U.S. patent application number 14/078212 was filed with the patent office on 2014-03-13 for direct fluid coating of drug eluting balloon.
This patent application is currently assigned to Abbott Cardiovascular Systems Inc.. The applicant listed for this patent is Abbott Cardiovascular Systems Inc.. Invention is credited to Anthony S. Andreacchi, Victoria M. Gong, Stephen D. Pacetti, Shih-Hsiung Albert Yuan.
Application Number | 20140072695 14/078212 |
Document ID | / |
Family ID | 44912016 |
Filed Date | 2014-03-13 |
United States Patent
Application |
20140072695 |
Kind Code |
A1 |
Gong; Victoria M. ; et
al. |
March 13, 2014 |
DIRECT FLUID COATING OF DRUG ELUTING BALLOON
Abstract
A system and method for coating an expandable member of a
medical device comprises providing a dispenser in fluid
communication with a fluid source with the dispenser having at
least one outlet to dispense fluid of the fluid source therefrom.
The outlet(s) of the dispenser is positioned proximate a surface of
an expandable member, with relative movement between the outlet(s)
and the surface of the expandable member established along a
coating path, and fluid is dispensed from the dispenser to form a
substantially continuous bead of fluid between the at least one
outlet and the surface of the expandable member along the coating
path, and simultaneously drying the fluid while dispensing the
fluid from the dispenser to control flow of fluid on the surface of
the expandable member. The fluid source can include a variety of
therapeutic agents.
Inventors: |
Gong; Victoria M.;
(Sunnyvale, CA) ; Pacetti; Stephen D.; (San Jose,
CA) ; Andreacchi; Anthony S.; (San Jose, CA) ;
Yuan; Shih-Hsiung Albert; (Sunnyvale, CA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Abbott Cardiovascular Systems Inc. |
Santa Clara |
CA |
US |
|
|
Assignee: |
Abbott Cardiovascular Systems
Inc.
Santa Clara
CA
|
Family ID: |
44912016 |
Appl. No.: |
14/078212 |
Filed: |
November 12, 2013 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
13108283 |
May 16, 2011 |
8632837 |
|
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14078212 |
|
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|
|
61345575 |
May 17, 2010 |
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Current U.S.
Class: |
427/2.3 ;
118/58 |
Current CPC
Class: |
B05D 1/002 20130101;
A61M 25/1027 20130101; A61L 29/08 20130101; B05D 3/0254 20130101;
B05D 1/26 20130101 |
Class at
Publication: |
427/2.3 ;
118/58 |
International
Class: |
A61L 29/08 20060101
A61L029/08 |
Claims
1. A method of coating an expandable member of a medical device,
comprising: providing a dispenser in fluid communication with a
fluid source, the dispenser having at least one outlet to dispense
fluid of the fluid source therefrom; positioning the at least one
outlet of the dispenser proximate a surface of an expandable
member; establishing relative movement between the at least one
outlet and the surface of the expandable member along a coating
path; dispensing fluid from the dispenser to form a substantially
continuous bead of fluid between the at least one outlet and the
surface of the expandable member along the coating path; and
simultaneously drying the fluid while dispensing the fluid from the
dispenser to control flow of fluid on the surface of the expandable
member.
2. The method of claim 1, wherein the fluid remains substantially
in a location where it contacts the surface of the expandable
member.
3. The method of claim 1, wherein relative movement provides a
velocity ranges approximately from 2 to 20 cm/sec.
4. The method of claim 1, wherein the dispenser is selected from
the group consisting of pipet, tubing, flexible tubing, hypotubes,
dies, and ball-bearing dispense tubing.
5. The method of claim 1, wherein the dispenser does not contact
the expandable member.
6. The method of claim 1, wherein the fluid includes a therapeutic
agent.
7. The method of claim 1, wherein the inflatable member is inflated
to a pressure of approximately 0.1 to 8 atm prior to coating.
8. The method of claim 1, wherein the dose density of therapeutic
agent on the expandable member is greater than 200
.mu.g/cm.sup.2.
9. The method of claim 1, wherein the relative movement includes
rotation, translation, or a combination thereof, of at least one of
the expandable member and the at least one outlet.
10. The method of claim 9, wherein the relative movement includes
rotation, axial translation, or a combination thereof, of the other
of the expandable member and the at least one outlet.
11. The method of claim 9, wherein the medical device further
includes a shaft extending from the expandable member, wherein
during rotation and translation of the expandable member, the shaft
remains straight.
12. The method of claim 9, wherein the medical device further
includes a shaft extending from the expandable member, wherein
during rotation and translation of the expandable member, a
rotation torque is applied to a proximal hub disposed on the
shaft.
13. The method of claim 9, wherein the relative movement includes
moving the expandable member relative a first axis, and moving the
at least one outlet relative a second axis.
14. The method of claim 9, wherein the relative movement defines a
helical coating path of the at least one outlet relative to the
expandable member.
15. The method of claim 1, wherein dispensing fluid to the surface
of the expandable member is repeated along a plurality of coating
paths.
16. The method of claim 15, wherein a first fluid is dispensed
during a first coating path, and a second fluid is dispensed during
a second coating path.
17. The method of claim 1, further comprising controlling
dispensing to apply a substantially uniform coating of fluid to a
predetermined area of the expandable member.
18. The method of claim 1, wherein the at least one outlet is
heated while dispensing fluid therefrom.
19. The method of claim 1, wherein the dispenser includes a
plurality of outlets offset from each other.
20. A system for coating an expandable member of a medical device,
the system comprising: a support structure to support an expandable
member of a medical device; a dispenser in fluid communication with
a fluid source, the dispenser having at least one outlet for
dispensing fluid of the fluid source therefrom, the dispenser
positioned with the at least one outlet proximate a surface of an
expandable member supported by the support structure; a dryer
proximate the dispenser to simultaneously dry the fluid while
dispensing the fluid from the dispenser to control flow of fluid on
the surface of the expandable member; and a drive assembly to
establish relative movement between the at least one outlet and the
surface of the expandable member to dispense fluid from the
dispenser as a substantially continuous bead between the at least
one outlet and the surface of the expandable member along a coating
path.
Description
CROSS-REFERENCE TO RELATED APPLICATION
[0001] This application is a continuation of U.S. patent
application Ser. No. 13/108,283, filed May 16, 2011, which claims
priority to U.S. Provisional Application No. 61/345,575 entitled
"Direct fluid coating of drug eluting balloon," filed May 17, 2010
which is incorporated herein by reference in its entirety.
BACKGROUND OF THE DISCLOSED SUBJECT MATTER
[0002] 1. Field of the Disclosed Subject Matter
[0003] The presently disclosed subject matter is related to the
delivery of therapeutic agents from an interventional medical
device. More particularly, the presently disclosed subject matter
relates to an interventional device for delivery of therapeutic
agents from an expandable member, such as a balloon. The disclosed
subject matter also relates to a method and apparatus for applying
one or more therapeutic agents onto the expandable member as well
as the assembly of the medical device.
[0004] 2. Description of related Subject Matter
[0005] Atherosclerosis is a syndrome affecting arterial blood
vessels. It is characterized by a chronic inflammatory response in
the walls of arteries, which is in large part due to the
accumulation of lipid, macrophages, foam cells and the formation of
plaque in the arterial wall. Atherosclerosis is commonly referred
to as hardening of the arteries, although the pathophysiology of
the disease manifests itself with several different types lesions
ranging from fibrotic to lipid laden to calcific. Angioplasty is a
vascular interventional technique involving mechanically widening
an obstructed blood vessel, typically caused by
atherosclerosis.
[0006] During angioplasty, a catheter having a folded balloon is
inserted into the vasculature of the patient and is passed to the
narrowed location of the blood vessel at which point the balloon is
inflated to the desired size by fluid pressure. Percutaneous
coronary intervention (PCI), commonly known as coronary
angioplasty, is a therapeutic procedure to treat the stenotic
regions in the coronary arteries of the heart, often found in
coronary heart disease. In contrast, peripheral angioplasty,
commonly known as percutaneous transluminal angioplasty (PTA),
generally refers to the use of mechanical widening of blood vessels
other than the coronary arteries. PTA is most commonly used to
treat narrowing of the leg arteries, especially, the iliac,
external iliac, superficial femoral and popliteal arteries. PTA can
also treat narrowing of carotid and renal arteries, veins, and
other blood vessels.
[0007] Although the blood vessel is often successfully widened by
angioplasty, sometimes the treated region of the blood vessel
undergoes vasospasm, or abrupt closure after balloon inflation or
dilatation, causing the blood vessel to collapse after the balloon
is deflated or shortly thereafter. One solution to such collapse is
stenting the blood vessel to prevent collapse. Dissection, or
perforation, of the blood vessel is another complication of
angioplasty that can be improved by stenting. A stent is a device,
typically a metal tube or scaffold that is inserted into the blood
vessel after, or concurrently with angioplasty, to hold the blood
vessel open.
[0008] While the advent of stents eliminated many of the
complications of abrupt vessel closure after angioplasty
procedures, within about six months of stenting a re-narrowing of
the blood vessel can form, a condition known as restenosis.
Restenosis was discovered to be a response to the injury of the
angioplasty procedure and is characterized by a growth of smooth
muscle cells and extracellular matrix analogous to a scar forming
over an injury. To address this condition, drug eluting stents were
developed to reduce the reoccurrence of blood vessel narrowing
after stent implantation. A drug eluting stent is a stent that has
been coated with a drug, often in a polymeric carrier, that is
known to interfere with the process of re-narrowing of the blood
vessel (restenosis). Examples of various known drug eluting stents
are disclosed in U.S. Pat. Nos. 5,649,977; 5,464,650; 5,591,227,
7,378,105; 7,445,792; 7,335,227, each of which are hereby
incorporated by reference in their entirety. However, a drawback of
drug eluting stents is a condition known as late stent thrombosis.
This is an event where a blood clot forms inside the stent, which
can occlude blood flow.
[0009] Drug coated balloons are believed to be a viable alternative
to drug eluting stents in the treatment of atherosclerotic lesions.
In a study which evaluated restenosis, and the rate of major
adverse cardiac events such as heart attack, bypass, repeat
stenosis, or death in patients treated with drug coated balloons
and drug eluting stents, the patients treated with drug coated
balloons experienced only 3.7 percent restenosis and 4.8% MACE
(material adverse coronary events) as compared to patients treated
with drug eluting stents, in which restenosis was 20.8 percent and
22.0 percent MACE rate. (See, PEPCAD II study, Rotenburg,
Germany).
[0010] However, drug coated balloons present certain unique
challenges. For example, the drug carried by the balloon needs to
remain on the balloon during delivery to the lesion site, and
released from the balloon surface to the blood vessel wall when the
balloon is expanded inside the blood vessel. For coronary
procedures, the balloon is typically inflated for less than one
minute, typically about thirty seconds. The balloon inflation time
may be longer for a peripheral procedure, however typically even
for peripheral procedures the balloon is expanded for less than 5
minutes. Due to the short duration of contact between the drug
coated balloon surface and the blood vessel wall, the balloon
coating must exhibit efficient therapeutic agent transfer and/or
efficient drug release during inflation. Thus, there are challenges
specific to drug delivery via a drug coated or drug eluting balloon
that are not present with a drug eluting stent.
[0011] Furthermore, conventional techniques for applying a coating,
such as a therapeutic agent, may not be desirable for coating
balloons, or other expandable members of medical devices. Such
convention techniques include spraying (air-atomization,
ultrasonic, electrostatic, etc.), dip-coating, spin-coating, vapor
deposition, roll coating, micro-droplet coating, etc. Balloons
present a cylindrical surface to be coated where it is desired to
uniformly coat only the working length of the balloon and no other
portion of the balloon or catheter. Many of these conventional
techniques do not provide sufficient coating uniformity or edge
control. Moreover, many of these techniques are not efficient in
their utilization of the therapeutic agent that can be costly. For
example, with the spray coating techniques commonly used to coat
drug eluting stents, only a fraction of the therapeutic agent
discharged is retained on the surface of the medical device. This
inefficiency is exacerbated with medical devices having larger
surface areas, such as peripheral balloons, wherein the amount of
therapeutic agent retained on the device can be as low as 2% of the
amount of therapeutic agent discharged.
[0012] Thus there remains a need, and an aim of the disclosed
subject matter is directed towards, the application of one or more
therapeutic agents to the surface of an expandable member of a
medical device.
SUMMARY OF THE DISCLOSED SUBJECT MATTER
[0013] The purpose and advantages of the disclosed subject matter
will be set forth in and are apparent from the description that
follows, as well as will be learned by practice of the disclosed
subject matter. Additional advantages of the disclosed subject
matter will be realized and attained by the methods and systems
particularly pointed out in the written description and claims
hereof, as well as from the appended drawings.
[0014] To achieve these and other advantages and in accordance with
the purpose of the disclosed subject matter, as embodied and
broadly described, the disclosed subject matter includes a system
and method of coating an expandable member of a medical device. The
method comprises providing a dispenser in fluid communication with
a fluid source containing at least one therapeutic agent, with the
dispenser having at least one outlet to dispense fluid of the fluid
source, and positioning the at least one outlet of the dispenser in
proximity to a surface of an expandable member. Relative movement
is established between the at least one outlet and the surface of
the expandable member along a coating path, and fluid is dispensed
from the dispenser to form a substantially continuous bead of fluid
between the outlet(s) and the surface of the expandable member
along the coating path, and simultaneously drying the fluid while
dispensing the fluid from the dispenser to control flow of fluid on
the surface of the expandable member.
[0015] The relative movement includes rotation, translation, or a
combination thereof about at least one axis, of at least one of the
expandable members and the at least one outlet. Additionally, the
relative movement can further include rotation, axial translation,
or a combination thereof, of the other of the expandable member and
the at least one outlet. For example, the relative movement can
define a helical path of the outlet with respect to the expandable
member, and/or the expandable member is moved along a first axis,
and the outlet can be moved along a second axis transverse to the
first axis.
[0016] The dispensing of fluid to the surface of the expandable
member can be repeated along a plurality of coating paths.
Additionally, or alternatively, a first fluid can be dispensed
during a first coating path, and a second fluid can be dispensed
during a second coating path. Additionally, the method can include
drying the fluid on the surface between successive coating paths.
The drying of the fluid on the surface can occur at specific
periods before and after dispensing or simultaneously with the
dispensing of the fluid along the coating path. The dispensing of
fluid can be controlled to apply a substantially uniform or
non-uniform coating of fluid to a predetermined area of the
expandable member. The method also includes at least partially
expanding the expandable member prior to dispensing fluid to the
surface of the expandable member.
[0017] The dispenser is selected from the group including pipet
tubing, flexible tubing, coaxial tubing, hypotubes, dies,
ball-bearing dispense tubing, syringe, needles, and other
non-contacting applicators capable of forming a continuous bead.
Additionally, the dispenser can include a plurality of outlets
arranged along a common axis, angularly offset form each other, or
combinations thereof. Each dispenser outlet can be in communication
with a different fluid source, and can be heated during the
dispensing operation.
[0018] The disclosed subject matter also includes a system for
coating an expandable member of a medical device. The system
includes a support structure to support an expandable member of a
medical device, and a dispenser in fluid communication with a fluid
source and having at least one outlet for dispensing fluid of the
fluid source therefrom, wherein the dispenser can be positioned
with the at least one outlet proximate a surface of an expandable
member supported by the support structure. A dryer is provided
proximate the dispenser to simultaneously dry the fluid while
dispensing the fluid from the dispenser to control flow of fluid on
the surface of the expandable member. A drive assembly is employed
to establish relative movement between the at least one outlet and
the surface of the expandable member to dispense fluid from the
dispenser as a substantially continuous bead between the at least
one outlet and the surface of the expandable member along a coating
path.
[0019] The dispenser is capable of varying the rate in which fluid
is dispensed from the at least one outlet. Additionally, the drive
assembly is capable of varying the speed of relative movement
between the at least one outlet and the surface of the expandable
member, as well as establishing a plurality of coating paths for
delivery of fluid from the dispenser to the surface of the
expandable member. A dryer can be provided to apply heat, forced
gas, cold temperature, vacuum, infra-red energy, microwave energy,
or a combination thereof to the surface of the expandable
member.
[0020] It is to be understood that both the foregoing general
description and the following detailed description are exemplary
and are intended to provide further explanation of the disclosed
subject matter claimed.
[0021] The accompanying drawings, which are incorporated in and
constitute part of this specification, are included to illustrate
and provide a further understanding of the method and system of the
disclosed subject matter. Together with the description, the
drawings serve to explain the principles of the disclosed subject
matter.
BRIEF DESCRIPTION OF THE DRAWINGS
[0022] FIG. 1 is a schematic side view representative balloon
catheter in accordance with the disclosed subject matter.
[0023] FIG. 1A is a cross-sectional view taken along lines A-A in
FIG. 1.
[0024] FIG. 1B is a cross-sectional view taken along lines B-B in
FIG. 1.
[0025] FIG. 2 is a schematic representative view of direct fluid
coating in accordance with the disclosed subject matter.
[0026] FIG. 3 is a schematic representation of a dispenser and
drying apparatus in accordance with the disclosed subject
matter.
[0027] FIG. 4 is a schematic cross-sectional view of the dispenser
and drying apparatus of FIG. 3.
[0028] FIG. 5 is a schematic cross-sectional view of a support
assembly for supporting the shaft of the catheter during a coating
process.
DETAILED DESCRIPTION
[0029] Reference will now be made in detail to embodiments of the
disclosed subject matter, an example of which is illustrated in the
accompanying drawing. The method and corresponding steps of the
disclosed subject matter will be described in conjunction with the
detailed description of the system.
[0030] The methods and systems presented herein can be used for
applying one or more coatings to a medical device. The disclosed
subject matter is particularly suited for directly applying
therapeutic agents, and other fluid compounds, to select portions
of an expandable member. While the disclosed subject matter
references application of a fluid to an expandable member, it is to
be understood that the methods and systems disclosed herein can
also be employed to apply therapeutic, polymeric, or matrix
coatings to various surfaces of medical devices, as so desired.
[0031] The disclosed subject matter provides a method, and
corresponding system, to coat an expandable member, or select
portions thereof, by a direct application process. The direct
application process applies a coating without atomization, or the
formation of droplets, of the coating fluid. Additionally, the
disclosed subject matter provides a system and method for improved
efficiency of the dispensing of a coating solution, which can be
controlled based on the volume of coating solution dispensed,
rather than via a weight based control. Indeed, the disclosed
subject matter provides a system and method for dispensing of a
coating solution which can achieve 95.0% or greater transfer
efficiency, i.e., 95.0% of the coating solution dispensed is
applied to the expandable member.
[0032] In accordance with the disclosed subject matter, a method of
coating an expandable member of a medical device comprises
providing a dispenser in fluid communication with a fluid source
with the dispenser having at least one outlet to dispense fluid of
the fluid source therefrom. The at least one outlet of the
dispenser is positioned proximate a surface of an expandable
member, with relative movement between the at least one outlet and
the surface of the expandable member established along a coating
path, and fluid is dispensed from the dispenser to form a
substantially continuous bead of fluid between the outlet and the
surface of the expandable member along the coating path.
[0033] For purpose of explanation and illustration, and not
limitation, an exemplary embodiment of a medical device having an
expandable member is shown schematically in FIGS. 1 and 1A.
Particularly, and as illustrated, the medical device embodied
herein is a balloon catheter 10, which includes an elongated
catheter shaft 12 having a proximal end and having a distal end and
an expandable member 30 located proximate the distal end of the
catheter shaft. The expandable member, or balloon as depicted
herein, has an outer surface and an inner surface disposed at the
distal end portion of the catheter shaft. In accordance with the
disclosed subject matter, a coating is applied to at least a
portion of the outer surface of the balloon.
[0034] The elongated catheter shaft 12 comprises an outer tubular
member 14 and an inner tubular member 16. The outer tubular member
14 defines an inflation lumen 20 disposed between the proximal end
portion and the distal end portion of the catheter shaft 12.
Specifically, as illustrated in FIG. 1A, the coaxial relationship
of this representative embodiment defines an annular inflation
lumen 20 between the inner tubular member 16 and the outer tubular
member 14. The expandable member 30 is in fluid communication with
the inflation lumen 20. The inflation lumen can supply an inflation
medium under positive pressure and can withdraw the inflation
medium, i.e. provide negative pressure, from the expandable member.
The expandable member 30 can thus be inflated and deflated. The
elongated catheter is sized and configured for delivery through a
tortuous anatomy, and can further include a guidewire lumen 22 that
permits it to be delivered over a guidewire 18. As illustrated in
FIG. 1A, the inner tubular member 16 defines the guidewire lumen 22
for the guidewire 18. Although FIGS. 1 and 1b illustrate the
guidewire lumen as having an over-the-wire (OTW) construction, the
guidewire lumen can be configured as a rapid-exchange (RX)
construction, as is well known in the art.
[0035] A wide variety of balloon catheters and balloon constructs
are known and suitable for use in accordance with the disclosed
subject matter. For example, the expandable member can be made from
polymeric material such as compliant, non-compliant or
semi-compliant polymeric material or polymeric blends. Examples of
such suitable materials include, but are not limited to, nylon 12,
nylon 11, nylon 9, nylon 6, nylon 6/12, nylon 6/11, nylon 6/9, and
nylon 6/6, polyurethane, silicone-polyurethane, polyesters,
polyester copolymers, and polyethylene. Examples of other balloon
and catheter embodiments which can be employed in accordance with
the disclosed subject matter include U.S. Pat. Nos. 4,748,982;
5,496,346; 5,626,600; 5,300,085, 6,406,457 and U.S. application
Ser. Nos. 12/371,426; 11/539,944; 12/371,422, each of which is
hereby incorporated by reference in their entirety.
[0036] In one embodiment, the coating is applied to the expandable
member of the fully assembled medical device. As described above
with reference to FIGS. 1A-B, medical devices such as the catheter
10 include a plurality of components which are typically
manufactured as separate discrete components and thereafter
assembled together. Applying a coating to the expandable member at
an upstream stage of an assembly line requires extensive measures
to minimize or prevent the coating from being exposed to various
equipment and processes during the downstream portion of the
assembly line. Such exposure can render the coating prone to damage
and/or contamination during final assembly of the catheter, and can
result in scrapping of the entire catheter. In order to avoid such
exposure and damage to the coating in conventional catheter
assembly lines additional equipment including monitoring and safety
controls would be required. Accordingly, applying the coating to
the expandable member of a fully assembled catheter avoids the
unnecessary complexity, and excessive costs associated with such a
modified assembly line.
[0037] In accordance with the disclosed subject matter, any of a
variety of fluid compositions can be applied to the expandable
member. For example, the fluid can include a therapeutic agent for
treatment of a disease state. Examples of suitable therapeutic
agents include anti-proliferative, anti-inflammatory,
antineoplastic, antiplatelet, anti-coagulant, anti-fibrin,
antithrombotic, antimitotic, antibiotic, antiallergic and
antioxidant compounds. Such therapeutic agents can be, again
without limitation, a synthetic inorganic or organic compound, a
protein, a peptide, a polysaccharides and other sugars, a lipid,
DNA and RNA nucleic acid sequences, an antisense oligonucleotide,
an antibodies, a receptor ligands, an enzyme, an adhesion peptide,
a blood clot agent including streptokinase and tissue plasminogen
activator, an antigen, a hormone, a growth factor, a ribozyme, and
a retroviral vector. However, the therapeutic agents can include,
cytostatic drug. The term "cytostatic" as used herein means a drug
that mitigates cell proliferation but allows cell migration. These
cytostatic drugs, include for the purpose of illustration and
without limitation, macrolide antibiotics, rapamycin, everolimus,
zotaroliumus, biolimus, temsirolimus, deforolimus, novolimus,
myolimus, structural derivatives and functional analogues of
rapamycin, structural derivatives and functional analogues of
everolimus, structural derivatives and functional analogues of
zotarolimus and any marcrolide immunosuppressive drugs. The term
"cytotoxic" as used herein means a drug used to inhibit cell
growth, such as chemotherapeutic drugs. Some non-limiting examples
of cytotoxic drugs include vincristine, actinomycin, cisplatin,
taxanes, paclitaxel, and protaxel.
[0038] Additionally or alternatively, the fluid can include other
compounds or additives, such as polymers, binding agents,
plasticizers, solvents, surfactants, additives, chelators, fillers,
and the like. Examples of possible compounds include zotarolimus,
polyvinylpyrrolidone and glycerol. In one embodiment the
therapeutic agent can be provided in liquid form or dissolved in a
suitable solvent. In another embodiment, the therapeutic agent is
provided as a particulate and mixed in a suitable carrier for
application as a fluid.
[0039] An embodiment of the coating process and system of the
disclosed subject matter is illustrated in FIG. 2 for purpose of
explanation and not limitation. The dispenser depicted herein is
shown as a pipet 100 having an outlet 102 positioned proximate
expandable member 30 such that the fluid dispensed from the pipet
is in continuous fluid contact with the expandable member 30
without atomization of the coating solution. As the coating
solution is delivered from a fluid source, e.g. reservoir (not
shown), through the dispenser outlet, a continuous fluid medium or
bead 200 of solution directly contacts the surface of the
expandable member.
[0040] A positive pressure is applied to assist with dispensing
fluid from the outlet. Alternatively, the fluid can be dispensed
from the outlet via capillary action only, i.e., the surface
tension pulls the bead of coating solution 200 onto the surface of
the expandable member. Furthermore, the outlet can be heated prior
to and/or during the dispensing of the coating solution. The
heating of the dispenser can reduce the viscosity of the coating
solution and therefore accelerate the coating process as well as
reduce the potential for clogging or occluding of the dispenser
outlet 102. FIG. 2 depicts the outlet generally at a right angle to
the balloon surface. However, alternative alignments and
orientations can be used as desired or needed for the type and
dimensions of expandable members.
[0041] Coating process and systems of the disclosed subject matter
can be performed with the expandable member in a fully or partially
inflated condition, as well as in a deflated condition. When
deflated, the expandable member can be pleated, folded, wrinkled or
pressed. In the embodiment illustrated in FIG. 2, the expandable
member is fully inflated to allow coating of all or select portions
of the outer surface.
[0042] As the fluid is delivered from the fluid source to the
outlet 102 of the dispenser in the form of a continuous bead,
relative movement is established between the outlet 102 and the
expandable member 30 to effect a uniform, or non-uniform, coating
path as desired. For example, and as depicted in FIG. 2, the
coating path can define a continuous spiral or helical pattern
along the outer surface of the expandable member. Alternatively,
coating paths can be established such as discrete circumferential
rings, discrete lines extending along the expandable members
longitudinal axis, and combinations thereof. Hence, the relative
movement can include rotation, translation, or combinations
thereof, of either, or both, the expandable member 30 and the
outlet 102.
[0043] For example, the expandable member can be rotated about its
central axis, as shown by arrows A in FIG. 2, and simultaneously
translated along the central axis, as shown by arrow B in FIG. 2.
Additionally, or alternatively the expandable member 30 can rotate
relative a first axis, and the outlet 102 translate relative a
second axis, e.g., to define a helical coating path. Accordingly,
any number of coating paths can be selected and provided on the
expandable member. The various movements described herein can be
performed simultaneously, sequentially, continuously or
intermittently, as so desired.
[0044] Movement of the medical device and/or the outlet of the
dispenser is accomplished by providing a support assembly. The
support assembly can maintain the position of one element, e.g. the
dispenser, while allowing movement of the other element, e.g., the
medical device. Alternatively, the support assembly can allow
movement of both elements. Movement can be performed manually, or
by providing a drive assembly with suitable drive source, such as a
motor or the like, and appropriate controller as know in the
art.
[0045] Simultaneous with the relative movement, the fluid is
dispensed from the outlet to form a continuous bead between the
outlet and the surface of the expandable member along the coating
path. Generally, it has been determined that the formation and
maintenance of the continuous bead of fluid will be a function of
the fluid density, and average velocity of the fluid from the
outlet. In one embodiment, the Reynolds number, i.e. ratio of
momentum or inertial force to viscosity, for the flow out of the
outlet is less than 2300 such that the flow remains substantially
laminar. The Reynolds number being defined by the equation
Re=(.rho.*v*l)/.mu. wherein "l" is a dimension of the outlet.
Additionally, the average volumetric flow rate of the fluid exiting
the outlet lies within the range of 3-110 .mu.l/min. It therefore
is possible to form a substantially continuous bead by controlling
one or more of these variables. For example, the average velocity
of the fluid can exit in the range of approximately 0.0411 to 4.11
cm/sec.
[0046] In one embodiment, the bead 200 diameter was maintained at a
predetermined size of at least 0.03 in. Alternatively, bead
diameters of between 0.8 mm (or 0.03 in)and 2.5 mm (-0.1 in) for
tubing inner diameters between 0.006 inch to 0.20 inch are
considered to be within the scope of the disclosed subject matter.
In another embodiment, a 3.0 mm.times.18 mm Pebax expandable member
was rotated at 100 rpm, and translated at a linear speed of 1.0
mm/sec which resulted in approximately 650 .mu.g/pass of a coating
solution applied to the expandable member. The cycle time for
applying a coating to an expandable member can vary depending on
the size of the expandable member, the flow rate of the coating
fluid, and the speed of relative movement, with a typical cycle
time lasting from about 1 to 15 minutes. The rotational movement of
the expandable member provides an additional advantage of
distributing the coating solution around the circumference of the
expandable member and preventing any accumulation on the downward
side due to gravity induced flow. Additionally, or alternatively,
as described further below, the applied bead is dried to control
and/or prevent a flow of the fluid on the surface of the expandable
member. To create the relative movement between the expandable
member and dispenser, the expandable member was positioned on a
motorized mandrel geared to rotate and/or translate as well as
provide inflation/deflation of the expandable member.
[0047] In accordance with another aspect of the disclosed subject
matter, the speed at which the expandable member and/or outlet is
moved can be varied to modify a variety of coating properties
including thickness, width and volume of the coating. For example,
a slower speed of relative movement between the elements will
result in greater volume of fluid per pass. Similarly, the rate in
which fluid is dispensed from the outlet also can be controlled to
adjust or control the coating properties applied to the surface of
the expandable member. That is, a greater rate of fluid dispensed
will result in a greater volume per pass if the speed of relative
movement is maintained constant. Hence, any number of coating
patterns and properties can be achieved by the disclosed method and
system.
[0048] The desired portions of the expandable member can be coated
with a single pass or cycle of relative movement between the
expandable member and dispenser. Alternatively, a plurality of
passes or cycles of coating operation discussed above can be
performed. Such multiple passes or cycles allows for further
variation in the coating properties along the expandable member
length. For example, one portion of the expandable member can be
coated with a different number of coating layers of fluid than
another portion of the expandable member thereby creating a
gradient of the coating solution on the expandable member. Further,
the methods and apparatus of the disclosed subject matter can be
employed to apply layers of different coating compositions to the
expandable member. For example, therapeutic-free primers,
concentrated therapeutic layers, and drug-excipient layers can be
applied. As discussed above, varied coating properties allow for
greater flexibility and customization of the catheter to provide a
greater range of applications and ability to meet patient
needs.
[0049] In accordance with another aspect of the disclosed subject
matter, a drying apparatus can be employed to control or prevent
the flow of fluid applied on the surface of the expandable member
and to accelerate the coating process. As shown in FIG. 2, a dryer
300 can be positioned downstream of the dispenser to apply heat,
forced gas, cooled gas, vacuum, infra-red energy, microwave energy,
or a combination thereof to the surface of the expandable member.
Additionally, or alternatively, the drying nozzle 300 can be
collinear or coaxial with the dispenser 100 by either
circumscribing the outlet 102 or otherwise surround the outlet as
with an annular opening, as shown in FIGS. 3-4. For example, the
drying operation can employ air, or ambient nitrogen, in a drying
nozzle of 0.081 in, at a pressure of 5 to 25 psi, and a flow rate
of about 100-700 ml/min. As embodied herein, the flow rate can be
calculated to equation: flow rate=(26.86*Pressure)+4.5204. Further,
applying a drying gas simultaneously, e.g. air or ambient nitrogen
at 10 psi, evaporates solvents contained in the fluid and
facilitates drying of the coating such that the coating disposed on
the expandable member does not flow. In some embodiments, a drying
operation can be conducted between successive coating passes or
cycles. Additionally, or alternatively, the drying operation can be
conducted concurrently with a coating pass or cycle, as depicted in
FIG. 2. Similar to the dispenser 100 discussed above, the drying
apparatus 300 can be oriented at any angle between
0.degree.-90.degree. with respect to the expandable member, and be
configured for relative movement.
[0050] While the dispenser of the embodiment illustrated in FIG. 2
depicts a dispenser configured as a pipet, additional or
alternative dispensers can be employed. Some examples of such
dispensers include flexible tubing, coaxial tubing, hypotubes,
dies, ball-bearing dispense tubing, syringe, needles, and other
non-contacting applicators that are capable of forming a continuous
bead. Furthermore, FIG. 2 depicts a dispenser having a single
outlet 102 perpendicular to the expandable member though
alternative angles between 0.degree.-90.degree. can be employed.
Also, the use of a plurality of outlets can be employed. Each
outlet can be oriented perpendicular, disposed adjacent each other
along the axis of the expandable member, and/or spaced
circumferentially about the expandable member.
[0051] In this regard, a plurality of reservoirs containing
distinct coating solutions can be provided with each dispenser in
fluid communication with a separate reservoir. As with the outlet
of FIG. 2, the dispensers can be positioned at various locations
and orientations relative to the expandable member. Additionally,
the expandable member 30 can be oriented in a generally horizontal
position, as shown in FIG. 2, vertically, or at or at any angle
between 0.degree.-90.degree., if desired. Orienting the expandable
member in a vertical configuration can be advantageous in larger
size expandable members, e.g. peripheral balloons, since the
gravitational force acts parallel the expandable member's
longitudinal axis thereby preventing deformation such as arching or
bowing of the expandable member and associated catheter shaft,
which the expandable member can be susceptible to when in the
horizontal position.
[0052] In accordance with another aspect of the disclosed subject
matter, the outlet of the dispenser is maintained at a
predetermined or fixed distance from the expandable member surface.
Maintaining a fixed distance between the dispenser outlet and the
expandable member, in combination with uniform rotation and
translation as discussed above, provides greater control over the
coating pattern to be applied to the expandable member surface.
Such control can be advantageous by providing a consistent dosage
of the therapeutic agent along the portion of the expandable
member.
[0053] Additionally, maintaining a fixed distance between the
dispenser outlet and the expandable member surface assists in
maintaining a continuous bead of fluid from the outlet. For
example, discrete droplets of fluid could form if the distance
between the outlet and the surface of the expandable member were
too great. Conversely, if the distance between the dispenser outlet
and the expandable member surface were too small, undesired or
accidental contact between the outlet and expandable member surface
can occur resulting in tearing or scratching of the expandable
member surface or abrasion to the coating applied to the expandable
member. The distance between the outlet and the surface of the
expandable member can depend upon a number of variables, including
viscosity of the fluid, surface tension of the fluid, pump rate of
the fluid, diameter of the dispenser exit orifice, volatility of
the solvents in the fluid, speed at which the fluid is dispensed
and/or size of the outlet opening. For example, when using a pipet
type dispenser, the distance between the outlet and the surface
generally should be less than 40 times the smallest cross dimension
of the outlet.
[0054] The fixed distance between the outlet and the surface of the
expandable member can be monitored in a number of ways in
accordance with the disclosed subject matter. Particularly, the
fixed distance can be monitored by displacing the outlet to track
the surface, or by controlling displacement of the surface of the
expandable member relative to the outlet. Examples of suitable
methods and systems are disclosed in U.S. patent application Ser.
No. 61/345,569, which is hereby incorporated by reference in its
entirety.
[0055] As discussed above, the coating method and system of the
disclosed subject matter can be performed on a previously assembled
medical device, e.g. balloon catheters. Often the force required to
rotate or otherwise move the expandable member is applied to a
location, and/or component, proximal of the expandable member.
Therefore, significant force may be required to overcome the
friction and inertia of the various components of the medical
device in order to achieve movement of the expandable member. Thus,
any reduction or minimization of points of contact between the
encasement and expandable member is advantageous as the frictional
forces generated during the relative movement will in turn be
minimized, thereby reducing the amount of force required by the
support assembly, or manual operator, to establish relative
movement. As the proximal components of medical device are often
polymeric and not torsionally rigid, undue friction on the
expandable member can lead to torsional loading and unloading of
the proximal members. This leads to inconsistent rotation of the
medical device, which in turns leads to non-uniform coating.
[0056] During the coating process, the catheter shaft 12 can be
positioned within a support assembly to counteract the
circumferential and rotational forces and maintain the catheter
shaft in a generally linear configuration. An example of such a
support assembly is shown in FIG. 5, which includes a generally
V-shaped structure 900 to define a channel for receiving the
catheter shaft 12. A retaining rod 1000 is positioned above the
shaft 12 and serves to obstruct or prevent the shaft 12 from being
displaced out of the support assembly 900. In one embodiment, the
retaining rod 1000 is configured with a cross-sectional dimension
that limits the depth the retaining rod 1000 can be positioned
within the V-shaped support assembly 900. Accordingly, the
retaining rod 1000 is spaced from the shaft 12 to minimize contact,
thereby minimizing the frictional forces generated during rotation
of the shaft. Similarly, the support structure 900 can be coated
with, or fabricated from, a lubricious material including Teflon,
PEEK.
[0057] If desired, a protective sheath can be provided to protect
the coating during shipping and storage and/or during delivery of
the coated expandable member through the body lumen. A variety of
sheaths are known, including removable sheaths or balloon covers,
retractable sheaths to be withdrawn prior to deployment of the
balloon, and elastic sheaths that conform to the balloon upon
expansion. Such elastic sheaths can be porous or include apertures
along a portion thereof. In operation, the inflation of the
expandable member causes the sheath to expand for release of the
coating and/or therapeutic agent through the porous wall or
apertures to the tissue of the arterial wall. For example, see U.S.
Pat. No. 5,370,614 to Amundson, the disclosure of which is
incorporated by reference in its entirety.
[0058] In accordance with in the disclosed subject matter, an
endoprosthesis, e.g. stent, can be mounted on the expandable
member. The type of stent that can be used includes, but is not
limited to, bare metal stent, drug eluting stent, bioabsorbable
stent, balloon-expandable stent, self-expanding stent, prohealing
stent, and self-expanding vulnerable plaque implant. The expandable
member can be coated independently of the stent or in conjunction
with the stent coating process. The stent coating can contain the
same or different therapeutic agents from the catheter or
expandable member. However, the particular coating on the catheter
or expandable member can have distinct release kinetics from the
therapeutic coating on the stent. The coating applied to the
expandable member can be allowed to dry prior to placement of the
stent thereon.
[0059] Alternatively, the coating could not be allowed to dry or
cure past a "tacky" state before the stent is positioned and/or
crimped onto it. This would enable the adhesion of the coating on
the expandable member to the inside of the prosthesis. This process
increases the retention of the prosthesis onto the expandable
member (acting as a prosthesis retention enhancer) thus reducing
the chance that the stent will move on the expandable member during
the torturous delivery through the vascular lumen.
[0060] While the disclosed subject matter is described herein in
terms of certain embodiments, those skilled in the art will
recognize that various modifications and improvements can be made
to the disclosed subject matter without departing from the scope
thereof. Moreover, although individual features of one embodiment
of the disclosed subject matter can 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 can
be combined with one or more features of another embodiment or
features from a plurality of embodiments.
[0061] In addition to the specific embodiments claimed below, the
disclosed subject matter is also directed to other embodiments
having any other possible combination of the dependent features
claimed below and those disclosed above. As such, the particular
features presented in the dependent claims and disclosed above can
be combined with each other in other manners within the scope of
the disclosed subject matter such that the disclosed subject matter
should be recognized as also specifically directed to other
embodiments having any other possible combinations. Thus, the
foregoing description of specific embodiments of the disclosed
subject matter has been presented for purposes of illustration and
description. It is not intended to be exhaustive or to limit the
disclosed subject matter to those embodiments disclosed.
[0062] It will be apparent to those skilled in the art that various
modifications and variations can be made in the method and system
of the disclosed subject matter without departing from the spirit
or scope of the disclosed subject matter. Thus, it is intended that
the disclosed subject matter include modifications and variations
that are within the scope of the appended claims and their
equivalents.
* * * * *