U.S. patent application number 15/091270 was filed with the patent office on 2016-07-28 for method and apparatus for treating benign prostatic hyperplasia with light-activated drug therapy.
This patent application is currently assigned to PURDUE PHARMACEUTICAL PRODUCTS L.P.. The applicant listed for this patent is PURDUE PHARMACEUTICAL PRODUCTS L.P.. Invention is credited to Jean Bishop, Phillip Burwell, James C. Chen, Steven Ross Daly, Zihong Guo, Erik Hagstrom, Joseph M. Hobbs, Llew Keltner, Gary Lichttenegger, Jennifer K. Matson, Hugh Narciso, David B. Shine, Jay Winship, Nick Yeo, Frank Zheng.
Application Number | 20160213945 15/091270 |
Document ID | / |
Family ID | 37960404 |
Filed Date | 2016-07-28 |
United States Patent
Application |
20160213945 |
Kind Code |
A1 |
Burwell; Phillip ; et
al. |
July 28, 2016 |
METHOD AND APPARATUS FOR TREATING BENIGN PROSTATIC HYPERPLASIA WITH
LIGHT-ACTIVATED DRUG THERAPY
Abstract
A photoreactive agent and a drug therapy device including a
support member configured to pass through a urethra having proximal
and distal ends and a longitudinal internal lumen. A light
generator carried by the support member, potted within the lumen,
and positioned within the urethra to deliver light to the prostate.
The light generator generates a light band with a peak at a
preselected wavelength. A power source external to the support
member powers the light generator. The positioning element locates
the support member within the urethra. A transparent/translucent,
integral window is positioned proximate to the prostate and allows
light to pass through. The window extends 360 degrees radially from
the support member. The light generator has at least LEDs or LOs
having a dimension of approximately 0.3 mm.times.0.3 mm.times.0.1
mm (length.times.width.times.thickness).
Inventors: |
Burwell; Phillip;
(Snohomish, WA) ; Guo; Zihong; (Bellevue, WA)
; Matson; Jennifer K.; (Renton, WA) ; Daly; Steven
Ross; (Sammamish, WA) ; Shine; David B.;
(Sammamish, WA) ; Lichttenegger; Gary;
(Woodinville, WA) ; Bishop; Jean; (Issaquah,
WA) ; Yeo; Nick; (Great Bookham, GB) ;
Narciso; Hugh; (Santa Barbara, CA) ; Keltner;
Llew; (Portland, OR) ; Winship; Jay;
(Bellevue, WA) ; Hagstrom; Erik; (Woodinville,
WA) ; Zheng; Frank; (Kirkland, WA) ; Chen;
James C.; (Clyde Hill, WA) ; Hobbs; Joseph M.;
(Issaquah, WA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
PURDUE PHARMACEUTICAL PRODUCTS L.P. |
STAMFORD |
CT |
US |
|
|
Assignee: |
PURDUE PHARMACEUTICAL PRODUCTS
L.P.
STAMFORD
CT
|
Family ID: |
37960404 |
Appl. No.: |
15/091270 |
Filed: |
April 5, 2016 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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11834572 |
Aug 6, 2007 |
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15091270 |
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|
10799357 |
Mar 12, 2004 |
7252677 |
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11834572 |
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12161323 |
Nov 19, 2008 |
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PCT/US2007/001324 |
Jan 18, 2007 |
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10799357 |
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60455069 |
Mar 14, 2003 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61N 5/062 20130101;
A61N 2005/063 20130101; A61B 2018/00285 20130101; A61B 2018/00547
20130101; A61N 5/0603 20130101; A61B 2018/00821 20130101; A61N
5/0601 20130101; A61N 2005/061 20130101; A61K 41/0071 20130101;
A61B 2017/00084 20130101; A61N 2005/0652 20130101; A61B 2017/22068
20130101; A61B 2017/00274 20130101; A61N 2005/067 20130101; A61N
2005/0602 20130101; A61B 2018/2261 20130101 |
International
Class: |
A61N 5/06 20060101
A61N005/06 |
Foreign Application Data
Date |
Code |
Application Number |
Jan 18, 2006 |
CN |
200620088987.8 |
Claims
1. A transurethral light-activate drug therapy system for the
treatment of prostate conditions in a male animal having an
enlarged prostate, comprising: a photoreactive agent comprising
mono-L-aspartyl chlorine e6; and a transurethral light activate
drug therapy device comprising: a flexible elongated support member
configured to pass through a urethra of the male animal, the
elongated support member having a proximal end and a distal end; at
least one longitudinal internal lumen through a majority of a
length of the elongated support member; a light delivery device
having a light generator carried by a distal region of the support
member and potted within the lumen, the light generator and a light
emitting region are configured to be positioned within the urethra
to deliver light to the prostate, wherein the light generator is
configured to generate a light band with a peak at a preselected
wavelength of about 664 nm radially at 360 degrees; a power source
external to the support member, in flexible electrical
communication with the light generator; and a positioning element
carried by the support member, wherein: the positioning element is
configured to locate the support member within the urethra; a
majority of the portion of the support member inserted into the
urethra of the male animal does not permit light from the light
generator to pass through; a transparent or translucent, integral
window along a portion of the length of the support member that is
proximate to the prostate when the distal end of the support member
is positioned in the bladder of the male animal and allows light
from the light generator to pass through the window, and the window
extends 360 degrees radially from the support member; the length of
the light generator is at least as long as a majority of the length
of the window; a majority of the length of the light generator is
fixed in place within the window; when the support member is
completely removed from the urethra, the light generator is
completely removed from the urethra; and wherein the light
generator comprises at least one or more of a light emitting diode
(LED), and solid-state laser diode (LO) having a dimension of
approximately 0.3 mm.times.0.3 mm.times.0.1 mm
(length.times.width.times.thickness).
2. The transurethral light-activated drug therapy system of claim 1
wherein the window comprises embedded light scattering
elements.
3. The transurethral light-activated drug therapy system of claim 2
wherein the array of LEDs is configured to provide from
approximately 5 mW to 55 mW per centimeter of array length.
4. The transurethral light-activated drug therapy system of claim 1
wherein the array of LEDs or LOs is fixed at a selected location
within the catheter during treatment.
5. The transurethral light-activated drug therapy system of claim
1, further comprising a fixation device at the distal end of the
catheter, wherein the fixation device is sized to be inserted into
the bladder of the male animal in a delivery configuration.
6. The transurethral light-activated drug therapy system of claim
5, wherein the fixation device comprises a balloon for releasably
retaining the catheter in the urethra of the patient during
treatment.
7. The transurethral light-activated drug therapy system of claim 5
wherein the fixation device is a balloon, umbrella, tines, and/or
disk.
8. The transurethral light-activated drug therapy system of claim 5
wherein the fixation device is retractable.
9. The transurethral light-activated drug therapy system of claim
1, further comprising echogenic markings on the distal end of the
catheter or on the light source or both.
10. The transurethral light-activated drug therapy system of claim
1, further comprising positioning indicia on the proximal end of
the catheter.
11. The transurethral light-activated drug therapy system of claim
1, wherein light generator produces light energy in a range from 50
J/cm to 1000 J/cm.
12. The transurethral light-activated drug therapy system of claim
11, wherein light generator produces light energy of approximately
200 J/cm.
13. The transurethral light-activated drug therapy system of claim
1, wherein each of LEDs or LOs is introduced into a corresponding
separate compartment.
14. The transurethral light-activated drug therapy system of claim
1, wherein each of LEDs or LOs is potted in a potting material that
is electrically insulating and substantially optically transparent
to light emitted from the light generator.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is a Continuation-In-Part application of a
co-pending U.S. patent application Ser. No. 11/834,572, filed on
Aug. 6, 2007 which is a Continuation-In-Part application of U.S.
Pat. No. 7,252,677 that issued Aug. 7, 2007 from U.S. patent
application Ser. No. 10/799,357, filed on Mar. 12, 2004, which is
based on a U.S. Provisional Application Ser. No. 60/455,069, filed
on Mar. 14, 2003. All of these applications are herein incorporated
by reference in their entirety.
[0002] This application is a Continuation-In-Part application of a
co-pending U.S. patent application Ser. No. 12/161,323, which
entered U.S. on Nov. 19, 2008, which in turn is the National Stage
of International Application PCT/US2007/01324, filed Jan. 18, 2007,
and published as WO 2007/084608 on Jul. 26, 2007. The International
Application claims priority to Chinese Application No.
200620088987.8, filed Jan. 18, 2006. All of the above referenced
applications are herein incorporated by reference in their
entirety.
FIELD OF THE INVENTION
[0003] The present invention relates generally to a prostate
treatment system for treating prostatic tissue in combination with
a photoactive agent, and more specifically a transurethral device
in combination with a light-activated drug for use in treating
benign prostatic hyperplasia (BPH).
BACKGROUND
[0004] Photodynamic therapy (PDT) is a process whereby light of a
specific wavelength or waveband is directed to tissues undergoing
treatment or investigation, which have been rendered photosensitive
through the administration of a photoreactive or photosensitizing
agent. Thus, in this therapy, a photoreactive agent having a
characteristic light absorption waveband is first administered to a
patient, typically by intravenous injection, oral administration,
or by local delivery to the treatment site. Abnormal tissue in the
body is known to selectively absorb certain photoreactive agents to
a much greater extent than normal tissue. Once the abnormal tissue
has absorbed or linked with the photoreactive agent, the abnormal
tissue can then be treated by administering light of an appropriate
wavelength or waveband corresponding to the absorption wavelength
or waveband of the photoreactive agent. Such treatment can result
in the necrosis of the abnormal tissue. PDT has proven to be very
effective in destroying abnormal tissue such as cancer cells.
[0005] Benign prostatic hyperplasia (BPH) and prostate cancer are
common conditions in the older male population. For people with
BPH, the enlarged prostate can compress the urethra causing
obstruction of the urine pathway, which results in difficulty
urinating. The enlarged prostate can also cause urethral stones,
inflammation, infection and in some instances, kidney failure.
[0006] Major treatment methods for BPH include surgical treatment
such as a prostatectomy or transurethral resection of the prostate.
These treatments require the patient to be hospitalized, which can
be a financial burden to the patient. Additionally, surgical
procedures can result in significant side effects such as bleeding,
infection, residual urethral obstruction or stricture, retrograde
ejaculation, and/or incontinence or impotence. Patients who are too
old or who have weak cardiovascular functions are not good
candidates for receiving these treatment methods. PDT, also known
as light-activated drug therapy, in comparison to surgical
alternatives, is minimally invasive, less costly, and has a lower
risk of complications.
[0007] One type of light delivery system used for light-activated
drug therapy comprises the delivery of light from a light source,
such as a laser, to the targeted cells using an optical fiber
delivery system with special light-diffusing tips on the fibers.
This type of light delivery system may further include optical
fiber cylindrical diffusers, spherical diffusers, micro-lensing
systems, an over-the-wire cylindrical diffusing multi-optical fiber
catheter, and a light-diffusing optical fiber guide wire. This
light delivery system generally employs a remotely located
high-powered laser, or solid-state laser diode array, coupled to
optical fibers for delivery of the light to the targeted cells.
[0008] The light source for the light delivery system used for
light-activated drug therapy may also be light emitting diodes
(LEDs) or solid-state laser diodes (LDs). LEDs or LDs may be
arrayed in an elongated device to form a "light bar" for the light
delivery system. The LEDs or LDs may be either wire bonded or
electrically coupled utilizing a "flip chip" technique that is used
in arranging other types of semiconductor chips on a conductive
substrate. Various arrangements and configurations of LEDs or LDs
are described in U.S. Pat. Nos. 5,445,608; 6,958,498; 6,784,460;
and 6,445,011, which are incorporated herein by reference.
[0009] One of the challenges in design and production of light bars
relates to size. The largest diameter of the light bar is defined
by human anatomy and the smallest diameter is defined by the size
of the light emitters that emit light of a desired wavelength or
waveband at a sufficient energy level, and the fragility of the bar
as its thickness is reduced, which increases the risk of breaking
in the patient.
[0010] Presently, there exists a need for an apparatus for
light-activated drug therapy for effectively treating prostate via
the urethra that is cost effective, less invasive than other
treatments, and has less risk of complications. Accordingly, there
is a need for smaller LEDs or LDs and other light sources that are
safe for use in a urethra tract introduced via a catheter-like
device.
SUMMARY
[0011] Thus, examples of the invention include a transurethral
light-activate drug therapy system for the treatment of prostate
conditions in a male animal having an enlarged prostate. The device
includes a photoreactive agent of mono-L-aspartyl chlorine e6 and a
transurethral light activate drug therapy device. The device
includes a flexible elongated support member configured to pass
through a urethra of the male animal, the elongated support member
having a proximal end and a distal end and at least one
longitudinal internal lumen through a majority of a length of the
elongated support member. A light delivery device having a light
generator carried by a distal region of the support member and
potted within the lumen, the light generator and a light emitting
region are configured to be positioned within the urethra to
deliver light to the prostate. The light generator is configured to
generate a light band with a peak at a preselected wavelength of
about 664 nm radially at 360 degrees. Also, a power source external
to the support member is in flexible electrical communication with
the light generator and a positioning element carried by the
support member.
[0012] The positioning element is configured to locate the support
member within the urethra while a majority of the portion of the
support member is inserted into the urethra of the male animal and
does not permit light from the light generator to pass through. A
transparent or translucent, integral window along a portion of the
length of the support member is proximate to the prostate when the
distal end of the support member is positioned in the bladder of
the male animal and allows light from the light generator to pass
through the window, and the window extends 360 degrees radially
from the support member. The length of the light generator is at
least as long as a majority of the length of the window, a majority
of the length of the light generator is fixed in place within the
window, and when the support member is completely removed from the
urethra, the light generator is completely removed from the
urethra. The light generator has at least one or more of a light
emitting diodes (LEDs), and solid-state laser diode (LO) having a
dimension of approximately 0.3 mm.times.0.3 mm.times.0.1 mm
(length.times.width.times.thickness).
[0013] The window, in some examples, has embedded light scattering
elements. Further, the each of LEDs or LOs is potted in a potting
material that is electrically insulating and substantially
optically transparent to light emitted from the light
generator.
BRIEF DESCRIPTION OF THE DRAWINGS
[0014] The following drawings are intended as an aid to an
understanding of the invention to present examples of the
invention, but do not limit the scope of the invention as described
and claimed herein. In the drawings, identical reference numbers
identify similar elements or acts. The sizes and relative positions
of elements in the drawings are not necessarily drawn to scale. For
example, the shapes of various elements and angles are not drawn to
scale, and some of these elements are arbitrarily enlarged and
positioned to improve drawing legibility. Further, the particular
shapes of the elements as drawn, are not intended to convey any
information regarding the actual shape of the particular elements,
and have been solely selected for ease of recognition in the
drawings.
[0015] FIG. 1 schematically illustrates a first embodiment of a
light-generating apparatus suitable for intravascular use in accord
with the present invention;
[0016] FIG. 2 is a longitudinal cross-sectional view of the
light-generating apparatus of FIG. 1;
[0017] FIGS. 3A and 3B are exemplary radial cross-sectional views
of two different embodiments of the light-diffusing portion of the
light-generating apparatus of FIG. 1;
[0018] FIG. 4A schematically illustrates a second embodiment of a
light-generating apparatus suitable for intravascular use in accord
with the present invention;
[0019] FIG. 4B is a longitudinal cross-section view of the
light-generating apparatus of FIG. 2;
[0020] FIG. 5 schematically illustrates yet another embodiment of a
light-generating apparatus suitable for intravascular use in accord
with the present invention;
[0021] FIG. 6 is an elevational side view of a prostate treatment
system having a transurethral treatment device according to one
embodiment of the invention;
[0022] FIG. 7 is a cross-sectional view taken along line 2-2 of
FIG. 6 illustrating one embodiment of lumens in the transurethral
treatment device;
[0023] FIG. 8 schematically illustrates a multicolor light array
for use in the light-generating apparatus of FIGS. 5-7;
[0024] FIGS. 9A and 9B schematically illustrate configurations of
light arrays including strain relief features for enhanced
flexibility for use in a light-generating apparatus in accord with
the present invention;
[0025] FIG. 9C is cross-sectional view of a light-generating
apparatus in accord with the present invention, showing one
preferred configuration of how the light emitting array is
positioned relative to the guidewire used to position the
light-generating apparatus;
[0026] FIG. 9D schematically illustrates a portion of a
light-generating apparatus in accord with the present invention,
showing how in another preferred configuration, the light emitting
array is positioned relative to the guidewire used to position the
light-generating apparatus;
[0027] FIG. 10 is side view of a transurethral treatment device
positioned in the urethra tract of a patient according to an
embodiment of the invention;
[0028] FIG. 11 is a cross-sectional view of a transurethral
treatment device in accordance with another embodiment of the
invention;
[0029] FIG. 12A schematically illustrates a modified guidewire for
use in the light-generating transurethral apparatus of FIGS. 10 and
11;
[0030] FIGS. 12B-12D are cross-sectional views of the guidewire of
FIG. 12A, showing details of how the light emitting elements are
integrated into the guidewire;
[0031] FIGS. 13A and 13B schematically illustrate a hollow
guidewire including a light source array disposed at its distal
end;
[0032] FIG. 13C schematically illustrates a connection jack that
can be used to electrically couple the array in the hollow
guidewire of FIGS. 13A and 13B to a power source;
[0033] FIG. 13D is a cross-sectional view of the connection jack
taken along section line A-A of FIG. 13C;
[0034] FIG. 13E is a cross-sectional view of the connection jack
taken along section line B-B of FIG. 13C;
[0035] FIG. 13F is a cross-sectional view of the guidewire of FIGS.
13A and 13B taken along section line C-C of FIG. 13B;
[0036] FIG. 13G is a side view of a first exemplary array for the
guidewire of FIGS. 13A and 13B;
[0037] FIG. 13H is a plan view of the first exemplary array for the
guidewire of FIGS. 13A and 13B;
[0038] FIG. 13I is a plan view of a second exemplary array for the
guidewire of FIGS. 13A and 13B;
[0039] FIG. 13J is a plan view of a third exemplary array for the
guidewire of FIGS. 13A and 13B;
[0040] FIG. 13K is a side view of a fourth exemplary array for the
guidewire of FIGS. 13A and 13B;
[0041] FIG. 13L is a plan view of the fourth exemplary array for
the guidewire of FIGS. 13A and 13B;
[0042] FIG. 13M is a plan view of a large array from which the
fourth exemplary array can be removed for facilitating
manufacturing of the fourth exemplary array;
[0043] FIG. 13N schematically illustrates yet another hollow
guidewire including a light source array disposed at its distal
end;
[0044] FIG. 13O is a cross-sectional view of the hollow guidewire
of FIG. 13N taken along section line D-D of FIG. 13N;
[0045] FIG. 13P is a cross-sectional view of the hollow guidewire
of FIG. 13N taken along section line E-E of FIG. 13N;
[0046] FIG. 14A schematically illustrates still another embodiment
of a light-generating apparatus, which includes a plurality of
inflatable balloons, as the apparatus is being positioned within a
urethra;
[0047] FIG. 14B is a cross-sectional view of the light-generating
apparatus of FIG. 14A;
[0048] FIG. 14C schematically illustrates an alternative
configuration of a light-generating apparatus including a plurality
of inflatable balloons, as the apparatus is being positioned within
a urethra;
[0049] FIG. 14D is a cross-sectional view of the light-generating
apparatus of FIG. 14C;
[0050] FIG. 15 schematically illustrates a plurality of balloons
included with a light-generating apparatus in accord with the
present invention;
[0051] FIG. 16A is a cross-sectional view of one example of a light
emitting catheter disposed in a central lumen of an introducer
catheter;
[0052] FIG. 16B is a side view of a light source array for use in
the light emitting catheter of FIG. 16A;
[0053] FIG. 17 is a cross-sectional view of a transurethral
treatment device in accordance with yet another embodiment of the
invention;
[0054] FIG. 18 is a cross-sectional view of a transurethral
treatment device in accordance with still another embodiment of the
invention; and
[0055] FIG. 19 is a cross-sectional view of a transurethral
treatment device in accordance with another embodiment of the
invention.
DETAILED DESCRIPTION
[0056] Exemplary embodiments are illustrated in referenced Figures
of the drawings. It is intended that the embodiments and Figures
disclosed herein are to be considered illustrative rather than
restrictive. No limitation on the scope of the technology and of
the claims that follow is to be imputed to the examples shown in
the drawings and discussed herein.
[0057] In the following description, certain specific details are
set forth in order to provide a thorough understanding of various
embodiments of the invention. However, one skilled in the relevant
art will recognize that the invention may be practiced without one
or more of these specific details, or with other methods,
components, materials, etc. In other instances, well-known
structures associated with light sources, catheters and/or
treatment devices have not been shown or described in detail to
avoid unnecessarily obscuring descriptions of the embodiments of
the invention.
[0058] Unless otherwise defined, it should be understood that each
technical and scientific term used herein and in the claims that
follow is intended to be interpreted in a manner consistent with
the meaning of that term as it would be understood by one of skill
in the art to which this invention belongs. The drawings and
disclosure of all patents and publications referred to herein are
hereby specifically incorporated herein by reference. In the event
that more than one definition is provided herein, the explicitly
defined definition controls.
[0059] Referring to FIG. 1, a light-generating apparatus 1, having
a distal end 6 and a proximal end 8, is embodied in a catheter
having an elongate, flexible body 4 formed from a suitable
biocompatible material, such as a polymer or metal. Catheter body 4
includes at least one lumen 18. While lumen 18 is shown as
centrally disposed within catheter body 4, it should be understood
that lumen 18 can be disposed in other positions, and that other
lumens, such as lumens for inflating a balloon or delivering a
fluid (neither separately shown) can also be included and disposed
at locations other than along a central axis of catheter body 4.
Lumen 18 has a diameter sufficient to accommodate a guidewire and
extends between distal end 6 and proximal end 8 of the catheter,
passing through each portion of light-generating apparatus 1. FIG.
1 is not drawn to scale, and a majority of light-generating
apparatus 1 shown in FIG. 1 relates to elements disposed near
distal end 6. It should be understood that light-generating
apparatus 1 is preferably of sufficient length to be positioned so
that distal end 6 is disposed at a treatment site within a
patient's body, while proximal end 8 is disposed outside of the
patient's body, so that a physician or surgeon can manipulate
light-generating apparatus 1 with the proximal end.
[0060] A light source array 10 includes a plurality of light
emitting devices, which are preferably LEDs disposed on conductive
traces electrically connected to lead 11. Lead 11 extends
proximally through lumen 18 and is coupled to an external power
supply and control device 3. While lead 11 is shown as a single
line, it should be understood that lead 11 includes at least two
separate conductors, enabling a complete circuit to be formed that
supplies current to the light emitting devices from the external
power supply. As an alternative to LEDs, other sources of light may
instead be used, including but not limited to: organic LEDs, super
luminescent diodes, laser diodes, and light emitting polymers. In a
preferred embodiment, each LED of light source array 10 is
encapsulated in a polymer layer 23. Preferably, collection optics
12 are similarly encapsulated in polymer layer 23. Light source
array 10 is preferably coupled to collection optics 12, although it
should be understood that collection optics 12, while preferred,
are not required. When present, collection optics 12 are coupled to
either a single optical fiber 14, or an optical fiber bundle (not
separately shown). Distal to optical fiber 14 is a light-diffusing
tip 16, which can be implemented using glass or plastic. Light
emitted from light source array 10 passes through collection optics
12, which focus the light toward optical fiber 14. Light conducted
along optical fiber 14 enters diffusing tip 16 at distal end 6 and
is scattered uniformly. Preferably, diffusing tip 16 includes a
radio-opaque marker 17 to facilitate fluoroscopic placement of
distal end 6.
[0061] FIG. 2 illustrates a longitudinal cross-section view of
light-generating apparatus 1. Collection optics 12 (e.g., a lens)
are bonded to light source array 10 and optical fiber 14 by polymer
layers 23, and the polymer layer is preferably an epoxy that is
optically transparent to the wavelengths of light required to
activate the photoreactive agent that is being used. Individual
LEDs 10a and leads 10b (each coupling to lead 11) can be clearly
seen.
[0062] FIG. 3A is a radial cross-sectional view of diffusing tip
16, which includes one diffusing portion 36 and lumen 18. FIG. 3B
is a radial cross-sectional view of an alternative diffusing tip
16a, which includes a plurality of diffusing portions 36
encapsulated in a polymer 33, and lumen 18. Polymer 33 preferably
comprises an epoxy, and such an epoxy will likely be optically
transparent to the wavelengths of light required to activate the
photoreactive agent being utilized; however, because the light will
be transmitted by diffusion portions 36, polymer 33 is not required
to be optically transparent to these wavelengths. In some
applications, it may be desirable to prevent light of any
wavelength that can activate the photoreactive agent from exiting a
light-generating apparatus other than from its distal end, and
polymers do not transmit such wavelengths can be used to block such
light.
[0063] Turning now to FIG. 4A, another embodiment of a light
generating catheter is schematically illustrated. A
light-generating apparatus 5 is similarly based a catheter having
body 4, including lumen 18, and includes distal end 6 and proximal
end 8. As discussed above, while only a single lumen configured to
accommodate a guidewire is shown, it should be understood that
light-generating apparatus 5 can be configured to include
additional lumens as well (such as those used for balloon
inflation/deflation). Note that FIGS. 4A and 4B are not drawn to
scale; with distal end 6 being emphasized over proximal end 8.
[0064] Light-generating apparatus 5 includes a light source array
40 comprising a plurality of LEDs 40a (seen in phantom view) that
are electrically coupled to lead 11 via leads 40c. As discussed
above, light source array 40 is preferably encapsulated in a
light-transmissive polymer 23, or at least, in an epoxy that
transmits the wavelengths of light required to activate the
photoreactive agent introduced into the target tissue. Positioned
immediately behind LEDs 40a (i.e., proximal of LEDs 40a) is a
highly-reflective disk 40b. Any light emitted from LEDs 40a in a
direction toward proximal end 8 is reflected back by reflective
disk 40b towards distal end 6. Additionally, a reflective coating
43 (such as aluminum or another reflective material), is applied to
the outer surface of body 4 adjacent to light source array 40. Any
light from LEDs 40a directed to the sides (i.e., towards body 4) is
redirected by reflective coating 43 towards distal end 6.
Reflective disk 40b and reflective coating 43 thus cooperatively
maximize the intensity of light delivered through distal end 6.
[0065] Light source array 40 is coupled to a focusing lens 42,
which in turn, is coupled to an optical fiber bundle 44.
Preferably, optical fiber bundle 44 tapers toward distal end 6, as
shown in FIGS. 4A and 4B; however, it should be understood that
this tapered shape is not required. Optical fiber bundle 44 is
coupled to a light-diffusing tip 46. An expandable member 47 (such
as an inflatable balloon) is included for centering
light-generating apparatus 5 within a urethra or blood vessel and
for occluding blood flow past distal end 6 that could reduce the
amount of light delivered to the targeted tissue. The expandable
member is preferably secured to distal end 6 so as to encompass
light-diffusing tip 46. Expandable member 47 may be formed from a
suitable biocompatible material, such as, polyurethane,
polyethylene, fluorinated ethylene propylene (PEP),
polytetrafluoroethylene (PIPE), or polyethylene terephthalate
(PET).
[0066] It should be understood that while light source array 40 has
been described as including a plurality of LEDs 40a disposed on
conductive traces electrically connected to lead 11, light source
array 40 can alternatively use other sources of light. As noted
above, possible light sources include, but are not limited to,
organic LEDs, super luminescent diodes, laser diodes, and light
emitting polymers. While not shown in FIGS. 4A and 4B, it should be
understood that light-generating apparatus 5 can beneficially
incorporate a radio-opaque marker, as described above in
conjunction with light-generating apparatus 1 (in regard to
radio-opaque marker 17 in FIGS. 1A and 1B).
[0067] FIG. 5 schematically illustrates yet another embodiment of a
light-generating catheter in accord with the present invention.
This embodiment employs a linear light source array configured so
that a more elongate treatment area can be illuminated. While the
first and second embodiments described above use an elongate light
diffusing element to illuminate an elongate treatment area, because
the light diffusing elements are directing light, not generating
light, increasing the length of the diffusing elements merely
distributes the light over a greater area. If diffused over too
great an area, insufficient illumination will be provided to each
portion of the treatment site. The embodiment shown in FIG. 5
includes a linear light source array that enables an elongate
treatment area to be illuminated with a greater amount of light
than can be achieved using the embodiments shown in FIGS. 1-4B.
[0068] Referring to FIG. 5, light-generating apparatus 50 is
illustrated. As with the embodiments described above (i.e., the
light-generating apparatus shown in FIGS. 1 and 4),
light-generating apparatus 50 is preferably based on a multi-lumen
catheter and includes an elongate, flexible body formed from a
suitable biocompatible polymer or metal, which includes a distal
portion 52 and a proximal portion 54. A plurality of light emitting
devices 53 are disposed on a flexible, conductive substrate 55
encapsulated in a flexible cover 56 (formed of silicone or other
flexible and light transmissive material). Light emitting devices
53 and conductive substrate 56 together comprise a light source
array. Preferably, light emitting devices 53 are LEDs, although
other light emitting devices, such as organic LEDs, super
luminescent diodes, laser diodes, or light emitting polymers can be
employed. Each a light source array preferably ranges from about 1
cm to about 20 cm in length, with a diameter that ranges from about
0.5 mm to about 5 mm. Flexible cover 56 can be optically
transparent or can include embedded light scattering elements (such
as titanium dioxide particles) to improve the uniformity of the
light emitted from light-generating apparatus 50. While not
specifically shown, it should be understood that proximal portion
54 includes an electrical lead enabling conductive substrate 56 to
be coupled to an external power supply and control unit, as
described above for the embodiments that have already been
discussed.
[0069] The array formed of light emitting devices 53 and conductive
substrate 56 is disposed between proximal portion 54 and distal
portion 52, with each end of the array being identifiable by
radio-opaque markers 58 (one radio-opaque marker 58 being included
on distal portion 52, and one radio-opaque marker 58 being included
on proximal portion 54). Radio-opaque markers 58 comprise metallic
rings of gold or platinum. Light-generating apparatus 50 includes
an expandable member 57 (such as a balloon) preferably configured
to encompass the portion of light-generating apparatus 50 disposed
between radio-opaque markers 58 (i.e., substantially the entire
array of light emitting devices 53 and conductive substrate 56). As
discussed above, expandable member 57 enables occlusion of blood
flow past distal portion 52 and/or centers the light-generating
apparatus. Where expandable member is implemented as a fluid filled
balloon, the fluid acts as a heat sink to reduce a temperature
build-up caused by light emitting devices 53. This cooling effect
can be enhanced if light-generating apparatus 50 is configured to
circulate the fluid through the balloon, so that heated fluid is
continually (or periodically) replaced with cooler fluid.
Preferably, expandable member 57 ranges in size (when expanded)
from about 2 mm to 15 mm in diameter. Preferably such expandable
members are less than 2 mm in diameter when collapsed, to enable
the apparatus to be used in a coronary vessel. Those of ordinary
skill will recognize that catheters including an inflation lumen in
fluid communication with an inflatable balloon, to enable the
balloon to the inflated after the catheter has been inserted into a
urethra or blood vessel are well known. While not separately shown,
it will therefore be understood that light-generating apparatus 50
(particularly proximal portion 54) includes an inflation lumen.
When light emitting devices 53 are energized to provide
illumination, expandable member 57 can be inflated using a
radio-opaque fluid, such as Renocal 76.RTM. or normal saline, which
assists in visualizing the light-generating portion of
light-generating apparatus 50 during computerized tomography (CT)
or angiography. The fluid employed for inflating expandable member
57 can be beneficially mixed with light scattering material, such
as Intralipid, a commercially available fat emulsion, to further
improve dispersion and light uniformity.
[0070] Light-generating apparatus 50 is distinguished from
light-generating apparatus 1 and 4 described above in that
light-generating apparatus 1 and 4 are each configured to be
positioned within a vessel or other passage using a guidewire that
extends within lumen 18 substantially throughout the apparatus. In
contrast, light-generating apparatus 50 is positioned at a
treatment site using a guidewire 51 that does not pass through the
portion of light-generating apparatus 50 that includes the light
emitting devices. Instead, guidewire 51 is disposed external to
light-generating apparatus 50--at least between proximal portion 54
and distal portion 52. Thus, the part of guidewire 51 that is
proximate to light emitting devices 53 is not encompassed by
expandable member 57. Distal portion 52 includes an orifice 59a,
and an orifice 59b. Guidewire 51 enters orifice 59a, and exits
distal portion 52 through orifice 59b. It should be understood that
guidewire 51 can be disposed externally to proximal portion 54, or
alternatively, the proximal portion can include an opening at its
proximal end through which the guidewire can enter the proximal
portion, and an opening disposed proximally of light emitting
devices 53, where the guidewire then exits the proximal
portion.
[0071] The length of the linear light source array (i.e., light
emitting devices 53 and conductive substrate 56) is only limited by
the effective length of expandable member 57. If the linear array
is made longer than the expandable member, light emitted from that
portion of the linear array will be blocked by blood within the
vessel and likely not reach the targeted tissue. As described below
in connection with FIGS. 14A-14D, the use of a plurality of
expandable members enables even longer linear light source arrays
(i.e., longer than any single expandable member) to be used in this
invention.
[0072] FIG. 6 illustrates a prostate treatment system 600. This
uses a light delivery device similar to the ones described above
and they can be used as described below. This example includes a
power supply 601 and a transurethral treatment device 621 having an
elongated support member 602 and a light delivery device 606
positioned along or within the support member 602. The
transurethral treatment device 620 may further includes a balloon
603 or other type of positioning element carried by the elongated
support member 602. The support member 602 can be a catheter having
a lumen 604, or the support member 602 can be a closed body without
a lumen. According to an embodiment, the support member 602 has a
total length of 400 to 450 mm and has an outer diameter of 3.327
mm, and the balloon 603 at the distal end of the support member 602
has a volume of 610 to 30 ml and is used to position and fix the
light delivery device 606 proximate to the treatment site such as
the prostate. In another example, the support member 602 has a
total length of 400 to 800 mm and has an outer diameter of
approximately 5.33 mm (or 16 French), and the balloon 603 at the
distal end of the support member 602 has a volume of 610 to 10 ml
(cc).
[0073] The light delivery device 606 can have a light generator
606a and a light emitting region 606b. In the embodiment shown in
FIG. 6, the light generator 606a and the light emitting region 606b
are at approximately the same location of the elongated member, but
in other embodiments shown below, the light generator 606a may not
be coincident with the light emitting region 606b. As shown below,
the light generator 606a may be located towards the proximal end of
the support member 602. When the support member 602 is a catheter
with a lumen 604, the light delivery device 606 can move within the
lumen to be positioned relative to the treatment site. In other
embodiments, the light delivery device 606 can be disposed on the
surface of the catheter 602 below the balloon 603 or other type of
positioning element. The power for the light generator can be
transmitted to the light delivery device 606 via a lead wire 607
coupled to the power source 601. According to an embodiment of the
invention, light could be emitted by a light emitting diode (LED),
a laser diode, light-emitting polymer, or a quartz fiber tip
optically coupled to another internal source of light energy.
[0074] As illustrated in FIG. 7, the support member 602 can include
a plurality of lumens therein. For example, the balloon 603 is
connected to a fluid inlet 605 via lumen 604. Gas or liquid can be
pumped into inlet 605 and through lumen 604 to inflate balloon 603.
Referring to FIGS. 6 and 7 together, the transurethral treatment
device 621 can optionally have a urine aperture 611 positioned at
the distal end of the support member 602 that is connected to a
urine collection bag 613 via a urine lumen 612. The urine aperture
611 can be used to collect the patient's urine during
treatment.
[0075] The transurethral treatment device 621 can also optionally
include a temperature measuring system having at least one of a
temperature sensor 608 and a temperature monitor 610. The
temperature sensor 608 can be a thermocouple or other sensor as is
known in the art. The temperature sensor 608 is disposed on or
thermally coupled to a surface of the support member 602 and is
electrically connected to the temperature monitor 610 via wires 609
disposed within the support member 602. The temperature sensor 608
measures a temperature at the treatment site, for example,
proximate to the prostate during treatment. A control loop (not
shown) may further be connected to the temperature monitor 610 to
automatically shut the treatment device off in the event that the
temperature at the treatment site exceeds a predetermined value.
Alternatively, the temperature monitor 610 may further include a
warning device (not shown), such as a visual indicator or audible
indicator, to provide an operator with a warning that a
predetermined temperature has been reached or is being exceeded
during treatment.
[0076] FIGS. 8, 9A, and 9B are enlarged views of light source
arrays that can be used in a light-generating apparatus that can be
used in a prostate treatment system. Light source array 80, shown
in FIG. 8, includes a plurality of LEDs 86a and 86b that are
coupled to a flexible, conductive substrate 82. LEDs 86a emit light
of a first color, having a first wavelength, while LEDs 86b emit
light of a different color, having a second wavelength. Such a
configuration is useful if two different photoreactive agents have
been administered, where each different photoreactive agent is
activated by light of a different wavelength. Light source array 80
also includes one or more light sensing elements 84, such as
photodiodes or a reference LED, similarly coupled to flexible,
conductive substrate 82. Each light sensing element 84 may be
coated with a wavelength-specific coating to provide a specific
spectral sensitivity, and different light sensing elements can have
different wavelength-specific coatings. While light source array 80
is configured linearly, with LEDs on only one side (as is the array
in light-generating apparatus 50a of FIG. 5), it will be understood
that different color LEDs and light sensing elements can be
beneficially included in any of the light source arrays described
herein.
[0077] Because the light source arrays of the present invention are
intended to be used in flexible catheters inserted into the urethra
or other body passages, it is important that the light source
arrays be relatively flexible, particularly where a light source
array extends axially along some portion of the catheter's length.
Clearly, the longer the light source array, the more flexible it
must be. Light source arrays 10 and 40 (FIGS. 1A/1B, and 4A/4B,
respectively) are configured in a radial orientation, and light
emitted from the light sources in those arrays is directed to the
distal end of the respective catheters (light-generating apparatus
1 and 4). Because light source arrays 10 and 40 do not extend
axially along a substantial portion of their respective catheters,
the relatively flexibility of light source arrays 10 and 40 is less
important. However, light source array 80 (FIG. 8), and the light
source arrays of light-generating apparatus 50 and 606 (FIGS. 5 and
6, respectively), are linearly configured arrays that extend
axially along a more significant portion of their respective
catheters. A required characteristic of a catheter for insertion
into a urethra is that the catheter be sufficiently flexible to be
inserted into the urethra and advanced along a somewhat tortuous
path. Thus, light source arrays that extend axially along a portion
of a catheter can unduly inhibit the flexibility of that catheter.
FIGS. 9A and 9B schematically illustrate axially extending light
source arrays that include strain relief features that enable a
more flexible linear array to be achieved.
[0078] FIG. 9A shows a linear array 88a having a plurality of light
emitting sources 90 (preferably LEDS, although other types of light
sources can be employed, as discussed above) mounted to both a
first flexible conductive substrate 92a, and a second flexible
conductive substrate 92b. Flexible conductive substrate 92b
includes a plurality of strain relief features 93. Strain relief
features 93 are folds in the flexible conductive substrate that
enable a higher degree of flexibility to be achieved. Note that
first flexible conductive substrate 92a is not specifically
required and can be omitted. Further, strain relief features 93 can
also be incorporated into first flexible conductive substrate
92a.
[0079] FIG. 9B shows a linear array 88b having a plurality of light
emitting sources 90 mounted on a flexible conductive substrate 92c.
Note that flexible conductive substrate 92c has a crenellated
configuration. As shown, light emitting sources 90 are disposed in
each "notch" of the crenellation. That is, light emitting sources
90 are coupled to both an upper face 93a of flexible conductive
substrate 92c, and a lower face 93b of flexible conductive
substrate 92c. Thus, when light emitting sources 90 are energized,
light is emitted generally outwardly away from both upper surface
93a and lower surface 93b. If desired, light emitting sources 90
can be disposed on only upper surface 93a or only on lower surface
93b (i.e., light emitting sources can be disposed in every other
"notch"), so that light is emitted generally outwardly away from
only one of upper surface 93a and lower surface 93b. The
crenellated configuration of flexible conductive substrate 92c
enables a higher degree of flexibility to be achieved, because each
crenellation acts as a strain relief feature.
[0080] External bond wires can increase the cross-sectional size of
an LED array, and are prone to breakage when stressed. FIGS. 1A and
1B illustrate leads 10b that are exemplary of such external bond
wires. FIG. 9C schematically illustrates a flip-chip mounting
technique that can be used to eliminate the need for external bond
wires on LEDs 94 that are mounted on upper and lower surfaces 93c
and 93d (respectively) of flexible conductive substrate 92d to
produce a light source array 97. Any required electrical
connections 95 pass through flexible conductive substrate 92d, as
opposed to extending beyond lateral sides of the flexible
conductive substrate, which would tend to increase the
cross-sectional area of the array. Light source array 97 is shown
encapsulated in a polymer layer 23. A guidewire lumen 98a is
disposed adjacent to light source array 97. An expandable balloon
99 can encompass the array and guidewire lumen. Note that either,
but not both, polymer layer 23 and expandable balloon 99 can be
eliminated (i.e., if the expandable balloon is used, it provides
protection to the array, but if not, then the polymer layer
protects the array).
[0081] FIG. 9D shows a linear array 96 including a plurality of
light emitting sources (not separately shown) that spirals around a
guidewire lumen 98b. Once again, balloon 99 encompasses the
guidewire lumen and the array, although if no balloon is desired, a
polymer layer can be used instead, as noted above. For each of the
implementations described above, the array of light sources may
comprise one or more LEDs, organic LEDs, super luminescent diodes,
laser diodes, or light emitting polymers ranging from about 1 cm to
about 10 cm in length and having a diameter of from about 1 mm to
about 2 mm.
[0082] As illustrated in FIG. 10, the treatment device is
positioned transurethrally to allow access to the prostate,
followed by administration of a photoactive drug, by injection,
intravenously, or orally. The transurethral treatment device 621,
and more specifically a portion of the support member 602, can be
directed into the urethra under topical anesthesia. Once the
support member is positioned, 4 to 10 ml of saline or air can be
pumped into the balloon 603 via the air pumping channel 604 to
inflate the balloon 603. After inflation of the balloon 603, the
support member 602 can be pulled slightly proximally such that the
balloon 603 can be fixed at the inner opening of the urethra.
Accordingly, the light delivery device 606 can be (by design)
positioned at least proximate to or within the prostate. The
photoactive drug can then be administered to the patient, and the
light generator 606b can be activated.
[0083] The support member 602 has a proximal portion and a distal
portion relative to a power controller. The distal portion of
support member 602 includes the light delivery device 606. In one
embodiment, the light delivery device comprises a plurality of LEDs
in electrical communication with the power supply via lead wires
607 as shown in FIG. 6. The lead wires may be selected from any
suitable conductor that can be accommodated within the dimensions
of the support member, for example: a bus bar that electronically
couples the LEDs to the controller; flexible wires; a conductive
film or ink applied to a substrate, and the like. Additionally or
alternatively, the light delivery device may include Bragg
reflectors to better control the wavelength of the light that is to
be transmitted to the target cells.
[0084] A power controller 601 may be programmed to activate and
deactivate LEDs of a light delivery device in a pulsed sequence or
a continuous sequence. For example, the LEDs may form two halves of
the light array that may be turned on and off independently from
each other. Alternatively, the system may be programmed to
selectively activate and deactivate (e.g., address) different
selected individual or groups of LEDs along the length of the bar.
In this manner, a treatment protocol, for example causing the LEDs
to be lit in a certain sequence or at a particular power level for
a selected period of time, may be programmed into the controller.
Therefore, by selectively timing the pulses and/or location of the
light, the system delivers light in accordance with a selected
program. Alternatively, LEDs can be powered by DC continuously.
Examples of addressable light transmission arrays are disclosed in
U.S. Pat. No. 6,096,066, herein incorporated in its entirety by
reference. Exemplary light transmission arrays which include
shielding or distal protection are disclosed in U.S. patent
application Ser. No. 10/799,357, now U.S. Pat. No. 7,252,677, and
Ser. No. 10/888,572 (now abandoned), herein incorporated in their
entirety by reference.
[0085] Without being bound by any theory, applicants believe that
by delivering light in pulses, the efficacy of the light-activated
drug therapy is improved, given that the treated tissue is allowed
to reoxygenate during the cycles when the light is off. Applicants
further believe that tissue oxygenation during therapy is improved
by using a lower frequency. In one embodiment the operational
frequency is 50 Hz-5 kHz, and in one embodiment, is 50-70 Hz.
[0086] According to a further embodiment of the invention, the
treatment device may further include a temperature monitoring
system for monitoring the temperature at the treatment site.
[0087] In one embodiment, the support member 602 is a Foley
catheter and the light delivery device 606 is disposed in the Foley
catheter. Alternatively, the treatment device has a light delivery
device disposed in a conventional balloon catheter. Foley catheters
are available in several sub-types, for example, a Coude catheter
has a 45.degree. bend at the tip to allow easier passage through an
enlarged prostate. Council tip catheters have a small hole at the
tip which allows them to be passed over a wire. Three-way catheters
are used primarily after bladder, prostate cancer or prostate
surgery to allow an irrigant to pass to the tip of the catheter
through a small separate channel into the bladder. This serves to
wash away blood and small clots through the primary arm that drains
into a collection device.
[0088] FIG. 11 is a cross-sectional view of still another
embodiment of a transurethral treatment device 621. In this
embodiment, the light delivery device includes a light generator
606a along the support member 602 at a location that is either
within or external (shown) to the patient. The light delivery
device can further include a light emitting region 606b positioned
at least proximate to the treatment site and a light transmitting
region 606c (e.g., fiber optic) between the light generator 606a
and the light emitting region 606b. In FIG. 11, the support member
602 can be a catheter through which the light delivery device 606
can be moved for positioning, or the support member can be a closed
body to which the light delivery device 606 is attached (e.g.,
fixed at a set position).
[0089] FIGS. 12A-12D provide details showing how light emitting
devices can be integrated into guidewires for even easier insertion
into the urethra. Referring to FIG. 12A, a solid guidewire 120
includes a conductive core 124 and a plurality of compartments 121
formed in the guidewire around the conductive core. Conductive core
124 is configured to be coupled to a source of electrical energy,
so that electrical devices coupled to conductive core 124 can be
selectively energized by current supplied by the source.
Compartments 121 can be formed as divots, holes, or slots in
guidewire 120, using any of a plurality of different processes,
including but not limited to, machining, and laser cutting or
drilling. Compartments 121 can be varied in size and shape. As
illustrated, compartments 121 are arranged linearly, although such
a linear configuration is not required. Preferably, each
compartment 121 penetrates sufficiently deep into guidewire 120 to
enable light emitting devices 122 to be placed into the
compartments and be electrically coupled to the conductive core, as
indicated in FIG. 12B. A conductive adhesive 123 can be
beneficially employed to secure the light emitting devices into the
compartments and provide the electrical connection to the
conductive core. Of course, conductive adhesive 123 is not
required, and any suitable electrical connections can alternatively
be employed. Preferably, LEDs are employed for the light emitting
devices, although as discussed above, other types of light sources
can be used. If desired, only one compartment 121 can be included,
although the inclusion of a plurality of compartments will enable a
light source array capable of simultaneously illuminating a larger
treatment area to be achieved.
[0090] Once light emitting devices 122 have been inserted into
compartments 121 and electrically coupled to conductive core 124, a
second electrical conductor 126, such as a flexible conductive
substrate or a flexible conductive wire, is longitudinally
positioned along the exterior of guidewire 120, and electrically
coupled to each light emitting device 122 using suitable electrical
connections 128, such as conductive adhesive 123 as (illustrated in
FIG. 12B) or wire bonding (as illustrated in FIG. 12C). Guidewire
120 (and conductor 126) is then coated with an insulating layer
129, to encapsulate and insulate guidewire 120 (and conductor 126).
The portion of insulating layer 129 covering light emitting devices
122 must transmit light of the wavelength(s) required to activate
the photoreactive agent(s). Other portions of insulating layer 129
can block such light transmission, although it likely will be
simpler to employ a homogenous insulating layer that transmits the
light. Additives can be included in insulating layer 129 to enhance
the distribution of light from the light emitting device, generally
as described above.
[0091] With respect to guidewires including integral light sources,
it should be noted that a guidewire that can emit light directly
simplifies light activated therapy, because clinicians are already
well versed in the use of guidewires to facilitate insertion of
catheters for procedures such as angioplasty or stent delivery. A
guidewire including integral light sources can be used with
conventional balloon catheters, to provide a light activated
therapy capability to catheters not originally exhibiting that
capability. Significantly, when such a guidewire is utilized with a
catheter including a central guidewire lumen and a non-compliant
angioplasty balloon, inflation of the balloon will center the
guidewire in the body lumen, and will hold the guidewire in place
during the light therapy (so long as the balloon is inflated). The
inflated balloon will exert pressure outwardly on the vessel wall
and inwardly on the guidewire. Preferably, the guidewires disclosed
herein with integral light sources will be similar in size, shape
and handling characteristics as compared to commonly utilized
conventional guidewires, such that clinicians can leverage their
prior experience with non-light emitting guidewires. It is also
possible to use the light emitting guidewires disclosed herein
without a balloon catheter. If the vessel being treated has a
diameter that is just slightly larger than the guidewire, there
will be a very thin layer of blood present between the light
emitting elements and the vessel wall. In this case, the light
emitting guidewire can be used alone, directing the light through
the thin layer of blood to treat the vessel wall. This has the
advantage of allowing treatment into extremely small vessels that
would otherwise not be accessible with conventional techniques.
[0092] Yet another exemplary embodiment of a guidewire
incorporating light sources at a distal end of the guidewire is
schematically illustrated in FIGS. 13A and 13B. A guidewire 200 is
based on a nitinol hypotube 202, which includes a flexible circuit
of LEDs (i.e., a light source array 220, shown in FIGS. 13B and
13F) disposed inside a distal end 204 of the hypotube. In at least
one exemplary embodiment, the distal end of the nitinol hypotube is
laser cut to remove a majority of the tube material proximate to
the LED array, yet retain the columnar structure of the tube. In a
particularly preferred embodiment, about 75-90% of the portion of
the tube surrounding the LED array is eliminated. FIG. 13B enables
additional details of distal end 204 of tube 202 to be identified.
Note that the material removal process (e.g., laser cutting,
although it should be recognized that other material removing
techniques can be employed) results in the formation of a plurality
of openings 206. As illustrated, the openings are generally
quadrilateral in shape, although it should be recognized that the
particular shape of the openings is not critical. Furthermore, it
should be recognized that the dimensions noted in FIG. 13B are
intended to be exemplary, rather than limiting. Openings 206 are
configured to enable light from the LEDs that are disposed within
the hypotube proximate to the openings to pass through the
openings. Conductors 208 and 210 extend from array 220 to a
proximal end of the guidewire, to enable the array to be
selectively energized by an external power source.
[0093] Many conventional guidewires are available having an outer
diameter of about 0.035 inches. Initial exemplary working
embodiments of guidewires including integral LED light sources have
ranged from about 0.0320 inches to about 0.0348 inches in diameter.
Fabrication techniques are discussed in greater detail below, but
in general, the LED array is potted inside the nitinol hypotube. A
heat shrink tube can be applied over the openings overlying the LED
array during potting/curing, to be removed afterwards, or simply
left in place.
[0094] Nitinol is an excellent material for guidewires, because it
exhibits sufficient flexibility and push-ability. It has
radio-opaque properties, such that the LED portion will likely be
readily identifiable under fluoroscopy, since the LED portion is
encompassed by the plurality of openings, and the openings will
reduce the radio-opacity of that portion of the guidewire relative
to portions of the guidewire that do not include such openings. If
necessary, additional markers can be included proximally and
distally of the plurality of openings, to enable that portion of
the guidewire to be precisely positioned in a body lumen. Another
benefit of nitinol is that its thermal conductivity will enable
heat generated by the LEDs to be more readily dissipated. Cooler
operating temperatures for the LED array will improve wall plug
efficiency and enable higher irradiance output. Standard steerable
and anti-traumatic guidewire tips can be attached to such nitinol
hypotube guidewires, distal of the light source array.
[0095] Note that guidewire 200 is configured such that a standard
angioplasty catheter can fit over the entire length of guidewire
200. Thus, some sort of connector that fits inside the guidewire
cross-sectional area is required, to enable the light source array
disposed within the distal end of the guidewire to be electrically
coupled to a power supply. In an empirical prototype, an "RCA-like"
jack with two electrical terminations was fabricated from
conductively-plated stainless steel capillary tubes. This connector
was mated with a female connector to provide the electrical control
for the LED light therapy. FIG. 13C schematically illustrates a
proximal end of guidewire 200 including such a connector jack.
Conductors 208 and 210 extend from the proximal end of guidewire
200 to the light source array (for example, an LED array) disposed
at the distal end of guidewire 200, to enable the light source
array to be energized by an external power supply (not separately
shown). The connector jack includes tubes 212 and 214. When the
connector jack is fully assembled, tube 214 is disposed inside tube
212, and a distal end of tube 212 is inserted into the proximal end
of guidewire 200. An insulating spacer 216 separates tube 212 into
a proximal portion and a distal portion. A proximal end of
conductor 210 is electrically coupled to the distal portion of tube
212. Conductor 208 passes through the distal portion of tube 212,
and completely through tube 214. Note that tube 214 passes through
insulating spacer 216, so that conductor 208 can be electrically
coupled to the proximal portion of tube 212. Any void spaces in
tubes 212 and 214 are filled with an insulating potting material
218. FIG. 13D is a cross-sectional view of the connector jack taken
along section line A-A of FIG. 13C, and FIG. 13E is a
cross-sectional view of the connector jack taken along section line
B-B of FIG. 13C. In an exemplary, but not limiting embodiment, tube
212 has an inner diameter of 0.020 inches, and an outer diameter of
0.025 inches, and tube 214 has an inner diameter of 0.012 inches,
and an outer diameter of 0.018 inches.
[0096] FIG. 13F is a cross-sectional view of the distal end of
guidewire 200, taken along section line C-C of FIG. 13B, enabling a
light source array 220 to be observed. As noted above, void space
surrounding array 220 can be filled with a potting material 218a,
which is electrically insulating and optically transparent (note
the potting material employed in the connector jack of FIG. 13C
need not be optically transparent). In an exemplary, but not
limiting embodiment, nitinol hypotube guidewire 200 has an inner
diameter of 0.0270 inches (0.64 mm), and an outer diameter of
0.0325 inches (0.76 mm). Conductors 208 and 210 can be implemented,
for example, using wire having an outer diameter of 0.009 inches
(0.23 mm), and the light source array has a generally rectangular
form factor, having maximum dimensions of 0.021 inches in width and
0.010 inches in height. It should be recognized that such stated
dimensions are intended to be exemplary, rather than limiting.
[0097] FIG. 13G is a cross-sectional view of light source array
220, which includes a plurality of LEDs 224 (oriented in a linear
array) mounted on a flexible non-conductive substrate 222. While no
specific number of LEDs is required, empirical devices including
more than 30 LEDs have been fabricated. Significantly, substrate
222 is substantially transparent to the light emitted by LEDs 224,
such that light emitted from the LEDs is able to pass through the
substrate. Each LED emits light from each of its six faces (the
LEDs being generally cubical). Compared to two sided arrays, a
single sided array offers the advantages of lower manufacturing
costs, a smaller form factor, and cooler operating temperatures
(resulting in a greater light output per LED). Polyimide represents
an acceptable substrate material. While some polyimides have a
generally yellowish tint, that tint does not substantially
interfere with the transmission of red light. Empirical devices
show less than a 5% transmission loss due to passage of the light
through the substrate, though losses as high as 10% are still
acceptable. If blue LEDs are used, higher transmission losses are
to be expected, and a thinner substrate, or a different material
that is more transparent to blue light, can be employed. Conductive
traces 228 and bonding wires 226 enable the LEDs to be coupled to
conductors 208 and 210 (not separately shown in FIG. 13G). The
LEDs, traces, and bonding wires are encapsulated in potting
material 218a, which as noted above, is electrically insulating and
substantially optically transparent to the light emitted by the
LEDs. It should be noted that the potting material need not achieve
the generally rectangular form factor shown. An array including no
potting material could be introduced into the distal end of the
nitinol hypotube, such that the void space in the guidewire
surrounding the array is filled with a potting material, thereby
achieving a cylindrical rather than rectangular form factor for the
potting material surrounding the array.
[0098] FIG. 13H is a plan view of array 220. Note that LEDs 224 are
arranged linearly, with conductive traces 228 extending parallel to
the linear array of LEDs, one trace on the right side of the LEDs,
and another trace on the left side of the LEDs, with bonding wires
226 coupling the LEDs to the traces. While not specifically shown,
it should be recognized that the traces are electrically coupled to
the conductors 208 and 210, thereby enabling the array to be
energized. In an alternative array 220a, shown in FIG. 13I, cutouts
are provided in a substrate 222a underneath the LEDS, so that the
flexible substrate does not interfere with the light emitted from
the LED faces parallel to and immediately adjacent to the substrate
(thus enabling less optically transparent substrate materials to be
employed). In yet another exemplary array 220b, shown in FIG. 13J,
the flexible substrate does not extend much beyond the conductive
traces, such that the LED array is disposed between two parallel
rails 234, each rail comprising a conductive trace deposited on top
of a flexible substrate. While such a configuration is initially
less structurally robust than configurations in which the
supporting substrate is lager, once array 220b is encapsulated in a
light transmissive potting material, such a configuration will be
sufficiently robust. Significantly, array 220b is easier to
manufacture than the other array designs. Each of the array
configurations of FIGS. 13H, 13I, and 13J enable the LEDs to be
wired in series or in parallel.
[0099] FIG. 13K is a cross-sectional view of yet another light
source array 220c, which has an even smaller form factor than
arrays 220, 220a, and 220b. Array 220c also includes a plurality of
LEDs 224 (again oriented in a linear array) mounted on a flexible
substrate 222b, with conductive traces 228a and bonding wires 226a,
to enable the LEDs to be coupled to conductors configured so that
the array can be energized using an external power supply (not
separately shown in FIG. 13K). Note that in array 220c, the width
of flexible substrate 222a is limited to the width of LEDs 224,
thereby enabling a reduction in the total width to be achieved. The
positions of bonding wires 226a are changed relative to their
orientation in arrays 220, 220a, and 220b. This change is clearly
illustrated in FIG. 13L, which shows a plan view of array 220c.
Note that traces 228a are oriented perpendicular to an axis 230
along which the linear LED array extends. Significantly, the LEDs
in array 220c can only be wired in series.
[0100] FIG. 13M schematically illustrates how array 220c can be
manufactured. A plurality of LEDs 224 and traces 228b are deposited
onto an extensive substrate 222c. Bonding wires 226a are used to
electrically couple the LEDs to the traces. The substrate is cut as
indicated by arrows 232, thereby creating three linear arrays 220c.
It should be recognized that each linear array 220c can include
more than two LEDs.
[0101] FIG. 13N is a schematic view of a guidewire 200a, enabling
details of distal end 204 of tube 202a to be identified. Guidewire
200a is smaller in diameter than guidewire 200, enabling the
narrower linear light source array (i.e., array 220c) to be
employed. In addition to the plurality of openings 206, guidewire
200a includes an opening 236 disposed distally of openings 206,
encompassing array 220c. Because the potting material encompassing
array 220a doesn't need to extend proximally of the array, the
portion of tube 202a extending proximally of array 220c defines a
substantial lumen that can be used to deliver a fluid, such as a
drug, to opening 236. In one exemplary embodiment, natural blood
flow in a body lumen will carry the drug downstream toward the
vessel wall that would be illuminated by the LEDs in array 220c.
Yet another structure that can be used to deliver such a drug
comprises an optional compliant balloon 238 with micro-pores
configured to leak the drug into the body lumen once a certain
pressure is reached, while the compliant balloon conforms to the
body lumen. If such a balloon is used, opening 236 is not required,
and the fluid entering the balloon is provided by the hollow tube
proximal of the array.
[0102] FIG. 13O is a cross-sectional view of a distal end of
guidewire 200a, taken along section line D-D of FIG. 13N, into
which array 220c has been inserted. Any void space surrounding
array 220c can be filled with potting material 218a, which is
electrically insulating and optically transparent. In an exemplary,
but not limiting embodiment, nitinol hypotube guidewire 200a has an
inner diameter of 0.0170 inches, and an outer diameter of 0.0204
inches. Significantly, guidewire 200a is implemented in this
embodiment using silver-coated nitinol, such that the guidewire
itself can be used as one of the paired conductors required to
energize array 220a. The silver coating is deposited on the
interior surface of the hypotube, forming a reflective interior
that enhances light emission from the LED array. It should be noted
however, that the conductive coating can also be applied to the
external surface of the guidewire. While a silver coating is
preferred, other conductive coatings (e.g., gold, copper, and/or
other conductive elements or alloys) can be employed. Because the
guidewire includes a conductive coating, only a single conductor
234 is required to be disposed within guidewire 200a. Conductor 234
is implemented using 36 gauge wire (AWG) for conveying a positive
signal, while the silver-coated nitinol hypotube conveys a ground
signal. As noted above, light source array 220a has a generally
rectangular form factor, having maximum dimensions of 0.015 inches
in width and 0.009 inches in height. Again, it should be recognized
that such stated dimensions are intended to be exemplary, rather
than limiting. While nitinol represents an exemplary material, it
should be recognized that many other materials, such as polymers
and other metals (such stainless steel, to mention just one
additional example), can be employed to implement a hollow
guidewire.
[0103] FIG. 13P is a cross-sectional view of guidewire 200a, taken
along section line E-E of FIG. 13N. Note that open lumen 235
surrounding conductor 234 can be used as a fluid delivery
lumen.
[0104] With respect to the LEDs employed in the arrays,
non-reflector LED semiconductors that emit light out all six sides
can be employed. These LED dies can be attached to a polyimide
flexible substrate without traces under the LED dies, such that
light is projected through the polyimide material. In the visible
red region the polyimide can pass over 90% of the light. If a
slightly less standard polyester flex circuit is used then the
entire visible spectrum down into UV ranges pass well over 95% of
the emitted light.
[0105] Groups of LEDs can be connected in series in order to
average the forward voltage drop variation of individual dies; as
this technique greatly improves manufacturing consistency. If
longer lightbars/arrays are required, then such serial grouping can
be connected in parallel. For example, in one empirical exemplary
embodiment, eight parallel groups of six LEDs connected in series
(i.e., 48 LEDs) were used to fabricate a linear array 5 cm in
length.
[0106] With respect to embodiments including a plurality of
expandable members, such a configuration enables a linear light
source array that is longer than any one expandable member to be
employed to illuminate a treatment area that is also longer than
any one expandable member. FIGS. 14A, 14B, 14C, and 14D illustrate
apparatus including such a plurality of expandable members. FIGS.
14A and 14B show an apparatus employed in connection with an
illuminated guidewire, while FIGS. 14C and 14D illustrate an
apparatus that includes a linear light source array combined with
the plurality of expandable members. In each embodiment shown in
these FIGURES, a relatively long light source array (i.e., a light
source array having a length greater than a length of any
expandable member) is disposed between a most proximally positioned
expandable member and a most distally positioned expandable
member.
[0107] FIG. 14A schematically illustrates a light-generating
apparatus 131 for treating relatively large prostates in a urethra
137. Light-generating apparatus 131 is based on a multi-lumen
catheter 130 in combination with an illuminated guidewire 135
having integral light emitting devices. Multi-lumen catheter 130 is
elongate and flexible, and includes a plurality of expandable
members 133a-133d. While four such expandable members are shown,
alternatively, more or fewer expandable members can be employed,
with at least two expandable members being particularly preferred.
As discussed above, such expandable members occlude urine flow and
center the catheter in the urethra. Multi-lumen catheter 130 and
expandable members 133a-133d preferably are formed from a suitable
bio-compatible polymer, including but not limited to: polyurethane,
polyethylene, PEP, PTFE, PET, PEBA, PEBAX or nylon. Each expandable
member 133a-133d preferably ranges from about 2 mm to about 15 mm
in diameter and from about 1 mm to about 60 mm in length. When
inflated, expandable members 133a-133d are pressurized from about
0.1 atmosphere to about 16 atmospheres. It should be understood
that between expandable member 133a and expandable member 133d,
multi-lumen catheter 130 is formed of a flexible material that
readily transmits light of the wavelengths required to activate the
photoreactive agent(s) with which light-generating apparatus 131
will be used. Bio-compatible polymers having the required optical
characteristics can be beneficially employed. As discussed above,
additives such as diffusion agents can be added to the polymer to
enhance the transmission or diffusion of light. Of course, all of
multi-lumen catheter 130 can be formed of the same material, rather
than just the portions between expandable member 133a and
expandable member 133d. Preferably, each expandable member
133a-133d is similarly constructed of a material that will transmit
light having the required wavelength(s). Further, any fluid used to
inflate the expandable members should similarly transmit light
having the required wavelength(s).
[0108] Referring to the cross-sectional view of FIG. 14B (taken
along lines section lines A-A of FIG. 14A), it will be apparent
that multi-lumen catheter 130 includes an inflation lumen 132a in
fluid communication with expandable member 133a, a second inflation
lumen 132b in fluid communication with expandable members 133b-c, a
flushing lumen 134, and a working lumen 136. If desired, each
expandable member can be placed in fluid communication with an
individual inflation lumen. Multi-lumen catheter 130 is configured
such that flushing lumen 134 is in fluid communication with at
least one port 138 (see FIG. 14A) formed through the wall of
multi-lumen catheter 130. As illustrated, a single port 138 is
disposed between expandable member 133a and expandable member 133b
and functions as explained below.
[0109] Once multi-lumen catheter 130 is positioned within urethra
137 so that a target area is disposed between expandable member
133a and expandable member 133d, inflation lumen 132a is first used
to inflate expandable member 133a. Then, the flushing fluid is
introduced into urethra 137 through port 138. The flushing fluid
displaces urine distal to expandable member 133a. After sufficient
flushing fluid has displaced the urine flow, inflation lumen 132b
is used to inflate expandable members 133b, 133c, thereby trapping
the flushing fluid in portions 137a, 137b, and 137c of urethra 137.
The flushing fluid readily transmits light of the wavelength(s)
used in administering PDT, whereas if urine were disposed in
portions 137a, 137b, and 137c of urethra 137, light transmission
would be blocked. An alternative configuration would be to provide
an inflation lumen for each expandable member, and a flushing port
disposed between each expandable member. The expandable members can
then be inflated, and each distal region can be flushed, in a
sequential fashion.
[0110] A preferred flushing fluid is saline. Other flushing fluids
can be used, so long as they are non toxic and readily transmit
light of the required wavelength(s). As discussed above, additives
can be included in flushing fluids to enhance light transmission
and dispersion relative to the target tissue. Working lumen 136 is
sized to accommodate light emitting guidewire 135, which can be
fabricated as described above. Multi-lumen catheter 130 can be
positioned using a conventional guidewire that does not include
light emitting devices. Once multi-lumen catheter 130 is properly
positioned and the expandable members are inflated, the
conventional guidewire is removed and replaced with a light
emitting device, such as an optical fiber coupled to an external
source, or a linear array of light emitting devices, such as LEDs
coupled to a flexible conductive substrate. While not specifically
shown, it will be understood that radio-opaque markers such as
those discussed above can be beneficially incorporated into
light-generating apparatus 131 to enable expandable members 133a
and 133d to be properly positioned relative to the target
tissue.
[0111] Still another embodiment of the present invention is
light-generating apparatus 141, which is shown in FIG. 14C disposed
in a urethra 147. Light-generating apparatus 141 is similar to
light-generating apparatus 131 describe above, and further includes
openings for using an external guide wire, as described above in
connection with FIG. 5. An additional difference between this
embodiment and light-generating apparatus 131 is that where light
emitting devices were not incorporated into multi-lumen catheter
130 of light-generating apparatus 131, a light emitting array 146
is incorporated into the catheter portion of light-generating
apparatus 141. FIGS. 1, 2, and 5 show exemplary configurations for
incorporating light emitting devices into a catheter.
[0112] Light-generating apparatus 141 is based on an elongate and
flexible multi-lumen catheter 140 that includes light emitting
array 146 and a plurality of expandable members 142a-142d. Light
emitting array 146 preferably comprises a linear array of LEDs. As
noted above, while four expandable members are shown, more or fewer
expandable members can be employed, with at least two expandable
members being particularly preferred. The materials and sizes of
expandable members 142a-142d are preferably consistent with those
described above in conjunction with multi-lumen catheter 130. The
walls of multi-lumen catheter 140 proximate to light emitting array
146 are formed of a flexible material that does not substantially
reduce the transmission of light of the wavelengths required to
activate the photoreactive agent(s) with which light-generating
apparatus 141 will be used. As indicated above, bio-compatible
polymers having the required optical characteristics can be
beneficially employed, and appropriate additives can be used.
Preferably, each expandable member is constructed of a material and
inflated using a fluid that readily transmit light of the required
wavelength(s).
[0113] Referring to the cross-sectional view of FIG. 14D (taken
along section line B-B of FIG. 14C), it can be seen that
multi-lumen catheter 140 includes an inflation lumen 143a in fluid
communication with expandable member 142a, a second inflation lumen
143b in fluid communication with expandable members 142b-c, a
flushing lumen 144, and a working lumen 149. Again, if desired,
each expandable member can be placed in fluid communication with an
individual inflation lumen. Multi-lumen catheter 140 is configured
so that flushing lumen 144 is in fluid communication with a port
148 (see FIG. 14C) formed in the wall of multi-lumen catheter 140,
which enables a flushing fluid to be introduced into portions
147a-147c of urethra 147 (i.e., into those portions distal of
expandable member 142a). Those portions are isolated using
inflation lumen 143b to inflate expandable members 142b-142d. The
flushing fluid is selected as described above. Working lumen 149 is
sized to accommodate light emitting array 146. Electrical leads
146b within working lumen 149 are configured to couple to an
external power supply, thereby enabling the light source array to
be selectively energized with an electrical current. A distal end
139 of multi-lumen catheter 140 includes an opening 160a in the
catheter side wall configured to enable guidewire 145 (disposed
outside of multi-lumen catheter 140) to enter a lumen (not shown)
in the distal end of the catheter that extends between opening 160a
and an opening 160b, thereby enabling multi-lumen catheter 140 to
be advanced over guidewire 145. Note that it is also possible to
create this device with a single lumen extrusion. For example, the
LED array and connection wires could share the lumen with the
inflation fluid. Each expandable member would also be in contact
with this lumen through inflation ports cut into the extrusion.
When the flushing fluid is provided it serves multiple
functions--1) it cools the LEDs directly, 2) it provides good
optical coupling between the LEDs and the outside of the catheter,
and 3) it inflates the expandable members (all at the same time).
This is a simpler version of the design, which does not require a
multi-lumen catheter.
[0114] FIG. 15 shows an alternative embodiment of the
light-generating apparatus illustrated in FIGS. 14A, 14B, 14C, and
14D. A light-generating apparatus 150 in FIG. 15 is based on a
multi-lumen catheter having an elongate, flexible body 154 formed
from a suitable bio-compatible polymer and expandable members
152a-152d. As indicated above, at least two expandable members are
particularly preferred. The difference between light-generating
apparatus 150 and light-generating apparatus 131 and 141, which
were discussed above, is that the expandable members in
light-generating apparatus 150 are fabricated as integral portions
of body 154, while the expandable members of light-generating
apparatus 131 and 141 are preferably implemented as separate
elements attached to a separate catheter body.
[0115] Yet another exemplary embodiment of a light generating
catheter disclosed herein is configured to be used with an
introducer catheter having a single lumen. A distal end of such a
light generating catheter includes a linear light source array.
This concept is schematically illustrated in FIG. 16A. This
exemplary embodiment has been designed to be used with an
introducer catheter 240 having an inner diameter of 0.65 inches
(1.65 mm) and an outer diameter of 0.050 inches (1.27 mm). It
should be recognized however, that the dimensions disclosed herein
are intended to be exemplary, and not limiting. A conventional
guidewire 244 (i.e., not a light emitting guidewire, as discussed
above) is disposed within a central lumen 242, in introducer
catheter 240. In an exemplary embodiment, guidewire 244 has an
outer diameter of 0.014 inches (0.36 mm). A light emitting catheter
246 is also disposed within central lumen 242. A flexible light
source array 248 is disposed in a distal end light emitting
catheter 246. FIG. 16B provides additional details relating to
array 248, which is generally similar to array 220 of FIG. 13G,
except for the use of a slightly thicker flexible substrate 222d.
Preferred dimensions for array 248 are a maximum width of 0.028
inches and a maximum height of 0.013 inches.
[0116] Referring once again to FIG. 16A, note that a push wire 250
is disposed under array 248. Significantly, push wire 250 serves as
a heat sink to enable heat from the LEDs in array 248 to be
dissipated, significantly increasing the efficiency of the array
(as measured by the amount of light output per LED--noting that
cooler LEDs emit higher intensity light). Array 248 and push wire
250 are encapsulated in optically transparent potting material 218a
(it should be apparent that the potting material need not be
transparent to all wavelengths, but should at least be transparent
to the wavelengths emitted by the light sources in array 248). The
potting material need not extend the entire length of light
emitting catheter 246. Instead, the potting compound need only be
disposed at the distal end of light emitting catheter 246, such
that array 248 is encapsulated. Thus, only a distal end of push
wire 250 need be encapsulated in the potting compound. Note also
that potting material 218a does not fill the entire interior of the
distal end of light emitting catheter 246. As a result, an annular
lumen 252 is defined between the inner diameter of the light
emitting catheter and the potting material encapsulating array 248.
Annular lumen 252 has a volume of at least 0.000177 cubic inches,
so that if the distal end of light emitting catheter 246 is
advanced distally of a distal end of introducer catheter 240, a
balloon can be incorporated into the distal end of light emitting
catheter to surround the light source array (generally as discussed
above), and annular lumen 252 will be sufficiently large to service
such a balloon. Proximally of array 248, annular lumen 252
significantly increases in size, since the only elements disposed
in the lumen will be push wire 250 and the electrical conductors
used to energize the array. The lumen in light emitting catheter
246 will be filled with a column of fluid.
[0117] FIGS. 17-19 are cross-sectional views showing additional
embodiments of portions of transurethral treatment devices. FIG.
17, more specifically, shows a device having a closed body support
member 602 and a light delivery device fixed to the support member
602. The light delivery device has a light generator 606a, a light
emitting region spaced apart from the light generator 606a distally
along the support member 602, and a light transmitting region 6c
between the light generator 606a and the light emitting region
606b. The light transmitting region 6c conducts light from the
light generator 606a to the light emitting region 606b. FIG. 18
illustrates a device having a solid or otherwise lumen-less support
member 602 and a light delivery device 6 with a light generator
606a and a light emitting region 606b at the same location
longitudinally along the support member 602. In FIGS. 17 and 18,
the light generator is within the support member 602. FIG. 19 shows
still another embodiment in which the light delivery device is on a
surface of the support member. More specifically, the light
delivery device 6 has the light generator 606a and the light
emitting region 606b disposed on an external surface of the support
member.
[0118] In one embodiment, a light delivery system that is sized to
fit into a standard or custom optically clear Foley catheter is
inserted into that catheter which has been placed via the urethra
at the prostate. The light delivery device can be used with a
sterile Foley catheter or can be delivered in a sterile pack kit
prepackaged with the catheter and/or an appropriate photoactive
agent dose so that it is convenient for prostatic procedures.
[0119] The light bar or light array may include a plurality of LEDs
contained in a catheter assembly or otherwise attached to a closed
elongated support member. The support member 602 may have an outer
diameter of about 0.8 to about 10 mm. Example of LED arrays are
disclosed in U.S. application Ser. No. 11/416,783 entitled "Light
Transmission system for Photo-reactive Therapy,", now U.S. Pat. No.
8,057,464 and U.S. application Ser. No. 11/323,319 entitled
"Medical Apparatus Employing Flexible Light Structures and Methods
for Manufacturing Same," (now abandoned) herein incorporated in
their entirety by reference. The die in these LED arrays can have a
size range from about 0.152 mm to about 0.304 mm. One exemplary
array can have the approximate dimensions of 0.3 mm in both length
and width and 0.1 mm in thickness.
[0120] Additional embodiments have a power controller drive circuit
capable of producing constant current D.C., A.C., square wave and
pulsed wave drive signals. This is accomplished by combining a
constant source with a programmable current steering network
allowing the controller to selectively change the drive wave form.
For example, the steering network may be modulated to achieve the
various functions described above, for example, producing the
desired impedance to fully discharge the battery. Furthermore, use
of an A.C. drive allows for a two-wire connection to the LEDs,
thereby reducing the cross-sectional diameter of the catheter,
while still permitting use of two back-to-back emission sources,
that when combined, produce a cylindrical light source emission
pattern.
[0121] Therefore, as discussed above, the transurethral treatment
device 621 can comprise a unitary, single use disposable system for
light-activated drug therapy. It should be noted that in certain
embodiments the catheter is fused to the power controller to form
an integrated single unit. Any attempt to disconnect the support
member in this embodiment results in damage to either the catheter,
or module, or both.
[0122] The prostate treatment system can be used in connection with
any light-activated drug of which there are many known in the art
and some of which are listed in U.S. Pat. No. 7,015,240 which is
fully incorporated by reference with regard to disclosed
photoactive compositions. In one particular embodiment, the
light-activated drug is Talaporfin Sodium. Talaporfin Sodium is a
chemically synthesized photosensitizer, having an absorption
spectrum that exhibits a maximum peak at 664 nm. In one embodiment,
the Talaporfin Sodium is presented as a lyophilized powder for
reconstitution. One hundred milligrams of Talaporfin Sodium is
reconstituted with 4 milliliters of 0.9% isotonic sterile sodium
chloride solution, to give a solution at a concentration of 25
mg/ml. Another example provides 150 mg of Talaporfin Sodium to be
reconstituted to the same 25 mg/ml concentration.
[0123] The drug must be activated with light, and light energy is
measured here in Joules (J) per centimeter of length of the light
transmitting array. Likewise the fluence of light is measured in
milli-watts (mW) per centimeter of length of the light emitting
array. Clearly, the amount of energy delivered will depend on
several factors, among them: the photoactive agent used, the dose
administered, the type of tissue being treated, the proximity of
the light array to the tissue being treated, among others. The
energy (E) delivered is the product of the fluence (F) and the time
period (T) over which the fluence is delivered: E=F.times.T. The
fluence may be delivered for only a fraction of the treatment time,
because the light array may be pulsed, for example in a frequency
such as 60 kHz, or may be controlled by a timing pattern. An
example of a timing pattern is that the array is at full fluence
for 20 seconds, then off for 10 seconds in a repetitive cycle. Of
course, any pattern and cycle that is expected to be useful in a
particular procedure may be used. The control module may further be
programmable in embodiments for such fractionated light
delivery.
[0124] In accordance with an embodiment, fifteen minutes to one
hour following Talaporfin Sodium administration, light energy in
the range from about 50 to about 1000 J/cm of light array fluence
in the range from about 5 to about 50 mW/cm, 55 mW/cm, to about 100
mW/cm of light array is delivered to the treatment site. As may be
expected, the equation discussed above relating energy time and
fluence plays a role in selection of the fluence and energy
delivered. For example, depending upon the patient, a certain time
period may be selected as suitable. In addition, the nature of
treatment might dictate the energy required. Thus, fluence F is
then determined by F=E/T. The light array should be capable of
providing that fluence in the allotted time period. For example, if
a total of 200 J/cm of light array must be delivered to the
treatment site at 20 mW/cm of light array, then the treatment
period is approximately 2.8 hours (10,000 seconds). The 200 J/cm
can also be delivered in approximately 60 minutes if the fluence is
increased to approximately 55 mW/cm.
[0125] In additional embodiments, the support member further has a
selective coating to control where light transmits to the prostatic
tissue thus directing the light activate drug therapy and reducing
the potential to treat adjacent tissue.
[0126] In another embodiment, the light delivery device is fixed in
place in the catheter. In yet another embodiment, the light
delivery device is movable within the catheter. According to this
embodiment, the treatment device may further include printed
markings or indicia on the catheter to aid in placement of the
light bar within the catheter. The light delivery device can also
have asymmetric light delivery to protect the colon or rectum. For
example, the light deliver device can be double sided and/or
shielded so that one side of the light bar emits light at a higher
intensity than another side. Exemplary light delivery devices are
disclosed in U.S. Pat. No. 5,876,427, herein incorporated in its
entirety by reference.
[0127] In additional embodiments, a Y-connection with a leakage
control valve is included to allow the light transmission source to
be inserted into the catheter through a separate lumen from a urine
collection lumen. The catheter may include two or more lumens as
needed to provide light transmission source manipulation and
placement.
[0128] In additional embodiments, the catheter includes a balloon
or other positional element to further aid in positioning the light
source transmission end proximate to the prostate using
non-incision type methods. In additional embodiments, the catheter
may include a retractable fixation device such as balloon,
umbrella, tines, disk or other means for fixation and placement
within the bladder.
[0129] In additional embodiments, to make the light bar visible to
ultrasound, the light source catheter and/or the light bar may
include echogenic material to reflect high-frequency sound waves
and thus be imageable by ultrasound techniques. In operation,
echogenic material will aid in proper placement of the catheter and
the light source.
[0130] In additional embodiments, the light transmission source
also includes temperature sensors which are electrically connected
to temperature monitors.
[0131] Several embodiments of the prostate treatment systems are
expected to provide highly efficient, low cost, and
minimally-invasive treatment of prostate conditions. The treatment
device may be used to treat prostate cancer, prostatis, cystitis,
bladder cancer, hypertrophic trigone, and hypertrophic urethral
sphincter. The present invention utilizes light-activated drug
therapy methods to minimally-invasively treat BPH or prostate
cancer via the urethra. As a result patients with BPH or prostate
cancer can be treated using the present invention without being
hospitalized, undergo general anesthesia and blood transfusion, and
thus have lower risk of complications.
[0132] B. Methods of Treating BPH Using the Treatment Device
[0133] The invention also provides methods of administering
photoactive therapy to treat targeted tissue of a human or
non-human patient. In one embodiment, the method includes
identifying a location of tissue to be treated in the prostate;
inserting a catheter into the urethra tract; inserting a light
delivery device at least proximate to the location of the targeted
tissue; and administering an effective dose of a photoactive drug.
The method may include confirming placement of the light source
prior to treatment. The method further includes treating the
targeted tissue by activating the light delivery device for a
predetermined period of treatment. In some embodiments, the
light-activated drug is mono-L-aspartyl chlorine e.sub.6, also
referred to herein as Talaporfin Sodium. Compositions and methods
of making Talaporfin Sodium are disclosed and taught in co-pending
U.S. Provisional Patent Application Ser. No. 60/817,769 entitled
"Compositions and Methods of Making a Photoactive Agent" filed Jun.
30, 2006, herein incorporated in its entirety. This compound has an
absorption spectrum that exhibits several peaks, including one with
the excitation wavelength of 664 nm, which is the wavelength
favored when it is used in photoreactive therapy. Alternative
light-activated drugs of suitable excitation wavelengths may also
be used as is known in the art.
[0134] The method further includes monitoring a temperature at
treatment site. The temperature measuring system includes a
temperature sensor for monitoring the temperature at the treatment
site. The temperature sensor may be a thermal couple or any
suitable device for providing temperature information at the
treatment site. The temperature sensor may be disposed at the
surface of the support member and is further electrically connected
to the temperature monitor via wires. Alternatively, the
temperature sensor may be wirelessly connected to the temperature
monitor. The temperature sensor provides the temperature proximate
to the treatment site during treatment to ensure safe operating
temperatures during the treatment at the treatment site.
[0135] The above description of illustrated embodiments, including
what is described in the Abstract, is not intended to be exhaustive
or to limit the invention to the precise forms disclosed. Although
specific embodiments of and examples are described herein for
illustrative purposes, various equivalent modifications can be made
without departing from the spirit and scope of the invention, as
will be recognized by those skilled in the relevant art. The
teachings provided herein of the invention can be applied to light
sources, catheters and/or treatment devices, not necessarily the
exemplary light sources, catheters and/or treatment devices
generally described above.
[0136] Unless the context requires otherwise, throughout the
specification and claims which follow, the word "comprise" and
variations thereof, such as, "comprises" and "comprising" are to be
construed in an open, inclusive sense that is as "including, but
not limited to."
[0137] Reference throughout this specification to "one embodiment"
or "an embodiment" means that a particular feature, structure or
characteristic described in connection with the embodiment is
included in at least one embodiment of the present invention. Thus,
the appearances of the phrases "in one embodiment" or "in an
embodiment" in various places throughout this specification are not
necessarily all referring to the same embodiment. Furthermore, the
particular features, structures, or characteristics may be combined
in any suitable manner in one or more embodiments. The headings
provided herein are for convenience only and do not interpret the
scope or meaning of the claimed invention.
[0138] The various embodiments described above can be combined to
provide further embodiments. All of the U.S. patents, U.S. patent
application publications, U.S. patent applications, foreign
patents, foreign patent applications and non-patent publications
referred to in this specification and/or listed in the Application
Data Sheet, are incorporated herein by reference, in their
entirety. Embodiments of the invention can be modified, if
necessary, to employ systems, circuits and concepts of the various
patents, applications and publications to provide yet further
embodiments of the invention.
[0139] These and other changes can be made to the invention in
light of the above-detailed description. In general, in the
following claims, the terms used should not be construed to limit
the invention to the specific embodiments disclosed in the
specification and the claims, but should be construed to include
all catheters, light transmission sources and treatment devices
that operate in accordance with the claims. Accordingly, the
invention is not limited by the disclosure, but instead its scope
is to be determined entirely by the following claims.
[0140] From the foregoing, it will be appreciated that specific
embodiments of the invention have been described herein for
purposes of illustration, but that various modifications may be
made without deviating from the spirit and scope of the invention.
Accordingly, the invention is not limited except as by the appended
claims.
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