U.S. patent application number 13/191336 was filed with the patent office on 2011-11-17 for methods for controlling the release rate and improving the mechanical properties of a stent coating.
This patent application is currently assigned to Abbott Cardiovascular Systems Inc.. Invention is credited to Syed Faiyaz Ahmed Hossainy.
Application Number | 20110281022 13/191336 |
Document ID | / |
Family ID | 44486245 |
Filed Date | 2011-11-17 |
United States Patent
Application |
20110281022 |
Kind Code |
A1 |
Hossainy; Syed Faiyaz
Ahmed |
November 17, 2011 |
Methods For Controlling The Release Rate And Improving The
Mechanical Properties Of A Stent Coating
Abstract
Methods for controlling the release rate and improving the
mechanical properties of a stent coating are disclosed.
Inventors: |
Hossainy; Syed Faiyaz Ahmed;
(Hayward, CA) |
Assignee: |
Abbott Cardiovascular Systems
Inc.
Santa Clara
CA
|
Family ID: |
44486245 |
Appl. No.: |
13/191336 |
Filed: |
July 26, 2011 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
11899845 |
Sep 7, 2007 |
8007857 |
|
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13191336 |
|
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60843068 |
Sep 8, 2006 |
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Current U.S.
Class: |
427/2.24 |
Current CPC
Class: |
A61L 2300/602 20130101;
A61L 31/16 20130101; A61L 2300/416 20130101; A61L 31/14 20130101;
A61L 31/08 20130101; C08L 27/20 20130101 |
Class at
Publication: |
427/2.24 |
International
Class: |
B05D 3/06 20060101
B05D003/06 |
Claims
1. A method comprising: exposing a stent coated with paclitaxel and
SIBS to either (1) electron beam radiation or (2) gamma radiation
in the presence of oxygen, wherein the radiation acts to decrease
the degree of cross-linking of the SIBS, thereby providing a means
for controlling the paclitaxel release rate and improving the
mechanical properties of the coating.
2. The method of claim 1, wherein the exposure is to electron beam
radiation.
3. The method of claim 1, wherein the exposure is to gamma
radiation.
Description
CROSS REFERENCE TO RELATED APPLICATION
[0001] This application is a division of co-pending U.S.
application Ser. No. 11/899,845, which was filed on Sep. 7, 2007,
and which claims the benefit of and incorporates by reference U.S.
patent application Ser. No. 60/843,068, which was filed on Sep. 8,
2006. U.S. application Ser. No. 11/899,845 is incorporated by
reference herein in its entirety, including any drawings.
FIELD OF THE INVENTION
[0002] The present invention is directed methods for controlling
the release rate and improving the mechanical properties of a stent
coating.
BACKGROUND OF THE INVENTION
[0003] Improving the compositions from which medical articles, such
as medical devices and coatings for medical devices, are produced
is an ongoing goal of biomaterials research. An example of such a
medical device is an implantable medical device.
[0004] A stent is an example of an implantable medical device that
can benefit from improvements such as, for example, a coating that
can be used as a vehicle for delivering pharmaceutically active
agents in a predictable manner.
[0005] Stents play an important role in a variety of medical
procedures such as, for example, percutaneous transluminal coronary
angioplasty (PTCA). Stents act as a mechanical intervention to
physically hold open and, if desired, expand a passageway within a
subject. However, problems with the use of stents can include
thrombosis and restenosis, which may develop several months after a
particular procedure and create a need for additional angioplasty
or a surgical by-pass operation.
[0006] To address these problems, stents are being developed to
provide for the local delivery of agents, i.e., anti thrombotic and
anti restenosis agents. One method of local delivery includes
coating the surface of a medical article, e.g., a stent, with a
polymeric carrier and attaching an agent to, or blending it with,
the polymeric carrier. Agents can be used alone, and in
combination. However, there is continual need for novel ways to
control the release rate of an agent from a coating and for
improving the mechanical properties of a stent coating.
[0007] The present invention provides such methods and is also
directed to overcoming other deficiencies in the art.
SUMMARY OF THE INVENTION
[0008] The present invention relates to a method that involves
exposing a stent coated with a drug and polymer to ionizing
radiation, wherein the radiation acts to either increase or
decrease the degree of cross-linking of the polymer. This method
provides a means for controlling the drug release rate and
improving the mechanical properties of a coating.
[0009] Another aspect of the present invention relates to a method
for exposing a stent coated with everolimus and
poly(vinylidene-co-hexafluoropropylene) (PVDF-HFP) to either (1)
electron beam radiation or (2) gamma radiation under vacuum,
wherein the radiation acts to increase the degree of cross-linking
of the PVDF-HFP. This method provides a means for controlling the
everolimus release rate and improving the mechanical properties of
the coating.
[0010] A further aspect of the present invention relates to a
method that involves exposing a stent coated with paclitaxel and
poly(styrene-b-isobutylene-b-styrene) (SIBS) to either (1) electron
beam radiation or (2) gamma radiation in the presence of oxygen
(O.sub.2), wherein the radiation acts to decrease the degree of
cross-linking of the SIBS. This method provides a means for
controlling the paclitaxel release rate and improving the
mechanical properties of the coating.
[0011] Another aspect of the present invention relates to a method
that involves exposing a stent coated with everolimus and PVDF-HFP
to either (1) electron beam radiation or (2) gamma radiation, in
the presence of oxygen, then exposing the stent to either (1)
electron beam radiation or (2) gamma radiation, under vacuum. This
method provides a means for controlling the everolimus release rate
and improving the mechanical properties of the coating.
[0012] A further aspect of the present invention relates to a
method that involves coating a stent with a drug and polymer,
wherein during the coating process the stent is exposed to ionizing
radiation. This method provides a means for controlling the drug
release rate and improving the mechanical properties of the
coating.
[0013] The present invention provides methods for altering the
molecular weight distribution (MWD) of fluoropolymers after
drug-eluting stent (DES) coating processes have been completed, or
in one situation, during the coating process. These methods act to
tailor desired drug release rates as well as stent mechanical
properties, and also act to promote favorable biological outcomes
such as pro-healing in DES applications.
[0014] The present invention takes advantage of the following
physical phenomena: [0015] The MWD of polymers and their state of
cross-linking can be altered upon exposure to high energy ionizing
radiation, such as electron-beam (e-beam) radiation, gamma
radiation and Bremsstrahlung X-ray radiation produced by an
accelerator. [0016] The penetration of X-rays can be as high as one
order of magnitude more than the penetration of e-beam radiation.
[0017] The G-factor, i.e., the extent a polymer changes as a result
of radiation sterilization, G(X), i.e., the extent of polymer
cross-linking, G(S), i.e., the extent of polymer chain scission,
and G(Gas), i.e., the extent of gaseous product of the polymer
post-sterilization, depends on the type of polymer and the dose of
ionizing radiation. [0018] G(X)<G(S) in the presence of O.sub.2,
in contrast to under vacuum. [0019] At low ionizing radiation
dosages, i.e., less than 20 Mrad, polyvinylidene fluoride (PVDF),
poly(tetrafluoroethylene) (PTFE) and ultra high molecular weight
polyethylene (UHMPE) increase in crystallinity while at high doses,
i.e., around 2000 Mrad, both the degree of crystallinity and the Tm
drops, e.g., the Tm drops by around 25.degree. C. for poly(ethylene
terephthalate) (PET). [0020] The presence of an aromatic group,
e.g., on polystyrene, has a protective effect on both G(S) and
G(X).
[0021] The present invention takes advantage of the above physical
phenomena to design improved stent coatings using fluoropolymers,
poly(styrene-b-isobutylene-b-styrene) (SIBS), and
styrene-butadiene-styrene (SBS) polymers in conjunction with
everolimus, paclitaxel and sirolimus as specific drugs, several
embodiments of which are presented below.
[0022] In a first embodiment, a
poly(vinylidene-co-hexafluoropropylene)
(PVDF-HFP)+everolimus-coated stent will be e-beam sterilized in a
vacuum. This will enhance the degree of cross-linking of the
PVDF-HFP polymer and improve its mechanical properties upon
deployment in vivo.
[0023] In a second embodiment, a SIBS+paclitaxel-coated stent will
be e-beam sterilized in the presence of O.sub.2 at 0.degree. C.
This will reduce the G(X) for the system, i.e., decrease the degree
of cross-linking of the SIBS.
[0024] In a third embodiment, a PVDF-HFP+everolimus-coated stent
will first be e-beam sterilized in O.sub.2, then in a vacuum. The
resultant polymer will have different structural properties than
PVDF-HFP, thereby altering the drug release rate and improving the
mechanical properties of the coating.
[0025] In a fourth embodiment, gamma irradiation will be used in
place of e-beam radiation for each of the first three embodiments
of the present invention.
[0026] In a fifth embodiment, instead of applying ionizing
radiation, i.e., e-beam or gamma radiation, to a DES after the
coating process has been completed, the radiation can be applied
during the coating process. This will be achieved by sequential
coating and exposure to ionizing radiation. Employing this strategy
will enable more changes in the bulk of the polymer coating;
however, the final objectives achieved will be similar to the
post-coating embodiments set forth above.
DETAILED DESCRIPTION
[0027] The present invention relates to a method that involves
exposing a stent coated with a drug and polymer to ionizing
radiation, wherein the radiation acts to either increase or
decrease the degree of cross-linking of the polymer. This method
provides a means for controlling the drug release rate and
improving the mechanical properties of a coating.
[0028] Another aspect of the present invention relates to a method
for exposing a stent coated with everolimus and PVDF-HFP to either
(1) electron beam radiation or (2) gamma radiation under vacuum,
wherein the radiation acts to increase the degree of cross-linking
of the PVDF-HFP. This method provides a means for controlling the
everolimus release rate and improving the mechanical properties of
the coating.
[0029] A further aspect of the present invention relates to a
method that involves exposing a stent coated with paclitaxel and
SIBS to either (1) electron beam radiation or (2) gamma radiation
in the presence of oxygen (O.sub.2), wherein the radiation acts to
decrease the degree of cross-linking of the SIBS. This method
provides a means for controlling the paclitaxel release rate and
improving the mechanical properties of the coating. Another aspect
of the present invention relates to a method that involves exposing
a stent coated with everolimus and PVDF-HFP to either (1) electron
beam radiation or (2) gamma radiation, in the presence of oxygen,
then exposing the stem to either (1) electron beam radiation or (2)
gamma radiation, under vacuum. This method provides a means for
controlling the everolimus release rate and improving the
mechanical properties of the coating.
[0030] A further aspect of the present invention relates to a
method that involves coating a stent with a drug and polymer,
wherein during the coating process the stent is exposed to ionizing
radiation. This method provides a means for controlling the drug
release rate and improving the mechanical properties of the
coating.
[0031] According to the present invention, a stent coated with a
drug and polymer will be exposed to ionizing radiation to provide a
means for controlling the drug release rate and improving the
mechanical properties of a stent coating, as well as promote
favorable biological outcomes such as pro-healing in DES
applications.
[0032] According to the present invention, a stent is a medical
substrate that can be implanted in a human or veterinary patient.
Examples of stents include self-expandable stents and
balloon-expandable stents. The underlying structure of the stent
can be of virtually any design. The stent can be made of a metallic
material or an alloy.
[0033] Suitable methods for coating a stent with a drug and polymer
are known to those skilled in the art. Suitable drugs are known to
those skilled in the art, but preferably include everolimus,
paclitaxel and sirolimus. Suitable polymers are known to those
skilled in the art, but preferably include fluoropolymers,
PVDF-HFP, SIBS and SBS.
[0034] According to the present invention, suitable sources of
ionizing radiation include electron beam radiation, gamma radiation
and Bremsstrahlung X-ray radiation.
[0035] The present invention provides several means for controlling
the drug release rate and improving the mechanical properties of a
stent coating. Each method involves exposing a drug/polymer-coated
stent to ionizing radiation, either in the presence of oxygen or
under vacuum. This ionizing radiation exposure acts to either
increase or decrease the degree of cross-linking of the polymer
present in the coating, thereby providing a means for controlling
the release rate and improving the mechanical properties of the
stent coating. Five mechanisms for achieving this, as encompassed
by the present invention, are described above in accordance with
the present invention.
[0036] While particular embodiments of the present invention have
been shown and described, it will be obvious to those skilled in
the art that changes and modifications can be made without
departing from this invention in its broader aspects. Therefore,
the claims are to encompass within their scope all such changes and
modifications as fall within the true sprit and scope of this
invention.
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