Abstract:
Methods and delivery devices for maximizing injectate dispersion in lesioned tissue using needle-based injection devices are herein disclosed. The delivery devices include injection devices with various needle arrays and/or modified needle tip configurations. The needle tip configurations can include linear, hooked or corkscrew tips and/or multiple circumferential openings.

Description:
FIELD OF INVENTION 
       [0001]    Modified needle apparatuses with needle arrays for delivery of substances into or withdrawal from a body. 
       BACKGROUND OF INVENTION 
       [0002]    Percutaneous transluminal coronary angioplasty (PTCA) is a procedure for treating heart disease, particularly, stenosis. “Stenosis” refers to a narrowing or constriction of the diameter of a vessel. In a typical PTCA procedure, a catheter assembly having a balloon portion is introduced percutaneously into the cardiovascular system of a patient via the brachial or femoral artery to treat stenosis at a lesion site. The catheter assembly is advanced through the coronary vasculature until the balloon portion is positioned across the occlusive lesion. Once in position across the lesion, the balloon is inflated to a predetermined size to radially compress the atherosclerotic plaque of the lesion against the inner wall of the artery to dilate the lumen. The balloon is then deflated to a smaller profile to allow the catheter to be withdrawn from the patient&#39;s vasculature. 
         [0003]    Restenosis of the artery commonly develops over several months after the procedure, which may require another angioplasty procedure or a surgical by-pass operation. “Restenosis” is the reoccurrence of stenosis in a blood vessel or heart valve after it has been treated with apparent success. Restenosis is thought to involve the body&#39;s natural healing process. Angioplasty or other vascular procedures often injure the vessel walls, including removing the vascular endothelium, disturbing the tunica intima, and causing the death of medial smooth muscle cells. Excessive neoinitimal tissue formation, characterized by smooth muscle cell migration and proliferation to the intima, follows the injury. Proliferation and migration of smooth muscle cells (SMC) from the media layer to the intima cause an excessive production of extra cellular matrices (ECM), which is believed to be one of the leading contributors to the development of restenosis. The extensive thickening of the tissues narrows the lumen of the blood vessel, constricting or blocking blood flow through the vessel. 
         [0004]    To reduce the chance of the development of restenosis, treatment substances can be administered to the treatment site. For example, anticoagulant and antiplatelet agents are commonly used to inhibit the development of restenosis. In order to provide an efficacious concentration to the target site, systemic administration of such medication often produces adverse or toxic side effects for the patient. Local delivery is a preferred method of treatment in that smaller total levels of medication are administered in comparison to systemic dosages, but are concentrated at a specific site. Local delivery, thus, produces fewer side effects and achieves more effective results. 
         [0005]    Techniques for the local delivery of a treatment substance into the tissue surrounding a vessel are disclosed in U.S. Pat. Nos. 6,944,490, 6,692,466 and 6,554,801 to Chow et al. In some applications, such techniques include a catheter with a needle cannula slidably disposed in a needle lumen and a balloon, which is coupled to the distal end of the catheter. When the balloon is inflated the needle lumen is brought into close engagement with the tissue and the needle cannula can be moved between a position inboard of the catheter distal surface and a position where the needle cannula is projected outboard of the catheter to deliver the treatment substance to the tissue. 
         [0006]    Needles which are used in conjunction with percutaneous injection devices and open-chest surgical injection devices generally include beveled single-port needle tips. Some of the problems associated with these types of needle tips include backflow of the injectate to non-focal areas, damage to surrounding tissue due to high focal injection pressure and reduced treatment agent dispersion due to localized delivery from a single port. Some studies have shown that up to 90 percent of the injectate never reaches the target tissue area due to backflow. As a result, treatment using needles often requires multiple injections which can result in increased pain and risk to the patient in addition to increased tissue damage due to multiple puncture wounds. 
         [0007]    The treatment of organs with injection devices, in particular dynamic organs, also presents unique challenges. For example, the heart will generally be contracting during a treatment which increases backflow during each muscle contraction and decreases treatment agent dispersion. Moreover, injection devices with a single needle can be inadequate to treat a large injury region on the heart. 
       SUMMARY OF INVENTION 
       [0008]    Methods and delivery devices for maximizing injectate dispersion in lesioned tissue using needle-based injection devices are herein disclosed. The delivery devices include injection devices with various needle arrays and/or modified needle tip configurations. The needle tip configurations can include, but are not intended to be limited to, linear, hooked, helical or corkscrew tips and/or one or more multiple circumferential openings. The needle tip configurations can additionally include recesses, grooves and/or indentations. 
     
     
       BRIEF DESCRIPTION OF DRAWINGS 
         [0009]      FIGS. 1A-1C  illustrate a substance delivery assembly which may be used in conjunction with embodiments of the present invention. 
           [0010]      FIG. 2A  illustrates an alternative delivery assembly which may be used in conjunction with embodiments of the present invention. 
           [0011]      FIG. 2B  illustrates a second alternative delivery assembly which may be used in conjunction with embodiments of the present invention. 
           [0012]      FIGS. 3A-3B  illustrate an embodiment of a modified needle apparatus with a needle array. 
           [0013]      FIGS. 4A-4B  illustrate an alternative embodiment of a modified needle apparatus with a needle array. 
           [0014]      FIGS. 5A-5B  illustrate a second alternative embodiment of a modified needle apparatus with a needle array. 
           [0015]      FIGS. 6A-6B  illustrate a third embodiment of a modified needle apparatus with a needle array. 
           [0016]      FIG. 7  illustrates an embodiment of a positioning device which may be used pursuant to methods of the present invention. 
       
    
    
     DETAILED DESCRIPTION 
     Delivery Devices 
       [0017]      FIGS. 1A ,  1 B, and  1 C illustrate a delivery assembly or device which can be used in conjunction with embodiments of the present invention. In general, the delivery assembly provides a system for delivering a substance, such as a treatment agent or a combination of treatment agent, to or through a desired area of a vessel in order to treat a localized area of the vessel or to treat a localized area of tissue located adjacent to the vessel. The delivery assembly includes a catheter assembly  100 , which is intended to broadly include any medical device designed for insertion into a vessel to permit injection and/or withdrawal of fluids, to maintain the patency of the vessel, or for any other purpose. It is contemplated that the delivery assembly has applicability for use with any vessel or organ, including blood vessels, urinary tract, intestinal tract, kidney ducts, wind pipes, and the like. 
         [0018]    In one embodiment, catheter assembly  100  is defined by an elongated catheter body  110  having a proximal end  120  and a distal end  130 . Catheter assembly  100  can include a guidewire lumen  140  for allowing catheter assembly  100  to be fed and maneuvered over a guidewire  150 . A balloon  160  is incorporated at distal end  130  of catheter assembly  100  and is in fluid communication with an inflation lumen  170  of catheter assembly  100 . 
         [0019]    Balloon  160  may be inflated by the introduction of a liquid into inflation lumen  170 . Liquids containing treatment and/or diagnostic agents may also be used to inflate balloon  160 . In one embodiment, balloon  160  may be made of a material that is permeable to such treatment and/or diagnostic liquids. To inflate balloon  160 , the fluid can be supplied into inflation lumen  170  at a predetermined pressure, for example, between about 1 and 20 atmospheres. The specific pressure depends on various factors, such as the thickness of balloon wall, the material from which balloon wall is made, the type of substance employed, and the flow-rate that is desired. 
         [0020]    Catheter assembly  100  also includes a substance delivery assembly  180  for injecting a substance into a wall of a vessel or tissue located adjacent to the vessel. In one embodiment, delivery assembly  180  includes a needle  190  movably disposed within a hollow delivery lumen  195 . Needle  190  includes a lumen with an inside diameter of, representatively, about 0.08 inches (0.20 centimeters). Delivery lumen  195  extends between distal end  130  and proximal end  120 . Delivery lumen  195  can be made from any suitable material, such as polymers and copolymers of polyamides, polyolefins, polyurethanes and the like. Access to the proximal end of delivery lumen  195  for insertion of needle  190  is provided through a hub  185 . 
         [0021]    Needle  190  is slidably or movably disposed in delivery lumen  195 . Needle  190  includes a tissue-piercing tip having a dispensing port (not shown). The dispensing port is in fluid communication with a central lumen (not shown) of needle  190 . In one embodiment, the central lumen of needle  190  can be pre-filled with a measured amount of a substance. The central lumen of needle  190  connects the dispensing port with substance injection port  155 , which is configured to be coupled to various substance dispensing means of the sort well known in the art, for example, a syringe or fluid pump. Injection port  155  allows a measured substance to be dispensed from a dispensing port as desired or on command. In some applications, catheter assembly  100  enters percutaneously through an arterial vessel of the heart. 
         [0022]      FIG. 2A  illustrates a cross-sectional side view of an alternative delivery device or apparatus which can be used in conjunction with embodiments of the present invention. In general, delivery assembly  200  provides an apparatus for delivering a substance, such as a treatment agent, to or through a desired area of a blood vessel (a physiological lumen) or tissue in order to treat a localized area of the blood vessel or to treat a localized area of tissue located adjacent to the blood vessel. 
         [0023]    Referring to  FIG. 2A , delivery assembly  200 , in one embodiment, may be in the form of a catheter device that includes delivery lumen  210  that may be formed in a larger catheter body (not shown). The larger catheter body may include one or more lumens to accommodate, for example, a guidewire, an inflation balloon, and/or an imaging device. Further, such a catheter body may accommodate one or more delivery lumens, such as delivery lumen  210 . Delivery lumen  210 , in this example, extends between distal portion  205  and proximal portion  215  of delivery assembly  200 . Delivery lumen  210  can be made from any suitable material, such as polymers and co-polymers of polyamides, polyolefins, polyurethanes, and the like. 
         [0024]    In one embodiment, delivery assembly  200  includes needle  220  movably disposed within delivery lumen  210 . Needle  220  is, for example, a stainless steel hypotube that extends a length of the delivery assembly. Needle  220  includes a lumen with an inside diameter of, representatively, about 0.16 inches (0.40 centimeters). In one example for a retractable needle catheter, needle  220  has a length of about 40 inches (1.6 meters) from distal portion  205  to proximal portion  215 . The needle  220  may include at least one opening  230 . At an end of proximal portion  215  is adapter  250  of, for example, a female luer housing. 
         [0025]    When loaded, a substance may be introduced according to known substance delivery techniques such as by advancing tip  240  of needle  220  into tissue (e.g., a wall of a blood vessel) and delivering the substance through back pressure (e.g., pressure applied at proximal portion  215 , such as by a needle luer). In some applications, delivery assembly  200  enters percutaneously through the left ventricle of the heart. 
         [0026]      FIG. 2B  illustrates an alternative delivery assembly which can be used in conjunction with embodiments of the present invention. In some embodiments, delivery device  260  is a syringe. Delivery device  260  may include a body  270 , a needle  280  and a plunger  290 . A shaft of plunger  290  has an exterior diameter slightly less than an interior diameter of body  270  so that plunger  290  can, in one position, retain a substance in body  270  and, in another position, push a substance through needle  280 . Syringes are known by those skilled in the art. In some applications, delivery device  260  may be applied directly to a treatment site during an open-chest surgery procedure. 
       Needle Arrays 
       [0027]    In some embodiments, modified needle apparatuses can be used to maximize injectate dispersion into tissue or organs. In some embodiments, the modified needle apparatuses can have an array of needles configured in various conformations to maximize injectate dispersion. In some embodiments, methods, apparatuses or compositions can be used to control dynamic organs to isolate a target tissue region thereby maximizing injectate dispersion. 
         [0028]      FIGS. 3A-3B  illustrate an embodiment of a modified needle apparatus. A needle apparatus  300  includes a body  310 , a plunger  320  (located at proximal end  350  of body  310 ) and an injectate region  330  (located at distal end  340 ). Injectate region  330  can include a series of needles  360  with openings (not shown) arranged in a suitable pattern to maximize injectate dispersion. Needles  360  can be in fluid communication with a fluid reservoir  340  to deliver injectate. Needles  360  can each have a diameter in the range of about 0.005 to 0.05 inches and a penetrating length in the range of about 0.5 to about 5.0 millimeters. In one embodiment, needles  360  can be arranged in a circular pattern, as shown in  FIG. 3B  (front view of injectate region  330 ). In some embodiments, needles  360  can be shaped in specific configurations, such as corkscrews or hooks. Such configurations can maximize injectate dispersion by providing multiple entries for injectate at a treatment site and by creating a non-linear pathway for the injectate to disperse throughout a wider area thereby decreasing backflow. As would be understood by one skilled in the art, other configurations can be provided in accordance with the teachings herein. 
         [0029]    To assist in targeted delivery of the injectate, needle apparatus  300  can include an anchor  370  disposed adjacent to distal end  340 . The anchor  370  includes a vacuum opening in fluid communication with a vacuum source (not shown) and helps to stabilize a treatment site when needle apparatus  300  is positioned thereon. For example, when the area to be treated is on the heart, the anchor  370  may be is necessary to specifically target the treatment site because the heart will be continually contracting throughout an application of injectate. Apparatuses which stabilize the heart during such procedures include the XPOSE™ 3 Access Device and the XPOSE™ 4 Access Device developed by Advanced Cardiovascular Systems, Inc., Santa Clara, Calif. The embodiments shown in  FIGS. 3A-3B  illustrate a needle apparatus to be used in an open-chest procedure, however, it is also contemplated that a modified version can be used with a catheter assembly. 
         [0030]      FIGS. 4A-4C  illustrate an alternative embodiment of a modified needle apparatus which may be used for percutaneous injection using a catheter assembly. A modified needle apparatus  400  includes a body  410  with an injectate region  430  covered by a moveable rubber skirt  470  located at a distal end  440 . Injectate region  430  can include a series of needles  460  with openings (not shown) arranged in a suitable pattern. The needles  460  can be in fluid communication with a fluid reservoir to deliver injectate. Additionally, needles  460  may be linear or directional. In one embodiment, needles  460  may be arranged in a linear fashion (see  FIG. 4B ) and angled in a direction away from the pathway in which needle apparatus  400  is delivered to the treatment site. 
         [0031]    In one application in which the area to be treated is on the heart, representatively shown in  FIG. 4C , needle apparatus  400  may be inserted intravenously (arrow  480 ) through a blood vessel until it reaches the treatment site. After insertion and throughout the positioning of needle apparatus  400 , rubber skirt  470  serves to protect the needles  460  from puncturing healthy tissue as it is being delivered to the treatment site. Moreover, in this embodiment, needles  460  are angled in a direction away from the pathway in which the needle apparatus  400  is delivered to the treatment site thereby reducing inadvertent puncturing of healthy tissue during delivery. To release injectate, needle apparatus  400  may be positioned at a point slightly past the treatment site. Needle apparatus  400  may then be retracted (arrow  490 ) such that needles  460  hook into the treatment site. The moveable rubber skirt  470  may splay adjacent to the injectate region  430  to stabilize and localize the injectate as it is dispensed through needles  460  from a fluid reservoir (not shown). In this manner, injectate dispersion can be maximized through multiple entries and by creating a non-linear pathway for the injectate to disperse throughout a wider area thereby decreasing backflow. 
         [0032]      FIGS. 5A-5B  illustrate another embodiment of a modified needle apparatus. A modified needle apparatus  500  includes a body  510  with a distal end  540  and a proximal end  550 . An extension and retraction knob  520  can be located at proximal end  550 . In some embodiments, the body can be approximately tubular and can house at least one retractable tube  570 . Retractable tubes  570  may be deployable by a spring-loaded mechanism or any other suitable mechanism. A needle  560  can be located at the distal end of each retractable tube  570 . Needle  560  can be in fluid communication with a fluid reservoir to deliver injectate via a lumen (not shown). 
         [0033]    In one application, needle apparatus  500  may be directed to a treatment site. The needle apparatus  500  remains in a retracted state with distal end  640  either positioned in body  600  or outside of body  610  ( FIG. 6A ) with the series of retractable tubes  570  resting in body  510  until the injectate is ready to be delivered to the treatment site. Once positioned on the treatment site, knob  520  may be depressed (arrow  580 ) so that the retractable tubes  570  can extend from body  510  into the treatment site ( FIG. 5B ). In some embodiments, retractable tubes  570  flare outwardly to contact multiple areas on the treatment site thereby maximizing injectate dispersion. In some embodiments, retractable tubes  570  may be connected by flexible webbing to stabilize the deployment of retractable tubes  570 . Thus, the injection pattern may be controllable and repeatable. 
         [0034]      FIGS. 6A-6B  illustrate still another embodiment of a modified needle apparatus. A modified needle apparatus  600  includes a body  610  with a distal end  640  and a proximal end  650 . An extension and retraction knob  620  can be located at proximal end  650 , while a hollow flexible member  670  may be located at distal end  640 . A needle array  630  may be located within flexible member  670 . Needle array  630  can include at least one needle  660 . Each needle  660  can be in fluid communication with a fluid reservoir to deliver injectate. 
         [0035]    In one application, needle apparatus  600  may be directed to a treatment site. Needle apparatus  600  remains in a retracted state ( FIG. 6A ) with the needle array  630  in a retracted position until the injectate is ready to be delivered to the treatment site. Once positioned on the treatment site, the knob  620  may be engaged (arrow  680 ) so that the needle array  630  extends from the flexible member  670  and into the treatment site ( FIG. 6B ). Simultaneously, the flexible member may splay outwardly into at least two arms  690 . The arms  690  may be connected by a hinge  695 . In this manner, the injection pattern may be controllable and repeatable. 
         [0036]      FIG. 7  illustrates a device which can be used to isolate a target tissue region to maximize injectate dispersion. The device may be, for example, a plastic plate  700  with an array of openings  760  attached to a distal end of a vacuum source (not shown). Plate  700  may be any suitable configuration. In some applications, plate  700  may be positioned over a treatment site during an open-chest procedure. The vacuum source may be used to immobilize the treatment site in preparation for delivering an injectate. Plate  700  can be made of an elastomer, such as silicon or any other biocompatible material, and can serve as an isolating mechanism for delivery of injectate to, for example, a treatment site on the heart. In one application, plate  700  is positioned over the treatment site by a positioning device (not shown). Plate  700  thereby serves to isolate the target tissue region. A needle assembly or a syringe, such as those described in relation to  FIGS. 1A-1B , may then be used to deliver injectate. 
         [0037]    In any of the above-described embodiments, the needles may include one or more circumferential openings to maximize injectate dispersion. In some embodiments, a substance may be added to the injectate to temporarily reduce contractility of the heart in order to maximize injectate dispersion throughout the treatment site. Such substances include, but are not limited to, heparin, diltiazem and verapamil. 
         [0038]    From the foregoing detailed description, it will be evident that there are a number of changes, adaptations and modifications of the present invention which come within the province of those skilled in the part. The scope of the invention includes any combination of the elements from the different species and embodiments disclosed herein, as well as subassemblies, assemblies and methods thereof. However, it is intended that all such variations not departing from the spirit of the invention be considered as within the scope thereof.