U.S. patent application number 09/754619 was filed with the patent office on 2001-05-24 for chamber for applying therapeutic substances to an implantable device.
Invention is credited to Wu, Steven Z..
Application Number | 20010001824 09/754619 |
Document ID | / |
Family ID | 23627266 |
Filed Date | 2001-05-24 |
United States Patent
Application |
20010001824 |
Kind Code |
A1 |
Wu, Steven Z. |
May 24, 2001 |
Chamber for applying therapeutic substances to an implantable
device
Abstract
A chamber is provided that allows a user to medicate an
implantable prosthesis such as a stent. The implantable prosthesis
is capable of securing a therapeutic substance and subsequently
delivering the therapeutic substance to local tissues. The chamber
allows a user to medicate the prosthesis subsequent to the
sterilization process and immediately prior to the implantation
procedure. The chamber includes a hollow body defining a chamber
cavity that encapsulates the prosthesis crimped on a balloon of a
catheter assembly. The chamber is removably mounted on the catheter
assembly. A user can supply therapeutic substances into the chamber
and allow the therapeutic substances to be secured by the
prosthesis. After allowing the prosthesis to be soaked by the
therapeutic substances for a predetermined amount of time, the
chamber is removed and the prosthesis is ready for the implantation
procedure.
Inventors: |
Wu, Steven Z.; (Santa Clara,
CA) |
Correspondence
Address: |
Cameron Kerrigan
SQUIRE, SANDERS & DEMPSEY L.L.P.
Suite 300
One Maritime Plaza
San Francisco
CA
94111-3492
US
|
Family ID: |
23627266 |
Appl. No.: |
09/754619 |
Filed: |
January 3, 2001 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
09754619 |
Jan 3, 2001 |
|
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09411029 |
Oct 4, 1999 |
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Current U.S.
Class: |
606/108 |
Current CPC
Class: |
A61F 2250/0067 20130101;
A61F 2/06 20130101; A61F 2/91 20130101; A61F 2/90 20130101; B05C
3/20 20130101 |
Class at
Publication: |
606/108 |
International
Class: |
A61F 011/00 |
Claims
What is claimed is:
1. A chamber which allows a user to medicate implantable devices,
comprising: (a) a hollow body defining a chamber cavity, said
chamber cavity is configured to encapsulate an implantable device;
and (b) an inlet disposed in said hollow body, said inlet allows a
user to supply a therapeutic substance into said chamber cavity,
wherein said therapeutic substance contacts said implantable
device.
2. The chamber of claim 1, additionally comprising an outlet
disposed in said hollow body, said outlet allows said therapeutic
substance to be discharged out of said chamber cavity.
3. The chamber of claim 1, wherein said hollow body comprises a
first end and a second end opposing said first end, said first end
having an aperture and a sealing member disposed on a periphery of
said aperture.
4. The chamber of claim 1, wherein said hollow body comprises a
pair of opposing ends, each of said ends having an aperture and a
sealing member disposed on a periphery of said aperture.
5. The chamber of claim 1, wherein said implantable device is a
stent.
6. The chamber of claim 1, wherein said hollow body comprises an
upper chamber body and a lower chamber body, said chamber bodies
configured to releasably secure together to form said chamber
cavity.
7. The chamber of claim 1, wherein said therapeutic substance is
selected from a group of antineoplastic, antiplatelet,
anticoagulant, fribrinolytic, antimitotic, thrombin inhibitor,
antiinflammatory and antiproliferative substances.
8. The chamber of claim 1, wherein said chamber is configured to
removably encapsulate a balloon portion of a catheter assembly.
9. A medical assembly, comprising: (a) a catheter assembly having a
balloon; (b) a stent mounted on said balloon, said stent is capable
of securing a therapeutic substance when exposed to said
therapeutic substance and said stent is capable of releasing said
therapeutic substance after said stent has been implanted in a
subject. (c) a chamber encapsulating said stent, said chamber
allows a user to expose said therapeutic substance to said
stent.
10. The medical assembly of claim 9, wherein said therapeutic
substance is added to a fluid and supplied into said chamber,
wherein said fluid soaks said stent.
11. The medical assembly of claim 9, wherein said stent is coated
with a polymeric material capable of being impregnated with said
therapeutic substance.
12. The medical assembly of claim 11, wherein said polymeric
material swells when in contact with a solvent carrying said
therapeutic substance and collapses when said solvent is
significantly removed from said polymeric material.
13. The medical assembly of claim 9, wherein said chamber
comprises: (a) a hollow body defining a chamber cavity, said hollow
body having a first end and an aperture formed on said first end;
(b) a sealing member disposed on a periphery on said aperture, said
sealing member is compressed against said catheter assembly and
prevents any significant leakage of fluids or gases out of said
chamber cavity from said aperture; (c) an inlet disposed in said
hollow body for allowing a user to supply said therapeutic
substance into said chamber cavity; and (d) an outlet disposed in
said hollow body for allowing a user to discharge said therapeutic
substance from said chamber cavity.
14. The medical assembly of claim 13, wherein said hollow body
comprises a second end opposing said first end, said second end
having an aperture formed therein and a sealing member disposed on
a periphery of said aperture of said second end, said sealing
member of said second end is compressed against said catheter
assembly and prevents any significant leakage of fluids or gases
out of said chamber cavity from said aperture of said second
end.
15. The medical assembly of claim 13, wherein said hollow body
comprises an upper chamber body and a lower chamber body, said
chamber bodies are configured to releasably secure together to form
said chamber cavity.
16. The medical assembly of claim 9, wherein said therapeutic
substance is selected from a group of antineoplastic,
antiinflammatory, antiplatelet, anticoagulant, fribrinolytic,
antimitotic, thrombin inhibitor, and antiproliferative
substances.
17. A method of medicating a prosthesis prior to implanting said
prosthesis in a subject, comprising the acts of: (a) providing a
catheter assembly, a balloon disposed on said catheter assembly, a
prosthesis mounted on said balloon, and a chamber encapsulating
said prosthesis; and (b) supplying a therapeutic substance into
said chamber, wherein said therapeutic substance is secured by said
prosthesis and is capable of being released after said prosthesis
is implanted in a subject.
18. The method of claim 17, additionally comprising the act of
sterilizing said prosthesis prior to said act of supplying said
therapeutic substance into said chamber.
19. The method of claim 18, wherein said act of sterilizing is
performed by electron beam radiation.
20. The method of claim 17, wherein said act of providing comprises
removing said catheter assembly having said balloon, said
prosthesis mounted on said balloon, and said chamber encapsulating
said prosthesis from a package.
21. The method of claim 17, wherein said act of providing comprises
removing said catheter assembly having said balloon and said
prosthesis mounted on said balloon from a first package, removing
said chamber from a second package, and mounting said chamber on
said catheter assembly.
22. The method of claim 17, wherein said act of providing comprises
removing said catheter assembly having said balloon from a first
package, removing said prosthesis from a second package, crimping
said prosthesis on said balloon, removing said chamber from a third
package, and mounting said chamber on said catheter assembly.
23. The method of claim 17, wherein said act of supplying a
therapeutic substance into said chamber comprises adding said
therapeutic substance to a fluid and supplying said fluid into said
chamber.
24. The method of claim 17, wherein during said act of supplying,
said therapeutic substance is not discharged from said chamber as
it is being supplied into said chamber.
25. The method of claim 24, additionally comprising the act of
discharging said therapeutic substance from said chamber after a
predetermined period of time.
26. The method of claim 17, wherein during said act of supplying,
said therapeutic substance is discharged out of said chamber as it
is being supplied into said chamber, said therapeutic substance is
supplied for a predetermined period of time.
27. The method of claim 17, additionally including the act of
removing said chamber from said catheter assembly subsequent to
exposing said therapeutic substance to said prosthesis for a
predetermined period of time.
28. The method of claim 17, additionally including the act of
implanting said prosthesis in a subject.
29. The method of claim 17, wherein said therapeutic substance is
selected from a group of antineoplastic, antiplatelet,
anticoagulant, fribrinolytic, antimitotic, thrombin inhibitor,
antiinflammatory and antiproliferative substances.
Description
BACKGROUND OF THE INVENTION
[0001] 1. Field of the Invention
[0002] This invention generally relates to implantable devices,
such as an expandable intraluminal prosthesis commonly known as
stents. More particularly, this invention relates to a structures
and techniques for applying therapeutic substances to an
implantable device in association with the implantation
procedure.
[0003] 2. Description of the Related Art
[0004] Percutaneous transluminal coronary angioplasty (PTCA) is a
procedure for treating heart disease. A catheter assembly having a
balloon portion is introduced into the cardiovascular system of a
patient via the brachial or femoral artery. The catheter assembly
is advanced through the coronary vasculature until the balloon
portion is positioned across the occlusive lesion. Once in position
across the lesion, the balloon is inflated to a predetermined size
to radially compress the atherosclerotic plaque of the lesion
against the inner wall of the artery to dilate the lumen. The
balloon is then deflated to a smaller profile to allow the catheter
to be withdrawn from the patient's vasculature.
[0005] A problem associated with the above procedure includes
formation of intimal flaps or torn arterial linings which can
collapse and occlude the conduit after the balloon is deflated.
Moreover, thrombosis and restenosis of the artery may develop over
several months after the procedure, which may require another
angioplasty procedure or a surgical by-pass operation. To reduce
the partial or total occlusion of the artery by the collapse of
arterial lining and to reduce the chance of the development of
thrombosis and restenosis, an expandable intraluminal prosthesis,
an example of which includes a stent, is implanted in the lumen to
maintain the vascular patency. A well known procedure for
delivering the stent to the diseased site includes crimping a
compressed stent about the balloon of the catheter such that when
the balloon is inflated, the stent dilates and is disposed within
the vasculature. FIG. 1 illustrates an example of the end result,
the balloon having been deflated and withdrawn. FIG. 1 shows a
stent 10, generally tubular in shape, in its expanded position,
functioning to hold open and, if desired, to expand a segment of an
anatomical lumen 12. As best shown by FIG. 1, stent 10 prevents
torn or injured arterial lining 14 from occluding lumen 12.
[0006] In treating the damaged vasculature tissue and to further
fight against thrombosis and restenosis, there is a need for
administrating therapeutic substances to the treatment site. For
example, anticoagulants, antiplatelets and cytostatic agents are
commonly used to prevent thrombosis of the coronary lumen, to
inhibit development of restenosis, and to reduce post-angioplasty
proliferation of the vascular tissue, respectively. 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 medication 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 effective results. One
commonly applied technique for the local delivery of the drugs is
through the use of medicated stents. Stents that are capable of
storing medication and releasing it at the implanted site are well
known in the art. A metallic stent coated with a polymeric material
which is impregnated with a drug or a combination of drugs is one
example. Once the stent is implanted within the lumen, the drug(s)
are released from the polymer. U.S. Pat. No. 5,605,696 to Eury et
al., U.S. Pat. No. 5,464,650 to Berg et al., and U.S. Pat. No.
5,700,286 to Tartaglia et al. are examples illustrating the use of
a polymeric coating for the local delivery of the drug(s).
[0007] Sterilization of medicated stents in preparation for stent
therapy significantly limits the choice of drugs with which the
stent can be medicated. More specifically, stents are sterilized by
ethylene oxide (Eto) gas or electron beam radiation. Some
therapeutic substances do not tolerate either the Eto or electron
beam radiation procedure. Although some therapeutic substances
tolerate Eto, Eto is the less preferred method of sterilization for
coronary procedures since the procedure leaves an ethylene residue
on the stent after sterilization, provoking an inflammatory
response.
[0008] The available choice of therapeutic substances for
medicating stents therefore includes substances that are not
adversely affected by electron beam radiation. The selections are
limited. Accordingly, it is desirable to medicate the stent
subsequent to the sterilization procedure.
[0009] Medicated stents also inhibit a treating physician's ability
to make an ad hoc selection of most suitable therapeutic substance
or combination of therapeutic substances, and dosage for a
particular patient. A physician cannot custom treat a stent
according to a patient's needs, but rather is limited to selections
that are already provided by a biomedical supplier. Accordingly, it
is desirable to allow a physician to medicate the stent in
accordance with the particular needs of a patient.
[0010] Stents are medicated by a biomedical supplier well in
advance of the stent therapy procedure and supplied to users in
sterile packages. The therapeutic substance concentration that is
secured by the stent diminishes during storage in sterile packages
due to inevitable diffusion of the substance from the stent. The
time lapse between treating a stent with a therapeutic substance
and implanting the stent may decrease the therapeutic substance's
efficacy or require the package to be discarded if extending beyond
the package expiration date. Accordingly, it is desirable to
medicate a stent immediately prior to the stent therapy.
SUMMARY OF THE INVENTION
[0011] In accordance with various aspects of the present invention,
a chamber is configured for usage with a catheter to apply one or
more therapeutic substances to an implantable device such as a
stent after sterilization but before implantation therapy. The
chamber is configured to be mounted on a catheter assembly having a
balloon portion and a stent crimped or mounted on the balloon
portion. The chamber comprises a hollow body defining a chamber
cavity, which encapsulates the stent. The chamber includes an inlet
duct and an outlet duct which allow a user to supply therapeutic
substance(s) into the chamber cavity and to discharge the
therapeutic substance(s) out of the chamber cavity.
[0012] In one embodiment, the hollow body includes a first end and
a second end opposing the first end, the first end having an
aperture and a sealing member disposed on a periphery of the
aperture.
[0013] In another embodiment, the second end additionally has an
aperture and a sealing member on a periphery of the aperture.
[0014] In another embodiment, the hollow body of the chamber
includes an upper chamber body and a lower chamber body. The upper
and lower chamber bodies can be releasably secured together to form
the chamber cavity.
[0015] Another aspect of the present invention is a method of
medicating the stent by supplying a therapeutic substance into the
chamber cavity wherein the substance is exposed to or soaks the
stent. The therapeutic substance is trapped in the chamber cavity
and discharged after a predetermined period of time. Alternatively,
the therapeutic substance is immediately discharged as it is
supplied into the chamber cavity, creating a continuous flow
through the chamber cavity. The continuous flow is maintained for a
predetermined amount of time. The stent used in conjunction with
the chamber of the present invention should be capable of storing
or securing the therapeutic substance(s) and releasing the
substance(s) at the site of treatment.
BRIEF DESCRIPTION OF THE DRAWINGS
[0016] FIG. 1 illustrates an expanded stent within a vessel after
withdrawal of a catheter assembly;
[0017] FIG. 2 is a prospective view of a catheter assembly having a
chamber mounted thereon in accordance with one embodiment of the
invention;
[0018] FIG. 3 is a cross-sectional view of the chamber,
encapsulating a stent crimped on a balloon of the catheter
assembly;
[0019] FIG. 4 is a prospective view of the chamber in accordance
with another embodiment of the present invention; and
[0020] FIG. 5 is a side view of the chamber in accordance with
another embodiment of the present invention.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0021] Referring to the drawings, wherein similar parts are
identified by like reference numeral, FIG. 2 illustrates a chamber
40 that is configured for usage with a catheter assembly 20. The
catheter assembly 20 can be any conventional catheter assembly that
is well known and used in a variety of medical procedures such as
percutaneous transluminal coronary angioplasty (PTCA), vascular
prosthetic implantation, and atherectomy.
[0022] Catheter assembly 20 includes catheter tube 22 having a
distal end 24 and a balloon 26 incorporated proximal to distal end
24. Balloon 26 is inflatable to dilate from a collapsed
configuration to an expanded configuration. Balloon 26 is
selectively deflatable after inflation to return to the collapsed
configuration. Balloon 26 can be fabricated, for example, from a
flexible polymer such as nylon, polyethylene, or polyethylene
terephthalate. The illustrative balloon 26 is adapted for inserting
and dilating an implantable device or an expandable prosthesis 28
(see FIG. 3), e.g., a stent. The selection of a particular
balloon-catheter assembly 20 is not critical so long as the
assembly 20 is capable of and suitable for delivering implantable
device 28.
[0023] As further illustrated in FIGS. 2-5 the chamber 40 is
provided that allows a user such as a physician to medicate stent
28 immediately prior to implantation procedure. Chamber 40 is
removably mounted on balloon 26 and encapsulates stent 28. Chamber
40 is generally defined by a hollow, tubular body 42 defining a
chamber cavity 44. Chamber 40 further has an inlet duct 46 and a
pair of outlet ducts 48. Inlet duct 48 and outlet ducts 48 are
typically apertures, conduits or tubes expanding out of tubular
body 42. Inlet duct 46 and outlet ducts 48 are typically open
passageways or closed passageways that are capable of penetration
by a syringe. Alternatively, inlet duct 46 and outlet ducts 48 can
be open passageways sealed by removable caps (not illustrated). In
various embodiments chamber 40 can have any number of inlet ducts
46 and outlet ducts 48 and extend beyond the specific structure
shown in FIGS. 2-5. Tubular body 42 has a pair of opposing ends 50
and 52 having apertures 53A and 53B formed therein. A pair of
sealing members 54A and 54B, illustratively "O" rings, are disposed
about the periphery of apertures 53A and 53B, respectively. Sealing
members 54A and 54B seal chamber 40 against balloon 26 and prevent
significant leakage of fluids or gases out of chamber cavity 44.
Chamber 40 is generally capable of insertion onto and removal from
catheter assembly 20 by threading and retracting distal end 24 of
catheter assembly 20 through apertures 53A and 53B. Sealing members
54A and 54B facilitate sliding of the chamber 40 onto balloon 26
and off balloon 26 to prevent significant variation or disturbance
to the positioning of stent 28 and prevent damage to the structure
of stent 28.
[0024] An alternative embodiment is illustrated in FIG. 4 in which
chamber 40 includes an upper chamber body 58 and a lower chamber
body 60 which are configured to mate to form chamber cavity 44.
Latching members 62 are disposed about the periphery of upper and
lower chamber bodies 58 and 60, and are used to releasably lock
upper chamber body 58 against lower chamber body 60. Stent 28 is
encapsulated by positioning balloon 26 between upper and lower
chamber bodies 58 and 60 and securely mating the upper and lower
chamber bodies 58 and 60 to one another. The encapsulation method
is more suitable for preventing significant disturbance to the
positioning of stent 28 and damage to structure of the stent than
the method of sliding chamber 40 on and off balloon 26. Other
conventional articles, such as screws, may alternatively be used to
secure upper chamber body 58 to lower chamber body 60. A sealing
member (not illustrated) may be disposed about lips 64 and 66 of
upper and lower chamber bodies 58 and 60 to prevent significant
leakage of fluids or gases from chamber cavity 44.
[0025] Chamber 40 is fabricated from any suitable material that
does not react adversely or erode when in contact with therapeutic
substances or the solvents carrying such substances. Alternatively,
the inside surfaces of chamber cavity 44 can be coated with a
suitable material for preventing pollution or degradation of
therapeutic substances that are introduced into chamber cavity 44.
By way of example and not limitation, chamber 40 may be fabricated
from any suitable polymer, such as a polytetrafluoroethylene or
high density polyethylene. Chamber 40 may also be fabricated from a
metallic material such as aluminum or stainless steel. It is
understood that chamber 40 can be of any suitable size and can have
a variety of suitable shapes, other than tubular body 42
illustrated in FIG. 2-5. As further illustrated in FIG. 5, chamber
40 can have a closed end 56 in lieu of aperture 53A of end 50.
[0026] In an illustrative commercial kit, the catheter assembly 20
with implantable device 28 (for example, stent) is sterilized and
packaged in combination with chamber 40 removably encapsulating the
implantable device 28, for usage by a user such as a physician. The
user removes the combined catheter assembly 20 and mounted chamber
40 from the sterile commercial kit immediately prior to the
implantation therapy and uses chamber 40 to medicate stent 28
according to the individual requirements of the patient. The user
then removes chamber 40 from balloon 26, and performs the
implantation procedure.
[0027] In an alternative commercial embodiment, the catheter
assembly 20 and the chamber 40 are packaged in separate sterile
kits. A user removes the sterilized catheter assembly 20 and the
chamber 40 from respective sterile kits. The user encapsulates
balloon 26 within chamber 40 and medicates stent 28. The user then
removes chamber 40 from balloon 26 and performs the implantation
procedure. In various embodiments, catheter assembly 20 may be
provided having stent 28 mounted on the assembly 20, or stent 28
may be provided in a separate sterile kit. In cases with separate
packaging for the catheter assembly 20 and stent 28, the user
crimps the stent 28 onto the balloon 26 prior to usage.
[0028] In further additional commercial embodiments, the chamber
40, catheter assembly 20 and stent 28 may be provided in
non-sterile kits in which case all articles are sterilized prior to
the treatment of a patient.
[0029] As described hereinafter with reference to Examples 1-4,
stent 28 is medicated by introducing a solution of a therapeutic
substance into chamber 40 encasing stent 28 through inlet duct 46
so that the therapeutic substance is in contact with stent 28.
According to a first illustrative technique, the solution is
trapped in chamber cavity 44 by closing outlet duct 48. Stent 28 is
soaked for a predetermined period of time, then the solution is
discharged from chamber cavity 44.
[0030] Alternatively, the therapeutic solution is introduced to
chamber 40 via inlet duct 46 with outlet duct 48 left open so that
the solution continuously flows through chamber cavity 44. The
medicated solution simultaneously discharges from outlet duct 48
substantially at the rate the solution is supplied through inlet
duct 46. Stent 28 is thus exposed to the continuous flow or soaked
by the medicated solution for a predetermined period of time. In
some applications a second solution such as a medicated solution,
an aqueous solution, water, or the like can be supplied through the
chamber 40 following application of the first solution. The type of
medicated solution, the number of solutions applied, the dosages,
dosage rates, concentrations of the solutions, and the duration of
exposure or soaking depend on the type of stent and the therapy
applied to the patient. Similarly, the therapy parameters are
interrelated so that the dosages, dosage rates, and durations of
exposure depend on the therapeutic substances, solvents, duration
of the local therapy, rate of release, and the cumulative amount of
release that is desired. Correlations and interrelations between
therapy parameters are well known in the art and are easily
calculated.
[0031] As discussed in the Background of the Invention,
sterilization of a stent after the stent is medicated but before
stent therapy limits the choice of drugs with which stent can be
medicated since many therapeutic drugs do not tolerate conventional
ethylene oxide (Eto) gas or electron beam radiation sterilization
procedures. Chamber 40 advantageously allows a user to change the
order of sterilization and medication of a stent so that the stent
is first sterilized, then medicated, before usage as an implant.
The chamber 40 thus expands the selection of therapeutic substances
that are available to the physician to substances that are
adversely affected by electron beam radiation. Chamber 40 also
allows the physician to treat a subject more effectively. In other
words, the physician can select on an ad hoc basis the most
suitable therapeutic substance or combination of substances and the
dosage(s) in accordance with the particular needs of a subject.
[0032] Examples in the expanded list of therapeutic substances or
agents used in conjunction with chamber 40 include, but are not
limited to, antineoplastic, anti-inflammatory, antiplatelet,
anticoagulant, fribrinolytic, thrombin inhibitor, antimitotic, and
antiproliferative substances. Examples of antineoplastics include
paclitaxel and docetaxel. Examples of antiplatelets,
anticoagulants, fribrinolytics, and thrombin inhibitors include
sodium heparin, low molecular weight heparin, hirudin, argatroban,
forskolin, vapiprost, prostacyclin and prostacyclin analogues,
dextran, D-phe-pro-arg-chloromethylketone (synthetic antithrombin),
dipyridamole, glycoprotein IIb/IIIa platelet membrane receptor
antibody, 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, flurouracil, adriamycin,
and mutamycin. Examples of suitable cytostatic or antiproliferative
agents include angiopeptin (a somatostatin analogue from Ibsen),
angiotensin converting enzyme inhibitors such as Captopril.RTM.
(available from Squibb), Cilazapril.RTM. (available from
Hofman-LaRoche), or Lisinopril.RTM. (available from Merck); calcium
channel blockers (such as Nifedipine), colchicine, fibroblast
growth factor (FGF) antagonists, fish oil (omega 3-fatty acid),
histamine antagonist, Lovastatin.RTM. (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, and dexamethasone. While
the foregoing therapeutic substances or agents are well known for
their preventative and treatment purposes, they are provided by way
of example and are not meant to be limiting. Other therapeutic
substances which are currently available or may be developed are
equally applicable for use with the present invention. The
treatment of patients using the above mentioned medicines is well
known in the art.
[0033] Referring to FIG. 3, stent 28 is crimped on balloon 26 in a
compressed configuration. Stent 28 is defined by a plurality of
radially expandable cylindrical elements 30 disposed coaxially and
interconnected by connecting elements 32. Connecting elements 32
are disposed between adjacent cylindrical elements 30. Cylindrical
30 and connecting 32 elements can be fabricated from a metallic
material or an alloy such as stainless steel (e.g., 316L), "MP35N,"
"MP20N," tantalum, nickel-titanium alloy (commercially available as
Nitinol.TM.), 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. It is understood, however, that the underlying
structure of stent 28 can be virtually any stent design. It is
further understood the aforementioned list is merely an exemplary
list of materials that can be used and that other materials, such
as polymeric materials, have been proven to function effectively.
Examples of polymeric material include, poly(ethylene
terephthalate), polyacetal, poly(lactic acid), and poly(ethylene
oxide)/poly(butylene terephthalate) copolymer.
[0034] A suitable stent 28 used in conjunction with chamber 40 is a
stent that stores or secures therapeutic substance(s) and allow the
substance(s) to be released at the implanted site for a
predetermined duration of time. Stents that are capable of being
impregnated with or securing therapeutic substance(s) and locally
releasing such substance(s) for a predetermined duration of time
are illustrated by the following set of examples by way of example
only and not by way of limitation. The structure of the stents, the
materials used, and the method of storing or securing therapeutic
substance(s) on to the stent should not be construed to limit the
scope of the invention.
EXAMPLE 1
[0035] An illustrative Stent 28 is a bare metallic stent such that
the metallic substrate is capable of absorbing or attaching to
therapeutic substance(s). To medicate stent 28, the metallic
substrate of stent 28 is exposed to or soaked with a solvent
carrying a therapeutic substance by supplying the solution through
inlet duct 46 of chamber 40. The therapeutic substance is dispersed
throughout the solvent in a true solution with the solvent and not
dispersed in fine particles. The medicated solution absorbs or
attaches to the metallic substrate and is released in vivo after
stent 28 is implanted. A suitable exposure of the metallic
substrate to the solvent does not adversely alter the composition
or characteristics of the therapeutic substance. Examples of some
suitable combinations of metallic substrates, solvents, and
therapeutic substances are set forth in Table I. Table I is an
exemplary list of a few suitable combinations, and it is understood
that many other combinations can be practiced with chamber 40.
1TABLE I Metallic Substrate Solvent Therapeutic Substance Stainless
Steel (e.g., 316L) ethanol dexamethasone Stainless Steel (e.g.,
316L) chloroform dexamethasone Stainless Steel (e.g., 316L) methyl
alcohol taxol Nitinol .TM. water aspirin Nitinol .TM. water
heparin
[0036] Therapeutic parameters such as dosages, dosage rates,
concentration of the solution, and the duration of exposure depend
on various factors including metallic substrate type, particular
selected therapeutic substance, particular selected solvent, and
the duration of the local release, the cumulative amount of
release, and the rate of release that is desired. Correlations and
interrelations between therapeutic parameters are well known in the
art and are easily calculated.
EXAMPLE 2
[0037] For some illustrative catheters the metallic material from
which stent 28 is made include a plurality of porous cavities, as
disclosed in U.S. Pat. No. 5,843,172 to John Y. Yan, which is
incorporated herein by reference in its entirety. The porous
cavities of stent 28 are typically formed by sintering the stent
material from metallic particles, filaments, fibers or other
materials as disclosed in Yan. As a result, a therapeutic substance
is loaded directly into the cavities. To load the cavities, stent
28 is soaked by supplying a solvent carrying a therapeutic
substance into chamber cavity 44. The substance is dispersed
throughout the chamber cavity 44 either in a true solution with the
solvent, or dispersed in fine particles in the solvent. The
medicated solute or the fine particles impregnate the cavities and
are generally released in vivo over a desired period of time.
Therapeutic parameters such as dosages, dosage rates, concentration
of the solution, size of the particles if not in true solution, and
the duration of exposure depend on various factors including size
of the cavities, particular selected therapeutic substance,
particular selected solvent, and the duration of the local release,
the cumulative amount of release, and the rate of release that is
desired. Correlations and interrelations between therapeutic
parameters are well known in the art and are easily calculated.
EXAMPLE 3
[0038] In another example, stent 28 has a coating of a polymeric
material capable of carrying and releasing the therapeutic
substance. Polymeric material for carrying therapeutic substances
are well known and practiced in the art. In order to medicate stent
28, chamber 40 is used to soak the polymeric coating with a solvent
carrying a therapeutic substance. The substance is dissolved
throughout the solvent to form a true solution with the solvent.
The medicated solute absorbs into the micropores or matrices of the
polymer and is capable of being released, in situ, over a
predetermined period of time. The polymeric material is preferably
a biocompatible material such as one or more polymers which, in the
amounts employed, are non-toxic, non-inflammatory, chemically
inert, and substantially non-immunogenetic. The polymer may either
be bioabsorbable or biostable. A bioabsorbable polymer biodegrades
or breaks down in the body and does not remain present long after
implantation to cause any adverse local response. Bioabsorbable
polymers are gradually absorbed or eliminated by the body by
hydrolysis, metabolic process, bulk or surface erosion, or similar
processes. Examples of bioabsorbable, biodegradable materials
include, but are not limited to, polycaprolactone (PCL), poly-D,
L-lactic acid (DL-PLA), poly-L-lactic acid (L-PLA),
poly(lactide-co-glycolide), poly(hydroxybutyrate),
poly(hydroxybutyrate-co-valerate), polydioxanone, polyorthoester,
polyanhydride, poly(glycolic acid), poly(glycolic
acid-cotrimethylene carbonate), polyphosphoester, polyphosphoester
urethane, poly (amino acids), cyanoacrylates, poly(trimethylene
carbonate), poly(iminocarbonate), copoly(ether-esters),
polyalkylene oxalates, polyphosphazenes, polyiminocarbonates, and
aliphatic polycarbonates. Biomolecules such as fibrin, fibrinogen,
cellulose, starch, and collagen may also be suitable. Examples of
biostable polymers include Parylene.RTM., Parylast.RTM.,
polyurethane (e.g., segmented polyurethanes such as Biospan.RTM.),
polyethylene, polyethlyene teraphthalate, ethylene vinyl acetate,
silicone and polyethylene oxide. It is essential for the polymeric
coating not to dissolve when exposed to the solvent. It is also
essential for the exposure of the solvent to the polymer not to
adversely alter the therapeutic substance's composition or
characteristic. Examples of suitable combinations of polymers,
solvents, and therapeutic substances are depicted in Table II.
Table II is an exemplary list of a few suitable combinations, and
it is understood that many other combinations can be practiced with
chamber 40.
2TABLE II Polymer Solvent Therapeutic Substance paralene water
IIb/Illa receptor antibody (e.g., ReoPro .RTM.) silicone chloroform
dexamethasone silicone ethanol dexamethasone silicone chloroform
aspirin urethane none liquid form Vitamin E urethane
dimethylsulfoxide (DMSO) vinblastine
[0039] Therapeutic parameters such as dosages, dosage rates,
concentration of the solution, and the duration of exposure depend
on various factors including particular selected polymeric coating,
particular selected therapeutic substance, particular selected
solvent, and the duration of the local release, the cumulative
amount of release, and the rate of release that is desired.
Correlations and interrelations between therapeutic parameters are
well known in the art and are easily calculated.
EXAMPLE 4
[0040] For polymeric carriers that are impregnated with a
therapeutic substance by a simple soaking operation, the duration
of release of the therapeutic substance from the polymeric carrier
is substantially equal to the time of exposure of the carrier. For
example, a two (2) hour soaking of the polymeric carrier has an
equivalent two (2) hour duration of in vivo release.
[0041] Typically it is advantageous to prolong the duration of in
vivo release to days or weeks, but impracticable and undesirable to
use chamber 40 to soak the polymeric carrier with a medicated
solution for such time durations. Accordingly, polymers that are
susceptible to swell loading or post-loading are advantageously
used to increase the release duration. Swell loading or
post-loading are well understood and practiced in the art. In a
conventional and well known swell loading method, the polymeric
carrier is soaked with a therapeutic substance/solvent solution. A
suitable solvent is capable of not only carrying (i.e., not
adversely affecting the therapeutic substance's characteristics or
chemically altering the substance, and the substance should be
capable of dissolving in the solvent) the therapeutic substance,
but causing the polymer to swell. Optimal loading of the substance
is obtained when the substance is highly soluble in the solvent,
for example, when the substance is saturated in the solvent.
Super-saturation of the solute is not desirable. Swelling of the
polymeric carrier causes a higher quantity of the substance solute
to diffuse into the matrices of the polymer in a shorter duration
of time than by simply soaking a polymer that is not susceptible to
swell loading.
[0042] Swell loading of a polymeric carrier using chamber 40
involves supplying a solution carrying a therapeutic substance into
chamber cavity 44. The solution can be either an aqueous solution
or a non-aqueous solution. A solvent which causes the greatest
amount of swelling with the particular polymer is most
advantageously chosen. After soaking stent 28 with either an
aqueous or a non-aqueous solution, chamber 40 is removed and stent
28 is rapidly dried for example by exposure to mild heat for
several minutes. The rapid removal or drying of the solvent from
the polymeric carrier causes the polymer to collapse, trapping a
high concentration of the substance into the polymer's
matrices.
[0043] Alternatively, if a non-aqueous solution is used, water can
be supplied into chamber cavity 44 to rinse the polymeric carrier.
Water precipitates the therapeutic substance and collapses the
polymer. If water is used to collapse the polymer, a water-miscible
solvent is generally most suitable. A suitable polymer does not
dissolve when exposed to the solvent. A suitable combination of
solvent and polymer does not chemically alter the composition of
the substance or adversely affect the substance characteristics.
Examples of some suitable combinations of polymers, solvents, and
therapeutic substances are set forth in Table III. Table III is an
exemplary list of a few suitable combinations. Other combinations
are also suitable for usage with chamber 40.
3TABLE III Polymer Solvent Therapeutic Substance TecoGel .RTM.
water IIb/IIIa receptor antibody (manufactured by Thermedics)
(e.g., ReoPro .RTM.) Tecophilic .RTM. water aspirin (manufactured
by Thermedics) Tecophilic .RTM. chloroform dexamethasone polyvinyl
alcohol chloroform dexamethasone polyvinyl alcohol water
heparin
[0044] Therapeutic parameters such as dosages, dosage rates,
concentration of the solution, and the duration of exposure depend
on various factors including particular selected polymer,
particular selected therapeutic substance, particular selected
solvent, and the duration of the local release, the cumulative
amount of release, and the rate of release that is desired.
Correlations and interrelations between therapeutic parameters are
well known in the art and are easily calculated.
[0045] While particular embodiments of the present invention have
been shown and described, it will be obvious to those skilled in
the art that changes and modifications can be made without
departing from this invention in its broader aspects 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 this invention.
* * * * *