U.S. patent application number 12/399532 was filed with the patent office on 2009-09-10 for balloon catheter devices with solvent-swellable polymer.
This patent application is currently assigned to BOSTON SCIENTIFIC SCIMED, INC.. Invention is credited to John Chen.
Application Number | 20090226502 12/399532 |
Document ID | / |
Family ID | 40578099 |
Filed Date | 2009-09-10 |
United States Patent
Application |
20090226502 |
Kind Code |
A1 |
Chen; John |
September 10, 2009 |
BALLOON CATHETER DEVICES WITH SOLVENT-SWELLABLE POLYMER
Abstract
Methods for making a balloon catheter device comprising a
solvent-swellable polymer are provided. The method includes
providing a balloon, wherein a wall of the balloon or a coating
over the balloon comprises a polymer, wherein the polymer is
swellable in an organic solvent. In certain embodiments of the
invention, the polymer on the balloon is exposed to a mixture of
said solvent and a therapeutic agent; and the solvent is thereafter
removing, leaving the therapeutic agent in the polymer.
Inventors: |
Chen; John; (Plymouth,
MN) |
Correspondence
Address: |
KENYON & KENYON LLP
1500 K STREET N.W., SUITE 700
WASHINGTON
DC
20005
US
|
Assignee: |
BOSTON SCIENTIFIC SCIMED,
INC.
Maple Grove
MN
|
Family ID: |
40578099 |
Appl. No.: |
12/399532 |
Filed: |
March 6, 2009 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
61034328 |
Mar 6, 2008 |
|
|
|
Current U.S.
Class: |
424/423 ;
427/2.14 |
Current CPC
Class: |
A61M 2025/1031 20130101;
A61L 29/16 20130101; B29L 2009/005 20130101; A61M 2025/105
20130101; A61L 29/085 20130101; A61M 25/10 20130101; A61L 2300/416
20130101; A61M 25/0045 20130101; A61M 2025/0056 20130101; A61M
25/1029 20130101; A61L 29/085 20130101; C08L 53/02 20130101 |
Class at
Publication: |
424/423 ;
427/2.14 |
International
Class: |
A61M 25/10 20060101
A61M025/10; B05D 3/00 20060101 B05D003/00 |
Claims
1. A method for making a medical device, comprising: providing a
balloon, wherein a wall of the balloon or a coating over the
balloon comprises a polymer, wherein the polymer is swellable in an
organic solvent; exposing said polymer on the balloon to a mixture
of said solvent and a therapeutic agent; and removing the
solvent.
2. The method of claim 1, wherein a wall of the balloon comprises
the polymer swellable in an organic solvent.
3. The method of claim 1, wherein a coating over the balloon
comprises the polymer swellable in an organic solvent.
4. The method of claim 3, wherein the polymer is grafted to a wall
of the balloon through chemical bonding.
5. The method of claim 1, wherein the polymer is a semi-crystalline
polymer comprising crystalline regions and amorphous regions.
6. The method of claim 1, wherein the polymer is partially
cross-linked.
7. The method of claim 1, wherein the polymer is selected from the
group consisting of block copolymers of
styrene-ethylene/butylene-styrene, block copolymers of
styrene-ethylene/propylene-styrene, block copolymers of
styrene-butadiene, block copolymers of styrene-isoprene,
polyolefins, polyurethane, polyoxymethylene-acetyl copolymers,
polyamide block copolymers, copolymers of acrylates and
methacrylates, and mixtures thereof.
8. The method of claim 7, wherein the polymer is selected from the
group consisting of block copolymers of
styrene-ethylene/butylene-styrene, block copolymers of
styrene-ethylene/propylene-styrene, block copolymers of
styrene-butadiene, block copolymers of styrene-isoprene,
polyurethane, and mixtures thereof.
9. The method of claim 1, wherein the solvent is a polar organic
solvent.
10. The method of claim 1, wherein the solvent is a non-polar
organic solvent.
11. The method of claim 1, wherein the boiling point of the solvent
is about 90.degree. C. or less.
12. The method of claim 1, wherein the solvent is selected from the
group consisting of dichloromethane, chloroform, carbon
tetrachloride, ethyl acetate, tetrahydrofuran, acetonitrile,
hexane, cyclohexane, and mixtures thereof.
13. The method of claim 1, wherein the solvent is removed by
evaporation.
14. The method of claim 1, wherein the therapeutic agent is
selected from the group consisting of paclitaxel, sirolimus,
tacrolimus, everolimus, zotarolimus, and mixtures thereof.
15. A method of releasing a therapeutic agent from the surface of a
balloon catheter comprising: providing a balloon, wherein a wall of
the balloon or a coating over the balloon comprises a polymer,
wherein the polymer is swellable in an organic solvent; exposing
said polymer on the balloon to a mixture of said solvent and a
therapeutic agent; removing the solvent; and expanding the balloon
to release the therapeutic agent.
16. The method of claim 15, wherein the polymer is grafted to a
wall of the balloon through chemical bonding.
17. The method of claim 15, wherein the polymer is a
semi-crystalline polymer comprising crystalline regions and
amorphous regions.
18. The method of claim 15, wherein the polymer is partially
cross-linked.
19. The method of claim 15, wherein the boiling point of the
solvent is about 90.degree. C. or less.
20. The method of claim 15, wherein the solvent is removed by
evaporation.
Description
RELATED APPLICATIONS
[0001] This application claims the benefit of provisional
application Ser. No. 61/034,328, filed Mar. 6, 2008, which is
incorporated herein by reference in its entirety.
TECHNICAL FIELD
[0002] The present invention relates to medical devices, more
particularly, to catheter devices.
BACKGROUND
[0003] Catheters are used in a wide variety of minimally-invasive
or percutaneous medical procedures. Balloon catheters having drug
coatings may be used to treat diseased portions of blood vessels.
Typically, the balloon is inserted through a peripheral blood
vessel and then guided via a catheter through the vascular system
to the target intravascular site. However, as the balloon travels
through the vascular system, the flow of blood may wash away some
of the drug coating. In addition, the control of the timing,
location and/or duration of the release of the drug can be an
issue. Therefore, there is a need for improved catheter-based
devices for drug delivery to an intravascular site.
SUMMARY
[0004] In one embodiment, the present invention provides a method
for making a medical device, comprising: providing a balloon,
wherein a wall of the balloon or a coating over the balloon
comprises a polymer, wherein the polymer is swellable in an organic
solvent; exposing said polymer to a mixture of said solvent and a
therapeutic agent; and removing the solvent.
BRIEF DESCRIPTION OF THE DRAWINGS
[0005] FIGS. 1A and 1B show a catheter device according to an
embodiment of the present invention. FIG. 1A shows the catheter
device with the balloon in a deflated state. FIG. 1B shows the
catheter device with the balloon in an inflated state.
[0006] FIGS. 2A-2C schematically illustrate a polymer matrix in a
balloon wall or a balloon coating according to an embodiment of the
present invention. FIG. 2A shows the polymer matrix prior to
solvent exposure. FIG. 2B shows the polymer matrix in an expanded
condition after exposure to a mixture of a solvent and a
therapeutic agent. FIG. 2C shows the polymer matrix in a contracted
condition after the removal of the solvent.
DETAILED DESCRIPTION
[0007] Catheter devices of the present invention use an expandable
balloon for delivering a therapeutic agent to a target site in the
body. The balloon is designed to be insertable in the body via a
catheter. The therapeutic agent can be associated with the balloon
in any of various ways, as further described below. Any of various
mechanisms conventionally used for the delivery, actuation, or
expansion (e.g., by inflation) of balloon catheter devices may be
used in the present invention. The balloon catheter may be designed
similar to those that have been known in the art, including but not
limited to angioplasty catheters, stent delivery catheters,
inflation catheters and/or perfusion catheters. The catheter
devices of the present invention may be used in conjunction with
other drug delivery devices, such as stents.
[0008] Referring to FIGS. 1A and 1B, in certain embodiments, a
balloon catheter 20 comprises a catheter body 22 having a balloon
24 mounted thereon. In FIG. 1A, the balloon is in a deflated state;
in FIG. 1B, the balloon is in an inflated state. The body of the
balloon can be single-layered or multiple-layered.
[0009] In one aspect of the present invention, a balloon comprises
a solvent-swellable polymer. The solvent-swellable polymer may have
a therapeutic agent incorporated therein and may be used to form a
wall of the balloon or to form a coating disposed over the
balloon.
[0010] Preferably, the polymer is swellable upon exposure to an
organic solvent. The organic solvent can be polar or non-polar.
Preferably, the organic solvent has a low boiling point.
Preferably, the organic solvent has a boiling point of about
90.degree. C. or less, about 80.degree. C. or less, or about
70.degree. C. or less. Solvents with low boiling points can be
removed relatively easier than those with high boiling points.
Non-limiting examples of organic solvents include dichloromethane,
chloroform, carbon tetrachloride, ethyl acetate, tetrahydrofuran,
acetonitrile, hexane, and cyclohexane.
[0011] Optionally, the solvent-swellable polymer is a
semi-crystalline polymer. The semi-crystalline polymer can form a
polymer matrix having crystalline portions and amorphous portions.
When the polymer matrix is exposed to a mixture of a suitable
organic solvent and a therapeutic agent, the solvent and the
therapeutic agent diffuses into and swells preferentially the
amorphous regions of the polymer matrix. The crystalline portions
of the polymer matrix are more resistant to swelling, and therefore
form a stable structure that maintains the physical structure of
the polymer-containing balloon wall or coating. When the solvent is
removed, the polymer matrix contracts to its original conformation,
entrapping the therapeutic agent within the polymer matrix.
[0012] For example, referring to the schematic illustration shown
in FIGS. 2A-2C, a catheter device comprises a balloon comprising a
solvent-swellable, semi-crystalline polymer. FIG. 2A shows a
polymer matrix 70 on the wall of the balloon prior to solvent
exposure. Polymer matrix 70 has crystalline regions 72, which are
represented schematically by the lines, and amorphous regions 74,
which are represented schematically by the spaces. Referring to
FIG. 2B, upon exposure to a mixture of a solvent and a therapeutic
agent, amorphous regions 74 absorb the solvent and therapeutic
agent 76, causing polymer matrix 70 to swell. Referring to FIG. 2C,
upon removal of the solvent, polymer matrix 70 contracts to its
original conformation such that therapeutic agent 76 is retained
within polymer matrix 70.
[0013] Optionally, the solvent-swellable polymer is a partially
cross-linked polymer. Preferably, the cross-linking density is low
to allow at least a portion of the polymer to swell in an organic
solvent. The cross-linking can be done using any known methods. For
example, the cross-linking may be induced by UV irradiation or
electron beam irradiation. The cross-linked portions of the polymer
serve as the stable structure, while the non-crosslinked portions
of the polymer swell upon exposure to an organic solvent and entrap
the therapeutic agent previously mixed with the solvent after the
solvent is removed.
[0014] Optionally, the solvent-swellable polymer is grafted onto
the surface of the balloon through chemical bonding. In this case,
the balloon wall base itself serves as the stable structure, while
the polymer swells upon exposure to an organic solvent and entraps
the therapeutic agent previously mixed with the solvent after the
solvent is removed.
[0015] Non-limiting examples of solvent-swellable polymers include
block copolymers of styrene-ethylene/butylene-styrene ("SEBS"),
block copolymers of styrene-ethylene/propylene-styrene ("SEPS"),
block copolymers of styrene-butadiene-styrene ("SBS"), block
copolymers of styrene-isoprene-styrene ("SIS"), polyolefins such as
polyethylene and polypropylene, polyurethane,
polyoxymethylene-acetyl copolymers, polyamide block copolymers, and
copolymers of acrylates and methacrylates. The SEBS, SEPS, SBS, and
SIS copolymers can be commercially-available copolymers, such as
those sold under the trade names KRATON G and KRATON D. Preferably,
the solvent-swellable polymer has unsaturated bonds to allow for
cross-linking or grafting.
[0016] After the therapeutic agent is loaded into the polymer, the
solvent may be removed by any known method, for example,
evaporation or vacuum drying. Preferably, the solvent is removed
without heating. Preferably, the solvent is removed by
evaporation.
[0017] In operation, the balloon comprising a therapeutic
agent-containing polymer is inserted into the body and delivered to
the target site. The balloon is then inflated, causing the polymer
(in the case of a semi-crystalline polymer being used, polymer
matrix 70) in the balloon wall to undergo expansion by mechanical
force. By enlarging the space within the polymer (e.g. polymer
matrix 70), the therapeutic agent (e.g. therapeutic agent 76) is
released from the wall of the balloon. Because the therapeutic
agent is preferably loaded through diffusion, it tends to locate
near the surface of the wall or coating and can be easily released
after the balloon catheter device is delivered to the target
site.
[0018] Medical devices of the present invention may also include a
vascular stent mounted on the balloon. The vascular stent may be
any of those known in the art, including those with or without
coatings that contain a therapeutic agent. The stent may also be
biostable, bioerodable, or biodegradable.
[0019] The balloons of the present invention may also be coated
with a low-molecular weight carbohydrate, such as mannitol. The
carbohydrate may be a separate coating or be blended with the
therapeutic agent. The balloons of the present invention may also
be coated with a radiocontrast agent (ionic or non-ionic), such as
iopromide. The contrast agent may be a separate coating or be
blended with the therapeutic agent.
[0020] The therapeutic agent used in the present invention may be
any pharmaceutically acceptable agent (such as a drug), a
biomolecule, a small molecule, or cells. Example drugs include
anti-proliferative agents or anti-restenosis agents such as
paclitaxel, sirolimus (rapamycin), tacrolimus, everolimus, and
zotarolimus. Other example drugs include those that are
anti-spasmodic agents and vasodilators. Example biomolecules
include peptides, polypeptides and proteins; antibodies;
oligonucleotides; nucleic acids such as double or single stranded
DNA (including naked and cDNA), RNA, antisense nucleic acids such
as antisense DNA and RNA, small interfering RNA (siRNA), and
ribozymes; genes; carbohydrates; angiogenic factors including
growth factors; cell cycle inhibitors; and anti-restenosis agents.
Example small molecules include hormones, nucleotides, amino acids,
sugars, and lipids and compounds have a molecular weight of less
than 100 kD. Example cells include stem cells, progenitor cells,
endothelial cells, adult cardiomyocytes, and smooth muscle
cells.
EXAMPLE 1
[0021] A double-layered balloon is manufactured. The inner layer is
made of high density polyethylene and the outer layer is made of
SEBS (KRATON G, Kraton Polymers, Houston, Tex.). The SEBS in the
outer layer is crosslinked by electron beam irradiation. The
balloon is then immersed in a mixture of cyclohexane and paclitaxel
for drug loading. After the balloon is taken out, the cyclohexane
is removed by evaporation. The balloon is then assembled onto a
balloon catheter device.
[0022] The foregoing description and examples have been set forth
merely to illustrate the invention and are not intended to be
limiting. Each of the disclosed aspects and embodiments of the
present invention may be considered individually or in combination
with other aspects, embodiments, and variations of the invention.
Modifications of the disclosed embodiments incorporating the spirit
and substance of the invention may occur to persons skilled in the
art and such modifications are within the scope of the present
invention.
* * * * *