U.S. patent application number 12/856431 was filed with the patent office on 2011-02-10 for coated medical implants.
This patent application is currently assigned to BOSTON SCIENTIFIC SCIMED, INC.. Invention is credited to Kalpana Kamath, Kathleen Miller, Marlene Schwarz.
Application Number | 20110034993 12/856431 |
Document ID | / |
Family ID | 23131441 |
Filed Date | 2011-02-10 |
United States Patent
Application |
20110034993 |
Kind Code |
A1 |
Schwarz; Marlene ; et
al. |
February 10, 2011 |
COATED MEDICAL IMPLANTS
Abstract
Coated medical devices are disclosed. In certain embodiments of
the invention, the coating materials include therapeutic agents,
polymers, sugars, waxes, or fats. In certain embodiments of the
invention, a medical device is coated on at least a portion of its
surface with a first coating comprising a therapeutic agent and a
wax or fat. The coated medical device may be a stent or
catheter.
Inventors: |
Schwarz; Marlene; (Newton,
MA) ; Miller; Kathleen; (Shrewsbury, MA) ;
Kamath; Kalpana; (Natick, MA) |
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: |
23131441 |
Appl. No.: |
12/856431 |
Filed: |
August 13, 2010 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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12146202 |
Jun 25, 2008 |
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12856431 |
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10699771 |
Nov 4, 2003 |
7407551 |
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12146202 |
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10084868 |
Mar 1, 2002 |
6730349 |
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10699771 |
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09804040 |
Mar 13, 2001 |
6607598 |
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10084868 |
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09551614 |
Apr 17, 2000 |
6368658 |
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09804040 |
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09293994 |
Apr 19, 1999 |
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09551614 |
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Current U.S.
Class: |
623/1.42 ;
604/523; 623/23.7 |
Current CPC
Class: |
A61L 29/08 20130101;
A61L 2420/02 20130101; C23C 16/458 20130101; B05B 13/02 20130101;
A61L 27/28 20130101; A61L 31/10 20130101; B05D 1/22 20130101; A61L
29/16 20130101; A61L 2300/608 20130101; B05B 13/0257 20130101; A61L
27/54 20130101; A61L 31/08 20130101; A61L 2300/258 20130101; B05C
13/00 20130101; A61L 31/14 20130101; B05B 13/0221 20130101; A61L
2300/252 20130101; B05B 13/025 20130101; A61L 31/16 20130101; A61L
2300/606 20130101; C23C 14/50 20130101 |
Class at
Publication: |
623/1.42 ;
604/523; 623/23.7 |
International
Class: |
A61L 27/54 20060101
A61L027/54; A61L 29/16 20060101 A61L029/16 |
Claims
1.-67. (canceled)
68. A medical device coated on at least a portion of its surface
with a first coating comprising a therapeutic agent and a wax or
fat.
69. A medical device as in claim 68 wherein said first coating has
a thickness of about 1 to 30 microns.
70. A medical device as in claim 68 wherein said first coating is
one layer or multiple layers of the same or different coating
materials.
71. A medical device as in claim 68 wherein the medical device
comprises a substrate formed of metal, polymer, ceramic, composite
or combinations thereof.
72. A medical device as in claim 68 wherein the medical device is
selected from the group consisting of catheters, needle injection
catheters, blood clot filters, vascular grafts, stent grafts,
biliary stents, colonic stents, bronchial/pulmonary stents,
esophageal stents, ureteral stents, aneurysm filling coils, other
coiled coil devices, trans myocardial revascularization devices,
and percutaneous myocardial revascularization devices.
73. A medical device as in claim 68 claim wherein the medical
device is a stent.
74. A medical device as in claim 68 wherein the therapeutic agent
comprises an anti-angiogenic agent.
75. A medical device as in claim 68 wherein the therapeutic agent
comprises an agent blocking smooth muscle cell proliferation.
76. A medical device as in claim 68 wherein the therapeutic agent
is a member of the group consisting of rapamycin, angiopeptin, and
monoclonal antibodies capable of blocking smooth muscle cell
proliferation.
77. A medical device as in claim 68 wherein the therapeutic agent
is rapamycin.
78. A medical device as in claim 68 wherein the therapeutic agent
comprises an antineoplastic/antiproliferative/anti-mitotic
agent.
79. A medical device as in claim 68 wherein the therapeutic agent
is a member of the group consisting of paclitaxel, 5-fluorouracil,
methotrexate, doxorubicin, daunorubicin, cyclosporine, cisplatin,
vinblastine, vincristine, colchicine, epothilones, endostatin,
angiostatin, Squalamine, and thymidine kinase inhibitors.
80. A medical device as in claim 68 wherein the therapeutic agent
is paclitaxel.
81. A medical device as in claim 68 wherein the coating comprises a
fat.
82. A medical device as in claim 68 wherein the coating comprises a
wax.
83. A medical device as in claim 68 wherein the medical device is a
catheter.
84. A stent having a coating thereon, the coating comprising a
therapeutic agent and a wax or fat.
85. A stent as in claim 84 wherein said stent is a vascular stent,
a biliary stent, a colonic stent, a bronchial/pulmonary stent, an
esophageal stent or a ureteral stent.
86. A stent as in claim 84 wherein the coating comprises a fat.
87. A vascular stent having a coating thereon, the coating
comprising a fat.
Description
[0001] This application is a continuation-in-part of pending
application Ser. No. 09/293,994 filed Apr. 19, 1999.
FIELD OF THE INVENTION
[0002] The present invention relates to coated medical devices, and
more particularly to medical devices that are coated using air
suspension.
BACKGROUND OF THE INVENTION
[0003] It is often beneficial to coat medical devices so that the
surfaces of such devices have desired properties or effects. For
example, it is useful to coat medical devices to provide for the
localized delivery of therapeutic agents to target locations within
the body, such as to treat localized disease (e.g., heart disease)
or occluded body lumens. Such localized drug delivery avoids the
problems of systemic drug administration, which may be accompanied
by unwanted effects on parts of the body which are not to be
treated, or because treatment of the afflicted part of the body
requires a high concentration of therapeutic agent that may not be
achievable by systemic administration. Localized drug delivery is
achieved, for example, by coating balloon catheters, stents and the
like with the therapeutic agent to be locally delivered. The
coating on medical devices may provide for controlled release,
which includes long-term or sustained release, of a bioactive
material.
[0004] Aside from facilitating localized drug delivery, medical
devices are coated with materials to provide beneficial surface
properties. For example, medical devices are often coated with
radiopaque materials to allow for fluoroscopic visualization during
placement in the body. It is also useful to coat certain devices to
achieve enhanced biocompatibility and to improve surface properties
such as lubriciousness.
[0005] Conventionally, coatings have been applied to medical
devices by processes such as dipping, spraying, vapor deposition,
plasma polymerization, and electrodeposition. Although these
processes have been used to produce satisfactory coatings, there
are numerous potential drawbacks associated therewith. For example,
it is often difficult to achieve coatings of uniform thicknesses,
both on individual parts and on batches of parts. Also, many of
these conventional coating processes require that the coated part
be held during coating, resulting in defects such as bare spots
where the part was held and thus requiring subsequent coating
steps. Further, many conventional processes require multiple
coating steps or stages for the application of a second coating
material, or to allow for drying between coating steps or after the
final coating step.
[0006] There is, therefore, a need for a cost-effective method of
coating medical devices that results in uniform, defect-free
coatings and uniform drug doses per unit device. The method would
allow for a multiple stage coating in order to apply a bioactive
material that may be environmentally sensitive, e.g., due to heat
and light (including ultra-violet) exposure and due to degradation
of the bioactive material due to process-related forces (e.g.,
shear). The method would thus allow for better control of the
sensitivity of the bioactive material and reduce any potential
degradation due to environmental issues. The method would also
reduce variations in the coating properties.
SUMMARY OF THE INVENTION
[0007] In one aspect, the present invention relates to methods for
coating at least a portion of a medical device which is used, at
least in part, to penetrate the body of a patient. In one
embodiment, the method comprises the steps of suspending the
medical device in an air stream that is substantially devoid of
suspending particles and introducing a coating material into the
air stream such that the coating material is dispersed therein and
coats at least a portion of the medical device. This process is
used to apply one or more coating materials, simultaneously or in
sequence. In certain embodiments of the invention, the coating
materials include therapeutic agents, polymeric materials; and
sugars, waxes, and fats. A coating substance that is comprised of
suspension particles may be utilized that are fused to the surface
of the medical device by a coating solution.
[0008] In another embodiment of the present invention, the medical
devices are suspended in an air stream substantially devoid of
suspending particles and a coating apparatus coats at least a
portion of the medical device with a coating material while the
medical devices are suspended in the air stream. The coating
apparatus may include a device that utilizes any number of
alternative coating techniques for coating the medical devices.
[0009] In another aspect, the present invention relates to coated
medical devices made by the method of the invention.
[0010] One advantage of the present invention is that it provides
coated medical devices with uniform coating thicknesses and
mechanical properties and minimal contaminants.
[0011] Another advantage of the present invention is that it allows
simultaneous coating of multiple numbers of medical devices at the
same time, thus leading to higher process efficiency.
[0012] Another advantage of the present invention is that it does
not require that the medical device be held during the coating
process, thereby eliminating bare spots and the need for subsequent
coating steps to coat such bare spots.
[0013] Another advantage of the present invention is that it
provides a method for coating medical devices by coating materials
that are otherwise difficult to use, such as incompatible,
insoluble/suspension, or unstable coating solutions.
[0014] Another advantage of the present invention is that it
reduces human exposure to materials used in conventional coating
processes such as solvents, polymers, drugs, and the like.
[0015] Another advantage of the present invention is that it allows
for the application of multiple coating materials to numerous
medical devices in a single batch coating process.
[0016] Yet another advantage of the present invention is that it
provides a method for coating a medical device that results in a
uniform drug dose per unit device.
BRIEF DESCRIPTION OF THE DRAWINGS
[0017] FIG. 1 is a cross-sectional view of an apparatus for coating
medical devices in accordance with a first embodiment of the
present invention.
[0018] FIG. 2 is a cross-sectional view of an apparatus for coating
medical devices in accordance with a second embodiment of the
present invention.
[0019] FIG. 3 illustrates a plasma coating apparatus in accordance
with the principles of the present invention.
DETAILED DESCRIPTION
[0020] The present invention provides methods for coating medical
devices, and devices thereby produced. By using air suspension to
coat medical devices, the methods of the present invention result
in coatings having minimal defects and uniform thicknesses and
mechanical properties. Further, the methods of the present
invention are time efficient and cost effective because they
facilitate the uniform coating of numerous medical devices in a
single batch.
[0021] Whereas the present invention allows multiple medical
devices to be coated as a batch, the present invention is not
limited to only coating medical devices in batches, i.e., coating a
group of devices in one batch process followed by coating a second
group of devices in a second batch process. The methods and
apparatuses of the present invention can be utilize to continuously
run medical devices through the apparatuses such that the process
does not have to be started and stopped for coating the medical
devices in batches. The medical devices can be run through a
continuous process.
[0022] In all embodiments of the present invention, single or
multiple coating materials are applied to medical devices by
suspending the medical devices in an air stream and coating at
least a portion of the medical device. As used herein, "air stream"
refers to a stream of any suitable gas, such as air, nitrogen,
argon and combinations thereof. The air stream is said to be
"substantially devoid of suspending particles", i.e., particles are
not utilized to suspend the medical devices within the air stream.
The air stream itself suspends the medical devices. Any non-coating
particles (i.e., particles that do not become at least partially
part of the coating materials) that may be present in the air
stream do not materially provide for suspending the medical
devices. Particles might be added to the air stream to enhance the
coating process, e.g., a polishing media and/or electrostatic
inhibitors in low ratios, however, these added particles are not
used to suspend the articles to be coated. Thus, the air stream,
since it is substantially devoid of suspending particles and only
requires the air itself in the air stream to suspend the medical
devices, may be termed a homogenous suspending air stream. As used
herein, "suspending" the medical device shall refer to a process
whereby the medical device is situated within the flow of an air
stream and may be moving within the air stream while unsupported by
any external means.
[0023] The medical devices used in conjunction with the present
invention include any device amenable to the coating processes
described herein. The medical device, or portion of the medical
device, to be coated or surface modified may be made of metal,
polymers, ceramics, composites or combinations thereof, and for
example, may be coated with one or more of these materials. Whereas
the present invention is described herein with specific reference
to avascular stent, other medical devices within the scope of the
present invention include any devices which are used, at least in
part, to penetrate the body of a patient. Examples include
implantable devices such as catheters, needle injection catheters,
blood clot filters, vascular grafts, stent grafts, biliary stents,
colonic stents, bronchial/pulmonary stents, esophageal stents,
ureteral stents, aneurysm filling coils and other coiled coil
devices, trans myocardial revascularization ("TMR") devices,
percutaneous myocardial revascularization ("PMR") devices etc., as
are known in the art, as well as devices such as hypodermic
needles, soft tissue clips, holding devices, and other types of
medically useful needles and closures. Any exposed surface of these
medical devices may be coated with the methods and apparatuses of
the present invention including, for example, the inside exposed
surface and the outside exposed surface of a tubular medical device
which is open at both ends.
[0024] The coating materials used in conjunction with the present
invention are any desired, suitable substances. In some
embodiments, the coating materials comprise therapeutic agents,
applied to the medical devices alone or in combination with
solvents in which the therapeutic agents are at least partially
soluble or dispersible or emulsified, and/or in combination with
polymeric materials as solutions, dispersions, suspensions,
latices, etc. The terms "therapeutic agents" and "drugs" are used
interchangeably herein and include pharmaceutically active
compounds, nucleic acids with and without carrier vectors such as
lipids, compacting agents (such as histones), virus, polymers,
proteins, and the like, with or without targeting sequences. The
coating on the medical devices may provide for controlled release,
which includes long-term or sustained release, of a bioactive
material.
[0025] Specific examples of therapeutic or bioactive agents used in
conjunction with the present invention include, for example,
pharmaceutically active compounds, proteins, oligonucleotides,
ribozymes, anti-sense genes, DNA compacting agents, gene/vector
systems (i.e., anything that allows for the uptake and expression
of nucleic acids), nucleic acids (including, for example,
recombinant nucleic acids; naked DNA, cDNA, RNA; genomic DNA, cDNA
or RNA in a non-infectious vector or in a viral vector which may
have attached peptide targeting sequences; antisense nucleic acid
(RNA or DNA); and DNA chimeras which include gene sequences and
encoding for ferry proteins such as membrane translocating
sequences ("MTS") and herpes simplex virus-1 ("VP22")), and viral,
liposomes and cationic polymers that are selected from a number of
types depending on the desired application. For example,
biologically active solutes include anti-thrombogenic agents such
as heparin, heparin derivatives, urokinase, and PPACK
(dextrophenylalanine proline arginine chloromethylketone);
prostaglandins; prostacyclins/prostacyclin analogs; antioxidants
such as probucol and retinoic acid; angiogenic and anti-angiogenic
agents; agents blocking smooth muscle cell proliferation such as
rapamycin, angiopeptin, and monoclonal antibodies capable of
blocking smooth muscle cell proliferation; anti-inflammatory agents
such as dexamethasone, prednisolone, corticosterone, budesonide,
estrogen, sulfasalazine, acetyl salicylic acid, and mesalamine,
lipoxygenase inhibitors; calcium entry blockers such as verapamil,
diltiazem and nifedipine;
antineoplastic/antiproliferative/anti-mitotic agents such as
paclitaxel, 5-fluorouracil, methotrexate, doxorubicin,
daunorubicin, cyclosporine, cisplatin, vinblastine, vincristine,
colchicine, epothilones, endostatin, angiostatin, Squalamine, and
thymidine kinase inhibitors; L-arginine; antimicrobials such as
triclosan, cephalosporins, aminoglycosides, and nitorfurantoin;
anesthetic agents such as lidocaine, bupivacaine, and ropivacaine;
nitric oxide (NO) donors such as lisidomine, molsidomine,
NO-protein adducts, NO-polysaccharide adducts, polymeric or
oligomeric NO adducts or chemical complexes; anti-coagulants such
as D-Phe-Pro-Arg chloromethyl ketone, an RGD peptide-containing
compound, heparin, antithrombin compounds, platelet receptor
antagonists, anti-thrombin antibodies, anti-platelet receptor
antibodies, enoxaparin, hirudin, Warafin sodium, Dicumarol,
aspirin, prostaglandin inhibitors, platelet inhibitors and tick
antiplatelet factors; interleukins, interferons, and free radical
scavengers; vascular cell growth promoters such as growth factors,
growth factor receptor antagonists, transcriptional activators, and
translational promotors; vascular cell growth inhibitors such as
growth factor inhibitors (e.g., PDGF inhibitor--Trapidil), growth
factor receptor antagonists, transcriptional repressors,
translational repressors, replication inhibitors, inhibitory
antibodies, antibodies directed against growth factors,
bifunctional molecules consisting of a growth factor and a
cytotoxin, bifunctional molecules consisting of an antibody and a
cytotoxin; Tyrosine kinase inhibitors, chymase inhibitors, e.g.,
Tranilast, ACE inhibitors, e.g., Enalapril, MMP inhibitors, (e.g.,
Ilomastat, Metastat), GP IIb/IIIa inhibitors (e.g., Intergrilin,
abciximab), seratonin antagnonist, and 5-HT uptake inhibitors;
cholesterol-lowering agents; vasodilating agents; agents which
interfere with endogeneus vascoactive mechanisms; survival genes
which protect against cell death, such as anti-apoptotic Bcl-2
family factors and Akt kinase; and combinations thereof; and beta
blockers. These and other compounds may be added to a coating
solution, including a coating solution that includes a polymer,
using similar methods and routinely tested as set forth in the
specification. Any modifications are routinely made by one skilled
in the art.
[0026] Polynucleotide sequences useful in practice of the invention
include DNA or RNA sequences having a therapeutic effect after
being taken up by a cell. Examples of therapeutic polynucleotides
include anti-sense DNA and RNA; DNA coding for an anti-sense RNA;
or DNA coding for tRNA or rRNA to replace defective or deficient
endogenous molecules. The polynucleotides of the invention can also
code for therapeutic proteins or polypeptides. A polypeptide is
understood to be any translation product of a polynucleotide
regardless of size, and whether glycosylated or not. Therapeutic
proteins and polypeptides include as a primary example, those
proteins or polypeptides that can compensate for defective or
deficient species in an animal, or those that act through toxic
effects to limit or remove harmful cells from the body. In
addition, the polypeptides or proteins that can be incorporated
into the polymer coating, or whose DNA can be incorporated, include
without limitation, angiogenic factors and other molecules
competent to induce angiogenesis, including acidic and basic
fibroblast growth factors, vascular endothelial growth factor,
hif-1, epidermal growth factor, transforming growth factor .alpha.
and .beta., platelet-derived endothelial growth factor,
platelet-derived growth factor, tumor necrosis factor .alpha.,
hepatocyte growth factor and insulin like growth factor; growth
factors; cell cycle inhibitors including CDK inhibitors;
anti-restenosis agents, including p15, p16, p18, p19, p21, p27,
p53, p57, Rb, nFkB and E2F decoys, thymidine kinase ("TK") and
combinations thereof and other agents useful for interfering with
cell proliferation, including agents for treating malignancies; and
combinations thereof. Still other useful factors, which can be
provided as polypeptides or as DNA encoding these polypeptides,
include monocyte chemoattractant protein ("MCP-1"), and the family
of bone morphogenic proteins ("BMP's"). The known proteins include
BMP-2, BMP-3, BMP-4, BMP-5, BMP-6 (Vgr-1), BMP-7 (OP-1), BMP-8,
BMP-9, BMP-10, BMP-11, BMP-12, BMP-13, BMP-14, BMP-15, and BMP-16.
Currently preferred BMPs are any of BMP-2, BMP-3, BMP-4, BMP-5,
BMP-6 and BMP-7. These dimeric proteins can be provided as
homodimers, heterodimers, or combinations thereof, alone or
together with other molecules. Alternatively, or in addition,
molecules capable of inducing an upstream or downstream effect of a
BMP can be provided. Such molecules include any of the "hedgehog"
proteins, or the DNA's encoding them.
[0027] Coating materials other than therapeutic agents include, for
example, polymeric materials, sugars, waxes, and fats, applied
alone or in combination with therapeutic agents, and monomers that
are cross-linked or polymerized. Such coating materials are applied
in the form of, for example, powders, solutions, dispersions,
suspensions, and/or emulsions of one or more polymers, optionally
in aqueous and/or organic solvents and combinations thereof or
optionally as liquid melts including no solvents. When used with
therapeutic agents, the polymeric materials are optionally applied
simultaneously with, or in sequence to (either before or after),
the therapeutic agents. Such polymeric materials employed as, for
example, primer layers for enhancing subsequent coating
applications (e.g., application of alkanethiols or sulfhydryl-group
containing coating solutions to gold-plated devices to enhance
adhesion of subsequent layers), layers to control the release of
therapeutic agents (e.g., barrier diffusion polymers to sustain the
release of therapeutic agents, such as hydrophobic polymers;
thermal responsive polymers; pH-responsive polymers such as
cellulose acetate phthalate or acrylate-based polymers,
hydroxypropyl methylcellulose phthalate, and polyvinyl acetate
phthalate), protective layers for underlying drug layers (e.g.,
impermeable sealant polymers such as ethylcellulose), biodegradable
layers, biocompatible layers (e.g., layers comprising albumin or
heparin as blood compatible biopolymers, with or without other
hydrophilic biocompatible materials of synthetic or natural origin
such as dextrans, cyclodextrins, polyethylene oxide, and polyvinyl
pyrrolidone), layers to facilitate device delivery (e.g.,
hydrophilic polymers, such as polyvinyl pyrrolidone, polyvinyl
alcohol, polyalkylene gylcol (i.e., for example, polyethylene
glycol), or acrylate-based polymer/copolymer compositions to
provide lubricious hydrophilic surfaces), drug matrix layers (i.e.,
layers that adhere to the medical device and have therapeutic agent
incorporated therein or thereon for subsequent release into the
body), and epoxies.
[0028] When used as a drug matrix layer for localized drug
delivery, the polymer coatings of the present invention comprise
any material capable of absorbing, adsorbing, entrapping, or
otherwise holding the therapeutic agent to be delivered. The
material is, for example, hydrophilic, hydrophobic, and/or
biodegradable, and is preferably selected from the group consisting
of polycarboxylic acids, cellulosic polymers, gelatin,
polyvinylpyrrolidone, maleic anhydride polymers, polyamides,
polyvinyl alcohols, polyethylene oxides, glycosaminoglycans,
polysaccharides, polyesters, polyurethanes, silicones, polyurea,
polyacrylate, polyacrylic acid and copolymers, polyorthoesters,
polyanhydrides such as maleic anhydride, polycarbonates,
polyethylene, polypropylenes, polylatic acids, polystyrene, natural
and synthetic rubbers and elastomers such as polyisobutylene,
polyisoprene, polybutadiene, including elastomeric copolymers, such
as Kraton.RTM., styrene-isobutylene-styrene (SIBS) copolymers;
polyglycolic acids, polycaprolactones, polyhydroxybutyrate
valerates, polyacrylamides, polyethers, polysaccharides such as
cellulose, starch, dextran and alginates; polypeptides and proteins
including gelatin, collagen, albumin, fibrin; copolymers of vinyl
monomers such as ethylene vinyl acetate (EVA), polyvinyl ethers,
polyvinyl aromatics; other materials such as cyclodextrins,
hyaluronic acid and phosphorylcholines; and mixtures and copolymers
thereof. Coatings from polymer dispersions such as polyurethane
dispersions (BAYHDROL, etc.) and acrylic latex dispersions are also
within the scope of the present invention. Preferred polymers
include polyurethanes; polyacrylic acid as described in U.S. Pat.
No. 5,091,205, the disclosure of which is incorporated herein by
reference; and aqueous coating compositions comprising an aqueous
dispersion or emulsion of a polymer having organic acid functional
groups and a polyfunctional crosslinking agent having functional
groups capable of reacting with organic acid groups, as described
in U.S. Pat. No. 5,702,754, the disclosure of which is incorporated
herein by reference.
[0029] The release rate of drugs from drug matrix layers is largely
controlled, for example, by variations in the polymer structure and
formulation, the diffusion coefficient of the matrix, the solvent
composition, the ratio of drug to polymer, potential chemical
reactions and interactions between drug and polymer, the thickness
of the drug adhesion layers and any barrier layers, and the process
parameters, e.g., drying, etc. The coating(s) applied by the
methods and apparatuses of the present invention may allow for a
controlled release rate of a coating substance with the controlled
release rate including both long-term and/or sustained release.
[0030] Additionally, a coating substance may include suspension
particles, e.g., a powder. The suspension particles are not
utilized for suspending the medical devices, but rather, are coated
onto the medical devices. For example, the suspension particles may
be fused to the surface of the medical device by a coating
solution.
[0031] The coatings of the present invention are applied such that
they result in a suitable thickness, depending on the coating
material and the purpose for which the coating(s) is applied. As an
example, coatings applied for localized drug delivery are typically
applied to a thickness of about 1 to 30 microns, preferably about 2
to 20 microns. Very thin coatings, e.g., of about 100 .ANG., and
much thicker coatings, e.g., more than 30 microns, are also
possible. It is also within the scope of the present invention to
apply multiple layers of the same or different coating materials,
which may perform identical or different functions (e.g., to
provide for biocompatibility, to control drug release, etc.).
[0032] In accordance with a first embodiment of the present
invention, medical devices are coated by suspending the medical
device in an air stream substantially devoid of suspending
particles having a first coating material dispersed therein, by any
corresponding, suitable method. For illustrative purposes only, the
first embodiment of the invention is described with specific
reference to the so-called "Wurster process" shown in FIG. 1. The
Wurster process is described in U.S. Pat. No. 3,253,944, which is
incorporated herein by reference. Such a process has been proposed
for use to coat pharmaceutical tablets with waxes (see, e.g., D. M.
Jones, "Factors to Consider in Fluid-Bed Processing," 9 Pharm.
Tech. 50-62 (1985), and A. M. Mehta, "Scale-Up Considerations in
the Fluid-Bed Process for Controlled-Release Products," 12 Pharm.
Tech. (1988)), but has not been proposed or used to coat medical
devices.
[0033] As stated above, the first embodiment for an apparatus for
coating medical devices 100 in accordance with the principles of
the present invention is illustrated in FIG. 1. In FIG. 1, medical
devices 110 are placed in a chamber 120. The chamber 120 includes a
top opening 121 for exhaust, a bottom opening 122 for introduction
of input air 140, and at least one side wall 123. Although the
chamber 120 is shown to generally include a structure having a
tapered, cylindrical shape, the chamber 120 may be of any suitable
shape, such as rectangular. The tapered configuration of the
chamber 120 as shown in FIG. 1 is generally preferred to facilitate
a cyclical air flow within the chamber 120. The coating process of
the present invention occurs within the chamber 120.
[0034] The embodiment 100 includes an air distribution plate 130,
which is secured to the side wall 123 of the chamber 120. The air
distribution plate 130 has openings 131 that are smaller than the
smallest dimension of the medical devices 110 so that the medical
devices 110 cannot fall through it. The purpose of the air
distribution plate 130 is to channel input air 140, introduced into
the chamber 120 from its bottom opening 122, into the coating
region 150 of the chamber 120 to assist in the fluidization and
coating of the medical devices 110. The air distribution plate 130
is of any suitable shape to achieve this purpose, such as planar
(as shown in FIG. 1) or concave configurations.
[0035] The air distribution plate 130 is of any suitable structure
that permits the flow of air therethrough such as, for example, a
perforated metal or ceramic plate or screen. Preferably, the air
distribution plate 130 has an open area (i.e., the planar surface
area of openings) of about 4 to about 30 percent, such as about 4,
6, 8, 12, 16 or 30 percent. A specific example of the air
distribution plate 130 is a stainless steel screen having an
opening size of about 60 to about 325 mesh. The open area and
opening size of the air distribution plate 130 are selected to
provide for the optimum suspension and coating of the medical
devices 110 within the coating region 150. For example, an air
distribution plate 130 having a large open area will result in a
relatively low velocity of air within the coating region 150, and
is thus used for low density medical devices 110. Conversely, an
air distribution plate 130 having a small open area will result in
a relatively high velocity of air within the coating region 150,
and is thus used for high density medical devices 110. The air
distribution plate can be either fixed or rotating to facilitate
more even distribution of air.
[0036] The embodiment 100 further includes a nozzle 160 extending
through the air distribution plate 130 and into the coating region
150. The nozzle injects an air stream 161, which in this embodiment
includes a coating material dispersed therein, into the coating
region 150. As shown in FIG. 1, the nozzle 160 is preferably
located at or near the longitudinal axis of the chamber 120. The
embodiment 100 optionally includes multiple nozzles situated at
various locations within the chamber 120, such as along the side
123, top, or bottom of the chamber 120. In this embodiment, the
nozzle 160 is used to introduce one or more coating materials,
sequentially or simultaneously, into the chamber 120. Where
multiple coating materials are introduced into chamber 120, they
may be either mixed and introduced at nozzle 160, i.e., in-line
mixed, or may be introduced into chamber 120 though nozzle 160
and/or from the nozzles located at the top or bottom of the
chamber.
[0037] Both air streams 161 and 140 are substantially devoid of
suspending particles, as discussed above, and the air streams may
consist of one or more gases. Because the air streams are
substantially devoid of any suspending particles, the surface areas
of the medical devices to be coated when in the air stream(s) are
not subject to being obscured by, and/or damaged by contact with,
the suspending particles, which could deleteriously impact the
coating of the surface areas of the medical devices. In an
embodiment, air stream 161 is characterized by a higher velocity
than air stream 140 that is channeled through the air distribution
plate 130 to cause a cyclical air flow and corresponding medical
device movement within the coating region 150. In other words, the
high-velocity air stream 161 causes the medical devices 110 to be
lifted from or near the air distribution plate 130 towards the top
opening 121 of the chamber 120. When the air stream 161 can no
longer support the medical devices 110, they fall through the
lower-velocity air stream 140 along the sides of the chamber 120.
The velocity of the air stream 140 is sufficient to slow, but not
to stop or reverse, the fall of the medical devices 110. When the
medical devices 110 approach or fall on the air distribution plate
130, they are again lifted by the high-velocity air flow 161. Thus,
air streams 161 and 140 are of a sufficient velocity such that the
air streams themselves are able to suspend the medical devices
within the coating region. Thus, no suspending particles are
required in the air streams to suspend the medical devices to be
coated.
[0038] In an embodiment where multiple nozzles are used, nozzle
160, centrally located near the air distribution plate 130 as shown
in FIG. 1, may be the only nozzle associated with a high-velocity
air stream. Any other nozzles may be only used to inject the
coating material(s) into the chamber 120 at a low velocity so as
not to disrupt the cyclical flow of air and medical devices.
[0039] An optional partition 170, which is preferably tubular in
shape, may be attached to the side wall 123 of the chamber 120 and
extend along the longitudinal axis of the chamber 120 to help
facilitate the cyclical air flow within the chamber 120 and to
ensure the separation of rising and falling medical devices 110,
thus minimizing potentially damaging interactions. Also optional is
a gas exhaust duct 180, which is preferably associated with top
opening 121 and which may include a filter.
[0040] In an alternative embodiment; the air streams 161 and 140
may be of substantially equal velocity. In this embodiment, the
flow/velocity of the two air streams at the center of the chamber
120 would be additive to effectively create a greater flow/velocity
of air at the center of the chamber in comparison to the
flow/velocity of the air at the sides of the chamber, thus
providing for cyclical movement of the medical devices as described
above.
[0041] In yet another alternative embodiment, only one of air
streams 161 or 140 are utilized. For example, the airstream 161 is
utilized to both suspend the medical devices and introduce the
coating material(s) into chamber 120. A cyclical flow of air within
the chamber could be provided by varying the velocity of the one
air stream across it's flow pattern, such as, for example, by
appropriately configuring the openings in air distribution plate
130.
[0042] Although the embodiment 100 making use of the Wurster
process is generally preferred for making the coated medical
devices of the present invention, any suitable method or apparatus
can be used. For example, medical devices may be loaded into a
conventional fluidized bed chamber, in which air is introduced into
a "bed" or layer of the medical devices from below while the
coating material is sprayed onto the fluidized devices from above.
In such a process, the medical devices will move randomly within a
fluidized bed. Airless and atomized air spray processes are also
within the scope of the present invention. Although not required by
the present invention, coating within a closed chamber is generally
preferred because of the corresponding ability to control the
coating processing parameters and the chamber environment. For
example, it is advantageous to control processing parameters such
as the fluidization air composition, temperature and humidity when
coating with drugs or polymers that degrade, oxidize, hydrolyze,
etc., upon exposure to specific environments. The present invention
may be utilized to coat medical devices with organic-based coating
materials. Thus, operating temperatures in at least some
embodiments of the apparatuses and methods of the present invention
are generally less than 500.degree. C., with some embodiments
having an operating temperature of between 0.degree. C.-200.degree.
C. The particular operating temperatures utilized are compatible
with the particular coating materials. Thus, operating temperatures
compatible with all of the coatings materials disclosed herein can
be established and maintained in the apparatuses and methods of the
present invention.
[0043] In other alternative embodiments of the present invention,
instead of applying a coating as a preformed substance, the
material of the coating would be generated in the spraying process.
The suspended medical devices to be coated could be sprayed first
with a polyfunctional condensation monomer followed by spraying
with a complementary condensation polyfunctional monomer to provide
a polymer coating by interfacial polymerization. For example, a
glycol or diamine could be sprayed on first followed by a
diisocyanate to form a polyurethane or polyurea. A potential
advantage of this process would be to avoid the need for volatile
solvents, application of lower viscosity fluids to improve
coverage, and to provide crosslinked polymer coating that would be
impossible to obtain by conventional coating techniques, e.g., by
use of trifunctional monomers.
[0044] Other alternative embodiments for coating of the medical
devices include apparatuses and methods that do not involve
dispensing the coating material using an air stream through, for
example, nozzle 160 as discussed above in connection with FIG. 1.
These alternative apparatuses and methods for coating the medical
devices still utilize an air stream and the structure of FIG. 1, as
described above, to suspend the medical devices in a coating
chamber; however, the medical devices could be coated by using
alternative coating techniques. These alternative coating
techniques could also be utilized with the fluidized bed chamber
contemplated above.
[0045] Thus, a second embodiment for an apparatus for coating
medical devices 200 in accordance with the principles of the
present invention is illustrated in FIG. 2. The embodiment of FIG.
2 utilizes a structure similar to that described for the embodiment
of FIG. 1, however, in the embodiment of FIG. 2, the coating
material may not be dispersed within air stream 161 by nozzle 160.
In the embodiment of FIG. 2, both or one of the air streams 161 and
140 are utilized to suspend the medical devices within chamber 120.
A coating apparatus 210 is utilized to apply the coating to the
suspended medical devices. Depending upon the particular coating
apparatus used, a coating material may be introduced into the
coating chamber by the coating apparatus itself, by one or both of
air streams 161 and 140, or through any other well-known means that
are associated with the particular coating apparatus utilized. For
reference purposes, the components for embodiment 200 in FIG. 2
that are common to those of embodiment 100 of FIG. 1 are designated
by like reference numerals.
[0046] In the embodiment of FIG. 2, the coating apparatus 210 may
include a device(s) that permit the use of any number of
alternative techniques for coating the medical devices. As
discussed previously, the coating apparatus may apply a single
coating or multiple coatings to the medical device. Additionally,
the coating apparatus may apply coatings to any of the different
types of medical devices disclosed previously in this
specification. The apparatus may also apply any of a variety of
coating materials as described previously.
[0047] The coating apparatus 210 may be utilized to apply one or
more coatings to medical devices by utilizing any of the following
exemplary techniques and the associated devices for these
techniques for application of the coatings.
[0048] Ionization deposition processes can be utilized to apply
coatings to medical devices. Ionization deposition processes such
as ion beam-assisted deposition (IBAD), ion beam (IB), and ion beam
implantation (IBI). Examples of materials that can be
deposited/implanted include nitrogen, gold, silver, tungsten,
titanium, aluminum, silicon, iron, nickel, selenium, tantalum,
diamond-like carbon (DLC), ceramics, radioactive materials such as
palladium-103, .sup.60Co, .sup.192Ir, .sup.32P, .sup.111In,
.sup.90Y, and .sup.99Tc.
[0049] Plasma treatment, grafting, or deposition processes can be
used to coat or modify the surface of the medical device or a part
of the medical device with the following materials: monomers or
oligomers, cyclic and acrylic siloxanes, silanes, silylimidazoles,
fluorine-based monomers (hydrofluorocarbons), aliphatic and
aromatic hydrocarbons, acrylic monomers, N-vinyl pyrrolidone, vinyl
acetate, ethylene oxide, one or more monomers used alone or in
combination in order to form blends, cross-linked polymers,
copolymers and interpenetrating network polymers. Plasma treatment
may also be used to enhance crosslinking and/or improve surface
properties such as adhesion, lubricity, or conductivity.
[0050] FIG. 3 illustrates a particular alternative embodiment for
an apparatus for coating medical devices 300 in accordance with the
principles of the present invention where the coating apparatus 210
of FIG. 2 is a plasma coater 305. As described in connection with
FIG. 2, in the embodiment of FIG. 3, both or one of the air streams
161 and 140 are utilized to suspend the medical devices within
chamber 120; however, a plasma coater 305 is utilized to coat the
suspended medical devices. For reference purposes, the components
for embodiment 300 in FIG. 3 that are common to those of
embodiments 100 and 200 of FIGS. 1 and 2, respectively, are
designated by like reference numerals. Plasma coater 305 includes
electrodes 310, a matching network 320, and a RF (radio frequency)
generator 330. The materials to be coated on the medical devices
may be introduced into chamber 120 through either of air streams
161 and/or 140 or through any other means, such as by depositing
the coating material on air distribution plate 130 and having the
air stream(s) dispense the coating material into the chamber. The
coating material(s) are then applied to the medical devices by
using plasma coater 305.
[0051] In continuing with the discussion of the alternative coating
techniques that may be utilized in the present invention, chemical
vapor deposition processes are also within the scope of the present
invention. Processes such as polyamide, polyimide, parylene, and
parylene derivatives, polyalkylene oxide, polyalkylene glycol,
polypropylene oxide, silicone based polymers, polymers of methane,
tetrafluoroethylene or tetramethyldisiloxane or polymers from
photopolymerizable monomers or combinations thereof.
[0052] Electroplating and electrostatic deposition processes may be
utilized in the present invention as well as deposition,
polymerization or treatment of part of the medical device surface
or the entire device surface using microwave, ultra-violet light
(UV), visible light, e-beam, and thermal evaporation
techniques.
[0053] In any embodiment of the present invention, the apparatuses
and methods of the present invention result in the complete or
partial coating of the medical device to be coated. Partial coating
is accomplished, for example, using known masking or similar
techniques to result in the coating of predetermined struts or
stent segments. The various coating techniques may be used in
conjunction with one another and, thus, they are not mutually
exclusive.
[0054] In addition to the previously described coating layers and
their purposes, in the present invention the coating layer or
layers may be applied for any of the following additional purposes
or combination of the following purposes: [0055] Alter surface
properties such as lubricity, contact angle, hardness, or barrier
properties. [0056] Improve corrosion, humidity and/or moisture
resistance. [0057] Improve fatigue, mechanical shock, vibration,
and thermal cycling. [0058] Change/control composition at surface
and/or produce compositionally graded coatings. [0059] Apply
controlled crystalline coatings. [0060] Apply conformal pinhole
free coatings. [0061] Minimize contamination. [0062] Change
radiopacity. [0063] Impact bio-interactions such as
tissue/blood/fluid/cell compatibility, anti-organism interactions
(fungus, microbial, parasitic microorganisms), immune response
(masking). [0064] Control release of incorporated therapeutic
agents (agents in the base material, subsequent layers or agents
applied using the above techniques or combinations thereof). [0065]
Or combinations of the above using single or multiple layers.
[0066] In addition to the benefits of the apparatus and methods of
the present invention that have been discussed previously in this
specification and in further amplification of some of the benefits
discussed previously, the present invention can provide the
following advantages. [0067] Coating in an air stream allows many
medical devices or parts of medical devices to be coated
simultaneously in batch process, which eliminates variability that
could arise if each object is coated and handled individually.
[0068] Part to part variability is minimized because all the
objects are coated under identical conditions at the same time.
[0069] Uniformity of the coated layer, layers, or surface
modification is achieved over the entire surface of interest using
careful control and optimization of the coating parameters. [0070]
In situations where the device, part of the device and/or any
subsequently coated layers contain one or more therapeutic agents,
the methods yield a uniform, well-defined rate controlling
membrane, or a uniformly coated layer incorporating the therapeutic
agents. This results in uniform controlled drug release for
devices, parts of devices, and/or coatings that contain active
components. [0071] Drug reconciliation and traceability (a critical
issue in finished pharmaceutical manufacturing processes) is
maximized using this type of contained manufacturing process in
situations where the device, part of the device, and/or any
subsequently coated layers contain one or more therapeutic agents.
[0072] No defects will form on the surface as a result of holding
the device during coating since the coating is applied to the
device while the device is levitated in the air stream. [0073]
Worker exposure to harmful chemicals, or components is minimized
because the process proceeds under sealed conditions. [0074] One
coater may be used to apply more than one type of coating and/or
surface modification if the equipment is designed to handle
combinations of several coating techniques such as air atomization,
ionization deposition, plasma, chemical vapor deposition,
electroplating, electrostatic, UV, microwave, visible, and
e-beam.
[0075] The invention is further described with reference to the
following non-limiting examples.
Example 1
[0076] Coronary stents are coated with a polymeric coating solution
in accordance with the present invention.
[0077] Numerous (approximately 300 to 600 in this example) NIR
stents (Medinol, Tel Aviv) are placed in a Wurster fluidized bed
chamber, such as a GPCG-1 (available from Glatt Air Techniques,
Ramesey, N.J.). The stents are each about 9 mm-32 mm in length,
about 1.5 mm-3.0 mm in diameter, about 7 mg-35 mg in weight, and
about 46-200 mm.sup.2 in surface area.
[0078] A coating solution of polyurethane is prepared by mixing the
following components (in approximate weight percentages): 0.5-1.0%
Corethane 50D (Corvita, Miami, Fla.), 1.0-10.0% dimethylacetamide,
and balance tetrahydrofuran. The solution components are mixed
using a magnetic stirrer for at least about 8 hours to form a
solution or dispersion, which is thereafter filtered with a 1.0
micron Teflon filter.
[0079] The stents are suspended using fluidizing air at about 2-20
psi, at a temperature of about 20-90.degree. C. and a dew point of
about 10-60.degree. C. The stents are coated by pumping about
100-400 gm of the coating solution at about 0.1-6 ml/min to a
nozzle located at the center of the perforated plate. The coating
solution is atomized with compressed atomizing air operating at a
pressure of about 2-40 psi and a flow rate of about 5 cfm. The
atomizing air has a temperature of about 10-60.degree. C. and a dew
point of about 0-40.degree. C.
[0080] Coating of the suspended stents continues until all of the
coating solution has been pumped through the nozzle. Following the
coating process, the stents are continued to be suspended for about
5-180 minutes to allow for the polymer coating layer to completely
dry. After drying, the stents are removed from the Wurster
fluidization chamber.
[0081] Because the stents are suspended in an air stream during the
coating process, the coated stents do not display surface defects
that normally result when a stent is held during coating. In
addition, this is a batch process in which each stent is exposed to
identical process conditions. The coating thickness depends on the
size of the stent and the amount of the coating solution applied.
As a result of the good control over processing parameters during
coating, the coating on each stent strut is substantially
identical.
Example 2
[0082] Coronary stents are coated with a layer that comprises both
polymeric and drug coating materials in accordance with the present
invention.
[0083] NIR stents are placed in a Wurster fluidized bed chamber, as
described in Example 1. A coating solution is prepared by mixing
the following components (in approximate weight percentages): about
0.5-2.0% Elvax 40W (available from Dupont, Wilmington, Del.), about
0.05-0.6% paclitaxel, balance chloroform. The coating solution
components are mixed with a magnetic stirrer for at least 8 hours
to form a solution or dispersion, which is thereafter filtered with
a 0.2 micron Teflon filter.
[0084] The stents are suspended and coated by the processing
parameters described in Example 1. The coating process results in
stents coated with uniform coating layers in which paclitaxel is
evenly distributed on each stent and substantially the same dose
applied to every stent in the batch.
Example 3
[0085] Coronary stents are coated with multiple polymer coating
layers in sequence distributed on each stent and the same dose
applied to every stent in the batch in accordance with the present
invention.
[0086] NIR stents are placed in a Wurster fluidized bed chamber, as
described in Example 1. A primer coating solution is prepared by
mixing the following components (in approximate weight
percentages): 0.01-2% Ultrathene UE631-04 (Equistar Chemical, LP,
Houston, Tex.) and 99% Chloroform. The stents are suspended and
coated by the processing parameters described in Example 1. When
the primer coating is completely dry, the stents are further coated
with a topcoat solution comprising (in approximate weight
percentages): 0.5-0.65% Corethane 50D polyurethane, 1.0-10.0%
dimethylacetamide, and balance tetrahydrofuran, prepared by the
process described in Example 1.
[0087] The coating process results in stents having uniform,
dual-layered coatings. The application of the primer coating
enhances the adhesion of the topcoat layer to the stents. In
addition, by applying several layers in sequence without removing
the stents from the fluidization chamber, exposure of the stents to
an outside environment between layers is minimized.
Example 4
[0088] As a variation to Example 2, a barrier layer is applied to
the stents coated with a polymer/drug layer in accordance with the
present invention. A barrier layer of ethylene vinyl acetate
copolymer or silicone protects the underlying polymer/drug layer
from atmospheric degradation such as by oxidative or hydrolytic
breakdown. The barrier layer also preferably improves abrasion
resistance and durability, or may be used to control the start or
rate of release of the drug from the underlying polymer/drug layer
in vivo.
[0089] The barrier layer is the same or different composition as
the polymer in the polymer/drug layer. For example, the barrier
layer optionally comprises a dilution of MED-6605 (Nusil Silicone
Technology, Carpinteria, Calif.) to 1% solids using chloroform. The
hydrophobic silicone barrier reduces the release rate from the
polyurethane/paclitaxel layer. Coating of both the barrier layer
and polymer/drug layer is preferably conducted in sequence without
removing the stents from the fluidization chamber.
[0090] The release profile of the drug may also be altered by
concurrently applying several layers of gradient concentrations to
yield a multi-phasic release profile. For example, the ratio of
copolymers of polylactic acid ("PLA") and polyglycolic acid ("PGA")
(Birmingham Polymers, Birmingham, Ala.) containing 0.1-10% of a
peptide analog such as an analog of Somatostatin may be varied
sequentially so that the drug has multiple peak release drug
concentrations. For example, the initial coated layer may comprise
PLA with drug, followed by 85:15 DL-PLG with drug, followed by
75:25 DL-PGA followed by 65:35 DL-PLG and 50:50 DL-PLG with drug,
and so on. The release rate from each layer is optionally different
such that the final result is several different peaks corresponding
to the release from each individual layer. Layers are not limited
to a single drug.
Example 5
[0091] The invention includes the sequential application of several
layers that contain components that are incompatible or do not
share a common solvent system. For example, an initial coating
layer applied to a medical device may contain paclitaxel and
corethane polyurethane coated from solutions containing
dimethylacetamide and tetrahydrofuran. A second coating layer may
comprise an aqueous-based coating formulation containing agents
that enhance surface biocompatibility such as heparin or albumin.
For example, paclitaxel-PU is applied as a solution in dimethyl
acetamide as a first layer, followed by application of heparin
and/or polyethyleneglycol in aqueous solution as a second layer. As
yet another example, benzalkonium chloride (a cationic
surface-active agent) is applied as a first layer, followed by
heparin (an anionic biocompatible polysaccharide) as a second
layer, thus forming an ionic bond.
[0092] The invention includes parallel applications of
drug(1)-solvent(1) and polymer(1)-solvent(2), where the drug and
polymer are soluble in different solvents or are incompatible or
unstable when present together. As an example, the invention is
used for the simultaneous application of aqueous solution of
doxorubicin hydrochloride and silicone polymer in tetrahydrofuran
from two separate feeds, wherein the latter is used to form a
drug-matrix in situ and to control release kinetics. As another
example, DNA solution is simultaneously applied with cationic lipid
systems from two separate feeds to eliminate shelf-life stability
issues associated with DNA-lipid complex formulations that exhibit
undesirable increases in size and turbidity as a function of salt
concentration.
[0093] The invention includes parallel applications of
drug(1)-polymer(1)-solvent(1) and drug(2)-polymer(2)-solvent(2) to
eliminate compatibility or solubility issues. Examples include the
simultaneous application of (i) cisplatin-hydroxypropyl methyl
cellulose-water and paclitaxel-PCL/PLA-chloroform from two
different feeds; (ii) albumin or gelatin solution from one feed and
gluraldehyde crosslinker from second feed; and (iii) acrylate
monomer solution from one feed and methylene bis acrylamide as
crosslinker for the second feed.
[0094] The simultaneous coating of medical devices with
incompatible coating materials is carried out, for example, by
introducing separate feed streams into a coating chamber via
separate nozzles. When compared to conventional coating techniques
such as dip coating and spray coating, this embodiment of the
invention substantially expands the number of coating formulations
and combinations of polymers and drugs that may be coated onto
medical devices. For example, an aqueous-based solution containing
a desired therapeutic substance is atomized simultaneously with a
solvent-based polymer coating solution.
Example 6
[0095] The invention includes the coating of medical devices with
coating materials from low-viscosity aqueous or non-aqueous
solutions that would otherwise be difficult to achieve via
dip-coating or spray coating applications. For example, peptide and
protein drugs, which often undergo denaturation in the presence of
organic solvents or excessive heat, are easily coated onto medical
devices in accordance with the present invention. In such
applications, the drug is applied from an aqueous formulation and
the coating process is controlled (i.e, in terms of temperature and
humidity) to minimize drug degradation. As another example, low
viscosity solutions of RGD peptides or phosphorylcholines are
deposited as monolayers or as thicker coatings for use as drug
delivery depots.
[0096] The present invention provides methods of coating medical
devices using air suspension, and devices thereby produced.
Although the present invention has been described with respect to
several exemplary embodiments, there are many other variations of
the above-described embodiments which will be apparent to those
skilled in the art, even where elements have not explicitly been
designated as exemplary. It is understood that these modifications
are within the teaching of the present invention, which is to be
limited only by the claims appended hereto.
* * * * *