US20160213945A1 - Method and apparatus for treating benign prostatic hyperplasia with light-activated drug therapy - Google Patents

Method and apparatus for treating benign prostatic hyperplasia with light-activated drug therapy Download PDF

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Publication number
US20160213945A1
US20160213945A1 US15/091,270 US201615091270A US2016213945A1 US 20160213945 A1 US20160213945 A1 US 20160213945A1 US 201615091270 A US201615091270 A US 201615091270A US 2016213945 A1 US2016213945 A1 US 2016213945A1
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United States
Prior art keywords
light
support member
array
drug therapy
catheter
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Pending
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US15/091,270
Inventor
Phillip Burwell
Zihong Guo
Jennifer K. Matson
Steven Ross Daly
David B. Shine
Gary Lichttenegger
Jean Bishop
Nick Yeo
Hugh Narciso
Llew Keltner
Jay Winship
Erik Hagstrom
Frank Zheng
James C. Chen
Joseph M. Hobbs
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Light Sciences Oncology Inc
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Purdue Pharma LP
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Publication date
Priority to US45506903P priority Critical
Priority to US10/799,357 priority patent/US7252677B2/en
Priority to CN200620088987.8 priority
Priority to CN 200620088987 priority patent/CN2885311Y/en
Priority to PCT/US2007/001324 priority patent/WO2007084608A2/en
Priority to US11/834,572 priority patent/US10376711B2/en
Priority to US16132308A priority
Application filed by Purdue Pharma LP filed Critical Purdue Pharma LP
Priority to US15/091,270 priority patent/US20160213945A1/en
Publication of US20160213945A1 publication Critical patent/US20160213945A1/en
Assigned to PURDUE PHARMACEUTICAL PRODUCTS L.P. reassignment PURDUE PHARMACEUTICAL PRODUCTS L.P. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: LICHTTENEGGER, GARY, HAGSTROM, ERIK, MATSON, JENNIFER K., HOBBS, JOSEPH M., WINSHIP, JAY, GUO, ZIHONG, DALY, STEVEN ROSS, NARCISO, HUGH, SHINE, DAVID B., YEO, NICK
Assigned to LIGHT SCIENCES ONCOLOGY INC. reassignment LIGHT SCIENCES ONCOLOGY INC. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: PURDUE PHARMACEUTICAL PRODUCTS L.P.
Application status is Pending legal-status Critical

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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61NELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00Radiation therapy
    • A61N5/06Radiation therapy using light
    • A61N5/0613Apparatus adapted for a specific treatment
    • A61N5/062Photodynamic therapy, i.e. excitation of an agent
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K41/00Medicinal preparations obtained by treating materials with wave energy or particle radiation; Therapies using these preparations
    • A61K41/0057Photodynamic therapy with a photosensitizer, i.e. agent able to produce reactive oxygen species upon exposure to light or radiation, e.g. UV or visible light; photocleavage of nucleic acids with an agent
    • A61K41/0071PDT with porphyrins having exactly 20 ring atoms, i.e. based on the non-expanded tetrapyrrolic ring system, e.g. bacteriochlorin, chlorin-e6, or phthalocyanines
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61NELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
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    • A61N5/0601Apparatus for use inside the body
    • AHUMAN NECESSITIES
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    • A61NELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
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    • A61N5/0601Apparatus for use inside the body
    • A61N5/0603Apparatus for use inside the body for treatment of body cavities
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00Surgical instruments, devices or methods, e.g. tourniquets
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    • A61B2017/00022Sensing or detecting at the treatment site
    • A61B2017/00084Temperature
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00Surgical instruments, devices or methods, e.g. tourniquets
    • A61B17/00234Surgical instruments, devices or methods, e.g. tourniquets for minimally invasive surgery
    • A61B2017/00238Type of minimally invasive operation
    • A61B2017/00274Prostate operation, e.g. prostatectomy, turp, bhp treatment
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00Surgical instruments, devices or methods, e.g. tourniquets
    • A61B17/22Implements for squeezing-off ulcers or the like on the inside of inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; Calculus removers; Calculus smashing apparatus; Apparatus for removing obstructions in blood vessels, not otherwise provided for
    • A61B2017/22051Implements for squeezing-off ulcers or the like on the inside of inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; Calculus removers; Calculus smashing apparatus; Apparatus for removing obstructions in blood vessels, not otherwise provided for with an inflatable part, e.g. balloon, for positioning, blocking, or immobilisation
    • A61B2017/22065Functions of balloons
    • A61B2017/22068Centering
    • AHUMAN NECESSITIES
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    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
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    • A61B2018/00053Mechanical features of the instrument of device
    • A61B2018/00273Anchoring means for temporary attachment of a device to tissue
    • A61B2018/00279Anchoring means for temporary attachment of a device to tissue deployable
    • A61B2018/00285Balloons
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    • A61B2018/00315Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body for treatment of particular body parts
    • A61B2018/00547Prostate
    • AHUMAN NECESSITIES
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    • A61B2018/00636Sensing and controlling the application of energy
    • A61B2018/00773Sensed parameters
    • A61B2018/00791Temperature
    • A61B2018/00821Temperature measured by a thermocouple
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    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B18/00Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
    • A61B18/18Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by applying electromagnetic radiation, e.g. microwaves
    • A61B18/20Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by applying electromagnetic radiation, e.g. microwaves using laser
    • A61B18/22Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by applying electromagnetic radiation, e.g. microwaves using laser the beam being directed along or through a flexible conduit, e.g. an optical fibre; Couplings or hand-pieces therefor
    • A61B2018/2255Optical elements at the distal end of probe tips
    • A61B2018/2261Optical elements at the distal end of probe tips with scattering, diffusion or dispersion of light
    • AHUMAN NECESSITIES
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    • A61N5/0601Apparatus for use inside the body
    • A61N2005/0602Apparatus for use inside the body for treatment of blood vessels
    • AHUMAN NECESSITIES
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    • A61N5/0601Apparatus for use inside the body
    • A61N5/0603Apparatus for use inside the body for treatment of body cavities
    • A61N2005/061Bladder and/or urethra
    • AHUMAN NECESSITIES
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    • A61NELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
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    • A61N2005/063Radiation therapy using light comprising light transmitting means, e.g. optical fibres
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    • A61N5/00Radiation therapy
    • A61N5/06Radiation therapy using light
    • A61N2005/065Light sources therefor
    • A61N2005/0651Diodes
    • A61N2005/0652Arrays of diodes
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61NELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00Radiation therapy
    • A61N5/06Radiation therapy using light
    • A61N2005/067Radiation therapy using light using laser light

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×0.3 mm×0.1 mm (length×width×thickness).

Description

    CROSS-REFERENCE TO RELATED APPLICATIONS
  • 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.
  • 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
  • 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
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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
  • 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.
  • 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×0.3 mm×0.1 mm (length×width×thickness).
  • 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
  • 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.
  • FIG. 1 schematically illustrates a first embodiment of a light-generating apparatus suitable for intravascular use in accord with the present invention;
  • FIG. 2 is a longitudinal cross-sectional view of the light-generating apparatus of FIG. 1;
  • 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;
  • FIG. 4A schematically illustrates a second embodiment of a light-generating apparatus suitable for intravascular use in accord with the present invention;
  • FIG. 4B is a longitudinal cross-section view of the light-generating apparatus of FIG. 2;
  • FIG. 5 schematically illustrates yet another embodiment of a light-generating apparatus suitable for intravascular use in accord with the present invention;
  • FIG. 6 is an elevational side view of a prostate treatment system having a transurethral treatment device according to one embodiment of the invention;
  • 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;
  • FIG. 8 schematically illustrates a multicolor light array for use in the light-generating apparatus of FIGS. 5-7;
  • 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;
  • 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;
  • 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;
  • 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;
  • FIG. 11 is a cross-sectional view of a transurethral treatment device in accordance with another embodiment of the invention;
  • FIG. 12A schematically illustrates a modified guidewire for use in the light-generating transurethral apparatus of FIGS. 10 and 11;
  • 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;
  • FIGS. 13A and 13B schematically illustrate a hollow guidewire including a light source array disposed at its distal end;
  • 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;
  • FIG. 13D is a cross-sectional view of the connection jack taken along section line A-A of FIG. 13C;
  • FIG. 13E is a cross-sectional view of the connection jack taken along section line B-B of FIG. 13C;
  • FIG. 13F is a cross-sectional view of the guidewire of FIGS. 13A and 13B taken along section line C-C of FIG. 13B;
  • FIG. 13G is a side view of a first exemplary array for the guidewire of FIGS. 13A and 13B;
  • FIG. 13H is a plan view of the first exemplary array for the guidewire of FIGS. 13A and 13B;
  • FIG. 13I is a plan view of a second exemplary array for the guidewire of FIGS. 13A and 13B;
  • FIG. 13J is a plan view of a third exemplary array for the guidewire of FIGS. 13A and 13B;
  • FIG. 13K is a side view of a fourth exemplary array for the guidewire of FIGS. 13A and 13B;
  • FIG. 13L is a plan view of the fourth exemplary array for the guidewire of FIGS. 13A and 13B;
  • 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;
  • FIG. 13N schematically illustrates yet another hollow guidewire including a light source array disposed at its distal end;
  • FIG. 13O is a cross-sectional view of the hollow guidewire of FIG. 13N taken along section line D-D of FIG. 13N;
  • FIG. 13P is a cross-sectional view of the hollow guidewire of FIG. 13N taken along section line E-E of FIG. 13N;
  • 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;
  • FIG. 14B is a cross-sectional view of the light-generating apparatus of FIG. 14A;
  • 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;
  • FIG. 14D is a cross-sectional view of the light-generating apparatus of FIG. 14C;
  • FIG. 15 schematically illustrates a plurality of balloons included with a light-generating apparatus in accord with the present invention;
  • FIG. 16A is a cross-sectional view of one example of a light emitting catheter disposed in a central lumen of an introducer catheter;
  • FIG. 16B is a side view of a light source array for use in the light emitting catheter of FIG. 16A;
  • FIG. 17 is a cross-sectional view of a transurethral treatment device in accordance with yet another embodiment of the invention;
  • FIG. 18 is a cross-sectional view of a transurethral treatment device in accordance with still another embodiment of the invention; and
  • FIG. 19 is a cross-sectional view of a transurethral treatment device in accordance with another embodiment of the invention.
  • DETAILED DESCRIPTION
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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 10 a and leads 10 b (each coupling to lead 11) can be clearly seen.
  • 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 16 a, 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.
  • 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.
  • Light-generating apparatus 5 includes a light source array 40 comprising a plurality of LEDs 40 a (seen in phantom view) that are electrically coupled to lead 11 via leads 40 c. 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 40 a (i.e., proximal of LEDs 40 a) is a highly-reflective disk 40 b. Any light emitted from LEDs 40 a in a direction toward proximal end 8 is reflected back by reflective disk 40 b 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 40 a directed to the sides (i.e., towards body 4) is redirected by reflective coating 43 towards distal end 6. Reflective disk 40 b and reflective coating 43 thus cooperatively maximize the intensity of light delivered through distal end 6.
  • 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).
  • It should be understood that while light source array 40 has been described as including a plurality of LEDs 40 a 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).
  • 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.
  • 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.
  • 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® 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.
  • 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 59 a, and an orifice 59 b. Guidewire 51 enters orifice 59 a, and exits distal portion 52 through orifice 59 b. 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.
  • 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.
  • 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).
  • The light delivery device 606 can have a light generator 606 a and a light emitting region 606 b. In the embodiment shown in FIG. 6, the light generator 606 a and the light emitting region 606 b are at approximately the same location of the elongated member, but in other embodiments shown below, the light generator 606 a may not be coincident with the light emitting region 606 b. As shown below, the light generator 606 a 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.
  • 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.
  • 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.
  • 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 86 a and 86 b that are coupled to a flexible, conductive substrate 82. LEDs 86 a emit light of a first color, having a first wavelength, while LEDs 86 b 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 50 a 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.
  • 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.
  • FIG. 9A shows a linear array 88 a 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 92 a, and a second flexible conductive substrate 92 b. Flexible conductive substrate 92 b 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 92 a is not specifically required and can be omitted. Further, strain relief features 93 can also be incorporated into first flexible conductive substrate 92 a.
  • FIG. 9B shows a linear array 88 b having a plurality of light emitting sources 90 mounted on a flexible conductive substrate 92 c. Note that flexible conductive substrate 92 c 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 93 a of flexible conductive substrate 92 c, and a lower face 93 b of flexible conductive substrate 92 c. Thus, when light emitting sources 90 are energized, light is emitted generally outwardly away from both upper surface 93 a and lower surface 93 b. If desired, light emitting sources 90 can be disposed on only upper surface 93 a or only on lower surface 93 b (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 93 a and lower surface 93 b. The crenellated configuration of flexible conductive substrate 92 c enables a higher degree of flexibility to be achieved, because each crenellation acts as a strain relief feature.
  • 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 10 b 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 93 c and 93 d (respectively) of flexible conductive substrate 92 d to produce a light source array 97. Any required electrical connections 95 pass through flexible conductive substrate 92 d, 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 98 a 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).
  • FIG. 9D shows a linear array 96 including a plurality of light emitting sources (not separately shown) that spirals around a guidewire lumen 98 b. 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.
  • 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 606 b can be activated.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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° 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.
  • 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 606 a 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 606 b positioned at least proximate to the treatment site and a light transmitting region 606 c (e.g., fiber optic) between the light generator 606 a and the light emitting region 606 b. 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).
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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 218 a, 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.
  • 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 218 a, 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.
  • 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 220 a, shown in FIG. 13I, cutouts are provided in a substrate 222 a 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 220 b, 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 220 b is encapsulated in a light transmissive potting material, such a configuration will be sufficiently robust. Significantly, array 220 b 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.
  • FIG. 13K is a cross-sectional view of yet another light source array 220 c, which has an even smaller form factor than arrays 220, 220 a, and 220 b. Array 220 c also includes a plurality of LEDs 224 (again oriented in a linear array) mounted on a flexible substrate 222 b, with conductive traces 228 a and bonding wires 226 a, 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 220 c, the width of flexible substrate 222 a is limited to the width of LEDs 224, thereby enabling a reduction in the total width to be achieved. The positions of bonding wires 226 a are changed relative to their orientation in arrays 220, 220 a, and 220 b. This change is clearly illustrated in FIG. 13L, which shows a plan view of array 220 c. Note that traces 228 a are oriented perpendicular to an axis 230 along which the linear LED array extends. Significantly, the LEDs in array 220 c can only be wired in series.
  • FIG. 13M schematically illustrates how array 220 c can be manufactured. A plurality of LEDs 224 and traces 228 b are deposited onto an extensive substrate 222 c. Bonding wires 226 a are used to electrically couple the LEDs to the traces. The substrate is cut as indicated by arrows 232, thereby creating three linear arrays 220 c. It should be recognized that each linear array 220 c can include more than two LEDs.
  • FIG. 13N is a schematic view of a guidewire 200 a, enabling details of distal end 204 of tube 202 a to be identified. Guidewire 200 a is smaller in diameter than guidewire 200, enabling the narrower linear light source array (i.e., array 220 c) to be employed. In addition to the plurality of openings 206, guidewire 200 a includes an opening 236 disposed distally of openings 206, encompassing array 220 c. Because the potting material encompassing array 220 a doesn't need to extend proximally of the array, the portion of tube 202 a extending proximally of array 220 c 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 220 c. 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.
  • FIG. 13O is a cross-sectional view of a distal end of guidewire 200 a, taken along section line D-D of FIG. 13N, into which array 220 c has been inserted. Any void space surrounding array 220 c can be filled with potting material 218 a, which is electrically insulating and optically transparent. In an exemplary, but not limiting embodiment, nitinol hypotube guidewire 200 a has an inner diameter of 0.0170 inches, and an outer diameter of 0.0204 inches. Significantly, guidewire 200 a 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 220 a. 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 200 a. 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 220 a 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.
  • FIG. 13P is a cross-sectional view of guidewire 200 a, 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.
  • 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.
  • 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.
  • 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.
  • 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 133 a-133 d. 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 133 a-133 d 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 133 a-133 d 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 133 a-133 d are pressurized from about 0.1 atmosphere to about 16 atmospheres. It should be understood that between expandable member 133 a and expandable member 133 d, 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 133 a and expandable member 133 d. Preferably, each expandable member 133 a-133 d 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).
  • 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 132 a in fluid communication with expandable member 133 a, a second inflation lumen 132 b in fluid communication with expandable members 133 b-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 133 a and expandable member 133 b and functions as explained below.
  • Once multi-lumen catheter 130 is positioned within urethra 137 so that a target area is disposed between expandable member 133 a and expandable member 133 d, inflation lumen 132 a is first used to inflate expandable member 133 a. Then, the flushing fluid is introduced into urethra 137 through port 138. The flushing fluid displaces urine distal to expandable member 133 a. After sufficient flushing fluid has displaced the urine flow, inflation lumen 132 b is used to inflate expandable members 133 b, 133 c, thereby trapping the flushing fluid in portions 137 a, 137 b, and 137 c of urethra 137. The flushing fluid readily transmits light of the wavelength(s) used in administering PDT, whereas if urine were disposed in portions 137 a, 137 b, and 137 c 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.
  • 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 133 a and 133 d to be properly positioned relative to the target tissue.
  • 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.
  • 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 142 a-142 d. 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 142 a-142 d 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).
  • 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 143 a in fluid communication with expandable member 142 a, a second inflation lumen 143 b in fluid communication with expandable members 142 b-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 147 a-147 c of urethra 147 (i.e., into those portions distal of expandable member 142 a). Those portions are isolated using inflation lumen 143 b to inflate expandable members 142 b-142 d. The flushing fluid is selected as described above. Working lumen 149 is sized to accommodate light emitting array 146. Electrical leads 146 b 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 160 a 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 160 a and an opening 160 b, 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.
  • 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 152 a-152 d. 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.
  • 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 222 d. Preferred dimensions for array 248 are a maximum width of 0.028 inches and a maximum height of 0.013 inches.
  • 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 218 a (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 218 a 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.
  • 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 606 a, a light emitting region spaced apart from the light generator 606 a distally along the support member 602, and a light transmitting region 6 c between the light generator 606 a and the light emitting region 606 b. The light transmitting region 6 c conducts light from the light generator 606 a to the light emitting region 606 b. 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 606 a and a light emitting region 606 b 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 606 a and the light emitting region 606 b disposed on an external surface of the support member.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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×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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • In additional embodiments, the light transmission source also includes temperature sensors which are electrically connected to temperature monitors.
  • 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.
  • B. Methods of Treating BPH Using the Treatment Device
  • 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.
  • 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.
  • 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.
  • 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.”
  • 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.
  • 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.
  • 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.
  • 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.

Claims (14)

We claim:
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×0.3 mm×0.1 mm (length×width×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.
US15/091,270 2003-03-14 2016-04-05 Method and apparatus for treating benign prostatic hyperplasia with light-activated drug therapy Pending US20160213945A1 (en)

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US45506903P true 2003-03-14 2003-03-14
US10/799,357 US7252677B2 (en) 2003-03-14 2004-03-12 Light generating device to intravascular use
CN200620088987.8 2006-01-18
CN 200620088987 CN2885311Y (en) 2006-01-18 2006-01-18 Via urethra prostate therapeutic equipment using photodynamic therapy
PCT/US2007/001324 WO2007084608A2 (en) 2006-01-18 2007-01-18 Method and apparatus for light-activated drug therapy
US11/834,572 US10376711B2 (en) 2007-08-06 Light generating guide wire for intravascular use
US16132308A true 2008-11-19 2008-11-19
US15/091,270 US20160213945A1 (en) 2003-03-14 2016-04-05 Method and apparatus for treating benign prostatic hyperplasia with light-activated drug therapy

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US15/091,270 US20160213945A1 (en) 2003-03-14 2016-04-05 Method and apparatus for treating benign prostatic hyperplasia with light-activated drug therapy
US15/406,057 US10307610B2 (en) 2006-01-18 2017-01-13 Method and apparatus for light-activated drug therapy

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US11/834,572 Continuation-In-Part US10376711B2 (en) 2003-03-14 2007-08-06 Light generating guide wire for intravascular use
US16132308A Continuation-In-Part 2008-11-19 2008-11-19

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