CA2082149A1 - Method for treating an arterial wall injured during angioplasty - Google Patents

Method for treating an arterial wall injured during angioplasty

Info

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
Application number
CA002082149A
Other languages
French (fr)
Inventor
James Richard Spears
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Wayne State University
Original Assignee
Individual
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Individual filed Critical Individual
Publication of CA2082149A1 publication Critical patent/CA2082149A1/en
Abandoned legal-status Critical Current

Links

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00Surgical instruments, devices or methods, e.g. tourniquets
    • A61B17/22Implements 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00Surgical instruments, devices or methods, e.g. tourniquets
    • A61B17/00491Surgical glue applicators
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00Surgical instruments, devices or methods, e.g. tourniquets
    • A61B17/22Implements 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
    • A61B17/22004Implements 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B18/00Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B18/00Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
    • A61B18/04Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by heating
    • A61B18/08Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by heating by means of electrically-heated probes
    • A61B18/082Probes or electrodes therefor
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B18/00Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
    • A61B18/18Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by applying electromagnetic radiation, e.g. microwaves
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B18/00Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
    • A61B18/18Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by applying electromagnetic radiation, e.g. microwaves
    • A61B18/20Surgical 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
    • A61B18/22Surgical 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
    • A61B18/28Surgical 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00Surgical instruments, devices or methods, e.g. tourniquets
    • A61B2017/00831Material properties
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00Surgical instruments, devices or methods, e.g. tourniquets
    • A61B17/22Implements 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
    • A61B2017/22001Angioplasty, e.g. PCTA
    • A61B2017/22002Angioplasty, e.g. PCTA preventing restenosis
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00Surgical instruments, devices or methods, e.g. tourniquets
    • A61B17/22Implements 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
    • A61B2017/22038Implements 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00Surgical instruments, devices or methods, e.g. tourniquets
    • A61B17/22Implements 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
    • A61B2017/22051Implements 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
    • A61B2017/22062Implements 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
    • A61B2017/22064Implements 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00Surgical instruments, devices or methods, e.g. tourniquets
    • A61B17/22Implements 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
    • A61B2017/22082Implements 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00Surgical instruments, devices or methods, e.g. tourniquets
    • A61B17/22Implements 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
    • A61B2017/22082Implements 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
    • A61B2017/22084Implements 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00Surgical instruments, devices or methods, e.g. tourniquets
    • A61B17/22Implements 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
    • A61B2017/22082Implements 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
    • A61B2017/22085Implements 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00Surgical instruments, devices or methods, e.g. tourniquets
    • A61B17/22Implements 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
    • A61B2017/22082Implements 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
    • A61B2017/22087Implements 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES 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
    • A61M25/00Catheters; Hollow probes
    • A61M25/10Balloon catheters
    • A61M2025/1043Balloon catheters with special features or adapted for special applications
    • A61M2025/105Balloon 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES 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
    • A61M25/00Catheters; Hollow probes
    • A61M25/10Balloon catheters
    • A61M25/104Balloon catheters used for angioplasty
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES 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
    • A61M37/00Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
    • A61M37/0092Other 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.

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
::.
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.
-:
Prior art angioplasty procedures also produce injuries in the arterial wall which become associated with inflammation. White cells will migrate to the area and will lay down scar tissue. Any kind of inflammatory response may cause the growth of new tissue. Restenosis or recurrence of the obstruction results because the smooth muscle cells which normally reside within the arterial wall proliferate. Such cells migrate to the area of the injury and multiply in response thereto.
., .
It therefore appears that in order to combat ;~ problems associated with cumulating plaque, attention ~ -must be paid to: (l) the importance of thrombus; (2) inflammatory changes; and (3) proliferation. Any combination of these factors probably accounts for most ;~ cases of restenosis.
.' '~''"~' '.
In order to address such problems, the cardiology community needs to administer drugs which are biocompatible and not induce toxic reactions.
` 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.
., .
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, .
~ .

,, .. , . . ,, . ~ . . - ................ ~. :, ,.. . ::

. - . . . - :.. . : -:: .. ~.: . . .:

~2~

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.
., :
. ':
.:: , .

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.
.

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;

' .
: .
. .

. - . .: , . . . . .:
., ., . . , , . .~ .
, . . : . :

:: - ~ . . . -: : .: . .

2 ~

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.
.
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 :;

... . . .. . .
:. :

. : .. ,:, i , ;~-, . ~ ; . ::

WO91/17731 2 ~ d ~ PCT/US~1/02929 '; _ g _ artery and the possibility of an acute myocardial ~ infarction.
., :
`~ Following prior art techniques, even less severe disruptions in the arterial wall commonly result in gradual restenosis within three to six months after conventional balloon angioplasty. This occurs in part because platelets adhere to exposed arterial tissue ~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. ~;
. ' .
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.
,~ .

, ' - , ~
,. ,. . . , . ., . , .. , . . -:

, . .
~` -- 10 --As a result, localized delivery of the bioprotective material 26.
, :
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.
.
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 ` ~

;
1.

~.

' ' ' ' ' ' '' ~ ' ' ` :

~ WO91/17731 2 ~ ~ 2 ~ PCr/USs1/02~2s . . .
1 1 - .
,i be treated. Microwave, radio-frequency, or electrical heating of the fluid each are possible techniques.
, ~ :
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.
.
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.
., .
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.
.. ' ,. .

. .

~ ~$.~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.
, - : .. : . .. ' . . : : . . . .

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.
.
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.
.
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 :

. ~ .

: ',. - - : , ' ~ .

WO 91/17731 ~ ~ 3 ~ PCT/US91/02929 ~ .
.~;

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 .

,, , : ": . . , , .: : .:.': . : : . . . . ., ' : ' ., ' ' . ' . ~ , ' . .. , ' . . . : : ' ' ,, '..... . ' ,., . ',: . . ' . . .`

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 .. . . .

:, . .. ~ . . ~ - .

~. :

WO91/17731 2~3~t ~1 s~ PCT/US91/02929 . .

addition, a chromophore may be encapsulated in order to enhance absorption of electromagnetic radiation.
.... .
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.
, . .
As discussed earlier, in addition to the ! pharmacologic benefit of the invention, cracks and recesses within the mechanically injured arterial wall are filled in with the insoluble material, thereby producing a smoother and, hence, less thrombogenic luminal surface.
.'': .
A further benefit of the invention results 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 ;

. ' .
:: .

.. . .. . . . . . .

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 . ~:~ . . . ,. . : : . :
.. ~ .

dJ

' 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 .
:

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, . .
.
~`
: . . " , .
~ .

~ WO91/17731 2 ~ PCT/US91/02929 ,~

.. . .

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.
.~ .
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 ' ., :
.:

:
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 ~ '.
:.
' '"; .

. . , , . .. ., . , .- . .i . .. . " . ... , . , . ," .. . - , .. . . ..

``W~9~/17731 ~ CT/US91/02929 ,~
' 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.
.
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 ~.' .
';
;.

.

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.
.
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, ,~
' .:

WO91/17731 ~ 2~ ~ PCT/US91/02929 ~ modifications, and variations as fall within the spirit~ and broad scope of the following claims.

. ~ .

' .

.' ~ , .' . ~ ','" '.

`~, ' ':
. :

, .

Claims (62)

WHAT IS CLAIMED IS:
1. A method for treating a lesion in an arterial wall having plaque thereon and a luminal surface, the arterial wall having been injured during an angioplasty procedure, the arterial wall and the plaque 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.
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.
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.
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.
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.
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.
CA002082149A 1990-05-17 1991-04-29 Method for treating an arterial wall injured during angioplasty Abandoned CA2082149A1 (en)

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
CA2082149A1 true CA2082149A1 (en) 1991-11-18

Family

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
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)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5634946A (en) * 1988-08-24 1997-06-03 Focal, Inc. Polymeric endoluminal paving process
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.
US5571169A (en) * 1993-06-07 1996-11-05 Endovascular Instruments, Inc. Anti-stenotic method and product for occluded and partially occluded arteries
US5934284A (en) * 1989-08-18 1999-08-10 Endovascular Instruments, Inc Method for increasing blood flow in vessels
WO1991003207A1 (en) * 1989-09-08 1991-03-21 Boston Scientific Corporation 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
US5824658A (en) * 1990-09-18 1998-10-20 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
US5910489A (en) * 1990-09-18 1999-06-08 Hyal Pharmaceutical Corporation Topical composition containing hyaluronic acid and NSAIDS
US5990096A (en) * 1990-09-18 1999-11-23 Hyal Pharmaceutical Corporation Formulations containing hyaluronic acid
US5354324A (en) * 1990-10-18 1994-10-11 The General Hospital Corporation Laser induced platelet inhibition
US5893840A (en) * 1991-01-04 1999-04-13 Medtronic, Inc. Releasable microcapsules on balloon catheters
US5324261A (en) * 1991-01-04 1994-06-28 Medtronic, Inc. Drug delivery balloon catheter with line of weakness
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
US5571166A (en) * 1992-03-19 1996-11-05 Medtronic, Inc. Method of making an intraluminal stent
DE69326631T2 (en) * 1992-03-19 2000-06-08 Medtronic Inc Intraluminal expansion device
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
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
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
US5443470A (en) * 1992-05-01 1995-08-22 Vesta Medical, Inc. Method and apparatus for endometrial ablation
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
US6033383A (en) * 1996-12-19 2000-03-07 Ginsburg; Robert Temperature regulating catheter and methods
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
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
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
US6620188B1 (en) 1998-08-24 2003-09-16 Radiant Medical, Inc. Methods and apparatus for regional and whole body temperature modification
EP0690736B1 (en) * 1993-03-23 1998-11-11 Focal, Inc. Apparatus and method for local application of polymeric material to tissue
US6004547A (en) 1997-09-29 1999-12-21 Focal, Inc. Apparatus and method for local application of polymeric material to tissue
US20020055710A1 (en) * 1998-04-30 2002-05-09 Ronald J. Tuch Medical device for delivering a therapeutic agent and method of preparation
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
DE69412474T2 (en) 1993-04-28 1998-12-17 Focal Inc DEVICE, PRODUCT AND USE REGARDING INTRALUMINAL PHOTOTHERMO MOLDING
US5716410A (en) * 1993-04-30 1998-02-10 Scimed Life Systems, Inc. Temporary stent and method of use
US5716981A (en) * 1993-07-19 1998-02-10 Angiogenesis Technologies, Inc. Anti-angiogenic compositions and methods of use
CA2468375A1 (en) * 1993-07-19 1995-02-02 Angiotech Pharmaceuticals, Inc. Anti-angiogenic compositions, uses and methods
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
US7550005B2 (en) * 1995-06-07 2009-06-23 Cook Incorporated Coated implantable medical device
US5591199A (en) * 1995-06-07 1997-01-07 Porter; Christopher H. Curable fiber composite stent and delivery system
US7896914B2 (en) * 1995-06-07 2011-03-01 Cook Incorporated Coated implantable medical device
US7846202B2 (en) * 1995-06-07 2010-12-07 Cook Incorporated Coated implantable medical device
US6774278B1 (en) * 1995-06-07 2004-08-10 Cook Incorporated Coated implantable medical device
US20070203520A1 (en) * 1995-06-07 2007-08-30 Dennis Griffin Endovascular filter
US7867275B2 (en) * 1995-06-07 2011-01-11 Cook Incorporated Coated implantable medical device method
US7611533B2 (en) * 1995-06-07 2009-11-03 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
US7022105B1 (en) * 1996-05-06 2006-04-04 Novasys Medical Inc. Treatment of tissue in sphincters, sinuses and orifices
US5921954A (en) * 1996-07-10 1999-07-13 Mohr, Jr.; Lawrence G. Treating aneurysms by applying hardening/softening agents to hardenable/softenable substances
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
US6419625B1 (en) 1997-01-03 2002-07-16 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
WO1998040033A2 (en) * 1997-03-12 1998-09-17 Cardiosynopsis, Inc. In situ formed stent
US6039757A (en) * 1997-03-12 2000-03-21 Cardiosynopsis, Inc. In situ formed fenestrated stent
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
EP1039944B1 (en) * 1997-12-19 2008-02-20 Cordis Corporation Catheter system having fullerenes
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
US6843800B1 (en) 1998-01-23 2005-01-18 Innercool Therapies, Inc. Patient temperature regulation method and apparatus
US6312452B1 (en) 1998-01-23 2001-11-06 Innercool Therapies, Inc. Selective organ cooling catheter with guidewire apparatus and temperature-monitoring device
US6096068A (en) * 1998-01-23 2000-08-01 Innercool Therapies, Inc. Selective organ cooling catheter and method of using the same
US6251130B1 (en) 1998-03-24 2001-06-26 Innercool Therapies, Inc. Device for applications of selective organ cooling
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
US6051019A (en) 1998-01-23 2000-04-18 Del Mar Medical Technologies, Inc. Selective organ hypothermia method and apparatus
US6471717B1 (en) 1998-03-24 2002-10-29 Innercool Therapies, Inc. Selective organ cooling apparatus and method
US6464716B1 (en) * 1998-01-23 2002-10-15 Innercool Therapies, Inc. Selective organ cooling apparatus and method
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
US6245095B1 (en) 1998-03-24 2001-06-12 Innercool Therapies, Inc. Method and apparatus for location and temperature specific drug action such as thrombolysis
US6558412B2 (en) * 1998-01-23 2003-05-06 Innercool Therapies, Inc. Selective organ hypothermia method and apparatus
US6254626B1 (en) 1998-03-24 2001-07-03 Innercool Therapies, Inc. Articulation device for selective organ cooling apparatus
US6491716B2 (en) 1998-03-24 2002-12-10 Innercool Therapies, Inc. Method and device for applications of selective organ cooling
US6991645B2 (en) * 1998-01-23 2006-01-31 Innercool Therapies, Inc. Patient temperature regulation method and apparatus
US6379378B1 (en) 2000-03-03 2002-04-30 Innercool Therapies, Inc. Lumen design for catheter
US6238428B1 (en) 1998-01-23 2001-05-29 Innercool Therapies, Inc. Selective organ cooling apparatus and method employing turbulence-inducing element with curved terminations
US7371254B2 (en) * 1998-01-23 2008-05-13 Innercool Therapies, Inc. Medical procedure
US6231595B1 (en) * 1998-03-31 2001-05-15 Innercool Therapies, Inc. Circulating fluid hypothermia method and apparatus
US6491039B1 (en) 1998-01-23 2002-12-10 Innercool Therapies, Inc. Medical procedure
US6325818B1 (en) 1999-10-07 2001-12-04 Innercool Therapies, Inc. Inflatable cooling apparatus for selective organ hypothermia
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
US6576002B2 (en) 1998-03-24 2003-06-10 Innercool Therapies, Inc. Isolated selective organ cooling method and apparatus
US6551349B2 (en) 1998-03-24 2003-04-22 Innercool Therapies, Inc. Selective organ cooling apparatus
US7208011B2 (en) * 2001-08-20 2007-04-24 Conor Medsystems, Inc. Implantable medical device with drug filled holes
US20040254635A1 (en) * 1998-03-30 2004-12-16 Shanley John F. Expandable medical device for delivery of beneficial agent
US7208010B2 (en) * 2000-10-16 2007-04-24 Conor Medsystems, Inc. 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
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
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
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
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
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
US6589271B1 (en) 1998-04-21 2003-07-08 Alsius Corporations Indwelling heat exchange catheter
US6458150B1 (en) * 1999-02-19 2002-10-01 Alsius Corporation Method and apparatus for patient temperature control
US6419643B1 (en) 1998-04-21 2002-07-16 Alsius Corporation Central venous catheter with heat exchange properties
US6368304B1 (en) 1999-02-19 2002-04-09 Alsius Corporation Central venous catheter with heat exchange membrane
US6716236B1 (en) 1998-04-21 2004-04-06 Alsius Corporation Intravascular catheter with heat exchange element having inner inflation element and methods of use
US6338727B1 (en) 1998-08-13 2002-01-15 Alsius Corporation Indwelling heat exchange catheter and method of using same
US8128595B2 (en) 1998-04-21 2012-03-06 Zoll Circulation, Inc. Method for a central venous line catheter having a temperature control system
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
US6582398B1 (en) 1999-02-19 2003-06-24 Alsius Corporation Method of managing patient temperature with a heat exchange catheter
US6405080B1 (en) 1999-03-11 2002-06-11 Alsius Corporation Method and system for treating cardiac arrest
US6299599B1 (en) 1999-02-19 2001-10-09 Alsius Corporation Dual balloon central venous line catheter temperature control system
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
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
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
US6663590B2 (en) 2000-01-11 2003-12-16 Integrated Vascular Interventional Technologies, L.C. (Ivit, Lc) Vascular occlusal balloons and related vascular access devices and systems
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
US6595941B1 (en) 2000-01-11 2003-07-22 Integrated Vascular Interventional Technologies, L.C. Methods for external treatment of blood
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
US6602246B1 (en) 2000-08-18 2003-08-05 Cryovascular Systems, Inc. Cryotherapy method for detecting and treating vulnerable plaque
US6955174B2 (en) * 2000-08-18 2005-10-18 Uryovascular 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
US6764507B2 (en) 2000-10-16 2004-07-20 Conor Medsystems, Inc. Expandable medical device with improved spatial distribution
ATE300255T1 (en) 2000-10-16 2005-08-15 Conor Medsystems Inc EXPANDABLE MEDICAL DEVICE FOR DELIVERING A MEDICINE
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
US20040073294A1 (en) 2002-09-20 2004-04-15 Conor Medsystems, Inc. Method and apparatus for loading a beneficial agent into an expandable medical device
US6964680B2 (en) * 2001-02-05 2005-11-15 Conor Medsystems, Inc. Expandable medical device with tapered hinge
US20080109030A1 (en) 2001-04-24 2008-05-08 Houser Russell A Arteriotomy closure devices and techniques
US7025776B1 (en) 2001-04-24 2006-04-11 Advanced Catheter Engineering, Inc. Arteriotomy closure devices and techniques
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
US20090143808A1 (en) * 2001-04-24 2009-06-04 Houser Russell A Guided Tissue Cutting Device, Method of Use and Kits Therefor
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
WO2004006976A1 (en) 2002-07-12 2004-01-22 Cook Incorporated Coated medical device
US8349348B2 (en) * 2002-08-06 2013-01-08 Matrix Medical, Llc Biocompatible phase invertible proteinaceous compositions and methods for making and using the same
EP3915541A1 (en) 2002-08-06 2021-12-01 BAXTER INTERNATIONAL INC. (a Delaware corporation) Biocompatible phase invertible 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
US10098981B2 (en) 2002-08-06 2018-10-16 Baxter International Inc. 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
WO2004026174A2 (en) * 2002-09-20 2004-04-01 Conor Medsystems, Inc. Expandable medical device with openings for delivery of multiple beneficial agents
DE10244847A1 (en) 2002-09-20 2004-04-01 Ulrich Prof. Dr. Speck Medical device for drug delivery
US20040127976A1 (en) * 2002-09-20 2004-07-01 Conor Medsystems, Inc. Method and apparatus for loading a beneficial agent into an expandable medical device
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
US20050015048A1 (en) 2003-03-12 2005-01-20 Chiu Jessica G. Infusion treatment agents, catheters, filter devices, and occlusion devices, and use thereof
US7250041B2 (en) * 2003-03-12 2007-07-31 Abbott Cardiovascular Systems Inc. Retrograde pressure regulated infusion
CA2519711C (en) * 2003-03-28 2012-01-17 Conor Medsystems, Inc. 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
CA2938411C (en) 2003-09-12 2019-03-05 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
US20070232996A1 (en) * 2004-04-29 2007-10-04 Cube Medical A/S Balloon for Use in Angioplasty with an Outer Layer of Nanofibers
EP1758633B1 (en) * 2004-05-13 2015-03-18 Medtronic Vascular, Inc. Methods for compounding 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
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
WO2006099137A1 (en) * 2005-03-10 2006-09-21 Uab Research Foundation Endothelial predecessor cell seeded wound healing scaffold
CN102125430A (en) 2005-03-28 2011-07-20 明诺医学有限公司 Intraluminal electrical tissue characterization and tuned RF energy for selective treatment of target tissues
DE102005024625B3 (en) * 2005-05-30 2007-02-08 Siemens Ag Stent for positioning in a body tube
US8641746B2 (en) * 2005-05-31 2014-02-04 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
US8486127B2 (en) * 2006-05-24 2013-07-16 Kambiz Dowlatshahi High temperature thermal therapy of breast cancer
KR101226256B1 (en) * 2006-07-03 2013-01-25 헤모텍 아게 Manufacture, method, and use of active substance-releasing medical products for permanently keeping blood vessels open
US8366734B2 (en) * 2006-08-01 2013-02-05 Cook Medical Technologies Llc Ultraviolet bonded occlusion balloon
EP2954868A1 (en) 2006-10-18 2015-12-16 Vessix Vascular, Inc. Tuned rf energy and electrical tissue characterization for selective treatment of target tissues
ES2560006T3 (en) 2006-10-18 2016-02-17 Vessix Vascular, Inc. Induction of desirable temperature effects on body tissue
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
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
US8414910B2 (en) 2006-11-20 2013-04-09 Lutonix, Inc. Drug releasing coatings for medical devices
US9700704B2 (en) 2006-11-20 2017-07-11 Lutonix, Inc. Drug releasing coatings for balloon catheters
US8998846B2 (en) 2006-11-20 2015-04-07 Lutonix, Inc. Drug releasing coatings for balloon catheters
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
US8425459B2 (en) 2006-11-20 2013-04-23 Lutonix, Inc. Medical device rapid drug releasing coatings comprising a therapeutic agent and a contrast agent
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
JP2010511427A (en) * 2006-12-01 2010-04-15 ウェイク・フォレスト・ユニヴァーシティ・ヘルス・サイエンシズ Medical device containing collagen inhibitor
NZ588816A (en) * 2007-01-21 2011-11-25 Hemoteq Ag Medical device for the treatment of stenoses of corporal lumina and for the prevention of impending restenoses
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
US8114049B2 (en) * 2008-03-06 2012-02-14 Boston Scientific Scimed, Inc. Balloon catheter devices with folded balloons
US8845627B2 (en) * 2008-08-22 2014-09-30 Boston Scientific Scimed, Inc. Regulating pressure to lower temperature in a cryotherapy balloon catheter
WO2010024898A2 (en) * 2008-08-29 2010-03-04 Lutonix, Inc. Methods and apparatuses for coating balloon catheters
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
US8076529B2 (en) * 2008-09-26 2011-12-13 Abbott Cardiovascular Systems, Inc. Expandable member formed of a fibrous matrix for intraluminal drug delivery
US8500687B2 (en) 2008-09-25 2013-08-06 Abbott Cardiovascular Systems Inc. Stent delivery system having a fibrous matrix covering with improved stent retention
EP2355737B1 (en) 2008-11-17 2021-08-11 Boston Scientific Scimed, Inc. Selective accumulation of energy without knowledge of tissue topography
NZ595417A (en) 2009-04-09 2013-10-25 Cardivascular Systems Tissue closure devices, device and systems for delivery, kits and methods 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
EP2451496B1 (en) * 2009-07-10 2015-07-22 Boston Scientific Scimed, Inc. Use of nanocrystals for a drug delivery balloon
JP5933434B2 (en) 2009-07-17 2016-06-08 ボストン サイエンティフィック サイムド,インコーポレイテッドBoston Scientific Scimed,Inc. Method for producing drug delivery balloon
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
EP2477617B1 (en) 2009-09-18 2018-01-31 Bioinspire Technologies Inc. Free-standing biodegradable patch
CA2795229A1 (en) 2010-04-09 2011-10-13 Vessix Vascular, Inc. Power generating and control apparatus for the treatment of tissue
WO2012031236A1 (en) 2010-09-02 2012-03-08 Boston Scientific Scimed, Inc. Coating process for drug delivery balloons using heat-induced rewrap memory
KR20130131471A (en) 2011-04-08 2013-12-03 코비디엔 엘피 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
US9056152B2 (en) 2011-08-25 2015-06-16 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
US10045881B2 (en) 2011-09-28 2018-08-14 Zoll Circulation, Inc. Patient temperature control catheter with helical heat exchange paths
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
US9314370B2 (en) 2011-09-28 2016-04-19 Zoll Circulation, Inc. Self-centering patient temperature control catheter
US8403927B1 (en) 2012-04-05 2013-03-26 William Bruce Shingleton Vasectomy devices and methods
US9433528B2 (en) 2012-09-28 2016-09-06 Zoll Circulation, Inc. Intravascular heat exchange catheter with rib cage-like coolant path
US9717625B2 (en) 2012-09-28 2017-08-01 Zoll Circulation, Inc. Intravascular heat exchange catheter with non-round coiled coolant path
US9801756B2 (en) 2012-09-28 2017-10-31 Zoll Circulation, Inc. Intravascular heat exchange catheter and system with RFID coupling
US9241827B2 (en) 2012-09-28 2016-01-26 Zoll Circulation, Inc. Intravascular heat exchange catheter with multiple spaced apart discrete coolant loops
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
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
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
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
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
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
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
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
US11337851B2 (en) 2017-02-02 2022-05-24 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
US20220111183A1 (en) * 2020-10-12 2022-04-14 Terumo Corporation 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)

* Cited by examiner, † Cited by third party
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

Also Published As

Publication number Publication date
EP0528869A1 (en) 1993-03-03
JPH05507010A (en) 1993-10-14
EP0528869A4 (en) 1994-03-24
US5092841A (en) 1992-03-03
WO1991017731A1 (en) 1991-11-28

Similar Documents

Publication Publication Date Title
US5092841A (en) Method for treating an arterial wall injured during angioplasty
US5199951A (en) Method of drug application in a transporting medium to an arterial wall injured during angioplasty
CA2569428C (en) Methods and devices for treating vulnerable plaque
US5914345A (en) Treatment of tissues to reduce subsequent response to injury
US5779673A (en) Devices and methods for application of intraluminal photopolymerized gels
US5662609A (en) Method and apparatus for treatment of focal disease in hollow tubular organs and other tissue lumens
US6039757A (en) In situ formed fenestrated stent
US5019075A (en) Method and apparatus for angioplasty
US4799479A (en) Method and apparatus for angioplasty
US5849035A (en) Methods for intraluminal photothermoforming
US7727184B2 (en) Biological revascularization
JPH10502267A (en) Luminal photopolymer gel injection device and method
JPH06503984A (en) drug delivery system
CA2292801A1 (en) Treating aneurysms by applying hardening/softening agents to hardenable/softenable substances
WO1998040033A9 (en) In situ formed stent
WO1998040033A2 (en) In situ formed stent
JPH0898893A (en) Medicine dosing catheter
US20030103932A1 (en) Compositions, methods and devices for treatment of urethral disorders
US10327846B1 (en) Methods for treating vascular stenoses including laser atherectomy and drug delivery via drug-coated balloons
JP3631777B2 (en) Drug administration catheter
Spears et al. Laser balloon angioplasty: potential for reduction of the thrombogenicity of the injured arterial wall and for local application of bioprotective materials
Spears In this chapter, the potential utility of a new technique, laser balloon angioplasty
CA2549131C (en) Devices and methods for application of intraluminal photopolymerized gels
CA2186752C (en) Drug treatment of diseased sites deep within the body
Spears Lasers and balloons

Legal Events

Date Code Title Description
FZDE Discontinued