U.S. patent number RE34,544 [Application Number 07/975,126] was granted by the patent office on 1994-02-15 for method of treatment of artherosclerosis and balloon catheter the same.
This patent grant is currently assigned to The Beth Israel Hospital Association. Invention is credited to J. Richard Spears.
United States Patent |
RE34,544 |
Spears |
February 15, 1994 |
Method of treatment of artherosclerosis and balloon catheter the
same
Abstract
A method for the treatment of atherosclerosis in a mammal by
destruction of atheromatous plaque is disclosed. The disclosed
method includes injecting a hematoporphyrin into the mammal for
selective uptake into the atheromatous plaque, and delivering light
to the diseased vessel so that the light activates the
hematoporphin for lysis of the plaque. The preferred method
utilizes a balloon catheter equipped with flexible optical fibers
for transmission of light from an external source for illumination
of the interior of the inflated balloon. By inflation of the
balloon, the opaque blood between the balloon and the atheromatous
plaque is displaced to facilitate activation of the
hematoporphyrin. The balloon may be illuminated and inflated and
deflated in a cycle responsive to the patient's pulse so as to
minimize interference with blood flow.
Inventors: |
Spears; J. Richard (Bloomfield
Hills, MI) |
Assignee: |
The Beth Israel Hospital
Association (Boston, MA)
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Family
ID: |
27559998 |
Appl.
No.: |
07/975,126 |
Filed: |
November 12, 1992 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
Issue Date |
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600121 |
Sep 18, 1990 |
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881588 |
Jul 2, 1986 |
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838393 |
Mar 5, 1986 |
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721995 |
Apr 11, 1985 |
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443958 |
Nov 23, 1982 |
4512762 |
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Reissue of: |
244698 |
Jan 14, 1988 |
04773899 |
Sep 27, 1988 |
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Current U.S.
Class: |
604/20;
604/96.01; 606/15; 606/7 |
Current CPC
Class: |
A61B
17/22 (20130101); A61B 18/245 (20130101); A61K
31/40 (20130101); A61M 25/104 (20130101); A61B
2017/00694 (20130101); A61B 2017/22038 (20130101); A61B
2017/22059 (20130101); A61B 2090/306 (20160201); A61B
2017/22087 (20130101); A61B 2018/2261 (20130101); A61B
2017/22085 (20130101) |
Current International
Class: |
A61B
17/22 (20060101); A61B 18/20 (20060101); A61B
18/24 (20060101); A61M 29/02 (20060101); A61K
31/40 (20060101); A61B 19/00 (20060101); A61B
18/22 (20060101); A61B 17/00 (20060101); A61N
001/30 () |
Field of
Search: |
;604/20,21,52,53,96-103
;606/14,15,17,27 ;128/398 |
References Cited
[Referenced By]
U.S. Patent Documents
Foreign Patent Documents
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8102109 |
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Aug 1981 |
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WO |
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8102110 |
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Aug 1981 |
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WO |
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8301893 |
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Jun 1983 |
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WO |
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2054385 |
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Jul 1980 |
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GB |
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Other References
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. Discovery Research Department, Chemical Research Div., American
Cyanamid Company, Bound Brook, NJ, pp. 1-156, (Jan. 1982). .
"Atherosclerosis", H. Wolinsky, Cardiovascular Diseases (USA), vol.
XIV, pp. 1218-1222. .
"The Photodynamic Properties of a Particular Hematoporphyrin
Derivative", R. Lipson et al., Archives of Dermatology, (U.S.A.),
82:76/508-84/516, (1960). .
"Fluorescence of Experimental Atheromatous Plaques with
Hematoporphyrin Derivative", J. Richard Spears, Juan Serur, Deborah
Shropshire, and Sven Paulin, J. Clin. Invest., 71:395-399, (1983).
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"In Vivo Coronary Angioscopy", J. Richard Spears, H. John Marais,
Juan Serur, Oleg Pomerantzeff, Robert P. Geyer, Robert S. Sipzener,
Ronald Weintraub, Robert Thurer, Sven Paulin, Richard Gerstin,
William Grossman, J. Am. Coll. Cardiol., 1:1311-1314, (1983). .
F. Gollan et al., "Oxygen Transport of Colloidal Fluorocarbon
Suspensions in Asanguineous Rabbits", American Journal of
Physiology, (USA), 29: 1045-1049, (Oct. 1975). .
K. Kanter et al., "Superiority of Perfluorocarbon Cardioplegia Over
Blood of Crystalloid Cardioplegia", Circulation, (USA), vol. 64,
Supplement II, pp. 11-75-11-80, (Aug. 1981). .
Cancer Therapy Abstracts, (U.S.A.), 79-0299, T. Dougherty,
"Photoradiation in the Treatment of Recurrent Breast Carcinoma", p.
69, (1979). .
Cancer Therapy Abstracts, (USA), 79-0463, T. Sory, "Photodynamic
Killing of Retinoblastoma Cells with Hematoporphyrin and Light",
pp. 160-161, (1979). .
Cancer Therapy Abstracts, (USA), 79-2363, J. Moan, "The
Photodynamic Inactivation of Human Cells in Vitro in the Presence
of Haematoporphyrin", pp. 735-736, (1979). .
R. Lipson et al., "Hematoporphyrin Derivative for Detection and
Management of Cancer", Cancer (U.S.A.), 20:2255-2257, (Dec. 1967).
.
R. Lipson et al., "The Use of a Derivative of Hematoporphyrin in
Tumor Detection", Journal of the National Cancer Institute,
(U.S.A.), 26:1-8, (Jan. 1961). .
D. Sanderson et al., "Hematoporphyrin as a Diagnostic Tool",
(U.S.A.), Cancer, 30:368-1372, (Nov. 1972)..
|
Primary Examiner: Rosenbaum; C. Fred
Assistant Examiner: Polutta; Mark O.
Attorney, Agent or Firm: Lorusso & Loud
Parent Case Text
This .Iadd.application is a continuation of Ser. No. 600,121 filed
on Sep. 18, 1990 now abandoned which is a reissue of Ser. No.
144,698 now U.S. Pat. No. 4,773,699, which .Iaddend.is a
continuation of copending application Ser. No. 881,588 filed on
7/2/86 now abandoned which is a continuation of copending
application Ser. No. 838,393 filed on 3/5/86 now abandoned which is
a continuation of copending application Ser. No. 721,995 filed on
4/11/85 now abandoned which is a divisional of Ser. No. 443,958
filed on 11/23/82 now U.S. Pat. No. 4,512,762.
Claims
I claim:
1. A balloon catheter for use in applying energy to a wall of an
artery for medical treatment, said catheter comprising:
a tube defining a lumen;
an inflatable balloon secured to the distal end of said tube for
inflation from a remote source of fluid, said balloon being
configured so that said tube may be navigated through the artery
when deflated and allow blood flow while said tube is being
navigated with the balloon in a deflated state and also configured
to displace blood within the artery when inflated;
fiber optic means connectable to an energy source at the proximal
end and extending through said lumen to emit energy into the
balloon for transmission of energy from an external energy source
to the interior of said balloon; and
means for diffusing energy that is transmitted by said fiber optic
means, said means for diffusing energy being in optical
communication with said fiber optic means and being within said
balloon so that the energy transmitted into said balloon via the
fiber optic means may be applied through said balloon to all part
of the walls of the artery surrounding said balloon
simultaneously.
2. The balloon catheter of claim 1 wherein the means for diffusing
energy is an elongated hollow member within and coextensive with
the length of said balloon and forming a junction with said fiber
optic means, said elongated hollow member being filled with a fluid
for scattering light throughout the interior of said balloon and to
the walls of the artery.
3. The balloon catheter of claim 2 further comprising a guide wire
extending through the center of said lumen and through the center
of said elongated hollow member and extending a variable distance
beyond the distal end of said balloon for facilitating insertion
and positioning of the catheter within an artery.
4. The balloon catheter of claim 2 wherein said fluid is a
refractive index liquid.
5. The balloon catheter of claim 1 wherein said means for diffusing
energy is a lens positioned at the terminal end of said fiber optic
means.
6. The balloon catheter of claim 1 wherein said means for diffusing
energy is a solid fiber coupled at the terminal end of said fiber
optic means capable of dispersing light along all or a portion of
its length.
7. A method for applying energy to the walls of an artery to be
treated so that the energy emitting portion of the catheter is
adjacent the part of the artery to be treated, the catheter
comprising:
a tube defining a lumen,
an inflatable balloon secured to the distal end of the tube for
inflation from a remote source of fluid, the balloon being
configured so that the tube may be navigated through the artery
when the balloon is deflated and allow blood flow while the tube is
being navigated with the balloon in a deflated state and also
configured to displace blood within the artery when inflated,
fiber optic means connectable to an energy source at the proximal
end and extending through said lumen to emit energy into the
balloon for transmission of energy from an external energy source,
and
means for diffusing energy that is transmitted by said fiber optic
means, said means for diffusing energy being in optical
communication with the fiber optic means and being within said
balloon so that energy transmitted into the balloon via the fiber
optic means may be applied through the balloon to all parts of the
walls of the artery surrounding the balloon simultaneously;
(B) displacing blood in the artery between the energy emitting
catheter and the portion of the artery to be treated by inflating
the balloon;
(C) energizing the entire balloon surface of the energy emitting
catheter by diffusing energy through the means for diffusing energy
to enable the entire balloon surface to transmit energy to all
parts of the walls of the surrounding artery simultaneously;
and
(D) deflating the balloon of the light emitting catheter and
removing the light emitting catheter after treatment.
8. The method of claim 4 wherein the step of displacing blood by
inflating the balloon of the energy emitting catheter illuminates
the walls of the artery with an intensity greater than would be the
case when blood is present in the artery.
9. The method of claim 8 wherein the balloon inflation is
intermittent.
10. The method of claim 9 wherein the balloon is intermittently
inflated responsive to ECG-gating so as to allow prolonged exposure
of the site to the transmitted energy and to enable the treatment
of the walls of the artery without compromising the patient from
disruption of blood flow.
11. The method of claim 9 wherein the balloon energizing occurs
only when the balloon is inflated.
12. The method of claim 7 wherein energy is transmitted from an
external light source to energize the interior of the balloon of
the energy emitting catheter and all parts of the walls of the
surrounding artery simultaneously.
13. The method of claim 7 wherein the insertion of the catheter in
an artery is facilitated by a guide wire extending through the
center of the lumen and of the elongated hollow member of the
energy emitting catheter and extending a variable distance beyond
the distal end of the balloon of the catheter.
14. The method of claim 7 wherein the energy is maximized by
transmitting energy through diffusing means comprising an elongated
hollow member within and coextensive with the length of the balloon
and forming an optical junction with the fiber optic means with a
liquid filling the elongated hollow member for scattering energy
through the interior of the balloon.
15. The method of claim 7 wherein the energy is maximized by
transmitting energy through diffusing means comprising a lens
positioned at the terminal end of the fiber optic means in the
energy emitting catheter.
16. The method of claim 7 wherein the energy is maximized by
transmitting energy through diffusing means comprising a solid
fiber coupled at the end of the fiber optic means capable of
dispersing energy along all or a portion of its length.
17. The method of claim 7 wherein the external energy source which
is connected to the fiber optic means is a source of ultraviolet
light.
18. The balloon catheter of claim 1 further comprising means to
intermittently inflate said inflatable balloon responsive to
ECG-gating so as to allow prolonged exposure of the site to the
transmitted energy and to enable treatment of the walls of the
artery without compromising the patient from disruption of blood
flow.
19. A balloon catheter for displacing blood within an artery to
enable the wall of the artery to be illuminated for medical
treatment while reducing the amount of light lost through the blood
which would otherwise occur comprising:
a tube defining a lumen, said tube being configured to navigate an
artery;
an inflatable balloon secured to one end of said tube for inflation
from a remote source of gas, said balloon being configured so as
not to interfere with the navigation of said tube through the
artery when deflated and allow blood flow while said tube is being
navigated with the balloon in a deflated state and also configured
to displace blood within the artery when inflated;
fiber optic means connectable to a light source at the proximal end
and extending through said lumen and into the balloon for
transmission of light from an external light source to the interior
of said balloon and to the walls of the artery for illuminating the
walls of the artery, when blood is displaced, with an intensity
greater than would be the case when blood is present in the
artery;
an elongated hollow member within and coextensive with the length
of said balloon and forming an optical junction with said fiber
optic means;
a liquid filling said elongated hollow member for scattering light
throughout the interior of said balloon and to the walls of the
arteries; and
a guidewire to which the distal end of said balloon is affixed;
said balloon and fiber optic means enabling the walls to be
illuminated by displacing blood so that the light from the fiber
optic means reaches the walls of the artery for treatment of
atheromatous plaque, and said inflatable balloon and said fiber
optic means enabling the transmission of light to be synchronized
for intermittent displacement of blood from a selected sight in the
artery at the same time as light is transmitted so as to allow
prolonged exposure of the sight to the transmitted light and to
enable the treatment of the walls of the arteries without
compromising the patient from disruption of blood flow. .Iadd.
20. A balloon catheter for use in applying energy to a wall of a
vessel for medical treatment, said catheter comprising:
a tube defining a lumen;
an inflatable balloon secured to the distal end of said tube for
inflation from a remote source of fluid, said balloon being
configured so that said tube may be navigated to the vessel when
deflated and allow flow of body fluids while said tube is being
navigated with the balloon in a deflated state and also configured
to displace the body fluid at the vessel when inflated;
fiber optic means connectable to an energy source at the proximal
end and extending through said lumen to emit energy into the
balloon for transmission of energy from an external energy source
to the interior of said balloon; and
means for diffusing energy that is transmitted by said fiber optic
means, said means for diffusing energy being in optical
communication with said fiber optic means and being within said
balloon so that energy transmitted into said balloon via the fiber
optic means may be applied through said balloon to all of the
vessel surrounding said balloon simultaneously. .Iaddend.
.Iadd.
21. The balloon catheter of claim 20 wherein the means for
diffusing energy is an elongated hollow member within and
coextensive with the length of said balloon and forming a junction
with said fiber optic means, said elongated hollow member being
filled with a fluid for scattering light throughout the interior of
said balloon and to the vessel. .Iaddend. .Iadd.22. The balloon
catheter of claim 21 further comprising a guide wire extending
through the center of said lumen and through the center of said
elongated hollow member an extending a variable distance beyond the
distal end of said balloon for facilitating insertion and
positioning of the catheter within the vessel. .Iaddend. .Iadd.23.
The balloon catheter of claim 21 wherein said fluid is a refractive
index liquid. .Iaddend.
.Iadd. 4. The balloon catheter of claim 20 wherein said means for
diffusing energy is a lens positioned at the terminal end of said
fiber optic means. .Iaddend. .Iadd.25. The balloon catheter of
claim 20 wherein said means for diffusing energy is a solid fiber
coupled at the terminal end of said fiber optic means capable of
dispersing light along all or a
portion of its length. .Iaddend. .Iadd.26. A method for applying
energy to a vessel to be treated said method comprising:
A) Providing a catheter comprising:
a tube defining a lumen,
an inflatable balloon secured to the distal end of the tube for
inflation from a remote source of fluid, the balloon being
configured so that the tube may be navigated through the body when
the balloon is deflated and allow flow of body fluid while the tube
is being navigated with the balloon in a deflated state and also
configured to displace the body fluid when inflated,
fiber optic means connectable to an energy source at the proximal
end and extending through said lumen to emit energy into the
balloon for transmission of energy from an external energy source,
and
means for diffusing energy that is transmitted by said fiber optic
means, said means for diffusing energy being in optical
communication with the fiber optic means and being within said
balloon so that energy transmitted into the balloon via the fiber
optic means may be applied through the balloon to all of the vessel
surrounding the balloon simultaneously;
B) displacing body fluid between the energy emitting catheter and
the vessel to be treated by inflating the balloon;
C) energizing the entire balloon surface of the energy emitting
catheter by diffusing energy through the means for diffusing energy
to enable the entire balloon surface to transmit energy to all of
the vessel surrounding the catheter simultaneously; and
D) deflating the balloon of the light emitting catheter and
removing the
light emitting catheter after treatment. .Iaddend. .Iadd.27. The
method of claim 26 wherein the step of displacing body fluid by
inflating the balloon of the energy emitting catheter illuminates
the vessel with an intensity greater than would be the case when a
body fluid is present in the area. .Iaddend. .Iadd.28. The method
of claim 27 wherein the balloon inflation is intermittent.
.Iaddend. .Iadd.29. The method of claim 28 wherein the balloon is
intermittently inflated responsive to ECG-gating so as to allow
prolonged exposure of the site to the transmitted energy and to
enable the treatment of the vessel without compromising the
patient
from disruption of flow of body fluid. .Iaddend. .Iadd.30. The
method of claim 28 wherein the balloon energizing occurs only when
the balloon is inflated. .Iaddend. .Iadd.31. The method of claim 26
wherein energy is transmitted from an external light source to
energize the interior of the balloon of the energy emitting
catheter and all of the vessel surrounding the catheter
simultaneously. .Iaddend. .Iadd.32. The method of claim 26 wherein
the insertion of the catheter into the body is facilitated by a
guide wire extending through the center of the lumen and of the
balloon of the energy emitting catheter and extending a variable
distance beyond the distal end of the balloon of the catheter.
.Iaddend. .Iadd.33. The method of claim 26 wherein the energy is
maximized by transmitting energy through diffusing means comprising
an elongated hollow member within and coextensive with the length
of the balloon and forming an optical junction with the fiber optic
means with a liquid filling the elongated hollow member for
scattering energy through the interior of the balloon. .Iaddend.
.Iadd.34. The method of claim 26 wherein the energy is maximized by
transmitting energy through diffusing means comprising a lens
positioned at the terminal end of the fiber optic means in the
energy
emitting catheter. .Iaddend. .Iadd.35. The method of claim 26
wherein the energy is maximized by transmitting energy through
diffusing means comprising a solid fiber coupled at the end of the
fiber optic means capable of dispersing energy along all or a
portion of its length. .Iaddend. .Iadd.36. The method of claim 26
wherein the external energy source which is connected to the fiber
optic means is a source of ultraviolet light. .Iaddend. .Iadd.37.
The balloon catheter of claim 20 further comprising means to
intermittently inflate said inflatable balloon responsive to
ECG-gating so as to allow prolonged exposure of the site to the
transmitted energy and to enable treatment of the vessel without
compromising the patient from disruption of flow of body fluids.
.Iaddend.
.Iadd.38. A balloon catheter for displacing body fluid to enable a
vessel to be illuminated for medical treatment while reducing the
amount of light lost through the body fluid which would otherwise
occur comprising:
a tube defining a lumen, said tube being configured to navigate in
the body;
an inflatable balloon secured to one end of said tube for inflation
from a remote source of gas, said balloon being configured so as
not to interfere with the navigation of said tube through the body
when deflated and allow flow of body fluid while said tube is being
navigated with the balloon in a deflated state and also configured
to displace body fluid at the vessel to be treated when
inflated;
fiber optic means connectable to a light source at the proximal end
and extending through said lumen and into the balloon for
transmission of light from an external light source to the interior
of said balloon and to the vessel for illuminating the vessel, when
body fluid is displaced, with an intensity greater than would be
the case when body fluid is present in the area;
an elongated hollow member within and coextensive with the length
of said balloon and forming an optical junction with said fiber
optic means;
a liquid filling said elongated hollow member for scattering light
throughout the interior of said balloon and to the surrounding
vessel; and
a guide wire to which the distal end of said balloon is
affixed;
said balloon and fiber optic means enabling the vessel to be
illuminated by displacing body fluid so that the light from the
fiber optic means reaches the vessel for treatment, and said
inflatable balloon and said fiber optic means enabling the
transmission of light to be synchronized for intermittent
displacement of body fluid from a selected site in the body at the
same time as light is transmitted so as to allow prolonged exposure
of the site to the transmitted light and to enable the treatment of
the vessel without compromising the patient from disruption of body
fluid.
.Iaddend. .Iadd.39. A balloon catheter for medical treatment, said
catheter comprising:
a tube defining a lumen;
an inflatable balloon secured to the distal end of said tube for
inflation from a remote source of fluid, said balloon being
configured to deflate to allow placement of the catheter and to
inflate for treatment;
fiber optic means connectable to an energy source at the proximal
end and extending through said lumen to emit energy into the
balloon for transmission of energy from a external energy source to
the interior of said balloon; and
means for diffusing energy that is transmitted by said fiber optic
means, said means for diffusing energy being in optical
communication with said fiber optic means and being within said
balloon so that energy transmitted into said balloon via the fiber
optic means may be applied through all parts of said balloon
simultaneously. .Iaddend. .Iadd.40. The balloon catheter of claim
39 wherein the means for diffusing energy is an elongated hollow
member within and coextensive with the length of said balloon and
forming a junction with said fiber optic means, said elongated
hollow member being filled with a fluid for scattering light
throughout the interior of said balloon. .Iaddend. .Iadd.41. The
balloon catheter of claim 40 further comprising a guide wire
extending through the center of said lumen and through the center
of said elongated hollow member and extending a variable distance
beyond the distal end of said balloon for facilitating insertion
and positioning of the catheter. .Iaddend. .Iadd.42. The balloon
catheter of claim 40 wherein said fluid is a refractive index
liquid. .Iaddend. .Iadd.43. The balloon catheter of claim 39
wherein said means for diffusing energy is a lens positioned at the
terminal end of said fiber optic means. .Iaddend. .Iadd.44. The
balloon catheter of claim 39 wherein said means for diffusing
energy is a solid fiber coupled at the terminal end of said fiber
optic means capable of dispersing light along all or a portion of
its length. .Iaddend. .Iadd.45. The balloon catheter of claim 39
further comprising means to intermittently inflate said inflatable
balloon responsive to ECG-gating so as to allow prolonged treatment
with the transmitted energy. .Iaddend. .Iadd.46. A method for
applying energy for medical treatment comprising:
A) providing a catheter comprising:
a tube defining a lumen,
an inflatable balloon secured to the distal end of the tube for
inflation from a remote source of fluid, the balloon being
configured to deflate to allow placement of the catheter and to
inflate for treatment,
fiber optic means connectable to an energy source at the proximal
end and extending through said lumen to emit energy into the
balloon for transmission of energy from an external energy source,
and
means for diffusing energy that is transmitted by said fiber optic
means, said means for diffusing energy being in optical
communication with the fiber optic means and being within said
balloon so that energy transmitted into the balloon via the fiber
optic means may be applied through all parts of the balloon
simultaneously;
B) inflating the balloon;
C) energizing the entire balloon surface of the energy emitting
catheter by diffusing energy through the means for diffusing energy
to enable the entire balloon surface to transmit energy
simultaneously; and
D) deflating the balloon of the light emitting catheter and
removing the
light emitting catheter after treatment. .Iaddend. .Iadd.47. The
method of claim 46 wherein the balloon inflation is intermittent.
.Iaddend. .Iadd.48. The method of claim 47 wherein the balloon is
intermittently inflated responsive to ECG-gating so as to allow
prolonged treatment with the transmitted energy. .Iaddend.
.Iadd.49. The method of claim 47 wherein the balloon energizing
occurs only when the balloon is inflated. .Iaddend. .Iadd.50. The
method of claim 46 wherein the positioning of the catheter is
facilitated by a guide wire extending through the center of the
lumen and of the balloon of the energy emitting catheter and
extending a variable distance beyond the distal end of the balloon
of the catheter. .Iaddend. .Iadd.51. The method of claim 46 wherein
the energy is maximized by transmitting energy through diffusing
means comprising an elongated hollow member within and coextensive
with the length of the balloon and forming an optical junction with
the fiber optic means with a liquid filling the elongated hollow
member for scattering energy through the interior of the balloon.
.Iaddend. .Iadd.52. The method of claim 46 wherein the energy is
maximized by transmitting energy through diffusing means comprising
a lens positioned at the terminal end of the fiber optic means in
the energy emitting catheter. .Iaddend. .Iadd.53. The method of
claim 46 wherein the energy is maximized by transmitting energy
through diffusing means comprising a solid fiber coupled at the end
of the fiber optic means capable of dispersing energy along all or
a portion of its length. .Iaddend. .Iadd.54. The method of claim 46
wherein the external energy source which is connected to the fiber
optic means is a source of ultraviolet light. .Iaddend. .Iadd.55. A
balloon catheter for medical treatment comprising:
a tube defining a lumen;
an inflatable balloon secured to one end of said tube for inflation
from a remote source of gas, said balloon being configured to
deflate to allow placement of the catheter and to inflate for
treatment;
fiber optic means connectable to a light source at the proximal end
and extending through said lumen and into the balloon for
transmission of light from an external light source to the interior
of said balloon;
an elongated hollow member within and coextensive with the length
of said balloon and forming an optical junction with said fiber
optic means;
a liquid filling said elongated hollow member for scattering light
throughout the interior of said balloon; and
a guide wire to which the distal end of said balloon is
affixed;
said inflatable balloon and said fiber optic means enabling the
transmission of light to be synchronized with the inflation of the
balloon to allow prolonged treatment without compromising the
patient. .Iaddend.
Description
Atherosclerosis is a coronary disease wherein fatty substances
(lipids), hereinafter referred to as atheromatous plaques, form
deposits in and beneath the intima which is the innermost membrane
lining arteries and veins. Atherosclerosis tends to involve large
and medium-sized arteries. Most commonly affected are the aorta and
the iliac, femoral, coronary, and cerebral arteries. Clinical
symptoms occur because the mass of the artherosclerotic plaque
reduces blood flow through the involved artery and thereby
compromises tissue or organ function distal to it.
Modern treatment of atherosclerosis revolves around highly
sophisticated coronary care units. In general, modern medicine
follows one of two approaches to the care of patients suffering
from atherosclerotic complications: either (1) the diseased
vascular segments are replaced with prosthetic or natural grafts,
even going as far as heart transplantation or (2) drugs such as
antiarrhythmic agents, anticoagulants and plasma lipid lowering
agents are administered to enable the patient to live with the
condition. Neither approach contemplates a cure of the diseased
members.
SUMMARY OF THE INVENTION
The present invention provides for treatment of a main artery or
other blood vessel afflicted with atherosclerosis. The method
involves administration of a hematoporphyrin, preferably by
intravenous injection, to the mammal to be treated. The invention
resides, in part, in the discovery that the hematoporphyrin so
administered is selectively absorbed into the atheromatous plaque,
with little or no absorption into healthy areas of the arterial
wall. Upon illumination of the atheromatous plaque, containing
absorbed hematoporphyrin, the hematoporphyrin is activated and
destroys the host atheromatous plaque tissue. Illumination of the
plaque may be achieved with either one of two different techniques.
With one technique, the patient is catheterized with a
light-emitting catheter inserted into the diseased artery or other
vessel so that the light-emitting portion of the catheter is
adjacent the atheromatous plaque. Alternatively, a form of liquid
light is injected into the vascular tree such that the liquid
light, which mixes freely with blood or a blood replacement,
perfuses the diseased artery.
In the preferred embodiment a special light-emitting balloon
catheter is employed. The balloon catheter includes an inflatable
balloon secured to one end of the catheter tube, for inflation of a
gas from a remote source, and optical fibers which extend through
the tube lumen for transmission of light from an external light
source to the interior of the balloon. Preferably, the
light-transmitting optical fibers are optically joined to a light
scattering device within the balloon in the form of a hollow,
liquid-filled fiber or tube. The liquid filling is selected for
optimum transmission of light and maximum light scattering.
Use of the preferred balloon catheter provides for displacement of
the light-opaque blood between the external balloon surface and the
atherosclerosis plaque by inflation of the balloon. Use of the
preferred catheter also allows for intermittent and cyclical
illumination and inflation/deflation of the balloon so as to
minimize interruption of blood flow to the vital organs and to
avoid potential problems attendant to heating of the balloon
material and the blood of the mammal undergoing treatment.
Activation of hematoporphyrin within atheromatous plaques may also
be achieved by injecting a form of liquid light into the vascular
tree. Examples of light-emitting liquids are the bioluminescent
system of firefly lucerin/lucerase and the chemiluminescent system
of the Cyalume Lightstick manufactured by the American Cyanamid
Company. Although the organic liquid-based Cyalume Lightstick is
incompatible with blood, an aqueous liquid-based chemiluminescent
system has recently been developed. See "Aqueous Peroxyoxalate
Chemiluminescence, Final Report to the Office of Naval Research,
Contact N00014-77-C-0634" by A. G. Mohan et al. at the American
Cyanamid Company, Bound Brook, N.J., January, 1982. Although the
light intensity of any liquid light is less than that which is
achievable with the fiberoptic delivery of a laser, activation of
hematoporphyrin is a function of the product of light intensity
times the duration of illumination, so that a relatively low level
of light intensity for a long duration is sufficient to activate
hematoporphyrin. A potential advantage of the use of liquid light
is that all diseased vessels can be perfused with the liquid light,
once intravascular injection of the liquid light and mixing with
blood have been completed. Knowledge of the exact location of
atheromatous plaques would be unnecessary, since all plaques would
be exposed to the light. Should blood prove to be too light-opaque
to allow a sufficient quantity of light to reach a plaque, blood
replacement with more translucent liquids, such as perfluorocarbon
emulsion-containing blood substitutes, may be performed prior to
injecting the liquid light. For an example, in animals, of total
blood exchange with perfluorocarbon chemicals, see Gollan et al, Am
J. Physiol 229:1045 (1975). Fluosol-DA, a commercially available
perfluorocarbon-containing blood substitute from Alpha
Therapeutics, a subsidiary of the Green Cross Corporation, is
currently undergoing clinical trials and has been used for massive
transfusions in patients with a remarkable lack of side
effects.
Since both the firefly luciferin/lucerifase system and the aqueous
peroxyoxylate system can be too toxic in the doses that are
required to activate hematoporphyrin within atheromatous plaques,
the toxicity of these systems can be reduced markedly by
modifications such as microencapsulation of some or all of the
reactants in these liquids.
Accordingly, it is an object of the present invention to provide a
method for treatment of atherosclerosis by destruction of the
atheromatous plaque.
It is a further object of the present invention to provide a
catheter for transmission of activating light directly into
atheromatous plaque by displacement of light-opaque blood between
the light-emitting portion of the catheter and the atheromatous
plaque.
It is yet a further object of the present invention to illuminate
artheromatous plaques, containing absorbed hematoporphyrin, with
minimum interruption of the flow of blood to the vital organs.
Yet another objective is to illuminate atheromatous plaques with
minimal elevation of the temperature of the mammal's blood.
Yet another objective is to illuminate atheromatous plaque by
perfusing the diseased vessel with liquid light.
Other objects and further scope of applicability of the present
invention will become apparent from the detailed description to
follow, taken in conjunction with the accompanying drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a schematic representation of use of the preferred
catheter, inserted into a main artery of a patient, for treatment
of atherosclerosis in accordance with the present invention;
and
FIG. 2 is a schematic representation of the use of a second type of
illuminating catheter in the treatment of atherosclerosis in
accordance with the present invention.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
The term "hematoporphyrin", as used herein, is intended to
encompass hematoporphyrin and its derivatives which are
preferentially taken up into atheromatous plaque and which respond
to a source of light to destroy the host cell tissue.
The preferred hematoporphyrin is the acetic acid-sulfuric acid
derivative of hematoporphyrin prepared, for example, as described
by Richard L. Lipson and Edward J. Baldes in "The Photodynamic
Properties of a Particular Hematoporphyrin Derivative", Arch. Derm.
82(4) 508-516, 1960 and by Richard L. Lipson et al in "The Use of a
Derivative of Hematoporphyrin in Tumor Detection", J. Natl. Cancer
Inst. 26(1):1-8, 1961. In general the method of Lipson et al
involves admixing a "crude" recrystallized hematoporphyrin with a
mixture of 19 parts glacial acetic acid and one part concentrated
sulfuric acid, followed by filtration to separate and remove the
undissolved residue. The solution is then neutralized, e.g. with of
3% sodium acetate solution, to precipitate out the hematoporphyrin
derivative (HPD). This hematoporphyrin derivative is recognized by
the trade designation HPD and is commercially available from
Oncology Research and Development, Inc. In practicing the present
invention, the HPD is used in the commercial form and is not
diluted in any way.
Sanderson et al, in "Hematoporphyrin as a Diagnostic Tool" Cancer
30(5) 1368-72 (1972) report that this hematoporphyrin derivative
(HPD) shows maximum fluorescence upon illumination with violet
light within a wave length range of about 400 to 410 nm. HPD
exhibits wide band absorbtion at about 500 nm with small peaks at
about 635 nm. For the purposes of the present invention, the
preferred activating illumination for the hematoporphyrin
derivative (HPD) is a monochromic red light at about 635 nanometers
because light at this wavelength penetrates tissue; and, the
preferred source for such illumination is a dye laser.
It has been well known for many years that HPD accumulates in
malignant tumors after intravenous injection and that HPD
fluorescence, upon exposure to ultraviolet light, facilitating
tumor localization. The aforementioned articles by Lipson et al
report on such findings. More recently, the cytotoxic effect of HPD
activated by light has been used to destroy malignant tumors in man
as well as in animals. Since normal tissues surrounding malignant
tumors absorb relatively small amounts of HPD, little or no damage
to these tissues occurs upon exposure to light. See, e.g.
"Photoradiation in the Treatment of Recurrent Breast Carcinoma", T.
J. Dougherty et al, J. Natl. Cancer Inst. 62(2):231-237 (1979).
In accordance with the present invention, it recently has been
discovered that HPD is selectively concentrated in atheromatous
plaques in the aorta of rabbits following intravenous injection.
Atheromatous plaques were found to fluoresce strongly when exposed
to ultraviolet light, while the normal plaque-free aortic wall
demonstrated no fluorescence. Since atheromatous plaques consist
primarily of cells which are engorged with lipids and other
materials, destruction of these cells by photoactivation of HPD
results in lysis of such plaques. It is believed that, upon
exposure to activating illumination, the hematoporphyrin produces
singlet oxygen which causes cell destruction. Thus, the present
invention involves photodynamic destruction of the atheromatous
plaques by activation of plaque-absorbed hematoporphyrin by a
process which may be characterized as photoatherolysis.
The preferred catheter of the invention is illustrated in FIG. 1.
In the representation of FIG. 1 the wall of the main artery
undergoing treatment is represented by the numeral 10. For
treatment, the mammal is catheterized with insertion of the
light-emitting portion of the catheter into the diseased blood
vessel to a position adjacent the deposit of atheromatous plaque to
be lysed. FIG. 1 depicts the preferred catheter positioned in this
manner. The preferred catheter includes a lumen tube 12 and a
balloon member 14 affixed to its distal end with the interior of
the balloon opening into the lumen of the catheter tube. FIG. 1
depicts the balloon 14 in its inflated state with its exterior
surface in direct contact with the atheromatous plaque 16 to be
lysed. The deflated state of the balloon is indicated by the dotted
line 18. Inflation of the balloon is provided for by the lumen of
the catheter which is in fluid communication with the interior of
the balloon and which may be connected, at its opposite end, to a
source of pressurized gas. At least one optical fiber 20 is
provided for transmitting light from an external source to liquid
22 contained in a hollow glass fiber 24. The liquid 22, for example
one of many refractive index liquids commercially available from
Cargille Laboratories, functions to transmit the scatter light
throughout the interior of balloon 14. A movable guidewire 28
extends through the center of the lumen of the catheter tube and
through the center of the hollow glass fiber. The distal end of the
guidewire 28 extends a variable distance beyond the distal end of
the balloon 14.
FIG. 2 depicts the use of a catheter which is not provided with a
balloon but which is otherwise similar. In FIG. 2, corresponding
components of the catheter are represented by like numerals. A
catheter of this design may be particularly advantageous for use in
small vessels, such as coronary arteries, wherein displacement of
the relatively small volume of blood with a balloon may be
unnecessary for light to be transmitted to a plaque.
A particularly advantageous feature of the preferred catheter
illustrated in FIG. 1 is the capability for delivering light to the
plaque in an intermittent fashion. Intermittent light transmission,
synchronized with intermittent balloon inflation, is advantageous
when a prolonged exposure of a plaque to light within and to a
vital organ is required. For example, inflation of the balloon with
a low viscosity gas during the only one part of each cardiac cycle,
may be performed utilizing counter-pulsation circulatory assist
devices, and can be synchronized with light transmission, so that a
long total, additive exposure of a plaque to light may be achieved
without significant compromise of blood flow. Although light may be
transmitted continuously along the optical fiber and exposure of
the plaque to light would then occur only when inflation of the
balloon is sufficiently great to displace intervening blood,
intermittent transmission of the light along the fiber would be
advantageous when the light intensity required would result in
heating the balloon material and/or blood. For example, a thick
plaque may require an intense light in order to activate HPD deep
within the plaque. The heat produced by the light could adversely
affect the balloon material and/or blood within the artery.
Intermittent transmission of light would allow both the balloon
material and the gas within the balloon to be cooled intermittently
by the flow of blood past the balloon during balloon deflation. A
period of 30 minutes or more may be required to photoactivate HPD
deep within a plaque. However, obstruction of blood flow with the
balloon inflated continuously for such a length of time cannot be
performed within arteries to vital organs without deliterious
effects. In such a case ECG-gated, intermittent balloon inflation,
as is commonly performed with an intra-aortic balloon used in a
counterpulsation circulatory assist device, may be employed so as
not to interfere with blood flow to vital organs, while at the same
time permitting a prolonged exposure of a plaque to light.
Others skilled in the art of fabrication of optical fibers and
catheters may proffer many modifications of the basic design of the
preferred catheter. For example, the optical fiber 20 may terminate
without coupling to any other fiber; a properly designed lens at
the terminal end of the optical fiber 20 might be used to disperse
light over the internal surface of the artery. Alternatively, the
optical fiber 20 may be coupled, at its distal end, to a specially
designed solid fiber which would be used to disperse light along
all or a portion of its length.
In accordance with the present invention, it has been discovered
that aqueous peroxyoxylate chemiluminescent liquids manufactured by
the American Cyanamid Company may be injected into the bloodstream
of rats and rabbits without producing any side effects. The liquid
reactants typically include a triflyl oxamide and hydrogen peroxide
along with sulfonated rubrene as a fluorescer and Deceresol NI as a
surfactant. A quantum yield of the reaction of 7% with a light
capacity of 62 lumen hours per liter of solution was reported
recently by A. G. Mohan et al in "Aqueous Peroxyoxalate
Chemiluminescence: Final Report to the Office of Naval Research,
Contract N0014-77-C-0634." This quantity of light is considerably
more than that needed to activate hematoporphyrin. Thus, the
injection of the chemiluminescent liquid light into the vascular
tree of mammals can be performed for activation of hematoporphyrin
within atheromatous plaques for lysis all of plaques throughout the
vascular tree.
Another form of liquid light which can be injected into the
bloodstream of mammals is the well-known firefly lucerin/lucerifase
bioluminescent system. Luciferin and luciferase are water soluble,
and light is emitted when adenosine triphosphate, which is also
water soluble, is added to these substances. A buffer such as
glycine and the metal ion, magnesium, are usually present in the
solution to facilitate the reaction. Intravenous injection of these
materials, obtained commercially from Sigma Chemical Company, into
dogs has produced no deliterious side effects.
If the light-opacity of blood prevents a sufficient quantity of
light, in the form of liquid light, to activate hematoporphyrin
within an atheromatous plaque, replacement of blood with a more
translucent blood substitute may be performed. Examples would
include normal saline, dextrose in water, and Frales-Linger
solution. For replacement of blood within the entire vascular tree
or within blood vessels to vital organs, perfluorocarbon
emulsion-containing blood substitutes, such as Fluosol-DA, may be
used. Fluosol-DA carries oxygen in a manner similar to hemoglobin
and has been approved by the FDA for use in clinical trials. For
examples of the use of Fluosol-DA as a blood substitutes, see
Engelman et al, Ann Thorac Surg 32: 528-535 (1981), Kanter et al,
Circulation 64:75-83 (1981).
An advantage in the use of liquid light of activate
hematophorphyrin within atheromatous plaques is that, once the
liquid light has mixed in sufficient quantity with blood or a blood
substitute throughout the vascular tree, it would be unnecessary to
know the location of the plaques in order to lyse all plaques
within the entire vascular tree. An other advantage is that a
catheterization procedure would be unnecessary to deliver the light
to a plaque in a vessel segment of interest.
The invention may be embodied in other specific forms without
departing from the spirit or essential characteristics thereof. The
present embodiments are therefore to be considered in all respects
as illustrated and not restricted, the scope of the invention being
indicated by the appended claims rather than by the foregoing
description and all changes which come within the meaning and range
of equivalency of the claims are therefore intended to be embraced
therein.
* * * * *