Patent Application
20110137155
The present disclosure relates to the delivery of a therapeutic agent, for example to the interior walls of a vessel such as a blood vessel, via a therapeutic agent delivery device, and to detection of lesions on the walls.
The deployment in the body of medications and other substances, such as materials useful in tracking biological processes through non-invasive imaging techniques, is an oft repeated and advantageous procedure performed during the practice of modern medicine. Such substances may be deployed through non-invasive procedures such as endoscopy and vascular catheterization, as well as through more invasive procedures that require larger incisions into the body of a patient.
In conventional minimally-invasive medical treatment, medical instruments are steered by physicians to the location within the patient's body at which the procedure is to be performed, using, for example, images from optical devices located at the end of the instruments' lumens or from non-invasive imaging techniques. Once placed at the desired site, the device at the distal end of the instrument can be actuated by the physician to perform the procedure.
These procedures often require careful, time-consuming monitoring of the placement of the instrument tip within the body. Even with such care, however, limitations on the quality of the available images and obstruction of views by surrounding tissues or fluids can degrade the accuracy of placement of the instrument. Such difficulties can result in less than optimal injection, infusion, inflation or sample collection. Moreover, even if positioned properly, the instrument might be aligned with areas in which performance of the medical procedure would not be desired, such as where an asymmetric plaque deposit inside a blood vessel would render infusion delivery or angioplasty ineffective or potentially dangerous.
U.S. Patent Application Publication No. 2004/0102733 to Naimark et al., which is expressly incorporated herein by reference, presents a solution to some of these inefficiencies. That publication describes a minimally-invasive smart device which can detect environmental conditions in the vicinity of a target site within a patient's body and determine whether the medical device on the distal end of the instrument should be activated to perform, or be inhibited from performing, a desired minimally-invasive medical procedure.
Despite these advances, a need exists for more accurate detection of diseased locations and localized delivery of therapeutic agents as well as for better and more reliable overall structural design of therapeutic agent delivery systems and the mechanisms that support their functions.
The disclosure is directed to improvements in devices for delivery of a therapeutic agent to a target location, such as the inside of a vessel, as well as in devices for detection of lesions, such as on the inside of a vessel.
In one embodiment of the disclosure, a therapeutic agent delivery device is provided comprising an elongate member having a distal end, an expandable member disposed on the distal end of the elongate member and a drug delivery matrix disposed on at least a portion of the expandable member. The drug delivery matrix comprises one or more drug delivery areas with each drug delivery area comprising an electroactive polymer, one or more sensors adapted to detect a condition of a target location on a vessel wall, and one or more conductive elements for transmitting one or more signals from the one or more sensors and for transmitting one or more signals to the electroactive polymer of the one or more drug delivery areas. In this embodiment, when a first sensor of the one or more sensors detects the condition of the target location, the first sensor transmits one or more signals, and based on such detection, one or more signals are transmitted to one or more drug delivery areas of the one or more drug delivery areas, thereby causing the therapeutic agent to be delivered from the electroactive polymer of the one or more drug delivery areas to the target location.
A disclosed further embodiment provides a method of delivering a therapeutic agent to a target location, the method comprising providing a therapeutic agent delivery device comprising an elongate member having a distal end, an expandable member disposed on the distal end of the elongate member and a drug delivery matrix disposed on at least a portion of the expandable member. The drug delivery matrix comprises one or more drug delivery areas with each drug delivery area comprising an electroactive polymer, one or more sensors adapted to detect a condition of the target location on a vessel wall, and one or more conductive elements for transmitting one or more signals from the one or more sensors and for transmitting one or more signals to the electroactive polymer of the one or more drug delivery areas. The method further comprises positioning the device in the vessel, detecting the condition of the target location and transmitting one or more signals from a first sensor of the one or more sensors that detected the condition, and, based on the detection, transmitting one or more signals to one or more drug delivery areas, thereby causing the therapeutic agent to be delivered from the electroactive polymer of the one or more drug delivery areas to the target location.
A disclosed further embodiment provides a method of delivering a therapeutic agent to a target location, the method comprising determining one or more target drug delivery areas on a vessel wall and providing a therapeutic agent delivery device comprising an elongate member having a distal end, an expandable member disposed on the distal end of the elongate member and a drug delivery matrix disposed on at least a portion of the expandable member. The drug delivery matrix comprises one or more drug delivery areas, with each drug delivery area comprising an electroactive polymer, and one or more conductive elements for transmitting a signal to the electroactive polymer of the one or more drug delivery areas. The method further comprises positioning the therapeutic agent delivery device in the vessel and transmitting a signal to one or more drug delivery areas, thereby causing the therapeutic agent to be delivered from the electroactive polymer of the one or more drug delivery areas to the target location.
A disclosed further embodiment provides a therapeutic agent delivery device comprising an elongate member having a distal end and an expandable member disposed on the distal end of the elongate member. The expandable member comprises a plurality of adjacent radially-expanding flexible walls that extend longitudinally in an axial direction along the length of the expandable member, the flexible walls forming a plurality of channels. The device further comprises a delivery lumen for delivering therapeutic agent to one or more of the plurality of channels. In this embodiment, the therapeutic agent is delivered from the delivery lumen to at least a first channel selected from the plurality of channels to a target location.
A disclosed further embodiment provides a method of delivering a therapeutic agent to a target location, the method comprising providing a therapeutic agent delivery device comprising an elongate member having a distal end, an expandable member disposed on the distal end of the elongate member, the expandable member comprising a plurality of adjacent radially-expanding flexible walls that extend longitudinally in an axial direction along the length of the expandable member, the flexible walls forming a plurality of channels, and a delivery lumen for delivering therapeutic agent. The method further comprises delivering the therapeutic agent from the delivery lumen to a first channel of the plurality of channels to a target location.
A disclosed further embodiment provides a method of determining the location of a lesion on a vessel wall, the method comprising flushing the vessel with a detectable agent and providing a lesion detection device comprising an elongate member having a distal end and a plurality of sensors disposed on the distal end of the elongate member, the plurality of sensors adapted to sense the detectable agent. The method further comprises positioning the lesion detection device in the vessel and determining a location of the lesion on the vessel wall based on signals received by the plurality of sensors from the detectable agent.
Depending on the embodiment, a device and/or method as disclosed herein can have advantages including reduced loss of therapeutic agent during and/or after the procedure, reduced delivery and/or application of therapeutic agent at undesired times or to undesired locations, simplicity of design, reduced procedural complications, improved ease of use, and/or improved overall performance during and/or after the procedure. These and other features and advantages of the disclosed devices and methods are described in, or apparent from, the following detailed description of various exemplary embodiments.
Various embodiments will be more readily understood through the following detailed description, with reference to the accompanying drawings, in which:
For a general understanding of the features of the illustrated embodiments of the disclosure, reference is made to the drawings. In the drawings, like reference numerals have been used throughout to designate like elements.
As illustrated in
As illustrated in
In the embodiment of
In the embodiment of
The condition of the target location that is sensed by the sensor 30 can be any medical condition relevant to the disease to be treated. For purposes of this disclosure, the condition will be described with respect to plaque or a lesion on the interior wall of a blood vessel commensurate with a cardiovascular condition. Other conditions such as, for example, ulcers or tumors can be detected with sensors within the scope and spirit of this disclosure.
In embodiments such as those illustrated in
In another embodiment, the one or more drug delivery areas 40 are also adapted to communicate with one or more other drug delivery areas of the plurality of drug delivery areas 40. In this embodiment, when a signal is transmitted to the one or more drug delivery areas 40, these drug delivery areas may communicate the signal to one or more other drug delivery areas 40, thereby causing the therapeutic agent to release from an electroactive polymer of the one or more other drug delivery areas 40 and be delivered to the target location 100. In this manner, the drug delivery matrix 50 is able to efficiently adapt to various sizes and shapes of target lesions 100 and deliver therapeutic agent to “fringe” areas of the matrix where the condition may be too weak to trigger the sensor 30 but where it would be advantageous to still supply drug.
The types of sensors used are not particularly limited. Micro-sized and nano-sized sensors suitable for use in biological applications are well known in the art. In certain embodiments, the sensors may comprise at least one of mechanical, environmental and biochemical sensors. For example, the sensor may be a temperature sensor that measures the plaque temperature of a lesion. Plaque temperature has been shown to be correlated directly with inflammatory cell density. See Mohammad Madjid, MD, Morteza Naghavi, MD, Basit A. Malik, MD; Thermal Detection of Vulnerable Plaque; The American Journal of Cardiology, Volume 90, Issue 10, Supplement 3, 21 Nov. 2002, pages L36-L39. Another example is the use of pH value as a triggering parameter. It has been shown that unstable vulnerable plaques have a lower pH value than surrounding tissue. Miniature-sized pH sensors are also known in the art. See Olga Korostynska , Khalil Arshak, Edric Gill and Arousian Arshak; Review on State-of-the-art in Polymer Based pH Sensors; Sensors 2007, 7, 3027-3042. Other suitable sensors are within the scope and spirit of this disclosure.
In the embodiment illustrated in
Examples of other polymeric materials from which the balloon 20 may be formed include polyethylene, HYTREL®, polyester, polyurethane, ABS (acrylonitrile-butadiene-styrene) block copolymer, ABS/Nylon blends, ABS/polycarbonate blends and combinations thereof, styrene-acrylonitrile block copolymers, other acrylonitrile copolymers, polyacrylamide, polyacrylates, polyacrylsulfones polyester/polycaprolactone blends, polyetheretherketone (PEEK), polyethersulfone (PES), polyetherimide (PEI), polyetherketone (PEK), polymethylpentene, polyphenylene ether, polyphenylene sulfide, polyolefins such as polyethylene and polypropylene, olefin copolymers, such as ethylene-propylene copolymer, ethylene-vinyl acetate copolymers, ethylene-vinyl alcohol copolymers and polyolefin ionomers, polyvinyl chloride, polycaprolactam, N-vinyl-pyrrolidone, polyurethanes and polysiloxanes.
Electroactive polymers are members of a family of polymers referred to as “conducting polymers.” They are a class of polymers characterized by their ability to change shape in response to electrical stimulation. They expand and contract upon application of an appropriate electrical potential. They typically structurally feature a conjugated backbone and have the ability to increase electrical conductivity under oxidation or reduction. In an example embodiment, the electroactive polymer may be polypyrrole. Polypyrrole exhibits superior stability under physiological conditions. The structure of polypyrrole is depicted below:
Known derivatives of polypyrrole include the following substituted polymers: poly(N-methylpyrrole), poly(N-butylpyrrole), poly[N-(2-cyanoethyl)pyrrole], poly[N-(2-carboxyethyl)pyrrole], poly(N-phenylpyrrole), poly[N(6-hydroxyhexyl)pyrrole] and poly[N-(6-tetrahydropyranylhexyl)pyrrole], among others. In addition to polypyrrole, other suitable conducting polymers, including analogs of polypyrrole, that exhibit suitable contractile or expansile properties may be used within the scope of the disclosure.
In one embodiment, the electroactive polymer is deposited, for example, by electro polymerization on an electrode. In such an embodiment, the polymer balloon surface may be covered with a patterned electrode using a sputtering process in combination with a mask. In another embodiment, the electroactive polymer can be deposited by an inkjet printing process.
The plurality of conductive elements may be configured in any suitable manner and may be around the outer surface of the expandable member 20. For example, the conductive elements may connect drug delivery areas 40 in a one-to-one relationship with adjacent drug delivery areas 40, or the conductive elements may be configured to connect with non-adjacent drug delivery areas 40 via a multiplexing scheme. In some embodiments, the conductive elements may comprise at least one of metal and polymer wiring. For example, the conductive elements may comprise Au, Ag, Pd, Pt, Fe, Mg or any suitable alloy thereof. Other suitable metals or metal alloys or conductive non-metal materials may be used for the conductive elements within the scope and spirit of this disclosure.
The therapeutic agent delivery device 10 according to these embodiments is practiced in the following manner with reference to
The operator or physician positions the delivery device 10 in the vessel by tracking the elongate member through the vessel until the expandable member 20 is at the desired position. Once in position, the delivery device 10 is activated. For example, the expandable member 20 may be expanded and the sensors 30 activated. Once activated, the sensors 30 of the plurality of drug delivery areas 40 detect any lesions 100 on the vessel wall. As illustrated in
In another embodiment, the target locations 100 on the vessel wall are detected or predetermined before the physician inserts the delivery device 10 into the vessel. In this embodiment, the three-dimensional location of the lesions on the vessel wall are mapped during a pre-scanning process using a scanning apparatus. The resulting data or map is then applied during use of the delivery device 10 by way of the delivery device 10 being coupled to or activated in accordance with the pre-scanned position and orientation data. The scanning apparatus may comprise any suitable device or devices known in the art of medical imaging. In embodiments, the pre-scan may be effectuated by X-Ray, CT, MRI or OCT scanning.
In certain embodiments, the pre-scan may be facilitated by first flushing the vessel with a detectable agent before scanning the vessel wall. In one example embodiment, the detectable agent is a super-paramagnetic iron particle. Super-paramagnetic iron particles have been coupled with polymer-lipid nanoparticles containing the antiangiogenic agent fumagillin and targeted against αvβ3 integrins of proliferating neovasculature in unstable plaques. For example, vascular cell adhesion molecule 1 (VCAM-1) is a known coupling agent. See Nahrendorf, M., Jaffer, F. A., Kelly, K. A., et al., Noninvasive Vascular Cell Adhesion Molecule-1 Imaging Identifies Inflammatory Activation of Cells in Atherosclerosis, Circulation 114:1504-1511 (2006). Noninvasive vascular cell adhesion molecule-1 imaging identifies inflammatory activation of cells in atherosclerosis. The detectable agent may also be a particle that assembles in macrophages, for example, that are present in inflamed atherosclerotic plaques. Several approaches to the use of such particles are known in the art. See Pavel Broz, Stephan Marsch and Patrick Hunzikel; Targeting of Vulnerable Plaque Macrophages with Polymer-Based Nanostructures; Trends in Cardiovascular Medicine, Volume 17, Issue 6, August 2007, pages 190-196.
Once in position, the delivery device 10 is activated to locally release the therapeutic agent to only those portions of the vessel that were predetermined to have lesions. The activation may be effected by suitable means. The drug delivery matrix 50 may be activated automatically similar to the embodiment of
In another embodiment, an imaging apparatus is provided that allows the physician to track the position of the delivery device 10 in the vessel. In this manner, the physician uses the pre-scanned data as an aid in aligning the delivery device 10 axially and rotationally. The physician may also manually send a signal to the drug delivery matrix 50 based on an external imaging apparatus once the delivery device 10 is in position. It is contemplated that positioning the delivery device 10 using the imaging apparatus will be facilitated by placing markers such as, for example, X-Ray or MRI markers, adjacent to or on the surface of the expandable member 20. Further, internal scanners, such as, for example, MRI imaging catheters using micro-coils or OCT, facilitate detailed imaging of the vessel wall. In this instance, the microcoil allows high resolution images of the vessel wall and as such enables detection of the SPIO particles after which the operator can activate the drug delivery areas on the balloon surface that are located opposed to the affected area.
On one side of the strip 28, shown in
On the opposite side of the strip 28, shown in
The drug delivery areas 42 are formed, for example, of an electroactive polymer as described herein. As just one possible example for this embodiment, the electroactive polymer may be polypyrrole (PPy), and the therapeutic agent may be charged Dexamethsone (Dex), a synthetic anti-inflammatory drug. Dexamethasone disodium phosphate can be obtained from Sigma-Aldrich Co. Other suitable therapeutic agents and electroactive polymers may be used, including, for example, therapeutic agents and electroactive polymers as described in U.S. Provisional Patent Application 61/074,456, which, as mentioned above, is incorporated herein by reference. The drug delivery areas 42 may be formed, for example, by growing PPy/Dex film potentiostatically on the silver islands or by another suitable method.
As shown in
The remainder of the strip 28 can run substantially along the length of the elongate member, which may be in the form of a catheter 17. The signals from the sensors 32 can be transmitted by conductive lines 38 to a device or processor outside of the body, thereby activating the transmission of signals by conductive lines 44 to activate the release of therapeutic agent by the electroactive polymer at the drug delivery areas 42.
While the distal end of the strip 28 is mounted on the expandable member 22, the portion of the strip 28 that runs along the length of the elongate member or catheter tubing may be mounted thereon using a heat shrink tube 24. As shown in cross-sectional view in
As shown in
The therapeutic agent delivery device 12 is used in a similar manner as described herein with respect to
In this embodiment, the conductive elements for the sensors 130 are mounted in or on the inner tube 119. As can be seen in
The sensors 130 can be micro Hall sensors or other sensors as described herein. The sensors 130 are mounted on the inner tube 119, for example in cavities that are formed, for example using an excimer laser, in the surface of the inner tube 119 to accommodate the sensors 130. In order to have a length of the conductive elements 136, 138 to attach to the sensors 130, the distal end of the inner tube 119 may be removed, for example using an excimer laser, by a process that removes the tubing but leaves the exposed wires. In this example, the conductive elements 136, 138 comprise two power supply conductive elements 136 and two conductive elements 138 for transmitting the signals from the sensors 130. In the illustrated embodiment comprising two sensors 130, both of the two sensors are attached to the power supply conductive elements 136 and each of the two sensors is attached to its own signal transmission conductive element 138. The exposed ends of the conductive elements 136, 138 are connected to the sensors 130, for example by soldering. The sensors 130 and conductive elements 136, 138 are folded backwards over the inner tube 119, and the sensors 130 are placed backside in the ablated cavities in the inner tube 119. A heat shrink tube may be shrunk over the sensors 130 and over the exposed conductive elements 136, 138. Also, a tip may be bonded to the distal end of the inner tube 119.
The inner tube 119 tube with the sensors 130 on it is positioned within the outer tube 121, with a distal portion of the inner tube 119 extending beyond the distal end of the outer tube 121. The balloon or expandable member 122 is attached, with the proximal end of the balloon or expandable member 122 affixed to the outer tube 121, and the distal end of the balloon or expandable member 122 affixed to the inner tube 119. A hub is affixed to the proximal part of the catheter 115.
The drug delivery matrix 150 can be a series of drug delivery areas positioned, for example, on one side of the balloon or expandable member 122. To place the drug delivery matrix 150 on the balloon or expandable member 122, the balloon or expandable member 122 is inflated or expanded, at which time the drug delivery matrix 150 is applied. The drug delivery matrix 150 may be applied to the same side of the device where the sensors 130 are positioned. The balloon or expandable member 122 is then deflated or brought back down to its unexpanded size for use.
During a procedure using the therapeutic agent delivery device 110, a patient may be infused intravenously with super-paramagnetic iron particles as described herein, and the patient may be scanned by MRI to locate the vulnerable plaques. A map is produced to be able to place the therapeutic agent delivery device 110 under fluoroscopy near the detected sites. Axial movement and rotation of the therapeutic agent delivery device 110 allows the physician to position the drug delivery matrix 150 based on the signals from the sensors 130. In this manner, the physician can superpose the drug delivery matrix 150 against the vulnerable plaque, after which the balloon is inflated to transfer the therapeutic agent to the target area. Thus, in this embodiment, only a part of the balloon carries a therapeutic agent, and the sensors allow the user to align the therapeutic agent to face the desired vessel wall section.
As shown in
As illustrated in
The flexible walls 260 may comprise a suitable flexible material, or a self-expanding or shape-memory material that is biocompatible. Non-limiting examples of flexible materials include, but are not limited to, stainless steels, such as 316, cobalt based alloys, such as MP35N or ELGILOY®, refractory metals, such as tantalum, and refractory metal alloys; precious metals, such as platinum or palladium, titanium alloys, such as high elasticity beta titanium, such as FLEXIUM®, nickel superalloys, and combinations thereof. Suitable shape-memory composite materials include Nitinol and others described in co-pending U.S. Patent Application Publication No. 2007/0200656 to Walak, which is expressly incorporated herein by reference.
The delivery device 210 may further comprise a plurality of sensors for locating the target location on a vessel wall. In such an embodiment, the sensors may be configured on the catheter or on a surface of the expandable member 220 according to one of the embodiments as described herein. In this regard, the sensors can be inserted inside the expandable member 220 to release drug from drug delivery areas on the surface of the expandable member (not shown).
In practice, the therapeutic agent delivery device 210 is positioned in a vessel at a target location. The physician moves the expandable member 220 into an expanded position, thus forming channels 270 in the vessel. One or more channels of the plurality of channels is then selected for drug delivery. Once the channel 270 is selected, the physician delivers the therapeutic agent from the delivery lumen through the first channel of the plurality of channels 270 to the target location 100. In this manner, therapeutic agent is delivered only within the confines of the selected channel 270 and not the entire vessel, as is often the case with conventional delivery devices. In this way, the device results in reduced loss of therapeutic agent and reduced delivery of therapeutic agent to undesired locations. In some embodiments, the channel 270 may be selected manually by a physician using an imaging apparatus, as disclosed herein. Alternatively, the channel 270 may be selected by using sensors to detect the location of a target lesion 100 on a vessel wall, as disclosed herein. In order to facilitate delivery to one or more specific channels 270, the physician may use a separate tube extending from outside of the patient to the desired channel(s). Additionally or alternatively, the outer catheter 215 may be sectioned into separate delivery lumens that correspond to the channels such that delivery through one or more lumens of the catheter results in delivery into one or more channels 270.
The delivery device 210 may incorporate the imaging and scanning features disclosed with respect to other embodiments described herein. In this regard, the delivery device 210 may be used with externally placed magnets to determine the location of the catheter within the body. For example the movement of the catheter due to the heart beat, breathing, and other body motions could be compensated for during imaging to provide still pictures such that if the catheter moves a distance x along the X-axis, then the image on the screen is moved by −xS, where S is a scaling factor, in order to compensate. Likewise, these features may be used to determine whether the delivery device 210 is in the correct position or to aid in its positioning to the desired site within the body.
When the expandable member 222 is deployed from the distal end of the catheter 213, it is expanded to its expanded position. The expansion may be accomplished by suitable means. For example, in the embodiment illustrated in
In the embodiment shown in
The catheter 217 further comprises an outer tube 221. The expandable member 222 is mounted on the distal end of the outer tube 221. The inner tube 219 extends through the outer tube 221 as well as through the,expandable member 222. The inner tube 219 and the expandable member 222 are joined together at their distal ends, at the tip 223 of the therapeutic agent delivery device 212.
The outer surface of the inner tube 219 is spaced from the inner surface of the outer tube 217 to leave a therapeutic agent delivery lumen 225. The therapeutic agent delivery lumen 225 extends from the proximal end of the therapeutic agent delivery device 212 to the expandable member 222, where it terminates at one or more ports 276.
In the illustrated embodiment, the ports 276 open into the channel 272, but no ports open into the other two channels 273. The channel 272 is closed off at its distal end by a membrane 274 extending between the adjacent radially-expanding flexible walls 262 on either side of the channel 272.
In practice, the therapeutic agent delivery device 212 is positioned in a vessel at a target location. Using the sensors in a similar manner to that described herein, for example with respect to the embodiment of
In alternative embodiments, the channel 272 may be oriented manually by a physician using an imaging apparatus, as disclosed herein. In such embodiments, the sensors 230 may be omitted.
Yet another embodiment is illustrated in
In this embodiment, the sensors 320 are Hall effect sensors. Hall effect sensors are capable of integration into microsystems. See Javad Frounchi, Michel Demierre, Zoran Randjelovic, Rade S. Popovic; ISSCC 2001/Integrated Hall Sensor Array Microsystem, Session 16/Integrated Mems and Display Drivers/16.3. Further, nano-sized (50 nm by 50 nm) Hall sensors are known in the art. See Adarsh Sandhu, Kouichi Kurosawai; 50 nm Hall Sensors for Room Temperature Scanning Hall Probe Microscopy; Japanese Journal of Applied Physics; Vol. 43, No. 2, 2004, pp. 777-778.
The Hall effect sensors may be arranged in a specific configuration in order to detect changes in magnetic field. In this manner, the sensors 320 identify the areas where the magnetic nanoparticles are accumulating. By flushing the vessel with magnetic nanoparticles as described herein, these particles accumulate in areas where the lesions are located in the vessel. The Hall effect sensor outputs a voltage or electrical signal in response to an applied magnetic field. The sensor is also directional in that it produces a stronger signal for incident magnetic field lines in one direction than for those at a different angle.
As illustrated in
It is contemplated that the lesion detection device 310 may be combined with the therapeutic agent delivery devices of previous embodiments. For example, in certain embodiments, the sensors 320 may be disposed on the catheter of the embodiment illustrated in
The following are some specific examples of devices that may be constructed in accordance with embodiments disclosed herein.
A device as illustrated in
PPy/Dex films are grown potentiostatically on the silver islands on the strip. A two electrode set-up is used. The electrochemical cell uses a 2 ml glass cuvette containing a working electrode (gold) and a platinum counter electrode. The coating process is controlled using the Gamry Potentiostat, FAS2/Femostat (Gamry Instruments) with Gamry framework software. The deposition solution (1 ml) contains 0.1 M pyrrole (Sigma) and 0.1 M dexamethasone disodium phosphate. In the potentiostatic mode, a constant potential of 1.8 V relative to the counter electrode is used. The amount of material deposited on the electrode surface is controlled by time via the total charge passed during deposition, 25 mC/cm2 charge density.
After depositing the EAP/drug layer, four Micro Hall sensors from Cryomagnetics, Oak Ridge, Tenn. (http://www.cryomagnetics.com/hall-effect-sensor.php), type HSU-1 are glued on the opposite site of the strip with a longitudinal distance of 2 mm between the sensors. A connection is made to the printed lines using conductive Silver Conductive Epoxy type 8330 (MG chemicals).
The strip is glued on the end to a balloon system with the Hall sensors positioned between the balloon and the strip, having the EAP layer facing outward. The remainder of the strip with printed wires is mounted on the catheter using a heat shrink tube (Advanced Polymers, 29 Northwestern Drive Salem, N.H. 03079-2838).
During operation, the Dexamethasone can be released from the EAP containers using a cyclic voltage, using a 100 mV/s between −0.8 and 1.4 Volt. Each individual island can be addressed individually upon analysis of the Hall sensor signal.
A device as illustrated in
The inner tube with the sensors is fed through a Pebax 72D outer tube (ID 0.03″, OD 0.035″), leaving a section of 20 mm of the inner tube sticking out beyond the distal end of the outer tube. A non-compliant Pebax 72D balloon is attached by laser bonding to the Pebax outer tube and bonded with cyano acrylate to the polyimide inner tube. The catheter is finished with a hub to the proximal part after which the balloon is inflated at 1 atm. to be able to apply the drug coating. At the tangential place where the two sensors are aligned, the balloon is pat printed with a 50/50 mixture of paclitaxel and Iopromid over an axial section ranging the inner section between the two sensors. Finally, the balloon is folded and is ready for use.
During use, the patient is infused intravenously with a saline solution containing USPIO super-paramagnetic particles (Sinerem (Guerbet, Roissy, France)) at 2.6 mg/kg. Accumulation of these magnetic particles occurs in macrophages and inflamed plaques. See Trivedi, R A, “Identifying Inflamed Carotid Plaques Using In Vivo USPIO-Enhanced MR Imaging to Label Plaque Macrophages,” Arterioscler. Thromb. Vasc. Biol. 2006; 26:1601-1606. The patient is scanned by MRI to locate the vulnerable plaques, and a roadmap is produced to be able to place the balloon catheter under fluoroscopy near the detected sites. Axial movement and rotation allows the physician to superpose the coated section of the balloon against the vulnerable plaque after which the balloon is inflated at low pressure (2 atm.) to transfer the drug to the desired target site.
A device as illustrated in
A tri-wing shaped soft silicon rubber piece (http://www.appliedsilicone.com/products-index.html, component part 40088) is cast and attached to an outer tube by using Loctite® 4981™ Super Bonder® Medical Device Adhesive. The rubber tri-shape has tipped wings such that upon retrieval in the delivery catheter they all will fold in the same direction. The three wings will make three channels (spaces between the wings), and one of them is closed by a silicon rubber membrane in place. In the valley of the closed chamber, one or more holes are punctured for the drug delivery ports.
The inner tube is fed through the outer tube and silicon wing shape and aligned such that the Hall sensors are located underneath the closed chamber after which the distal end of the inner tube is glued to the distal end of the outer part (the distal end of the expandable member). A soft rubber tip is glued to this assembly to finish off the product on the distal end. The space between outer tube and inner tube can now be used as a delivery lumen to inject a fluid (containing a drug) which then can emerge in the closed chamber through the drug delivery ports. In use, the closed chamber can be filled with a fluid drug content, while the other two chambers allow a continuous blood flow downstream to the distal part of the vessel.
Disclosed embodiments have been described with reference to several exemplary embodiments. There are many modifications of the disclosed embodiments which will be apparent to those of skill in the art. It is understood that these modifications are within the teaching of the present disclosure which is to be limited only by the claims.
The present application claims priority to U.S. provisional application Ser. No. 61/267,944 filed Dec. 9, 2009, the disclosure of which is incorporated herein by reference in its entirety.
| Number | Date | Country | |
|---|---|---|---|
| 61267944 | Dec 2009 | US |
