visibility by use of a marker that generates a magnetic
susceptibility artifact such as a paramagnetic, ferromagnetic,
non-ferromagnetic, ferromagnetic, or superparamagnetic substance.
In another embodiment, the test of the present invention achieves
visibility by x-ray by use of a radiopaque marker.
[0015] The markers may be applied to the stent in any number of
ways for insertion or use in the body, including but limited to,
application as a ribbon that is crimped onto a strut of the stent
and a partially sputter heavy metal coating.
DESCRIPTION OF THE FIGURES
[0016] FIG. 1 illustrates a stent comprising one marker.
[0017] FIG. 2 illustrates a stent comprising two markers placed
such that the diameter of the stent can be determined.
[0018] FIG. 3 illustrates a stent comprising three markers placed
such that the three-dimensional orientation of the stent can be
determined.
DETAILED DESCRIPTION OF A PREFERRED EMBODIMENT
[0019] It will be appreciated by those skilled in the art that
although the following Detailed Description will proceed with
reference being made to preferred embodiments, the present
invention is not intended to be limited to these embodiments.
[0020] In one embodiment, the present invention is directed to a
polymer stent that comprises at least one marker, where the marker
is provided to track the stent during its placement within the
body. The stent of the present invention can have virtually any
configuration that is compatible with the body lumen in which it is
implanted for the purpose of repairing the same. Typically, stents
are composed of an intricate geometric pattern of circumferential
and longitudinally extending members. These elements are commonly
referred to as struts.
I. Detectable Marker
[0021] The markers can be made of any material that may be detected
external to the body. The only limitation on the type of marker
used is that it be visible by external means and may be released
safety from the stent as the stent degrades. If the marker is
involved in the arterial remodeling, it may be retained by the body
at the location of its initial placement. It is readily understood
that many factors must be weighed in considering what marker will
be used.
[0022] In one embodiment, the marker is detected by MRI. An ideal
marker detectable by MRI would be one that generates a magnetic
susceptibility artifact such as a paramagnetic, ferromagnetic,
non-ferromagnetic, ferromagnetic, or superparamagnetic substance.
If the marker is metal, then it may be, but is not limited to,
ruthenium, rhodium, osmium, silver, palladium, platinum, lead, tin,
uranium, molybdenum, brass, copper, tungsten, tantalum, gold, or
other paramagnetic or ferromagnetic metals, gadolinium salts,
gadolinium complexes, Gd-DTPA (gadolinium
diethylenetriaminepentacetic acid), gadopentetate dimeglumine,
compounds of copper, nickel, manganese, chromium, dysprosium and
gadolinium. The marker may also contain organic components, such as
a heme or porphyrin ring.
[0023] If the stent is to be viewed via x-ray, then the marker used
may be any appropriate radiopaque material, including but not
limited to, powder of barium sulfate, bismuth subcarbonate, bismuth
trioxide, bismuth oxychloride, tungsten, tantalum, iridium, gold,
platinum, palladium or other dense metal. Such radiopaque materials
include particles of an iodinated contrast agent and bismuth salts.
It is preferred that the radiopaque marker be a metal with a high
atomic number element, preferably from the row of the periodic
table coincident with the third row of the transition metal
block.
[0024] The marker may be made by any means. If the marker is a
metal, for example, gold, then the marker may be made by
mechanically deforming the metal to form a sheet layer or ribbon.
Examples of methods to mechanically deform the metal include, but
are not limited to, rolling at a high temperature until a desired
thickness of the layer is reached, folding the metal, and pounding
the metal with heavy objects, heating the metal until the metal
melts, then pouring the metal into a mold. If the metal is made
into a sheet layer, then it may be cut by any means into any form
that conforms to the invention.
[0025] It is further understood that the marker may be applied to
the stent by any means. If the marker is a ribbon, then it may be
placed onto the stent by any means. Preferably, the marker is a
ribbon that is crimped upon a strut of the polymer after the stent
is formed. Examples include, but are not limited to, crimping,
folding, tying, melting, use of a knitten mesh, binding by use of a
gluing compound, and winding around the polymer in a helical or
zig-zag design. The application of the marker is only limited by
the coefficients of expansion. The marker should be such that the
coefficient of expansion of the stent is not significantly altered
by the application of the marker.
[0026] Other methods contemplated for adding the marker to a
polymer material include dip coating the marker onto the polymeric
structure of a stent. Moreover, the marker, alone or blended with
other materials, can be added to the surface of a device by way of
a plasma spray or etch or by employing thermal pressure or heat and
pressure. Steriolithography and blow molding are other contemplated
approaches. In addition, the marker can be mixed with a
biocompatible epoxy resin, whereby the marker is blended with
another material and coated to the inner diameters, outer diameter
or sides of structures defining the stent. The marker can also be
chemically bonded to portions of the polymers used in the stents
before or after manufacture of the stent. In any event, the metal
marker can be applied to an entire surface of a device or in a
partial, spot-like manner or as stripes or a series of spots or
stripes, or any other combination. Further, it is also contemplated
to use more than one type of marker, whereby each type of marker is
separately detected by external means.
[0027] In addition, the marker may be of any thickness as long as
the thickness does not alter the coefficient of expansion of the
stent. Preferably, the marker thickness is approximately 0.25 to 30
microns. More preferably, the marker thickness is approximately 5
microns.
[0028] It is further contemplated that a polymeric stent may be
made radiopaque by any means. For instance, one or more radiopaque
materials may be introduced into the polymer solution before the
stent is manufactured. In addition, to visualize the stent
placement, a polymeric stent can be coated with a radiopaque
material to allow real time visualization of the stent by the
cardiologist or interventional radiologist. In this situation, it
is preferred that the radiopaque material not flake off the
polymeric material and have a coefficient of expansion that is
consistent with the stent coefficient of expansion, thereby
allowing both materials to expand equally.
[0029] Finally, it is contemplated that the marker is placed on the
stent to form a pattern such that one can determine the type of
stent inserted within a lumen or within the pre-surgery packaging
of the stent. The pattern can be a geometric one, or a pattern of
using different markers on the same stent, such as gold and
platinum, which will provide a unique marker signature. This
feature may greatly assist in determining what type of stent is
located within a crate as the stent travels through the supply
chain. This feature may also assist in determining what type of
stent is located within a person post-surgery.
II. Stent Fabrication and Properties
[0030] The stents may be formed from any biodegradable,
biocompatible, bioresorbable polymer, preferably a thermoplastic
polymer. As used herein, a bioresorbable polymer is one whose
degradative products are metabolized in vivo or excreted from the
body via natural pathways. The polymer of the stent can be a
homopolymer or a copolymer. Preferably, the stent is formed from a
thin layer of one or more amorphous, bioresorbable polymers, i.e.,
the polymers used to form the stent preferably are not crystalline.
It is also preferred that the polymers used to form the stent do
not generate crystalline residues upon degradation in vivo. It is
also contemplated that the chains of the polymer may be or may not
be cross-linked. Light cross-linking, however, is acceptable
provided that thermal and viscoelastic characteristics that allow
education, crimping, and deployment of the device are sufficiently
maintained.
[0031] Appropriate biodegradable polymers may include, but are not
limited to, poly(L-lactide), polyglycolide, poly(D,L-lactide),
copolymers of lactide and glycolide, polycaprolactone,
polyhydroxyvalerate, polyhydroxybutyrate,
polytrimethylenecarbonate, polyorthoesters, polyanhydrides, and
polyphosphazenes. Examples of the types of preferred polymers for
the stent of the present invention include, but are not limited to,
lactic acid-based stereocopolymers (PLAx copolymers composed of L
and D units, where X is the percentage of L-lactyl units)
(55<Tg<60), copolymers of lactic and glycolic acids (PLAxGAy,
where X, the percentage of L-lactyl units, and Y, the percentage of
glycolyl units, are such that the Tg of the copolymer is above
45.degree. C.), and Poly(lactic-co-glycolic-co-gluconic acid) where
the OH groups of the gluconyl units can be more or less substituted
(pLAxGayGLx, where X, the percentage of Llactyl units, and Y, the
percentage of glycolyl units, and Z the percentage of gluconyl
units are such that the Tg of the polymer is above 45.degree. C.).
Other suitable polymers include, but are not limited to, polylactic
acid (PLA), polyglycolic acid (PGA) polyglactin (PLAGA copolymer),
polyglyconate (copolymer of trimethylene carbonate and glycolide,
and a copolymer of polyglycolide or lactide acid or polylactic acid
with .epsilon.-caprolactone), provided that the polymer has a glass
transition temperature, Tg, of at least 45.degree. C. or
greater.
[0032] In one preferred embodiment, the stent comprises a
polylactic acid stereocopolymer produced from L and DL lactides.
The polymer is designated herein as "PLAX" where X represents the
percentage of the L-lactic acid units in the mixture of monomers
used to prepare the lactides. Preferably X is in the range of 10 to
90, more preferably 25 to 75. In another preferred embodiment, the
stent comprises a poly-lactic acid, glycolic acid copolymer
produced from L and DL lactides and glycolides. The polymer is
designated herein as "PLAXGAY" where Y represents the percentage of
glycolic acid units in the mixture of monomers used to prepare the
copolymers. Preferably, the copolymers do not contain glycolyl
repeating units since such units are known to be more inflammatory
than lactyl repeating units. Preferably, the polymers are prepared
using Zn metal or Zn lactate as initiator. To ensure good initial
mechanical properties of the stent, the molecular weight of the
polymer in the region having the second in vivo lifetime is
preferably above 20,000 daltons, more preferably 100,000 daltons or
larger. The polydispersity, I=Mw/Mn, is preferably below two and
should not greatly reflect the presence of low molecular weight
oligomers smaller than 2,000 daltons as determined by size
exclusion chromatography. Optionally, the polymeric layer used to
make the stent may be impregnated with an anticoagulant agent, such
as heparin, anti-oxidants, such as vitamin E, compounds that
regulate cellular proliferation, or anti-inflammatory drugs, such
as corticosteroids, to provide localized drug delivery. Such drugs
are incorporated into the polymeric layer or coated on the layer
using techniques known in the art. Agents may also be incorporated
into the base polymer that forms the body of the stent, as long as
the incorporation does not have significant adverse effects on
stent desired physical characteristics such as radial stent
deployment and degradation time. For intravascular stents, it is
preferred that the film have a thickness of from about 0.05 mm to
0.2 mm.
[0033] It is contemplated that the stent may be made by any method.
In one preferred embodiment, the stent is a formed from a
biodegradable polymeric band comprising a head having a slot and a
tongue comprising a catch or locking mechanism proximate the
longitudinal edge thereof. The cylindrical element, which has an
inner and outer surface, is formed by inserting a portion of the
tongue through the slot to provide a cylindrical element having a
first reduced diameter configuration. Following deployment, the
cylindrical element is in a second expanded diameter configuration
wherein the distal catch mechanism engages the inner surface of the
head and prevents radial collapse or recoil of the polymeric stent.
In a second preferred embodiment, the stent is formed from a
plurality of interconnected polymeric bands each of which comprises
a head having a slot and a tongue comprising a catch mechanism
proximate the longitudinal edge thereof.
[0034] In one embodiment, the stent is formed by laser cutting of a
cylindrical tube. In another embodiment, the stent is formed by
laser cutting a flat polymeric sheet in the form of the stent, and
then rolling the pattern into the shape of the cylindrical stent
and providing a longitudinal weld to form the stent. In another
embodiment, the stents are created by chemically etching a flat
polymeric sheet and then rolling and welding it to form the stent,
or coiling a polymeric wire to form the stent.
[0035] In another preferred embodiment, the stent may also be
formed by molding or injection molding of a thermoplastic or
reaction injection molding of a thermoset polymeric material. The
flat grid is then rolled and extremities are welded or glued to
form a cylinder. 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. In other embodiments,
the stent is formed as a cylindrical tube and then a pattern is cut
with a laser or other device.
[0036] Generally, the struts are arranged in patterns that are
designed to contact the lumen walls of a vessel and to maintain
patency of the vessel thereby. A myriad of strut patterns are known
in the art for achieving particular design goals.
[0037] It is contemplated that a crimped stent may incorporate
slits or open spaces to allow for the temporary reduction in
diameter of the cylindrical tube without substantially altering the
wall thickness. Moreover, a stent embodying the present invention
can include teeth and corresponding catching structure that
operates to maintain an expanded form. Moreover, polymer based
stents embodying structure defined by a wire or ribbon coil or
helix or a knitted mesh configuration are possible examples of
self-expanding stents. Other important design characteristics of
stents include radial or hoop strength, expansion ratio or coverage
area, and longitudinal flexibility. One strut pattern may be
selected over another in an effort to optimize those parameters
that are of importance for a particular application.
[0038] It is also contemplated that the biodegradable stent may
have a programmed pattern of in vivo degradation. Stent polymeric
structure allows for differential speed degradation. See, for
example, U.S. Pat. No. 5,957,975, the entirety of which is
incorporated by reference. In one embodiment, the stent comprises
at least one substantially cylindrical element having two open ends
and a plurality of regions circumferentially spaced around the
cylindrical element and extending from one open end to the other
open end of the cylindrical element. Each of the regions is
configured or designed to have a desired in vivo lifetime. At least
one of the regions is designed to have a shorter in vivo lifetime
than the other region or regions. This means that the region having
the shorter in vivo lifetime degrades sooner after deployment than
the regions having a longer in vivo lifetime. Thus, when stents
designed in accordance with the present invention are deployed
within the lumen of a vessel of a patient, the cylindrical element
acquires one or more fissures which extend from one open end of the
cylindrical element to the other open end of the cylindrical
element within a desired, predetermined period of time after the
stent is deployed in the patient. It has been determined that such
fragmentation within a predetermined period of time after
deployment allows for enlargement of the lumen of the vessel via
the process of arterial remodeling.
[0039] The regions of the stent with the different in vivo
lifetimes can be made in a variety of ways. Preferably, such stents
are made by producing regions having a first in vivo lifetime,
i.e., a shorter in vivo lifetime, in a polymeric layer having the
predetermined second, or longer, in vivo lifetime. The regions
having the first in vivo lifetime are produced by heating the
respective regions of the polymeric layer having a second in vivo
lifetime for a time and at a temperature sufficient to cause local
partial degradation of the polymeric chains. Such treatment, which
can be accomplished using a piloted hot needle, laser beam, or flow
of hot air, renders the polymer in the heated region more sensitive
to hydrolytic degradation. The regions can also be designed with
struts of differing thickness where the degradation is thickness
dependent. Alternatively, the regions having a first in vivo
lifetime may be produced in a polymeric layer having a second in
vivo lifetime by incorporating a sufficient number of acidic ions
into the respective regions of the polymeric layer. Preferably, the
acidic ions are provided by compounds that are not soluble in
blood.
[0040] Regions having a first in vivo lifetime can also be produced
in a polymeric film having a second in vivo lifetime by exposure of
the respective regions to beta radiation or gamma radiation for a
sufficient time to induce partial cleavage of the polymeric chains
within the respective regions. Provided the polymeric layer has a
thickness of less than 0.3 mm, regions having a first in vivo
lifetime can also be produced in a polymeric film having a second
in vivo lifetime by introducing areas of mechanical weakness into
the polymer. One method of introducing mechanical weakness is by
reducing the thickness of the polymer in the respective region or
forming holes therein. Regions having a first in vivo lifetime can
also be produced in a polymeric film having a second in vivo
lifetime by applying mechanical stress to the respective region.
However, this latter process is difficult to control and, thus, is
less preferred. Differing lifetimes can also be created by
providing one or more different coatings over different regions of
the biodegradable stent.
[0041] Another method for producing a polymeric layer in which one
region or a plurality of spaced apart regions have a first in vivo
lifetime and other regions have a second in vivo lifetime is to
incorporate strips or fibers of a faster degrading bioresorbable
polymer into a film made from a slower degrading polymer. For
example, a mesh or a parallel array of fibers or strips of PGA or
any other faster degrading bioresorbable polymer can be embedded
into the respective regions of a polymeric film of PLA that may be
designed to be slower degrading. Embedding can be achieved by
inserting the mesh or fibers between two melted sheets of the
slower degrading polymer. Provided the relative solubilities are
compatible, the fibers or mesh can be placed in an organic solution
of the slower degrading polymer and the desired polymeric film
formed by evaporation of the organic solvent. One example of a
method for embedding a mesh made from one polymer into a polymeric
layer made from a second polymer is described in U.S. Pat. No.
4,279,249 issued to Vert et al. on Jul. 21, 1981, which is
specifically incorporated herein by reference. A stent having the
desired shape and orientation of regions is then formed from the
polymeric layer by standard techniques such as stamping, employing
a laser beam, or any other technique used in the art to tool a
polymeric film.
[0042] The initial polymeric cylindrical device that is formed by
any of these processes can be configured to have the final
predetermined shape, length, wall thickness and diameter, all of
which are tailored to the application for which the stent is to be
utilized. For example, for cardiovascular applications the initial
polymeric device that is formed by these processes can have a final
predetermined length ranging from 0.5 cm to approximately 3 cm. For
certain applications, the initial polymeric cylindrical device can
have a final, predetermined diameter ranging from 0.50 mm to 8.0 mm
with a final, predetermined wall thickness ranging from 0.05 to 0.5
mm. Alternatively, the initial cylindrical device that is formed by
any of these processes can have a smaller diameter than the final
predetermined diameter.
[0043] In those instances where the initial polymeric cylindrical
device has a smaller diameter than the final predetermined
diameter, slits or openings are formed in the cylindrical device as
described above, and then the cylindrical device is deformed or
expanded to the final shape and diameter. This can be achieved by
inserting an expandable device such as a balloon into the
stent.
[0044] The length, diameter, and strut thickness of the stent can
be of any size. However, it is contemplated that these parameters
will be limited by the performance features desired. Further, the
stent maybe used for any tubular body structure, including but not
limited to, coronary, neurological, carotid, renal, iliac, biliary,
aortic, femoral, or other peripheral indication.
III. Education and Crimping the Stent
[0045] While it is at the final predetermined shape, size, and
diameter, the cylindrical device is educated by heating the device
to a temperature above the Tg of the polymer from which the device
is formed. The device is heated for a time sufficient to erase any
former process-related memory and to impart a new memory of the
final predetermined shape and diameter to the polymeric cylindrical
device. It is believed that such conditions allow the polymer
chains to relax and reorganize themselves from an entanglement
typical of the former processing stages to an entanglement typical
of the high temperature at which the cylindrical device is
compatible with the final or deformed shape and size. When the
polymeric cylindrical device has an initial diameter that is less
than the final predetermined diameter, it is desired to heat to a
temperature well above the Tg of the polymer. This heating step
erases the anisotropic stresses promoted by the extrusion or
molding process and the former processing-related memory of the
polymer chains. Good results have been obtained by heating a
laser-precut polymeric cylindrical device formed from PLA75 and
deformed from a diameter of 1.0 mm to 4 mm at a temperature of
80.degree. C. for 30 minutes. Temperatures of from about 45.degree.
C. to about 120.degree. C. and times of 5 minutes or more should be
suitable for educating stents made from PLAx with 0<x<100,
PLAxGAy with 0<X<25 and 75<Y<100, or any
PLAxGAyGLz.
[0046] The polymeric cylindrical device is then crimped. "Crimping"
as used herein refers to a process that involves radial pressing on
a polymeric cylindrical device having slits, or openings in the
wall thereof to allow a decrease in the diameter of the device
without substantially affecting the thickness of the wall or struts
of the cylindrical device. Such process may also result in an
increase in length of the cylindrical device. Examples of crimping
may be found in U.S. application Ser. No. 10/541,421, which is
incorporated by reference.
[0047] To crimp the educated cylindrical device, it is mounted onto
a device with a smaller diameter. The diameter of the educated
cylinder is reduced by heating the cylinder to a temperature below
the Tg of the polymer while evenly applying pressure on the
exterior surface of the wall of the cylindrical device.
[0048] In some embodiments, the polymeric stent is crimped onto an
inflatable device such as an inflatable balloon catheter. In this
instance, the stent assembly after crimping comprises an inflatable
balloon catheter and an expandable, educated, polymeric stent
snugly and stably disposed thereon. Slits or open spaces that allow
for a reduction in diameter of the cylindrical device without
substantially altering the wall thickness during crimping are
incorporated into the cylindrical device prior to the time the
cylindrical device is crimped on the inflatable balloon catheter.
The temperature at which the cylindrical device is heated during
crimping is high enough to allow reduction in diameter of the
cylindrical device but low enough to not erase the memory of the
final predetermined shape and diameter of the educated cylindrical
device. Ideally, the temperature is less than the glass transition
state of the polymer. More preferably, the temperature is at about
50.degree. C. Thus, the temperature at which the educated
cylindrical device is heated during crimping is less than the
temperature at which the cylindrical device is heated during
education of the cylindrical device. Further, the time it takes to
crimp the educated cylindrical device can vary, depending upon the
temperature, size and composition of the stent
[0049] In accordance with the present method, expansion of the
polymeric stent can be achieved by any means. In one embodiment, a
balloon is used merely as a carrier for the stent through the body.
In this preferred embodiment, the stent expansion occurs by the
positive recoil properties of the stent; thus, the expansion is
balloon inflation independent. In another preferred embodiment, a
balloon is inflates and/or heated to initiates the stent expansion.
It is contemplated that the positive recoil properties of the stent
would expand the stent to its final predetermined diameter. The
temperature used to initiate the stent expansion may be any
temperature at or below the Tg of the polymer. In a less preferred
embodiment, a balloon is inflated to expand the polymeric stent to
its final predetermined shape.
[0050] In another aspect, the method of the present invention
starts with a polymeric tube whose diameter initially is less than
the final predetermined diameter. Such tube is first heated to a
temperature close to or above the Tg of the polymer and expanded to
provide a cylindrical device whose diameter is equal to the final
desired diameter. Thereafter the cylindrical device is educated as
described above to provide an educated cylindrical device having a
memory of the final predetermined shape and diameter, and then
crimped on a balloon catheter as described above to provide an
assembly comprising the balloon catheter and an expandable,
educated, polymeric stent snugly and stably disposed thereon.
[0051] The present invention also provides an assembly comprising
an inflatable balloon catheter and a polymeric stent prepared in
accordance with the present method.
[0052] Advantageously, the stent of the present invention exhibits
little to no relaxation-related negative recoil when deployed in
the blood vessel of a subject. Advantageously, the assembly of the
present invention has a diameter that allows it to be easily
inserted into a blood vessel of the subject and advanced to a
target site. Advantageously, the stent of the present invention
exhibits expansion (positive recoil) and adaptation to the geometry
of the artery when the stent is not fully deployed up to its final
diameter during deployment. Positive recoil over several days will
create outward radial pressure for long periods of time. This
outward radial pressure aids in positive vascular remodeling by
assisting stabilizing the injured artery, assist in cellular
progress to repair injury of original acute expansion, assist in
security of tissue flaps, and the like.
[0053] In addition, the stent of the present invention is stably
disposed on the balloon, meaning that a mechanical restraint is not
required to prevent the stent from rapidly expanding to its final
diameter during storage at room temperature. Thus, although not
required, the assembly of the present invention, optionally, also
comprises a retractable sheath covering the exterior surface of the
stent. Such sheath serves to prevent deformation of the stent and
preclude or slow expansion during storage.
IV. Stent Placement and Tracking
[0054] The stent may be implanted within the body by any means. For
instance, it is contemplated that stent of the invention is mounted
upon a catheter having a lumen and an inflation member such as a
balloon. The stent and catheter are inserted into the lumen of an
arterial wall, duct, or other tubular body structure. The stent may
be expanded by any means. After expansion, the stent remains within
the body to provide radial support for the treated tubular body
structure. For instance, the stent may be used to repair an
arterial dissection, or an intimal flap, both of which are commonly
found in the coronary arteries, peripheral arteries and other
vessels.
[0055] However, in all cases, the placement of the stent must be
accurate. Therefore, it is critical that the markers on the stent
be sufficiently visible external to the body so that the physician
can visually locate the stent during the implantation procedure.
Because the stent of the present invention can be made visible
under, for example, x-ray and MRI, it gives the physician the
option of selecting the imaging modality most appropriate for the
procedure. It is preferred that the movement of the stent can be
detected by the physician in real time as the stent is advanced
through the vessel or duct. By knowing the exact location and
orientation of the stent at any time, the physician can advance to
the stent to the area of the lumen that requires the stent. One
embodiment is show in FIG. 1, where by stent (B) comprises one
marker (A) which is crimped onto one strut of the stent.
[0056] The stent may be delivered to the lumen of the vessel or
duct by any means. In one embodiment, an assembly comprising the
stent with the markers of the present invention is mounted on an
expandable catheter, preferably a balloon catheter, is
percutaneously introduced into a vessel. Optionally, if the stent
is provided with a membrane that keeps the stent secured to the
balloon catheter, the stent may be heated for a time to a
temperature sufficient to provide greater malleability to the
stent. The catheter is advanced with the aid of a guidewire and
under fluoroscopic control to the site of the stenotic lesion. The
balloon and stent are then disposed within the constricted portion
of the vessel.
[0057] After the stent and balloon are delivered to the locus of
the stenotic lesion, the optional membrane is removed. The balloon
is first heated and then inflated to expand the stent from the
first configuration that has a reduced diameter to a second
configuration having an enlarged diameter greater than or equal to
the interior of the passageway wall so that the stent abuts the
wall of the vessel. The diameters of the cylindrical element depend
on the size of the passageway into which the stent is introduced.
Typically, for coronary arteries, the reduced diameter of the
cylindrical element prior to deployment is from about 0.5 to about
1 mm and expanded diameter after deployment is from about 3 mm to
about 5 mm.
[0058] It is further contemplated that fracturing of the plaque and
deployment of the stent may be done concurrently. In such cases,
the balloon is inflated to a pressure of about 8 to 12 atmospheres
to crack the plaque and expand the stent. Alternatively, the vessel
may be pre-dilated using angioplasty without the stent. Thereafter,
the stent is introduced into the desired site on a separate
expandable catheter, preferably a balloon catheter.
[0059] After the stent is positioned at the site but before
expansion, the stent is heated to a temperature greater than the
glass transition temperature of the polymers used to form the
stent. Heating is for less than 30 seconds, preferably less than 10
seconds. Heating of the stent prior to expansion thereof makes the
stent more malleable and avoids development of unprogrammed
ruptures in the stent. Heating prior to expansion also permits the
tongue to go through the slot without breaking, thereby avoiding
damage to the locking mechanism. Such heating also gives the
polymeric stent a second memory of the second expanded diameter
configuration. Such second memory aids in preventing radial
collapse of the stent before the time period defined by the first
in vivo lifetime. Suitable methods for heating the stent during or
after expansion include, for example, use of a laser balloon or a
radiofrequency balloon.
[0060] In another preferred embodiment, the stent comprises at
least two markers placed such that the length of the stent can be
determined. The length of the stent may be determined by examining
the location of the two markers relative to one another. The
determination of the length may be done by any mean, including but
not limited to, complex algorithms and software programs. The
length of the stent may then be compared to the ideal length of the
stent to find if there was any error or issue with the stent
deployment.
[0061] In another preferred embodiment, the stent comprises at
least two markers placed such that the diameter of the stent can be
determined. For instance, FIG. 2 illustrates a stent (B) comprising
two markers (A) crimped onto the struts of the stent. The two
markers (A) placed such that the diameter (X) can be determined.
The diameter of the stent may be determined by examining the
location of the two markers relative to one another (X). The
determination of the diameter may be done by any mean, including
but not limited to, complex algorithms and software programs. The
diameter of the stent may then be compared to the ideal diameter of
the stent to find if there was any error or issue with the stent
deployment.
[0062] In one preferred embodiment, to determine the length of
stent placed within a body lumen of a patient, a first and second
marker are upon the struts of a stent so that the markers are
spatially oriented such that the markers lie on a line with a
component vector parallel to the longitudinal axis of the stent.
The polymer stent is then placed within a body lumen of patient and
a signal is generated using a machine external to the body lumen.
The location of the first and second marker is determined relative
to one another and the distance between them is calculated by a
software program or algorithm. This method may also be used to
determine the diameter of the stent within the body lumen by
crimping the first and second marker so that they lie on a line
with a component vector perpendicular to the longitudinal axis of
the stent.
[0063] Once expanded, the stents are ideally retained in position
by friction with the inner wall of the vessel and the memory
imparted by heating the stent prior to expansion. However, it is
also recognized that the three dimensional orientation of a stent
with at least three markers can be determined. In one embodiment,
the three dimensional orientation of the stent may be determined by
crimping a first and second marker upon a stent so that the markers
are spatially oriented such that the markers lie on a line with a
component vector perpendicular to the longitudinal axis of the
stent, and then crimping a third marker upon the stent so that the
third marker is spatially oriented such that the third marker lies
on a line with a component vector parallel to the longitudinal axis
of the stent. For example, FIG. 3 illustrates a stent (B)
comprising multiple markers (A) that are crimped onto a strut of
the stent. The multiple markers (A) are placed such that they have
a different X, Y and Z orientation from each other. By examining
the positioning of the markers (A) to one another, one can
determine the X, Y and Z coordinates of the stent to find the three
dimensional location. Once the three dimensional location is
determined, one can find if the stent is correctly retained in
position or if the stent is rotating within the lumen. Rotation
within the lumen is disfavored as the rotation may increase blood
flow turbidity and thus increase thrombis formation. Further, the
determination of the three-dimensional orientation of the stent may
be done by any means, including but not limited to, complex
algorithms and software programs.
[0064] It is further contemplated that the markers may be placed
such that the in Vivo lifetime of the stent regions can be
determined. For instance, in one preferred embodiment the markers
are placed within different regions of the stent. In some
embodiments, the gold foil or marker can be placed under mechanical
tension due to the attachment to the stent walls. As the regions
degrade, the markers assume orientation that differ from their
original placement. Thus, examining the marker placement over time
can show the pattern of degradation of the stent in vivo.
Eventually, when the regions having the first in vivo lifetime are
degraded, the stent is fragmented and the regions having a second
in vivo lifetime are entrapped within the arterial intima.
* * * * *