Ultrasonic disbursement of magnetically delivered substances

A system and method are provided for attracting a magnetically responsive substance inserted in a subject's body towards a target area within the body to treat the area. The system generally comprises a medical device having a proximal end, a distal end, and at least one magnetic element disposed at the distal end of the medical device for orienting the distal end in a desired direction to place an aperture against the opposite wall of the vessel. The system further includes a voltage that may be applied to a coil that is disposed on the side of the medical device and proximally spaced from the magnetic element. A voltage is applied to the coil to attract the magnetically responsive substances inserted into the body around the coil. A high frequency alternating current voltage is applied to an adjacent transducer to ultrasonically disperse the collected magnetically responsive substances into the surrounding target tissue.

FIELD OF THE INVENTION

The present invention relates to delivery of substances to target areas within a subject body, and more particularly to percutaneous transluminal procedures for the targeted delivery of substances.

BACKGROUND OF THE INVENTION

Interventional medicine is the collection of medical procedures in which access to the site of treatment is made through one of the patient's blood vessels, body lumens or cavities. For example, treatment of vascular defects may be performed using a catheter which enters the patient's arterial system through a puncture of an artery, and is referred to as a Percutaneous (through the skin), Transluminal (through the blood vessel) procedure. The heretofore major impediment to particle drug delivery through the vasculature has been an inability to retain a significant fraction of the particles at the site where needed, because of the dominant viscous forces acting to rapidly drag the particles downstream in vessels with blood flowing rapidly. Even with the highest magnetic gradients available and the largest practical magnetic particles the effective delivery at the point of interest has been fractions of a percent for velocities found in all vasculatures of the body butt the capillaries. Moreover, delivery of various medical substances through the tenuous vascular wall can be difficult.

Interventional medicine is the collection of medical procedures in which access to the site of treatment is made through one of the patient's blood vessels, body cavities or lumens. For example, treatment of vascular defects may be performed using a catheter which enters the patient's arterial system through a puncture of an artery, and is referred to as a Percutaneous (through the skin), Transluminal (through the blood vessel) procedure. The heretofore major impediment to particle drug delivery through the vasculature has been an inability to retain a significant fraction of the particles at the site where needed, because of the dominant viscous forces acting to rapidly drag the particles downstream in vessels with blood flowing rapidly. Even with the highest magnetic gradients available and the largest practical magnetic particles the effective delivery at the point of interest has been fractions of a percent for velocities found in all vasculatures except the capillaries of the body. Moreover, delivery of various medical substances through the tenuous vascular wall can be difficult.

SUMMARY OF THE INVENTION

Embodiments of the present invention provide a system and method for delivery of a magnetically responsive substance to a desired target area within a subject body. A catheter is inserted in the body vasculature and navigated to the target area, briefly held against the vascular wall, and a magnetically responsive substance is inserted through the catheter into the subject's body, and then attracted towards the target area through an aperture in the catheter. In one embodiment, a system is provided for attracting a magnetically responsive substance that is inserted into a subject's body towards a target area to treat the target area within the body with the magnetically responsive substance. The system generally includes an elongate medical device (preferably a catheter) having a proximal end, a distal end, and at least one magnetically responsive element disposed at the distal end of the medical device that may be oriented in a desired direction by an external magnetic field. The system further includes a coil disposed on the side of the elongate medical device that is spaced proximally from the distal end of the device. The coil faces an aperture in the elongate medical device. Within the catheter and attached to or near to the coil, and in a plane approximately parallel to the coil is an ultrasound transducer. The system further includes leads for applying a direct current voltage that may be applied to the coil. A direct current voltage may be applied to the coil to attract and preferentially collect magnetically responsive substances inserted into the body around the coil. Upon collecting a sufficient amount of the magnetically responsive substance around the coil, a high frequency alternating current voltage may be applied to the attached transducer to ultrasonically disperse the collected magnetically responsive substances into the tissue adjacent to the coil.

DETAILED DESCRIPTION OF THE EMBODIMENTS

The following descriptions of the various embodiments are merely exemplary in nature and are in no way intended to limit the invention, its application, or uses.

Embodiments of the present invention provide for delivery of a magnetically responsive substance to a desired target area within a subject body, where the magnetically responsive substance may be inserted within an elongated medical device into the subject's body and then migrated towards the target area. In one embodiment, a system is provided for introducing a magnetically responsive substance into a subject's body towards a target area to treat the target area within the body with the magnetically responsive substance. The system generally comprises an elongate medical device having a proximal end, a distal end, and at least one magnetically responsive element disposed at the distal end of the medical device that may be oriented in a desired direction by an external magnetic field applied to the distal end of the medical device. The system further comprises a coil disposed on the side of the elongate medical device, the coil being spaced proximally from the distal end so as to reduce interference from the external magnetic field applied to the magnetically responsive element. In this embodiment, the coil is disposed in a recessed area on the side of the elongate medical device, which recessed area also serves as a staging area for disbursement of the substance into the target tissue. The system further contains a disk-like transducer for generating ultrasound waves into the aperture through which the substance is passed to the wall of the blood vessel. In other embodiments, the coil and transducer may be separate components that are inserted or assembled into a conventional magnetically navigable catheter device. The system further comprises a direct current or low frequency alternating current voltage source (a), a high frequency alternating current source (b), and a control device for controlling the application of voltage (a) to the coil and the application of high frequency voltage (b) to the ultrasound transducer. The control device accordingly may apply a voltage (a) to the coil to attract and collect magnetically responsive substances inserted into the catheter around the coil. Upon collecting a sufficient amount of the magnetically responsive substance around the coil, the control device may then apply a high frequency alternating current voltage to the transducer to ultrasonically transfect the collected magnetically responsive substances into the tissue surrounding the coil.

Referring toFIG. 1, an elongate medical device20is depicted within a vessel50of a subject body's vasculature system. The elongate medical device20has a magnetic tip element28disposed near the distal end of the device20, which is responsive to a magnetic field30applied external from the subject body or patient to orient the distal end of the medical device20. The direction of the applied magnetic field30responsively causes the magnetic element28to orient the distal end of medical device20into the configuration shown inFIG. 1, due to the magnetic moment. In this position, the portion of the elongate medical device20opposite the direction of the tip bending and that includes the coil34is forced against the side wall of the vessel. In this embodiment, the coil34is spaced from the magnetic element28by a distance that is effective to minimize interference with the magnetic field of the magnetic tip element. When a DC (or in some cases AC) voltage is applied to the coil34, the coil generates a field that attracts a magnetically responsive substance42that may be inserted within the catheter, where an outlet40adjacent the coil34as shown inFIG. 1provides for injecting the magnetically responsive substance42through the coil and into the patient's vasculature. In this embodiment, the magnetically responsive substance42as shown inFIG. 2is comprised of micro-bubbles that may be injected into the subject body's vasculature system. The micro-bubbles42are configured to hold a substance to be delivered to a target location within the subject body, as well as a magnetically responsive material of a quantity sufficient to permit the micro-bubble42to be attracted by a magnetic field. Upon application of ultrasound pulses of selected frequencies and sufficient power the micro-bubble will destruct and the enclosed substances will be projected into the surrounding tissue. This mechanism is especially advantageous for the delivery of substances to target areas such as vessel walls, which have a tenuous inner surface that is not easily penetrated. The ultrasound burst that destructs the micro-bubbles will also project the substances within the micro-bubble towards and through the surrounding tissue, a process called transfection. The ultrasound disbursement of the magnetically responsive substances accordingly provides for improved delivery of substances to target tissues within a subject's body.

In various embodiments of a system for delivering a substance within a subject body, the coil34is used to attract the magnetically responsive substance42, and to collect or retain the magnetically responsive substance42near to the coil34. The magnetically responsive substance42may comprise micro-bubbles that will destruct and disburse when subjected to ultrasonic pulses from the transducer35, and includes at least one of a group of magnetically responsive material consisting of magnetite, iron, iron oxide, cobalt, or other magnetic compounds. The micro-bubbles may also comprise substances, such as anti-cancer drugs or a modified gene for gene therapy, for example, that may be disbursed into tissues within the subject's body for treating an affected target area. The micro-bubbles42preferably will destruct and disburse when subjected to ultrasonic pulses in the range of 1 to 40 MHz, which are preferably generated by the transducer35when powered by an alternating current voltage at the required transducer excitation frequency. With the aid of an external magnetic field source, a magnetic field30may be applied to the distal end of the medical device20. The applied magnetic field will cause the magnetically responsive element28to orient the distal end of medical device20and force the portion of the elongate medical device20including the coil34against the side wall50of a vessel, as shown inFIG. 1. The medical device20may be constructed with a preferential bend direction so that the application of a magnetic field causes the device to bend in a predetermined manner. This helps ensure that the coil34and the transducer35are properly positioned. The medical device20accordingly provides for navigation within the vasculature system of a subject body, to allow for placement of a coil disposed on the medical device against a target tissue surface within the subject's body for subsequent delivery of a magnetically responsive substance to the target tissue.

In one embodiment of an elongate medical device for delivering a magnetically responsive substance, the medical device comprises a tubular member having a proximal end, a distal end, and at least one magnetically responsive element disposed at the distal end of the tubular member. The medical device further comprises a coil disposed on the side of the tubular member that is spaced proximally from the magnetically responsive element. The coil is preferably spaced from the magnetically responsive element by a distance that is effective to reduce interference with an external magnetic field applied to the magnetically responsive element. The coil generates a field that attracts and collects magnetically responsive substances that are inserted within the body when a direct or alternating current voltage is applied to the coil. Upon application of a high frequency excitation voltage the transducer generates ultrasonic vibrations that disburse the collected magnetically responsive substances into the surrounding tissue. In one preferred embodiment the transducer is parallel to and supported a small distance from the coil to permit a passage of micro bubble particles to and through the coil. The ultrasonic vibrations are preferably generated by the transducer35when powered by an alternating current voltage having a frequency of about 20 MHz. The transducer is preferably used to generate a short burst of ultrasound for a time period of at least several seconds.

In the embodiment shown inFIG. 1, the medical device20comprises a recessed area (defined by elements41and43as shown inFIG. 1) on the side of the tubular member spaced proximally from the magnetically responsive element, wherein the coil is received in the recessed area. The coil34may be secured within the recess area, and may be at least partially embedded within the tubular member of the elongate medical device20. The coil34further includes wires36and38extending through the lumen26of the tubular member. Wires36and38extend through the medical device20to the proximal end24outside of the subject's body, where a voltage52may be applied via control54to the wires36and38and accordingly the coil34. When a voltage is applied to the coil34, the coil attracts the magnetically responsive substance42. A magnetic substance such as magnetite may be coated onto the micro-bubble shells, or magnetic particles inserted within the shell. When an AC voltage56is applied via control54to the transducer through wires37and39, it generates an ultrasound burst that destructs the micro-bubbles. The ultrasound burst will cause the micro-bubbles42(as shown inFIG. 2) to destruct or explode, and the recessed area provides shaping for directing the explosion towards the target tissue to disburse the substance towards the target. The device is preferably construed to bend in the vicinity of the recess, so that the recess is held closely adjacent the curves of the vessel. In one embodiment, and as shown inFIG. 1, the distal end22of the tubular element is closed by capping element32to prevent delivering the micro bubbles and magnetically responsive substance in the vicinity of magnetic tip element28. The capping element32may further comprise a self closing aperture appropriate for insertion of medical device20over a guide wire and designed to reduce or eliminate micro bubble or substance leakage from the device lumen distal end22to the blood vessel.

In other embodiments used where the blood velocity is very low, and as illustrated inFIG. 3, the medical device may further comprise an opening40in the tubular member near to the coil34through which a magnetically responsive substance may be delivered and injected into the patient's vasculature. In this embodiment the particles will not be swept away from the ultrasound impaction region.FIG. 4illustrates the process of transfection using the embodiment ofFIG. 3. In some cases this embodiment may be used in faster flowing vessels wherein the ultrasound bursts can be timed with release of particles into the region of the opening40.