Abstract:
An ultrasonic catheter drug delivery device comprises an ultrasound transducer to produce ultrasonic waves, which transducer is mechanically attached to a catheter body or chamber. The ultrasonic transducer has a distal tip with a distal radiation surface, and when a therapeutic agent from a fluid source is directed to the catheter body or chamber, the radiation surface creates ultrasonic pressure and delivers liquid and simultaneously ultrasonic energy to a patient&#39;s vascularity or a selected body lumen. The method applies therapeutic agent and ultrasonic waves to the vascular area, lung or any body lumen without requiring direct contact between ultrasound transducer and body, dissolves blood clots, and stimulates tissue cells.

Description:
FIELD OF THE INVENTION  
         [0001]    The present invention generally relates to medical devices and methods. More particularly, the present invention relates to apparatus and methods for the ultrasonically enhanced delivery of therapeutic or contrast agents within the vascular and lung areas or other corporeal lumens.  
         BACKGROUND OF THE INVENTION  
         [0002]    Despite the significant progress of medical technology, vascular and lung diseases, as well as arterial thrombosis (blood clots in arteries), remain frequent, costly and serious problems in health care. Current methods of treatment such as drugs, interventional devices, and/or bypass surgery are usually expensive and not always effective, even sometimes causing additional problems. For example, drugs can also dissolve beneficial clots or interventional devices can injure healthy tissue to cause potentially fatal bleeding complications or to form scarring or cellular growth which may itself eventually become a serious obstruction in, for example, a blood vessel (a process known as restenosis).  
           [0003]    Ultrasonic energy has been used for enhancing the intravascular delivery of drug, to dissolve clot acoustically, disrupt mechanically and inhibit restenosis. Such energy can be delivered intravascularly using specialized catheters having ultrasonically vibrating surface at or near their distal ends. One type of ultrasonic catheter delivery system uses a wire or other axial transmission element to deliver energy from an ultrasonic energy source, located outside the patient to the internal organs, to desired corporeal lumens. (See, for example, U.S. Pat. Nos. 5,002,059, 5,324,255, 5,345,940, and 5,699,805, each of which is incorporated herein by reference.) Such catheters are rigid and cannot be easily inserted through narrow and tortuous vessels and may cause serious damage to vascular walls.  
           [0004]    A second type of catheter has ultrasonic transducers mounted directly on their distal ends. See, for example; U.S. Pat. Nos. 5,362,309, 5,318,014, 5,315,998, 5,269,291, 5,197,946, 6,001,069, and 6,024,718, each of which is incorporated herein by reference. Despite enhanced safety and the fact that there is no need to employ a transmission element along the entire length, these catheters suffer from limited ultrasound energy, and the transducer-catheter design is still problematic.  
           [0005]    Another type of catheter has an ultrasonic transducer or ultrasound transmission element with a central orifice in the distal end to impart ultrasonic energy into liquid and simultaneously deliver it to a corporeal lumen. See, for example, U.S. Pat. Nos. 5,735,811 and 5,197,946, each of which is incorporated herein by reference. Although these catheters are more effective and liquid delivery is more convenient, there are design difficulties and limitation of ultrasound energy from longitudinal waves.  
         OBJECT OF THE INVENTION  
         [0006]    It is an object of the invention to provide an improved method and device for catheter drug delivery.  
           [0007]    It is also an object of this invention to provide a method and device for catheter drug delivery using ultrasound energy.  
           [0008]    It is another object of the invention to mix different drugs ultrasonically and deliver them to a desired corporeal lumen ultrasonically.  
           [0009]    It is a yet another object of the invention to mix drug-liquid solutions with a gas (for example, saline with oxygen) ultrasonically and deliver the mixture to a desired corporeal lumen ultrasonically.  
           [0010]    It is a further object of the invention to provide a method and device for delivering drugs to an intravascular area or/and a corporeal lumen, to dissolve blood clots.  
           [0011]    It is a yet further object of the invention to treat a blocked and narrowed blood vessel with ultrasound waves.  
           [0012]    These and other objects of the invention will become more apparent from the discussion below.  
         SUMMARY OF THE INVENTION  
         [0013]    The present invention relates to apparatus and method for the ultrasonically enhanced delivery of therapeutic or contrast agents within the vascular and lung area or other desired corporeal lumens. Ultrasonic waves are applied to a vascular area, lung or any corporeal lumen without requiring direct contact between ultrasound transducer tip and the patient&#39;s body, particularly to dissolve blood clots.  
           [0014]    According to the present invention, a catheter system comprises an ultrasound transducer having a distal tip with a radial surface and a distal end surface. The ultrasound transducer is disposed in a chamber at the proximal end of the catheter, and the transducer radiation surface or tip directs ultrasound waves or energy forward into the catheter coaxially via liquid. Longitudinal ultrasound waves induce wave motion in fluid adjacent to the transducer distal end. While particularly intended to enhance the absorption of therapeutic agents delivered to certain body lumens, the catheter system of the present invention is also useful for the delivery of ultrasonic energy to a desired location. The transducer radiation surface or transducer tip, may be cylindrical, flat, concave, convex, irregular or have a different shape-geometry to radiate ultrasound energy into catheter.  
           [0015]    The catheter of the present invention may comprise a proximal tubing for delivering therapeutic agent from a reservoir by pump or syringe. The tubing may be located in front of or behind the radiation surface.  
           [0016]    In a first embodiment of the invention, an ultrasound transducer and tip are mounted in a proximal portion of a catheter body, located outside of the body of a patient. The remainder of the catheter distal to the proximal portion may be inserted into a blood vessel or attached to a body lumen, to drive a therapeutic agent ultrasonically and/or deliver ultrasonic energy.  
           [0017]    In a second embodiment, the distal tip of the transducer does not have an orifice, which is very important to create and deliver ultrasound energy fully to a vessel or body lumen.  
           [0018]    In a third embodiment, the catheter system comprises a catheter body, mechanically coupled with an ultrasound transducer through a housing or tip node, which is where the transducer body is outside the catheter. In this way, the catheter body can be provided with two or more tubing inlets (sleeves) for different therapeutic agents, even one or more different gases such as oxygen, and agents to be mixed and delivered ultrasonically.  
           [0019]    The catheter system of the invention is particularly advantageous on tissues for which local topical application of a therapeutic agent is desirable but contact with the tissue is to be avoided. Furthermore, ultrasound waves used in the method energize the drug, dissolve the clots and cause the penetration of the drug within the narrow and blocked vessels. 
       
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       [0020]    [0020]FIG. 1 is a perspective, partly cross-sectional view of an ultrasonic catheter drug delivery system for use according to the present invention;  
         [0021]    [0021]FIG. 2 is a lateral view of an ultrasonic catheter system chamber of the invention with two horizontally located sleeves;  
         [0022]    [0022]FIG. 3 is a frontal view of an ultrasonic catheter system chamber of the invention with three peripherally located sleeves;  
         [0023]    [0023]FIG. 4 is a lateral, cross-sectional view of a catheter system chamber, mechanically coupled with an ultrasound transducer through the tip; and  
         [0024]    [0024]FIG. 5 is a lateral, cross-sectional view of an ultrasonic catheter drug delivery system for delivering therapeutic agent to the catheter body or chamber through a central orifice of the ultrasonic tip. 
     
    
     DETAILED DESCRIPTION OF THE INVENTION  
       [0025]    The present invention is a method and device, which provides treatment of luminal conditions, particularly for the treatment of coronary and peripheral arterial disease and thrombosis, where the purpose is to dissolve or disrupt the clot, plague or other stenotic lesions which cause the disease, and for dilation of narrowed vessels. The method and device of the present invention also useful to enhance the administration of therapeutic agents primarily responsible for the disruption of the clots or other stenotic material. The ultrasonic energy agitates and promotes the penetration of the drug into the stenotic material. Due to delivery of therapeutic agent and ultrasound energy through the agent, this method and device of the present invention are further useful for treatment of other body lumens, such as the urethra, ureter, fallopian tubes, or urological disorders related with prostate gland (BPH—Benigh Proctatic Hyperplasia), and can be used for impotency (erectile dysfunction) treatment by ultrasonically stimulating sexual organs, urinary tract, and the like.  
         [0026]    The present invention can be used for targeted and localized drug delivery for treatment of lung, vasculature, vasopasm and tumor treatment. In addition, this invention is very useful for the treatment of closed wounds as a fistulas, canals, etc., by destroying bacteria cells and stimulating healthy tissue cells.  
         [0027]    The invention can perhaps be better appreciated by referring to the drawings. FIG. 1 is a perspective view of ultrasound catheter drug delivery system  2 , comprising an ultrasound generator  4 , a connector  6  operatively connecting ultrasound generator  4  with a transducer  8 , a housing  10  surrounding transducer  8 , and a catheter  12  having a proximal portion  14  with a chamber  16  containing a therapeutic agent  18 . Transducer  8  has a tip  20  with a radial surface  22  and a distal radiation surface  24 . Chamber  16  is in fluid communication through tubing  26  with a fluid source  28 , and directly with at least one lumen  30  of the distal portion  32  of catheter  12  that extends to catheter distal end  34 . Fluid source  28  can be, for example, a reservoir with a pressure pump or syringe.  
         [0028]    The proximal section  36  of catheter proximal portion  14  sealingly engages housing  10 . Preferably the inner surface  38  of proximal section  36  has threads  40  that engage reciprocal threads  42  on the outer surface  44  of housing  10 . This arrangement will allow the operator to vary the distance between distal radiation surface  24  and the distal end  46  of chamber  16  to regulate ultrasonic pressure and energy level. While radial surface  22  can be smooth or substantially smooth, it is preferred that this surface is not smooth, for example, with rings, threads, barbs, or the like, which will create more ultrasonic pressure in catheter  12 .  
         [0029]    In the embodiment of the invention shown in FIG. 1, ultrasonic energy at a preselected frequency is sent through the catheter  10  with fluid such as a therapeutic agent as a transmission member. Ultrasound energy will pass through therapeutic agent  18  to catheter distal end  34 . Catheter  12  may be formed from a conventional rigid or flexible material, dependent upon the application. It would be appropriate for catheter  12  to be flexible if the catheter is to be inserted into tortuous vascularity or if catheter distal end  34  is to be attached to a vessel, fistula, or the like.  
         [0030]    A second embodiment of the invention is shown in FIG. 2, where transducer  50  is fixedly, optionally removably, attached to the proximal section  52  of the proximal portion  54  of a catheter  56 . Transducer  50  has a tip  58  with a radial surface  60  and a distal radiation surface  62 . Catheter proximal portion  54  has a chamber  64  with a therapeutic agent  66  that is in fluid communication with each of two fluid sources  68 , 70  through lumens  72 , 74 , respectively. Fluid sources  68 , 70  may provide two or more fluids, e.g., liquid or gas, such as saline or oxygen, to be ultrasonically mixed and delivered through lumen  76  to catheter distal end  78 .  
         [0031]    [0031]FIG. 3 is a semi-cross-sectional view of the proximal end of a catheter according to the invention wherein three fluid sources  80  are each in fluid communication through a lumen  82  with chamber  84  of catheter proximal section  86 . The distal radiation surface  88  of a transducer (not shown) is positioned within chamber  84 .  
         [0032]    In FIG. 4, a connector  110  operatively connects an ultrasound generator (not shown) with a transducer  112 , which has a tip  114  with a radial surface  116  and a distal end surface  118 . A catheter  120  has a proximal portion  122  with a chamber  124  containing a therapeutic agent  126 . Chamber  124  is in fluid communication through tubing  130  with a fluid source  132 , and directly with at least one lumen  134  of the distal portion  136  of catheter  120  that extends to catheter distal end  140 . Fluid source  132  can be, for example, a reservoir with a pressure pump or syringe.  
         [0033]    The proximal section  142  of catheter proximal portion  122  sealingly engages radial surface  116 . Chamber  124  must be attached to ultrasonic transducer distal tip  114  at the mechanical resonant node, such as node  144 . If chamber  124  is not connected to the resonant node (either a little before or a little after the mechanical node), the intensity of the ultrasound energy at distal end  140  will be attenuated, i.e., damped, and ultrasound waves and/or energy will be transferred to the walls of chamber  126 , possibly damaging the chamber  126  structure assembly, which may cause leakage.  
         [0034]    In the embodiment of the invention set forth in FIG. 5, a connector  150  operatively connects an ultrasound generator (not shown) with a transducer  152 , which has a distal tip  154  with a radial surface  156  and a distal end surface  158 . A catheter  160  has a proximal portion  162  with a chamber  164  containing a therapeutic agent  166 .  
         [0035]    Transducer distal tip  154  has a central orifice  170 . Chamber  164  is in fluid communication with at least one fluid source  172  through central orifice  170 , which can be smooth, waved, ringed, slotted, grooved, or threaded, and infusion lumen  174  within tubing  176 . Two or more fluid sources  172  and infusion lumens  174  can mix and deliver different therapeutic agents. Chamber  164  is also in fluid communication with lumen  180  in the distal portion  182  of catheter  160  that extends to distal end  184 . The non-smooth surface of orifice  170 , such as rings or threads, increases the pressure of liquid in chamber  164 .  
         [0036]    Chamber  164  should be attached to ultrasonic transducer distal tip  158  at a mechanical resonant node, such as node  190 . Similarly, each lumen  174  should intersect central orifice  170  at a resonant node, such as node  192 .  
         [0037]    The catheter systems herein are comprised of conventional materials. The transducer and catheter chamber are preferably comprised of suitable metallic or even polymeric substances. Most preferably the transducer distal tip is comprised of a metal such as titanium or nitinol.  
         [0038]    As is mentioned throughout, the invention here can deliver one or more liquid or gaseous substances to a catheter distal end. Such substances include, but are not limited to, therapeutic agents such as antibiotics or antiseptics, saline, oil, water, oxygen, anticoagulants such as heparin or cumadine, or even liquid medical polymers, or mixtures of two or more thereof.  
         [0039]    The preceding specific embodiments are illustrative of the practice of the invention. It is to be understood, however, that other expedients known to those skilled in the art or disclosed herein, may be employed without departing from the spirit of the invention or the scope of the appended claims.