CA2082149A1 - Method for treating an arterial wall injured during angioplasty - Google Patents
Method for treating an arterial wall injured during angioplastyInfo
- Publication number
- CA2082149A1 CA2082149A1 CA002082149A CA2082149A CA2082149A1 CA 2082149 A1 CA2082149 A1 CA 2082149A1 CA 002082149 A CA002082149 A CA 002082149A CA 2082149 A CA2082149 A CA 2082149A CA 2082149 A1 CA2082149 A1 CA 2082149A1
- Authority
- CA
- Canada
- Prior art keywords
- arterial wall
- bioprotective material
- luminal surface
- bioprotective
- fissures
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
- A61B17/22—Implements for squeezing-off ulcers or the like on the inside of inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; Calculus removers; Calculus smashing apparatus; Apparatus for removing obstructions in blood vessels, not otherwise provided for
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- A—HUMAN NECESSITIES
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- A61B17/00491—Surgical glue applicators
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- A61B17/22—Implements for squeezing-off ulcers or the like on the inside of inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; Calculus removers; Calculus smashing apparatus; Apparatus for removing obstructions in blood vessels, not otherwise provided for
- A61B17/22004—Implements for squeezing-off ulcers or the like on the inside of inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; Calculus removers; Calculus smashing apparatus; Apparatus for removing obstructions in blood vessels, not otherwise provided for using mechanical vibrations, e.g. ultrasonic shock waves
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- A61B18/04—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by heating
- A61B18/08—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by heating by means of electrically-heated probes
- A61B18/082—Probes or electrodes therefor
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- A61B18/20—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by applying electromagnetic radiation, e.g. microwaves using laser
- A61B18/22—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by applying electromagnetic radiation, e.g. microwaves using laser the beam being directed along or through a flexible conduit, e.g. an optical fibre; Couplings or hand-pieces therefor
- A61B18/28—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by applying electromagnetic radiation, e.g. microwaves using laser the beam being directed along or through a flexible conduit, e.g. an optical fibre; Couplings or hand-pieces therefor for heating a thermal probe or absorber
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- A61B2017/22001—Angioplasty, e.g. PCTA
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- A61B2017/22038—Implements for squeezing-off ulcers or the like on the inside of inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; Calculus removers; Calculus smashing apparatus; Apparatus for removing obstructions in blood vessels, not otherwise provided for with a guide wire
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- A61B2017/22051—Implements for squeezing-off ulcers or the like on the inside of inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; Calculus removers; Calculus smashing apparatus; Apparatus for removing obstructions in blood vessels, not otherwise provided for with an inflatable part, e.g. balloon, for positioning, blocking, or immobilisation
- A61B2017/22062—Implements for squeezing-off ulcers or the like on the inside of inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; Calculus removers; Calculus smashing apparatus; Apparatus for removing obstructions in blood vessels, not otherwise provided for with an inflatable part, e.g. balloon, for positioning, blocking, or immobilisation to be filled with liquid
- A61B2017/22064—Implements for squeezing-off ulcers or the like on the inside of inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; Calculus removers; Calculus smashing apparatus; Apparatus for removing obstructions in blood vessels, not otherwise provided for with an inflatable part, e.g. balloon, for positioning, blocking, or immobilisation to be filled with liquid transparent liquid
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- A61B17/22—Implements for squeezing-off ulcers or the like on the inside of inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; Calculus removers; Calculus smashing apparatus; Apparatus for removing obstructions in blood vessels, not otherwise provided for
- A61B2017/22082—Implements for squeezing-off ulcers or the like on the inside of inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; Calculus removers; Calculus smashing apparatus; Apparatus for removing obstructions in blood vessels, not otherwise provided for after introduction of a substance
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- A61B17/22—Implements for squeezing-off ulcers or the like on the inside of inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; Calculus removers; Calculus smashing apparatus; Apparatus for removing obstructions in blood vessels, not otherwise provided for
- A61B2017/22082—Implements for squeezing-off ulcers or the like on the inside of inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; Calculus removers; Calculus smashing apparatus; Apparatus for removing obstructions in blood vessels, not otherwise provided for after introduction of a substance
- A61B2017/22084—Implements for squeezing-off ulcers or the like on the inside of inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; Calculus removers; Calculus smashing apparatus; Apparatus for removing obstructions in blood vessels, not otherwise provided for after introduction of a substance stone- or thrombus-dissolving
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- A61B17/22—Implements for squeezing-off ulcers or the like on the inside of inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; Calculus removers; Calculus smashing apparatus; Apparatus for removing obstructions in blood vessels, not otherwise provided for
- A61B2017/22082—Implements for squeezing-off ulcers or the like on the inside of inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; Calculus removers; Calculus smashing apparatus; Apparatus for removing obstructions in blood vessels, not otherwise provided for after introduction of a substance
- A61B2017/22085—Implements for squeezing-off ulcers or the like on the inside of inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; Calculus removers; Calculus smashing apparatus; Apparatus for removing obstructions in blood vessels, not otherwise provided for after introduction of a substance light-absorbing
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
- A61B17/22—Implements for squeezing-off ulcers or the like on the inside of inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; Calculus removers; Calculus smashing apparatus; Apparatus for removing obstructions in blood vessels, not otherwise provided for
- A61B2017/22082—Implements for squeezing-off ulcers or the like on the inside of inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; Calculus removers; Calculus smashing apparatus; Apparatus for removing obstructions in blood vessels, not otherwise provided for after introduction of a substance
- A61B2017/22087—Implements for squeezing-off ulcers or the like on the inside of inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; Calculus removers; Calculus smashing apparatus; Apparatus for removing obstructions in blood vessels, not otherwise provided for after introduction of a substance photodynamic
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- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M25/00—Catheters; Hollow probes
- A61M25/10—Balloon catheters
- A61M2025/1043—Balloon catheters with special features or adapted for special applications
- A61M2025/105—Balloon catheters with special features or adapted for special applications having a balloon suitable for drug delivery, e.g. by using holes for delivery, drug coating or membranes
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M25/00—Catheters; Hollow probes
- A61M25/10—Balloon catheters
- A61M25/104—Balloon catheters used for angioplasty
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- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
- A61M37/0092—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin using ultrasonic, sonic or infrasonic vibrations, e.g. phonophoresis
Abstract
A method for treating a lesion in an arterial wall (28) having plaque (14) thereon and a luminal surface (16), the arterial wall having been mechanically injured during an angioplasty procedure, the arterial wall and the plaque including fissures resulting therefrom, the method comprising the steps of positioning an angioplasty catheter adjacent to the lesion being treated (fig. 1B);
delivering a bioprotective material (fig. 2) between the arterial wall and the angioplasty catheter (20) so that the bioprotective material (26) is entrapped therebetween and permeates into the fissures and small vessels of the arterial wall during apposition of the angioplasty catheter to the arterial wall; applying thermal energy to the lesion (27), thereby bonding the bioprotective material to the arterial wall and within the fissures; and removing the angioplasty catheter (fig. 3), the bioprotective material remaining adherent to the arterial wall and within the fissures, thereby coating the luminal surface of the arterial wall with an insoluble layer of the bioprotective material so that the insoluble layer provides at least semi-permanent protection to the arterial wall, despite contact with blood flowing adjacent thereto.
delivering a bioprotective material (fig. 2) between the arterial wall and the angioplasty catheter (20) so that the bioprotective material (26) is entrapped therebetween and permeates into the fissures and small vessels of the arterial wall during apposition of the angioplasty catheter to the arterial wall; applying thermal energy to the lesion (27), thereby bonding the bioprotective material to the arterial wall and within the fissures; and removing the angioplasty catheter (fig. 3), the bioprotective material remaining adherent to the arterial wall and within the fissures, thereby coating the luminal surface of the arterial wall with an insoluble layer of the bioprotective material so that the insoluble layer provides at least semi-permanent protection to the arterial wall, despite contact with blood flowing adjacent thereto.
Description
WO 91/17731 PCr/US91/02929 :Itl~D D~IRI~ A~GlSOP~8g!~1 8~ATB~IEN~ OF FBD~RALLY 8P0~80R}~D RESB~RCH
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The funding for work described herein was provided in part by the Federal Government, under a grant from the National Institute of Health. The government may have certain rights in this invention.
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` TECHNICAL :FIELD
This invention relates to angioplasty, and lo more particularly to a method for treating an arterial wall injured during angioplasty.
~ACRGROUND ART
; Atherosclerosis is a progressive disease wherein f~tty, 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.
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The mortality and morbidity from ischemic ;~ 25 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.
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' :' ' WO9~/17731 2 ~ 8 ~ 9 PCT/US9~/02929 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 o~ coronary atherosclerosis.
During cardiac catheterization, an inflatable balloon is inserted in a coronary artery in the region of coronary narrowing. Inflation o~ 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 infl~tion, 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 ~requently, 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 ma;or 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 . . , . - . .. . .. , ~. .-. ~ ,, . - .
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The funding for work described herein was provided in part by the Federal Government, under a grant from the National Institute of Health. The government may have certain rights in this invention.
.
` TECHNICAL :FIELD
This invention relates to angioplasty, and lo more particularly to a method for treating an arterial wall injured during angioplasty.
~ACRGROUND ART
; Atherosclerosis is a progressive disease wherein f~tty, 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 ;~ 25 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.
:.:
. . .
' :' ' WO9~/17731 2 ~ 8 ~ 9 PCT/US9~/02929 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 o~ coronary atherosclerosis.
During cardiac catheterization, an inflatable balloon is inserted in a coronary artery in the region of coronary narrowing. Inflation o~ 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 infl~tion, 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 ~requently, 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 ma;or 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 . . , . - . .. . .. , ~. .-. ~ ,, . - .
2 ~ 9 PCT/US91/0~929 fibroblasts in the region to multiply. Further, there is often a complate 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.
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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.
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It therefore appears that in order to combat ;~ problems associated with cumulating plaque, attention ~ -must be paid to: (l) the importance of thrombus; (2) inflammatory changes; and (3) proliferation. Any combination of these factors probably accounts for most ;~ cases of restenosis.
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In order to address such problems, the cardiology community needs to administer drugs which are biocompatible and not induce toxic reactions.
` 30 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, 2 ~82~
WO91/17731 PCT/US91/0~929 ,:
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.
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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. Patent No. 4,512,762 which issued on April 23, 1985, and which is herein incorporated by reference. This patent discloses a method of injecting ~5 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 a flap of material occasionally is formed during the ~` treatment which, after withdrawal of the i instrumentation, falls bacX into the artery, thereby causing abrupt reclosure. This may necessitate ~; emergency coronary artery bypass surgery. Accordingly, .
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such techniques often provide only a temporary treatment for symptoms associated with arterial atherosclerosis.
My U.S. Patent No. 4,799,479 was issued on January 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 de~lation, a smooth cylindrically shaped channel results.
Approaches such as those disclosed in U.S.
Patent Nos. 4,512,762 and 4,799,47g, however, are directed mainly to producing an enhanced luminal result wherein a smooth luminal wall is produced. Problems of biocompatability, including thrombosis, and I proliferation of cells tend to remain. Accordingly, the 1 20 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.
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WO91/17731 PCT/US91/0~929 ~UMM~RY OF ?~E INVEN~ION
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 bioprotective material is delivered between the arterial wall and the angioplasty catheter so that the bioprotective material is entrapped therebetween and permeates into fissures in the arterial wall during apposition thereto of the angioplasty catheter. To 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 coating the luminal surface of the arterial wall with an insoluble layer of the bioprotective material so that the insoluble layer provides at least semi-permanent protection to the arterial wall, despite contact with blood flowing adjacent thereto.
................... .......................................................... ' ' 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.
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Figure lA 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;
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Figure lB is a cross-sectional view of the procedure disclosed by the present invention, in which . a bioprotective material is delivered to a lesion during : distention of an uninflated balloon;
: 5 Figure lC is a cross-sectional view of the procedure disclosed by the present invention, in which the balloon is inflated and the bioprotective material is entrapped between the balloon and the arterial wall, the bioprotective material also entering vessels of the arterial wall and fissures which result from previously administered angioplasty procedure;
Figure 2 is a cross-sectional view including enlarged portions 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 bioprotective i material and bonded by thermal energy delivered to the bioprotective material within the arterial wall being treated; and ,' Figure 3 is a cross-sectional view of the result of utilizing the procedure of the present invention, illustrating a smooth channel ormed by the insoluble layer of bioprotective material at the luminal surface and 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.
BB8T MODE5 FOR CARRYING OIJT T~I~3 lNVENq!ION
Figure lA shows a guide wire 10 which is ` 30 inserted along an artery and through a region 12 which is occluded primarily by plaque 14. Surrounding the ,, 2~
WO91/17731 PCT/US91/0~929 plaque 14 are media 60 and adventitia 18. As is now known, the plaque 14 forms an occlusion. The guide wire lO is usually a stainless steel wire having tightly coiled, but flexible springs. Conventionally, the catheter 20 is made of a plastic, or an elastomeric material and is disposed around the guide wire 10.
Following conventional angioplasty, and before applying bioprotective material 26, the balloon section 22 is maneuvered so as to lie adjacent to the plaque 14.
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Figure lB illustrates the positioning of the uninflated balloon 22 after conventional angioplasty has been performed. Expansion of the balloon 22 to position 22' (Figure lC) 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 22l 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.
The mild residual tissue pressure is helpful in applying the bioprotective material 26 to the arterial wall 28. -Referring again to Figure lC, 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 :;
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WO91/17731 2 ~ d ~ PCT/US~1/02929 '; _ g _ artery and the possibility of an acute myocardial ~ infarction.
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`~ 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 ~urfaces. Figure lC 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. ~;
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To overcome these and other problems resulting ' from prior art approaches, the method of the present invention applies the 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 20 is first positioned adjacent to the lesion 27 being treated.
Next, ths bioprotective material 26 is delivered between the arterial wall 28 and the angioplasty catheter 20.
Before completing inflation of the balloon, the bioprotective material 26 lies within fissures and vessels of the arterial wall and between the arterial wall 28 and the angioplasty catheter 20, and downstream thereof. During apposition of the angioplasty catheter 20 to the arterial wall 28, a layer of the bioprotective - 30 material 28 is entrapped therebetween. Because of capillary action and pressure exerted radially ~utwardly by the balloon, the bioprotective material 26 further enters and permeates the vessels of the arterial wall as well as the fissures and dissected planes of tissue 24.
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Turning now to Figure 2, it may be seen that thermal energy generated ~rom an optical diffusing tip 32 is r0presented schematically by radially emanating wavy lines. The thermal energy bonds the bioprotective material 26 to the arterial wall 28 and within the tissues 24.
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The guide wire lO may be replaced with an optical ~iber 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 there~rom and impinges upon the bioprotective material 26 and the arterial wall 28 after fracture or dissection o~ the plaque l4 has occurred following prior angioplasty. It will be apparent that there exist a variety of ways to deliver thermal energy to the area to ` ~
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,i be treated. Microwave, radio-frequency, or electrical heating of the fluid each are possible techniques.
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The invention disclosed contemplates injection of the bioprotective material 26 through the guiding catheter 20, the tip of which lies near the origin of, for example, a coronary artery before passage of a small balloon catheter through an inner channel of the guiding catheter. The bioprotectiYe material may be injected through the guiding catheter along with flowing blood.
Alternatively, the physician may use a small tube that fits over the shaft of the balloon catheter 20 and inject drugs proximal to or upstream from the balloon's location. If the physician wishes, a separate channel within the angioplasty catheter could be used to inject the bioprotective material through exit holes located in the shaft of the catheter, proximal to the balloon.
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In practicing the invention, the guide wire lO
may extend through a central channel in the balloon and extend down the arterial lesion path. Alternatively, the guide wire lO can be fixed to a central channel in the balloon or be freely movable with respect thereto.
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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 thicker layers of - bioprotective material 26 are required, then the disclosed technique can be used repeatedly.
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~ ~$.~9 W~91/17731 PCT/US91/0~929 Referring now to Figure 3, after removing the angioplasty catheter 20, 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. Although balloons can be used to deliver stents which act as scaffolding devices, the struts of the stents generally are inherently thrombogenic as a result of disruption of laminar flow adjacent to each stent and at the axial ends thereof. Continuous, smooth-walled stents can be fabricated, but use of such stents could result in occlusion of large side branches which are invariably present in coronary arteri~s. In addition, stents may elicit a foreign body inflammatory reaction, are technically difficult to place, and are relatively unforgiving if placed inappropriately.
As a result of the ~ontribution 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 '.' " ~' ' .
WO91/17731 ~ ~ PCT/US91/02929 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 ; 5 present invention, thermal energy is applied ~o 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. Following the teachings of the present invention, drugs may now be incorporated into the biocompatible layer to mitigate any adverse biologic responses of the arterial wall to mechanical or ' thermal injury.
One method of applying the biocompatible layer to the luminal surface contemplates injecting a solution or fine dispersion o~ one or a combination of materials into the artery during balloon inflation. At least one component of the materials becomes bonded to the luminal surface by undergoing a physical change such as a phase transition, transient breakage of non-covalent bonds with subsequent cross-linkage with both itself and the arterial wall upon cooling, or by a chemical reaction, such as polymerization. The coating of bioprotective ; material thereby provided is a relatively water-insoluble layer which is bonded to tissues at the luminal surface. This layer will persist chronically, -despite contact with flowing blood, unlike a water-soluble material.
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A preferred techni~ue calls for the use of albumin in solution, which is trapped between the balloon 22 and luminal surface 29 during balloon inflation. 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 cellsl fibrinogen, and collagen.
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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 precipitated layer of albumin is insoluble, it may persist on the luminal surface for at least four weeks before the layer of albumin disappears.
By that time, the surface may be completely healed with a new confluent layer of ingrowing endothelial cells, which typically takes about two weeks.
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It is also possible to apply directly to the arterial wall 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 :
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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 drug which is physically and/or chemically trapped within or by the precipitated layer of albumin. Microspheres 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 cros~-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 are injected into the artery, with or without albumin in solution, 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. 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 glycolide, lactide, silicone, polyvinylpyrrolidone, poly (methyl methacrylate), and polyamide polymers; ethylene-vinyl acetate copolymer; polyesters such as polyglactin, vicryl, Dexon, and polydioxanone polymers; and .
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W091/17731 21~q~2~ ~ PCT/US91/~2929 ;
hydrogels, such as poly (hydroxyethyl methacrylate), polyacrylamide, polyvinyl alcohol, and gamma-irradiated polyelectrolytes. Additionally, endogenous platelets, removed from the same patient to he 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, 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 balloon-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.
~oth 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 (heparan sulfate;
dermatan sulfate and equivalents), collagen inhibitors (colchicine; D-penicillamine; l, lO phenanthroline, and equivalents), and endothelial cell growth promotors. In .. . . .
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WO91/17731 2~3~t ~1 s~ PCT/US91/02929 . .
addition, a chromophore may be encapsulated in order to enhance absorption of electromagnetic radiation.
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Alternatively, a photosensitive drug such as a porphyrin may be encapsulated in order to enhance photodynamic therapy of tissues within which the microcapsules are thermally bonded. When a chromophore , is encapsulated at the surface of microcapsules, the use ;~ of pulsed electromagnetic radiation, the wavelength of which matches the absorption spectrum of the chromophore, could be used to selectively and briefly heat only the surface of each microcapsule to bond the microcapsules to the luminal surface, without damaging thermally labile materials encapsulated within the interior of the microcapsules. It will be apparent to those of ordinary skill that many variations of the concept are possible.
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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.
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A further benefit of the invention results m from the small vessels within the plaque and normal ` 25 arterial wall (vasa vasorum) being filled with the ~-material delivered during balloon inflation. Thermal .
cross-linking of at least one of the materials, such as albumin, effectively bonds the materials to the luminal surface of the small vessels. In addition, the material fills and become bonded to tissues lining fissures and dissections. Drugs are therefore delivered throughout ;~ the full thickness of the plaque and arterial wall.
Moreover, the bioprotective material, when trapped ;
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WO91/17731 ~}~ PCT/US91/02929 between dissected tissues, could additionally be used to enhance thermal fusion thereof. A level of coagulation or precipitation achieved by thermal exposure alone is generally insufficient to obliterate side branches larger than about 0.5 mm because the radially directed pressure applied by the inflated balloon does not bring opposing walls of the lumen of a side branch firmly together, a necessary condition for thermal closure of such arteries.
.. ~ , Obliteration of the lumina of small vessels of the arterial wall is achievable by thermally coagulating a sufficient amount of albumin within the lumina or by thermally bonding opposing walls of the small vessels which are coapted by pressure. As a result, the entire balloon-dilated arterial segment would be rendered relatively impermeable to blood and blood-born components. For example, infiltration of leukocytes into the plaque and arterial wall is greatly slowed, and permeation of growth factors and of mediators of inflammation is impeded. Likewise, the thermally treated arterial wall provides a semi-permanent depot for entrapped drugs, the diffusion of which is slowed by the relatively impermeable nature of the arterial wall.
Disclosure of the invention thus far has contemplated the injection of bioprotective material 26 between the inflating balloon and the arterial wall.
Another method of administering the bioprotective material 26 contemplates applying a thin sleeve of such material to the externaI surface of the LBA balloon.
The thin sleeve is then transferred to the luminal surface as a result of heat and pressure. Prior to heating, one or more components of the bioprotective material may be either soluble or insoluble in water.
If the component is soluble, it would be covered with a . ~:~ . . . ,. . : : . :
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' thermally labile, insoluble layer, or it could be micro encapsulated in a water insoluble, thermally labile medium. Thermal coagulation of one or more of the components of the material on the balloon would result in transfer of the balloon coating material to the luminal surface, to which it will be persistently affixed. Before transfer of the bioprotective material 26 from the balloon 22, he material could be either weakly or strongly adherent to the balloon surface. If strongly adherent, heat would destroy the adhesion between the balloon surface and the materials. This approach avoids the injection of bioprotective material ; 26 into the bloodstream. ~fter the balloon is deflated, it is likely to have a temperature between 50C and 70C. At this time, the temperature of the tissue is well above normal. Accordingly, a preferred approach is to attach the bioprotective material to the balloon with a biocompatible adhesive which remains liquid at slightly elevated temperatures, thereby allowing the bioprotective material to become preferentially bonded to the tissue rather than to the balloon.
It will thus be apparent that the invention contemplates the application of a bioprotective layer 26 to the arterial wall 28, wherein the bioprotective layer 26 is pharmacologically active and delivers high concentrations of drugs locally, so that problems of systemic toxicity are circumvented. As the balloon 22 is inflated, bioprotective materials 26 are entrapped between the balloon surface and the surface of the tissue. Such material 26 is also entrapped within fracture planes deeper within the arterial wall and within the vasa vasorum. After full inflation of the balloon 22' and physical entrapment within the arterial interstices, thermal energy is applied to the entire wall or selectively to the bioprotective material, if .
WO91/17731 '~$~ PCT/US91/02929 .
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there is provided a strongly absorbing chromophore therewithin which absorbs laser energy preferentially.
.:' The invention may be practiced by applying laser energy to heat the entire arterial wall 28 or the luminal surface alone to an elevated level above body temperature, preferably to 100C or less for a duration typically between about 15 and 60 seconds and most preferably between 15 and 30 seconds. The laser energy emanates from the interior of the balloon in a generally cylindrical pattern of light. Typically about five s~conds are needed to reach the desired temperature.
The optimal duration at the elevated level is probably between about 10 and 60 seconds. More energy is administered initially, typically ~or about 5 seconds, to rapidly raise the tissue temperature up to a target level. The delivered energy is then diminished so that the target temperature may be maintained. As the tissue is cooled by terminating laser exposure, the ~ bioprotective material, such as albumin or starch, is ; 20 bonded to the tissue.
Another technique of administering the bioprotective material is to use a perforated balloon which has tiny apertures therein and which allows the injection of bioprotective materials into the arterial wall. Such materials may then be injected under ~ pressure through the balloon material. They must ;~ ordinarily be water-soluble or, in the case of microspheres, non-aggregating, in order to avoid obstruction of capillaries in the likely event that the material will enter the general circulation through side branches adjacent to the balloons. one problem with the ; use of water soluble materials and non-aggregating microspheres is that the materials or microspheres will be washed away quickly from the arterial wall. However, . .
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by heating the material after injection, and heating only the material that is trapped in the wall, it is not free to embolize downstream and obstruct anything else.
In addition, when heat is applied to render the material both adhierent and water-insoluble or, in the case or microspheres, to induce adherence of the insoluble microspheres, the material will stay more permanently within the tissue. Although the use of thermal energy to bond bioprotective materials to the arterial wall is the preferred method, it is apparent that application of pressure alone by the angioplasty catheter could be used to rupture pressure-sensitive microcapsules, thereby releasing bioprotective materials and physiologic adhesives which would bond the bioprotective materials to tissue.
Reference was made earlier to the use of microspheres containing the drug to be administered.
Factors which influence speed of distribution of drug from a microsphere include the degree of albumin cross-linkage, for example, the size of the encapsulated molecules, and the size of the microspheres. Such ; factors can be varied in order to produce fast or slow diffusion rates. The drug emanating from such microspheres may be entrapped not only at the luminal surface where the effect of the drug is governed by the diffusion rate. But the microspheres may also be entrapped within the deep interior of cracks and the vascularity of the vasa vasorum. Such cracks will be obliterated by thermal treatment, so that the entire crack no longer will have vascular access to the general ~ blood circulation and minimal material will be irrigated : away.
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As a result of practicing the invention, there ; results a wide open, smooth channel because of thermal . . .
WO91/17731 ~ PCT/US91/02929 remodeling and bondin~ of the bioprotective material 26 to the lesion 27. Thermal energy dries up any clot, and produces a favorable luminal result. In addition, there remains a coating of drug in a bioprotective layer because a water-insoluble layer, such as albumin or - starch, is bonded to the arterial wall. Enclosed therewithin may be microcapsules containing a pharmacologically active drug disposed along the luminal - surface as well as within the deeper layers of the wall.
As another example of practicing the technique disclosed, there will now be described a recently conducted animal study. Dogs were first given a suitable dosage of pentobarbital. Selected arteries were injured. Albumin microcapsules which entrapped both heparin and a fluorescent dye were fabricated and injected intraluminally into the injured arteries bilaterally in three animals. Balloon pressure was applied without heat to ipsilateral arteries, and LBA
was applied to contralateral arteries. Blood flow was restored for one hour in one animal and for four hours ;~ in another. These animals were sacrificed after the period o~ blood flow restoration. The third animal was sacrificed acutely in order to provide a baseline for comparing the density and quantity of bioprotective material remaining adherent to the luminal sacrifice after blood flow restoration. It was found that without heat, there was minimal evidence of adherence of the fluorescent dye. At the contralateral sites, as a result of the laser exposure, fluorescent granules of the microcapsules were apparent and still present at the luminal surface. By fluorescence microscopy, no loss of bioprotective material was noted in arteries pPrfused ' ., :
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WO91/17731 2 ~ .Ç~ ~ ~ 4 -~ PCTIUS91/02929 for one and four hours, compared to the arteries of the animal sacrificed acutely.
In another example of the invention disclosed, microspheres of albumin were prepared with standard techniques using an oil/water interface and sonicating an albumin solution in an organic material such as cottonseed oil. The albumin in the microspheres ranged - in size from less than a micron up to 40-50 microns.
Such microspheres can easily be made, if required, to be uniform in size and be less than a micron in diameter.
A suspension of microspheres in physiologic saline was then applied onto the luminal surface of pig aortas in vitro. Albumin was identifiable by the presence of a fluorescent dye incorporated therewithin. When the ; 15 albumin microspheres were exposed to ultraviolet light, the dye fluoresced red. The bioprotective material was then applied to the tissue surface and covered with a sheet of polyethylene terephthalate (PET), a highly cross-linked form of polyethylene used for the LBA
balloon. Then, a transparent glass slide was applied above the PET material and the combination was subjected to pressure. Excess fluid was expressed away from the surface. While pressure was applied, the surface was ;~ exposed to about 70 watts continuous wave Nd:YAG laser ` 25 radiation for about twenty to thirty seconds over a surface area of approximately 2 square centimeters. All tissue sections were then vigorously washed in saline warmed to body temperature.
About a dozen treatment sections were examined. Absent laser exposure, all control segments showed no adherence of the microspheres to the surface.
All the laser-exposed surfaces, however, showed albumin in several different ways. A pale red color of the dye in the albumin was readily apparent both to the naked ~ '.
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' eye and with the aid of a microscope. Additionally, ; fluorescent microscopy confirmed the presenc~ of albumin in frozen sections of the tissue. Further, clumps of microsphere granules were prominent in the crevices of the tissue. The frozen sections studied revealed a satisfactory layer of the bioprotective material at the luminal surface. Stereomicroscopy confirmed that the crevices were filled by coagulated microspheres. By filling in such crevices with coagulated materials, a smoother luminal surface resulted, which produces less turbulent flow patterns and thus less tendency for clots to form.
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In a separate in vitro study, a solution of hydroxyethyl starch, a potentially clinically useful volume expander, was applied to about a dozen pig and human atheromatous aortic tissue sections. Laser exposure was performed in a manner similar to that described for the albumin microsphere study. After washing the tissue sections in normal saline, control sections not exposed to laser radiation showed no adherence of the starch, while all laser-exposed sections showed significant adherence. Light microscopy showed a uniform layer of precipitated starch granules, approximately 2 microns in size, on the luminal surface, and all laser-exposed sections demonstrated a characteristic blue color when iodine, added to the luminal surface, reacted with the precipitated, adherent starch.
Although conventional balloon angioplasty is by far the commonest angioplasty procedure which injures the arterial wall, virtually every other angioplasty procedure currently practiced or under experimental development also results in injury to the arterial wall.
Examples of alternative angioplasty techniques include ~.' .
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WO91/]7731 ~ h _ ~ ~ PCT/US91/02929 mechanical, laser-based, and ultrasonic atherectomy procedures as well as use of stents. In each case, the present invention could be used to apply bioprotective ' materials after angioplasty injury in order to reduce the incidence of lesion recurrence. Moreover, ; angioplasty catheters other than balloon catheters could be used to deliver thermal en~rgy. For example, a metal probe, positioned adjacent to the lesion to be treated, could be heated with laser, electrical resistive, radio-frequency, or microwave energy, and the bioprotective material could be heated by thermal conductiDn from the probe.
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While the preferred method of applying thermal ; energy is the use of electromagnetic radiation, ;~ 15 including laser, electrical resistive, radio-frequency, i and microwave energy sources, alternative methods may be ; used. Such methods include chemical and ultrasonic ; techni~ues. Moreover, externally focussed energy sources directed inwardly, including ultrasonic and microwave energy, could alternatively be used to heat the balloon, arkerial wall, or bioprotective material without the use of an energy-delivering catheter.
. ~ , There ha~ been provided in accordance with the invention a method for applying bioprotective materials 25 to the luminal surface and arterial wall during balloon angioplasty which addresses the needs and solves the problems remaining from conventional approaches. While the invention has been described in conjunction with specific modes for practicing the invention, it is 30 evident that many alternatives, modifications, and variations will be apparent to those sXilled in the art in light of the foregoing description. Accordingly, it is intended to embrace all such alternatives, ,~
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WO91/17731 ~ 2~ ~ PCT/US91/02929 ~ modifications, and variations as fall within the spirit~ and broad scope of the following claims.
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Combination of the loss of the endothelial layer and tearing within the wall often generates a surface which is quite thrombogenic.
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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.
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It therefore appears that in order to combat ;~ problems associated with cumulating plaque, attention ~ -must be paid to: (l) the importance of thrombus; (2) inflammatory changes; and (3) proliferation. Any combination of these factors probably accounts for most ;~ cases of restenosis.
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In order to address such problems, the cardiology community needs to administer drugs which are biocompatible and not induce toxic reactions.
` 30 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, 2 ~82~
WO91/17731 PCT/US91/0~929 ,:
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.
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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. Patent No. 4,512,762 which issued on April 23, 1985, and which is herein incorporated by reference. This patent discloses a method of injecting ~5 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 a flap of material occasionally is formed during the ~` treatment which, after withdrawal of the i instrumentation, falls bacX into the artery, thereby causing abrupt reclosure. This may necessitate ~; emergency coronary artery bypass surgery. Accordingly, .
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such techniques often provide only a temporary treatment for symptoms associated with arterial atherosclerosis.
My U.S. Patent No. 4,799,479 was issued on January 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 de~lation, a smooth cylindrically shaped channel results.
Approaches such as those disclosed in U.S.
Patent Nos. 4,512,762 and 4,799,47g, however, are directed mainly to producing an enhanced luminal result wherein a smooth luminal wall is produced. Problems of biocompatability, including thrombosis, and I proliferation of cells tend to remain. Accordingly, the 1 20 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.
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WO91/17731 PCT/US91/0~929 ~UMM~RY OF ?~E INVEN~ION
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 bioprotective material is delivered between the arterial wall and the angioplasty catheter so that the bioprotective material is entrapped therebetween and permeates into fissures in the arterial wall during apposition thereto of the angioplasty catheter. To 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 coating the luminal surface of the arterial wall with an insoluble layer of the bioprotective material so that the insoluble layer provides at least semi-permanent protection to the arterial wall, despite contact with blood flowing adjacent thereto.
................... .......................................................... ' ' 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.
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Figure lA 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;
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Figure lB is a cross-sectional view of the procedure disclosed by the present invention, in which . a bioprotective material is delivered to a lesion during : distention of an uninflated balloon;
: 5 Figure lC is a cross-sectional view of the procedure disclosed by the present invention, in which the balloon is inflated and the bioprotective material is entrapped between the balloon and the arterial wall, the bioprotective material also entering vessels of the arterial wall and fissures which result from previously administered angioplasty procedure;
Figure 2 is a cross-sectional view including enlarged portions 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 bioprotective i material and bonded by thermal energy delivered to the bioprotective material within the arterial wall being treated; and ,' Figure 3 is a cross-sectional view of the result of utilizing the procedure of the present invention, illustrating a smooth channel ormed by the insoluble layer of bioprotective material at the luminal surface and 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.
BB8T MODE5 FOR CARRYING OIJT T~I~3 lNVENq!ION
Figure lA shows a guide wire 10 which is ` 30 inserted along an artery and through a region 12 which is occluded primarily by plaque 14. Surrounding the ,, 2~
WO91/17731 PCT/US91/0~929 plaque 14 are media 60 and adventitia 18. As is now known, the plaque 14 forms an occlusion. The guide wire lO is usually a stainless steel wire having tightly coiled, but flexible springs. Conventionally, the catheter 20 is made of a plastic, or an elastomeric material and is disposed around the guide wire 10.
Following conventional angioplasty, and before applying bioprotective material 26, the balloon section 22 is maneuvered so as to lie adjacent to the plaque 14.
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Figure lB illustrates the positioning of the uninflated balloon 22 after conventional angioplasty has been performed. Expansion of the balloon 22 to position 22' (Figure lC) 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 22l 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.
The mild residual tissue pressure is helpful in applying the bioprotective material 26 to the arterial wall 28. -Referring again to Figure lC, 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 :;
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WO91/17731 2 ~ d ~ PCT/US~1/02929 '; _ g _ artery and the possibility of an acute myocardial ~ infarction.
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`~ 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 ~urfaces. Figure lC 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. ~;
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To overcome these and other problems resulting ' from prior art approaches, the method of the present invention applies the 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 20 is first positioned adjacent to the lesion 27 being treated.
Next, ths bioprotective material 26 is delivered between the arterial wall 28 and the angioplasty catheter 20.
Before completing inflation of the balloon, the bioprotective material 26 lies within fissures and vessels of the arterial wall and between the arterial wall 28 and the angioplasty catheter 20, and downstream thereof. During apposition of the angioplasty catheter 20 to the arterial wall 28, a layer of the bioprotective - 30 material 28 is entrapped therebetween. Because of capillary action and pressure exerted radially ~utwardly by the balloon, the bioprotective material 26 further enters and permeates the vessels of the arterial wall as well as the fissures and dissected planes of tissue 24.
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~` -- 10 --As a result, localized delivery of the bioprotective material 26.
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Turning now to Figure 2, it may be seen that thermal energy generated ~rom an optical diffusing tip 32 is r0presented schematically by radially emanating wavy lines. The thermal energy bonds the bioprotective material 26 to the arterial wall 28 and within the tissues 24.
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The guide wire lO may be replaced with an optical ~iber 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 there~rom and impinges upon the bioprotective material 26 and the arterial wall 28 after fracture or dissection o~ the plaque l4 has occurred following prior angioplasty. It will be apparent that there exist a variety of ways to deliver thermal energy to the area to ` ~
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,i be treated. Microwave, radio-frequency, or electrical heating of the fluid each are possible techniques.
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The invention disclosed contemplates injection of the bioprotective material 26 through the guiding catheter 20, the tip of which lies near the origin of, for example, a coronary artery before passage of a small balloon catheter through an inner channel of the guiding catheter. The bioprotectiYe material may be injected through the guiding catheter along with flowing blood.
Alternatively, the physician may use a small tube that fits over the shaft of the balloon catheter 20 and inject drugs proximal to or upstream from the balloon's location. If the physician wishes, a separate channel within the angioplasty catheter could be used to inject the bioprotective material through exit holes located in the shaft of the catheter, proximal to the balloon.
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In practicing the invention, the guide wire lO
may extend through a central channel in the balloon and extend down the arterial lesion path. Alternatively, the guide wire lO can be fixed to a central channel in the balloon or be freely movable with respect thereto.
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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 thicker layers of - bioprotective material 26 are required, then the disclosed technique can be used repeatedly.
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~ ~$.~9 W~91/17731 PCT/US91/0~929 Referring now to Figure 3, after removing the angioplasty catheter 20, 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. Although balloons can be used to deliver stents which act as scaffolding devices, the struts of the stents generally are inherently thrombogenic as a result of disruption of laminar flow adjacent to each stent and at the axial ends thereof. Continuous, smooth-walled stents can be fabricated, but use of such stents could result in occlusion of large side branches which are invariably present in coronary arteri~s. In addition, stents may elicit a foreign body inflammatory reaction, are technically difficult to place, and are relatively unforgiving if placed inappropriately.
As a result of the ~ontribution 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 '.' " ~' ' .
WO91/17731 ~ ~ PCT/US91/02929 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 ; 5 present invention, thermal energy is applied ~o 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. Following the teachings of the present invention, drugs may now be incorporated into the biocompatible layer to mitigate any adverse biologic responses of the arterial wall to mechanical or ' thermal injury.
One method of applying the biocompatible layer to the luminal surface contemplates injecting a solution or fine dispersion o~ one or a combination of materials into the artery during balloon inflation. At least one component of the materials becomes bonded to the luminal surface by undergoing a physical change such as a phase transition, transient breakage of non-covalent bonds with subsequent cross-linkage with both itself and the arterial wall upon cooling, or by a chemical reaction, such as polymerization. The coating of bioprotective ; material thereby provided is a relatively water-insoluble layer which is bonded to tissues at the luminal surface. This layer will persist chronically, -despite contact with flowing blood, unlike a water-soluble material.
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WO9~/17731 PC~/US91/0~929 :`
A preferred techni~ue calls for the use of albumin in solution, which is trapped between the balloon 22 and luminal surface 29 during balloon inflation. 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 cellsl fibrinogen, and collagen.
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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 precipitated layer of albumin is insoluble, it may persist on the luminal surface for at least four weeks before the layer of albumin disappears.
By that time, the surface may be completely healed with a new confluent layer of ingrowing endothelial cells, which typically takes about two weeks.
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It is also possible to apply directly to the arterial wall 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 :
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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 drug which is physically and/or chemically trapped within or by the precipitated layer of albumin. Microspheres 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 cros~-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 are injected into the artery, with or without albumin in solution, 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. 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 glycolide, lactide, silicone, polyvinylpyrrolidone, poly (methyl methacrylate), and polyamide polymers; ethylene-vinyl acetate copolymer; polyesters such as polyglactin, vicryl, Dexon, and polydioxanone polymers; and .
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W091/17731 21~q~2~ ~ PCT/US91/~2929 ;
hydrogels, such as poly (hydroxyethyl methacrylate), polyacrylamide, polyvinyl alcohol, and gamma-irradiated polyelectrolytes. Additionally, endogenous platelets, removed from the same patient to he 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, 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 balloon-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.
~oth 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 (heparan sulfate;
dermatan sulfate and equivalents), collagen inhibitors (colchicine; D-penicillamine; l, lO phenanthroline, and equivalents), and endothelial cell growth promotors. In .. . . .
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WO91/17731 2~3~t ~1 s~ PCT/US91/02929 . .
addition, a chromophore may be encapsulated in order to enhance absorption of electromagnetic radiation.
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Alternatively, a photosensitive drug such as a porphyrin may be encapsulated in order to enhance photodynamic therapy of tissues within which the microcapsules are thermally bonded. When a chromophore , is encapsulated at the surface of microcapsules, the use ;~ of pulsed electromagnetic radiation, the wavelength of which matches the absorption spectrum of the chromophore, could be used to selectively and briefly heat only the surface of each microcapsule to bond the microcapsules to the luminal surface, without damaging thermally labile materials encapsulated within the interior of the microcapsules. It will be apparent to those of ordinary skill that many variations of the concept are possible.
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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.
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A further benefit of the invention results m from the small vessels within the plaque and normal ` 25 arterial wall (vasa vasorum) being filled with the ~-material delivered during balloon inflation. Thermal .
cross-linking of at least one of the materials, such as albumin, effectively bonds the materials to the luminal surface of the small vessels. In addition, the material fills and become bonded to tissues lining fissures and dissections. Drugs are therefore delivered throughout ;~ the full thickness of the plaque and arterial wall.
Moreover, the bioprotective material, when trapped ;
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WO91/17731 ~}~ PCT/US91/02929 between dissected tissues, could additionally be used to enhance thermal fusion thereof. A level of coagulation or precipitation achieved by thermal exposure alone is generally insufficient to obliterate side branches larger than about 0.5 mm because the radially directed pressure applied by the inflated balloon does not bring opposing walls of the lumen of a side branch firmly together, a necessary condition for thermal closure of such arteries.
.. ~ , Obliteration of the lumina of small vessels of the arterial wall is achievable by thermally coagulating a sufficient amount of albumin within the lumina or by thermally bonding opposing walls of the small vessels which are coapted by pressure. As a result, the entire balloon-dilated arterial segment would be rendered relatively impermeable to blood and blood-born components. For example, infiltration of leukocytes into the plaque and arterial wall is greatly slowed, and permeation of growth factors and of mediators of inflammation is impeded. Likewise, the thermally treated arterial wall provides a semi-permanent depot for entrapped drugs, the diffusion of which is slowed by the relatively impermeable nature of the arterial wall.
Disclosure of the invention thus far has contemplated the injection of bioprotective material 26 between the inflating balloon and the arterial wall.
Another method of administering the bioprotective material 26 contemplates applying a thin sleeve of such material to the externaI surface of the LBA balloon.
The thin sleeve is then transferred to the luminal surface as a result of heat and pressure. Prior to heating, one or more components of the bioprotective material may be either soluble or insoluble in water.
If the component is soluble, it would be covered with a . ~:~ . . . ,. . : : . :
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' thermally labile, insoluble layer, or it could be micro encapsulated in a water insoluble, thermally labile medium. Thermal coagulation of one or more of the components of the material on the balloon would result in transfer of the balloon coating material to the luminal surface, to which it will be persistently affixed. Before transfer of the bioprotective material 26 from the balloon 22, he material could be either weakly or strongly adherent to the balloon surface. If strongly adherent, heat would destroy the adhesion between the balloon surface and the materials. This approach avoids the injection of bioprotective material ; 26 into the bloodstream. ~fter the balloon is deflated, it is likely to have a temperature between 50C and 70C. At this time, the temperature of the tissue is well above normal. Accordingly, a preferred approach is to attach the bioprotective material to the balloon with a biocompatible adhesive which remains liquid at slightly elevated temperatures, thereby allowing the bioprotective material to become preferentially bonded to the tissue rather than to the balloon.
It will thus be apparent that the invention contemplates the application of a bioprotective layer 26 to the arterial wall 28, wherein the bioprotective layer 26 is pharmacologically active and delivers high concentrations of drugs locally, so that problems of systemic toxicity are circumvented. As the balloon 22 is inflated, bioprotective materials 26 are entrapped between the balloon surface and the surface of the tissue. Such material 26 is also entrapped within fracture planes deeper within the arterial wall and within the vasa vasorum. After full inflation of the balloon 22' and physical entrapment within the arterial interstices, thermal energy is applied to the entire wall or selectively to the bioprotective material, if .
WO91/17731 '~$~ PCT/US91/02929 .
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there is provided a strongly absorbing chromophore therewithin which absorbs laser energy preferentially.
.:' The invention may be practiced by applying laser energy to heat the entire arterial wall 28 or the luminal surface alone to an elevated level above body temperature, preferably to 100C or less for a duration typically between about 15 and 60 seconds and most preferably between 15 and 30 seconds. The laser energy emanates from the interior of the balloon in a generally cylindrical pattern of light. Typically about five s~conds are needed to reach the desired temperature.
The optimal duration at the elevated level is probably between about 10 and 60 seconds. More energy is administered initially, typically ~or about 5 seconds, to rapidly raise the tissue temperature up to a target level. The delivered energy is then diminished so that the target temperature may be maintained. As the tissue is cooled by terminating laser exposure, the ~ bioprotective material, such as albumin or starch, is ; 20 bonded to the tissue.
Another technique of administering the bioprotective material is to use a perforated balloon which has tiny apertures therein and which allows the injection of bioprotective materials into the arterial wall. Such materials may then be injected under ~ pressure through the balloon material. They must ;~ ordinarily be water-soluble or, in the case of microspheres, non-aggregating, in order to avoid obstruction of capillaries in the likely event that the material will enter the general circulation through side branches adjacent to the balloons. one problem with the ; use of water soluble materials and non-aggregating microspheres is that the materials or microspheres will be washed away quickly from the arterial wall. However, . .
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by heating the material after injection, and heating only the material that is trapped in the wall, it is not free to embolize downstream and obstruct anything else.
In addition, when heat is applied to render the material both adhierent and water-insoluble or, in the case or microspheres, to induce adherence of the insoluble microspheres, the material will stay more permanently within the tissue. Although the use of thermal energy to bond bioprotective materials to the arterial wall is the preferred method, it is apparent that application of pressure alone by the angioplasty catheter could be used to rupture pressure-sensitive microcapsules, thereby releasing bioprotective materials and physiologic adhesives which would bond the bioprotective materials to tissue.
Reference was made earlier to the use of microspheres containing the drug to be administered.
Factors which influence speed of distribution of drug from a microsphere include the degree of albumin cross-linkage, for example, the size of the encapsulated molecules, and the size of the microspheres. Such ; factors can be varied in order to produce fast or slow diffusion rates. The drug emanating from such microspheres may be entrapped not only at the luminal surface where the effect of the drug is governed by the diffusion rate. But the microspheres may also be entrapped within the deep interior of cracks and the vascularity of the vasa vasorum. Such cracks will be obliterated by thermal treatment, so that the entire crack no longer will have vascular access to the general ~ blood circulation and minimal material will be irrigated : away.
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As a result of practicing the invention, there ; results a wide open, smooth channel because of thermal . . .
WO91/17731 ~ PCT/US91/02929 remodeling and bondin~ of the bioprotective material 26 to the lesion 27. Thermal energy dries up any clot, and produces a favorable luminal result. In addition, there remains a coating of drug in a bioprotective layer because a water-insoluble layer, such as albumin or - starch, is bonded to the arterial wall. Enclosed therewithin may be microcapsules containing a pharmacologically active drug disposed along the luminal - surface as well as within the deeper layers of the wall.
As another example of practicing the technique disclosed, there will now be described a recently conducted animal study. Dogs were first given a suitable dosage of pentobarbital. Selected arteries were injured. Albumin microcapsules which entrapped both heparin and a fluorescent dye were fabricated and injected intraluminally into the injured arteries bilaterally in three animals. Balloon pressure was applied without heat to ipsilateral arteries, and LBA
was applied to contralateral arteries. Blood flow was restored for one hour in one animal and for four hours ;~ in another. These animals were sacrificed after the period o~ blood flow restoration. The third animal was sacrificed acutely in order to provide a baseline for comparing the density and quantity of bioprotective material remaining adherent to the luminal sacrifice after blood flow restoration. It was found that without heat, there was minimal evidence of adherence of the fluorescent dye. At the contralateral sites, as a result of the laser exposure, fluorescent granules of the microcapsules were apparent and still present at the luminal surface. By fluorescence microscopy, no loss of bioprotective material was noted in arteries pPrfused ' ., :
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WO91/17731 2 ~ .Ç~ ~ ~ 4 -~ PCTIUS91/02929 for one and four hours, compared to the arteries of the animal sacrificed acutely.
In another example of the invention disclosed, microspheres of albumin were prepared with standard techniques using an oil/water interface and sonicating an albumin solution in an organic material such as cottonseed oil. The albumin in the microspheres ranged - in size from less than a micron up to 40-50 microns.
Such microspheres can easily be made, if required, to be uniform in size and be less than a micron in diameter.
A suspension of microspheres in physiologic saline was then applied onto the luminal surface of pig aortas in vitro. Albumin was identifiable by the presence of a fluorescent dye incorporated therewithin. When the ; 15 albumin microspheres were exposed to ultraviolet light, the dye fluoresced red. The bioprotective material was then applied to the tissue surface and covered with a sheet of polyethylene terephthalate (PET), a highly cross-linked form of polyethylene used for the LBA
balloon. Then, a transparent glass slide was applied above the PET material and the combination was subjected to pressure. Excess fluid was expressed away from the surface. While pressure was applied, the surface was ;~ exposed to about 70 watts continuous wave Nd:YAG laser ` 25 radiation for about twenty to thirty seconds over a surface area of approximately 2 square centimeters. All tissue sections were then vigorously washed in saline warmed to body temperature.
About a dozen treatment sections were examined. Absent laser exposure, all control segments showed no adherence of the microspheres to the surface.
All the laser-exposed surfaces, however, showed albumin in several different ways. A pale red color of the dye in the albumin was readily apparent both to the naked ~ '.
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' eye and with the aid of a microscope. Additionally, ; fluorescent microscopy confirmed the presenc~ of albumin in frozen sections of the tissue. Further, clumps of microsphere granules were prominent in the crevices of the tissue. The frozen sections studied revealed a satisfactory layer of the bioprotective material at the luminal surface. Stereomicroscopy confirmed that the crevices were filled by coagulated microspheres. By filling in such crevices with coagulated materials, a smoother luminal surface resulted, which produces less turbulent flow patterns and thus less tendency for clots to form.
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In a separate in vitro study, a solution of hydroxyethyl starch, a potentially clinically useful volume expander, was applied to about a dozen pig and human atheromatous aortic tissue sections. Laser exposure was performed in a manner similar to that described for the albumin microsphere study. After washing the tissue sections in normal saline, control sections not exposed to laser radiation showed no adherence of the starch, while all laser-exposed sections showed significant adherence. Light microscopy showed a uniform layer of precipitated starch granules, approximately 2 microns in size, on the luminal surface, and all laser-exposed sections demonstrated a characteristic blue color when iodine, added to the luminal surface, reacted with the precipitated, adherent starch.
Although conventional balloon angioplasty is by far the commonest angioplasty procedure which injures the arterial wall, virtually every other angioplasty procedure currently practiced or under experimental development also results in injury to the arterial wall.
Examples of alternative angioplasty techniques include ~.' .
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WO91/]7731 ~ h _ ~ ~ PCT/US91/02929 mechanical, laser-based, and ultrasonic atherectomy procedures as well as use of stents. In each case, the present invention could be used to apply bioprotective ' materials after angioplasty injury in order to reduce the incidence of lesion recurrence. Moreover, ; angioplasty catheters other than balloon catheters could be used to deliver thermal en~rgy. For example, a metal probe, positioned adjacent to the lesion to be treated, could be heated with laser, electrical resistive, radio-frequency, or microwave energy, and the bioprotective material could be heated by thermal conductiDn from the probe.
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While the preferred method of applying thermal ; energy is the use of electromagnetic radiation, ;~ 15 including laser, electrical resistive, radio-frequency, i and microwave energy sources, alternative methods may be ; used. Such methods include chemical and ultrasonic ; techni~ues. Moreover, externally focussed energy sources directed inwardly, including ultrasonic and microwave energy, could alternatively be used to heat the balloon, arkerial wall, or bioprotective material without the use of an energy-delivering catheter.
. ~ , There ha~ been provided in accordance with the invention a method for applying bioprotective materials 25 to the luminal surface and arterial wall during balloon angioplasty which addresses the needs and solves the problems remaining from conventional approaches. While the invention has been described in conjunction with specific modes for practicing the invention, it is 30 evident that many alternatives, modifications, and variations will be apparent to those sXilled in the art in light of the foregoing description. Accordingly, it is intended to embrace all such alternatives, ,~
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WO91/17731 ~ 2~ ~ PCT/US91/02929 ~ modifications, and variations as fall within the spirit~ and broad scope of the following claims.
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Claims (62)
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 including fissures resulting therefrom, the method comprising the steps of:
positioning an angioplasty catheter adjacent to the lesion being treated;
delivering a bioprotective material between the arterial wall and the angioplasty catheter so that the bioprotective material is entrapped therebetween and permeates into the fissures and vessels of the arterial wall during apposition of the angioplasty catheter thereto;
applying thermal energy to the lesion, thereby bonding 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 arterial wall and within the fissures and vessels thereof, thereby coating the luminal surface with an insoluble layer of the bioprotective material so that the insoluble layer provides at least semi-permanent protection to the arterial wall, despite contact with blood flowing adjacent thereto.
positioning an angioplasty catheter adjacent to the lesion being treated;
delivering a bioprotective material between the arterial wall and the angioplasty catheter so that the bioprotective material is entrapped therebetween and permeates into the fissures and vessels of the arterial wall during apposition of the angioplasty catheter thereto;
applying thermal energy to the lesion, thereby bonding 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 arterial wall and within the fissures and vessels thereof, thereby coating the luminal surface with an insoluble layer of the bioprotective material so that the insoluble layer provides at least semi-permanent protection to the arterial wall, despite contact with blood flowing adjacent thereto.
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 bioprotective material between the AMENDED CLAIMS
[received by the International Bureau on 4 September 1991 (04.09.91) original claims 4,8,26-36 amended; remaining claims unchanged (4 pages)]
arterial wall and the inflatable balloon so that the layer of the bioprotective material may be formed therebetween.
[received by the International Bureau on 4 September 1991 (04.09.91) original claims 4,8,26-36 amended; remaining claims unchanged (4 pages)]
arterial wall and the inflatable balloon so that the layer of the bioprotective material may be formed therebetween.
4. The method of claim 1 wherein the bioprotective material utilized is macro aggregated albumin which upon being trapped between the inflatable balloon and the luminal surface 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 utilized comprises platelets, injected as a suspension, which upon being trapped between the inflatable balloon and the luminal surface 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, injected as a suspension, which upon being trapped between the inflatable balloon and the luminal surface 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, injected as a suspension, which upon being trapped between the inflatable balloon and the luminal surface 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 bioprotective material utilized is gelatin which upon being trapped between the inflatable balloon and the luminal surface 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 is a solution of fibrinogen which upon being trapped between the inflatable balloon and 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.
10. The method of claim 1 wherein the bioprotective material utilized is a solution of collagen which upon being trapped between the inflatable balloon and 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 is a solution of a high molecular carbohydrate which upon being trapped between the inflatable balloon and 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.
12. 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 deeper layers of the arterial wall.
13. The method of claim 12 wherein the useful pharmaceutical agent is an anti-coagulant.
14. The method of claim 12 wherein the useful pharmaceutical agent is a fibrinolytic agent.
15. The method of claim 12 wherein the useful pharmaceutical agent is a thrombolytic agent.
16. The method of claim 12 wherein the useful pharmaceutical agent is an anti-inflammatory agent.
17. The method of claim 12 wherein the useful pharmaceutical is an anti-proliferative compound.
18. The method of claim 12 wherein the useful pharmaceutical is an immunosuppressant.
19. The method of claim 12 wherein the useful pharmaceutical is a collagen inhibitor.
20. The method of claim 12 wherein the useful pharmaceutical is an endothelial cell growth promotor.
21. The method of claim 12 wherein the useful pharmaceutical is a sulfated polysaccharide.
22. The method of claim 1 wherein the bioprotective material includes a drug which is bound to albumin in solution prior to injection so that the drug is permanently affixed thereto by application of the thermal energy.
23. The method of claim 1 wherein the bioprotective material includes a drug which is physically trapped within a precipitated layer of albumin after the drug is injected with a solution of albumin.
24. The method of claim 1 wherein the bioprotective material comprises microspheres.
25. The method of claim 1 wherein the bioprotective material includes a drug preparation having an encapsulating medium.
26. The method of claim 25 wherein the encapsulating medium comprises albumin.
27. The method of claim 25 wherein the encapsulating medium comprises carbohydrates.
28. The method of claim 25 wherein the encapsulating medium comprises platelets.
29. The method of claim 25 wherein the encapsulating medium comprises liposomes.
30. The method of claim 25 wherein the encapsulating medium comprises red blood cells.
31. The method of claim 25 wherein the encapsulating medium comprises gelatin.
32. The method of claim 25 wherein the encapsulating medium comprises fibrin.
33. The method of claim 25 wherein the encapsulating medium comprises a synthetic polymer.
34. The method of claim 25 wherein the encapsulating medium comprises a sulfated polysaccharide.
35. The method of claim 25 wherein the encapsulating medium comprises an inorganic salt.
36. The method of claim 25 wherein the encapsulating medium comprises a phosphate glass.
37. The method of claim 1 wherein the bioprotective material is a suspension of microspheres in a physiologic solution.
38. The method of claim 1 wherein the bioprotective material remaining adherent to the arterial wall, and filling cracks and recesses therewithin after removal of the angioplasty catheter, provides a smooth, luminal surface.
39. The method of claim 1 wherein the bioprotective material is delivered from a sleeve thereof provided upon the angioplasty catheter, the sleeve being disposed adjacent the arterial wall during apposition of the angioplastic catheter thereto, so that the sleeve of bioprotective material is transferred therefrom to the luminal surface, thereby becoming persistently affixed thereto upon applying the thermal energy and removing the angioplasty catheter.
40. 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 bioprotective material.
41. The method of claim 1 wherein a drug, simultaneously injected with the bioprotective material, is entrapped within microspheres.
42. 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.
43. The method of claim 1 wherein the bioprotective material includes a chromophore which enhances absorption of electromagnetic radiation.
44. The method of claim 1 wherein a photosensitive dye is entrapped within the bioprotective material.
45. The method of claim 25 wherein the encapsulating medium comprises a chromophore which enhances absorption of electromagnetic radiation.
46. The method of claim 45 wherein the encapsulating medium entraps a photosensitive dye.
47. The method of claim 1 wherein the angioplasty catheter is a metal probe.
48. The method of claim 1 wherein the applied thermal energy is electromagnetic radiation.
49. The method of claim 48 wherein the applied thermal energy is continuous wave electromagnetic radiation.
50. The method of claim 48 wherein the applied thermal energy is pulsed electromagnetic radiation.
51. The method of claim 48 wherein the electromagnetic radiation is laser radiation.
52. The method of claim 48 wherein the electromagnetic radiation is radio-frequency radiation.
53. The method of claim 48 wherein the electromagnetic radiation is microwave radiation.
54. The method of claim 48 wherein the electromagnetic radiation is generated from electrical resistance.
55. The method of claim 1 wherein the bioprotective material is injected into the artery through the angioplasty catheter which is placed proximal to the lesion being treated.
56. The method of claim 2 wherein the bioprotective material is injected through a channel within the angioplasty catheter to the arterial wall by exiting through ports located proximal to the inflatable balloon.
57. The method of claim 2 wherein the bioprotective material is injected through the angioplasty catheter to the arterial wall through microscopic perforations provided within the inflatable balloon.
58. 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 including fissures resulting therefrom, the method comprising the steps of:
positioning an angioplasty catheter adjacent to the lesion being treated;
delivering a bioprotective material between the arterial wall and the angioplasty catheter so that the bioprotective material is entrapped therebetween and permeates into the fissures and vessels of the arterial wall during apposition of the angioplasty catheter thereto; and removing the angioplasty catheter, the bioprotective material remaining adherent to the arterial wall and within the fissures and vessels thereof, thereby coating the luminal surface with an insoluble layer of the bioprotective material so that the insoluble layer provides at least semi-permanent protection to the arterial wall, despite contact with blood flowing adjacent thereto.
positioning an angioplasty catheter adjacent to the lesion being treated;
delivering a bioprotective material between the arterial wall and the angioplasty catheter so that the bioprotective material is entrapped therebetween and permeates into the fissures and vessels of the arterial wall during apposition of the angioplasty catheter thereto; and removing the angioplasty catheter, the bioprotective material remaining adherent to the arterial wall and within the fissures and vessels thereof, thereby coating the luminal surface with an insoluble layer of the bioprotective material so that the insoluble layer provides at least semi-permanent protection to the arterial wall, despite contact with blood flowing adjacent thereto.
59. A method for treating a lesion in an arterial wall having plaque thereon and a luminal surface, the arterial wall and the plaque including fissures resulting therefrom, the method comprising the steps of:
performing angioplasty;
positioning an angioplasty catheter adjacent to the lesion being treated;
delivering a bioprotective material between the arterial wall and the angioplasty catheter so that the bioprotective material is entrapped therebetween and permeates into the fissures and vessels of the arterial wall during apposition of the angioplasty catheter thereto; and removing the angioplasty catheter, the bioprotective material remaining adherent to the arterial wall and within the fissures and vessels thereof, thereby coating the luminal surface with an insoluble layer of the bioprotective material so that the insoluble layer provides at least semi-permanent protection to the arterial wall, despite contact with blood flowing adjacent thereto.
performing angioplasty;
positioning an angioplasty catheter adjacent to the lesion being treated;
delivering a bioprotective material between the arterial wall and the angioplasty catheter so that the bioprotective material is entrapped therebetween and permeates into the fissures and vessels of the arterial wall during apposition of the angioplasty catheter thereto; and removing the angioplasty catheter, the bioprotective material remaining adherent to the arterial wall and within the fissures and vessels thereof, thereby coating the luminal surface with an insoluble layer of the bioprotective material so that the insoluble layer provides at least semi-permanent protection to the arterial wall, despite contact with blood flowing adjacent thereto.
60. The method of claim 59, further comprising the steps of:
applying thermal energy to the lesion, thereby bonding the bioprotective material to the arterial wall and within the fissures and vessels of the arterial wall.
applying thermal energy to the lesion, thereby bonding the bioprotective material to the arterial wall and within the fissures and vessels of the arterial wall.
61. 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.
62. The method of claim 1 wherein the step of applying thermal energy to the lesion comprises delivering the thermal energy from a source thereof disposed outside the arterial wall radially inwardly.
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US07/525,104 US5092841A (en) | 1990-05-17 | 1990-05-17 | Method for treating an arterial wall injured during angioplasty |
US525,104 | 1990-05-17 | ||
PCT/US1991/002929 WO1991017731A1 (en) | 1990-05-17 | 1991-04-29 | Method for treating an arterial wall injured during angioplasty |
Publications (1)
Publication Number | Publication Date |
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CA2082149A1 true CA2082149A1 (en) | 1991-11-18 |
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ID=24091939
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA002082149A Abandoned CA2082149A1 (en) | 1990-05-17 | 1991-04-29 | Method for treating an arterial wall injured during angioplasty |
Country Status (5)
Country | Link |
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US (1) | US5092841A (en) |
EP (1) | EP0528869A4 (en) |
JP (1) | JPH05507010A (en) |
CA (1) | CA2082149A1 (en) |
WO (1) | WO1991017731A1 (en) |
Families Citing this family (318)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5843156A (en) | 1988-08-24 | 1998-12-01 | Endoluminal Therapeutics, Inc. | Local polymeric gel cellular therapy |
DE68922497T2 (en) * | 1988-08-24 | 1995-09-14 | Marvin J Slepian | ENDOLUMINAL SEAL WITH BISDEGRADABLE POLYMERS. |
US5634946A (en) * | 1988-08-24 | 1997-06-03 | Focal, Inc. | Polymeric endoluminal paving process |
US5662701A (en) * | 1989-08-18 | 1997-09-02 | Endovascular Instruments, Inc. | Anti-stenotic method and product for occluded and partially occluded arteries |
US5571169A (en) * | 1993-06-07 | 1996-11-05 | Endovascular Instruments, Inc. | Anti-stenotic method and product for occluded and partially occluded arteries |
CA2067110C (en) * | 1989-09-08 | 2001-07-31 | John E. Abele | Physiologic low stress angioplasty |
US5624392A (en) | 1990-05-11 | 1997-04-29 | Saab; Mark A. | Heat transfer catheters and methods of making and using same |
US5290271A (en) * | 1990-05-14 | 1994-03-01 | Jernberg Gary R | Surgical implant and method for controlled release of chemotherapeutic agents |
US5199951A (en) * | 1990-05-17 | 1993-04-06 | Wayne State University | Method of drug application in a transporting medium to an arterial wall injured during angioplasty |
US5190540A (en) * | 1990-06-08 | 1993-03-02 | Cardiovascular & Interventional Research Consultants, Inc. | Thermal balloon angioplasty |
US5910489A (en) * | 1990-09-18 | 1999-06-08 | Hyal Pharmaceutical Corporation | Topical composition containing hyaluronic acid and NSAIDS |
CA2061703C (en) * | 1992-02-20 | 2002-07-02 | Rudolf E. Falk | Formulations containing hyaluronic acid |
US5990096A (en) * | 1990-09-18 | 1999-11-23 | Hyal Pharmaceutical Corporation | Formulations containing hyaluronic acid |
US5824658A (en) * | 1990-09-18 | 1998-10-20 | Hyal Pharmaceutical Corporation | Topical composition containing hyaluronic acid and NSAIDS |
US5354324A (en) * | 1990-10-18 | 1994-10-11 | The General Hospital Corporation | Laser induced platelet inhibition |
US5324261A (en) * | 1991-01-04 | 1994-06-28 | Medtronic, Inc. | Drug delivery balloon catheter with line of weakness |
US5893840A (en) * | 1991-01-04 | 1999-04-13 | Medtronic, Inc. | Releasable microcapsules on balloon catheters |
US5171217A (en) * | 1991-02-28 | 1992-12-15 | Indiana University Foundation | Method for delivery of smooth muscle cell inhibitors |
US5977088A (en) * | 1991-07-03 | 1999-11-02 | Hyal Pharmaceutical Corporation | Formulations containing hyaluronic acid |
US5990095A (en) | 1991-07-03 | 1999-11-23 | Hyal Pharmaceutical Corporation | Use of hyaluronic acid and forms to prevent arterial restenosis |
US5222949A (en) * | 1991-07-23 | 1993-06-29 | Intermed, Inc. | Flexible, noncollapsible catheter tube with hard and soft regions |
CA2074304C (en) * | 1991-08-02 | 1996-11-26 | Cyril J. Schweich, Jr. | Drug delivery catheter |
WO1993006792A1 (en) | 1991-10-04 | 1993-04-15 | Scimed Life Systems, Inc. | Biodegradable drug delivery vascular stent |
US5500013A (en) | 1991-10-04 | 1996-03-19 | Scimed Life Systems, Inc. | Biodegradable drug delivery vascular stent |
US5176692A (en) * | 1991-12-09 | 1993-01-05 | Wilk Peter J | Method and surgical instrument for repairing hernia |
US6218373B1 (en) | 1992-02-20 | 2001-04-17 | Hyal Pharmaceutical Corporation | Formulations containing hyaluronic acid |
US5767106A (en) * | 1992-02-21 | 1998-06-16 | Hyal Pharmaceutical Corporation | Treatment of disease and conditions associated with macrophage infiltration |
US5344398A (en) * | 1992-02-25 | 1994-09-06 | Japan Crescent, Inc. | Heated balloon catheter |
US5599352A (en) * | 1992-03-19 | 1997-02-04 | Medtronic, Inc. | Method of making a drug eluting stent |
US5510077A (en) * | 1992-03-19 | 1996-04-23 | Dinh; Thomas Q. | Method of making an intraluminal stent |
US5591224A (en) * | 1992-03-19 | 1997-01-07 | Medtronic, Inc. | Bioelastomeric stent |
US5571166A (en) * | 1992-03-19 | 1996-11-05 | Medtronic, Inc. | Method of making an intraluminal stent |
EP0566245B1 (en) * | 1992-03-19 | 1999-10-06 | Medtronic, Inc. | Intraluminal stent |
US5330490A (en) * | 1992-04-10 | 1994-07-19 | Wilk Peter J | Endoscopic device, prosthesis and method for use in endovascular repair |
US5578008A (en) * | 1992-04-22 | 1996-11-26 | Japan Crescent, Inc. | Heated balloon catheter |
US5443470A (en) * | 1992-05-01 | 1995-08-22 | Vesta Medical, Inc. | Method and apparatus for endometrial ablation |
US5277201A (en) * | 1992-05-01 | 1994-01-11 | Vesta Medical, Inc. | Endometrial ablation apparatus and method |
US5562720A (en) * | 1992-05-01 | 1996-10-08 | Vesta Medical, Inc. | Bipolar/monopolar endometrial ablation device and method |
US6623516B2 (en) * | 1992-08-13 | 2003-09-23 | Mark A. Saab | Method for changing the temperature of a selected body region |
US5807306A (en) * | 1992-11-09 | 1998-09-15 | Cortrak Medical, Inc. | Polymer matrix drug delivery apparatus |
US5304117A (en) * | 1992-11-27 | 1994-04-19 | Wilk Peter J | Closure method for use in laparoscopic surgery |
US5409483A (en) * | 1993-01-22 | 1995-04-25 | Jeffrey H. Reese | Direct visualization surgical probe |
US5837003A (en) * | 1993-02-10 | 1998-11-17 | Radiant Medical, Inc. | Method and apparatus for controlling a patient's body temperature by in situ blood temperature modification |
US6849083B2 (en) * | 1993-02-10 | 2005-02-01 | Radiant Medical, Inc. | Method and apparatus for controlling a patients's body temperature by in situ blood temperature modification |
US5486208A (en) * | 1993-02-10 | 1996-01-23 | Ginsburg; Robert | Method and apparatus for controlling a patient's body temperature by in situ blood temperature modification |
US6110168A (en) * | 1993-02-10 | 2000-08-29 | Radiant Medical, Inc. | Method and apparatus for controlling a patient's body temperature by in situ blood temperature modifications |
US6033383A (en) * | 1996-12-19 | 2000-03-07 | Ginsburg; Robert | Temperature regulating catheter and methods |
US6620188B1 (en) * | 1998-08-24 | 2003-09-16 | Radiant Medical, Inc. | Methods and apparatus for regional and whole body temperature modification |
US6004547A (en) | 1997-09-29 | 1999-12-21 | Focal, Inc. | Apparatus and method for local application of polymeric material to tissue |
DE69414558T2 (en) * | 1993-03-23 | 1999-07-15 | Focal Inc | DEVICE AND METHOD FOR LOCAL APPLICATION OF POLYMER MATERIAL ON FABRIC |
US5464650A (en) * | 1993-04-26 | 1995-11-07 | Medtronic, Inc. | Intravascular stent and method |
US5824048A (en) * | 1993-04-26 | 1998-10-20 | Medtronic, Inc. | Method for delivering a therapeutic substance to a body lumen |
US20020055710A1 (en) * | 1998-04-30 | 2002-05-09 | Ronald J. Tuch | Medical device for delivering a therapeutic agent and method of preparation |
US5849035A (en) * | 1993-04-28 | 1998-12-15 | Focal, Inc. | Methods for intraluminal photothermoforming |
US5716410A (en) * | 1993-04-30 | 1998-02-10 | Scimed Life Systems, Inc. | Temporary stent and method of use |
CN100998869A (en) * | 1993-07-19 | 2007-07-18 | 血管技术药物公司 | Anti-angiogene compositions and methods of use |
US5994341A (en) * | 1993-07-19 | 1999-11-30 | Angiogenesis Technologies, Inc. | Anti-angiogenic Compositions and methods for the treatment of arthritis |
US5599307A (en) * | 1993-07-26 | 1997-02-04 | Loyola University Of Chicago | Catheter and method for the prevention and/or treatment of stenotic processes of vessels and cavities |
WO1995008289A2 (en) | 1993-09-16 | 1995-03-30 | Scimed Life Systems, Inc. | Percutaneous repair of cardiovascular anomalies and repair compositions |
US5443495A (en) * | 1993-09-17 | 1995-08-22 | Scimed Lifesystems Inc. | Polymerization angioplasty balloon implant device |
US5545209A (en) * | 1993-09-30 | 1996-08-13 | Texas Petrodet, Inc. | Controlled deployment of a medical device |
WO1995010989A1 (en) * | 1993-10-19 | 1995-04-27 | Scimed Life Systems, Inc. | Intravascular stent pump |
US5397307A (en) * | 1993-12-07 | 1995-03-14 | Schneider (Usa) Inc. | Drug delivery PTCA catheter and method for drug delivery |
US5417689A (en) * | 1994-01-18 | 1995-05-23 | Cordis Corporation | Thermal balloon catheter and method |
US5411016A (en) | 1994-02-22 | 1995-05-02 | Scimed Life Systems, Inc. | Intravascular balloon catheter for use in combination with an angioscope |
US5470307A (en) * | 1994-03-16 | 1995-11-28 | Lindall; Arnold W. | Catheter system for controllably releasing a therapeutic agent at a remote tissue site |
US5415636A (en) * | 1994-04-13 | 1995-05-16 | Schneider (Usa) Inc | Dilation-drug delivery catheter |
US5665063A (en) * | 1994-06-24 | 1997-09-09 | Focal, Inc. | Methods for application of intraluminal photopolymerized gels |
US5514092A (en) * | 1994-08-08 | 1996-05-07 | Schneider (Usa) Inc. | Drug delivery and dilatation-drug delivery catheters in a rapid exchange configuration |
US5914345A (en) * | 1994-10-11 | 1999-06-22 | Endoluminal Therapeutics, Inc. | Treatment of tissues to reduce subsequent response to injury |
US5786214A (en) * | 1994-12-15 | 1998-07-28 | Spinal Cord Society | pH-sensitive immunoliposomes and method of gene delivery to the mammalian central nervous system |
US5749851A (en) * | 1995-03-02 | 1998-05-12 | Scimed Life Systems, Inc. | Stent installation method using balloon catheter having stepped compliance curve |
SE510517C2 (en) * | 1995-05-12 | 1999-05-31 | Prostalund Operations Ab | Device for maintaining passage through the prostate gland |
US7867275B2 (en) * | 1995-06-07 | 2011-01-11 | Cook Incorporated | Coated implantable medical device method |
US5591199A (en) * | 1995-06-07 | 1997-01-07 | Porter; Christopher H. | Curable fiber composite stent and delivery system |
US7846202B2 (en) * | 1995-06-07 | 2010-12-07 | Cook Incorporated | Coated implantable medical device |
US20070203520A1 (en) * | 1995-06-07 | 2007-08-30 | Dennis Griffin | Endovascular filter |
US7896914B2 (en) * | 1995-06-07 | 2011-03-01 | Cook Incorporated | Coated implantable medical device |
US7611533B2 (en) * | 1995-06-07 | 2009-11-03 | Cook Incorporated | Coated implantable medical device |
US6774278B1 (en) * | 1995-06-07 | 2004-08-10 | Cook Incorporated | Coated implantable medical device |
US7550005B2 (en) * | 1995-06-07 | 2009-06-23 | Cook Incorporated | Coated implantable medical device |
US5779673A (en) * | 1995-06-26 | 1998-07-14 | Focal, Inc. | Devices and methods for application of intraluminal photopolymerized gels |
US5769882A (en) * | 1995-09-08 | 1998-06-23 | Medtronic, Inc. | Methods and apparatus for conformably sealing prostheses within body lumens |
US5827265A (en) * | 1996-02-07 | 1998-10-27 | Regents Of The University Of California | Intraluminal tissue welding for anastomosis |
US5921954A (en) * | 1996-07-10 | 1999-07-13 | Mohr, Jr.; Lawrence G. | Treating aneurysms by applying hardening/softening agents to hardenable/softenable substances |
US7022105B1 (en) * | 1996-05-06 | 2006-04-04 | Novasys Medical Inc. | Treatment of tissue in sphincters, sinuses and orifices |
US6958059B2 (en) * | 1996-05-20 | 2005-10-25 | Medtronic Ave, Inc. | Methods and apparatuses for drug delivery to an intravascular occlusion |
US5876426A (en) * | 1996-06-13 | 1999-03-02 | Scimed Life Systems, Inc. | System and method of providing a blood-free interface for intravascular light delivery |
US5954713A (en) | 1996-07-12 | 1999-09-21 | Newman; Fredric A. | Endarterectomy surgical instruments and procedure |
US5709653A (en) * | 1996-07-25 | 1998-01-20 | Cordis Corporation | Photodynamic therapy balloon catheter with microporous membrane |
US6464660B2 (en) * | 1996-09-05 | 2002-10-15 | Pharmasonics, Inc. | Balloon catheters having ultrasonically driven interface surfaces and methods for their use |
US8353908B2 (en) | 1996-09-20 | 2013-01-15 | Novasys Medical, Inc. | Treatment of tissue in sphincters, sinuses, and orifices |
US7749585B2 (en) * | 1996-10-08 | 2010-07-06 | Alan Zamore | Reduced profile medical balloon element |
US5833651A (en) | 1996-11-08 | 1998-11-10 | Medtronic, Inc. | Therapeutic intraluminal stents |
AU5806098A (en) | 1997-01-03 | 1998-07-31 | Robin G. Smith | Methods and devices for ex vivo irradiation of autologous coronary bypass conduit |
US5845640A (en) * | 1997-01-24 | 1998-12-08 | Spectra Science Corporation | Chemiluminescent sources for photodynamic therapy and photomedicine |
US6338726B1 (en) | 1997-02-06 | 2002-01-15 | Vidacare, Inc. | Treating urinary and other body strictures |
AU6698398A (en) * | 1997-03-12 | 1998-09-29 | Cardiosynopsis, Inc. | (in situ) formed stent |
US5899917A (en) * | 1997-03-12 | 1999-05-04 | Cardiosynopsis, Inc. | Method for forming a stent in situ |
US6223085B1 (en) | 1997-05-06 | 2001-04-24 | Urologix, Inc. | Device and method for preventing restenosis |
US6200307B1 (en) * | 1997-05-22 | 2001-03-13 | Illumenex Corporation | Treatment of in-stent restenosis using cytotoxic radiation |
SE518946C2 (en) * | 1997-07-28 | 2002-12-10 | Prostalund Operations Ab | Device for combined heat treatment of body tissue |
US5902299A (en) * | 1997-07-29 | 1999-05-11 | Jayaraman; Swaminathan | Cryotherapy method for reducing tissue injury after balloon angioplasty or stent implantation |
US9023031B2 (en) * | 1997-08-13 | 2015-05-05 | Verathon Inc. | Noninvasive devices, methods, and systems for modifying tissues |
DE69828963T2 (en) * | 1997-10-01 | 2006-01-26 | Medtronic AVE, Inc., Santa Rosa | Drug delivery and gene therapy delivery system |
US6233481B1 (en) | 1997-10-09 | 2001-05-15 | Spectra Science Corporation | Diagnostic application of sono-chemical excitation of fluorescent photosensitizers |
US5971979A (en) * | 1997-12-02 | 1999-10-26 | Odyssey Technologies, Inc. | Method for cryogenic inhibition of hyperplasia |
US5957975A (en) * | 1997-12-15 | 1999-09-28 | The Cleveland Clinic Foundation | Stent having a programmed pattern of in vivo degradation |
DE69839157T2 (en) * | 1997-12-19 | 2009-05-14 | Cordis Corp., Miami Lakes | FULLURENE KATHERDERSYSTEM CONTAINING |
US6464716B1 (en) * | 1998-01-23 | 2002-10-15 | Innercool Therapies, Inc. | Selective organ cooling apparatus and method |
US6251130B1 (en) | 1998-03-24 | 2001-06-26 | Innercool Therapies, Inc. | Device for applications of selective organ cooling |
US6379378B1 (en) | 2000-03-03 | 2002-04-30 | Innercool Therapies, Inc. | Lumen design for catheter |
US6261312B1 (en) | 1998-06-23 | 2001-07-17 | Innercool Therapies, Inc. | Inflatable catheter for selective organ heating and cooling and method of using the same |
US6719779B2 (en) * | 2000-11-07 | 2004-04-13 | Innercool Therapies, Inc. | Circulation set for temperature-controlled catheter and method of using the same |
US6383210B1 (en) | 2000-06-02 | 2002-05-07 | Innercool Therapies, Inc. | Method for determining the effective thermal mass of a body or organ using cooling catheter |
US6585752B2 (en) * | 1998-06-23 | 2003-07-01 | Innercool Therapies, Inc. | Fever regulation method and apparatus |
US6325818B1 (en) | 1999-10-07 | 2001-12-04 | Innercool Therapies, Inc. | Inflatable cooling apparatus for selective organ hypothermia |
US6245095B1 (en) | 1998-03-24 | 2001-06-12 | Innercool Therapies, Inc. | Method and apparatus for location and temperature specific drug action such as thrombolysis |
US6251129B1 (en) | 1998-03-24 | 2001-06-26 | Innercool Therapies, Inc. | Method for low temperature thrombolysis and low temperature thrombolytic agent with selective organ temperature control |
US6231595B1 (en) * | 1998-03-31 | 2001-05-15 | Innercool Therapies, Inc. | Circulating fluid hypothermia method and apparatus |
US6096068A (en) * | 1998-01-23 | 2000-08-01 | Innercool Therapies, Inc. | Selective organ cooling catheter and method of using the same |
US6991645B2 (en) | 1998-01-23 | 2006-01-31 | Innercool Therapies, Inc. | Patient temperature regulation method and apparatus |
US6254626B1 (en) | 1998-03-24 | 2001-07-03 | Innercool Therapies, Inc. | Articulation device for selective organ cooling apparatus |
US6312452B1 (en) | 1998-01-23 | 2001-11-06 | Innercool Therapies, Inc. | Selective organ cooling catheter with guidewire apparatus and temperature-monitoring device |
US6558412B2 (en) * | 1998-01-23 | 2003-05-06 | Innercool Therapies, Inc. | Selective organ hypothermia method and apparatus |
US6491039B1 (en) | 1998-01-23 | 2002-12-10 | Innercool Therapies, Inc. | Medical procedure |
US7371254B2 (en) * | 1998-01-23 | 2008-05-13 | Innercool Therapies, Inc. | Medical procedure |
US6843800B1 (en) | 1998-01-23 | 2005-01-18 | Innercool Therapies, Inc. | Patient temperature regulation method and apparatus |
US6238428B1 (en) | 1998-01-23 | 2001-05-29 | Innercool Therapies, Inc. | Selective organ cooling apparatus and method employing turbulence-inducing element with curved terminations |
US6491716B2 (en) | 1998-03-24 | 2002-12-10 | Innercool Therapies, Inc. | Method and device for applications of selective organ cooling |
US6471717B1 (en) * | 1998-03-24 | 2002-10-29 | Innercool Therapies, Inc. | Selective organ cooling apparatus and method |
US6051019A (en) | 1998-01-23 | 2000-04-18 | Del Mar Medical Technologies, Inc. | Selective organ hypothermia method and apparatus |
US6599312B2 (en) | 1998-03-24 | 2003-07-29 | Innercool Therapies, Inc. | Isolated selective organ cooling apparatus |
US6224624B1 (en) | 1998-03-24 | 2001-05-01 | Innercool Therapies, Inc. | Selective organ cooling apparatus and method |
US6551349B2 (en) | 1998-03-24 | 2003-04-22 | Innercool Therapies, Inc. | Selective organ cooling apparatus |
US6576002B2 (en) | 1998-03-24 | 2003-06-10 | Innercool Therapies, Inc. | Isolated selective organ cooling method and apparatus |
US20040254635A1 (en) * | 1998-03-30 | 2004-12-16 | Shanley John F. | Expandable medical device for delivery of beneficial agent |
US6241762B1 (en) * | 1998-03-30 | 2001-06-05 | Conor Medsystems, Inc. | Expandable medical device with ductile hinges |
US7208010B2 (en) | 2000-10-16 | 2007-04-24 | Conor Medsystems, Inc. | Expandable medical device for delivery of beneficial agent |
US7208011B2 (en) * | 2001-08-20 | 2007-04-24 | Conor Medsystems, Inc. | Implantable medical device with drug filled holes |
US6685732B2 (en) | 1998-03-31 | 2004-02-03 | Innercool Therapies, Inc. | Method and device for performing cooling- or cryo-therapies for, e.g., angioplasty with reduced restenosis or pulmonary vein cell necrosis to inhibit atrial fibrillation employing microporous balloon |
US6905494B2 (en) | 1998-03-31 | 2005-06-14 | Innercool Therapies, Inc. | Method and device for performing cooling- or cryo-therapies for, e.g., angioplasty with reduced restenosis or pulmonary vein cell necrosis to inhibit atrial fibrillation employing tissue protection |
US7291144B2 (en) | 1998-03-31 | 2007-11-06 | Innercool Therapies, Inc. | Method and device for performing cooling- or cryo-therapies for, e.g., angioplasty with reduced restenosis or pulmonary vein cell necrosis to inhibit atrial fibrillation |
US7001378B2 (en) | 1998-03-31 | 2006-02-21 | Innercool Therapies, Inc. | Method and device for performing cooling or cryo-therapies, for, e.g., angioplasty with reduced restenosis or pulmonary vein cell necrosis to inhibit atrial fibrillation employing tissue protection |
US6602276B2 (en) * | 1998-03-31 | 2003-08-05 | Innercool Therapies, Inc. | Method and device for performing cooling- or cryo-therapies for, e.g., angioplasty with reduced restenosis or pulmonary vein cell necrosis to inhibit atrial fibrillation |
US8128595B2 (en) | 1998-04-21 | 2012-03-06 | Zoll Circulation, Inc. | Method for a central venous line catheter having a temperature control system |
US6419643B1 (en) | 1998-04-21 | 2002-07-16 | Alsius Corporation | Central venous catheter with heat exchange properties |
US6589271B1 (en) | 1998-04-21 | 2003-07-08 | Alsius Corporations | Indwelling heat exchange catheter |
US6716236B1 (en) | 1998-04-21 | 2004-04-06 | Alsius Corporation | Intravascular catheter with heat exchange element having inner inflation element and methods of use |
US6458150B1 (en) * | 1999-02-19 | 2002-10-01 | Alsius Corporation | Method and apparatus for patient temperature control |
US6368304B1 (en) | 1999-02-19 | 2002-04-09 | Alsius Corporation | Central venous catheter with heat exchange membrane |
US6338727B1 (en) | 1998-08-13 | 2002-01-15 | Alsius Corporation | Indwelling heat exchange catheter and method of using same |
US6267747B1 (en) * | 1998-05-11 | 2001-07-31 | Cardeon Corporation | Aortic catheter with porous aortic root balloon and methods for inducing cardioplegic arrest |
US6280411B1 (en) * | 1998-05-18 | 2001-08-28 | Scimed Life Systems, Inc. | Localized delivery of drug agents |
US8177743B2 (en) | 1998-05-18 | 2012-05-15 | Boston Scientific Scimed, Inc. | Localized delivery of drug agents |
US6206283B1 (en) * | 1998-12-23 | 2001-03-27 | At&T Corp. | Method and apparatus for transferring money via a telephone call |
US20020022588A1 (en) * | 1998-06-23 | 2002-02-21 | James Wilkie | Methods and compositions for sealing tissue leaks |
SE521014C2 (en) | 1999-02-04 | 2003-09-23 | Prostalund Operations Ab | Apparatus for heat treatment of prostate |
US6450990B1 (en) | 1998-08-13 | 2002-09-17 | Alsius Corporation | Catheter with multiple heating/cooling fibers employing fiber spreading features |
US6620189B1 (en) | 2000-02-28 | 2003-09-16 | Radiant Medical, Inc. | Method and system for control of a patient's body temperature by way of a transluminally insertable heat exchange catheter |
US6673098B1 (en) * | 1998-08-24 | 2004-01-06 | Radiant Medical, Inc. | Disposable cassette for intravascular heat exchange catheter |
US6293967B1 (en) | 1998-10-29 | 2001-09-25 | Conor Medsystems, Inc. | Expandable medical device with ductile hinges |
US6869440B2 (en) * | 1999-02-09 | 2005-03-22 | Innercool Therapies, Inc. | Method and apparatus for patient temperature control employing administration of anti-shivering agents |
US6830581B2 (en) | 1999-02-09 | 2004-12-14 | Innercool Therspies, Inc. | Method and device for patient temperature control employing optimized rewarming |
US6299599B1 (en) | 1999-02-19 | 2001-10-09 | Alsius Corporation | Dual balloon central venous line catheter temperature control system |
US6405080B1 (en) | 1999-03-11 | 2002-06-11 | Alsius Corporation | Method and system for treating cardiac arrest |
US6582398B1 (en) | 1999-02-19 | 2003-06-24 | Alsius Corporation | Method of managing patient temperature with a heat exchange catheter |
US6428534B1 (en) | 1999-02-24 | 2002-08-06 | Cryovascular Systems, Inc. | Cryogenic angioplasty catheter |
US6432102B2 (en) | 1999-03-15 | 2002-08-13 | Cryovascular Systems, Inc. | Cryosurgical fluid supply |
US6648879B2 (en) | 1999-02-24 | 2003-11-18 | Cryovascular Systems, Inc. | Safety cryotherapy catheter |
US6514245B1 (en) | 1999-03-15 | 2003-02-04 | Cryovascular Systems, Inc. | Safety cryotherapy catheter |
WO2000051538A1 (en) | 1999-03-01 | 2000-09-08 | Uab Research Foundation | Porous tissue scaffolding materials and uses thereof |
US6290673B1 (en) | 1999-05-20 | 2001-09-18 | Conor Medsystems, Inc. | Expandable medical device delivery system and method |
US6165207A (en) * | 1999-05-27 | 2000-12-26 | Alsius Corporation | Method of selectively shaping hollow fibers of heat exchange catheter |
US6287326B1 (en) | 1999-08-02 | 2001-09-11 | Alsius Corporation | Catheter with coiled multi-lumen heat transfer extension |
US20060216313A1 (en) * | 1999-08-10 | 2006-09-28 | Allergan, Inc. | Methods for treating a stricture with a botulinum toxin |
US6767544B2 (en) * | 2002-04-01 | 2004-07-27 | Allergan, Inc. | Methods for treating cardiovascular diseases with botulinum toxin |
US6447474B1 (en) | 1999-09-15 | 2002-09-10 | Alsius Corporation | Automatic fever abatement system |
US6738661B1 (en) | 1999-10-22 | 2004-05-18 | Biosynergetics, Inc. | Apparatus and methods for the controllable modification of compound concentration in a tube |
US6595941B1 (en) | 2000-01-11 | 2003-07-22 | Integrated Vascular Interventional Technologies, L.C. | Methods for external treatment of blood |
US7131959B2 (en) * | 2003-01-23 | 2006-11-07 | Integrated Vascular Interventional Technologies, L.C., (“IVIT LC”) | Apparatus and methods for occluding an access tube anastomosed to sidewall of an anatomical vessel |
WO2001051117A1 (en) | 2000-01-11 | 2001-07-19 | Blatter Duane D | Vascular occlusal balloons and related vascular access devices and systems |
US7118546B2 (en) * | 2000-01-11 | 2006-10-10 | Integrated Vascular Interventional Technologies, L.C. | Apparatus and methods for facilitating repeated vascular access |
US6656151B1 (en) * | 2000-01-11 | 2003-12-02 | Integrated Vascular Interventional Technologies, L.C. (Ivit, Lc) | Vascular access devices and systems |
US6692486B2 (en) * | 2000-05-10 | 2004-02-17 | Minnesota Medical Physics, Llc | Apparatus and method for treatment of cerebral aneurysms, arterial-vascular malformations and arterial fistulas |
US6726708B2 (en) | 2000-06-14 | 2004-04-27 | Innercool Therapies, Inc. | Therapeutic heating and cooling via temperature management of a colon-inserted balloon |
US6955174B2 (en) * | 2000-08-18 | 2005-10-18 | Uryovascular Systems, Inc. | Cryotherapy method for detecting and treating vulnerable plaque |
US6602246B1 (en) | 2000-08-18 | 2003-08-05 | Cryovascular Systems, Inc. | Cryotherapy method for detecting and treating vulnerable plaque |
US6953560B1 (en) | 2000-09-28 | 2005-10-11 | Advanced Cardiovascular Systems, Inc. | Barriers for polymer-coated implantable medical devices and methods for making the same |
US6716444B1 (en) | 2000-09-28 | 2004-04-06 | Advanced Cardiovascular Systems, Inc. | Barriers for polymer-coated implantable medical devices and methods for making the same |
US7306591B2 (en) | 2000-10-02 | 2007-12-11 | Novasys Medical, Inc. | Apparatus and methods for treating female urinary incontinence |
AU9463401A (en) | 2000-10-16 | 2002-04-29 | Conor Medsystems Inc | Expandable medical device for delivery of beneficial agent |
US6764507B2 (en) | 2000-10-16 | 2004-07-20 | Conor Medsystems, Inc. | Expandable medical device with improved spatial distribution |
US7803149B2 (en) | 2002-07-12 | 2010-09-28 | Cook Incorporated | Coated medical device |
US6530945B1 (en) | 2000-11-28 | 2003-03-11 | Alsius Corporation | System and method for controlling patient temperature |
US6663662B2 (en) | 2000-12-28 | 2003-12-16 | Advanced Cardiovascular Systems, Inc. | Diffusion barrier layer for implantable devices |
US6764504B2 (en) * | 2001-01-04 | 2004-07-20 | Scimed Life Systems, Inc. | Combined shaped balloon and stent protector |
US6529775B2 (en) | 2001-01-16 | 2003-03-04 | Alsius Corporation | System and method employing indwelling RF catheter for systemic patient warming by application of dielectric heating |
US6964680B2 (en) * | 2001-02-05 | 2005-11-15 | Conor Medsystems, Inc. | Expandable medical device with tapered hinge |
US20040073294A1 (en) * | 2002-09-20 | 2004-04-15 | Conor Medsystems, Inc. | Method and apparatus for loading a beneficial agent into an expandable medical device |
US8992567B1 (en) | 2001-04-24 | 2015-03-31 | Cardiovascular Technologies Inc. | Compressible, deformable, or deflectable tissue closure devices and method of manufacture |
US8961541B2 (en) | 2007-12-03 | 2015-02-24 | Cardio Vascular Technologies Inc. | Vascular closure devices, systems, and methods of use |
US20080114394A1 (en) | 2001-04-24 | 2008-05-15 | Houser Russell A | Arteriotomy Closure Devices and Techniques |
US20090143808A1 (en) * | 2001-04-24 | 2009-06-04 | Houser Russell A | Guided Tissue Cutting Device, Method of Use and Kits Therefor |
US7025776B1 (en) | 2001-04-24 | 2006-04-11 | Advanced Catheter Engineering, Inc. | Arteriotomy closure devices and techniques |
EP1273314A1 (en) * | 2001-07-06 | 2003-01-08 | Terumo Kabushiki Kaisha | Stent |
US7682669B1 (en) * | 2001-07-30 | 2010-03-23 | Advanced Cardiovascular Systems, Inc. | Methods for covalently immobilizing anti-thrombogenic material into a coating on a medical device |
US6786900B2 (en) * | 2001-08-13 | 2004-09-07 | Cryovascular Systems, Inc. | Cryotherapy methods for treating vessel dissections and side branch occlusion |
WO2003015672A1 (en) * | 2001-08-15 | 2003-02-27 | Innercool Therapies, Inc. | Method and apparatus for patient temperature control employing administration of anti-shivering |
US7056338B2 (en) | 2003-03-28 | 2006-06-06 | Conor Medsystems, Inc. | Therapeutic agent delivery device with controlled therapeutic agent release rates |
US6753071B1 (en) * | 2001-09-27 | 2004-06-22 | Advanced Cardiovascular Systems, Inc. | Rate-reducing membrane for release of an agent |
US6572640B1 (en) | 2001-11-21 | 2003-06-03 | Alsius Corporation | Method and apparatus for cardiopulmonary bypass patient temperature control |
US7756583B2 (en) | 2002-04-08 | 2010-07-13 | Ardian, Inc. | Methods and apparatus for intravascularly-induced neuromodulation |
US8347891B2 (en) | 2002-04-08 | 2013-01-08 | Medtronic Ardian Luxembourg S.A.R.L. | Methods and apparatus for performing a non-continuous circumferential treatment of a body lumen |
ES2703438T3 (en) | 2002-08-06 | 2019-03-08 | Baxter Int | Biocompatible reversible phase protein compositions and methods for preparing and using them |
US8349348B2 (en) * | 2002-08-06 | 2013-01-08 | Matrix Medical, Llc | Biocompatible phase invertible proteinaceous compositions and methods for making and using the same |
US10098981B2 (en) | 2002-08-06 | 2018-10-16 | Baxter International Inc. | Biocompatible phase invertable proteinaceous compositions and methods for making and using the same |
US9101536B2 (en) * | 2002-08-06 | 2015-08-11 | Matrix Medical Llc | Biocompatible phase invertable proteinaceous compositions and methods for making and using the same |
DE10236152A1 (en) * | 2002-08-07 | 2004-02-19 | Marker Deutschland Gmbh | Ski and ski binding combination |
EP2668933A1 (en) * | 2002-09-20 | 2013-12-04 | Innovational Holdings, LLC | Expandable medical device with openings for delivery of multiple beneficial agents |
US20040127976A1 (en) * | 2002-09-20 | 2004-07-01 | Conor Medsystems, Inc. | Method and apparatus for loading a beneficial agent into an expandable medical device |
DE10244847A1 (en) | 2002-09-20 | 2004-04-01 | Ulrich Prof. Dr. Speck | Medical device for drug delivery |
US7278984B2 (en) * | 2002-12-31 | 2007-10-09 | Alsius Corporation | System and method for controlling rate of heat exchange with patient |
US7124570B2 (en) * | 2003-01-23 | 2006-10-24 | Integrated Vascular Interventional Technologies, L.C. | Apparatus and methods for fluid occlusion of an access tube anastomosed to an anatomical vessel |
US7300453B2 (en) * | 2003-02-24 | 2007-11-27 | Innercool Therapies, Inc. | System and method for inducing hypothermia with control and determination of catheter pressure |
US7250041B2 (en) * | 2003-03-12 | 2007-07-31 | Abbott Cardiovascular Systems Inc. | Retrograde pressure regulated infusion |
US20050015048A1 (en) * | 2003-03-12 | 2005-01-20 | Chiu Jessica G. | Infusion treatment agents, catheters, filter devices, and occlusion devices, and use thereof |
AU2004226327A1 (en) * | 2003-03-28 | 2004-10-14 | Innovational Holdings, Llc | Implantable medical device with beneficial agent concentration gradient |
US7072460B2 (en) * | 2003-05-27 | 2006-07-04 | Vtech Telecommunications Limited | System and method for retrieving telephone numbers |
US7060062B2 (en) * | 2003-06-04 | 2006-06-13 | Cryo Vascular Systems, Inc. | Controllable pressure cryogenic balloon treatment system and method |
US7169179B2 (en) * | 2003-06-05 | 2007-01-30 | Conor Medsystems, Inc. | Drug delivery device and method for bi-directional drug delivery |
AU2004285412A1 (en) | 2003-09-12 | 2005-05-12 | Minnow Medical, Llc | Selectable eccentric remodeling and/or ablation of atherosclerotic material |
US7785653B2 (en) * | 2003-09-22 | 2010-08-31 | Innovational Holdings Llc | Method and apparatus for loading a beneficial agent into an expandable medical device |
US7349971B2 (en) * | 2004-02-05 | 2008-03-25 | Scenera Technologies, Llc | System for transmitting data utilizing multiple communication applications simultaneously in response to user request without specifying recipient's communication information |
JP2007534389A (en) * | 2004-04-29 | 2007-11-29 | キューブ・メディカル・アクティーゼルスカブ | Balloon used for angiogenesis |
US20090204104A1 (en) * | 2004-05-13 | 2009-08-13 | Medtronic Vascular, Inc | Methods for Compounding and Delivering a Therapeutic Agent to the Adventitia of a Vessel |
US9561309B2 (en) | 2004-05-27 | 2017-02-07 | Advanced Cardiovascular Systems, Inc. | Antifouling heparin coatings |
US8177779B2 (en) * | 2004-06-02 | 2012-05-15 | Boston Scientific Scimed, Inc. | Controllable pressure cryogenic balloon treatment system and method |
US20060136023A1 (en) * | 2004-08-26 | 2006-06-22 | Dobak John D Iii | Method and apparatus for patient temperature control employing administration of anti-shivering agents |
US8396548B2 (en) | 2008-11-14 | 2013-03-12 | Vessix Vascular, Inc. | Selective drug delivery in a lumen |
US9277955B2 (en) | 2010-04-09 | 2016-03-08 | Vessix Vascular, Inc. | Power generating and control apparatus for the treatment of tissue |
US7742795B2 (en) | 2005-03-28 | 2010-06-22 | Minnow Medical, Inc. | Tuned RF energy for selective treatment of atheroma and other target tissues and/or structures |
US7604631B2 (en) * | 2004-12-15 | 2009-10-20 | Boston Scientific Scimed, Inc. | Efficient controlled cryogenic fluid delivery into a balloon catheter and other treatment devices |
US20090232784A1 (en) * | 2005-03-10 | 2009-09-17 | Dale Feldman | Endothelial predecessor cell seeded wound healing scaffold |
DE102005024625B3 (en) * | 2005-05-30 | 2007-02-08 | Siemens Ag | Stent for positioning in a body tube |
US8460357B2 (en) * | 2005-05-31 | 2013-06-11 | J.W. Medical Systems Ltd. | In situ stent formation |
US7951182B2 (en) | 2005-07-14 | 2011-05-31 | Zoll Circulation, Inc. | System and method for leak detection in external cooling pad |
US20140025056A1 (en) * | 2006-05-24 | 2014-01-23 | Kambiz Dowlatshahi | Image-guided removal and thermal therapy of breast cancer |
WO2007140278A2 (en) * | 2006-05-24 | 2007-12-06 | Rush University Medical Center | High temperature thermal therapy of breast cancer |
KR20090045916A (en) * | 2006-07-03 | 2009-05-08 | 헤모텍 아게 | Manufacture, method and use of drug-eluting medical devices for permanently keeping blood vessels open |
US8366734B2 (en) * | 2006-08-01 | 2013-02-05 | Cook Medical Technologies Llc | Ultraviolet bonded occlusion balloon |
JP5479901B2 (en) | 2006-10-18 | 2014-04-23 | べシックス・バスキュラー・インコーポレイテッド | Induction of desired temperature effects on body tissue |
CA2666661C (en) | 2006-10-18 | 2015-01-20 | Minnow Medical, Inc. | Tuned rf energy and electrical tissue characterization for selective treatment of target tissues |
EP2455034B1 (en) | 2006-10-18 | 2017-07-19 | Vessix Vascular, Inc. | System for inducing desirable temperature effects on body tissue |
US8414526B2 (en) | 2006-11-20 | 2013-04-09 | Lutonix, Inc. | Medical device rapid drug releasing coatings comprising oils, fatty acids, and/or lipids |
US8430055B2 (en) * | 2008-08-29 | 2013-04-30 | Lutonix, Inc. | Methods and apparatuses for coating balloon catheters |
US8425459B2 (en) | 2006-11-20 | 2013-04-23 | Lutonix, Inc. | Medical device rapid drug releasing coatings comprising a therapeutic agent and a contrast agent |
US20080276935A1 (en) | 2006-11-20 | 2008-11-13 | Lixiao Wang | Treatment of asthma and chronic obstructive pulmonary disease with anti-proliferate and anti-inflammatory drugs |
US8414910B2 (en) | 2006-11-20 | 2013-04-09 | Lutonix, Inc. | Drug releasing coatings for medical devices |
US8998846B2 (en) | 2006-11-20 | 2015-04-07 | Lutonix, Inc. | Drug releasing coatings for balloon catheters |
US9700704B2 (en) | 2006-11-20 | 2017-07-11 | Lutonix, Inc. | Drug releasing coatings for balloon catheters |
US20080175887A1 (en) | 2006-11-20 | 2008-07-24 | Lixiao Wang | Treatment of Asthma and Chronic Obstructive Pulmonary Disease With Anti-proliferate and Anti-inflammatory Drugs |
US8414525B2 (en) | 2006-11-20 | 2013-04-09 | Lutonix, Inc. | Drug releasing coatings for medical devices |
US9737640B2 (en) | 2006-11-20 | 2017-08-22 | Lutonix, Inc. | Drug releasing coatings for medical devices |
US8883190B2 (en) * | 2006-12-01 | 2014-11-11 | Wake Forest University Health Sciences | Urologic devices incorporating collagen inhibitors |
RU2447901C2 (en) * | 2007-01-21 | 2012-04-20 | Хемотек Аг | Medical device for treating lumen obturations and preventing threatening recurrent obturations |
US8496653B2 (en) | 2007-04-23 | 2013-07-30 | Boston Scientific Scimed, Inc. | Thrombus removal |
JP2008305262A (en) * | 2007-06-08 | 2008-12-18 | Konica Minolta Business Technologies Inc | Printer introduction method in server and thin client environment |
US9192697B2 (en) | 2007-07-03 | 2015-11-24 | Hemoteq Ag | Balloon catheter for treating stenosis of body passages and for preventing threatening restenosis |
HUE025522T2 (en) | 2007-12-03 | 2016-02-29 | Tenaxis Medical Inc | Biocompatible phase invertible proteinaceous compositions |
WO2009111716A1 (en) * | 2008-03-06 | 2009-09-11 | Boston Scientific Scimed, Inc. | Balloon catheter devices with sheath covering |
US8845627B2 (en) | 2008-08-22 | 2014-09-30 | Boston Scientific Scimed, Inc. | Regulating pressure to lower temperature in a cryotherapy balloon catheter |
US8076529B2 (en) * | 2008-09-26 | 2011-12-13 | Abbott Cardiovascular Systems, Inc. | Expandable member formed of a fibrous matrix for intraluminal drug delivery |
US8226603B2 (en) * | 2008-09-25 | 2012-07-24 | Abbott Cardiovascular Systems Inc. | Expandable member having a covering formed of a fibrous matrix for intraluminal drug delivery |
US8049061B2 (en) | 2008-09-25 | 2011-11-01 | Abbott Cardiovascular Systems, Inc. | Expandable member formed of a fibrous matrix having hydrogel polymer for intraluminal drug delivery |
CN102271603A (en) | 2008-11-17 | 2011-12-07 | 明诺医学股份有限公司 | Selective accumulation of energy with or without knowledge of tissue topography |
JP5807970B2 (en) | 2009-04-09 | 2015-11-10 | カーディオバスキュラー テクノロジーズ、インク. | Tissue suturing device, transfer device and system, kit and method therefor |
US9155815B2 (en) | 2009-04-17 | 2015-10-13 | Tenaxis Medical, Inc. | Biocompatible phase invertible proteinaceous compositions and methods for making and using the same |
WO2010124098A2 (en) * | 2009-04-24 | 2010-10-28 | Boston Scientific Scimed, Inc. | Use of drug polymorphs to achieve controlled drug delivery from a coated medical device |
US20100285085A1 (en) * | 2009-05-07 | 2010-11-11 | Abbott Cardiovascular Systems Inc. | Balloon coating with drug transfer control via coating thickness |
US8551096B2 (en) | 2009-05-13 | 2013-10-08 | Boston Scientific Scimed, Inc. | Directional delivery of energy and bioactives |
EP3064230B1 (en) | 2009-07-10 | 2019-04-10 | Boston Scientific Scimed, Inc. | Use of nanocrystals for a drug delivery balloon |
EP2453938B1 (en) | 2009-07-17 | 2015-08-19 | Boston Scientific Scimed, Inc. | Nucleation of drug delivery balloons to provide improved crystal size and density |
WO2011028419A1 (en) * | 2009-08-27 | 2011-03-10 | Boston Scientific Scimed, Inc. | Balloon catheter devices with drug-coated sheath |
US9271925B2 (en) | 2013-03-11 | 2016-03-01 | Bioinspire Technologies, Inc. | Multi-layer biodegradable device having adjustable drug release profile |
WO2011035020A1 (en) | 2009-09-18 | 2011-03-24 | Bioinspire Technologies, Inc. | Free-standing biodegradable patch |
WO2011119536A1 (en) | 2010-03-22 | 2011-09-29 | Abbott Cardiovascular Systems Inc. | Stent delivery system having a fibrous matrix covering with improved stent retention |
EP2611476B1 (en) | 2010-09-02 | 2016-08-10 | Boston Scientific Scimed, Inc. | Coating process for drug delivery balloons using heat-induced rewrap memory |
US20120259269A1 (en) | 2011-04-08 | 2012-10-11 | Tyco Healthcare Group Lp | Iontophoresis drug delivery system and method for denervation of the renal sympathetic nerve and iontophoretic drug delivery |
US8669360B2 (en) | 2011-08-05 | 2014-03-11 | Boston Scientific Scimed, Inc. | Methods of converting amorphous drug substance into crystalline form |
WO2013028208A1 (en) | 2011-08-25 | 2013-02-28 | Boston Scientific Scimed, Inc. | Medical device with crystalline drug coating |
US9283110B2 (en) | 2011-09-20 | 2016-03-15 | Zoll Circulation, Inc. | Patient temperature control catheter with outer sleeve cooled by inner sleeve |
US9314370B2 (en) | 2011-09-28 | 2016-04-19 | Zoll Circulation, Inc. | Self-centering patient temperature control catheter |
US9259348B2 (en) | 2011-09-28 | 2016-02-16 | Zoll Circulation, Inc. | Transatrial patient temperature control catheter |
US8888832B2 (en) | 2011-09-28 | 2014-11-18 | Zoll Circulation, Inc. | System and method for doubled use of patient temperature control catheter |
US10045881B2 (en) | 2011-09-28 | 2018-08-14 | Zoll Circulation, Inc. | Patient temperature control catheter with helical heat exchange paths |
US8403927B1 (en) | 2012-04-05 | 2013-03-26 | William Bruce Shingleton | Vasectomy devices and methods |
US9717625B2 (en) | 2012-09-28 | 2017-08-01 | Zoll Circulation, Inc. | Intravascular heat exchange catheter with non-round coiled coolant path |
US9241827B2 (en) | 2012-09-28 | 2016-01-26 | Zoll Circulation, Inc. | Intravascular heat exchange catheter with multiple spaced apart discrete coolant loops |
US9433528B2 (en) | 2012-09-28 | 2016-09-06 | Zoll Circulation, Inc. | Intravascular heat exchange catheter with rib cage-like coolant path |
US9801756B2 (en) | 2012-09-28 | 2017-10-31 | Zoll Circulation, Inc. | Intravascular heat exchange catheter and system with RFID coupling |
US9278023B2 (en) | 2012-12-14 | 2016-03-08 | Zoll Circulation, Inc. | System and method for management of body temperature |
US9474644B2 (en) | 2014-02-07 | 2016-10-25 | Zoll Circulation, Inc. | Heat exchange system for patient temperature control with multiple coolant chambers for multiple heat exchange modalities |
US10792185B2 (en) | 2014-02-14 | 2020-10-06 | Zoll Circulation, Inc. | Fluid cassette with polymeric membranes and integral inlet and outlet tubes for patient heat exchange system |
US11033424B2 (en) | 2014-02-14 | 2021-06-15 | Zoll Circulation, Inc. | Fluid cassette with tensioned polymeric membranes for patient heat exchange system |
US10500088B2 (en) | 2014-02-14 | 2019-12-10 | Zoll Circulation, Inc. | Patient heat exchange system with two and only two fluid loops |
US10709490B2 (en) | 2014-05-07 | 2020-07-14 | Medtronic Ardian Luxembourg S.A.R.L. | Catheter assemblies comprising a direct heating element for renal neuromodulation and associated systems and methods |
US9784263B2 (en) | 2014-11-06 | 2017-10-10 | Zoll Circulation, Inc. | Heat exchange system for patient temperature control with easy loading high performance peristaltic pump |
US11359620B2 (en) | 2015-04-01 | 2022-06-14 | Zoll Circulation, Inc. | Heat exchange system for patient temperature control with easy loading high performance peristaltic pump |
US10537465B2 (en) | 2015-03-31 | 2020-01-21 | Zoll Circulation, Inc. | Cold plate design in heat exchanger for intravascular temperature management catheter and/or heat exchange pad |
US11213423B2 (en) | 2015-03-31 | 2022-01-04 | Zoll Circulation, Inc. | Proximal mounting of temperature sensor in intravascular temperature management catheter |
US10022265B2 (en) | 2015-04-01 | 2018-07-17 | Zoll Circulation, Inc. | Working fluid cassette with hinged plenum or enclosure for interfacing heat exchanger with intravascular temperature management catheter |
US11337851B2 (en) | 2017-02-02 | 2022-05-24 | Zoll Circulation, Inc. | Devices, systems and methods for endovascular temperature control |
US11116657B2 (en) | 2017-02-02 | 2021-09-14 | Zoll Circulation, Inc. | Devices, systems and methods for endovascular temperature control |
US11185440B2 (en) | 2017-02-02 | 2021-11-30 | Zoll Circulation, Inc. | Devices, systems and methods for endovascular temperature control |
WO2019231763A1 (en) | 2018-05-27 | 2019-12-05 | Christos Angeletakis | Tissue adhesives and sealants using naturally derived aldehydes |
CN116507380A (en) * | 2020-10-12 | 2023-07-28 | 泰尔茂株式会社 | Pulmonary embolism removal system |
US20230270498A1 (en) * | 2021-10-22 | 2023-08-31 | Endo Uv Tech | Device and method for dilation of a tubular anatomical structure |
Family Cites Families (22)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3975350A (en) * | 1972-08-02 | 1976-08-17 | Princeton Polymer Laboratories, Incorporated | Hydrophilic or hydrogel carrier systems such as coatings, body implants and other articles |
US3988782A (en) * | 1973-07-06 | 1976-11-02 | Dardik Irving I | Non-antigenic, non-thrombogenic infection-resistant grafts from umbilical cord vessels and process for preparing and using same |
US4378017A (en) * | 1980-03-21 | 1983-03-29 | Kureha Kagaku Kogyo Kabushiki Kaisha | Composite material of de-N-acetylated chitin and fibrous collagen |
JPS5892414A (en) * | 1981-11-30 | 1983-06-01 | Asahi Glass Co Ltd | Separation of liquid mixture |
JPS58180162A (en) * | 1982-04-19 | 1983-10-21 | 株式会社高研 | Anti-thrombosis medical material |
US4784132A (en) * | 1983-03-25 | 1988-11-15 | Fox Kenneth R | Method of and apparatus for laser treatment of body lumens |
US4854320A (en) * | 1983-10-06 | 1989-08-08 | Laser Surgery Software, Inc. | Laser healing method and apparatus |
US4879135A (en) * | 1984-07-23 | 1989-11-07 | University Of Medicine And Dentistry Of New Jersey | Drug bonded prosthesis and process for producing same |
US4799479A (en) * | 1984-10-24 | 1989-01-24 | The Beth Israel Hospital Association | Method and apparatus for angioplasty |
US4824436A (en) * | 1985-04-09 | 1989-04-25 | Harvey Wolinsky | Method for the prevention of restenosis |
US4713402A (en) * | 1985-08-30 | 1987-12-15 | Becton, Dickinson And Company | Process for preparing antithrombogenic/antibiotic polymeric plastic materials |
DE3608158A1 (en) * | 1986-03-12 | 1987-09-17 | Braun Melsungen Ag | VESSELED PROSTHESIS IMPREGNATED WITH CROSSLINED GELATINE AND METHOD FOR THE PRODUCTION THEREOF |
US4749585A (en) * | 1986-04-11 | 1988-06-07 | University Of Medicine And Dentistry Of New Jersey | Antibiotic bonded prosthesis and process for producing same |
US4754752A (en) * | 1986-07-28 | 1988-07-05 | Robert Ginsburg | Vascular catheter |
JPH0696023B2 (en) * | 1986-11-10 | 1994-11-30 | 宇部日東化成株式会社 | Artificial blood vessel and method for producing the same |
WO1988007841A1 (en) * | 1987-04-13 | 1988-10-20 | Massachusetts Institute Of Technology | Method and apparatus for laser angiosurgery |
US4776836A (en) * | 1987-06-02 | 1988-10-11 | Stanley Sharon O | Swab applicator for generation of heated medicament |
JPH088933B2 (en) * | 1987-07-10 | 1996-01-31 | 日本ゼオン株式会社 | Catheter |
DE3821544C2 (en) * | 1988-06-25 | 1994-04-28 | H Prof Dr Med Just | Dilatation catheter |
DE3831141A1 (en) * | 1988-09-13 | 1990-03-22 | Zeiss Carl Fa | METHOD AND DEVICE FOR MICROSURGERY ON EYE BY LASER RADIATION |
US4994033A (en) * | 1989-05-25 | 1991-02-19 | Schneider (Usa) Inc. | Intravascular drug delivery dilatation catheter |
DE8912478U1 (en) * | 1989-10-20 | 1989-12-07 | Terrex-Rumpus Import Und Export Ag, 2000 Oststeinbek, De |
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- 1990-05-17 US US07/525,104 patent/US5092841A/en not_active Expired - Fee Related
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- 1991-04-29 JP JP91508884A patent/JPH05507010A/en active Pending
- 1991-04-29 WO PCT/US1991/002929 patent/WO1991017731A1/en not_active Application Discontinuation
- 1991-04-29 EP EP19910908940 patent/EP0528869A4/en not_active Withdrawn
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EP0528869A1 (en) | 1993-03-03 |
WO1991017731A1 (en) | 1991-11-28 |
US5092841A (en) | 1992-03-03 |
JPH05507010A (en) | 1993-10-14 |
EP0528869A4 (en) | 1994-03-24 |
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FZDE | Discontinued |