U.S. patent application number 10/894897 was filed with the patent office on 2004-12-30 for stent coating apparatus.
Invention is credited to Pacetti, Stephen D., Roorda, Wouter E..
Application Number | 20040261698 10/894897 |
Document ID | / |
Family ID | 33541757 |
Filed Date | 2004-12-30 |
United States Patent
Application |
20040261698 |
Kind Code |
A1 |
Roorda, Wouter E. ; et
al. |
December 30, 2004 |
Stent coating apparatus
Abstract
An apparatus for coating stent is disclosed. The apparatus can
be used to coat multiple stents or a large number of stents
simultaneously. The apparatus includes a chamber that can be
rotated or tumbled during the application of a coating substance to
the stents.
Inventors: |
Roorda, Wouter E.; (Palo
Alto, CA) ; Pacetti, Stephen D.; (San Jose,
CA) |
Correspondence
Address: |
SQUIRE, SANDERS & DEMPSEY LLP
1 MARITIME PLAZA
SUITE 300
SAN FRANCISCO
CA
94111
US
|
Family ID: |
33541757 |
Appl. No.: |
10/894897 |
Filed: |
July 19, 2004 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
10894897 |
Jul 19, 2004 |
|
|
|
09966420 |
Sep 27, 2001 |
|
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Current U.S.
Class: |
118/416 ;
118/500 |
Current CPC
Class: |
B05B 13/0257
20130101 |
Class at
Publication: |
118/416 ;
118/500 |
International
Class: |
B05C 013/00; B05C
003/00 |
Claims
What is claimed is:
1. A large-scale stent coating apparatus, comprising a chamber to
hold a multitude of stents, the chamber being configured to agitate
so as to shake the stents within the chamber; and an applicator for
depositing a coating substance into the chamber for coating the
stents.
2. The apparatus of claim 1, additionally comprising means for
applying a gas into the chamber.
3. The apparatus of claim 1, additionally comprising means for
drying the coating applied to the stents within the chamber.
4. The apparatus of claim 1, additionally comprising means for
applying a gas at a temperature of 15 deg. C to 200 deg. C into the
chamber.
5. A large-scale stent coating apparatus, comprising a chamber for
holding a large number of stents, the chamber being configured to
shake so as to tumble the stents by the shaking motion of the
chamber; an applicator for depositing a coating substance into the
chamber for coating the stents.
6. The apparatus of claim 5, additionally comprising a nozzle for
applying a gas into the chamber.
7. A large-scale stent coating apparatus, comprising a chamber
configured to hold a multitude of stents, the chamber being
configured to rotate about an axis that is parallel to the
horizontal plane so as to tumble the stents in the chamber; and an
applicator for depositing a coating substance into the chamber for
coating the stents.
8. The apparatus of claim 7, wherein the chamber is configured to
rotate between 5 to 400 rpm.
9. The apparatus of claim 7, additionally including means for
blowing a gas into the chamber.
Description
CROSS REFERENCE
[0001] This is a continuation of application Ser. No. 09/966,420,
filed on Sep. 27, 2001.
BACKGROUND
[0002] This invention relates to a stent coating apparatus.
Percutaneous transluminal coronary angioplasty (PTCA) is a
procedure for treating heart disease. A catheter assembly having a
balloon portion is introduced percutaneously into the
cardiovascular system of a patient via the brachial or femoral
artery. The catheter assembly is advanced through the coronary
vasculature until the balloon portion is positioned across the
occlusive lesion. Once in position across the lesion, the balloon
is inflated to a predetermined size to radially press against the
atherosclerotic plaque of the lesion for remodeling of the vessel
wall. The balloon is then deflated to a smaller profile to allow
the catheter to be withdrawn from the patient's vasculature.
[0003] A problem associated with the above procedure includes
formation of intimal flaps or torn arterial linings which can
collapse and occlude the conduit after the balloon is deflated.
Vasospasms and recoil of the vessel wall also threaten vessel
closure. Moreover, thrombosis and restenosis of the artery may
develop over several months after the procedure, which may require
another angioplasty procedure or a surgical by-pass operation. To
reduce the partial or total occlusion of the artery by the collapse
of arterial lining and to reduce the chance of the development of
thrombosis and restenosis, a stent is implanted in the lumen to
maintain the vascular patency.
[0004] 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.
[0005] Stents may be used not only as a mechanical intervention but
also as a vehicle for providing biological therapy. As a mechanical
intervention, stents may 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 cavities via catheters, and
then expanded to a larger diameter once they are at the desired
location. Examples in patent literature disclosing stents which
have been applied in PTCA procedures include stents illustrated in
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.
Mechanical intervention via stents has reduced the rate of
restenosis as compared to balloon angioplasty; restenosis, however,
is still a significant clinical problem. When restenosis does occur
in the stented segment, its treatment can be challenging, as
clinical options are more limited as compared to lesions that were
treated solely with a balloon.
[0006] Biological therapy can be achieved by medicating the stents.
Medicated stents provide for the local administration of a
therapeutic substance at the diseased site. In order to provide an
efficacious concentration to the treated site, systemic
administration of such medication often produces adverse or toxic
side effects for the patient. Local delivery is a preferred method
of treatment in that smaller total levels of medication are
administered in comparison to systemic dosages, but are
concentrated at a specific site. Local delivery thus produces fewer
side effects and achieves more favorable results.
[0007] Although stents work well mechanically, the chronic issues
of restenosis and, to a lesser extent, stent thrombosis remain.
These events are affected by, and made worse, by mechanical aspects
of the stent such as the degree of injury and disturbance of
hemodynamics. To the extent that the mechanical functionality of
stents has been optimized, it has been postulated that continued
improvements could be made by pharmacological therapies. Many
systemic therapies have been tried. A challenge is maintaining the
necessary concentration of drug at the lesion site for the
necessary period of time. This can be done via brute force methods
using oral or intravenous administration but the issues of systemic
toxicity and side effects arise. Therefore, a preferred route may
be achieved by local delivery of drug from the stent itself. Stents
are composed of struts that are typically 50-150 microns wide.
Being made of metal, plain stents are not useful for drug delivery.
Therefore, a coating, usually of a polymer, is applied to serve as
a drug reservoir.
[0008] Slotted tube stents are made by laser cutting a solid metal
hypotube. Leading stent manufacturers can produce thousands of
stents per day. Consequently, the drug coating process, which is
added on to the existing stent manufacturing process, needs to be
rapid and reproducible. Stents are difficult to coat evenly due to
their intricate geometry and small size. Conventional coating
techniques fill in the spaces between struts creating webbing and
bridging. A versatile method of stent coating is by a spray process
that avoids webbing by the application of small droplets.
[0009] In order to coat a stent, it typically must be held in some
manner. This allows it to be positioned and moved under a spray
nozzle in a controlled and repeatable manner. However, holding a
stent requires making contact with it. At these contact points, the
liquid coating can web, accumulate or wick. After drying, this
leads to thick coating deposits at the contacts between the stent
and the fixture. These deposits can also attach the stent to the
holding fixture, which creates tearing and bare spots when the two
are eventually separated. It is desirable that the stent be
completely coated on all surfaces with no significant bare spots.
It is also desirable that there be no significant defects
associated with the fixturing. It is further desirable that a
coating process is capable of allowing the coating of a large
amount or number of stents at one time.
SUMMARY OF THE INVENTION
[0010] A large-scale stent coating apparatus is disclosed,
comprising a chamber to hold a multitude of stents, the chamber
being configured to agitate so as to shake the stents within the
chamber; and an applicator for depositing a coating substance into
the chamber for coating the stents.
[0011] In some embodiments, the apparatus additionally includes a
system for applying a gas into the chamber.
[0012] A large-scale stent coating apparatus is disclosed,
comprising a chamber for holding a large number of stents, the
chamber being configured to shake so as to tumble the stents by the
shaking motion of the chamber; an applicator for depositing a
coating substance into the chamber for coating the stents.
[0013] A large-scale stent coating apparatus is disclosed,
comprising a chamber configured to hold a multitude of stents, the
chamber being configured to rotate about an axis that is parallel
to the horizontal plane so as to tumble the stents in the chamber;
and an applicator for depositing a coating substance into the
chamber for coating the stents.
BRIEF DESCRIPTION OF THE DRAWINGS
[0014] FIG. 1 illustrates a conventional stent; and
[0015] FIG. 2 is a schematic flow diagram illustrating a process
for coating an implantable device in accordance with an embodiment
of the present invention.
DETAILED DESCRIPTION
[0016] FIG. 2 is a schematic flow diagram illustrating a general
overview of a process 200 for coating an implantable device, such
as a stent, in accordance with an embodiment of the present
invention. At least one stent 202 is deposited in a pan 204 (see A
of FIG. 2).
[0017] The pan 204 is agitated to tumble the stent(s) 202 in the
pan 204 (see B of FIG. 2). Agitation of the pan 204 may be achieved
utilizing a variety of modes including, but not limited to, shaking
of the pan 204 to tumble the stent(s) 202 therein. As illustrated
in FIG. 2, in one embodiment, agitation of the pan 204 may be
achieved by tilting the pan 204 with respect to a horizontal plane
206 such that an axis 208 of the pan 204 extends at an acute angle
(e.g., extending at an angle between 0 degrees and 90 degrees) to
the horizontal plane 206. The pan 204 can be rotated about the axis
208 to tumble the stent(s) 202 in the pan 204. As an option, the
rotating axis 208 may extend at about 45 degrees with respect to
the horizontal plane 206. In one embodiment, the pan 204 may be
rotated between about 5 revolutions per minute (rpm) and about 400
rpm and in a preferred embodiment between about 10 rpm and about
200 rpm.
[0018] Continuing the process 200, a coating substance is
introduced to coat the tumbling stent(s) 202. In one embodiment,
the coating substance 210 may be sprayed into the pan 204 to coat
the tumbling stent(s) 202 with the coating substance (see C of FIG.
2). Because of the continuous tumbling motion, the spray coating
solution is divided equally over the stents 202. In one embodiment,
the coating substance may comprise a polymer dissolved in a fluid
and, optionally, an active agent added thereto. The actual spray
time chosen may depend on various factors such as, for example, the
equipment used, the number of stents being deposited in the pan
204, and the volatility of the solvent.
[0019] As a further option, gaseous composition 212 may be directed
over the tumbling stent(s) 202 to aid in the drying of the coating
substance on the stent(s) 202. In the embodiment illustrated in
FIG. 2, the gaseous compound 212 may be blown into the rotating pan
204 to aid drying of the coating substance 210 on the tumbling
stent(s) 202 (see D of FIG. 2). In one such embodiment, the gaseous
composition 212 may comprise air. As another option, the gaseous
composition 212 may have a temperature between about 15.degree. C.
and about 200.degree. C.
[0020] It should further be noted that one or more subsequent
coating substances may also be sequentially introduced to the
tumbling implantable device to apply one or more further coatings
on the implantable device.
[0021] Embodiments of the disclosed process may be utilized to coat
one or more stents (especially large numbers of stents)--including
drug delivery stents. The process may be utilized used to apply
primers, drug containing layers, and/or topcoats. The significance
of this process is two-fold: this process simplifies the spray
process and increases its reproducibility by virtue of being a
simpler process. Additionally, since the stent is not contacted
continuously at any one point, the issue of end ring defects should
be reduced or essentially eliminated. It should also be noted that
embodiments of the disclosed process maybe used on any drug eluting
stent. Such coatings can be used on balloon expandable or
self-expanding stents. The stent may be utilized in any part of the
vasculature including neurological, carotid, coronary, renal,
aortic, iliac, femoral, or other peripheral vasculature. There may
also be no limitations on stent length, diameter, strut thickness,
strut pattern, or stent material.
[0022] Implantable Devices
[0023] While the process detailed herein is often described with
reference to coating a stent, it should be understood that the
device or prosthesis coated in accordance with the embodiments of
the present invention may be any suitable medical substrate that
can be implanted in a human or veterinary patient. Examples of such
implantable devices include stent-grafts, grafts (e.g., aortic
grafts), artificial heart valves, cerebrospinal fluid shunts,
anastomosis devices (e.g., AXIUS Coronary Shunt available from
Guidant Corporation), pacemaker electrodes, and endocardial leads
(e.g., FINELINE and ENDOTAK, available from Guidant Corporation).
The underlying structure of the device can be of virtually any
design. The device can be made of a metallic material or an alloy
such as, but not limited to, cobalt chromium alloy (ELGILOY),
stainless steel (316L), "MP35N," "MP20N," ELASTINITE (Nitinol),
tantalum, nickel-titanium alloy, platinum-iridium alloy, gold,
magnesium, or combinations thereof. "MP35N" and "MP20N" are trade
names for alloys of cobalt, nickel, chromium and molybdenum
available from standard Press Steel Co., Jenkintown, Pa. "MP35N"
consists of 35% cobalt, 35% nickel, 20% chromium, and 10%
molybdenum. "MP20N" consists of 50% cobalt, 20% nickel, 20%
chromium, and 10% molybdenum. Devices made from bioabsorbable or
biostable polymers could also be used with the embodiments of the
present invention. A polymeric implantable device should be
compatible with the composition. The ethylene vinyl alcohol
copolymer, however, adheres very well to metallic materials, more
specifically to stainless steel.
[0024] Coating Substance
[0025] In an embodiment of the present invention, the coating
substance may include a polymer dissolved in a fluid and
optionally, an active agent added thereto. As a further option, the
coating substance may include radiopaque elements, or radioactive
isotopes.
[0026] 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-co-glycolide); 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; 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 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.
[0027] In an embodiment of the present invention, the fluid in
which the polymer is dissolved may comprise a solvent which may be
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.
[0028] The embodiments of the composition may be prepared by
conventional methods wherein all components are combined, then
blended. For example, in an illustrative embodiment, a
predetermined amount of an ethylene vinyl alcohol copolymer may be
added to a predetermined amount of dimethyl acetamide (DMAC or
DMAc). If necessary, heating, stirring and/or mixing can be
employed to effect dissolution of the copolymer into the
solvent--for example in an 80.degree. C. water bath for one to two
hours.
[0029] Active Agent
[0030] The active agent may be in true solution or saturated in the
blended composition. If the active agent is not completely soluble
in the composition, operations including mixing, stirring, and/or
agitation can be employed to effect homogeneity of the residues.
The active agent may be added in fine particles. The mixing of the
active agent can be conducted at ambient pressure and at room
temperature such that supersaturating the active ingredient is not
desired. The active agent can 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 Cl.
The active agent can also fall under the genus of antineoplastic,
anti-inflammatory, antiplatelet, anticoagulant, antifibrin,
antithrombin, antimitotic, antibiotic, antiallergic and antioxidant
substances. Examples of such antineoplastics and/or antimitotics
include paclitaxel (e.g. TAXOL.RTM. 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 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-chloromet- hylketone (synthetic antithrombin),
dipyridamole, glycoprotein IIb/IIIa platelet membrane receptor
antagonist antibody, recombinant hirudin, and thrombin inhibitors
such as Angiomax a (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.
[0031] 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.
[0032] The dosage or concentration of the active agent required to
produce a favorable therapeutic effect should be less than the
level at which the active agent produces toxic effects and greater
than the level at which non-therapeutic results are obtained. The
dosage or concentration of the active agent required to inhibit the
desired cellular activity of the vascular region can depend upon
factors such as the particular circumstances of the patient; the
nature of the trauma; the nature of the therapy desired; the time
over which the ingredient administered resides at the vascular
site; and if other therapeutic agents are employed, the nature and
type of the substance or combination of substances. Therapeutic
effective dosages can be determined empirically, for example by
infusing vessels from suitable animal model systems and using
immunohistochemical, fluorescent or electron microscopy methods to
detect the agent and its effects, or by conducting suitable in
vitro studies. Standard pharmacological test procedures to
determine dosages are understood by one of ordinary skill in the
art.
[0033] Application Process
[0034] In accordance with an embodiment of the present invention,
the coating substance may be sprayed on to the stents utilizing a
spray apparatus, such as, for example, an EFD 780S spray device
with VALVEMATE 7040 control system (manufactured by EFD Inc., East
Providence, R.I.). EFD spray device is an air-assisted external
mixing atomizer. The composition is atomized into small droplets by
air and uniformly applied to the stent surface. The atomization
pressure can be maintained at a range of about 5 to 20 psi. The
droplet size depends on such factors as viscosity of the solution,
surface tension of the solvent, and atomizing 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.
[0035] The flow rate of the solution from the spray nozzle can be
from about 0.01 mg/second to about 1.0 mg/second, for example about
0.1 mg/second. As an option, multiple repetitions for applying the
composition can be performed, wherein each repetition is about 1
second to about 10 seconds, for example about 5 seconds, in
duration. The amount of coating applied by each repetition can be
about 0.1 micrograms/cm (of stent surface) to about 10
micrograms/cm, for example less than about 2 micrograms/cm per 5
second spray.
[0036] Each repetition can be followed by removal of a significant
amount of the solvent(s). The removal of the solvent(s) can be
performed following a waiting period of about 0.1 second to about 5
seconds after the application of the coating composition so as to
allow the liquid sufficient time to flow and spread over the stent
surface before the solvent(s) is removed to form a coating. The
waiting period is particularly suitable if the coating composition
contains a volatile solvent, such as solvents having boiling points
>130.degree. C. at ambient pressure, since such solvents are
typically removed quickly.
[0037] Removal of the solvent(s) can be induced by the application
of a gas or air. The application of a warm gas between each
repetition prevents coating defects and minimizes interaction
between the active agent and the solvent. Any suitable gas can be
employed, examples of which include air or nitrogen. The
temperature of the gas can be from about 15.degree. C. to about
200.degree. C. In one embodiment, for temperature stable drugs, the
drying air temperature can be from ambient temperature up to about
100.degree. C. and for drugs that are temperature sensitive, the
temperature may be from ambient temperature up to about 50.degree.
C. The flow speed of the gas can be from about 0.5
feet.sup.3/second (0.01 meters.sup.3/second) to about 50
feet.sup.3/second (1.42 meters.sup.3/second), more narrowly about
2.5 feet.sup.3/second (0.07 meters.sup.3/second) to about 15
feet.sup.3/second (0.43 meters.sup.3/second). The gas can be
applied for about 1 second to about 100 seconds, more narrowly for
about 2 seconds to about 20 seconds. By way of example, warm gas
applications can be performed at a temperature of about 60.degree.
C., at a flow speed of about 10 feet.sup.3/second, and for about 10
seconds.
[0038] In one embodiment, the stent can be warmed to a temperature
of from about 35.degree. C. to about 80.degree. C. prior to the
application of the coating composition so as to facilitate faster
removal of the solvent(s). The particular temperature selected
depends, at least in part, on the particular active agent employed
in the coating composition. By way of example, pre-heating of the
stent prior to applying a composition containing actinomycin D
should be performed at a temperature not greater than about
55.degree. C. Pre-heating is particularly suitable for embodiments
in which the solvent(s) employed in the coating composition has a
high boiling point, i.e., volatile solvents having boiling points
of, for example, >130.degree. C. at ambient pressure (e.g.,
dimethylsulfoxide (DMSO), dimethylformamide (DMF), and
dimethylacetamide (DMAC)).
[0039] 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. In embodiments in
which the coating composition contains a volatile solvent, a
waiting period of from about 0.1 second to about 20 seconds can be
employed between solvent removal of one repetition and composition
application of the subsequent repetition so as to ensure that the
wetting rate of the coating composition is slower than the
evaporation rate of the solvent within the composition, thereby
promoting coating uniformity.
[0040] Coating Layers
[0041] To form an optional primer layer on the surface of the
device, an embodiment of the composition free from any active
agents is applied to the surface of the device. For the
thermoplastic polymers, the composition could be exposed to a heat
treatment at a temperature range of greater than about the glass
transition temperature and less than about the melting temperature
of the copolymer. The device should be exposed to the heat
treatment for any suitable duration of time (e.g., 30 minutes)
which would allow for the formation of the primer layer on the
surface of the device and allows for the evaporation of the
solvent. The primer can be used for increasing the retention of a
reservoir coating containing the active agent on the surface of the
device, particularly metallic surfaces such as stainless steel. The
primer can act as an intermediary adhesive tie layer between the
surface of the device and the coating carrying the active
agent--which, in effect, allows for the quantity of the active
agent to be increased in the reservoir coating.
[0042] For the formation of the reservoir coating containing an
active agent, an embodiment of the composition containing an active
agent or combination of agents is applied to the device. If a
primer layer is employed, the application should be performed
subsequent to the drying of the primer layer.
[0043] An optional topcoat can be formed over the reservoir coating
containing the active agents. An embodiment of the composition,
free from any active agents, can be applied to the reservoir region
subsequent to the drying of the reservoir region. The solvent is
then allowed to evaporate, for example, by exposure to a selected
temperature, to form the rate-limiting diffusion barrier.
[0044] For the reservoir coating containing the active agent and
the optional top coat, a final heat treatment could be conducted to
remove essentially all of the solvent(s) from the composition on
the stent. The heat treatment can be conducted at about 30.degree.
C. to about 200.degree. C. for about 15 minutes to about 16 hours,
more narrowly at about 50.degree. C. to about 100.degree. C. for
about 1 hour to about 4 hours. By way of example, the heat
treatment can be conducted at about 75.degree. C. for 1 hour. The
temperature of exposure should not adversely affect the
characteristics of the active agent or of the coating. The heating
can be conducted in an anhydrous atmosphere and at ambient
pressure. The heating can, alternatively, be conducted under a
vacuum condition. It is understood that essentially all of the
solvent(s) will be removed from the composition but traces or
residues can remain blended in the coating.
[0045] Method of Use
[0046] A stent having the above-described coating is useful for a
variety of medical procedures, including, by way of example,
treatment of obstructions caused by tumors in bile ducts,
esophagus, trachea/bronchi and other biological passageways. A
stent having the above-described coating is particularly useful for
treating occluded regions of blood vessels caused abnormal or
inappropriate migration and proliferation of smooth muscle cells,
thrombosis, and restenosis. Stents may be placed in a wide array of
blood vessels, both arteries and veins. Representative examples of
sites include the iliac, renal, and coronary arteries.
[0047] Briefly, an angiogram is first performed to determine the
appropriate positioning for stent therapy. Angiogram is typically
accomplished by injecting a radiopaque contrasting agent through a
catheter inserted into an artery or vein as an x-ray is taken. A
guidewire is then advanced through the lesion or proposed site of
treatment. Over the guidewire is passed a delivery catheter which
allows a stent in its collapsed configuration to be inserted into
the passageway. The delivery catheter is inserted either
percutaneously or by surgery into the femoral artery, brachial
artery, femoral vein, or brachial vein, and advanced into the
appropriate blood vessel by steering the catheter through the
vascular system under fluoroscopic guidance. A stent having the
above described coating may then be expanded at the desired area of
treatment. A post insertion angiogram may also be utilized to
confirm appropriate positioning.
[0048] 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 and,
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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