Abstract:
The present invention relates to a device and method for endoluminal delivery of fluid, such as therapeutic fluid, into the vessel wall that minimizes loss of the fluid. In one embodiment, a catheter for delivering fluid or therapeutic into a vessel wall is provided, wherein the catheter has at least one injector for delivering fluid and a sealing mechanism for preventing or minimizing passage of fluid through an unengaged injector.

Description:
TECHNICAL FIELD  
         [0001]    The present invention regards the delivery of therapeutic agents to a target site of an organic vessel. More particularly the invention regards the delivery of a therapeutic agent through injectors engaged with the interior wall of a lumen.  
         BACKGROUND  
         [0002]    The delivery of therapeutic to the interior lumen walls of a diseased vessel is an important, often repeated, procedure in the practice of modern medicine. Therapeutic agents may be used to treat, regenerate, or otherwise affect the interior lumen wall surface or the vessel wall itself. For example, therapeutic agent may be infused into the walls of blood vessels to inhibit or prevent restenosis of plaque within the artery. The delivery of the therapeutic can be completed by injection of the therapeutic, near the target site, through injectors. These injectors, located on the exterior of a balloon catheter inserted into the lumen, engage and embed into the interior wall of a vessel when the balloon is inflated.  
           [0003]    Examples of catheters with therapeutic injectors are shown in U.S. Pat. Nos. 5,681,281; 5,713,863; and 6,210,392, all to Vigil et al. FIGS. 1 and 2, which are taken from U.S. Pat. No. 5,681,281, illustrate such a catheter, defined as device  10 . FIG. 2, an enlarged longitudinal section view taken along line  3 - 3  of FIG. 1, shows injectors,  20   a ,  20   b ,  20   c , and  20   d , engaging and embedding into the interior vessel wall  54  upon inflating balloon  16 . With the injectors embedded into the vessel wall, therapeutic is pumped from fluid source  60  (shown in FIG. 1) into the infusion chamber  26  and delivered into the vessel wall through channel  48  of each injector.  
           [0004]    None of the above discussed patents, however, addresses the problem of the release of therapeutic directly into the bloodstream from injectors that do not engage the vessel wall. When the diseased or otherwise targeted area is irregularly shaped due to plaque deposits along the interior wall surface, or is near a side vessel or bifurcated branch vessel, the injectors may not engage the vessel wall. For example, FIG. 3 depicts catheter  10  with therapeutic injectors,  20   a  through  20   d , in a bifurcated vessel  70 . Bifurcated vessel  70  contains a side vessel branch  71  that prevents injector  20   a  from embedding into the interior vessel wall  72 . As another example, injector  20   a  of FIG. 4 does not engage or embed into interior vessel wall  73  because the vessel wall is irregularly shaped. Crater  74  of the vessel wall  73  precludes the injector  20   a  from engaging. Cratered or otherwise irregularly shaped vessel walls are typical in arteries inflicted with arteriosclerosis.  
           [0005]    Accordingly, when delivery of therapeutic agent is initiated, the therapeutic released from unengaged injector  20   a  flows directly into the bloodstream instead of into the walls of the lumen. Due to the toxic nature of some therapeutics, a therapeutic delivery catheter should minimize washing away of therapeutic agents into the blood stream. Further, more therapeutic will flow into the blood stream from an unengaged injector than will be delivered to the vessel wall from an engaged injector because the flow through an engaged injector, such as injectors  20   b ,  20   c , and  20   d  of FIG. 4, encounters greater resistance, induced by the pressure of interior vessel wall  73 , than the unimpeded flow through unengaged injector  20   a . Thus, loss of therapeutic through unengaged injectors due to irregularly shaped or bifurcated vessels presents an impediment to the safe and effective delivery of therapeutic agents.  
         SUMMARY OF THE INVENTION  
         [0006]    The present invention regards a catheter for endoluminal delivery of fluid, such as therapeutic fluid, into the vessel wall that minimizes loss of the fluid. In one embodiment, a catheter for delivering fluid or therapeutic into a vessel wall is provided, wherein the catheter has at least one injector for delivering fluid and a sealing mechanism for preventing or minimizing passage of fluid through an unengaged injector.  
           [0007]    In an alternative embodiment of the present invention, another catheter for endoluminal delivery of fluid into the vessel wall that minimizes loss of the fluid is provided wherein the catheter has at least one injector for delivering fluid, a sealing mechanism for preventing or minimizing passage of fluid through an unengaged injector, and a combined inflation/infusion chamber for inflating the balloon and infusing the fluid into the vessel wall.  
           [0008]    In an alternative embodiment of the present invention, a method for delivering fluid into a vessel wall is provided wherein the method includes inserting a catheter into the vessel of a patient, inflating a balloon by forcing fluid into an inflation chamber to embed an injector into the vessel wall, infusing therapeutic into a vessel wall through the injector by forcing therapeutic fluid into an infusion chamber, and selectively sealing an injector that does not embed into a vessel wall.  
           [0009]    In another alternative embodiment of the present invention, another method for delivering fluid into a vessel wall is provided wherein the method includes inserting a catheter into the vessel of a patient, inflating a balloon by forcing fluid into an inflation/infusion chamber to embed an injector into the vessel wall, infusing therapeutic into a vessel wall through the injector by forcing therapeutic fluid into the inflation/infusion chamber, and selectively sealing an injector that does not embed into a vessel wall. 
       
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       [0010]    [0010]FIG. 1 is a perspective view of a prior therapeutic delivery catheter.  
         [0011]    [0011]FIG. 2 is an enlarged longitudinal section view of a prior therapeutic delivery catheter taken along line  3 - 3  of FIG. 1 and positioned in an artery of a patient for delivery of fluid into the vessel wall.  
         [0012]    [0012]FIG. 3 is an enlarged longitudinal section view of a prior therapeutic delivery catheter taken along line  3 - 3  of FIG. 1 and positioned in a bifurcated artery of the patient for delivery of fluid into the vessel wall.  
         [0013]    [0013]FIG. 4 is an enlarged longitudinal section view of a prior therapeutic delivery catheter taken along line  3 - 3  of FIG. 1 and positioned in an irregularly shaped artery of the patient for delivery of fluid into the vessel wall.  
         [0014]    [0014]FIG. 5 is a perspective view of the device of the present invention.  
         [0015]    [0015]FIG. 6 is an enlarged longitudinal section view of an embodiment of the device of the present invention taken along line  6 - 6  of FIG. 5 and positioned in a bifurcated artery of the patient for delivery of fluid into the vessel wall.  
         [0016]    [0016]FIG. 7 is an enlarged sectional view of the device of FIG. 6 illustrating the injectors and sealing units positioned in a bifurcated artery of the patient.  
         [0017]    [0017]FIG. 8 is a perspective view of an alternative embodiment of the present invention.  
         [0018]    [0018]FIG. 9 is an enlarged longitudinal section view of the embodiment of FIG. 8 taken along line  9 - 9  of FIG. 8.  
         [0019]    [0019]FIG. 10 is an enlarged sectional view of another alternative embodiment of the present invention illustrating injectors and sealing units positioned in an irregularly shaped artery of the patient.  
         [0020]    [0020]FIG. 11 is an enlarged sectional view of another alternative embodiment of the present invention illustrating injectors and sealing units.  
         [0021]    [0021]FIG. 12 is an enlarged sectional view of another alternative embodiment of the present invention illustrating injectors and sealing units.  
         [0022]    [0022]FIG. 13 is an enlarged sectional view of another alternative embodiment of the present invention illustrating injectors and sealing units.  
         [0023]    [0023]FIG. 14 is an enlarged sectional view of another alternative embodiment of the present invention illustrating engaged injectors and sealing units positioned in an artery of the patient.  
         [0024]    [0024]FIG. 15 is an enlarged sectional view of another alternative embodiment of the present invention illustrating injectors and sealing units.  
         [0025]    [0025]FIG. 16 is an enlarged sectional view of another alternative embodiment of the present invention illustrating engaged injectors and sealing units positioned in an artery of the patient.  
     
    
     DETAILED DESCRIPTION  
       [0026]    As discussed above, FIG. 1 illustrates a prior therapeutic delivery catheter  10  having injectors,  20   a  through  20   d , to deliver therapeutic agents from a therapeutic fluid source  60  into a vessel wall. Therapeutic agents may be used to treat, regenerate, or otherwise affect the interior lumen wall surface or the vessel wall itself. The treated vessel may be any vessel located within or outside of the body of a patient. It may include blood-carrying vessels such as the veins, arteries, and chambers of the heart, it may also include the esophagus, the ureters, the intestines, the pockets of fluid located within the individual vertebrae of the spinal column and any other suitable vessel as apparent to one of skill in the art. Organs and tissues that may be treated by the methods of the present invention include any mammalian tissue or organ, whether located in vivo or ex vivo. Non-limiting examples include the heart, the lungs, the brain, the liver, the kidneys, the bladder, the intestines, the stomach, the pancreas, the ovaries, the prostate, the eyes, as well as tumors, cartilage and bone.  
         [0027]    [0027]FIG. 2, an enlarged longitudinal section view of prior therapeutic delivery catheter  10  taken along line  3 - 3  of FIG. 1, shows injectors,  20   a ,  20   b ,  20   c , and  20   d , engaging and embedding into the interior vessel wall  54  upon inflating balloon  16 . Balloon  16  is inflated by injecting fluid into inflation chamber  32 . With the injectors,  20   a  through  20   d , embedded into the vessel wall  54 , therapeutic is pumped from fluid source  60  (shown in FIG. 1) into the infusion chamber  26  and delivered into the vessel wall through channel  48  of each injector.  
         [0028]    [0028]FIG. 3, another enlarged longitudinal section view of prior therapeutic delivery catheter  10 , shows a plurality of injectors  20  comprising a base  76  and a hollow protrusion  77  projecting outward from the base  76  to form a fluid channel  48  traversing the base and hollow protrusion for delivering therapeutic. Of these injectors  20 , the injectors defined as  20   a ,  20   b ,  20   c , and  20   d  are exemplary. Further, one skilled in the art will appreciate that base  76  can be elongated to accommodate a plurality of hollow protrusions  77 . The distal end of hollow protrusion  77  may have a cutting edge  78  formed to assist in penetrating a vessel wall upon engagement. The injector  20  may be made from numerous materials, including stainless steel, plastic, and other suitably rigid polymers. In one embodiment, the injector  20  is made from nickel or a nickel alloy and formed by punching out material from the base  76  forming a hollow protrusion  77  extending outwardly from the base  76 .  
         [0029]    Prior therapeutic delivery catheters, including the devices described above, did not selectively occlude the flow of therapeutic through the injectors. Accordingly, when the injectors could not engage a vessel wall due to a branch vessel or an irregular shape of the interior vessel wall, therapeutic would flow from the unengaged injector into the blood stream. FIGS. 3 and 4 illustrate problems associated with these prior devices when placed in such a vessel. FIG. 3 is an enlarged longitudinal section view of the catheter  10  taken along line  3 - 3  of FIG. 1 and positioned in a bifurcated vessel  70  of the patient for delivery of fluid into the vessel wall. As shown in FIG. 3, injectors  20   b ,  20   c , and  20   d  engage and embed into vessel wall  72 . However, bifurcated vessel  70  contains a side vessel branch  71  that prevents injector  20   a  from embedding into the interior vessel wall  72 .  
         [0030]    As another example, injector  20   a  of FIG. 4 does not engage or embed into interior vessel wall  73  because the vessel wall is irregularly shaped. FIG. 4, an enlarged longitudinal section view of the catheter  10  taken along line  3 - 3  of FIG. 1 and positioned in an irregularly shaped vessel, depicts crater  74  of the vessel wall  73  precluding injector  20   a  from engaging the vessel wall. Irregularly shaped vessel walls can be caused by built up deposits of plaque on the inside of the vessel wall, by natural physical configuration of the vessel wall, or by calcified deposits located within the vessel wall  73 . Calcified deposits can place pressure on the interior lumen wall surface, causing it to deform into an irregular shape. Accordingly, when delivery of therapeutic agent is initiated, the therapeutic released from unengaged injector  20   a  flows directly into the bloodstream instead of into the walls of the lumen. The flow arrow A demonstrates the direction of flow of therapeutic agent through unengaged injector  20   a  into the bloodstream. Where the injector  20  engages vessel wall  73 , the therapeutic agent is properly released into the vessel wall. The flow arrow B demonstrates the direction of flow of therapeutic agent through engaged injector  20   d  into the vessel wall  73 .  
         [0031]    In FIG. 5, a device in accordance with the present invention for endoluminal delivery of therapeutic agents that minimizes loss of therapeutic is shown and generally designated as  80 . As seen in FIG. 5, the components of device  80  include a double-lumen catheter  81  with an inflatable balloon  82  mounted on the exterior surface of catheter  81 . FIG. 6 shows inflatable balloon  82  attached at a distal end  94  of catheter  81 , thereby creating an inflation chamber  100 . Inflation chamber  100  fluidly communicates with the first internal lumen of catheter  81  and an inflator  89  (shown in FIG. 5). A fluid passageway, shown in FIG. 5 as a tubular sleeve  84 , surrounds a substantial portion of the inflatable balloon  82 , attached at a distal end  95  of inflatable balloon  82 , thereby creating an infusion chamber  101 . The fluid passageway may be a sleeve that circumferentially surrounds a portion of the inflatable balloon or may be tube strips, with either a substantially round or rectangular internal lumen, placed longitudinally along the exterior surface of the inflatable balloon. The fluid passageway may be flexible or rigid. A plurality of injectors  83  are shown and are mounted on the exterior surface of tubular sleeve  84 . Infusion chamber  101  fluidly communicates with the second internal lumen of catheter  81 , therapeutic fluid source  85  (shown in FIG. 5), and injectors  83  to deliver therapeutic fluid into the vessel wall. A sealing unit  90  (shown in FIGS. 6 and 7) is included to occlude flow of therapeutic through unengaged injectors  83 .  
         [0032]    Of these injectors  83 , injectors defined as  83   a ,  83   b ,  83   c , and  83   d  are exemplary. A skilled artisan will appreciate that the injector  83  can be mounted on balloon  82  in any manner well known in the pertinent art, such as by bonding or other mechanical attachment means. While the illustrated embodiment of device  80  in FIG. 5 discloses rows of three injectors  83  as being evenly and uniformly spaced along tubular sleeve  84 , these injectors  83  may be of different sizes or different shapes and may be located at different spacings along the catheter. In this exemplary embodiment, however, these injectors will be evenly spaced along the catheter to facilitate the even distribution of therapeutic into vessel wall. The injectors may be conical in shape, substantially cylindrical in shape, or formed with a substantially conical tip.  
         [0033]    [0033]FIG. 6 is an enlarged longitudinal section view of the device of the present invention taken along line  6 - 6  of FIG. 5 and positioned in a bifurcated artery  70  of the patient for delivery of fluid into the vessel wall. Sealing unit  90  controls the flow of therapeutic through injectors  83 . FIG. 7, an enlarged sectional view, illustrates injectors  83 , and sealing unit  90  comprising seal  91 .  
         [0034]    In the operation of the device of the present invention, a guidewire  87  (shown in FIG. 5) is first positioned into an artery of the patient to establish a pathway for the therapeutic delivery catheter device  80  to reach the target area. The proximal end of guidewire  87  is then inserted into catheter  81  and the device  80  is advanced over the guidewire to the target area for delivery of therapeutic.  
         [0035]    Referring to FIG. 6, delivery of therapeutic is initiated by first inflating the balloon  82  with inflator  89  (shown in FIG. 5) to embed injectors  83  into the vessel wall  72 . Inflatable balloon  82 , the first internal lumen of catheter  81  and inflator  89  are in fluid communication with each other. Inflator  89 , located at the proximal end of catheter  81 , may include an inflation fluid source and fluid pump (not shown). Pumping action by the fluid pump causes a bio-compatible non-compressible fluid from the inflation fluid source to be pumped from the proximal end of catheter  81  along the first internal lumen of catheter  81  and expelled into an inflation chamber  100  (shown in FIG. 6), thereby inflating balloon  82  under pressure of the fluid from a first unexpanded diameter to a second expanded diameter.  
         [0036]    Inflation fluid source may be a non-toxic fluid source, such as contrast solutions used in ultrasound, fluoroscopy, and MRI procedures, or various brine solutions. The non-toxic inflation fluid source may be utilized for inflating the inflatable balloon to ensure that no toxic fluids, such as some therapeutic fluids, are washed into the bloodstream in the event that the inflatable balloon bursts upon expansion.  
         [0037]    Fluid pump may be a syringe or any other pumping means that can apply a pressure on the fluid to carry it into the balloon. These alternative means could include a micro-pump and a collapsible bladder. In a preferred embodiment, the amount of fluid being injected into the catheter, and/or the infusion pressure placed on the fluid, will be measured to help monitor the expansion of the balloon  82  within the lumen  70  and to preclude an overabundance of fluid from being injected into the balloon  82 . By measuring the amount of pressure placed on the fluid the operator can monitor the progress of the procedure. In this preferred embodiment, the amount of pressure generated in the vessel will not exceed a known tolerable pressure level for the vessel being treated.  
         [0038]    The inflatable balloon  82  may be made with any material that is flexible and resilient. Latex, silicone, polyurethane, rubber (including styrene and isobutylene styrene), and nylon, are each examples of materials that may be used in manufacturing the inflatable balloon. The catheter body  81  may be made from numerous materials, including stainless steel, plastic, and other suitably rigid polymers. It is preferable that the materials used are compatible with the target sites in which they can be used and that they are able to withstand the pressures generated by the fluids passing through them. In addition, they should be flexible enough such that the catheter may be effectively snaked down through a vessel in the body having an irregularly shaped lumen.  
         [0039]    As illustrated in FIG. 7, injectors  83   b  and  83   c  engage and embed into vessel wall  72  when the inflatable balloon  82  (shown in FIG. 6) is inflated. Upon engagement, the pushing force arrow E demonstrates the direction of a force that may be generated at the distal end  92  of injectors  83 , thereby urging the seal  91  to translate from a first position adjacent the distal end  92  of injector  83   c , to a second position disposed between the distal and proximal ends,  92  and  93 , of injector  83   c . Accordingly, an orifice  96  is opened at the distal end  92  of injector  83   c . Pumping action of fluid pump  86  pressurizes the therapeutic fluid causing it to flow from therapeutic fluid source  85  ( 85  and  86  are shown in FIG. 5) along the second internal lumen of catheter  81  into infusion chamber  101 , formed between balloon  82  and tubular sleeve  84 , and into vessel wall  72  through the opened orifice  96  of engaged and embeded injectors  83   b  and  83   c . Therapeutic flows in the direction indicated by flow arrow F. Fluid pump  86  may be any of the alternate pumping means discussed above.  
         [0040]    However, where irregularities of the vessel wall  72  occur, as illustrated by bifurcated side vessel branch  71 , causing an injector  83   a  to not engage and embed into vessel wall  72 , sealing unit  90  prevents the flow of therapeutic through an unengaged injector  83 . As shown in FIG. 7, injector  83   a  does not engage and embed into vessel wall  72  because it is positioned at a bifurcated side vessel branch  71 . Thus, the vessel wall  72  will not push against seal  91 . Accordingly, seal  91  remains in a first position adjacent the distal end  92  of injector  83   a  and prevents the release of the therapeutic agent directly into the bloodstream from unengaged injectors, thereby minimizing the release of toxic therapeutic agents into the blood stream. Mechanical, chemical, fluid or other forces may be used to maintain seal  91  of unengaged injector  83   a  in a first position adjacent the distal end  92  of injector  83   a , thereby preventing release of therapeutic agent into the bloodstream. Alternative embodiments of these forces are discussed in detail below. The seal  91  in the present embodiment and in alternative embodiments discussed below, may be made from numerous materials, including stainless steel, plastic, and other suitably rigid polymers.  
         [0041]    Rather than have a separate inflation chamber  100  and infusion chamber  101 , an alternate embodiment of therapeutic delivery catheter  102 , illustrated in FIGS. 8 and 9, may comprise of one inflation/infusion chamber  103 . Because the sealing unit  90  occludes flow through the injectors  83 , thereby maintaining the pressure within device  102  while inflating the balloon, the separate inflation and infusion chambers can be combined into a single inflation/infusion chamber. FIG. 8 is a perspective view in accordance with an alternate embodiment  102  of the present invention. FIG. 9 is a longitudinal section view along line  9 - 9  of FIG. 8. As shown in FIG. 9, an inflatable balloon  104  is mounted on the exterior surface of catheter  105 , attached directly to the surface of catheter  105  at the distal end  106  of catheter  105 , thereby creating an inflation/infusion chamber  103  of device  102 . A plurality of injectors  83  are mounted on the exterior surface of inflatable balloon  104 . Sealing units  90  may selectively occlude the flow of fluid through injectors  83  as disclosed above. Inflation/infusion chamber  103  fluidly communicates with an internal lumen of catheter  105 , an inflation fluid source  88 , a therapeutic fluid source  85  and injectors  83 . Valve  108  selectively controls fluid flow into inflation/infusion chamber  103  from inflation fluid source  88  and from therapeutic fluid source  85 . A person skilled in the art would appreciate that the valve  108  can be designed in any manner well known in the pertinent art, such as by utilizing a stopcock valve or by other mechanical valve means.  
         [0042]    Operation of alternate embodiment of therapeutic delivery catheter  102  begins by inflating inflatable balloon  104  to engage and embed injectors  83  into the vessel wall (not shown). As illustrated in FIG. 8, inflating inflatable balloon  104  from a first unexpanded diameter to a second expanded diameter is achieved by pumping action of fluid pump  109 . Valve  108  is selectively opened to permit inflation fluid to flow from inflation fluid source  88 , and to preclude therapeutic fluid from flowing from therapeutic fluid source  85 . Pumping action of fluid pump  109  pressurizes and causes inflation fluid to be expelled from inflation fluid source  88  into inflation/infusion chamber  103 . Seals  91  of sealing units  90  prevent inflation fluid from being expelled into bloodstream through unengaged injectors  83  while inflatable balloon  104  is being inflated. As discussed above, mechanical, chemical, fluid or other forces may be used to maintain seal  91  in a position that occludes the orifice  96  of injectors  83 . Also as described above, once the injectors  83  engage and embed into the vessel wall, seal  91  translates away from the vessel wall, and an orifice  96  is opened at the distal end  92  of injector  83 . Valve  108  is then selectively opened to permit therapeutic fluid to flow from therapeutic fluid source  85 , and to prevent inflation fluid from flowing from inflation fluid source  88 . Pumping action of fluid pump  109  then pressurizes and causes therapeutic fluid to be expelled from therapeutic fluid source  85  to the inflation/infusion chamber  103  and into the vessel wall through injector  83 .  
         [0043]    In another alternate embodiment of the present device (not shown), rather than having two fluid sources—one non-toxic inflation fluid source and one therapeutic fluid source—a single non-toxic or minimally toxic therapeutic fluid source can be used. The single therapeutic fluid source will first serve as the fluid to inflate the balloon and then be expelled into the vessel wall through the injectors once the seal is pushed away from the injector orifice thereby permitting flow into the vessel wall.  
         [0044]    A person skilled in the art would appreciate that a variety of seal configurations can be designed to accommodate the variety of injector configurations. In the above embodiments, such as shown in FIG. 7, seal  91  of sealing unit  90  may be spherically shaped to accommodate the conical internal passageway of injector  83 . A skilled artisan would also appreciate that using a spherical or similarly round seal helps minimize trauma on the interior wall of the vessel where the possibility of thrombosis is high.  
         [0045]    In FIG. 10, another embodiment of sealing unit, designated  150 , is shown to accommodate the cylindrical internal passageway  151  of injector  152 . Sealing unit  150  comprises seal  153  attached to stem  154 . Stem  154  extends beyond the distal end  155  of injector  152 , to engage the vessel wall  72 . Upon engagement with vessel wall  72 , the stem  154  translates radially inward, forcing seal  153  to open, thereby allowing therapeutic fluid to flow into the vessel wall through cylindrical internal passageway  151  of injector  152 . Fluid flow arrow H demonstrates the direction of fluid flow. It will be appreciated by one skilled in the art that stem  154  and the geometry of sealing unit  150  may be modified in order to allow therapeutic fluid to flow into the vessel wall only when a predetermined force induced by vessel wall  72 , illustrated as pressure force E in FIG. 7, is met.  
         [0046]    Also, a cutting edge may be formed or separately attached to the distal end  155  of injector  152  (shown in FIG. 11), the distal end  92  of injector  83  (shown in FIG. 7), or the distal end of stem  154  (shown in FIG. 10). A skilled artisan will appreciate that a variety of cutting devices and injector geometries and shapes would permit puncturing through plaque formed on the interior wall of the vessel without puncturing completely through the vessel wall, so that therapeutic may be delivered into the vessel.  
         [0047]    A variety of forces may be utilized to maintain the seal in a position to prevent the flow of therapeutic from an unengaged injector into the bloodstream. In FIG. 7, pressurizing a therapeutic fluid source  85  (not shown) may induce a fluid pressure upon seal  91 , thereby maintaining seal  91  in a position blocking the flow of therapeutic from the injector  83  to the vessel wall  72 . The force arrow G demonstrates the direction of fluid pressure on seal  91 . In another alternate embodiment, seal  91  may be formed such that the drag coefficient of the seal  91  is greater than the drag coefficient of the interior surface of the injector, thereby imparting a viscous drag force induced by the flow of therapeutic fluid around seal  91  of unengaged injector  83  and urging seal  91  radially outward in a position to block the flow of therapeutic. Seal  91  can either be patterned with a rough surface, coated with a surface treatment, or geometrically formed to increase the drag force upon seal  91 .  
         [0048]    Similarly, sealing unit  150  of FIG. 10 can be modified to increase the viscous drag force urged upon the sealing unit  150 , as illustrated in FIG. 11. In FIG. 11, sealing unit  180  is shown comprising stem  154 , seal  153 , and cups  181 . Cups  181  cause a drag force urged upon sealing unit  180  as therapeutic fluid flows around cups  181  in the direction demonstrated by flow arrow J. This force urges sealing unit  180  to translate radially outward thereby sealing the proximal end  182  of injector  152 . Although several cups  181  are illustrated in FIG. 11, a skilled artisan would appreciate that one cup may be used to translate sealing unit  180 . In another alternative embodiment shown in FIG. 12, sealing unit  184  comprises block  183  attached to stem  154  to cause a drag force urged upon sealing unit  184 .  
         [0049]    In another alternate embodiment, a mechanical force may be used to exert pressure against sealing unit  150 . As illustrated in FIG. 13, sealing unit  190  includes spring  160 , which can be attached to the exterior surface of inflatable balloon  82  (shown in FIG. 6) to physically communicate with seal  153 . Spring  160  exerts a radially outward force upon seal  153  in the direction demonstrated by force arrow K. Accordingly, seal  153  is urged against proximal end  156  of injector  152 , and stem  154  extends beyond distal end  155  of injector  152 . Sealing unit  190  may also include a compliant gasket  158  attached to exterior surface  157  of seal  153  to assist in sealing seal  153  against proximal end  156  of injector  152 . The compliant gasket  158  maybe included in any embodiment of sealing unit  150  described herein. Once injector  152  engages vessel wall  72 , as shown in FIG. 14, the pressure force exerted on stem  154  by the vessel wall  72  will overcome the spring force, thereby urging the stem  154  and seal  153  radially inward and permitting flow of therapeutic agents into the vessel wall  72  through the cylindrical internal passageway  151  of injector  152 . The direction of flow of therapeutic is demonstrated by directional arrow H. It will be relevant to one skilled in the art that the spring force can be modified by adjusting the spring constant of the spring.  
         [0050]    Alternatively, mechanical force K may be exerted upon seal  153  by an elastic band  170 , as shown in sealing unit  191  of FIG. 15. Elastic band  170  can be attached to the surface of the tubular sleeve  84  or to the base of injector  152 . Further, elastic band  170  would be attached as to permit the flow of therapeutic fluid around or through the elastic band  170  when the injector  152  engages the vessel wall. A skilled artisan will know that the force properties of elastic band  170  may be modified such that when the pressure force exerted by the vessel wall  72  on sealing unit  191  overcomes the elastic band force K, the seal  153  is urged radially inward as seen in FIG. 16, thereby permitting flow of therapeutic agents into the vessel wall  72  in the direction demonstrated by directional arrow H. In the alternative embodiments discussed above, the spring  160  and elastic band  170  may be made from numerous materials, including stainless steel, plastic, and other suitably rigid polymers. Further, spring  160  and elastic band  170  can be attached in any manner well known in the pertinent art, such as by bonding or other mechanical attachment means.  
         [0051]    In still another embodiment, other forces, such as chemical or static forces, may also be used to prevent the flow of fluid through the injectors. The seal can be initially maintained in a sealed position against the injector by bonding the seal to the injector&#39;s orifice. The seal would seal the unengaged injector while the balloon inflates. However, when the injector engages and embeds into the vessel wall, the pressure force of the vessel wall would overcome the bond strength of the bonding agent, thereby translating the seal away from the injector&#39;s orifice and permitting therapeutic to flow into the vessel wall. The bond may be an adhesive bond, an electrostatic bond, chemical bond, or other bonding agents known in the pertinent art.  
         [0052]    The term “therapeutic” as used throughout includes one or more “therapeutic agents” or “drugs.” The terms “therapeutic” and “drugs” are used interchangeably herein and include pharmaceutically active compounds, nucleic acids with and without carrier vectors such as lipids, compacting agents (such as histones), virus (such as adenovirus, adenoassociated virus, retrovirus, lentivirus and α-virus), polymers, hyaluronic acid, proteins, cells and the like, with or without targeting sequences. The therapeutics administered in accordance with the invention includes the therapeutic agent(s) and solutions thereof.  
         [0053]    Specific examples of therapeutic agents used in conjunction with the present invention include, for example, pharmaceutically active compounds, proteins, cells, oligonucleotides, ribozymes, anti-sense oligonucleotides, DNA compacting agents, gene/vector systems (i.e., any vehicle that allows for the uptake and expression of nucleic acids), nucleic acids (including, for example, recombinant nucleic acids; naked DNA, cDNA, RNA; genomic DNA, cDNA or RNA in a non-infectious vector or in a viral vector and which further may have attached peptide targeting sequences; antisense nucleic acid (RNA or DNA); and DNA chimeras which include gene sequences and encoding for ferry proteins such as membrane translocating sequences (“MTS”) and herpes simplex virus-1 (“VP22”)), and viral, liposomes and cationic and anionic polymers and neutral polymers that are selected from a number of types depending on the desired application. Non-limiting examples of virus vectors or vectors derived from viral sources include adenoviral vectors, herpes simplex vectors, papilloma vectors, adeno-associated vectors, retroviral vectors, and the like. Non-limiting examples of biologically active solutes include anti-thrombogenic agents such as heparin, heparin derivatives, urokinase, and PPACK (dextrophenylalanine proline arginine chloromethylketone); antioxidants such as probucol and retinoic acid; angiogenic and anti-angiogenic agents and factors; agents blocking smooth muscle cell proliferation such as rapamycin, angiopeptin, and monoclonal antibodies capable of blocking smooth muscle cell proliferation; anti-inflammatory agents such as dexamethasone, prednisolone, corticosterone, budesonide, estrogen, sulfasalazine, acetyl salicylic acid, and mesalamine; calcium entry blockers such as verapamil, diltiazem and nifedipine; antineoplastic/antiproliferative/anti-mitotic agents such as paclitaxel, 5-fluorouracil, methotrexate, doxorubicin, daunorubicin, cyclosporine, cisplatin, vinblastine, vincristine, epothilones, endostatin, angiostatin and thymidine kinase inhibitors; antimicrobials such as triclosan, cephalosporins, aminoglycosides, and nitorfurantoin; anesthetic agents such as lidocaine, bupivacaine, and ropivacaine; nitric oxide (NO) donors such as lisidomine, molsidomine, L-arginine, NO-protein adducts, NO-carbohydrate adducts, polymeric or oligomeric NO adducts; anti-coagulants such as D-Phe-Pro-Arg chloromethyl ketone, an RGD peptide-containing compound, heparin, antithrombin compounds, platelet receptor antagonists, anti-thrombin antibodies, anti-platelet receptor antibodies, enoxaparin, hirudin, Warafin sodium, Dicumarol, aspirin, prostaglandin inhibitors, platelet inhibitors and tick antiplatelet factors; vascular cell growth promotors such as growth factors, growth factor receptor antagonists, transcriptional activators, and translational promoters; vascular cell growth inhibitors such as growth factor inhibitors, growth factor receptor antagonists, transcriptional repressors, translational repressors, replication inhibitors, inhibitory antibodies, antibodies directed against growth factors, bifunctional molecules consisting of a growth factor and a cytotoxin, bifunctional molecules consisting of an antibody and a cytotoxin; cholesterol-lowering agents; vasodilating agents; agents which interfere with endogeneus vascoactive mechanisms; survival genes which protect against cell death, such as anti-apoptotic Bcl-2 family factors and Akt kinase; and combinations thereof. Cells can be of human origin (autologous or allogenic) or from an animal source (xenogeneic), genetically engineered if desired to deliver proteins of interest at the injection site. The delivery mediated is formulated as needed to maintain cell function and viability. Any modifications are routinely made by one skilled in the art.  
         [0054]    Polynucleotide sequences useful in practice of the invention include DNA or RNA sequences having a therapeutic effect after being taken up by a cell. Examples of therapeutic polynucleotides include anti-sense DNA and RNA; DNA coding for an anti-sense RNA; or DNA coding for tRNA or rRNA to replace defective or deficient endogenous molecules. The polynucleotides of the invention can also code for therapeutic proteins or polypeptides. A polypeptide is understood to be any translation product of a polynucleotide regardless of size, and whether glycosylated or not. Therapeutic proteins and polypeptides include as a primary example, those proteins or polypeptides that can compensate for defective or deficient species in an animal, or those that act through toxic effects to limit or remove harmful cells from the body. In addition, the polypeptides or proteins that can be injected, or whose DNA can be incorporated, include without limitation, angiogenic factors and other molecules competent to induce angiogenesis, including acidic and basic fibroblast growth factors, vascular endothelial growth factor, hif-1, epidermal growth factor, transforming growth factor α and β, platelet-derived endothelial growth factor, platelet-derived growth factor, tumor necrosis factor α, hepatocyte growth factor and insulin like growth factor; growth factors; cell cycle inhibitors including CDK inhibitors; anti-restenosis agents, including p15, p16, p18, p19, p21, p27, p53, p57, Rb, nFkB and E2F decoys, thymidine kinase (“TK”) and combinations thereof and other agents useful for interfering with cell proliferation, including agents for treating malignancies; and combinations thereof. Still other useful factors, which can be provided as polypeptides or as DNA encoding these polypeptides, include monocyte chemoattractant protein (“MCP-1”), and the family of bone morphogenic proteins (“BMP&#39;s”). The known proteins include BMP-2, BMP-3, BMP-4, BMP-5, BMP-6 (Vgr-1), BMP-7 (OP-1), BMP-8, BMP-9, BMP-10, BMP-11, BMP-12, BMP-13, BMP-14, BMP-15, and BMP-16. Currently preferred BMP&#39;s are any of BMP-2, BMP-3, BMP-4, BMP-5, BMP-6 and BMP-7. These dimeric proteins can be provided as homodimers, heterodimers, or combinations thereof, alone or together with other molecules. Alternatively or, in addition, molecules capable of inducing an upstream or downstream effect of a BMP can be provided. Such molecules include any of the “hedgehog” proteins, or the DNA&#39;s encoding them.  
         [0055]    The therapeutic delivery catheter may be used, for example, in any application for treating, preventing, or otherwise affecting the course of a disease or tissue or organ dysfunction. For example, the methods of the invention can be used to induce or inhibit angiogenesis, as desired, to prevent or treat restenosis, to treat a cardiomyopathy or other dysfunction of the heart, for treating Parkinson&#39;s disease or a stroke or other dysfunction of the brain, for treating cystic fibrosis or other dysfunction of the lung, for treating or inhibiting malignant cell proliferation, for treating any malignancy, and for inducing nerve, blood vessel or tissue regeneration in a particular tissue or organ.  
         [0056]    One of skill in the art will realize that the examples described and illustrated herein are merely illustrative, as numerous other embodiments may be implemented without departing from the spirit and scope of the present invention.