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Claims  |
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What is claimed is:
1. A method for treating a lesion in an arterial wall having plaque thereon
and a luminal surface, the arterial wall having been injured during an
angioplasty procedure, the arterial wall and the plaque defining
therewithin fissures resulting therefrom, the method comprising the steps
of:
providing a layer of a transporting medium disposed about an angioplasty
catheter balloon, said transporting medium having a bioprotective material
distributed therewithin, the layer of bioprotective material being
surrounded by a removable sheath to prevent premature dissolution of the
bioprotective material;
positioning the angioplasty catheter adjacent to the lesion being treated
so that the transporting medium and the bioprotective material are
entrapped therebetween;
removing the sheath so that the lesion is exposed to the bioprotective
material;
applying thermal energy, thereby liquefying the transporting medium under
pressure and promoting contact of the bioprotective material with the
fissures and the luminal surface, whereby the thermal energy bonds the
bioprotective material to the arterial wall and within the fissures and
vessels of the arterial wall; and
removing the angioplasty catheter, the bioprotective material remaining
adherent to the fissures and vessels within the arterial wall, thereby
treating the injured luminal surface with the bioprotective material,
whereby at least semi-permanent protection to the arterial wall is
provided, despite contact with blood flowing adjacent thereto, the blood
dissolving and removing the transporting medium.
2. The method of claim 1 wherein the angioplasty catheter utilized includes
an inflatable balloon.
3. The method of claim 2 wherein the inflatable balloon is at least
partially inflated before delivering the transporting medium and
bioprotective material between the arterial wall and the inflatable
balloon, thereby promoting localized application of the bioprotective
material to the arterial wall.
4. The method of claim 1 wherein the bioprotective material utilized is a
macroaggregated albumin which bonds to the luminal surface and within
fissures and vessels of the arterial wall as a result of the application
of thermal energy.
5. The method of claim 1 wherein the bioprotective material comprises
platelets carried by the transporting medium, which become adherent to the
luminal surface and to tissues adjacent to fissures and vessels of the
arterial wall as a result of the application of thermal energy.
6. The method of claim 1 wherein the bioprotective material comprises red
blood cells carried by the transporting medium, which become adherent to
the luminal surface and to tissues adjacent to fissures and vessels of the
arterial wall as a result of the application of thermal energy.
7. The method of claim 1 wherein the bioprotective material comprises
liposomes carried by the transporting medium, which become adherent to the
luminal surface and to tissues adjacent to fissures and vessels of the
arterial wall as a result of the application of thermal energy.
8. The method of claim 1 wherein the transporting medium comprises a
gelatin which liquifies upon application of thermal energy, whereby the
bioprotective material within the liquified transporting medium bonds to
the luminal surface and within fissures and vessels of the arterial wall
as a result of the application of thermal energy.
9. The method of claim 1 wherein the bioprotective material utilized bonds
to the luminal surface and within fissures and vessels of the arterial
wall as a result of the application of thermal energy.
10. The method of claim 1 wherein the bioprotective material comprises a
high molecular weight carbohydrate which bonds to the luminal surface
precipitates onto the luminal surface and within fissures and vessels of
the arterial wall as a result of the application of thermal energy.
11. The method of claim 1 wherein the bioprotective material utilized
entraps a useful pharmaceutical agent in order to provide local drug
therapy directly to the luminal surface, and to fissures defined within
the arterial wall.
12. The method of claim 11 wherein the useful pharmaceutical agent is an
anti-coagulant.
13. The method of claim 11 wherein the useful pharmaceutical agent is a
fibrinolytic agent.
14. The method of claim 11 wherein the useful pharmaceutical agent is a
thrombolytic agent.
15. The method of claim 11 wherein the useful pharmaceutical agent is an
anti-inflammatory agent.
16. The method of claim 11 wherein the useful pharmaceutical is an
anti-proliferative compound.
17. The method of claim 11 wherein the useful pharmaceutical is an
immunosuppressant.
18. The method of claim 11 wherein the useful pharmaceutical is a collagen
inhibitor.
19. The method of claim 11 wherein the useful pharmaceutical is an
endothelial cell growth promotor.
20. The method of claim 11 wherein the useful pharmaceutical is a sulfated
polysaccharide.
21. The method of claim 1 wherein the bioprotective material includes a
drug which is bound to albumin prior to injection, so that the drug is
permanently affixed thereto by application of the thermal energy.
22. The method of claim 1 wherein the bioprotective material includes a
drug which is physically trapped within albumin during the application of
thermal energy.
23. The method of claim 1 wherein the bioprotective material comprises
microspheres.
24. The method of claim 1 wherein the bioprotective material includes a
drug preparation having an encapsulating medium.
25. The method of claim 24 wherein the encapsulating medium comprises
albumin.
26. The method of claim 24 wherein the encapsulating medium comprises
carbohydrates.
27. The method of claim 24 wherein the encapsulating medium comprises
platelets.
28. The method of claim 24 wherein the encapsulating medium comprises
liposomes.
29. The method of claim 24 wherein the encapsulating medium comprises red
blood cells.
30. The method of claim 24 wherein the encapsulating medium comprises
gelatin.
31. The method of claim 24 wherein the encapsulating medium comprises
hemoglobin.
32. The method of claim 24 wherein the encapsulating medium comprises a
synthetic polymer.
33. The method of claim 24 wherein the encapsulating medium comprises a
sulfated polysaccharide.
34. The method of claim 24 wherein the encapsulating medium comprises ghost
red cells.
35. The method of claim 24 wherein the encapsulating medium comprises
heparin.
36. The method of claim 1 wherein the bioprotective material is a confluent
layer of microspheres impregnated on the surface of the transporting
medium.
37. The method of claim 1 wherein the step of removing the angioplasty
catheter is (followed) by the step of cooling the liquified transporting
medium and tissues, thereby enhancing bonding of the bioprotective
material to the lesion so that the bioprotective material remains adherent
to the arterial wall, and fills cracks and recesses therewithin, thereby
providing localized delivery of the bioprotective material.
38. The method of claim wherein the transporting medium becomes
re-solidified upon cooling, and is dissolved by blood flowing adjacent
thereto after removal of the catheter.
39. The method of claim 1 wherein microspheres are formed in situ at the
luminal surface and within the arterial wall as a result of the thermal
energy applied to the transporting medium and the bioprotective material.
40. The method of claim 1 wherein a drug, simultaneously injected with the
bioprotective material, is entrapped within microspheres.
41. The method of claim 1 wherein the bioprotective material functions as a
physiologic glue, thereby enhancing thermal fusion of fissured tissues
within the arterial wall.
42. The method of claim 1 wherein the bioprotective material includes a
chromophore which enhances absorption of electromagnetic radiation.
43. The method of claim 24 wherein the encapsulating medium comprises a
chromophore which enhances absorption of electromagnetic radiation.
44. The method of claim 1 wherein the angioplasty catheter is a metal
probe.
45. The method of claim 1 wherein the applied thermal energy is
electromagnetic radiation.
46. The method of claim 45 wherein the applied thermal energy is continuous
wave electromagnetic radiation.
47. The method of claim 45 wherein the applied thermal energy is pulsed
electromagnetic radiation.
48. The method of claim 45 wherein the electromagnetic radiation is laser
radiation.
49. The method of claim 45 wherein the electromagnetic radiation is
radio-frequency radiation.
50. The method of claim 45 wherein the electromagnetic radiation is
microwave radiation.
51. The method of claim 45 wherein the electromagnetic radiation is
generated from electrical resistance.
52. A method for treating a lesion in an arterial wall having plaque
thereon and a luminal surface, the arterial wall and the plaque defining
therewithin fissures resulting therefrom, the method comprising the steps
of:
performing angioplasty;
providing a layer of a transporting medium disposed about an angioplasty
catheter balloon, said transporting medium having a bioprotective material
distributed therewithin, the layer of bioprotective material being
surrounded by a removable sheath to prevent premature dissolution of the
bioprotective material;
positioning the angioplasty catheter adjacent to the lesion being treated
so that the transporting medium and the bioprotective material are
entrapped therebetween;
removing the sheath so that the lesion is exposed to the bioprotective
material;
applying thermal energy, thereby liquefying the transporting medium under
pressure and promoting contact of the bioprotective material with the
fissures and the luminal surface, whereby the thermal energy bonds the
bioprotective mate rail to the arterial wall and within the fissures and
vessels of the arterial wall; and
removing the angioplasty catheter, the bioprotective material remaining
adherent to the fissures and vessels within the arterial wall, thereby
treating the injured luminal surface with the bioprotective material,
whereby at least semi-permanent protection to the arterial wall is
provided, despite contact with blood flowing adjacent thereto, the blood
dissolving and removing the transporting medium.
53. The method of claim 1 wherein the step of applying thermal energy to
the lesion comprises applying the thermal energy from the angioplasty
catheter radially outwardly.
54. The method of claim 1 wherein the step of applying thermal energy to
the lesion comprises the step of applying thermal energy so that the
temperature within the bioprotective material is raised to at least
40.degree. C.
55. The method of claim 1 wherein the transporting medium is a soluble
gelatin film.
56. The method of claim 55 wherein the gelatin is removed from the luminal
surface of the tissue by ambient blood flow upon removal of the
angioplasty catheter.
57. The method of claim 1 wherein the layer of a transporting medium has a
thickness between about 5-200 microns.
58. The method of claim 11 wherein the useful pharmaceutical agent is an
inhibitor of collagen cross-linking.
59. The method of claim 11 wherein the useful pharmaceutical agent is an
inhibitor of elastin cross-linking.
60. The method of claim 11 wherein the useful pharmaceutical agent
comprises deoxyribonucleic acid.
61. The method of claim 11 wherein the useful pharmaceutical agent material
comprises ribonucleic acid.
62. The method of claim 11 wherein the useful pharmaceutical agent
comprises one or more genes.
63. A method of treating a lesion in an arterial wall having plaque thereon
and a luminal surface, the arterial wall having been injured during an
angioplasty procedure, the arterial wall and the plaque defining
therewithin fissures resulting therefrom, the method comprising the steps
of:
positioning a layer of a transporting medium disposed about an angioplasty
catheter balloon, said transporting medium having a bioprotective material
distributed therewithin upon a balloon angioplasty catheter adjacent to
the lesion being treated, the layer being surrounded by a removable sheath
to prevent premature dissolution of the bioprotective material;
removing the sheath so that the lesion is exposed to the bioprotective
material;
applying thermal energy to the lesion and inflating the balloon, thereby
liquefying the transporting medium and promoting contact of the
bioprotective material with the fissures and luminal surface, whereby the
thermal energy bonds the bioprotective material to the arterial wall and
within the fissures and vessels of the arterial wall;
allowing the transporting medium to cool, thereby enabling it to become
re-solidified;
removing the angioplasty catheter, the bioprotective material remaining
bonded to the fissures and vessels within the arterial wall, thereby
treating the injured luminal surface with the bioprotective material,
whereby at least semi-permanent protection to the arterial wall is
provided, the blood flowing adjacent thereto, thereby dissolving and
removing the resolidified transporting medium. |
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Claims |
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Description |
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TECHNICAL FIELD
This invention relates to angioplasty, and more particularly to a method
for treating an arterial wall injured during angioplasty.
BACKGROUND ART
Atherosclerosis is a progressive disease wherein fatty, fibrous, calcific,
or thrombotic deposits produce atheromatous plaques, within and beneath
the intima which is the innermost layer of arteries. Atherosclerosis tends
to involve large and medium sized arteries. The most commonly affected are
the aorta, iliac, femoral, coronary, and cerebral arteries. Clinical
symptoms occur because the mass of the atherosclerotic plaque reduces
blood flow through the afflicted artery, thereby compromising tissue or
organ function distal to it.
The mortality and morbidity from ischemic heart disease results primarily
from atheromatous narrowings of the coronary arteries. Although various
medical and surgical therapies may improve the quality of life for most
patients with coronary atherosclerosis, such therapies do not favorably
change the underlying anatomy responsible for the coronary luminal
narrowings. Until recently, there has not been a non-surgical means for
improving the perfusion of blood through the lumina of coronary arteries
compromised by atheromatous plaque.
Percutaneous transluminal coronary angioplasty has been developed as an
alternative, non-surgical method for treatment of coronary
atherosclerosis. During cardiac catheterization, an inflatable balloon is
inserted in a coronary artery in the region of coronary narrowing.
Inflation of the balloon for 15-30 seconds results in an expansion of the
narrowed lumen or passageway. Because residual narrowing is usually
present after the first balloon inflation, multiple or prolonged
inflations are routinely performed to reduce the severity of the residual
stenosis or tube narrowing. Despite multiple or prolonged inflations, a
mild to moderately severe stenosis usually is present, even after the
procedure is otherwise performed successfully.
The physician will often prefer not to dilate lesions that are not severe
because there is a good chance that they will recur. Because the occlusion
recurs frequently, conventional angioplasty is often considered to be a
suboptimal procedure. As a result, it is sometimes attempted only when a
patient does not wish to undergo major cardiac surgery.
There are several reasons why the lesions reappear. One is that small clots
form on the arterial wall. Tears in the wall expose blood to foreign
material and proteins, such as collagen, which are highly thrombogenic.
Resulting clots can grow gradually, or can contain growth hormones which
are released by platelets within the clot. Additionally, growth hormones
released by other cells, such as macrophages, can cause smooth muscle
cells and fibroblasts in the region to multiply. Further, there is often a
complete loss of the normal single layer of cells constituting the
endothelial lining following angioplasty. This layer normally covers the
internal surface of all vessels, rendering that surface compatible, i.e.
non-thrombogenic and non-reactive with blood. Mechanically, when an
angioplasty balloon is inflated, the endothelial cells are torn away.
Combination of the loss of the endothelial layer and tearing within the
wall often generates a surface which is quite thrombogenic.
Prior art angioplasty procedures also produce injuries in the arterial wall
which become associated with inflammation. White cells will migrate to the
area and will lay down scar tissue. Any kind of inflammatory response may
cause the growth of new tissue. Restenosis or recurrence of the
obstruction results because the smooth muscle cells which normally reside
within the arterial wall proliferate. Such cells migrate to the area of
the injury and multiply in response thereto.
It therefore appears that in order to combat problems associated with
cumulating plaque, attention must be paid to: (1) the importance of
thrombus; (2) inflammatory changes; and (3) proliferation. Any combination
of these factors probably accounts for most cases of restenosis.
In order to address such problems, the cardiology community needs to
administer drugs which are biocompatible and not induce toxic reactions.
Therefore, it would be helpful to invoke a technique which allows
localized administration of drugs that counteract clotting, interfere with
inflammatory responses, and block proliferative responses. However, many
such drugs when administered are toxic and are associated with potentially
serious side effects which make the treatment and prevention of restenosis
impractical. Accordingly, even though there is a number of potentially
useful drugs, there is a tendency to avoid using them.
One of the other major problems with conventional methods of treatment is
that the injured arterial wall exhibits a reduced hemocompatability
compared to that associated with a normal arterial wall. Adverse responses
which are associated with reduced hemocompatability include platelet
adhesion, aggregation, and activation; potential initiation of the
coagulation cascade and thrombosis; inflammatory cell reactions, such as
adhesion and activation of monocytes or macrophages; and the infiltration
of leukocytes into the arterial wall. Additionally, cellular proliferation
results in the release of a variety of growth factors. Restenosis probably
results from one or a combination of such responses.
Methods for treating atherosclerosis are disclosed in my U.S. Pat. No.
4,512,762 which issued on Apr. 23, 1985, and which is herein incorporated
by reference. This patent discloses a method of injecting a
hematoporphyrin into a mammal for selective uptake into the atheromatous
plaque, and delivering light to the diseased vessel so that the light
activates the hematoporphyrin for lysis of the plaque. However, one of the
major problems with such treatments is that the thermal energy does not
produce a significant rise in temperature. Also, a flap of material
occasionally is formed during the treatment which, after withdrawal of the
instrumentation, falls back into the artery, thereby causing abrupt
reclosure. This may necessitate emergency coronary artery bypass surgery.
Accordingly, such techniques often provide only a temporary treatment for
symptoms associated with arterial atherosclerosis.
My U.S. Pat. No. 4,799,479 was issued on Jan. 24, 1989 and is also herein
incorporated by reference. This patent discloses a method used in
percutaneous transluminal coronary angioplasty wherein a balloon is heated
upon inflation. Disrupted tissues of plaque in the arterial wall are
heated in order to fuse together fragmented segments of tissue and to
coagulate blood trapped with dissected planes of tissues and within
fissures created by the fracture. Upon subsequent balloon deflation, a
smooth cylindrically shaped channel results. Such heating in that
disclosure, however, is used to bond tissue to tissue--not to bond a
bioprotective material to tissue.
Approaches such as those disclosed in U.S. Pat. Nos. 4,512,762 and
4,799,479, however, are directed mainly to producing an enhanced luminal
result wherein a smooth luminal wall is produced. Problems of
biocompatability, including thrombosis, and proliferation of cells tend to
remain. Accordingly, the need has arisen to enable a physician to treat
patients having atherosclerosis so that the problems of reduced
hemocompatability and restenosis are avoided.
As a result of problems remaining unsolved by prior art approaches, there
has been a growing disappointment in the cardiology community that until
now, no new technology or procedure has been available to dramatically
reduce the rate of restenosis.
SUMMARY OF THE INVENTION
The present invention solves the above and other problems by providing a
method for treating an arterial wall which has been injured during an
angioplasty procedure. The method comprises the steps of positioning an
angioplasty catheter adjacent to a lesion to be treated. A soluble
transporting medium in the form of a gel which carries a bioprotective
material is delivered between the arterial wall and the angioplasty
catheter so that the transporting medium and the bioprotective material
are entrapped therebetween and permeate into fissures in the arterial wall
during apposition thereto of the angioplasty catheter. To liquify the
transporting medium and bond the bioprotective material to the arterial
wall and within the tissues, thermal energy is applied to the lesion.
After removal of the angioplasty catheter, the bioprotective material
remains adherent to the arterial wall and within the tissues, thereby
providing localized drug therapy and, if desired, coating the luminal
surface of the arterial wall with an insoluble layer of the bioprotective
material. As a result, at least semi-permanent protection is imparted to
the arterial wall, despite contact with blood flowing adjacent thereto.
Such blood flow carries away the dissolved transporting medium.
The objects, features, and advantages of the present invention are readily
apparent from the following detailed description of the best modes for
carrying out the invention when taken in connection with the accompanying
drawings.
BRIEF DESCRIPTION OF DRAWINGS
FIG. 1A is a cross-sectional view of a lesion to be treated by a
percutaneous transluminal angioplasty procedure, in which plaque is formed
within an artery;
FIG. 1B is a cross-sectional view of the procedure disclosed by the present
invention, in which a transporting medium and bioprotective material are
delivered to a lesion during distention of an uninflated balloon;
FIG. 1C is a cross-sectional view of the procedure disclosed by the present
invention, in which the balloon is inflated and the transporting medium
and bioprotective material are entrapped between the balloon and the
arterial wall, the transporting medium and the bioprotective material also
entering vessels of the arterial wall and fissures which result from
previously administered angioplasty procedure;
FIG. 2 is a cross-sectional view of one embodiment of the anatomical
environment and apparatus used to practice the subject invention, in which
the area immediately surrounding the inflated balloon is permeated by the
transporting medium bioprotective material, the latter being bonded by
thermal energy within the arterial wall being treated, the former being
liquified by the thermal energy;
FIG. 2A is an enlarged portion of the circled area depicted in FIG. 2;
FIG. 3 is a cross-sectional view of the result of utilizing the procedure
of the present invention, illustrating a smooth channel formed by the
insoluble layer of bioprotective material within sealed fissures and
sealed vessels of the arterial wall, thereby providing at least
semi-permanent protection to the arterial wall, despite contact with blood
flowing adjacent thereto; and
FIGS. 4A-E depict the main process steps involved in practicing the
disclosed method for treating the injured arterial wall.
BEST MODES FOR CARRYING OUT THE INVENTION
The method taught by the present invention can best be appreciated after a
preliminary discussion of what now are conventional angioplasty
procedures.
FIG. 1A shows a guide wire 10 used in such procedures which is inserted
along an artery and through a region 12 which is occluded primarily by
plaque 14. Surrounding the plaque 14 are media 60 and adventitia 18. As is
now known, the plaque 14 forms an occlusion. The guide wire 10 is usually
a stainless steel wire having tightly coiled, but flexible springs.
Traditionally, the catheter 20 is made of a plastic, or an elastomeric
material and is disposed around the guide wire 10. Following conventional
angioplasty, the balloon section 22 is maneuvered so as to lie adjacent to
the plaque 14.
FIG. 1B illustrates the positioning of the uninflated balloon 22 after
conventional angioplasty has been performed. Expansion of the balloon 22
to position 22' (FIG. 1C) stretches out the lesion by tissue pressure.
Larger balloons are capable of applying more pressure. Between about half
an atmosphere and ten atmospheres may be necessary to dilate balloon 22'
within the luminal surface 29. Before the balloon 22' is fully expanded,
its pressure approximates the tissue pressure. However, once the balloon
22' cracks the plaque and is fully expanded, the outer layers of the
tissue are somewhat elastic and the tissue pressure therefore no longer
approximates the balloon pressure.
Referring now to FIG. 1C, the balloon section 22 having been placed
adjacent to the plaque 14, is inflated to position 22', thereby opening
the artery. At the same time, the fissures and dissected planes of tissue
24 are also opened.
After the catheter 20 is removed, following the teachings of conventional
angioplasty procedures, the plaque 14 can collapse into the center of the
artery, thereby resulting in an abrupt reclosure of the artery and the
possibility of an acute myocardial infarction.
Following prior art techniques, even less severe disruptions in the
arterial wall commonly result in gradual restenosis within three to six
months after conventional balloon angioplasty. This occurs in part because
platelets adhere to exposed arterial tissue surfaces. FIG. 1C is helpful
in illustrating the fissures or dissected planes of tissue 24 which result
from conventional angioplasty procedures. The presence of regions of blood
flow separation and turbulence within the arterial lumen 36 predispose to
microthrombi deposition and cellular proliferation within the arterial
wall 28.
To overcome these and other problems resulting from prior art approaches,
the method of the present invention depicted in FIGS. 4A-4E calls for
application of the transporting medium 48 and bioprotective material 26 to
a lesion 27 of the luminal surface 29 of the arterial wall 28 and to
deeper surfaces lining fissures and vessels of the arterial wall. The
angioplasty catheter or balloon 20 is first positioned adjacent to the
lesion 27 being treated. Next, a sleeve of the transporting medium 48 and
bioprotective material 26 is disposed on the angioplasty catheter 20. The
sleeve is then delivered to the arterial wall 28, to which it is pressed
by inflation of the balloon angioplasty catheter 20 (FIG. 4A). Before
completing inflation of the balloon, the transporting medium 48 and
bioprotective material 26 lie within fissures and vessels of the arterial
wall, between it and the angioplasty catheter 20. During apposition of the
angioplasty catheter 20 to the arterial wall 28, a layer of the solid or
gelatinous transporting medium 48 and insoluble bioprotective material 28
is entrapped therebetween. Because of pressure exerted radially outwardly
by the balloon 34, the transporting medium 48 and bioprotective material
26 further penetrate and permeate the vessels of the arterial wall as well
as the fissures and dissected planes of tissue 24. As a result, localized
delivery of the bioprotective material 26 occurs.
Application of thermal energy, as shown in FIG. 4B, liquifies the soluble
transporting medium 48. Urged by mechanical pressure exerted by the
inflated balloon 20, and liquification of the transporting medium 48 the
insoluble bioprotective material 26 migrates further into the fissures and
dissected planes of tissue 24 upon heating. Some of the bioprotective
material 26 establishes contact with the luminal surface of the arterial
wall 28.
Upon cooling, the transporting medium 48 re-solidifies (FIG. 4C). The
bioprotective material 26 becomes bonded to the fissures and along the
luminal surface of the arterial wall 28. When the balloon angioplasty
catheter 34 is removed (FIG. 4D), the coursing of blood adjacent to the
soluble transporting medium 48 results in dissolution and removal thereof
(FIG. 4E).
In the treatment method disclosed by the present application, the
transporting medium 48 is preferably a soluble gelatin film which is
fabricated in the form of a sleeve before placement on the external
surface of the balloon 22. Alternatively, the transporting medium 48 may
be prepared from a soluble collagen, or heparin in the form of a viscous
gel. One or more bioprotective materials 26, including pharmacologic
agents, either free or bound to the insoluble carrier, are impregnated
within the sleeve. During treatment, inflation of the balloon 22 places
the transporting medium 48 and bioprotective material 26 in contact with
the arterial tissue.
Upon balloon deflation, the liquified transporting medium 48 rapidly
disappears from the luminal surface of the tissue because of its
solubility. As a result, the origin of adjacent side branches remain open,
since the impregnated bioprotective materials 26, now bonded to the
tissue, provide no mechanical support. The bonded bioprotective materials
26 remain at the luminal surface of the tissue by virtue of thermal
bonding and their insoluble nature.
Unlike conventional approaches which may require repeated application of
the angioplasty procedure with intermittent inflation of the balloon to
avoid prolonged interruption of blood flow, the procedure taught by the
present invention does not require multiple inflations, and is applied
only once for about a twenty second period of thermal treatment followed
by about a twenty second period of cooling before balloon deflation. If
required, the disclosed technique can be used repeatedly.
Referring now to FIG. 3, after removing the angioplasty catheter 20, and
dissolution of the transporting medium 48, the bioprotective material 26
remains adherent to the arterial wall 28. As a result, the luminal surface
29, fissured tissues, and vessels of the arterial wall are coated with an
insoluble layer of the bioprotective material 26. The insoluble layer
provides at least semi-permanent protection to the arterial wall 28,
despite contact with blood flowing adjacent thereto.
It will be appreciated that until the invention disclosed herein, there
existed no technique for coating the luminal surface and deeper tissue
layers of arteries with a bioprotective material after injury sustained in
conventional angioplasty.
As a result of the contribution made by the present invention, it is now
possible to coat the luminal surface and deeper layers of injured arteries
with insoluble, and therefore permanent or semi-permanent bioprotective
materials. One or more of such bioprotective materials could, depending
upon the physician's preference, be pharmacologically active.
Thrombogenic, inflammatory, or proliferative adverse reactions, or other
adverse reactions which normally occur after angioplasty may therefore be
reduced. As a result, both short and long term luminal results are
improved.
In a preferred method of practicing the present invention, thermal energy
is applied to the lesion to bond the bioprotective material 26 to the
arterial wall using laser balloon angioplasty (LBA). In this procedure,
heat (including heat emanating from non-laser energy sources) and pressure
are applied simultaneously to remodel the arterial lumen. The protective
biocompatible layer 26 can then be applied to the luminal surface and
deeper layers of the arterial wall in ways which are not possible with any
other type of angioplasty procedure.
Turning now to FIGS. 2 and 4B, it may be seen that thermal energy generated
from an optical diffusing tip 32 is represented schematically by radially
emanating wavy lines. The thermal energy liquifies the transporting medium
48 and bonds the bioprotective material 26 to the arterial wall 28 and
within the tissues 24.
The guide wire 10 may be replaced with an optical fiber 30 having an
optical diffusion area or tip 32 located within the inflated balloon 22'.
The catheter 20 is inserted around the optical fiber in lumen 36.
Expansion of the balloon 22 is produced by a transparent fluid through
inflation port 38 in termination apparatus generally located at 40. The
fluid utilized for inflation of the balloon may be a contrast medium or
crystalloids, such as normal saline, or five percent dextrose in water.
Each is relatively transparent to such thermal energy as radiation. After
passing through the catheter wall 42, the fluid continues through a
channel 44 in the outer catheter sheath, thereby inflating the balloon 34.
After inflation, for example, laser radiation 46 is introduced into the
optical fiber 30 for transmission to the optical diffusion tip 32. The
laser radiation is then diffused therefrom and impinges upon the
transporting medium 48 and bioprotective material 26 and the arterial wall
28 after fracture or dissection of the plaque 14 has occurred following
prior angioplasty.
It will be apparent that there exist a variety of ways to deliver thermal
energy to the area to be treated. Microwave, radio-frequency, or
electrical heating of the fluid each are possible techniques.
A preferred technique calls for the use of albumin as the bioprotective
material 26. The albumin precipitates onto and is bonded to the luminal
surface 29 and deeper layers of the arterial wall as a result of thermal
denaturation. It will be appreciated that other types of potentially
injectable, heat-transformable materials may be used. Such materials
include high molecular carbohydrates such as starch and dextran,
liposomes, platelets, red blood cells, fibrinogen, and collagen.
Chemically or thermally cross-linked albumin has been used by others to
coat surfaces of prosthetic vascular grafts in order to provide a
non-thrombogenic layer. Since a bonded layer of albumin is insoluble, it
may persist on the luminal surface for at least four weeks before
disappearance. By that time, the surface may be completely healed with a
new confluent layer of ingrowing endothelial cells, which typically takes
about two weeks.
It is also possible to use one or more of a wide variety of therapeutically
useful pharmaceutical agents coupled to the albumin, thus providing local
drug therapy to prevent restenosis of the angioplastied lesion. Examples
of such drugs include anticoagulants (e.g. heparin, hirudin, anti-platelet
agents, and equivalents), fibrinolytic and thrombolytic agents,
anti-inflammatory agents (e.g. steroidal and non-steroidal compounds), and
anti-proliferative compounds (e.g. suramin, monoclonal antibodies to
growth factors, and equivalents). Drugs may be bound covantly to albumin
in solution, prior to injection, so the drug will be permanently fixed to
the heat-precipitated layer of albumin.
Also considered within the scope of the present invention is the use of a
bioprotective material or drug 26 which is physically and/or chemically
trapped within or by the precipitated layer of albumin. Microspheres 26
could be fabricated in vitro to trap virtually any type of drug
therewithin prior to injection into the lumen of the artery. In such an
environment, the rate of diffusion of the drug through the walls of the
microspheres could be adjusted by the degree of albumin cross-linking
induced thermally or chemically. With a currently well-developed
technology of fabrication of albumin microspheres, the half life for
diffusion of entrapped drugs from the microspheres can be varied from
minutes to many months. The dimensions of the microspheres can be made to
be smaller than 3 microns, thereby avoiding the problem of capillary
plugging. When the drug-containing albumin microspheres is injected into
the artery, with or without albumin, thermal cross-linking during thermal
exposure will induce adherence of the microspheres to the arterial wall.
Similar concepts could also be applied to a wide variety of other types of
microencapsulated drug preparations delivered by the transporting medium
48. The encapsulating medium may consist of liposomes, both high and low
molecular weight carbohydrates, sulfated polysaccharides, platelets, red
blood cells, gelatin, fibrin, inorganic salts, phosphate glasses, and
synthetic polymeric materials. Examples of synthetic polymeric materials
include glycoside, lactide, silicone, polyvinylpyrrolidone, poly (methyl
methacrylate), and polyamide polymers; ethylene-vinyl acetate copolymer;
polyesters such as polyglactin, vicryl, Dexon, and polydioxanone polymers;
and hydrogels, such as poly (hydroxyethyl methacrylate), polyacrylamide,
polyvinyl alcohol, and gamma-irradiated polyelectrolytes. Additionally,
endogenous platelets, removed from the same patient to be treated, can be
made to incorporate virtually any water-soluble drug. It should be noted
that thermal denaturation of proteins on the surface of a platelet during
application of this blood element to the arterial wall can be expected to
prevent the platelet from functioning normally as an initiator or promotor
of thrombus formation.
Microspheres of any material, when injected along with an albumin solution,
or macroaggregated albumin would be similarly trapped with heat-induced
precipitation and cross-linking of the albumin. Alternatively, the
microcapsules could be thermally bonded directly to tissues, without the
use of any additional cross-linkable material. Microcapsules could also be
formed in situ at the sleeve-tissue interface as a result of heating the
bioprotective material in solution. A water soluble drug which is injected
simultaneously with the bioprotective material in solution would thereby
become encapsulated upon thermal treatment.
Both water soluble and water-insoluble drugs may be encapsulated within the
microspheres. In addition to anti-coagulants, thrombolytic, fibrinolytic,
anti-inflammatory, or anti-proliferative agents, other potentially useful
drugs or materials may be encapsulated. Examples include immunosuppressant
agents (cyclosporin; alkylating agents; adriamycin; and equivalents),
glycosaminoglycans (heparin sulfate; dermatan sulfate and equivalents),
collagen inhibitors (colchicine; B-aminoproprionitrile; D-penicillamine;
1, 10 phenanthroline, and equivalents), and endothelial cell growth
promoters. In addition, a chromophore may be encapsulated in order to
enhance absorption of electromagnetic radiation.
As discussed earlier, in addition to the pharmacologic benefit of the
invention, cracks and recesses within the mechanically injured arterial
wall are filled in with the insoluble material, thereby producing a
smoother and, hence, less thrombogenic luminal surface.
A further benefit of the invention results from the drugs being delivered
throughout the full thickness of the plaque and arterial wall.
Disclosure of the invention thus far has contemplated administering the
bioprotective material 26 as a thin sleeve of a transporting medium, 48
with such material to the external surface of the LBA balloon. The thin
sleeve is then transferred to the luminal surface as a result of heat and
pressure.
As an example of the preferred embodiment of the invention, a solution of
about 5 grams of powdered gelatin in 100 cc's of water was prepared.
Heparin at a final concentration of greater than 1000 units per cc was
dissolved in the gelatin solution. Gelatin has been found to possess
excellent mechanical characteristics, including flexibility and tensile
strength for the desired application. Virtually any agent or drug carrier
can be impregnated within the film by addition of the bioprotective
material before dehydration of the gelatin solution. Dehydration occurs
after the transporting medium 48 and the bioprotective material 26 are
placed between sheets of, for example, silicone rubber and polyethelene.
Dry gelatin films are then produced with a thickness ranging between about
5 to 200 microns. The gelatin films are then mounted on the surface of a
laser balloon angioplasty catheter.
Good results have been obtained when a thin lipid coating is applied to the
external surface of the mounted film to prevent premature dissolution
before deployment. To prevent premature dissolution, the gelatin may also
be lightly cross-linked by exposure to a vapor of 50% glutaraldehyde for
several minutes or by the use of succinylated gelatin. If the latter
approaches are not used, a protective sheath 64 (FIG. 1C) applied to cover
the gelatin sleeve 26 during advancement of the balloon 22 to the lesion
to be created. After the protective sheath is withdrawn, the sleeve of
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