U.S. patent application number 10/004954 was filed with the patent office on 2002-05-30 for method for manufacturing a medical device having a coated portion by laser ablation.
This patent application is currently assigned to Scimed Life System, Inc.. Invention is credited to Weber, Jan.
Application Number | 20020065553 10/004954 |
Document ID | / |
Family ID | 24910671 |
Filed Date | 2002-05-30 |
United States Patent
Application |
20020065553 |
Kind Code |
A1 |
Weber, Jan |
May 30, 2002 |
Method for manufacturing a medical device having a coated portion
by laser ablation
Abstract
The present invention is directed to a method for manufacturing
a medical device having a coated portion which comprises obtaining
a structure having an inner surface and an outer surface; coating
at least a portion of the inner or outer surface with a first
coating material; and ablating the coated tubular structure with a
laser to form at least one opening therein to form the coated
portion. A plate can be used instead of the structure, and the
plate is folded to form the structure after the ablation. A
plurality of medical devices, made of any materials and having
uniform coating(s), can be easily manufactured by the method of the
present invention.
Inventors: |
Weber, Jan; (Tuam,
IE) |
Correspondence
Address: |
PENNIE AND EDMONDS
1155 AVENUE OF THE AMERICAS
NEW YORK
NY
100362711
|
Assignee: |
Scimed Life System, Inc.
|
Family ID: |
24910671 |
Appl. No.: |
10/004954 |
Filed: |
December 3, 2001 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10004954 |
Dec 3, 2001 |
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09724503 |
Nov 28, 2000 |
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Current U.S.
Class: |
623/1.46 ;
427/2.28; 604/264 |
Current CPC
Class: |
B23K 26/0624 20151001;
B23K 2103/05 20180801; A61L 2400/18 20130101; B23K 26/382 20151001;
B23K 2101/34 20180801; B23K 2103/50 20180801; B23K 26/40 20130101;
A61F 2/91 20130101; B23K 2103/14 20180801; A61L 31/14 20130101;
A61F 2240/001 20130101; B23K 2103/42 20180801; B23K 2103/52
20180801; B23K 2103/08 20180801; A61L 31/08 20130101; B23K 2103/16
20180801 |
Class at
Publication: |
623/1.46 ;
604/264; 427/2.28 |
International
Class: |
A61M 005/00; A61F
002/04 |
Claims
We claim:
1. A method for manufacturing a coated medical device having a
coated portion which comprises the steps of: (a) obtaining a
structure having an inner surface and an outer surface; (b) coating
at least a portion of the inner or outer surface with a first
coating material; and (c) ablating the coated structure with an
ultrashort-pulse laser to form at least one opening therein to form
the coated portion of the medical device.
2. The method of claim 1, wherein the structure is a tubular
structure.
3. The method of claim 1, wherein the medical device is a
stent.
4. The method of claim 1, wherein step (b) comprises only coating
the inner surface of the structure with the first coating
material.
5. The method of claim 1, wherein step (b) comprises only coating
the outer surface of the structure with the first coating
material.
6. The method of claim 1, wherein step (b) comprises: (i) coating
the inner surface of the structure with the first coating material
and (ii) coating the outer surface of the structure with a second
coating material.
7. The method of claim 7, wherein the first coating material and
the second coating material are the same.
8. The method of claim 1, wherein the first coating material is a
coating composition and the surface is coated by dipping the
surface into the coating composition.
9. The method of claim 1, wherein the first coating material is a
coating composition and the surface is coated by spray-coating the
coating composition onto the surface.
10. The method of claim 1, wherein the first coating material
comprises a polymer and a biologically active material.
11. The method of claim 1, wherein the first coating material
comprises a biologically active material, and the coating step (b)
is conducted by immobilizing the first coating material onto at
least of a portion of the surface.
13. The method of claim 1, wherein the coated structure is ablated
to form a plurality of openings therein that define a plurality of
struts.
13. The method of claim 1, which further comprises cutting the
coated structure into sections to form more than one coated
portion.
14. The method of claim 13, wherein the cutting step is conducted
between coating step and the ablating step.
15. A method for manufacturing a coated medical device having a
coated portion which comprises the steps of: (a) obtaining a plate
having a first surface and a second surface; (b) coating at least a
portion of the first surface or second surface which a first
coating material; (c) ablating the coated plate with an
ulrashort-pulse laser to form at least one opening therein; and (d)
forming the coated portion with the ablated plate.
16. The method of claim 15, wherein the coated portion is a
tube-like portion.
17. The method of claim 15, wherein the medical device is a
stent.
18. The method of claim 15, wherein step (b) comprises only coating
the first surface of the plate with the first coating material.
19. The method of claim 15, wherein step (b) comprises only coating
the second surface of the plate with the first coating
material.
20. The method of claim 15, wherein step (b) comprises: (i) coating
the first surface of the plate with the first coating material and
(ii) coating the second surface of the plate with a second coating
material.
21. The method of claim 15, wherein the first coating material and
the second coating material are the same.
22. The method of claim 15, wherein the first coating material is a
coating composition and the surface is coated by dipping the
surface into the coating composition.
23. The method of claim 15, wherein the first coating material is a
coating composition and the surface is coated by spray-coating the
coating composition onto the surface.
24. The method of claim 15, wherein the first coating material
comprises a biologically active material, and coating is conducted
by immobilizing the first coating material onto at least of a
portion of the surface.
25. The method of claim 15, wherein the first coating material
comprises a polymer and a biologically active material.
26. The method of claim 15, wherein the coated plate is ablated to
form a plurality of openings therein that define a plurality of
struts.
27. The method of claim 15, which further comprises cutting the
coated plate into sections to form more than one coated tube-like
portion.
28. The method of claim 27, wherein the cutting step is conducted
between the coating step and the ablating step.
29. The method of claim 27, wherein the coated plate is cut as it
is ablated.
Description
FIELD OF THE INVENTION
[0001] This invention relates generally to a method for
manufacturing a medical device. More particularly, the invention is
directed to a method for manufacturing a medical device having a
coated portion by laser ablation.
BACKGROUND OF THE INVENTION
[0002] Implantable medical devices, such as prosthesis or stents,
are used to reduce restenosis after balloon angioplasty or other
procedures involving catheters. Usually, the suitable medical
device or stent is cylindrical in shape. The walls of the
cylindrical structure can be formed of metal or polymer with
openings therein, e.g., a mesh. The stent is implanted into a body
lumen, such as a blood vessel, where it stays permanently, to keep
the vessel open and to improve blood flow to the heart muscle and
relieve symptoms. Stents can also be positioned in other parts of
the body, such as the kidneys or the brain. The stent procedure is
fairly common, and various types of stents have been developed and
actually used. However, since the bare metal surface of the stents
may trigger restenosis, the stent surface should be altered to make
it more biocompatible. Stents coated with polymers have been
offered to reduce likelihood of restenosis caused by the metal
surface of stents. Further, there are various types of polymer
coats for stents which contain drugs which are delivered to an
afflicted area of a body lumen. Drugs may be either bonded
chemically, physically or absorbed in the polymer matrix. Also, for
the purpose of obtaining drug delivery stents, the drugs may be
directly coated or immobilized onto the stents, e.g. using a
binding molecule between the drug molecule and the stent
surface.
[0003] Previously, such coated stents have been manufactured by
shaping the body of the stents first by photo-etching, laser
ablation, electron beam ablation, or any other means, and then
coating the stents with polymer compositions or drug compositions
by dip-coating, spray-coating or any other means. However, due to
the complex geometry of the stent, applying an even coating on a
metal stent is very difficult. Therefore, methods for easily
manufacturing a stent with uniform coating(s) are necessary.
[0004] In addition, the polymer coating, when applied by methods in
the art, tends to create bridges at small gaps or corners between
stent struts. Also, in the conventional methods, wherein a coating
process takes place after a shaping process, it is almost
impossible to selectively coat the stent. For example, it is
impossible to coat one side of a stent without coating the other
side or to apply different coatings to the outside and inside of a
stent. Therefore, there is a need for methods of making a stent,
especially coated stent, wherein the coating(s) does not form
bridges at gaps or corners, and wherein selective coating of the
stent can be readily achieved.
SUMMARY OF THE INVENTION
[0005] These and other objectives are accomplished by the present
invention. To achieve the aforementioned objectives, a method has
been invented for manufacturing a medical device having a coated
portion by laser ablation.
[0006] An embodiment of the present invention is a method for
manufacturing a medical device having a coated portion which
comprises obtaining a structure having an inner surface and an
outer surface. At least a portion of the inner or outer surface is
coated with a first coating material. Then, the coated structure is
ablated with a laser to form at least one opening therein to form
the coated portion.
[0007] In another embodiment of the present invention, the method
for manufacturing a medical device having a coated portion
comprises obtaining a plate having a first surface and a second
surface. At least a portion of the first surface or second surface
is coated with a first coating material. The coated plate is then
ablated with a laser to form at least one opening in the coated
plate. Afterward, the coated and ablated plate is formed by folding
or shaping into the medical device.
DESCRIPTION OF THE FIGURES
[0008] FIGS. 1A through 1D show the steps of an embodiment of the
present invention.
[0009] FIG. 1A depicts a cross-sectional view of a tubular
structure.
[0010] FIG. 1B depicts a cross-sectional view of the tubular
structure after a coating is applied on its inner surface.
[0011] FIG. 1C depicts a cross-sectional view of the tubular
structure after another coating is applied on its outer
surface.
[0012] FIG. 1D depicts a cross-sectional view of a coated tube-like
portion of a medical device formed by ablating the tubular
structure with a laser.
[0013] FIG. 2A through 2E show steps of another embodiment of the
present invention.
[0014] FIG. 2A depicts a cross-sectional view of a plate.
[0015] FIG. 2B depicts a cross-sectional view of the plate after a
coating is applied on its first surface.
[0016] FIG. 2C depicts a cross-sectional view of the plate after
another coating is applied on its second surface.
[0017] FIG. 2D depicts a cross-sectional view of the coated plate
after laser ablation.
[0018] FIG. 2E depicts a cross-sectional view of a coated tube-like
portion of a medical device made by forming the ablated plate into
a desired shape.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0019] In a method of the present invention, a structure or a plate
is coated first, and then, ablated by a laser to form openings.
Such ablation may be conducted with a ultrashort-pulse laser.
"Ultrashort-pulse lasers" refer to lasers (light amplification by
stimulated emission of radiation) consisting of pulses with
durations shorter than about 10 pico (=10.sup.-11) second. The
ultrashort-pulse laser is clearly distinguished from conventional
continuous wave and long-pulse lasers (nanosecond (10.sup.-9 sec)
laser) which have significantly longer pulses.
[0020] When a material is ablated by a conventional laser, the
material is removed by thermal ablation wherein the material is
locally heated to near melting point or boiling point. Thus,
ablation using conventional lasers has various problems. For
example, the ablation is furthermore accompanied by a heat transfer
and a strong thermal shock to surrounding material which might
cause serious damage, such as cracking. Also, the material once
removed tends to redeposit or re-solidify on the surrounding
surface. Thus, a material ablated by a conventional laser must be
cleaned to remove the redeposited material surrounding the cut
surface. Hence, if a material having an immobilized molecule on its
surface is ablated by a conventional laser, because a clearing step
is required, the immobilized molecule may be washed away at the
cleaning step. Also, since process parameters for a conventional
laser ablation, such as boiling point and absorption of the laser
light, varies according to materials to be ablated, a layered
material consisting of layers made of different materials cannot be
ablated by a conventional laser.
[0021] On the other hand, ablation using an ultrashort-pulse laser
is free from such problems. The ultrashort-pulse deposits its
energy so quickly that it does not interact at all with the plume
of vaporized material, which would distort and bend the incoming
beam and produce a rough-edged cut. The plasma plume leaves the
surface very rapidly, ensuring that it is well beyond the cut edges
before the arrival of the next laser pulse. Since the pulse is very
short, atoms in a material to be ablated are stationary in space
with respect to the pulse duration. As a result, the
ultrashort-pulse laser does not react differently between
dielectric materials and electric materials. Thus, any material,
including glasses, polymers, ceramics, silicon, and metals, can be
ablated with very high precision without damage in surrounding area
by ultrashort-pulse lasers due to the absence of heat shock waves.
In addition, the surface ablated with a ultrashort-pulse laser has
an excellent quality which does not need further polishing as
required for a surface ablated with a conventional laser because
redeposition is less or absent.
[0022] The lasers suitable for use in the method of the present
invention are preferably ultrashort-pulse lasers consisting of
pulses shorter than about 10.sup.-11 second, preferably shorter
than about 10.sup.-12 second, and most preferably shorter than
about 10.sup.-13 second which are referred to as femtosecond
lasers. The ultrashort-pulse laser used for the
[0023] The intensity (fluence) of the laser radiation that is
required to ablate a material is dependent on the material to be
ablated. Specifically each material has its own laser-induced
optical breakdown (LIOB) threshold which characterizes the fluence
required to ablate the material at a particular pulse width. Also
the fluence of the ultrashort-pulse laser suitable for the present
invention can be chosen according to the thickness of the tube
wall, the thickness of the coating and each material. Furthermore,
the number of pulses needed to ablate completely through a material
can be calculated for a given energy or fluence.
[0024] For example, a hole without any redeposition can be drilled
into a 0.7 mm thick stainless steel plate coated with a 0.3
mm-thick poly(ethylene terephthalate) coating on its one surface,
using a laser with a pulse duration of 220 femtosecond and a
fluence of 0.6 J/cm.sup.2 at a wavelength of 780 nm with a
repetition rate of 1 kHz commercial femtosecond Ti:sapphire laser
and amplifier system (SPECTRA-PHYSICS, SPITFIRE). As another
example, a hole without any redeposition can be drilled into a 0.7
mm-thick piece of tantalum with a 0.3 mm-thick poly(ethylene
oxide)/poly(butylene terephthalate) copolymer coating using a laser
with a pulse duration of 120 femtosecond and a fluence of 0.5
J/cm.sup.2 with the same system used above.
[0025] The laser ablation of the present invention can be conducted
using any additional techniques for improved accuracy and
efficiency of such ultrashort-pulse laser ablation, e.g.
diffractive optical elements (DOEs) and/or polarization trepanning.
See C. Momma et al., Beam delivery of femtosecond laser radiation
by diffractive optical elements, Appl. Phys. A 67, 517-520 (1998);
S. Nolte et al., Polarization effects in ultrashort-pulse laser
drilling, Appl. Phys. A 68, 563-567 (1999), both are incorporated
herein by reference.
[0026] The ultrashort-pulse lasers are known to artisans. For
example, they are thoroughly disclosed by M. D. Perry et al. in
Ultrashort-Pulse Laser Machining, Section K-ICALEO 1998, pp. 1-20,
which is incorporated herein by reference.
[0027] An embodiment of the present invention is illustrated in
FIGS. 1A-1D in which a tubular structure made of a suitable medical
device material is coated with a coating material or composition.
FIG. 1A depicts a cross-sectional view of a tubular structure 10
made of a suitable medical device material. The inner surface of
the tubular structure 10 is coated with first coating material or
composition 12 (FIG. 1B). Then, the outer surface of the tubular
structure 10 is also coated with second coating material or
composition 14 (FIG. 1C) which can be the same as the first coating
material or composition. The tubular structure 10 having an inner
coating 12 and outer coating 14 is ablated by an ultrashort-pulse
laser to form openings that made up a geometric pattern in the
tubular structure (FIG. 1D). In this manner, a coated tube-like
portion of a medical device 16 is formed. Alternatively, only one
of the surfaces, e.g. inner or outer, may be coated.
[0028] Another embodiment is illustrated in FIGS. 2A-2E. FIG. 2A
depicts a cross-sectional view of a plate 20 made of a suitable
medical device material. A first surface of the plate 20 is coated
with first coating material or composition 22 (FIG. 2B). Then, the
second surface of the plate 20 is also coated with second coating
material or composition 24, which can be the same as the first
coating material or composition (FIG. 2C). The plate 20 having
first coating 22 and second coating 24 is ablated by an
ultrashort-pulse laser to form openings that make up a geometric
pattern (FIG. 2D). The plate is then folded into a desired shape to
form a coated tube-like portion of a medical device 26.
[0029] The term "structure" used in relation to a medical device
means any structure which is at least a part of a medical device,
such as a tubular structure. Likewise, the term "coated portion"
used in relation to a medical device means any portion of a medical
device which has (a) coating(s) on its surface(s). An example of
such coated portion is a coated tube-like portion. Medical devices
that can be fabricated by the method of the present invention
includes those that include a tube-like or cylindrical-like
portion. The tube-like portion of the medical device need not to be
completely cylindrical. For instance, the cross-section of the
tube-like portion can be any shape, such as rectangle, a triangle,
etc., not just a circle. Such devices include, without limitation,
stents and grafts. A bifurcated stent is also included among the
medical devices which can be fabricated by the method of the
present invention.
[0030] Preferably, the medical device is a stent. Stents suitable
for the present invention include vascular stents such as
self-expanding stents and balloon expandable stents. Examples of
self-expanding stents are illustrated in U.S. Pat. Nos. 4,655,771
and 4,954,126 issued to Wallsten and 5,061,275 issued to Wallsten
et al. Examples of appropriate balloon-expandable stents are shown
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.
[0031] Appropriate materials for making the medical device are not
limited for the present invention, and any material including
ceramics, polymers and metals can be used for manufacturing the
device by the method of the present invention. Preferably, the
device is made of a biocompatible material. Examples for such
polymers include poly(ethylene terephthalate), polyacetal,
poly(lactic acid), poly(ethylene oxide)/poly(butylene
terephthalate) copolymer, and polycarbonate. Examples for such
metals include titanium, stainless steel, platinum, tantalum or
gold/platinum alloy.
[0032] In the present invention, the term "coating" encompasses all
ways of coating, such as using plasma, dipping, spraying, etching,
covering, plating, co-extruding and all modern chemical ways of
attaching bio-molecules to surfaces as well as conventional
coating. The surface is coated with a material by a method known to
the artisans, such as dipping into a polymer, spraying a coating
composition onto the surface, or attaching biomolecules to
surfaces. The surface of the structure or plate is optionally
subjected to a pre-treatment, such as roughing, oxidizing or adding
a primer, and then coated. Adding a primer is preferable as such
pre-treatment. In another embodiment, the structure or plate can be
covered with a film. Further, in another embodiment, the structure
or plate can be made by co-extrusion of the medical device material
and the coating material. More than one coating method can be used
to make a medical device. Thickness of coatings can range from
almost a single layer of molecules to about 0.1 mm. Suitable
thickness as of the coating are known in the art and can be
selected by artisans.
[0033] Medical devices coating materials suitable for the present
invention include any coating material for the stent which are
known to the skilled artisan. Suitable coating materials include,
without limitation, metals, such as tantalum, stainless steel,
nitinol, titanium, and alloys, polymeric materials, such as
poly-L-lactic acid, polycarbonate, polyethylene terephtalate,
silicones, polyurethanes, thermoplastic elastomers, ethylene vinyl
acetate copolymers, polyolefin elastomers, hydrogels and EPDM
rubbers. Such coatings include biologically active molecules, such
as heparine or insuline molecules, directly attached to oxide
molecules on the surface of the structure as explained below.
[0034] Also, the coating can be a drug-releasing coating which
immediately or gradually releases a biologically active material.
Coating polymer useful for drug coating includes hydrogel polymers
which are often used to contain the biologically active material
and are disclosed in U.S. Pat. No. 5,304,121, U.S. Pat. No.
5,464,650, PCT publication WO95/03083 and U.S. Pat. No. 5,120,322,
which are incorporated by reference. However, a non-hydrogel can be
also used. Although polymeric molecules can be combined with
biologically active molecules, biologically active materials can be
directly immobilized on the surface. As disclosed in U.S. Pat. No.
5,356,433 to Rowland et al., polysaccharides can be immobilized to
metallic surfaces by applying an organosilane coating with amine
functionality and then applying a polysaccharide using carbodiimide
as a coupling gent. U.S. Pat. No. 5,336,518 to Narayanan et al also
discloses that a polysaccharide can be immobilized on a surface by
applying a coat of heptafluorobutylmethacrylate (HFBMA) by
radiofrequency (RF) plasma deposition, creating functional groups
on the surface by RF plasma with water vapor, and then applying the
polysaccharide using carbodiimide. Moreover, examples of medical
devices, in particular, stents coated with polymer/biologically
active material coatings are described in U.S. Pat. No. 5,879,697
which is incorporated herein by reference.
[0035] The term "biologically active material" encompasses
therapeutic agents, such as drugs, and also genetic materials and
biological materials. The genetic materials mean DNA or RNA,
including, without limitation, of DNA/RNA encoding a useful protein
stated below, intended to be inserted into a human body including
viral vectors and non-viral vectors. Viral vectors include
adenoviruses, gutted adenoviruses, adeno-associated virus,
retroviruses, alpha virus (Semliki Forest, Sindbis, etc.),
lentiviruses, herpes simplex virus, ex vivo modified cells (e.g.,
stem cells, fibroblasts, myoblasts, satellite cells, pericytes,
cardiomyocytes, sketetal myocytes, macrophage), replication
competent viruses (e.g., ONYX-015), and hybrid vectors. Non-viral
vectors include artificial chromosomes and mini-chromosomes,
plasmid DNA vectors (e.g., pCOR), cationic polymers (e.g.,
polyethyleneimine, polyethyleneimine (PEI)) graft copolymers (e.g.,
polyether-PEI and polyethylene oxide-PEI), neutral polymers PVP,
SP1017 (SUPRATEK), lipids or lipoplexes, nanoparticles and
microparticles with and without targeting sequences such as the
protein transduction domain (PTD). The biological materials include
cells, yeasts, bacteria, proteins, peptides, cytokines and
hormones. Examples for peptides and proteins include growth factors
(FGF, FGF-1, FGF-2, VEGF, Endotherial Mitogenic Growth Factors, and
epidermal growth factors, transforming growth factor .alpha. and
.beta. platelet derived endothelial growth factor, platelet derived
growth factor, tumor necrosis factor .alpha., hepatocyte growth
factor and insulin like growth factor), transcription factors,
proteinkinases, CD inhibitors, thymidine kinase, and bone
morphogenic proteins (BMP's), such as BMP-2, BMP-3, BMP-4, BMP-5,
BMP-6 (Vgr-1), BMP-7 (OP-1), BMP-8. BMP-9, BMP-10, BMP-11, BMP-12,
BMP-13, BMP-14, BMP-15, and BMP-16. Currently preferred BMP's are
BMP-2, BMP-3, BMP-4, BMP-5, BMP-6, BMP-7. These dimeric proteins
can be provided as homodimers, heterodimers, or combinations
thereof, alone or together with other molecules. Cells can be of
human origin (autologous or allogeneic) or from an animal source
(xenogeneic), genetically engineered, if desired, to deliver
proteins of interest at the transplant site. The delivery media can
be formulated as needed to maintain cell function and viability.
Cells include whole bone marrow, bone marrow derived mono-nuclear
cells, progenitor cells (e.g., endothelial progentitor cells) stem
cells (e.g., mesenchymal, hematopoietic, neuronal), pluripotent
stem cells, fibroblasts, macrophage, and satellite cells.
[0036] Biologically active material also includes non-genetic
therapeutic agents, such as:
[0037] anti-thrombogenic agents such as heparin, heparin
derivatives, urokinase, and PPack (dextrophenylalanine proline
arginine chloromethylketone);
[0038] anti-proliferative agents such as enoxaprin, angiopeptin, or
monoclonal antibodies capable of blocking smooth muscle cell
proliferation, hirudin, and acetylsalicylic acid, amlodipine and
doxazosin;
[0039] anti-inflammatory agents such as glucocorticoids,
betamethasone, dexamethasone, prednisolone, corticosterone,
budesonide, estrogen, sulfasalazine, and mesalamine;
[0040] antineoplastic/antiproliferative/anti-miotic agents such as
paclitaxel, 5-fluorouracil, cisplatin, vinblastine, vincristine,
epothilones, methotrexate, azathioprine, adriamycin and mutamycin;
endostatin, angiostatin and thymidine kinase inhibitors, taxol and
its analogs or derivatives;
[0041] anesthetic agents such as lidocaine, bupivacaine, and
ropivacaine;
[0042] anti-coagulants such as D-Phe-Pro-Arg chloromethyl keton, an
RGD peptide-containing compound, heparin, antithrombin compounds,
platelet receptor antagonists, anti-thrombin anticodies,
anti-platelet receptor antibodies, aspirin (aspirin is also
classified as an analgesic, antipyretic and anti-inflammatory
drug), dipyridamole, protamine, hirudin, prostaglandin inhibitors,
platelet inhibitors and tick antiplatelet peptides;
[0043] vascular cell growth promotors such as growth factors,
Vascular Endothelial Growth Factors (FEGF, all types including
VEGF-2), growth factor receptors, transcriptional activators, and
translational promotors;
[0044] vascular cell growth inhibitors such as antiproliferative
agents, growth factor inhibitors, growth factor receptor
antagonists, transcriptional repressors, translational repressors,
replication inhibitors, inhibitory antibodies, antibodies directed
against growth factors, bifunctional molecules consisting of a
growth factor and a cytotoxin, bifunctional molecules consisting of
an antibody and a cytotoxin;
[0045] cholesterol-lowering agents; vasodilating agents; and agents
which interfere with endogenous vasoactive mechanisms;
[0046] anti-oxidants, such as probucol;
[0047] antibiotic agents, such as penicillin, cefoxitin, oxacillin,
tobranycin
[0048] angiogenic substances, such as acidic and basic fibrobrast
growth factors, estrogen including estradiol (E2), estriol (E3) and
17-Beta Estradiol; and
[0049] drugs for heart failure, such as digoxin, beta-blockers,
angiotensin-converting enzyme (ACE) inhibitors including captopril
and enalopril.
[0050] In the devices made by the method of the invention, both
surfaces of the tube-like portion can be coated with a same
material at the same time.
[0051] Also, one surface of the structure or plate need not be
coated, while the other surface has a coating. A medical device
having such portion is preferable for a drug-delivery medical
device for delivering a biologically active material to a blood
vessel surface while minimizing the amount of biologically active
material which is delivered into the blood stream. Such a medical
device is also preferable when the coating is easily damaged during
implantation of the medical device, e.g., because of the unfolding
shear-action of the delivery balloon.
[0052] Further in another embodiment, inner and outer surfaces of
the portion of the medical device can be coated with different
materials. For example, a stent can have a polymer coating having
an anti-thrombogenic agent on the inner surface which directly
contacts blood flow and a polymer coating having an
anti-inflammatory agent on the outer surface which directly
contacts blood vessel wall. The inner surface and the outer surface
can be coated by the different methods. Also, there can be more
than one coating on a surface. Furthermore, an entire surface of
the medical device is not necessarily coated.
[0053] In the present invention, the coated structure or plate is
ablated by a laser to form openings. The openings along with the
remaining parts of the structure or plate make up the geometric
pattern structure of the medical device. The structure or plate can
be moved while the laser is held stationary to ablate the structure
or plate into pattern, or alternatively, the laser can be
programmed to move along a predetermined pattern by a method known
to artisans. A combination of both, i.e. moving both the laser and
the structure or plate, is also possible. In the present invention,
even a coated stent having a complex stent pattern can be made with
high precision. A medical devices having multiple coating layers
and a complicated geometry pattern can also be easily manufactured
by the method of the present invention without flaws such as
polymer-bridges at gaps or corners. Also, the layer thickness can
be easily controlled by the method of the present invention.
[0054] In the case where a plate is coated and ablated, the plate
is formed into a portion of the medical device in the way known to
artisans. In case the coated portion is a tube-like portion, it is
formed by forming the flat plate into a tube-like shape and
attaching the opposing edges of the plate together such as by
fusing the two opposing sides. A method of fusing appropriate to a
stent material can be chosen. Methods of fusing include fusing by
heat or using adhesive.
[0055] After the ablation of the present invention, there is no
need to polish the ablated medical device to avoid rough cut
surface because of the high quality of the cut surface.
[0056] Furthermore, a plurality of medical devices can be
manufactured by coating one large structure and, as ablatin it as
explained above, cutting the structure into individual coated
portions. For example, if the coated portion is a tube-like
portion, a long tubular structure is coated first, and then
ablated, and then cut into individual tube-like portions of medical
devices. Likewise, a large plate can be coated first, cut into a
smaller plate, and then formed into an individual coated structure
and ablated. Alternatively, a large coated plate can be shaped into
a large coated structure, and then it is cut into individual coated
structures as ablated. In this way, a plurality of medical devices
be made by using one coating step. Also, all of the medical devices
will have uniform coating thicknesses.
[0057] If necessary, the thickness of the coating can be easily
measured before the ablation step. For example, it is very useful
to know an amount of a biologically active material contained in a
medical material. This amount can be calculated in the present
invention by measuring the thickness of the coating after the
coating is placed on the medical device. For example, based on the
concentration of biologically active material in the coating
composition, the thickness of the coating, the amount of
biologically active material placed on the device can be
determined.
[0058] The description contained herein is for purposes of
illustration and not for purposes of limitation. Changes and
modifications may be made to the embodiments of the description and
still be within the scope of the invention. Furthermore, obvious
changes, modifications or variations will occur to those skilled in
the art. Also, all references cited above are incorporated herein,
in their entirety, for all purposes related to this disclosure.
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