U.S. patent application number 10/813845 was filed with the patent office on 2004-09-23 for apparatus and method for coating implantable devices.
Invention is credited to Pacetti, Stephen D..
Application Number | 20040182312 10/813845 |
Document ID | / |
Family ID | 32327110 |
Filed Date | 2004-09-23 |
United States Patent
Application |
20040182312 |
Kind Code |
A1 |
Pacetti, Stephen D. |
September 23, 2004 |
Apparatus and method for coating implantable devices
Abstract
A method of forming a coating for an implantable medical device,
such as a stent, is provided which includes applying a composition
to the device in an environment having a selected pressure. An
apparatus is also provided for coating the devices. The apparatus
comprises a chamber for housing the device wherein the pressure of
the chamber can be adjusted during the coating process.
Inventors: |
Pacetti, Stephen D.; (San
Jose, CA) |
Correspondence
Address: |
Squire, Sanders & Dempsey L.L.P.
Suite 300
1 Maritime Plaza
San Francisco
CA
94111
US
|
Family ID: |
32327110 |
Appl. No.: |
10/813845 |
Filed: |
March 30, 2004 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10813845 |
Mar 30, 2004 |
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09872816 |
May 31, 2001 |
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6743462 |
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Current U.S.
Class: |
118/665 ;
118/300 |
Current CPC
Class: |
B05B 16/00 20180201;
B05D 3/0493 20130101; A61L 31/16 20130101; A61L 2300/00 20130101;
B05B 13/0235 20130101; A61L 31/10 20130101; B05D 1/02 20130101;
B05D 3/0486 20130101 |
Class at
Publication: |
118/665 ;
118/300 |
International
Class: |
B05D 003/00; B05C
005/00 |
Claims
What is claimed is:
1. An apparatus for coating implantable devices, comprising: a) a
chamber in which a coating composition comprising a coating solvent
can be applied to an implantable device; b) a pressure controller
for adjusting the pressure of the chamber during the coating
process to other than ambient pressure, wherein other than ambient
pressure is greater than 760 torr if the coating solvent is
non-volatile, and alternatively, wherein other than ambient
pressure is less than 760 torr if the coating solvent is
volatile.
2. The apparatus of claim 1 additionally including an applicator
for spraying a composition at the device.
3. The apparatus of claim 1 additionally including a support
assembly for holding the device during the coating process.
4. The apparatus of claim 1 additionally including means for
rotating the device during the coating process.
5. The apparatus of claim 1 additionally including means for moving
the device in a linear direction during the coating process.
6. The apparatus of claim 1 additionally including means for
creating convection flow within the chamber.
7. The apparatus of claim 1 wherein the coating process comprises
the application of the composition to the device and wherein the
composition further comprises a polymer and optionally a
therapeutic substance.
8. The apparatus of claim 1 additionally including a temperature
controller for adjusting the temperature of the chamber.
9. An apparatus for coating implantable devices, comprising: a) a
chamber in which a coating composition comprising a coating solvent
can be applied to an implantable device; b) a pressure controller
for adjusting the pressure of the chamber during the coating
process to other than ambient pressure, wherein other than ambient
pressure is greater than 760 torr if the coating solvent
evaporation rate is to be decreased, and alternatively, wherein
other than ambient pressure is less than 760 torr if the coating
solvent evaporation rate is to be increased.
10. The apparatus of claim 9 additionally including an applicator
for spraying the composition at the device.
11. The apparatus of claim 9 additionally including a support
assembly for holding the device during the coating process.
12. The apparatus of claim 9 additionally including means for
rotating the device during the coating process.
13. The apparatus of claim 9 additionally including means for
moving the device in a linear direction during the coating
process.
14. The apparatus of claim 9 additionally including means for
creating convection flow within the chamber.
15. The apparatus of claim 9 wherein the coating process comprises
the application of the composition to the device and wherein the
composition further comprises a polymer and optionally a
therapeutic substance.
16. The apparatus of claim 9 additionally including a temperature
controller for adjusting the temperature of the chamber.
17. An apparatus for coating implantable devices, comprising: a) a
chamber in which a coating composition comprising a coating solvent
can be applied to an implantable device; b) a pressure controller
for selecting the pressure of the chamber during the coating
process to a pressure, wherein pressure is other than ambient
pressure and is based on the vapor pressure of the coating
solvent.
18. The apparatus of claim 17 additionally including an applicator
for spraying the composition at the device.
19. The apparatus of claim 17 additionally including a support
assembly for holding the device during the coating process.
20. The apparatus of claim 17 additionally including means for
rotating the device during the coating process.
21. The apparatus of claim 17 additionally including means for
moving the device in a linear direction during the coating
process.
22. The apparatus of claim 17 additionally including means for
creating convection flow within the chamber.
23. The apparatus of claim 17 wherein the coating process comprises
the application of the composition to the device and wherein the
composition further comprises a polymer and optionally a
therapeutic substance.
24. The apparatus of claim 17 additionally including a temperature
controller for adjusting the temperature of the chamber.
Description
[0001] This is a Divisional of U.S. Ser. No. 09/872,816 filed on
May 31, 2001, allowed.
BACKGROUND OF THE INVENTION
[0002] 1. Field of the Invention
[0003] This invention relates to an apparatus and method for
coating implantable devices such as stents.
[0004] 1. Description of the Background
[0005] Stents act as scaffoldings, functioning to physically hold
open and, if desired, to expand the wall of the passageway.
Typically, stents are capable of being compressed, so that they can
be inserted through small cavities via catheters, and then expanded
to a larger diameter once they are at the desired location.
Mechanical intervention via stents has reduced the rate of
restenosis; restenosis, however, is still a significant clinical
problem. Accordingly, stents have been modified to perform not only
as a mechanical scaffolding, but also to provide biological
therapy.
[0006] Biological therapy can be achieved by medicating the stents.
Medicated stents provide for the local administration of a
therapeutic substance at the diseased site. In order to provide an
efficacious concentration to the treated site, systemic
administration of such medication often produces adverse or toxic
side effects for the patient. Local delivery is a preferred method
of treatment in that smaller total levels of medication are
administered in comparison to systemic dosages, but are
concentrated at a specific site. Local delivery thus produces fewer
side effects and achieves more favorable results.
[0007] A common method of medicating a stent is by depositing a
polymeric coating, impregnated with the therapeutic substance, on
the surface of the stent. A polymer dissolved in a solvent is
applied to the stent. A therapeutic substance can be dissolved or
dispersed in the composition. The solvent is allowed to evaporate
to form the coating. The application of the composition can be
performed by spraying the composition on the stent or immersing the
stent in the composition.
[0008] The solvents employed with the composition can be
categorized as having a high vapor pressure or low vapor pressure.
Non-volatile solvents evaporate very slowly from the composition
causing coating defects such as inconsistency in the coating
thickness and formation of "cob webs" or "pool webs" between the
stent struts. A solution to this problem is to coat the stent at
elevated temperatures to increase the evaporation rate of the
solvent. However, not all drugs are stable at elevated
temperatures. Volatile solvents have the tendency to evaporate very
quickly from the composition resulting in a coating which has a
powdered consistency and adheres poorly to the surface of the
stent. Accordingly, what is needed is an apparatus and process for
coating stents that does not suffer from the aforementioned
drawbacks.
SUMMARY OF THE INVENTION
[0009] In accordance with one aspect of the invention, a method of
forming a coating for an implantable medical device, such as a
stent, is provided. The method comprises applying a composition to
the stent in an environment having a pressure other than ambient
pressure. For compositions including a non-volatile solvent, the
pressure can be less that 760 torr; for compositions including a
volatile solvent, the pressure can be greater than 760 torr. The
composition can include a polymer, such as an ethylene vinyl
alcohol copolymer dissolved in a solvent, such as
dimethylacetamide. Optionally, a therapeutic substance can be added
to the composition, such as actinomycin D, paclitaxel, docetaxel,
or rapamycin. In accordance to one embodiment, the composition can
be applied by spraying the composition on the stent. During the act
of applying, the stent can be rotated and/or moved in a linear
direction along the longitudinal axis of the stent. The stent can
be a radially expandable stent, such as a balloon expandable or
self-expandable type.
[0010] In accordance with another aspect of the invention, a method
of forming a coating for a stent is provided, comprising
positioning a stent in a chamber; applying a fluid to the stent;
and adjusting the pressure of the chamber to increase or decrease
the evaporation rate of the fluid.
[0011] In accordance with another aspect of the invention, an
apparatus for coating implantable medical devices such as stents is
provided. The apparatus includes a chamber for housing a stent and
a pressure controller for adjusting the pressure of the chamber
during the coating process to a pressure below or above 760 torr.
In one embodiment, an applicator can be provided for spraying a
composition at the stent. A support assembly holds the stents in
the chamber and can be connected to a motor for providing
rotational and/or translational motion to the stent. A temperature
controller can also be provided for adjusting the temperature of
the chamber.
BRIEF DESCRIPTION OF THE FIGURE
[0012] FIG. 1 illustrates a pressure chamber for forming a coating
on a stent.
DETAILED DESCRIPTION OF THE EMBODIMENTS
[0013] Embodiments of the Pressure Chamber
[0014] Referring to FIG. 1, there is illustrated a pressure chamber
10 defining a workspace 12 for depositing a composition on a stent
14 for forming a coating. A chamber opening (number omitted) can be
provided for allowing a user to gain access into workspace 12. A
hatch 16 can be placed over the chamber opening for tightly sealing
the opening during the deposition process. The size of workspace 12
needs to be large enough so as to enclose a support assembly 18,
such as a mandrel, for adequately supporting stent 14 during the
coating process. Workspace 12 can be large enough so as to support
any suitable number of support assemblies 18 and stents 14.
[0015] In one embodiment, support assembly 18 can be connected to a
first motor assembly 20A for rotation of support assembly 18 along
the central, longitudinal axis x of stent 14. A second motor
assembly 20B can be additionally provided for translational
movement of support assembly 18 in a linear direction, back and
forth, along a railing 22. The rotational and translational motion
of stent 14 during the application of the composition can result in
a more uniform deposition of the coating.
[0016] An applicator 24, such as a spray valve, penetrates through
the wall of pressure chamber 10 and is positioned in the vicinity
of stent 14. Commercial applicators are available from Spray
Systems Co., EFD International Inc., and Badger Air-Brush Co., one
specific model of which is the EFD 780S spray device with VALVEMATE
7040 control system. To avoid spray rate alterations due to the
pressure difference, applicator 24 can be placed entirely within
pressure chamber 10. The nose of applicator 24 can be positioned at
any suitable distance away from stent 14, for example at about 1 cm
to about 10 cm. An operator should be capable of adjusting the
distance depending on the particular circumstances of the
deposition process. Applicator 24 is capable of applying the
composition at a pressure of, for example, about 10 torr to about
1000 torr. In accordance with an alternative embodiment, support
element 18 can be in a vertical position and applicator 24 spraying
in a horizontal direction.
[0017] A pressure controller such as a pump 26 is in fluid
communication with workspace 12 so as to create pressures below or
above 760 torr (1 atm) in pressure chamber 10. In one embodiment, a
cold trap 28 can be provided for preventing the solvent or
condensation from penetrating into pump 26 should pump 26 be used
to create a vacuum in pressure chamber 10. A filter 30, such as a
mist filter, can also be provided to prevent droplets of coating
composition from possibly reaching and damaging pump 26. Other
components of pressure chamber 10 can include a throttle valve 32
for opening and closing the communication line to pump 26, a
baratron vacuum gauge 34 for measuring the pressure in workspace 12
independent of the type and composition of the solvent vapor, and
an absorbent 36 for capturing the bulk of the composition
over-spray. Gas, such as air, can be pumped or bled into pressure
chamber 10 for creating a convection flow inside pressure chamber
10, to actively scavenge the solvent vapor from workspace 12 and
out through pump 26 so as to prevent solvent vapor build-up. A
diffuser 38 can be used to diffuse or "spread out" the flow of gas
so as to minimize disturbance of the spraying process. A bleed
valve 40 can be used for adjusting the flow rate of gas through
diffuser 38. In addition to rapidly removing the solvent vapor from
pressure chamber 10, bleed valve 40 can also be used to control the
chamber pressure by working in concert with throttle valve 32.
[0018] Pressure chamber 10 can also be connected to a heating
and/or cooling source 44 so as to control the temperature of
workspace 12. A cooler deposition environment, such as temperatures
of less than 50.degree. C. may be preferred depending on the
chemical stability of the therapeutic substance and the type
solvent used. In lieu of providing an external heating source, an
internal component, such as heating and/or cooling coils, can be
provided.
[0019] Method of Applying the Composition
[0020] To form a coating on a surface of stent 14, the surface of
stent 14 should be clean and free from contaminants that may be
introduced during manufacturing. However, the surface of stent 14
requires no particular surface treatment to retain the applied
coating. Stent 14 is mounted on mandrel 18 and the composition is
sprayed via applicator 24 at a pressure of, for example between 10
to 1000 torr. During the spraying of the composition, stent 14 can
be rotated at about 1 to about 120 rotations per minute. Stent 14
can also be moved in a linear direction at speed of about 1 to
about 20 cm/sec. The temperature of chamber 10 should be maintained
at a temperature that does not adversely affect the therapeutic
substance or the coating process--for example at about 20.degree.
C. to about 50.degree. C.
[0021] For a solvent having a low vapor pressure (e.g., below 30
torr at the temperature of application), or in other words
non-volatile substances, the solvent evaporates very slowly from
the composition, leading to irregularities in the coating thickness
and "cob webs" or "pool webs" between the stent struts.
Accordingly, compositions have been applied in short bursts,
interrupted by the drying of the composition between each
application step to minimize coating defects. Reducing the pressure
of chamber 10 below ambient pressure during the coating process
allows the solvent to evaporate more rapidly. Rapid evaporation of
the solvent allows the composition to be applied continuously for
depositing a coating of a suitable thickness or weight while
minimizing coating defects such as "pool webs." The pressure
employed in pressure camber 10 depends on the type of solvent
employed. Table 1 is an exemplary list of non-volatile solvents and
the suitable range of pressure which can be used in the process of
the present invention:
1 TABLE 1 Exemplary Pressure Ranges Solvent torr @ 20.degree. C.
Dimethylsulfoxide 0.8-<760 Dimethlacetamide 0.9-<760
Dimethylformamide 5.4-<760
[0022] For a solvent having a high vapor pressure (e.g., above 30
torr at the temperature of application), or in other words volatile
solvents, the solvent evaporates extremely rapidly from the
composition, leading to difficulties in the application of the
composition to the stent. Application of such compositions often
lead to coatings having powdered consistency and poor adhesion of
the coating to the surface of the stent. Increasing the pressure in
pressure chamber 10 above ambient pressure causes the solvent to
evaporate more slowly leading to a coating with a smoother surface,
more uniform composition, and better adhesion. Table 2 is an
exemplary list of volatile solvents and the suitable range of
pressure which can be used in the process of the present
invention:
2 TABLE 2 Exemplary Pressure Ranges Solvent torr @ 20.degree. C.
Toluene >760-2000 n-propanol >760-3400 Acetone
>760-9000
[0023] The Composition
[0024] The embodiments of the composition can be prepared by
conventional methods wherein all components are combined, then
blended. More particularly, in accordance to one embodiment, a
predetermined amount of a polymer or combination of polymers can be
added to a predetermined amount of a solvent or a combination of
solvents. If necessary, heating, stirring and/or mixing can be
employed to effect dissolution of the polymer(s) into the
solvent(s)--for example in an 80.degree. C. water bath for two
hours. A therapeutic substance can be also added to the
composition. The therapeutic substance should be in true solution
or saturated in the blended composition. If the therapeutic
substance is not completely soluble in the composition, operations
including mixing, stirring, and/or agitation can be employed to
effect homogeneity of the residues. The therapeutic substance may
be added so that dispersion is in fine particles. The mixing of the
therapeutic substance can be conducted at ambient pressure and at
room temperature.
[0025] The polymer or combination of polymers chosen must be
biocompatible and minimize irritation to the vessel wall when the
device is implanted. The polymer may be either a biostable or a
bioabsorbable polymer. Bioabsorbable polymers that could be used
include poly(hydroxyvalerate), poly(L-lactic acid),
polycaprolactone, poly(lactide-co-glycolide),
poly(hydroxybutyrate), poly(hydroxybutyrate-co-valerate),
polydioxanone, polyorthoester, polyanhydride, poly(glycolic acid),
poly(D,L-lactic acid), poly(glycolic acid-co-trimethylene
carbonate), polyphosphoester, polyphosphoester urethane, poly(amino
acids), cyanoacrylates, poly(trimethylene carbonate),
poly(iminocarbonate), copoly(ether-esters) (e.g. PEO/PLA),
polyalkylene oxalates, polyphosphazenes and biomolecules such as
fibrin, fibrinogen, cellulose, starch, collagen and hyaluronic
acid. Also, biostable polymers with a relatively low chronic tissue
response such as polyurethanes, silicones, and polyesters could be
used. Other polymers include polyolefins, polyisobutylene and
ethylene-alphaolefin copolymers; acrylic polymers and copolymers;
vinyl halide polymers and copolymers, such as polyvinyl chloride;
polyvinyl ethers, such as polyvinyl methyl ether; polyvinylidene
halides, such as polyvinylidene fluoride and polyvinylidene
chloride; polyacrylonitrile; polyvinyl ketones; polyvinyl
aromatics, such as polystyrene; polyvinyl esters, such as polyvinyl
acetate; copolymers of vinyl monomers with each other and olefins,
such as ethylene-methyl methacrylate copolymers,
acrylonitrile-styrene copolymers, ABS resins, and ethylene-vinyl
acetate copolymers; polyamides, such as Nylon 66 and
polycaprolactam; alkyd resins; polycarbonates; polyoxymethylenes;
polyimides; polyethers; epoxy resins; polyurethanes; rayon;
rayon-triacetate; cellulose, cellulose acetate; cellulose butyrate;
cellulose acetate butyrate; cellophane; cellulose nitrate;
cellulose propionate; cellulose ethers; and carboxymethyl
cellulose. Ethylene vinyl alcohol is functionally a very suitable
choice of polymer. The copolymer possesses good adhesive qualities
to the surface of a stent, particularly stainless steel surfaces,
and has illustrated the ability to expand with a stent without any
significant detachment of the copolymer from the surface of the
stent. The copolymer, moreover, allows for good control
capabilities over the release rate of the therapeutic
substance.
[0026] Representative examples of solvents include chloroform,
acetone, water (buffered saline), dimethylsulfoxide (DMSO),
propylene glycol methyl ether (PM,) isopropyl alcohol (IPA),
n-propyl alcohol, methanol, ethanol, tetrahydrofuran (THF),
dimethylformamide (DMF), dimethyl acetamide (DMAC), benzene,
toluene, xylene, hexane, cyclohexane, heptane, octane, nonane,
decane, decalin, ethyl acetate, butyl acetate, isobutyl acetate,
isopropyl acetate, butanol, diacetone alcohol, benzyl alcohol,
acetone, 2-butanone, cyclohexanone, dioxane, methylene chloride,
carbon tetrachloride, tetrachloroethylene, tetrachloroethane,
chlorobenzene, 1,1,1-trichloroethane, formamide, and combination
thereof. The solvent should be capable of placing the selected
polymer into dissolution at the selected concentration and should
not adversely react with the therapeutic substance.
[0027] The therapeutic substance can include any agent capable of
exerting a therapeutic or prophylactic effect in the practice of
the present invention such as inhibition of migration and/or
proliferation of smooth muscle cells. The agent can also be for
enhancing wound healing in a vascular site and improving the
structural and elastic properties of the vascular site. Examples of
agents include antiproliferative substances as well as
antineoplastic, antiinflammatory, antiplatelet, anticoagulant,
antifibrin, antithrombin, antimitotic, antibiotic, antioxidant, and
combinations thereof. One suitable example of an antiproliferative
substance includes actinomycin D--synonyms of which include
dactinomycin, actinomycin IV, actinomycin I.sub.1, actinomycin
X.sub.1, and actinomycin C.sub.1. Examples of suitable
antineoplastics include paclitaxel and docetaxel. Examples of
suitable antiplatelets, anticoagulants, antifibrins, and
antithrombins include sodium heparin, low molecular weight heparin,
hirudin, argatroban, forskolin, vapiprost, prostacyclin and
prostacyclin analogs, dextran, D-phe-pro-argchloromethylketone
(synthetic antithrombin), dipyridamole, glycoprotein IIb/IIIa
platelet membrane receptor antagonist, recombinant hirudin,
thrombin inhibitor (available from Biogen), and 7E-3B.RTM. (an
antiplatelet drug from Centocore). Examples of suitable antimitotic
agents include methotrexate, azathioprine, vincristine,
vinblastine, fluorouracil, adriamycin, and mutamycin. Examples of
suitable cytostatic or antiproliferative agents include angiopeptin
(a somatostatin analog from Ibsen), angiotensin converting enzyme
inhibitors such as CAPTOPRIL (available from Squibb), CILAZAPRIL
(available from Hoffman-LaRoche), or LISINOPRIL (available from
Merck); calcium channel blockers (such as Nifedipine), colchicine,
fibroblast growth factor (FGF) antagonists, fish oil (omega 3-fatty
acid), histamine antagonist, LOVASTATIN (an inhibitor of HMG-CoA
reductase, a cholesterol lowering drug from Merck), monoclonal
antibodies (such as PDGF receptors), nitroprusside,
phosphodiesterase inhibitors, prostaglandin inhibitor (available
form Glazo), Seramin (a PDGF antagonist), serotonin blockers,
steroids, thioprotease inhibitors, triazolopyrimidine (a PDGF
antagonist), and nitric oxide. Other therapeutic substances or
agents which may be appropriate include alpha-interferon,
genetically engineered epithelial cells, rapamycin, and
dexamethasone.
[0028] The dosage or concentration of the active agent required to
produce a favorable therapeutic effect should be less than the
level at which the active agent produces toxic effects and greater
than the level at which non-therapeutic results are obtained. The
dosage or concentration of the active agent required to inhibit the
desired cellular activity of the vascular region can depend upon
factors such as the particular circumstances of the patient; the
nature of the trauma; the nature of the therapy desired; the time
over which the ingredient administered resides at the vascular
site; and if other therapeutic agents are employed, the nature and
type of the substance or combination of substances. Therapeutic
effective dosages can be determined empirically, for example by
infusing vessels from suitable animal model systems and using
immunohistochemical, fluorescent or electron microscopy methods to
detect the agent and its effects, or by conducting suitable in
vitro studies. Standard pharmacological test procedures to
determine dosages are understood by one of ordinary skill in the
art.
[0029] Stent is broadly intended to include self-expandable stents,
balloon-expandable stents, and stent-grafts. One of ordinary skill
in the art, however, understands that other medical devices on
which a polymer can be coated can be used with the practice of the
present invention, such as grafts (e.g., aortic grafts),
endocardial leads, valves, and the like. The underlying structure
of the device can be virtually any design. Stents are typically
defined by a tubular body having a plurality of bands or
cylindrical elements interconnected by connecting elements. The
device can be made of a metallic material or an alloy such as, but
not limited to, cobalt chromium alloy (ELGILOY), stainless steel
(316L), "MP35N," "MP20N," ELASTINITE (Nitinol), tantalum,
nickel-titanium alloy, platinum-iridium alloy, gold, magnesium, or
combinations thereof. "MP35N" and "MP20N" are trade names for
alloys of cobalt, nickel, chromium and molybdenum available from
standard Press Steel Co., Jenkintown, Pa. "MP35N" consists of 35%
cobalt, 35% nickel, 20% chromium, and 10% molybdenum. "MP20N"
consists of 50% cobalt, 20% nickel, 20% chromium, and 10%
molybdenum. Devices made from bioabsorbable or biostable polymers
could also be used with the blended composition.
[0030] While particular embodiments of the present invention have
been shown and described, it will be obvious to those skilled in
the art that changes and modifications can be made without
departing from the embodiments this invention in its broader
aspects and, therefore, the appended claims are to encompass within
their scope all such changes and modifications as fall within the
true spirit and scope of the embodiments this invention.
[0031] This is a divisional of U.S. Ser. No. 09/872,816, the entire
disclosure of which is incorporated by reference.
* * * * *