U.S. patent application number 12/139263 was filed with the patent office on 2008-10-09 for medical device chemically modified by plasma polymerization.
This patent application is currently assigned to ADVANCED CARDIOVASCULAR SYSTEMS, INC.. Invention is credited to Charles D. Claude, Jeong S. Lee.
Application Number | 20080245474 12/139263 |
Document ID | / |
Family ID | 25250419 |
Filed Date | 2008-10-09 |
United States Patent
Application |
20080245474 |
Kind Code |
A1 |
Claude; Charles D. ; et
al. |
October 9, 2008 |
MEDICAL DEVICE CHEMICALLY MODIFIED BY PLASMA POLYMERIZATION
Abstract
Medical devices, and particularly intracorporeal devices for
therapeutic or diagnostic uses, having a component chemically
modified by plasma polymerization. The medical device comprises a
substrate with a plasma polymerized functionality bonded to a
surface of at least a section thereof. The plasma polymerized film
on a first component of the medical device allows for bonding an
agent or a second component to the first component. In one
embodiment, the plasma polymerized film facilitates fusion or
adhesive bonding of a first component to a second component formed
of a material which is dissimilar to, incompatible with, or
otherwise not readily bondable to the substrate material of the
first component. In another embodiment, a bioactive agent is bonded
to the plasma polymerized film on the component, for presenting or
delivering the bioactive agent within a body lumen of the
patient.
Inventors: |
Claude; Charles D.; (San
Jose, CA) ; Lee; Jeong S.; (Diamond Bar, CA) |
Correspondence
Address: |
FULWIDER PATTON, LLP (ABBOTT)
6060 CENTER DRIVE, 10TH FLOOR
LOS ANGELES
CA
90045
US
|
Assignee: |
ADVANCED CARDIOVASCULAR SYSTEMS,
INC.
Santa Clara
CA
|
Family ID: |
25250419 |
Appl. No.: |
12/139263 |
Filed: |
June 13, 2008 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
09827887 |
Apr 6, 2001 |
7396582 |
|
|
12139263 |
|
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Current U.S.
Class: |
156/273.3 ;
427/2.3 |
Current CPC
Class: |
Y10T 428/265 20150115;
Y10T 428/31504 20150401; Y10T 428/263 20150115; B05D 1/62 20130101;
Y10T 428/31544 20150401; Y10T 428/31721 20150401; A61M 25/1027
20130101; A61L 31/10 20130101; Y10T 428/31663 20150401; A61L 29/085
20130101; Y10T 428/31855 20150401; A61M 25/0014 20130101; A61M
25/1029 20130101; Y10T 428/26 20150115; Y10T 428/31551 20150401;
A61M 25/1034 20130101; A61M 25/0009 20130101; C08J 7/123 20130101;
Y10T 428/3154 20150401; Y10S 623/926 20130101 |
Class at
Publication: |
156/273.3 ;
427/2.3 |
International
Class: |
B32B 37/02 20060101
B32B037/02; A61L 33/06 20060101 A61L033/06 |
Claims
1-22. (canceled)
23. A method of treating a surface of at least a section of a
medical device, comprising exposing at least a section the medical
device formed of a polymeric material having a node and fibril
microstructure to a plasma to deposit a plasma polymerized
functionality on the section of the medical device.
24. The method of claim 23 wherein the polymeric material of the
section of the medical device is expanded polytetrafluoroethylene,
and depositing the functionality on the section of the medical
device comprises exposing the section to a plasma without
decomposing the polymeric material of the section of the medical
device.
25. The method of claim 23 wherein depositing the functionality on
the section of the medical device comprises exposing the section to
an acrylic acid plasma to form a carboxylate plasma polymerized
film thereon.
26. The method of claim 25 including providing carbon dioxide in
the acrylic acid plasma to limit a rate of decarboxylation from the
section of the medical device.
27. The method of claim 23 including bonding an agent selected from
the group consisting of a bioactive agent and an adhesive to at
least a portion of the section of the medical device having the
plasma polymerized functionality.
28. A method of making a medical device, comprising a) exposing at
least a section of a first component formed at least in part of a
first polymeric material to a plasma to deposit a plasma
polymerized functionality on the section of the first component of
the device; and b) bonding a second component formed of a second
polymeric material different from the first polymeric material to
the section of the first component having the plasma polymerized
functionality thereon.
29. The method of claim 28 wherein the plasma is applied at a high
pressure to chemically modify an inner surface of the first
component.
30. The method of claim 28 wherein the plasma polymerized
functionality is selected from the group consisting of carboxylate,
amine, and sulfate, and the plasma polymerized functionality is a
film formed with a thickness of about 10 nm to about 150 nm.
31. The method of claim 28 wherein the plasma polymerized
functionality is selected from the group consisting of a
carboxylate, an amine, and a sulfate, and (b) comprises fusion
bonding the first component to the second component.
32. The method of claim 28 wherein the second polymeric material is
incompatible with the first polymeric material, and (b) comprises
fusion bonding the first component to the second component.
33. A method of making a medical device, comprising a) exposing at
least a section of a substrate of the medical device formed at
least in part of a first polymeric material to an acrylic acid
plasma, to deposit a plasma polymerized carboxylate functionality
on the section of the medical device substrate; and b) bonding a
material different from the first polymeric material to the section
of the substrate having the plasma polymerized functionality
deposited thereon.
34. The method of claim 33 wherein b) comprises fusion or
adhesively bonding the material to the substrate.
35. The method of claim 33 including generating the acrylic acid
plasma by passing argon enriched in acrylic acid monomer through a
radio frequency transducer.
36. The method of claim 35 wherein carbon dioxide is included with
the argon, to limit the rate of decarboxylation from the surface of
the substrate having the plasma polymerized and deposited
carboxylate functionality.
37. The method of claim 33 including minimizing the degree of
crosslinking in the plasma polymerized and deposited carboxylate
functionality to less than about 5%.
38. The method of claim 33 wherein the substrate is exposed to the
acrylic acid plasma for about 3 minutes or more to form a plasma
polymerized and deposited film having a thickness of about 10 to
about 150 nm and having a surface with the same composition as a
bulk of the film.
39. The method of claim 33 including, before a), treating the
substrate with an argon plasma to prepare a surface of the
substrate.
40. The method of claim 33 wherein following exposure to the
acrylic acid plasma, the plasma field is purged with argon under no
radio frequency power to allow surface free-radicals to recombine
before exposure to atmospheric oxygen.
Description
BACKGROUND OF THE INVENTION
[0001] This invention generally relates to medical devices, and
particularly intracorporeal devices for therapeutic or diagnostic
uses, such as balloon catheters.
[0002] In percutaneous transluminal coronary angioplasty (PTCA)
procedures, a guiding catheter is advanced until the distal tip of
the guiding catheter is seated in the ostium of a desired coronary
artery. A guidewire, is first advanced out of the distal end of the
guiding catheter into the patient's coronary artery until the
distal end of the guidewire crosses a lesion to be dilated. Then
the dilatation catheter having an inflatable balloon on the distal
portion thereof is advanced into the patient's coronary anatomy,
over the previously introduced guidewire, until the balloon of the
dilatation catheter is properly positioned across the lesion. Once
properly positioned, the dilatation balloon is inflated with fluid
one or more times to a predetermined size at relatively high
pressures (e.g. greater than 8 atmospheres) so that the stenosis is
compressed against the arterial wall and the wall expanded to open
up the passageway. Generally, the inflated diameter of the balloon
is approximately the same diameter as the native diameter of the
body lumen being dilated so as to complete the dilatation but not
overexpand the artery wall. Substantial, uncontrolled expansion of
the balloon against the vessel wall can cause trauma to the vessel
wall. After the balloon is finally deflated, blood flow resumes
through the dilated artery and the dilatation catheter can be
removed therefrom.
[0003] In such angioplasty procedures, there may be restenosis of
the artery, i.e. reformation of the arterial blockage, which
necessitates either another angioplasty procedure, or some other
method of repairing or strengthening the dilated area. To reduce
the restenosis rate and to strengthen the dilated area, physicians
frequently implant an intravascular prosthesis, generally called a
stent, inside the artery at the site of the lesion. Stents may also
be used to repair vessels having an intimal flap or dissection or
to generally strengthen a weakened section of a vessel. Stents are
usually delivered to a desired location within a coronary artery in
a contracted condition on a balloon of a catheter which is similar
in many respects to a balloon angioplasty catheter, and expanded to
a larger diameter by expansion of the balloon. The balloon is
deflated to remove the catheter and the stent left in place within
the artery at the site of the dilated lesion. Stent covers on an
inner or an outer surface of the stent have been used in, for
example, the treatment of pseudo-aneurysms and perforated arteries,
and to prevent prolapse of plaque. Similarly, vascular grafts
comprising cylindrical tubes made from tissue or synthetic
materials such as DACRON, may be implanted in vessels to strengthen
or repair the vessel, or used in an anastomosis procedure to
connect vessels segments together.
[0004] In the manufacture of catheters, one difficulty has been the
bonding of dissimilar materials together. The fusion bonding of a
dissimilar material to a substrate material can be extremely
difficult if the substrate has a low surface energy. For example,
lubricious materials such as HDPE and PTFE, often used to form
inner tubular members of catheters to provide good guidewire
movement therein, have low surface energies of 31 dynes/cm and 18
dynes/cm, respectively, that make bonding to balloons formed of a
dissimilar material such as a polyamide difficult. Prior attempts
to address this problem involved providing a multilayered shaft
having an outer layer on the shaft configured to be bondable to the
balloon. However, a decrease in shaft collapse pressure resistance
may result in some cases when the outer layer has a lower stiffness
than the a shaft material. While adhesives may be used in some
cases to bond dissimilar materials together, they are not ideal
because they can increase stiffness of the component at the bond
and some materials do not bond well to adhesives commonly used in
medical devices.
[0005] It would be a significant advance to provide a catheter or
other medical device component with improved bondability.
SUMMARY OF THE INVENTION
[0006] This invention is directed to medical devices, and
particularly intracorporeal devices for therapeutic or diagnostic
uses, having a component chemically modified by plasma
polymerization. The medical device comprises a substrate with a
plasma polymerized functionality bonded to a surface of at least a
section thereof. The plasma polymerized functionality generally
comprises a film covalently bonded to the substrate. The plasma
polymerized film on a first component of the medical device allows
for bonding an agent or a second component to the first component.
In one embodiment, the plasma polymerized film facilitates fusion
or adhesive bonding of a first component to a second component
formed of a material which is dissimilar to, incompatible with, or
otherwise not readily bondable to the substrate material of the
first component. In another embodiment, a bioactive agent, or a
spacer attached to a bioactive agent, is bonded to the plasma
polymerized film on the component, for presenting or delivering the
bioactive agent within a body lumen of the patient.
[0007] The plasma polymerized film may comprise a variety of
suitable functionalities including carboxylate, amine, and
sulfonate groups, which are polymerized on at least a surface of
the substrate of the medical device component. In one embodiment,
the plasma polymerized film, or functionality thereof, is an
acrylate, and preferably acrylic acid. The plasma polymerized film
is typically crosslinked to varying degrees depending on the nature
of the compounds in the plasma which form the film and the
radiofrequency (RF) intensity used in the plasma polymerization
process. In a presently preferred embodiment, the degree of
crosslinking is minimized in order to maximize the chemical
modification, i.e., the amount of the plasma polymerized
functionality on the surface of the component. In one embodiment,
the degree of crosslinking in the plasma polymerized film is less
than about 5%. The medical device component substrate may be formed
of a variety of suitable materials including fluoropolymers such as
polytetrafluoroethylene (PTFE) or expanded polytetrafluoroethylene
(ePTFE), polyolefins such as high density polyethylene (HDPE), and
engineering thermoplastic or thermoset polymers such as
polyetherether ketone (PEEK) or polyimide.
[0008] In one embodiment, the medical device component having a
plasma polymerized functionality bonded thereto is a shaft or
balloon of an intravascular catheter. However, a variety of medical
devices may be chemically modified by plasma polymerization
according to the invention, including a cover for a stent, and a
vascular graft. Balloon catheters of the invention such as an
angioplasty catheter or a stent delivery catheter have a component,
such as the catheter balloon, shaft, or a stent cover, which is
chemically modified by plasma polymerization, and generally
comprise an elongated shaft with at least one lumen and balloon on
a distal shaft section with an interior in fluid communication with
the shaft lumen. Vascular grafts and stent covers of the invention
generally comprise a tubular body formed at least in part of a
substrate chemically modified by plasma polymerization. The
terminology vascular graft as used herein should be understood to
include grafts and endoluminal prostheses which are surgically
attached to vessels in procedures such as vascular bypass or
anastomosis, or which are implanted within vessels, as for example
in aneurysm repair or at the site of a balloon angioplasty or stent
deployment. The terminology component as used herein should be
understood to include medical devices such as catheters having
multiple components, as well as single component devices such as
vascular grafts.
[0009] In one embodiment, the component is a catheter balloon
formed at least in part of ePTFE, which, in accordance with the
invention, has a plasma polymerized film on at least one of an
inner and an outer surface of the ePTFE. The plasma polymerized
film on the ePTFE balloon enhances adhesion of polymeric materials
such as elastomers, adhesives, and structural polymers, and agents
such as bioactive materials, to the ePTFE balloon. For example, in
a presently preferred embodiment, the ePTFE balloon has a plasma
polymerized film which facilitates bonding an elastomeric material
to the chemically modified surface of at least a section of the
ePTFE, so that the porous ePTFE layer can be inflated.
Additionally, in one embodiment, the plasma polymerized film
facilitates bonding the ePTFE balloon to the catheter shaft. In a
presently preferred embodiment, the entire length of the ePTFE
layer has the plasma polymerized film. ePTFE is PTFE which as been
expanded, and the expanded ePTFE typically has a microporous
structure comprising nodes interconnected by fibrils. ePTFE is
extremely difficult to bond to, and one difficulty has been
adhesively bonding ePTFE, absent some pretreatment causing
decomposition of the fibril structure or the use of adhesives
interlocking in the pore structure of the ePTFE. Unlike chemical
modification involving decomposition (i.e., defluoronation) of the
ePTFE using compounds including bases (i.e., alkali metal
compounds) such as sodium napthalide, or using irradiation with
.lamda.-ray or electron beams, corona discharge, glow discharge or
plasma etching processes such as oxygen or trifluoroamine -etching,
the plasma polymerization chemical modification of the invention
has minimal effect on the structural integrity of the ePTFE
material. The plasma polymerization of the invention deposits an
organic layer onto the ePTFE surface which prevents or inhibits
etching of the ePTFE microstructure from occurring during the
plasma polymerization process. Thus, in one embodiment, the bulk
and the surface of the ePTFE material of the component of the
invention has a bulk and a surface in a nondecomposed state. The
medical device component of the invention has insubstantial or no
etching or decomposition of the node and fibril structure of the
component substrate from the plasma polymerization process, so that
performance characteristics such as tensile strength or average
burst pressure of the component are not disadvantageously effected
by the plasma polymerization, unlike the effects caused by
defluoronation processes or processes otherwise causing
decomposition of the substrate structure. Although discussed
primarily in terms of ePTFE, it should be understood that the
component of the therapeutic or diagnostic device may comprise
other substrates including polyethylene, and other substrates
having a node and fibril microstructure such as polypropylene,
nylon, and ultrahigh molecular weight polyethylene, where plasma
etching or other decomposition processes used to allow adhesive
bonding are to be avoided.
[0010] In another embodiment, the component is a catheter shaft,
which in accordance with the invention has a plasma polymerized
film on at least a section thereof. The plasma polymerized film
provides for improved ability to bond the catheter shaft section to
other device components such as a balloon or a second catheter
shaft section. The shaft section having the plasma polymerized film
is typically formed of materials such as HDPE, fluoropolymers,
polyether ether ketone (PEEK), and polyimide. For example, in one
embodiment, the shaft has at least a section formed at least in
part of a first polymeric material such as HDPE, bonded to a
balloon formed at least in part of a second polymeric material such
as a. polyamide which is incompatible with the first material, and
which thus is not otherwise readily fusion bondable to the first
material. The plasma polymerized film provides a surface compatible
with the second polymeric material to facilitate fusion bonding
thereto. Alternatively, the plasma polymerized film provides a
surface which facilitates adhesive bonding the shaft to the second
polymeric material. In one embodiment, the surface of a shaft
formed of HDPE or fluoropolymer is modified by plasma
polymerization according to the invention to provide for bonding to
other, typically incompatible materials such as polyamides
including nylon and polyether block amide (PEBAX). Similarly, the
surface of a shaft formed of PEEK or polyimide, modified by plasma
polymerization according to the invention, provides for bonding to
other materials such as polyamides including PEBAX. The thin plasma
polymerized film provides for improved manufacturability and low
profile, and without a disadvantageous decrease in shaft collapse
pressure resistance.
[0011] The invention also comprises methods of treating a surface
of at least a section of a medical device, generally comprising
exposing the at least a section to a plasma to form a plasma
polymerized film thereon. The thickness of the plasma polymerized
film is controlled by the duration of the applied plasma, and in
one embodiment the plasma polymerized film is about 10 nm to about
150 nm thick, preferably about 50 nm to about 125 nm thick. The
section may be first treated with an argon plasma to prepare the
surface prior to exposure to the plasma polymerized film
deposition. In one embodiment, the method comprises exposing at
least a section of a first component to a plasma to form a plasma
polymerized film on the section of the first component, wherein the
first component of the therapeutic or diagnostic device is formed
at least in part of first polymeric material, and then bonding a
second component formed of a polymeric material different from or
incompatible with the first polymeric material. In another
embodiment, the method comprises exposing at least a section a
component to a plasma to form a plasma polymerized film on the
section of the component, wherein the component is formed at least
in part of a polymeric material having a node and fibril
microstructure, without decomposing the polymeric material of the
component.
[0012] In the plasma polymerization according to the invention,
free-radical organic species, such as fragmented acrylic acid, in
the plasma will couple with the surface of a substrate such as
ePTFE, HDPE, PEEK, or polyimide, resulting in a crosslinked thin
film which is covalently bonded to the substrate. Selection of the
appropriate RF field strength, monomer, and co-reactant results in
a thin surface and polymer bulk film which is rich in the organic
functionality, such as carboxylate. The plasma polymerized film
exhibits minimum re-organization to minimize its surface energy
since the surface has a similar molecular composition as the thin
bulk film.
[0013] The medical device component of the invention, such as
catheter balloons and shafts, stent covers, and vascular grafts,
have improved manufacturability and/or performance due to the
plasma polymerized film, which allows for bonding of polymeric
materials, and agents such as adhesives and bioactive agents to the
chemically modified substrate material forming the component. The
chemical modification of the invention is a permanent surface
modification, unlike plasma etching processes in which any
beneficial effects on the surface energy of the substrate quickly
decrease as a function of time as described by Yasuda and Sharma,
J. Polym. Sci. Polym. Phys., Ed. 19:1285 (1981), incorporated by
reference herein. Additionally, the deposition of the plasma
polymerized film on the medical device component produces little or
no decomposition of the chemical structure of the component
substrate material. These and other advantages of the invention
will become more apparent from the following detailed description
when taken in conjunction with the accompanying exemplary
drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
[0014] FIG. 1 is an elevational view, partially in section, of a
balloon catheter for delivering a stent, that embodies features of
the invention.
[0015] FIG. 2 is a transverse cross-section of the catheter shown
in FIG. 1 taken at line 2-2.
[0016] FIG. 3 is a transverse cross-section of the catheter shown
in FIG. 1 taken at line 3-3, showing the stent disposed over the
inflatable balloon.
[0017] FIG. 4 is an elevational view, partially in section, of a
vascular graft or stent cover which embodies features of the
invention.
[0018] FIG. 5 is a transverse cross-section of the graft or cover
shown in FIG. 4, taken along lines 5-5.
DETAILED DESCRIPTION OF THE INVENTION
[0019] FIGS. 1-3 illustrate an over-the-wire type stent delivery
balloon catheter 10 embodying features of the invention. Catheter
10 generally comprises an elongated catheter shaft 12 having an
outer tubular member 14 and an inner tubular member 16. Inner
tubular member 16 defines a guidewire lumen 18 configured to
slidingly receive a guidewire 20. The coaxial relationship between
outer tubular member 14 and inner tubular member 16 defines annular
inflation lumen 22. An inflatable balloon 24 is disposed on a
distal section of catheter shaft 12, having a proximal skirt 25
sealingly secured to the distal end of outer tubular member 14 and
a distal skirt 26 sealingly secured to the distal end of inner
tubular member 16, so that its interior is in fluid communication
with inflation lumen 22. An adapter 36 at the proximal end of
catheter shaft 12 is configured to direct inflation fluid through
arm 38 into inflation lumen 22 and to provide access to guidewire
lumen 18. Balloon 24 has an inflatable working length 27 located
between tapered sections of the balloon. An expandable stent 30 is
mounted on balloon working length. FIG. 1 illustrates the balloon
24 in an uninflated configuration prior to deployment of the stent
30. The distal end of catheter may be advanced to a desired region
of a patient's body lumen 32 in a conventional manner, and balloon
24 inflated to expand stent 30, seating the stent in the body lumen
32.
[0020] In the embodiment illustrated in FIG. 1, the balloon 24
comprises a microporous material having a node and fibril
microstructure, such as ePTFE. Balloon 24 has a layer 33 of ePTFE,
and a second layer 34 formed from a material such as an elastomeric
material including polyurethanes such as BIONATE available from PTG
or PELLETHANE available from Dow, silicone rubbers,
styrene-butadiene-styrene block copolymers, and polyamide block
copolymers, and the like. In a preferred embodiment, layer 34 is on
the interior of balloon 24, although in other embodiments it may be
on the exterior or the balloon 24. Layer 34 formed of an
elastomeric material limits or prevents leakage of inflation fluid
through the microporous ePTFE to allow for inflation of the balloon
24, and expands elastically to facilitate deflation of the balloon.
24 to a low profile deflated configuration. The elastomeric
material forming layer 34 may consist of a separate layer which
neither fills the pores nor disturbs the node and fibril structure
of the ePTFE layer, or it may at least partially fill the pores of
the ePTFE layer. Typically, the ePTFE comprises a film of stretched
material which is formed into the tubular member layer 33 by
wrapping the ePTFE material around a mandrel to form a tube and
then heating the wrapped material to fuse the wrapped material
together.
[0021] At least a section of the ePTFE of the balloon 24 is
chemically modified by plasma polymerization in accordance with the
invention. In the embodiment of FIG. 1, the entire length of at
least an inner surface of ePTFE layer 33 has a plasma polymerized
film, which in accordance with the invention, facilitates bonding
layer 33 to layer 34. However, in alternative embodiments, less
than the entire length may be chemically modified by masking a part
of the substrate using methods conventionally known in the field.
Layer 33 is preferably fusion bonded to layer 34. In the embodiment
illustrated in FIG. 1, layer 34 is fusion or adhesively bonded to
the outer surface of the shaft outer tubular member and inner
tubular member to secure the balloon 24 to the shaft. However, in
an alternative embodiment, the elastomeric layer 34 does not extend
the entire length of the ePTFE layer 33, and the thus exposed one
or both end sections of the chemically modified ePTFE layer 33 are
fusion or adhesively bonded to the shaft (not shown).
[0022] The chemically modified surfaces of the balloon comprise a
film (not shown) deposited on the surface of the ePTFE by plasma
polymerization. In a presently preferred embodiment, the balloon is
chemically modified to create a carboxylate-rich surface. However,
a variety of suitable functionalities can be plasma polymerized on
the surface of the balloon including amine, and sulfate
functionalities. In a presently preferred embodiment, the plasma
polymerized carboxylate film comprises an acrylate or acrylate-like
polymer layer deposited onto the ePTFE by exposing the ePTFE film
to a plasma, which in a presently preferred embodiment is an
acrylic acid plasma. One of skill in the art will recognize that
some fragmentation of the acrylate typically occurs during plasma
polymerization, resulting in an acrylate-like polymer layer of
fragmented acrylate. In a presently preferred embodiment, the
acrylate is acrylic acid. While discussed below primarily in terms
of applying a carboxylate film by plasma polymerization of acrylic
acid on ePTFE, it should be understood that a variety of
functionalities on a variety of substrates may be used.
[0023] In a presently preferred embodiment, the ePTFE is chemically
modified to create a carboxylic acid rich surface by exposure to an
acrylic acid plasma. In one embodiment, the method comprises
introducing the ePTFE into an argon plasma field to remove organic
processing debris from the surface of the ePTFE film before
deposition of the plasma polymerized film. Preferably, ePTFE film
is pre-treated in the argon plasma field at about 200 to 250 mTorr,
preferably about 230 mTorr, with an applied RF field of about 100
to 250 W, preferably about 150 W, for about 1 to 3 minutes,
preferably about 3 minutes. An acrylic acid plasma is then applied
to the ePTFE to produce a carboxylate rich film on the ePTFE. The
power of the acrylic acid plasma is about 80 to about 200 W, and
preferably about 100 W, with an acrylic acid flow rate of about 0.5
ml/min, at a pressure of about 150 mtorr. The concentration of the
carboxylate is dependent on the plasma power, wherein the
carboxylate concentration decreases as the RF power increases. The
acrylic acid plasma is applied for about 3 to about 10 minutes,
preferably about 5 to about 10 minutes, depending on the desired
thickness of the carboxylate rich film. The thickness of the
carboxylate rich film is about 25 to about 150 nm, preferably about
50 to about 125 nm in the embodiment in which the carboxylate rich
film is deposited on a balloon shaft section for bonding to a
catheter shaft. In one embodiment, following exposure to the
acrylic acid plasma, the plasma field is purged with argon under no
RF power to allow surface free-radicals to recombine before
exposure to atmospheric oxygen.
[0024] In a presently preferred embodiment, carbon dioxide is
included in the acrylic acid plasma to limit the rate of
decarboxylation from the surface of the ePTFE. The plasma
polymerization is a competitive reaction in which polymerization of
acrylic acid with surface radical functionalities is greater than
the rate of decarboxylation. The decarboxylation of the acrylic
acid is caused by fragmentation of the carboxylate, resulting in
the formation of carbon dioxide gas and the crosslinking of the
deposited film and the loss of carboxylate functionality. Thus, by
adding carbon dioxide to the acrylic acid plasma, the
decarboxylation of the organic reactive species in the RF field can
be decreased. In a preferred embodiment, the carbon dioxide
concentration in the acrylic acid plasma is about 8 to about 10%,
preferably about 9%.
[0025] The plasma polymerization results in a thin carboxylate film
deposited onto the substrate. The surface of the substrate has the
same polymer composition as the bulk of the substrate, so that the
surface and the bulk of the substrate have similar carboxylate
concentration following deposition of the plasma polymerized film.
The similar carboxylate concentration minimizes the time dependent
variation of the surface energy. The structural integrity of the
ePTFE layer 33 of the balloon is minimally or not effected by the
plasma polymerization.
[0026] In the embodiment in which the plasma polymerized film is
deposited on an inner surface of the medical device component such
as the inner surface of tubular layer 33, the plasma polymerized
film is preferably formed using a high pressure RF plasma. For
example, in a presently preferred embodiment, a high pressure RF
plasma of about 1 atm (760 Torr) to about 1.25 atm (950 Torr), and
preferably about 1.05 atm (798 Torr) to about 1.22 atm (927 Torr)
is used in embodiments in which the plasma polymerized film is
deposited on an inner surface (i.e., a surface defining a medical
device lumen) of the medical device component. Specifically, in one
embodiment, a plasma polymerized film of acrylic acid is deposited
on an inner surface of a tubular substrate according to the
following process. Argon and carbon dioxide are bubbled through
acrylic acid monomer, at flow rates of about 9.5 to about 15
standard liters per minute (slpm), preferably about 10.5 slpm, and
about 0.05 to about 0.2 slpm, preferably about 0.1 slpm,
respectively, and through a gas dispersion plate. The argon and
carbon dioxide enriched in monomer is then passed through an RF
transducer, forming a plasma which is passed through the inner
lumen of the substrate. Due to the limited stability of the plasma
species, the velocity of the plasma through the inner lumen of the
substrate must be sufficiently high that the desired length of the
substrate is chemically modified. The velocity of the plasma
through the lumen is typically about 30 to about 350 meters per
second (m/s), more specifically about 280 to 300 m/s. The pressure
of the system is about 1.05 atm (798 Torr) to about 1.22 atm (927
Torr), and the concentration of acrylic acid, which is controlled
by the vapor pressure and thus the temperature, is about
5.times.10.sup.-5 moles/liter of gas.
[0027] In another embodiment of the invention, the component
chemically modified by plasma polymerization comprises a catheter
shaft similar to shaft 12 of FIG. 1. While discussed below in terms
of the catheter 10 illustrated in FIG. 1, it should be understood
that in the embodiment in which the component chemically modified
by plasma polymerization is the catheter shaft, the catheter
balloon 24 is not necessarily an ePTFE balloon or a balloon with
layer 34 on layer 33. The plasma polymerized film is applied to at
least a section of one or both of the outer tubular member 14 and
inner tubular member, depending on the purpose of the plasma
polymerized film. The film is preferably deposited on an outer
surface of the shaft, however, it may be deposited on an inner
surface of the shaft, as discussed above in relation to the
embodiment having the film deposited on an inner surface of the
balloon. To avoid the necessity of masking part of the shaft, the
plasma polymerized film may be applied to the entire surface of the
shaft, even though it is only needed at the section of the shaft
being bonded to another component. The discussion of the plasma
polymerized film disclosed above in relation to the embodiment
having an ePTFE balloon chemically modified by plasma
polymerization applies also to the embodiment having the plasma
polymerized film on the shaft. However, because the plasma
polymerized film is preferably deposited on an outer surface of the
shaft, the plasma is preferably a low pressure RF plasma, and not a
high pressure plasma as discussed above. Preferably, a low pressure
acrylic acid/carbon dioxide plasma of about 125 mTorr to about 150
mTorr, preferably at least about 145 mTorr (i.e., under vacuum), is
used to deposit the carboxylate rich film on the outer surface of
the shaft.
[0028] In one embodiment, to facilitate bonding the shaft to
balloon 24, the plasma polymerized film is applied to at least the
distal outer surface of inner tubular member 16. In one embodiment,
at least the distal section of the inner tubular member 16 is
formed of a lubricious material such as HDPE or a fluoropolymer
including PTFE, and has the plasma polymerized film on an outer
surface of at least a section thereof. In a presently preferred
embodiment, balloon 24 is a single or multilayered balloon, formed
of a material dissimilar or incompatible with the substrate
material of the inner tubular member 16. For example, balloon
material may be a polyamide such as nylon or a polyamide copolymer
such as polyether block amide (PEBAX).
[0029] The resulting inner tubular member having a chemically
modified distal section can be fusion bonded to a polyamide or
PEBAX balloon using conventional heat/laser bonding methods.
Typically, the balloon distal skirt 26 is placed over the
chemically modified distal section of the inner tubular member, and
heat applied to the distal skirt 26 to melt or soften the polymeric
material. A heat shrink sleeve may also be used during fusion
bonding which shrinks to provide pressure at the bond site. The
thickness of the plasma polymerized film forming the chemically
modified section of the inner tubular member 16 is typically about
50 to about 75 nm. Similarly, a plasma polymerized film can be
provided on a surface, and preferably an outer surface, of a distal
section of the outer tubular member 14 to facilitate bonding the
outer tubular member to the proximal skirt 25 of the balloon
24.
[0030] In another embodiment, the plasma polymerized film is
deposited on at least a section of the shaft 12 to facilitate
bonding a first shaft section to a second shaft section. For
example, a proximal shaft section having the plasma polymerized
film thereon can be bonded to a distal shaft section formed of a
different material than the proximal shaft section. In one
embodiment, the proximal shaft section is formed of a polymeric
material such as PEEK or polyimide which is stiffer than a material
such as PEBAX forming the distal shaft section.
[0031] Although discussed primarily in terms of the embodiment in
which the first component is fusion bonded to the second component,
in an alternative embodiment, the two components are adhesively
bonded together after the plasma polymerized film is deposited on
the first component. A variety of suitable adhesives commonly used
in the medical device field may be used, and the adhesive is
applied as is conventionally known by spraying, dipping or
otherwise coating a section of the shaft to be bonded.
[0032] The dimensions of catheter 10 are determined largely by the
size of the balloon and guidewires to be employed, catheter type,
and the size of the artery or other body lumen through which the
catheter must pass or the size of the stent being delivered.
Typically, the outer tubular member 14 has an outer diameter of
about 0.025 to about 0.04 inch (0.064 to 0.10 cm), usually about
0.037 inch (0.094 cm), the wall thickness of the outer tubular
member 14 can vary from about 0.002 to about 0.008 inch (0.0051 to
0.02 cm), typically about 0.003 to 0.005 inch (0.0076 to 0.013 cm).
The inner tubular member 16 typically has an inner diameter of
about 0.01 to about 0.018 inch (0.025 to 0.046 cm), usually about
0.016 inch (0.04 cm), and wall thickness of 0.004 to 0.008 inch
(0.01 to 0.02 cm). The overall length of the catheter 10 may range
from about 100 to about 150 cm, and is typically about 135 cm.
Preferably, balloon 24 may have a length about 0.5 cm to about 4 cm
and typically about 2 cm, and an inflated working diameter of about
1 to about 8 mm, and in a preferred embodiment, an uninflated
diameter of not greater than about 1.3 mm. Inner tubular member 16
and outer tubular member 14 can be formed by conventional
techniques, for example by extruding and necking materials already
found useful in intravascular catheters such a polyethylene,
polyvinyl chloride, polyesters, polyamides, polyimides,
polyurethanes, and composite materials.
[0033] In alternative embodiments, the medical device component
chemically modified by plasma polymerization in accordance with the
invention comprises a stent cover, or a vascular graft. In a
presently preferred embodiment, the stent cover or vascular graft
comprises a tubular body formed of a substrate comprising ePTFE or
other node and fibril material. However, a variety of suitable
materials may be used to form the stent cover or vascular graft of
the invention. In the embodiment illustrated in FIG. 1, a stent
cover 40 is disposed on an outer surface of the stent 30. Stent
cover 40 in accordance with the invention has a plasma polymerized
functionality bonded to at least a section thereof. Stent cover 40
is secured to the surface of the stent 30 before the stent is
introduced into the patient's vasculature, and expanded, together
with the stent, to implant the stent and stent cover thereon in the
vessel lumen. Stent cover 40 secured to the stent has a generally
tubular structure conforming to a surface of the stent. The stent
cover 40 length may be selected to fit a variety of conventionally
sized stents, with a typical diameter of about 2 mm to about 10 mm.
The stent cover 40 wall thickness is typically about 20 .mu.m to
about 400 .mu.m, preferably about 40 .mu.m to about 100 .mu.m. The
stent cover 40 provides a biocompatible, biostable surface on the
stent, and reduces plaque prolapse through the stent struts. A
stent cover may be provided on an inner surface of the stent (not
shown).
[0034] FIG. 5 illustrates vascular graft 50, which in accordance
with the invention has a plasma polymerized functionality bonded to
at least a section thereof. Vascular graft 50 generally comprises a
tubular body 51 having a lumen 52 therein, and ports 53,54 at
either end of the graft 50. The graft is configured for being
implanted in the patient, and it may be expanded into place within
a vessel or surgically attached to a vessel, such as at a free end
of a vessel. The graft 50 length is generally about 4 to about 80
mm, and more specifically about 10 to about 50 mm, depending on the
application, and wall thickness is typically about 40 .mu.m to
about 2000 .mu.m, preferably about 100 .mu.m to about 1000 .mu.m.
The diameter is generally about 1 to about 35 mm, preferably about
3 to about 12 mm, depending on the application.
[0035] A variety of suitable plasma polymerized functionalities may
be deposited on the stent cover 40 or vascular graft 50 of the
invention, as discussed above in relation to the embodiment having
the plasma polymerized functionality on a catheter component.
Presently preferred functionalities for the stent cover 40 or
vascular graft 50 include an amine functionality such as is derived
from allyl amine, and a carboxylate functionality derived from
acrylic acid.
[0036] In one embodiment, the plasma polymerized film is used to
attach bioactive agents, or a spacer or anti-fouling agent such as
polyethylene glycol (PEG) attached to the bioactive agent, to the
surface of the medical device component. A variety of suitable
bioactive agents may be used including antithrombogenic agents,
antibiotic agents, antitumor agents, antiviral agents,
antiangiogenic agents, angiogenic agents, anti-inflammatory agents
such as a superoxide dismutase mimic (SODm), and, most preferably
for vascular grafts, cell adhesion promoters such as a RGD (i.e.,
arginine-glycine-aspartic acid) peptide sequence or RGD mimetic
peptide sequence, and the like.
[0037] While the present invention is described herein in terms of
certain preferred embodiments, those skilled in the art will
recognize that various modifications and improvements may be made
to the invention without departing from the scope thereof. For
example, in the embodiment illustrated in FIG. 1, the catheter is
over-the-wire stent delivery catheter. However, one of skill in the
art will readily recognize that other types of intravascular
catheters may be used, such as and rapid exchange dilatation
catheters having a distal guidewire port and a proximal guidewire
port and a short guidewire lumen extending between the proximal and
distal guidewire ports in a distal section of the catheter.
Moreover, although individual features of one embodiment of the
invention may be discussed herein or shown in the drawings of the
one embodiment and not in other embodiments, it should be apparent
that individual features of one embodiment may be combined with one
or more features of another embodiment or features from a plurality
of embodiments.
* * * * *