METHOD AND APPARATUS FOR TREATING BENIGN PROSTATIC HYPERPLASIA WITH LIGHT-ACTIVATED DRUG THERAPY
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).
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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.
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.
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.
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.
Turning now to
Light-generating apparatus 5 includes a light source array 40 comprising a plurality of LEDs 40a (seen in phantom view) that are electrically coupled to lead 11 via leads 40c. As discussed above, light source array 40 is preferably encapsulated in a light-transmissive polymer 23, or at least, in an epoxy that transmits the wavelengths of light required to activate the photoreactive agent introduced into the target tissue. Positioned immediately behind LEDs 40a (i.e., proximal of LEDs 40a) is a highly-reflective disk 40b. Any light emitted from LEDs 40a in a direction toward proximal end 8 is reflected back by reflective disk 40b towards distal end 6. Additionally, a reflective coating 43 (such as aluminum or another reflective material), is applied to the outer surface of body 4 adjacent to light source array 40. Any light from LEDs 40a directed to the sides (i.e., towards body 4) is redirected by reflective coating 43 towards distal end 6. Reflective disk 40b and reflective coating 43 thus cooperatively maximize the intensity of light delivered through distal end 6.
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
It should be understood that while light source array 40 has been described as including a plurality of LEDs 40a disposed on conductive traces electrically connected to lead 11, light source array 40 can alternatively use other sources of light. As noted above, possible light sources include, but are not limited to, organic LEDs, super luminescent diodes, laser diodes, and light emitting polymers. While not shown in
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 59a, and an orifice 59b. Guidewire 51 enters orifice 59a, and exits distal portion 52 through orifice 59b. It should be understood that guidewire 51 can be disposed externally to proximal portion 54, or alternatively, the proximal portion can include an opening at its proximal end through which the guidewire can enter the proximal portion, and an opening disposed proximally of light emitting devices 53, where the guidewire then exits the proximal portion.
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
The light delivery device 606 can have a light generator 606a and a light emitting region 606b. In the embodiment shown in
As illustrated in
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.
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 (
External bond wires can increase the cross-sectional size of an LED array, and are prone to breakage when stressed.
As illustrated in
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
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.
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
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
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.
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.
Referring to the cross-sectional view of
Once multi-lumen catheter 130 is positioned within urethra 137 so that a target area is disposed between expandable member 133a and expandable member 133d, inflation lumen 132a is first used to inflate expandable member 133a. Then, the flushing fluid is introduced into urethra 137 through port 138. The flushing fluid displaces urine distal to expandable member 133a. After sufficient flushing fluid has displaced the urine flow, inflation lumen 132b is used to inflate expandable members 133b, 133c, thereby trapping the flushing fluid in portions 137a, 137b, and 137c of urethra 137. The flushing fluid readily transmits light of the wavelength(s) used in administering PDT, whereas if urine were disposed in portions 137a, 137b, and 137c of urethra 137, light transmission would be blocked. An alternative configuration would be to provide an inflation lumen for each expandable member, and a flushing port disposed between each expandable member. The expandable members can then be inflated, and each distal region can be flushed, in a sequential fashion.
A preferred flushing fluid is saline. Other flushing fluids can be used, so long as they are non toxic and readily transmit light of the required wavelength(s). As discussed above, additives can be included in flushing fluids to enhance light transmission and dispersion relative to the target tissue. Working lumen 136 is sized to accommodate light emitting guidewire 135, which can be fabricated as described above. Multi-lumen catheter 130 can be positioned using a conventional guidewire that does not include light emitting devices. Once multi-lumen catheter 130 is properly positioned and the expandable members are inflated, the conventional guidewire is removed and replaced with a light emitting device, such as an optical fiber coupled to an external source, or a linear array of light emitting devices, such as LEDs coupled to a flexible conductive substrate. While not specifically shown, it will be understood that radio-opaque markers such as those discussed above can be beneficially incorporated into light-generating apparatus 131 to enable expandable members 133a and 133d to be properly positioned relative to the target tissue.
Still another embodiment of the present invention is light-generating apparatus 141, which is shown in
Light-generating apparatus 141 is based on an elongate and flexible multi-lumen catheter 140 that includes light emitting array 146 and a plurality of expandable members 142a-142d. Light emitting array 146 preferably comprises a linear array of LEDs. As noted above, while four expandable members are shown, more or fewer expandable members can be employed, with at least two expandable members being particularly preferred. The materials and sizes of expandable members 142a-142d are preferably consistent with those described above in conjunction with multi-lumen catheter 130. The walls of multi-lumen catheter 140 proximate to light emitting array 146 are formed of a flexible material that does not substantially reduce the transmission of light of the wavelengths required to activate the photoreactive agent(s) with which light-generating apparatus 141 will be used. As indicated above, bio-compatible polymers having the required optical characteristics can be beneficially employed, and appropriate additives can be used. Preferably, each expandable member is constructed of a material and inflated using a fluid that readily transmit light of the required wavelength(s).
Referring to the cross-sectional view of
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
Referring once again to
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.
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.
Filed: Apr 5, 2016
Publication Date: Jul 28, 2016
Applicant: PURDUE PHARMACEUTICAL PRODUCTS L.P. (STAMFORD, CT)
Inventors: Phillip Burwell (Snohomish, WA), Zihong Guo (Bellevue, WA), Jennifer K. Matson (Renton, WA), Steven Ross Daly (Sammamish, WA), David B. Shine (Sammamish, WA), Gary Lichttenegger (Woodinville, WA), Jean Bishop (Issaquah, WA), Nick Yeo (Great Bookham), Hugh Narciso (Santa Barbara, CA), Llew Keltner (Portland, OR), Jay Winship (Bellevue, WA), Erik Hagstrom (Woodinville, WA), Frank Zheng (Kirkland, WA), James C. Chen (Clyde Hill, WA), Joseph M. Hobbs (Issaquah, WA)
Application Number: 15/091,270