Abstract:
A catheter comprises an elongated carrier and a balloon carried by the carrier in sealed relation thereto. The balloon has an outer surface and is arranged to receive a fluid therein that inflates the balloon. The catheter further comprises a shock wave generator within the balloon that forms mechanical shock waves within the balloon, and a medicinal agent carried on the outer surface of the balloon. The medicinal agent is releasable from the balloon by the shock waves.

Description:
PRIORITY CLAIM 
     The present application claims the benefit of U.S. Provisional Patent Application Ser. No. 61/111,196, filed Nov. 4, 2008, which application is incorporated herein by reference in its entirety. 
    
    
     BACKGROUND OF THE INVENTION 
     The present invention relates to a treatment system for percutaneous coronary angioplasty or peripheral angioplasty in which a dilation catheter is used to cross a lesion in order to dilate the lesion and restore normal blood flow in the artery. It is particularly useful when the lesion is a calcified lesion in the wall of the artery. Calcified lesions require high pressures (sometimes as high as 10-15 atmospheres) to break the calcified plaque and push it back into the vessel wall. With such pressures comes trauma to the vessel wall which can contribute to vessel rebound, dissection, thrombus formation, and a high level of restenosis. Non-concentric calcified lesions can result in undue stress to the free wall of the vessel when exposed to high pressures. An angioplasty balloon when inflated to high pressures can have a specific maximum diameter to which it will expand but the opening in the vessel under a concentric lesion will typically be much smaller. As the pressure is increased to open the passage way for blood the balloon will be confined to the size of the open in the calcified lesion (before it is broken open). As the pressure builds a tremendous amount of energy is stored in the balloon until the calcified lesion breaks or cracks. That energy is then released and results in the rapid expansion of the balloon to its maximum dimension and may stress and injure the vessel walls. Anti-proliferative drugs such as Paclitaxel delivered to the site of balloon expansion or stent deployment is known to reduce the response of the vessel to the injury or the stent. Such drugs are currently coated on the stent surface and provide long term deployment to prevent restenosis due to cell proliferation. 
     SUMMARY OF THE INVENTION 
     In one embodiment, a catheter comprises an elongated carrier, a balloon carried by the carrier in sealed relation thereto, the balloon having an outer surface and being arranged to receive a fluid therein that inflates the balloon, and a shock wave generator within the balloon that forms mechanical shock waves within the balloon. The catheter further includes a medicinal agent carried on the outer surface of the balloon. The medicinal agent is releasable from the balloon by the shock waves. 
     The medicinal agent may be in the form of a plurality of microspheres. The microspheres may have a diameter of between about 2 microns and about 100 microns. 
     Alternatively, the medicinal agent may in the form of a plurality of microcapsules having a drug therein, wherein the drug is releasable from the microcapsules by the shock waves. The microcapsules may have a diameter of between about 2 microns and about 100 microns. The microcapsules may be arranged to crack open upon exposure to the shock waves. The microcapsules may be formed of a polymer, a starch, or glucose. 
     The medicinal agent may still alternatively be in the form of a layer of a drug bonded to the balloon outer surface. 
     According to another embodiment, a method comprises the step of providing a catheter having an elongated carrier and a balloon carried by the carrier in sealed relation thereto. The balloon has an outer surface. The method further comprises the steps of applying a medicinal agent to the outer surface of the balloon, inflating the balloon with a liquid, and producing mechanical shock waves within the balloon to release the medicinal agent from the balloon outer surface. 
     The applying step may include providing the medicinal agent in the form of a plurality of microspheres. The microspheres may be formed to have a diameter of between about 2 microns and about 100 microns. 
     The applying step may alternatively include providing the medicinal agent in the form of a plurality of microcapsules having a drug therein, wherein the drug is releasable from the microcapsules by the shock waves. The microcapsules may be formed to have a diameter of between about 2 microns and about 100 microns. The mechanical shocks waves are preferably provided with sufficient energy to cause the microcapsules to crack open to release the drug. The microcapsules are formed of a polymer, a starch, or glucose. 
     The applying step may further alternatively include providing the medicinal agent in the form of a layer of a drug bonded to the balloon outer surface. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       The features of the present invention which are believed to be novel are set forth with particularity in the appended claims. The various embodiments of the invention, together with representative features and advantages thereof, may best be understood by making reference to the following description taken in conjunction with the accompanying drawings, in the several figures of which like reference numerals identify identical elements, and wherein: 
         FIG. 1  is a view of the therapeutic end of a typical prior art over-the-wire angioplasty balloon catheter; 
         FIG. 2  is a side view of a dilating angioplasty balloon catheter with two electrodes within the balloon attached to a source of high voltage pulses according to one embodiment of the invention; 
         FIG. 3  is a schematic of a high voltage pulse generator; 
         FIG. 3A  shows voltage pulses that may be obtained with the generator of  FIG. 3 ; 
         FIG. 4  is a side view of the catheter of  FIG. 2  showing an arc between the electrodes and simulations of the shock wave flow; 
         FIG. 5  is a side view of a dilating catheter with insulated electrodes within the balloon and displaced along the length of the balloon according to another embodiment of the invention; 
         FIG. 6  is a side view of a dilating catheter with insulated electrodes within the balloon displaced with a single pole in the balloon and a second being the ionic fluid inside the balloon according to a further embodiment of the invention; 
         FIG. 7  is a side view of a dilating catheter with insulated electrodes within the balloon and studs to reach the calcification according to a still further embodiment of the invention; 
         FIG. 8  is a side view of a dilating catheter with insulated electrodes within the balloon with raised ribs on the balloon according to still another embodiment of the invention. 
         FIG. 8A  is a front view of the catheter of  FIG. 8 ; 
         FIG. 9  is a side view of a dilating catheter with insulated electrodes within the balloon and a sensor to detect reflected signals according to a further embodiment of the invention; 
         FIG. 10  is a pressure volume curve of a prior art balloon breaking a calcified lesion; 
         FIG. 10A  is a sectional view of a balloon expanding freely within a vessel; 
         FIG. 10B  is a sectional view of a balloon constrained to the point of breaking in a vessel; 
         FIG. 10C  is a sectional view of a balloon after breaking within the vessel; 
         FIG. 11  is a pressure volume curve showing the various stages in the breaking of a calcified lesion with shock waves according to an embodiment of the invention. 
         FIG. 11A  is a sectional view showing a compliant balloon within a vessel; 
         FIG. 11B  is a sectional view showing pulverized calcification on a vessel wall; 
         FIG. 12  illustrates shock waves delivered through the balloon wall and endothelium to a calcified lesion; 
         FIG. 13  shows calcified plaque pulverized and smooth a endothelium restored by the expanded balloon after pulverization; 
         FIG. 14  is a schematic of a circuit that uses a surface EKG to synchronize the shock wave to the “R” wave for treating vessels near the heart; 
         FIG. 15  is a side view, partly cut away, of a dilating catheter with a parabolic reflector acting as one electrode and provides a focused shock wave inside a fluid filled compliant balloon; 
         FIG. 16  is a shockwave angioplasty balloon similar to  FIG. 2  with micro-balloons or microspheres filled with a drug on the surface of the balloon; and 
         FIG. 17  is a layered shockwave balloon similar to  FIG. 2  with an added layer of drug bonded to the balloon. 
     
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
       FIG. 1  is a view of the therapeutic end of a typical prior art over-the-wire angioplasty balloon catheter  10 . Such catheters are usually non-complaint with a fixed maximum dimension when expanded with a fluid such as saline. 
       FIG. 2  is a view of a dilating angioplasty balloon catheter  20  according to an embodiment of the invention. The catheter  20  includes an elongated carrier, such as a hollow sheath  21 , and a dilating balloon  26  formed about the sheath  21  in sealed relation thereto at a seal  23 . The balloon  26  forms an annular channel  27  about the sheath  21  through which fluid, such as saline, may be admitted into the balloon to inflate the balloon. The channel  27  further permits the balloon  26  to be provided with two electrodes  22  and  24  within the fluid filled balloon  26 . The electrodes  22  and  24  are attached to a source of high voltage pulses  30 . The electrodes  22  and  24  are formed of metal, such as stainless steel, and are placed a controlled distance apart to allow a reproducible arc for a given voltage and current. The electrical arcs between electrodes  22  and  24  in the fluid are used to generate shock waves in the fluid. The variable high voltage pulse generator  30  is used to deliver a stream of pulses to the electrodes  22  and  24  to create a stream of shock waves within the balloon  26  and within the artery being treated (not shown). The magnitude of the shock waves can be controlled by controlling the magnitude of the pulsed voltage, the current, the duration and repetition rate. The insulating nature of the balloon  26  protects the patient from electrical shocks. 
     The balloon  26  may be filled with water or saline in order to gently fix the balloon in the walls of the artery in the direct proximity with the calcified lesion. The fluid may also contain an x-ray contrast to permit fluoroscopic viewing the catheter during use. The carrier  21  includes a lumen  29  through which a guidewire (not shown) may be inserted to guide the catheter into position. Once positioned the physician or operator can start with low energy shock waves and increase the energy as needed to crack the calcified plaque. Such shockwaves will be conducted through the fluid, through the balloon, through the blood and vessel wall to the calcified lesion where the energy will break the hardened plaque without the application of excessive pressure by the balloon on the walls of the artery. 
       FIG. 3  is a schematic of the high voltage pulse generator  30 .  FIG. 3A  shows a resulting waveform. The voltage needed will depend on the gap between the electrodes and generally 100 to 3000 volts. The high voltage switch  32  can be set to control the duration of the pulse. The pulse duration will depend on the surface area of the electrodes  22  and  24  and needs to be sufficient to generate a gas bubble at the surface of the electrode causing a plasma arc of electric current to jump the bubble and create a rapidly expanding and collapsing bubble, which creates the mechanical shock wave in the balloon. Such shock waves can be as short as a few microseconds. 
       FIG. 4  is a cross sectional view of the shockwave catheter  20  showing an arc  25  between the electrodes  22  and  24  and simulations of the shock wave flow  28 . The shock wave  28  will radiate out from the electrodes  22  and  24  in all directions and will travel through the balloon  26  to the vessel where it will break the calcified lesion into smaller pieces. 
       FIG. 5  shows another dilating catheter  40 . It has insulated electrodes  42  and  44  within the balloon  46  displaced along the length of the balloon  46 . 
       FIG. 6  shows a dilating catheter  50  with an insulated electrode  52  within the balloon  56 . The electrode is a single electrode pole in the balloon, a second pole being the ionic fluid  54  inside the balloon. This unipolar configuration uses the ionic fluid as the other electrical pole and permits a smaller balloon and catheter design for low profile balloons. The ionic fluid is connected electrically to the HV pulse generator  30 . 
       FIG. 7  is another dilating  60  catheter with electrodes  62  and  64  within the balloon  66  and studs  65  to reach the calcification. The studs  65  form mechanical stress risers on the balloon surface  67  and are designed to mechanically conduct the shock wave through the intimal layer of tissue of the vessel and deliver it directly to the calcified lesion. 
       FIG. 8  is another dilating catheter  70  with electrodes  72  and  74  within the balloon  76  and with raised ribs  75  on the surface  77  of the balloon  76 . The raised ribs  75  (best seen in  FIG. 8A ) form stress risers that will focus the shockwave energy to linear regions of the calcified plaque. 
       FIG. 9  is a further dilating catheter  80  with electrodes  82  and  84  within the balloon  86 . The catheter  80  further includes a sensor  85  to detect reflected signals. Reflected signals from the calcified plaque can be processed by a processor  88  to determine quality of the calcification and quality of pulverization of the lesion. 
       FIG. 10  is a pressure volume curve of a prior art balloon breaking a calcified lesion.  FIG. 10B  shows the build up of energy within the balloon (region A to B) and  FIG. 10C  shows the release of the energy (region B to C) when the calcification breaks. At region C the artery is expanded to the maximum dimension of the balloon. Such a dimension can lead to injury to the vessel walls.  FIG. 10A  shows the initial inflation of the balloon. 
       FIG. 11  is a pressure volume curve showing the various stages in the breaking of a calcified lesion with shock waves according to the embodiment. The balloon is expanded with a saline fluid and can be expanded to fit snugly to the vessel wall (Region A) ( FIG. 11A ) but this is not a requirement. As the High Voltage pulses generate shock waves (Region B and C) extremely high pressures, extremely short in duration will chip away the calcified lesion slowly and controllably expanding the opening in the vessel to allow blood to flow un-obstructed ( FIG. 11B ). 
       FIG. 12  shows, in a cutaway view, shock waves  98  delivered in all directions through the wall  92  of a saline filled balloon  90  and intima  94  to a calcified lesion  96 . The shock waves  98  pulverize the lesion  96 . The balloon wall  92  may be formed of non-compliant or compliant material to contact the intima  94 . 
       FIG. 13  shows calcified plaque  96  pulverized by the shock waves. The intima  94  is smoothed and restored after the expanded balloon (not shown) has pulverized and reshaped the plaque into the vessel wall. 
       FIG. 14  is a schematic of a circuit  100  that uses the generator circuit  30  of  FIG. 3  and a surface EKG  102  to synchronize the shock wave to the “R” wave for treating vessels near the heart. The circuit  100  includes an R-wave detector  102  and a controller  104  to control the high voltage switch  32 . Mechanical shocks can stimulate heart muscle and could lead to an arrhythmia. While it is unlikely that shockwaves of such, short duration as contemplated herein would stimulate the heart, by synchronizing the pulses (or bursts of pulses) with the R-wave, an additional degree of safety is provided when used on vessels of the heart or near the heart. While the balloon in the current drawings will provide an electrical isolation of the patient from the current, a device could be made in a non-balloon or non-isolated manner using blood as the fluid. In such a device, synchronization to the R-wave would significantly improve the safety against unwanted arrhythmias. 
       FIG. 15  shows a still further dilation catheter  110  wherein a shock wave is focused with a parabolic reflector  114  acting as one electrode inside a fluid filled compliant balloon  116 . The other electrode  112  is located at the coaxial center of the reflector  114 . By using the reflector as one electrode, the shock wave can be focused and therefore pointed at an angle (45 degrees, for example) off the center line  111  of the catheter artery. In this configuration, the other electrode  112  will be designed to be at the coaxial center of the reflector and designed to arc to the reflector  114  through the fluid. The catheter can be rotated if needed to break hard plaque as it rotates and delivers shockwaves. 
       FIG. 16  shows a shock wave balloon  126  similar to  FIG. 2  with microspheres or microcapsules  120  attached to the surface. Such micro spheres may contain an antiproliferative drug such as Paclitaxel, Serolimus or Evrolimus or other similar drug. The spheres may be designed to be rigid and resist breaking when exposed to normal balloon inflation pressures of several atmospheres. However, when exposed to high pressure shock waves, the microspheres will break and release the drug contained within. Shockwaves delivered from such a balloon have the added advantage of creating a permeable cell wall membrane which aides in the transfer of the released drug to the walls of the vessel. Such drugs are known to reduce the restenosis rate in vessels treated. These micro-encapsulations can range in size typically from 2 to 100 microns in diameter although the size is not critical if they are small relative to the balloon size. The material can be a rigid polymer, a starch, glucose or any number of materials chosen to crack when exposed to shock waves and resist cracking when exposed to normal pressures of an angioplasty dilation procedure. 
       FIG. 17  is a layered shockwave balloon  226  similar to  FIG. 2  with an added layer  122  of drug chemically bonded to the balloon. The drug is released from its bond to the balloon material by the mechanical force of a shockwave. Thus the drug (paclitaxel for example) will be released at the site of a lesion while the lesion is being expanded with the predilitation balloon. As with the micro-encapsulated drug the shock waves from the balloon can also create a permeable cell wall membrane aiding in the drug uptake in the vessel wall. 
     While particular embodiments of the present invention have been shown and described, modifications may be made. It is therefore intended in the appended claims to cover all such changes and modifications which fall within the true spirit and scope of the invention as defined by those claims.