U.S. patent application number 10/662223 was filed with the patent office on 2004-04-01 for stent mounting device.
Invention is credited to Pacetti, Stephen D., Villareal, Plaridel K..
Application Number | 20040060508 10/662223 |
Document ID | / |
Family ID | 29737289 |
Filed Date | 2004-04-01 |
United States Patent
Application |
20040060508 |
Kind Code |
A1 |
Pacetti, Stephen D. ; et
al. |
April 1, 2004 |
Stent mounting device
Abstract
A stent mounting device and a method of coating a stent using
the device are provided.
Inventors: |
Pacetti, Stephen D.; (San
Jose, CA) ; Villareal, Plaridel K.; (San Jose,
CA) |
Correspondence
Address: |
Paul J. Meyer, Jr.
Squire, Sanders & Dempsey L.L.P.
Suite 300
1 Maritime Plaza
San Francisco
CA
94111
US
|
Family ID: |
29737289 |
Appl. No.: |
10/662223 |
Filed: |
September 12, 2003 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10662223 |
Sep 12, 2003 |
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09896000 |
Jun 28, 2001 |
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6673154 |
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Current U.S.
Class: |
118/264 ;
118/205; 118/232 |
Current CPC
Class: |
B05D 1/002 20130101;
B05B 13/0442 20130101 |
Class at
Publication: |
118/264 ;
118/205; 118/232 |
International
Class: |
B05C 001/00; B05C
011/00 |
Claims
What is claimed is:
1. An apparatus for supporting a stent during a process of coating
the stent, comprising: a member for supporting a stent during the
coating process, wherein a section of the member includes a porous
surface capable of receiving the coating substance during the
coating process.
2. The apparatus of claim 1, wherein the pores have a diameter
between about 0.2 microns and about 50 microns.
3. The apparatus of claim 1, wherein the member includes a first
member for making contact with a first end of the stent and a
second member for making contact with a second end of the stent and
wherein the pores are located on at least a region of the surface
of the first or second members.
4. The apparatus of claim 3, wherein the first or second member is
made from a metallic material selected from a group of 300 Series
stainless steel, 400 Series stainless steel, titanium, tantalum,
niobium, zirconium, hafnium, and cobalt chromium alloys.
5. The apparatus of claim 3, wherein the first or second member is
made from a polymeric material.
6. The apparatus of claim 5, wherein the polymeric material is
selected from a group of regenerated cellulose, cellulose acetate,
polyacetal, polyetheretherketone, polyesters, highly hydrolyzed
polyvinyl alcohol, nylon, polyphenylenesulfide, polyethylene,
polyethylene terephthalate, polypropylene, and combinations
thereof.
7. The apparatus of claim 3, wherein the first or second member is
made from a ceramic material selected from a group of zirconia,
silica, glass, sintered calcium phosphates, calcium sulfate, and
titanium dioxide.
8. The apparatus of claim 3, wherein the first and second members
have inwardly tapered ends that penetrate at least partially in the
first and second ends of the stent and are in contact with the
first and second ends of the stent.
9. The apparatus of claim 3, additionally comprising a third member
for extending within the stent and for securing the first member to
the second member.
10. The apparatus of claim 9, wherein the outer surface of the
third member does not make contact with the inner surface of the
stent.
11. The apparatus of claim 1, wherein the member includes a first
member for making contact with a first end of the stent, a second
member for making contact with a second end of the stent, and a
layer disposed on the surface of the first or second member to
absorb coating material that comes into contact with the layer.
12. A mounting assembly for supporting a stent during the
application of a coating composition onto the stent, comprising: a
support member including means for receiving and containing the
excess coating composition applied to the stent during the
application process.
13. The mounting assembly of claim 12, wherein the means is defined
by a plurality of pores made on a selected region of the support
member.
14. The mounting assembly of claim 12, wherein the support member
includes a first member for supporting a first end of the stent and
a second member for supporting a second end of the stent and
wherein the surface of the first or second member includes
cavities.
15. The mounting assembly of claim 14, wherein the support member
additionally includes a third member for extending within the stent
and for securing the first member to the second member and wherein
the distance between the first member and the second member can be
adjusted by inserting the third member deeper into the first member
or the second member.
16. The mounting assembly of claim 12, wherein the support member
includes a first member for supporting a first end of the stent, a
second member for supporting a second end of the stent, and a layer
disposed on the surface of the first or second member to absorb
coating material that comes into contact with the layer.
17. A method of coating a stent, comprising: positioning a stent on
a mounting assembly, wherein a section of the mounting assembly
includes a porous surface; and applying a coating composition to
the stent, wherein at least some of the coating composition that
overflows from the stent is received by the pores.
18. The method of claim 17, wherein the mounting assembly includes
a first member for making contact with a first end of the stent and
a second member for making contact with a second end of the stent
and wherein the pores are located on at least a region of the
surface of the first or second members.
19. The method of claim 17, additionally comprising at least
partially expanding the stent prior to the act of applying.
20. The method of claim 17, wherein the coating composition
includes a solvent, a polymer dissolved in the solvent, and
optionally a therapeutic substance.
21. The method of claim 17, additionally comprising rotating the
stent about the longitudinal axis of the stent during the act of
applying.
22. The method of claim 17, additionally comprising moving the
stent in a linear direction along the longitudinal axis of the
stent during the act of applying.
23. The method of claim 17, wherein the act of applying a coating
composition comprises spraying the coating composition onto the
stent.
24. A support assembly for a stent, comprising: a member for
supporting a stent, wherein the member includes an absorbing layer
for at least partially absorbing some of the coating material that
comes into contact with the absorbing layer.
Description
BACKGROUND OF THE INVENTION
[0001] 1. Field of the Invention
[0002] This invention relates to a stent mounting device and a
method of coating a stent using the device.
[0003] 2. Description of the Background
[0004] Blood vessel occlusions are commonly treated by mechanically
enhancing blood flow in the affected vessels, such as by employing
a stent. Stents act as scaffoldings, functioning to physically hold
open and, if desired, to expand the wall of the passageway.
Typically stents are capable of being compressed, so that they can
be inserted through small lumens via catheters, and then expanded
to a larger diameter once they are at the desired location.
Examples in the patent literature disclosing stents include U.S.
Pat. No. 4,733,665 issued to Palmaz, U.S. Pat. No. 4,800,882 issued
to Gianturco, and U.S. Pat. No. 4,886,062 issued to Wiktor.
[0005] FIG. 1 illustrates a conventional stent 10 formed from a
plurality of struts 12. The plurality of struts 12 are radially
expandable and interconnected by connecting elements 14 that are
disposed between adjacent struts 12, leaving lateral openings or
gaps 16 between adjacent struts 12. Struts 12 and connecting
elements 14 define a tubular stent body having an outer,
tissue-contacting surface and an inner surface.
[0006] Stents are used not only for mechanical intervention but
also as vehicles for providing biological therapy. Biological
therapy can be achieved by medicating the stents. Medicated stents
provide for the local administration of a therapeutic substance at
the diseased site. Local delivery of a therapeutic substance is a
preferred method of treatment because the substance is concentrated
at a specific site and thus smaller total levels of medication can
be administered in comparison to systemic dosages that often
produce adverse or even toxic side effects for the patient.
[0007] One method of medicating a stent involves the use of a
polymeric carrier coated onto the surface of the stent. A
composition including a solvent, a polymer dissolved in the
solvent, and a therapeutic substance dispersed in the blend is
applied to the stent by immersing the stent in the composition or
by spraying the composition onto the stent. The solvent is allowed
to evaporate, leaving on the stent strut surfaces a coating of the
polymer and the therapeutic substance impregnated in the
polymer.
[0008] A shortcoming of the above-described method of medicating a
stent is the potential for coating defects. While some coating
defects can be minimized by adjusting the coating parameters, other
defects occur due to the nature of the interface between the stent
and the apparatus on which the stent is supported during the
coating process. A high degree of surface contact between the stent
and the supporting apparatus can provide regions in which the
liquid composition can flow, wick, and collect as the composition
is applied. As the solvent evaporates, the excess composition
hardens to form excess coating at and around the contact points
between the stent and the supporting apparatus. Upon the removal of
the coated stent from the supporting apparatus, the excess coating
may stick to the apparatus, thereby removing some of the coating
from the stent and leaving bare areas. Alternatively, the excess
coating may stick to the stent, thereby leaving excess coating as
clumps or pools on the struts or webbing between the struts.
[0009] Thus, it is desirable to minimize the potential for coating
defects generated by the interface between the stent and the
apparatus supporting the stent during the coating process.
Accordingly, the present invention provides for a device for
supporting a stent during the coating application process. The
invention also provides for a method of coating the stent supported
by the device.
SUMMARY OF THE INVENTION
[0010] The present invention provides an apparatus for supporting a
stent during a process of coating the stent. The apparatus includes
a member for supporting a stent during the coating process, wherein
a section of the member includes a porous surface capable of
receiving the coating substance during the coating process. The
pores can have a diameter between about 0.2 microns and about 50
microns.
[0011] In one embodiment, the member includes a first member for
making contact with a first end of the stent and a second member
for making contact with a second end of the stent. In such an
embodiment, the pores can be located on at least a region of the
surface of the first or second members. The first or second member
can be made from a metallic material such as 300 Series stainless
steel, 400 Series stainless steel, titanium, tantalum, niobium,
zirconium, hafnium, and cobalt chromium alloys. The first or second
member can also be made from a polymeric material such as, but not
limited to, regenerated cellulose, cellulose acetate, polyacetal,
polyetheretherketone, polyesters, highly hydrolyzed polyvinyl
alcohol, nylon, polyphenylenesulfide, polyethylene, polyethylene
terephthalate, polypropylene, and combinations thereof. The first
or second member can also be made from ceramics such as, but not
limited to, zirconia, silica, glass, sintered calcium phosphates,
calcium sulfate, and titanium dioxide. In another embodiment, a
layer can be disposed on the surface of the first or second member
to absorb coating material that comes into contact with the
layer.
[0012] In one embodiment, the first and second members have
inwardly tapered ends that penetrate at least partially in the
first and second ends of the stent and are in contact with the
first and second ends of the stent. In another embodiment, the
apparatus additionally includes a third member for extending within
the stent and for securing the first member to the second
member.
[0013] The present invention also provides a method of coating a
stent. The method includes positioning a stent on a mounting
assembly, wherein a section of the mounting assembly includes a
porous surface. The method additionally includes applying a coating
composition to the stent, wherein at least some of the coating
composition that overflows from the stent is received by the pores.
The act of applying a coating composition can include spraying the
composition onto the stent.
[0014] In one embodiment, the method also includes at least
partially expanding the stent prior to the act of applying. The
method can also include rotating the stent about the longitudinal
axis of the stent during the act of applying and/or moving the
stent in a linear direction along the longitudinal axis of the
stent during the act of applying.
[0015] Also provided is a support assembly for a stent. The support
assembly includes a member for supporting a stent, wherein the
member includes an absorbing layer for at least partially absorbing
some of the coating material that comes into contact with the
absorbing layer.
BRIEF DESCRIPTION OF THE FIGURES
[0016] FIG. 1 illustrates a conventional stent.
[0017] FIG. 2A illustrates a mounting assembly for supporting a
stent in accordance with one embodiment of the present
invention.
[0018] FIG. 2B illustrates an expanded view of the mounting
assembly in accordance with one embodiment of the present
invention.
[0019] FIG. 3A illustrates the interface between the mounting
assembly and the stent.
[0020] FIG. 3B is a cross-sectional view of the interface between
the mounting assembly and the stent in FIG. 3A.
[0021] FIG. 4A illustrates a fluid on a solid substrate having a
contact angle .phi..sub.A;
[0022] FIG. 4B illustrates a fluid on a solid substrate having a
contact angle .phi..sub.B;
[0023] FIG. 5 illustrates an end view of a coning end portion
having a porous covering over the outer surface thereof.
DETAILED DESCRIPTION
Embodiments of the Mounting Assembly
[0024] Referring to FIG. 2A, a mounting assembly 18 for supporting
stent 10 is illustrated to include a support member 20, a mandrel
22, and a lock member 24. Support member 20 can connect to a motor
26A so as to provide rotational motion about the longitudinal axis
of stent 10, as depicted by arrow 28, during the coating process.
Another motor 26B can also be provided for moving support member 20
in a linear direction, back and forth, along a rail 29. The type of
stent 10 is not of critical importance and can include radially
expandable stents and stent-grafts.
[0025] Referring to FIG. 2B, support member 20 includes a coning
end portion 30, tapering inwardly at an angle .phi..sub.1 of about
15.degree. to about 75.degree., more narrowly from about 30.degree.
to about 60.degree.. By way of example, angle .phi..sub.1 can be
about 45.degree.. In accordance with one embodiment, mandrel 22 can
be permanently affixed to coning end portion 30. Alternatively,
support member 20 can include a bore 32 for receiving a first end
34 of mandrel 22. First end 34 of mandrel 22 can be threaded to
screw into bore 32. Alternatively, a non-threaded first end 34 and
bore 32 combination can be employed such that first end 34 can be
press-fitted or friction-fitted within bore 32 to prevent movement
of stent 10 on mounting assembly 18. Bore 32 should be deep enough
so as to allow mandrel 22 to securely mate with support member 20.
The depth of bore 32 can also be over-extended so as to allow a
significant length of mandrel 22 to penetrate bore 32. This would
allow the length of mandrel 22 to be adjusted to accommodate stents
of various sizes. In commercial embodiments, support member 20 can
be disposable or capable of being cleaned after each use, for
example in a solvent or oxidizing bath, or by pyrolizing out any
absorbed coating materials via heating at high temperatures.
[0026] The outer diameter of mandrel 22 should be smaller than the
inner diameter of stent 10 so as to prevent the outer surface of
mandrel 22 from making contact with the inner surface of stent 10.
A sufficient clearance between the outer surface of mandrel 22 and
the inner surface of stent 10 should be provided to prevent mandrel
22 from obstructing the pattern of the stent body during the
coating process. By way of example, the outer diameter of mandrel
22 can be from about 0.010 inches (0.254 mm) to about 0.017 inches
(0.432 mm) when stent 10 has an inner diameter of between about
0.025 inches (0.635 mm) and about 0.035 inches (0.889 mm).
[0027] Lock member 24 includes a coning end portion 36 having an
inwardly tapered angle .phi..sub.2. Angle .phi..sub.2 can be the
same as or different than the above-described angle .phi..sub.1. A
second end 38 of mandrel 22 can be permanently affixed to lock
member 24 if end 34 is disengagable from support member 20.
Alternatively, in accordance with another embodiment, mandrel 22
can have a threaded second end 38 for screwing into a bore 40 of
lock member 24. Bore 40 can be of any suitable depth that would
allow lock member 24 to be incrementally moved closer to support
member 20. Accordingly, stents 10 of any length can be securely
pinched between support and lock members 20 and 24. In accordance
with yet another embodiment, a non-threaded second end 38 and bore
40 combination is employed such that second end 38 can be
press-fitted or friction-fitted within bore 40. In commercial
embodiments, lock member 24 can be disposable or capable of being
cleaned after each use.
[0028] Mounting assembly 18 supports stent 10 via coning end
portions 30 and 36. FIGS. 3A and 3B illustrate the interface
between coning end portions 30 and 36 and each end of stent 10 so
as to provide minimal contact between stent 10 and mounting
assembly 18. Opposing forces exerted from support and lock members
20 and 24, for securely pinching stent 10, should be sufficiently
strong so as to prevent any significant movement of stent 10 on
mounting assembly 18. However, the exerted force should not
compress stent 10 so as to distort the body of stent 10. Over or
under application of support force can lead to coating defects,
such as non-uniformity of the coating thickness.
[0029] In addition to supporting stent 10 with minimal contact,
coning end portions 30 and 36 also function to reduce buildup of
coating materials at the stent 10-mounting assembly 18 interface.
Coning end portions 30 and 36 should be able to absorb the coating
substance applied to stent 10. Thus, excess coating substance is
absorbed into coning end portions 30 and 36 and drawn away from
stent 10 during the coating process, further minimizing the
potential for webbing and other coating defects at the interface
between stent 10 and mounting assembly 18.
[0030] In one embodiment, the particular material selected for
coning end portions 30 and 36 can be any material having a
plurality of pores 44 suitable to receive or absorb the coating
substance deposited thereon during the coating process. Pores 44
can be interconnected. Interconnected pore structures are also
known as open pore systems as opposed to closed pore systems in
which pores 44 are isolated from one another. Interconnected pores
44 provide a network for moving and holding the coating substance,
thus enabling coning end portions 30 and 36 to hold a larger amount
of the coating substance than coning end portions 30 and 36 having
discrete pores 44, each with a fixed capacity for uptake of the
substance. The diameter of pores 44 can be from about 0.2 microns
to about 50 microns, for example about 1 micron.
[0031] Coning end portions 30 and 36 can be made of materials
having a porous body or porous surfaces. Such materials can include
ceramics, metals, and polymeric materials. In accordance with
another embodiment, support member 20, mandrel 22, and/or lock
member 24 can also be made to have a porous surface. Examples of
suitable ceramics include, but are not limited to, zirconia,
silica, glass, sintered calcium phosphates, calcium sulfate, and
titanium dioxide.
[0032] Examples of suitable metals include, but are not limited to,
300 Series stainless steel, 400 Series stainless steel, titanium,
tantalum, niobium, zirconium, hafnium, and cobalt chromium alloys.
Surfaces having pores 44 can be made, for example, by sintering
pre-formed metallic particles together to form porous blanks that
can then be machined to a suitable shape or by sintering metallic
particles together in a suitably-shaped mold. In alternative
embodiments, the metal can be etched or bead-blasted to form a
porous surface. Etching can be conducted by exposing the surface to
a laser discharge, such as that of an excimer laser, or to a
suitable chemical etchant.
[0033] Examples of suitable polymeric materials include, but are
not limited to, regenerated cellulose, cellulose acetate,
polyacetal, polyetheretherketone, polyesters, highly hydrolyzed
polyvinyl alcohol, nylon, polyphenylenesulfide, polyethylene,
polyethylene terephthalate, polypropylene, and combinations
thereof. Methods of making polymers having pores 44, such as by
foaming, sintering particles to form a porous block, and phase
inversion processing, are understood by one of ordinary skill in
the art. The polymeric material selected should not be capable of
swelling, dissolving, or adversely reacting with the coating
substance.
[0034] In one suitable embodiment, the polymeric material from
which the components are made is selected to allow the coating
substance to have a high capillary permeation when a droplet of the
coating substance is placed thereon. Capillary permeation or
wetting is the movement of a fluid on a solid substrate driven by
interfacial energetics. Capillary permeation is quantitated by a
contact angle, defined as an angle at the tangent of a droplet in a
fluid phase that has taken an equilibrium shape on a solid surface.
A low contact angle indicates a higher wetting liquid. A suitably
high capillary permeation corresponds to a contact angle less than
about 90.degree.. FIG. 4A illustrates a droplet 46 of the coating
substance on a flat, nonporous surface 48A composed of the same
material as coning end portion 30 or 36. Fluid droplet 46 has a
high capillary permeation that corresponds to a contact angle
.phi..sub.A, which is less than about 90.degree.. By contrast, FIG.
4B illustrates fluid droplet 46 on a surface 48B having a low
capillary permeation that corresponds to a contact angle
.phi..sub.B, which is greater than about 90.degree.. Surface
treatments understood by one of ordinary skill in the art, such as
plasma treating, corona treating, chemical oxidation, and etching,
can be used to modify the surface to render the surface more
capable of allowing the coating substance to have a suitably high
capillary permeation.
[0035] FIG. 5 illustrates an embodiment in which the outer surface
of coning end portions 30 and/or 36 is covered with a layer 50. In
such an embodiment, coning end portions 30 and/or 36 can have
either porous or non-porous surfaces, while layer 50 can be made of
an absorbent material, such as a sponge. Accordingly, layer 50 can
absorb excess coating substance flowing off of stent 10. In
addition, support member 20, mandrel 22, and/or lock member 24 can
also be covered with layer 50.
[0036] While the device of the present invention has been described
herein as having coning end portions 30 and 36 that support the
respective ends of a stent and draw excess coating materials away
from the stent via pores 44, it should be understood that the
present invention is not limited thereto. Rather, the stent
mounting assembly of the present invention can be any device that
includes porous regions for supporting a stent as well as for
absorbing excess coating materials to minimize coating defects.
Coating a Stent Using the Mounting Assembly
[0037] The following method of application is being provided by way
of illustration and is not intended to limit the embodiments of
mounting assembly 18 of the present invention. A spray apparatus,
such as EFD 780S spray device with VALVEMATE 7040 control system
(manufactured by EFD Inc., East Providence, R.I.), can be used to
apply a composition to a stent. EFD 780S spray device is an
air-assisted external mixing atomizer. The composition is atomized
into small droplets by air and uniformly applied to the stent
surfaces. The atomization pressure can be maintained at a range of
about 5 psi to about 20 psi. The droplet size depends on such
factors as viscosity of the solution, surface tension of the
solvent, and atomization pressure. Other types of spray
applicators, including air-assisted internal mixing atomizers and
ultrasonic applicators, can also be used for the application of the
composition.
[0038] During the application of the composition, a stent supported
by mounting assembly 18 can be rotated about the stent's central
longitudinal axis. Rotation of the stent can be from about 1 rpm to
about 300 rpm, more narrowly from about 50 rpm to about 150 rpm. By
way of example, the stent can rotate at about 120 rpm. The stent
can also be moved in a linear direction along the same axis. The
stent can be moved at about 1 mm/second to about 12 mm/second, for
example about 6 mm/second, or for a minimum of at least two passes
(i.e., back and forth past the spray nozzle). The flow rate of the
solution from the spray nozzle can be from about 0.01 mg/second to
about 0.1 mg/second, more narrowly about 0.1 mg/second. Multiple
repetitions for applying the composition can be performed, wherein
each repetition can be, for example, about 1 second to about 10
seconds in duration. The amount of coating applied by each
repetition can be about 0.1 micrograms/cm.sup.2 (of stent surface)
to about 40 micrograms/cm.sup.2, for example less than about 2
micrograms/cm.sup.2 per 5-second spray.
[0039] Each repetition can be followed by removal of a significant
amount of the solvent. Depending on the volatility of the
particular solvent employed, the solvent can evaporate essentially
upon contact with the stent. Alternatively, removal of the solvent
can be induced by baking the stent in an oven at a mild temperature
(e.g., 60.degree. C.) for a suitable duration of time (e.g., 2-4
hours) or by the application of warm air. The application of warm
air between each repetition prevents coating defects and minimizes
interaction between the active agent and the solvent. The
temperature of the warm air can be from about 30.degree. C. to
about 60.degree. C., more narrowly from about 40.degree. C. to
about 50.degree. C. The flow rate of the warm air can be from about
20 cubic feet/minute (CFM) (0.57 cubic meters/minute (CMM)) to
about 80 CFM (2.27 CMM), more narrowly about 30 CFM (0.85 CMM) to
about 40 CFM (1.13 CMM). The warm air can be applied for about 3
seconds to about 60 seconds, more narrowly for about 10 seconds to
about 20 seconds. By way of example, warm air applications can be
performed at a temperature of about 50.degree. C., at a flow rate
of about 40 CFM, and for about 10 seconds. Any suitable number of
repetitions of applying the composition followed by removing the
solvent(s) can be performed to form a coating of a desired
thickness or weight. Excessive application of the polymer in a
single application can, however, cause coating defects.
[0040] Operations such as wiping, centrifugation, or other web
clearing acts can also be performed to achieve a more uniform
coating. Briefly, wiping refers to the physical removal of excess
coating from the surface of the stent; and centrifugation refers to
rapid rotation of the stent about an axis of rotation. The excess
coating can also be vacuumed off of the surface of the stent.
[0041] In accordance with one embodiment, the stent can be at least
partially pre-expanded prior to the application of the composition.
For example, the stent can be radially expanded about 20% to about
60%, more narrowly about 27% to about 55% the measurement being
taken from the stent's inner diameter at an expanded position as
compared to the inner diameter at the unexpanded position. The
expansion of the stent, for increasing the interspace between the
stent struts during the application of the composition, can further
prevent "cob web" formation between the stent struts.
[0042] In accordance with one embodiment, the composition can
include a solvent and a polymer dissolved in the solvent. The
composition can also include active agents, radiopaque elements, or
radioactive isotopes. Representative examples of polymers that can
be used to coat a stent include ethylene vinyl alcohol copolymer
(commonly known by the generic name EVOH or by the trade name
EVAL), poly(hydroxyvalerate); poly(L-lactic acid);
polycaprolactone; poly(lactide-coglycolide); poly(hydroxybutyrate);
poly(hydroxybutyrate-co-valerate); polydioxanone; polyorthoester;
polyanhydride; poly(glycolic acid); poly(D,L-lactic acid);
poly(glycolic acid-co-trimethylene carbonate); polyphosphoester;
polyphosphoester urethane; poly(amino acids); cyanoacrylates;
poly(trimethylene carbonate); poly(iminocarbonate);
copoly(ether-esters) (e.g. PEO/PLA); polyalkylene oxalates;
polyphosphazenes; biomolecules, such as fibrin, fibrinogen,
cellulose, starch, collagen and hyaluronic acid; polyurethanes;
silicones; polyesters; polyolefms; 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 fluoride and polyvinylidene
chloride; polyacrylonitrile; polyvinyl ketones; polyvinyl
aromatics, such as polystyrene; polyvinyl esters, such as polyvinyl
acetate; copolymers of vinyl monomers with each other and olefins,
such as ethylene-methyl methacrylate copolymers,
acrylonitrile-styrene copolymers, ABS resins, and ethylene-vinyl
acetate copolymers; polyamides, such as Nylon 66 and
polycaprolactam; alkyd resins; polycarbonates; polyoxymethylenes;
polyimides; polyethers; epoxy resins; polyurethanes; rayon;
rayon-triacetate; cellulose; cellulose acetate; cellulose butyrate;
cellulose acetate butyrate; cellophane; cellulose nitrate;
cellulose propionate; cellulose ethers; and carboxymethyl
cellulose.
[0043] "Solvent" is defined as a liquid substance or composition
that is compatible with the polymer and is capable of dissolving
the polymer at the concentration desired in the composition.
Examples of solvents include, but are not limited to,
dimethylsulfoxide (DMSO), chloroform, acetone, water (buffered
saline), xylene, methanol, ethanol, 1-propanol, tetrahydrofuran,
1-butanone, dimethylformamide, dimethylacetamide, cyclohexanone,
ethyl acetate, methylethylketone, propylene glycol monomethylether,
isopropanol, isopropanol admixed with water, N-methyl
pyrrolidinone, toluene, and combinations thereof.
[0044] The active agent could be for inhibiting the activity of
vascular smooth muscle cells. More specifically, the active agent
can be aimed at inhibiting abnormal or inappropriate migration
and/or proliferation of smooth muscle cells for the inhibition of
restenosis. The active agent can also include any substance capable
of exerting a therapeutic or prophylactic effect in the practice of
the present invention. For example, the agent can be for enhancing
wound healing in a vascular site or improving the structural and
elastic properties of the vascular site. Examples of agents include
antiproliferative substances such as actinomycin D, or derivatives
and analogs thereof (manufactured by Sigma-Aldrich 1001 West Saint
Paul Avenue, Milwaukee, Wis. 53233; or COSMEGEN available from
Merck). Synonyms of actinomycin D include dactinomycin, actinomycin
IV, actinomycin I.sub.1, actinomycin X.sub.1, and actinomycin
C.sub.1. The active agent can also fall under the genus of
antineoplastic, antiinflammatory, antiplatelet, anticoagulant,
antifibrin, antithrombin, antimitotic, antibiotic, antiallergic and
antioxidant substances. Examples of such antineoplastics and/or
antimitotics include paclitaxel (e.g. TAXOL.degree. by
Bristol-Myers Squibb Co., Stamford, Conn.), docetaxel (e.g.
Taxotere.RTM., from Aventis S.A., Frankfurt, Germany) methotrexate,
azathioprine, vincristine, vinblastine, fluorouracil, doxorubicin
hydrochloride (e.g. Adriamycin.RTM. from Pharmacia & Upjohn,
Peapack N.J.), and mitomycin (e.g. Mutamycin.RTM. from
Bristol-Myers Squibb Co., Stamford, Conn.) Examples of such
antiplatelets, anticoagulants, antifibrin, and antithrombins
include sodium heparin, low molecular weight heparins, heparinoids,
hirudin, argatroban, forskolin, vapiprost, prostacyclin and
prostacyclin analogues, dextran, D-phe-pro-arg-chloromethylketone
(synthetic antithrombin), dipyridamole, glycoprotein IIb/IIIa
platelet membrane receptor antagonist antibody, recombinant
hirudin, and thrombin inhibitors such as AngiomaxT.TM. (Biogen,
Inc., Cambridge, Mass.) Examples of such cytostatic or
antiproliferative agents include angiopeptin, angiotensin
converting enzyme inhibitors such as captopril (e.g. Capoten.RTM.
and Capozide.RTM. from Bristol-Myers Squibb Co., Stamford, Conn.),
cilazapril or lisinopril (e.g. Prinivil.RTM. and Prinzide.RTM. from
Merck & Co., Inc., Whitehouse Station, N.J.); calcium channel
blockers (such as nifedipine), colchicine, fibroblast growth factor
(FGF) antagonists, fish oil (omega 3-fatty acid), histamine
antagonists, lovastatin (an inhibitor of HMG-CoA reductase, a
cholesterol lowering drug, brand name Mevacor.RTM. from Merck &
Co., Inc., Whitehouse Station, N.J.), monoclonal antibodies (such
as those specific for Platelet-Derived Growth Factor (PDGF)
receptors), nitroprusside, phosphodiesterase inhibitors,
prostaglandin inhibitors, suramin, serotonin blockers, steroids,
thioprotease inhibitors, triazolopyrimidine (a PDGF antagonist),
and nitric oxide. An example of an antiallergic agent is
permirolast potassium. Other therapeutic substances or agents which
may be appropriate include alpha-interferon, genetically engineered
epithelial cells, rapamycin and dexamethasone. Exposure of the
active ingredient to the composition should not adversely alter the
active ingredient's composition or characteristic. Accordingly, the
particular active ingredient is selected for compatibility with the
solvent or blended polymer-solvent.
[0045] Examples of radiopaque elements include, but are not limited
to, gold, tantalum, and platinum. An example of a radioactive
isotope is P.sup.32. Sufficient amounts of such substances may be
dispersed in the composition such that the substances are not
present in the composition as agglomerates or flocs.
[0046] 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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