Abstract:
A method for preventing a restenosis within a vessel wall requires a medicament be delivered at predetermined locations into the vessel wall and allowed to subsequently disperse in a predetermined pattern. To deliver the medicament, a catheter with an expanding member is advanced into the vasculature of a patient until the expanding member is located as desired. The expanding member is then expanded to force dispensers into the vessel wall to the proper depth. A medicament is then pumped through the dispensers to create a plurality of equally spaced, localized medicinal deliveries which subsequently disperse to medicate an annulus shaped volume within the vessel wall.

Description:
[0001]    This application is a continuation-in-part of application Ser. No. 09/232,392, filed on Jan. 15, 1999, which is currently pending. The contents of application Ser. No. 09/232,392 are incorporated herein by reference. 
     
    
     FIELD OF THE INVENTION 
       [0002]    The present invention pertains generally to a method for treating the vessel of a patient. More specifically, the present invention pertains to a medical method for treating a vessel of a patient&#39;s cardiovascular system by injecting a fluid directly into the vessel wall. The present invention is particularly, but not exclusively, useful for preventing a restenosis by releasing a medicament at several predetermined locations within the vessel wall to circumferentially disperse the medicament in the vessel wall. 
       BACKGROUND OF THE INVENTION 
       [0003]    Angioplasty is a widely used procedure for treating a stenosis within a body vessel such as a human artery. During an angioplasty procedure, a medical catheter having an inflatable balloon attached to a catheter shaft is advanced within the lumen of the body vessel until the balloon is adjacent to the stenosis. Next, the balloon is inflated causing the stenosis to compress into the vessel wall and the lumen of the vessel to dilate. 
         [0004]    Although the angioplasty procedure is generally successful in dilating the lumen of the vessel and thereby allowing increased blood flow through the vessel, often times a restenosis occurs soon after the angioplasty procedure. It is widely recognized that the bodies response (inflammation) to tissue damage that occurs during the angioplasty procedure contributes to the restenosis. Several medicaments are known to be efficacious in the prevention of a restenosis if properly delivered near the site of the inflammation. 
         [0005]    Heretofore, a number of devices have been suggested for use in conjunction with an angioplasty procedure to obviate a restenosis. For example, one such device utilizes a balloon to position a plurality of apertures against the vessel wall near the stenosis. After positioning the apertures, a medicament is released from the apertures, where the medicament contacts the endothelium layer of the vessel. Unfortunately, use of the aperture device generally results in an insufficient amount of medicament being delivered to the target area because a large portion of the released medicament does not penetrate the vessel wall, but rather, is washed away into the blood stream. Further, due to the toxic nature of some of the medicaments used in this procedure, the large portion of medicament entering the bloodstream can cause adverse health effects to the patient. 
         [0006]    Also heretofore, devices capable of penetrating the wall of a vessel with a dispenser and releasing a medicament within the vessel wall have been disclosed. For example, U.S. Pat. No. 5,713,863, filed on Jan. 11, 1996 and entitled “Catheter With Fluid Medication Dispensers” and which is assigned to the same assignee of the present invention, discloses such a device. 
         [0007]    It is to be appreciated that the use of devices with expanding members and penetrating dispensers will cause some trauma to the vessel wall. Specifically, as indicated above, dilation of the vessel lumen with a balloon or other expanding member is generally known to cause tissue injury to the vessel wall. Further, penetration of the vessel wall with a dispenser will certainly cause some injury to vessel wall tissue. Finally, the release of a medicament within the vessel wall will also cause some injury to the tissue of the vessel wall. 
         [0008]    These various forms of tissue injury will trigger an inflammation response. As indicated above, this inflammation response is widely recognized to contribute to the restenosis of the vessel. It is also known that this inflammation response will cause localized changes near the injured tissue including increased permeability and increased blood flow. This localized increase in blood flow and permeability will generally increase the dispersion rate of medicaments released near an injury in a vessel wall. 
         [0009]    For a medicament to be effective in preventing a restenosis it must be delivered to a prescribed area and in a prescribed dosage. As indicated above, the size, shape and location of the prescribed treatment area is dependent on the amount and location of tissue injury. On the other hand, the amount of tissue injury is dependent on a number of factors including the size of the balloon, the number of penetrating dispensers and the amount of medicament released. Further, the dispersion rate of the medicament will be affected by the amount of inflammation, the type of medicament, and the amount of medicament released. Consequently, all of these factors must be considered when determining the arrangement of the dispensers and the amount of medicament to be released at each dispenser that will result in a uniform dispersion of medication at the prescribed treatment area. 
         [0010]    In light of the above, it is an object of the present invention to provide a method useful for preventing a restenosis caused by trauma to vessel tissue from an intravascular procedure. It is another object of the present invention to provide a method for preventing a restenosis in a vessel by delivering a medicament at predetermined locations within the vessel wall for dispersion into a prescribed shape that takes advantage of the increased medicinal dispersion rate due to the localized inflammation created by the procedure. It is yet another object of the present invention to prevent a restenosis by delivering a medicament at predetermined locations within a vessel wall to create a circumferential dispersion of the medicament within the vessel wall near a stenosis. Another object of the present invention is to safely deliver dangerous medicaments into a vessel wall while minimizing the amount of medicament which is washed away into the blood stream. Still another object of the present invention is to provide a method for treating a vessel which is easy to perform, safe, relatively simple, and inexpensive to perform. 
       SUMMARY OF THE PREFERRED EMBODIMENTS 
       [0011]    The present invention is directed to a method for preventing a restenosis from occurring near the site of an intervascular catheter procedure such as a balloon angioplasty procedure. In accordance with the present method, the restenosis is prevented by medicating a prescribed treatment area within the vessel wall near the site of the angioplasty procedure. For the present method, a medicament known to prevent restenosis is delivered at predetermined locations within the vessel wall and allowed to subsequently disperse thereby medicating the prescribed treatment area. The delivery of the medicament can be accomplished either during the angioplasty procedure or shortly thereafter. 
         [0012]    In accordance with the present method, first, the shape, size and location of the treatment area to be medicated is prescribed. For purposes of the present invention, the treatment area is generally a circumferentially shaped volume (or annulus) within the vessel wall near the site of the catheter procedure. For angioplasty procedures that dilate the lumen of the vessel near an existing stenosis, the present method contemplates medication of an annulus near the treated stenosis having a annulus length of approximately the size of the stenosis. Further, the prescribed annulus is preferably wholly contained within a particular vessel layer. For example, in the case of an arterial vessel, the particular vessel layer may be the intima or the media. Next, the delivery locations, delivery rates and delivery amounts are calculated after considering the dispersion rate of the medicament and the various factors that affect the dispersion rate such as the effect of inflammation. Once the delivery locations, rates and amounts are determined, the arrangement and size of the medicament dispensers can be determined and used to configure a catheter for delivering the medicament. 
         [0013]    To deliver the medicament in accordance with the present method, a catheter with an expanding member, such as a balloon, is advanced along a catheter shaft within the lumen of a body vessel until the expanding member is located adjacent to the prescribed treatment area. A plurality of dispensers are mounted on the expanding member and an extracorporeal mechanism for pumping a medicinal fluid to the dispensers through a lumen in the catheter is provided. Importantly, in order to medicate an annulus within the vessel wall as contemplated by the present method, all of the dispensers are positioned on the expanding member in a plane oriented substantially perpendicular to the axis of the catheter shaft. 
         [0014]    Once the expanding member is positioned adjacent to the treatment area, it can be activated to force the dispensers into the vessel wall. By the proper design and dimension of the expanding member and dispensers, the dispensers can be made to penetrate to the prescribed vessel layer. Once the dispensers have penetrated the vessel wall to the proper depth, a medicament can be selectively pumped through each dispenser for release at the predetermined locations. Preferably, the dispensers create a plurality of equally spaced localized medicinal deliveries which subsequently disperse to substantially medicate an annulus within the vessel wall. Simultaneously, the expanding member, which may be a balloon, can dilate the lumen of the vessel, thereby producing results similar to the balloon angioplasty procedure described above. 
         [0015]    As provided below, the expanding member selectively and accurately controls the movement of the dispensers, and the medicament source selectively provides a pressurized supply of medicament to the dispensers. Thus, the expanding member mechanism which causes the dispensers to penetrate the vessel wall operates independently from the extracorporeal mechanism for pumping the medicinal fluid to the dispensers, thereby allowing greater freedom in medicinal delivery. 
         [0016]    For the method of the present invention, the expanding member may include a balloon which is expandable from a contracted, first configuration to an expanded, second configuration. Preferably, the dispensers extend radially from the balloon and move with the balloon between the first configuration and the second configuration. This structure allows the dispensers to penetrate into a prescribed target vessel layer such as the intima or media for selective release of a medicament when the balloon is at the second configuration. When properly designed, this structure allows both the depth of penetration of the dispensers into the vessel wall and the force used to penetrate the vessel wall to be precisely controlled. 
         [0017]    Further, for the method of the present invention, at least one fluid passageway provides for fluid communication between the medicament source and the dispensers. For example, the fluid passageway can include a flexible tubular sleeve which substantially encompasses and encloses at least a portion of an outer surface of the balloon. The medicament source can also include an extracorporeal fluid pump which is in fluid communication with the fluid passageway for selectively providing a pressurized supply of medicament from the medicament source to the dispensers. 
         [0018]    Each dispenser can be a substantially tubular protrusion having an attachment end and a penetrating section for penetrating the wall of the vessel. The attachment end includes a base plate which mounts directly onto the tubular sleeve. In some of the devices disclosed herein for use in the present method, an open edge defines the penetrating section of the dispenser. In alternative devices useful for the present method and disclosed herein, each dispenser can include a porous section or an opening through the dispenser wall which defines the penetrating section. 
         [0019]    Depending upon the medicament and the desired treatment, the medicament can be released while the dispenser penetrates the treatment area or there can be a time delay between the dispenser penetration and the release of the medicament from the dispensers. 
         [0020]    An alternative structure for the expanding member may include a multi-lumen catheter, a grommet, a plurality of flexible tubes which connect the grommet to the catheter and a dispenser secured to each of the flexible tubes. The grommet is movable relative to the catheter to reposition the flexible tubes near the vessel wall. 
         [0021]    Various medicaments can be used in the method of the present invention depending on the needs of the individual patient. As indicated above, a medicament suitable for the treatment of a stenosis or disease de novo, inhibiting a restenosis by minimizing the effects of a previous intravascular procedure and/or inhibiting a stenosis in a vessel may be used. For example, to inhibit a restenosis, the medicament may contain an anti-proliferative agent which inhibits the proliferation of smooth muscle cell growth in a vessel under certain pathological conditions. Further, medicaments which selectively kill rapidly dividing cells can also be- used to inhibit the proliferation of smooth tissue growth. Other suitable medicaments can include anti-proliferative agents such as methotrexate, prednisone, adriamycin, mitomycin C, protein synthesis inhibitors, toxin fragments such as pseudomonas exotoxin (PE) or Ricin A (RA) Toxin, and radioactive isotopes such as  111 Indium,  90 Yttrium,  67 Gallium,  99m Tc(Technetium 99),  205 Thallium, and  32 P(Phosphorous 32) radiopharmaceutical. Alternatively, a medicament which stimulates the production of collateral vessels can be delivered to the target area by the present method. This provides preventative treatment for the patient by creating new collateral vessels in the event the original vessel develops a stenosis. A medicament which includes an angiogenis factor can be utilized for this purpose. 
         [0022]    In order to decrease the amount of medicament washed away into the blood stream, a portion of the medicament could precipitate at approximately the vessel pH level of the vessel. Typically, the vessel pH is approximately 7. Thus, a medicament having a pH level of less than approximately 6 or greater than approximately 8 can be utilized. After the medicament is dispensed into the wall of the vessel, the medicament pH level approaches 7 and a portion of the medicament precipitates. For these purposes, the fluid can include a precipitator, an active component attached to or included within the precipitator and a carrier component which carries the precipitator and the active component. The precipitator precipitates in the wall of the vessel while the carrier component gets washed away into the blood stream. Because the active component is attached to or included within the precipitator, the active component of the fluid remains in the vessel wall. This minimizes the amount of the active component of the fluid medicament which is washed away into the blood stream. For these purposes, the active component of the medicament, for example, can include an anti-proliferative agent as discussed above. Alternatively, the precipitator and active component, for example, can include a radionuclide or radiopharmaceutical precipitate, such as gold colloidal, i.e.  198 Au and  199 Au, and/or an inorganic precipitate. 
         [0023]    Additionally, the active component of the medicament can be designed to have a slow, time-release formulation so that the active component is released to the vessel wall over an extended period of time. Stated another way, the active component can biodegrade slowly over a period of time to gradually release the active component of the medicament into the vessel wall. A biodegradable polymer could be used to provide a control release formulation to the active component. 
         [0024]    Alternatively, the medicament could include a binder secured to the active component of the medicament. The binder binds, attaches or crosslinks to at least a portion of the wall of the vessel. The binder can include a ligand which binds to a portion of the vessel wall such as collagen or the smooth muscle cell component of the vessel wall. This ensures that the bulk of the active component of the medicament remains in the vessel wall and minimizes the amount of the active component of the medicament which is washed away into the blood stream. Examples of ligands binding to the vessel wall components include PDGF receptors, adhesive molecules including, but not limited to certain molecules of the integrin family and receptors on activated platelets such as thrombin receptors. Alternatively, for example, phoshorous tridentate which binds to collagen can be utilized. Further, a binder that has a direct affinity to form ionic bonds, covalent bonds or Van der Waal attractions to the wall of the vessel or some component thereof can be used in the method of the present invention. 
         [0025]    Further, a medicament for performing gene therapy on the vessel wall can be used. For example, the medicament could include either retroviral, adenoviral vectors or Adenovirus Associated Vectors (AAV) carrying the appropriate DNA payload for appropriate gene switching. The method of the present invention also allows for the use of medicaments which genetically alter the specific treatment site of the vessel without effecting the rest of the body. Additionally, the method of the present invention may be used to inject radioactive isotopes directly into the vessel wall. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0026]    The novel features of this invention, as well as the invention itself, both as to its structure and its operation will be best understood from the accompanying drawings, taken in conjunction with the accompanying description, in which: 
           [0027]      FIG. 1A  is a perspective view of a patient with a device positioned in an artery of the patient in accordance with the method of the present invention; 
           [0028]      FIG. 1B  is a perspective view of a portion of an artery of a patient showing the intima, media and adventitia layers; 
           [0029]      FIG. 1C  is a perspective view of a portion of an artery of a patient showing a circumferential dispersement of a medicament (in phantom) in accordance with the method of the present invention; 
           [0030]      FIG. 2  is a perspective view of a device suitable for use in the method of the present invention; 
           [0031]      FIG. 3A  is a cross-sectional view of the device of  FIG. 2  as seen along line  3 - 3  in  FIG. 2 , positioned in an artery of a patient; 
           [0032]      FIG. 3B  is a cross-sectional view of an artery showing a dispenser positioned for release of a fluid medicament in the media layer of the artery; 
           [0033]      FIG. 4A  is a perspective view of a first embodiment for a dispenser suitable for use in the present invention; 
           [0034]      FIG. 4B  is a perspective view of a second embodiment for a dispenser suitable for use in the present invention; 
           [0035]      FIG. 5A  is a side plan view of a third embodiment of a dispenser suitable for use in the present invention; 
           [0036]      FIG. 5B  is a side plan view of a fourth embodiment of a dispenser suitable for use in the present invention; 
           [0037]      FIG. 5C  is a side plan view of a fifth embodiment of a dispenser suitable for use in the present invention; 
           [0038]      FIG. 6  is a perspective view of another embodiment of a device suitable for use in the present invention; 
           [0039]      FIG. 7  is a cross-sectional view of the device shown in  FIG. 6  as seen along line  7 - 7  in  FIG. 6 ; 
           [0040]      FIG. 8  is a perspective view of yet another embodiment of a device suitable for use in the present invention; 
           [0041]      FIG. 9  is a cross-sectional view of the device of  FIG. 8  shown in a retracted configuration, as seen along line  9 - 9  in  FIG. 8 ; 
           [0042]      FIG. 10  is a cross-sectional view of the device of  FIG. 8  shown in an expanded configuration, as seen along the line  9 - 9  in  FIG. 8 ; 
           [0043]      FIG. 11  is a cross-sectional view of the device of  FIG. 8  positioned in the blood vessel of a patient; 
           [0044]      FIG. 12A  is a longitudinal cross-sectional view of a portion of the vessel and a device prior to a dispenser penetrating the vessel wall; 
           [0045]      FIG. 12B  is a longitudinal cross-sectional view of a portion of the vessel and a portion of the device after a dispenser penetrates the vessel wall; 
           [0046]      FIG. 12C  is an axial cross-sectional view of the vessel and the device illustrating the dispensers penetrating the vessel wall; 
           [0047]      FIG. 12D  illustrates a longitudinal cross-sectional view of the intima layer of the vessel wall after the fluid medicament has been injected into the vessel wall; 
           [0048]      FIG. 12E  is an axial cross-sectional view illustrating the intima layer of the vessel wall after the fluid medicament has been injected into the vessel wall; 
           [0049]      FIG. 12F  is a longitudinal cross-sectional view of a portion of the intima layer of the vessel and the device illustrating the fluid medicament after dispersion in the vessel wall; 
           [0050]      FIG. 12G  is an axial cross-sectional view of the intima layer of the vessel and the device illustrating the fluid medicament after dispersion in the vessel wall; 
           [0051]      FIG. 13A  is a longitudinal cross sectional view of the vessel and a device illustrating a fluid medicament containing a radioactive isotope being injected into the vessel wall; 
           [0052]      FIG. 13B  is a longitudinal cross sectional view of a portion of the vessel and the device after a fluid medicament containing a radioactive isotope is injected into the vessel wall; 
           [0053]      FIG. 14A  is a longitudinal cross-sectional view of a portion of the vessel and the device after a fluid medicament containing a precipitant is injected into the vessel wall; 
           [0054]      FIG. 14B  is a longitudinal cross-sectional view of a portion of the vessel and the device after a portion of an injected fluid medicament precipitates within the vessel wall; 
           [0055]      FIG. 15A  is a longitudinal cross-sectional view of a portion of the vessel and the device after a fluid medicament with a binder has been injected into the vessel wall; 
           [0056]      FIG. 15B  is a longitudinal cross-sectional view of a portion of the vessel and the device showing the binder of an injected medicament binding to a portion of the vessel wall; 
           [0057]      FIG. 16A  is a longitudinal cross-sectional view of a portion of a vessel and device illustrating the cell genes of the vessel prior to penetration of the vessel with the dispenser; 
           [0058]      FIG. 16B  is a longitudinal cross-sectional view of a portion of a vessel and device illustrating the vessel after a fluid medicament that includes a virus gene is injected into the wall of the vessel by the device; and 
           [0059]      FIG. 16C  is a longitudinal cross-sectional view of a portion of the vessel and device illustrating the vessel wall after the injected virus genes have attacked and replaced the cell genes. 
           [0060]      FIG. 17  is a perspective view of a device according to another embodiment of the present invention. 
           [0061]      FIG. 18  is a perspective view of a device according to another embodiment of the present invention. 
           [0062]      FIG. 19  is a perspective view of a device according to another embodiment of the present invention. 
       
    
    
     DESCRIPTION OF THE PREFERRED EMBODIMENTS 
       [0063]    Referring initially to  FIG. 1A , a device  10  for injecting a fluid medicament  13  into a wall  23  of a living blood vessel  11  in accordance with the method of the present invention is shown positioned in an upper body, blood vessel  11  of a patient  12 . It is to be appreciated that the present method can be used in arteries and other vessels throughout the body of the patient  12 .  FIG. 1B  shows the wall  23  of an arterial blood vessel  11  having three layers of importance for the present invention, the intima  35 , the media  37  and the adventitia  39 . As shown in  FIG. 1C , the intima  35  surrounds the lumen  21  of the blood vessel  11 . Importantly, as provided in detail below, the device  10  when used in accordance with the method provided herein, allows for a substantially circumferential dispersion of the fluid medicament  13  within the wall  23  of the blood vessel  11 , as shown in  FIG. 1C . Further, in accordance with the present method, a circumferential dispersion of fluid medicament  13  can be made within one of the layers  35 ,  37 ,  39  of wall  23  of the blood vessel  11 . 
         [0064]    Referring to  FIGS. 2 and 3A , a first version of a device  10  suitable for the method of the present invention includes a multi-lumen catheter  14 , an expanding member  15  mounted thereon, a tubular sleeve  18  and a plurality of  20  dispensers  20 . Although  FIGS. 2 and 3A  show the expanding member  15  as an inflatable balloon  16 , any expanding member known in the art may be used. The balloon  16  is inflatable and deflatable between a first, substantially deflated configuration and a second, substantially expanded configuration. The balloon  16 , while in the second configuration, can be anywhere from partially inflated to fully inflated depending upon the size of the blood vessel  11 . The balloon  16  and tubular sleeve  18  can be made of a number of materials including polyethylene terephthalate (PET). As shown in  FIG. 2 , the tubular balloon  16  defines a longitudinal axis  17 . 
         [0065]    Further,  FIG. 2  indicates that the tubular sleeve  18  surrounds a substantial portion of the balloon  16 , and that a plurality of dispensers  20  are mounted onto the tubular sleeve  18 . Of these, the number of dispensers  20  illustrated is only exemplary. Importantly for the present method, all dispensers  20  are positioned in a single plane  19  that, as shown, is oriented substantially normal to the longitudinal axis  17 . Also, it is preferable for the present method that the dispensers  20  be equally spaced around the axis  17 . 
         [0066]    A more complete appreciation of the structural cooperation between the balloon  16 , the tubular sleeve  18  and the dispensers  20  is provided by  FIG. 3A  wherein, it will be seen that a distal end  22  of tubular sleeve  18  is attached directly to an outer surface  25  of balloon  16 . By cross-referencing  FIGS. 2 and 3A  it can be seen that the tubular sleeve  18  substantially surrounds and encloses the balloon  16  and that a proximal end  24  of tubular sleeve  18  extends proximally from and beyond the balloon  16  over catheter  14 . The tubular sleeve  18  cooperates with the outer surface  25  of the balloon  16  to define a portion of a fluid passageway  26 . The proximal end  24  can be connected to an outer lumen  27  (not shown in  FIG. 3A ) of the catheter  14  to complete the fluid passageway  26 . 
         [0067]      FIG. 3A  further shows that the distal end  28  of balloon  16  is affixed to the catheter  14 , and that the proximal end  30  of the balloon  16  attaches onto the catheter  14  to create an inflation chamber  32  in the interior of the balloon  16 . A balloon port  34  provides fluid access into the inflation chamber  32 . For purposes of the present invention, the balloon port  34  can be connected in fluid communication with a balloon lumen (not shown) of the catheter  14 .  FIG. 3A  also shows that catheter  14  is formed with an inner lumen  36  which is dimensioned to receive a guidewire  38  therethrough. 
         [0068]    As discussed previously, the wall  23  of the blood vessel  11  includes multiple layers. To facilitate the present discussion, some of the layers, namely, the intima layer  35 , the media layer  37 , and the adventitia layer  39  are illustrated in  FIG. 1B  and again in  FIG. 3B . Importantly, when the device  10  is used in accordance with the present method, the depth of penetration of each dispenser  20  can be precisely controlled by controlling the length  41  (shown in  FIG. 5A ) of each dispenser  20 . In accordance with the method of the present invention, the dispensers  20  extend a length  41  of between approximately 0.005 inches and approximately 0.02 inches from the tubular sleeve  18  when the balloon  16  is inflated. However, those skilled in the pertinent art will recognize that these distances are merely exemplary. Thus, the device  10  is able to deliver the fluid medicament  13  to a desired, target layer in the wall  23  of the blood vessel  11 . For example, as illustrated in  FIG. 3B , the dispenser  20  penetrates through the intima layer  35  and precisely delivers the fluid medicament  13  to the media layer  37 , i.e. the target layer in this example. It is to be appreciated that a shorter dispenser  20  could be utilized to deliver the fluid medicament  13  to the intima layer  35 . Additionally, in accordance with the method of the present invention, the device  10  can be used to simultaneously release the fluid medicament  13  within a target layer and dilate the lumen  21  of the blood vessel  11 . 
         [0069]    Referring now to  FIG. 4A , each dispenser  20  includes a base plate  40  and a tubular protrusion  42  having an attachment end  44  and a penetrating section  46 . Further, it is seen that the attachment end  44  of the tubular protrusion  42  affixes to and is an integral part of the base plate  40 . Preferably, the dispenser  20  is made of nickel and the tubular protrusion  42  is formed by punching out the base plate  40 . In the dispenser embodiment illustrated in  FIG. 4A , the penetrating section  46  is defined by an opening which is opposite the base plate  40 . The tubular protrusion  42  defines a fluid channel  48  which extends through the dispenser  20 . The penetrating section  46  of the dispenser  20  shown in  FIG. 4A  is substantially annular shaped. 
         [0070]      FIG. 4B  shows another embodiment of the dispenser  20 . In this embodiment, each tubular protrusion  42  is substantially conical shaped as shown in  FIG. 4B . Like the embodiment shown in  FIG. 4A , the dispenser  20  shown in  FIG. 4B  is preferably made of nickel and is formed with a fluid channel  48  which extends through the dispenser  20 . 
         [0071]      FIGS. 5A ,  5 B and  5 C illustrate additional, alternative embodiments of the dispenser  20 . In the embodiments illustrated in  FIGS. 5A ,  5 B and  5 C, the tubular protrusion  42  is substantially conical shaped. However, in  FIG. 5A , the penetrating section  46  is defined by an opening which extends through the side of the tubular protrusion  42 . Somewhat similarly, in  FIG. 5B , the penetrating section  46  is defined by a pair of openings which extend through the side of each tubular protrusion  42 . This feature inhibits plugging of the penetrating section  46  during insertion into the wall  23  of the blood vessel  11 . In  FIG. 5C , the tubular protrusion  42  is made of a porous material. Thus, the porous material defines the penetrating section  46  of each dispenser  20 . In the embodiment shown in  FIG. 5C , the fluid medicament  13  is forced through the pores  49  of the porous tubular protrusion  42 . 
         [0072]    Referring now to  FIG. 3A , the dispensers  20  are mounted on the tubular sleeve  18  so that the fluid channel  48  of each respective dispenser  20  is aligned with a hole  52  in the tubular sleeve  18 . This is done to establish fluid communication between the particular dispenser  20  and the fluid passageway  26 . As a practical matter, it may be preferable in the construction of the device  10  to first mount the dispenser  20  on the tubular sleeve  18 , which can be done in any manner well known in the pertinent art, such as by bonding, and then pierce a hole  52  in the tubular sleeve  18  through the dispenser  20 . 
         [0073]    An alternative structure for a device  10  suitable for use in the present method is shown in  FIG. 6 . As shown, the alternative device  10  includes a multi-lumen catheter  14  formed to accommodate a guidewire  38 , a balloon  16 , a plurality of dispensers  20  and a plurality of tubular channels  64  mounted on the outer surface  25  of the balloon  16 . Each tubular channel  64  has a smaller diameter than the balloon  16  and is positioned to be substantially parallel with a longitudinal axis  65  of the balloon  16 . 
         [0074]      FIG. 6  further shows that mounted on the surface of each tubular channel  64  is a dispenser  20 . The dispensers  20  are positioned on the surface of tubular channel  64  so that when balloon  16  is inflated, the dispensers  20  move outwardly from the longitudinal axis  65  in a radial direction. Importantly for the present method, all dispensers  20  are positioned in a single plane  67  that is oriented substantially normal to the longitudinal axis  65  of the balloon  16 . Further, it is preferable for the present method that the dispensers  20  be equally spaced around the longitudinal axis  65 . 
         [0075]    Referring now to  FIG. 7 , the cross-sectional view of the alternative device  10  shows the tubular channel  64  in more detail. More specifically, a distal end  66  of tubular channel  64  is sealed to create a portion of the fluid passageway  26  which connects the dispensers  20  to the fluid source  60 . Referring to  FIGS. 6 and 7 , it is to be appreciated that the proximal end  68  of the tubular channel  64  is in fluid communication with the outer lumen  27  of the catheter  14 . In turn, the outer lumen  27  is connected in fluid communication with the fluid pump  58  and the fluid medicament source  60 . 
         [0076]    Still referring to  FIG. 7 , the dispensers  20  are shown mounted on the surface of the tubular channel  64 . As  FIG. 7  further shows in detail, a base plate  40  of a dispenser  20  is mounted on the tubular channel  64  over a corresponding hole  70 . From this view, it can be appreciated that any number of tubular channels  64  could be mounted on the external surface of balloon  16 . 
         [0077]      FIG. 8  shows yet another version of a device  10  suitable for the method of the present invention. In this version of the device  10 , the expanding member  15  includes a multi-lumen catheter  80  and a grommet  82 . Both the multi-lumen catheter  80  and the grommet  82  are disposed about the same longitudinal axis  97  with the grommet  82  positioned distally, and separated from, the distal end  88  of the multi-lumen catheter  80 . 
         [0078]    A mechanism is provided to move the grommet  82  translationally along the longitudinal axis  97 . For example, referring to  FIG. 8 , a push-pull wire  84 , is shown connected to the grommet  82 . The push-pull wire  84  extends through one of the lumens of the multi-lumen catheter  80  allowing the push-pull wire  84  to move translationally in line with the longitudinal axis  97 . The translational movement of the push-pull wire  84  causes the grommet  82  to undergo a similar translational displacement. Further, this version of the device  10  can be used in combination with the guidewire  38 , as shown in  FIG. 8 . Specifically, the push-pull wire  84  may be formed with an internal lumen, allowing the catheter  80  and push-pull wire  84  to pass over the guidewire  38 . 
         [0079]    In the version of the device  10  shown: in  FIG. 8 , a plurality of hollow, flexible tubes  86  are attached between the grommet  82  and the multi-lumen catheter  80 . Each of the flexible tubes  86  includes a distal end  88 , a proximal end  90  and a central region  92 . The proximal end  90  of each tube  86  is joined to the multi-lumen catheter  80 . The distal end  88  of each tube  86  is joined to the grommet  82 . Preferably, the tubes  86  are distributed radially around the multi-lumen catheter  80  and grommet  82  in a manner substantially as shown in  FIG. 8 . 
         [0080]    Referring now to  FIGS. 9-11 , it may be seen that each flexible tube  86  is formed with a lumen  94 . The lumen  94  of each flexible tube  86  passes through the multi-lumen catheter  80  allowing fluid medicament  13  to be passed through multi-lumen catheter  80  and into flexible tubes  86 . The lumen  94  of each flexible tube  86  passes separately through multi-lumen catheter  80  allowing a different fluid medicament  13  to be passed into each flexible tube  86 . Alternatively, the lumen  94  of each flexible tube  86  may be attached to one or more common lumens within the multi-lumen catheter  80 . 
         [0081]    Referring to  FIGS. 8 and 9 , it is shown that a dispenser  20  is attached to the central region  92  of each flexible tube  86 . Each flexible tube  86  is formed with a hole  96  which correspond to a respective dispenser  20 . Functionally, each hole  96  connects the fluid channel  48  of a respective dispenser  20  to lumen  94  allowing the fluid pump  58  to pump fluid medicaments  13  from the fluid source  60  into lumen  94  to be expelled through the dispensers  20 . Importantly for the present method, all dispensers  20  are positioned in a single plane  95  oriented normal to the longitudinal axis  97  defined by the expanding member  15 . Further, it is preferable for the present method that the dispensers  20  are equally spaced around the longitudinal axis  97 . 
         [0082]    Referring now to  FIGS. 9 and 10 , it is shown that the device  10  is movable between the first, contracted configuration (shown in  FIG. 9 ) and the second, expanded configuration (shown in  FIG. 10 ). Specifically, it may be seen that the grommet  82  and the multi-lumen catheter  80  are distanced by a first separation distance  98 . The device  10  shown in  FIG. 9  also has a first overall width designated  100 . In comparison, the grommet  82  and the multi-lumen catheter  80  shown in  FIG. 10  are distanced by a second separation distance  102  which is smaller than the first separation distance  98  of  FIG. 9 . The device  10 , shown in  FIG. 10  also has a second overall width  104  which is greater than the first overall width  100  shown in  FIG. 9 . 
         [0083]    The movement between the first, contracted configuration shown in  FIG. 9  and the second, expanded configuration shown in  FIG. 10  is accomplished by the translational movement of the grommet  82  along the longitudinal axis  97 . Specifically, as the push-pull wire  84  causes the grommet  82  to move towards the multi-lumen catheter  80 , each of the flexible tubes  86  bows outwardly away from the longitudinal axis  97 . In this manner, the push-pull wire  84  may be used to move the grommet  82  translationally to cause the flexible tubes  86  to alternately bow, as seen in  FIG. 10 , and straighten, as seen in  FIG. 9 . In some cases, it will be preferable to fabricate the flexible tubes  86  from a resilient material and shape the flexible tubes  86  to be initially biased in either a bowed or straight configuration. 
         [0084]      FIGS. 12A-12F  show the process whereby the fluid medicament  13  is pumped from each dispenser  20  into the intima layer  35  of an exemplary blood vessel  11  and then allowed to disperse.  FIGS. 12A-12F  further show that the fluid medicament  13  can be pumped into a target layer, in this case the intima  35 , and allowed to disperse until a circumferential dispersion of fluid medicament  13  is achieved. First, as shown in  FIG. 12A , the dispenser  20  is positioned adjacent to the target area of the blood vessel  11 . Next, as shown in  FIGS. 12B and 12C , the expanding member  15  is expanded, forcing the dispenser  20  to penetrate the target layer (in this case, the intima  35 ). Preferably, as illustrated in  FIG. 12C , the dispensers  20  are circumferentially spaced to create a plurality of spaced apart medicinal deliveries  106 .  FIGS. 12D and 12E  show the medicinal deliveries  106  which are confined to the intima layer  35 .  FIGS. 12F and 12G  show the subsequent dispersion of the fluid medicament  13  around a circumference of the wall  23  of the blood vessel  11 , creating a circumferential dispersion. The pumping rate required to achieve the desired circumferential dispersion depends upon the viscosity of the fluid medicament  13  utilized. Typically, between approximately 400 microliters and 700 microliters of the fluid medicament  13  is dispensed during a period of between approximately five and forty-five seconds to create the desired medicinal delivery  106  that will result in a circumferential dispersion. However, it should be recognized that the amounts and time frames provided herein are merely exemplary. It is also to be appreciated that the medicinal dispersion rate will be affected by the body&#39;s response (inflammation) to the tissue injury caused by the present method. 
         [0085]    Further, the spacing required to create a plurality of spaced apart medicinal deliveries  106  which subsequently disperse the fluid medicament  13  along the treatment area  54  will also vary according to the fluid medicament  13  utilized. It is contemplated for the present method that the dispensers  20  are to be spaced a circumferential distance  108  of between approximately 1 millimeter and  6  millimeters, roughly 70 degrees and 140 degrees apart. 
         [0086]    The composition of the fluid medicament  13  to be injected into the wall  23  of the blood vessel  11  depends upon the treatment being performed and the physical characteristics of the patient  12 . More specifically, the fluid medicament  13  can be designed to treat a stenosis or disease de novo, inhibit a restenosis by minimizing the effects of a previous intravascular procedure and/or inhibit a stenosis in a blood vessel  11 . For example, to inhibit a restenosis, the fluid medicament  13  can contain anti-proliferative agents which inhibit the proliferation of smooth muscle cell growth in the vessel in certain pathological conditions. These fluids selectively kill rapidly dividing cells and can be utilized to inhibit the proliferation of smooth tissue growth. Suitable fluids can include anti-proliferative agents such as methotrexate, prednisone, adriamycin, mitomycin C, protein synthesis inhibitors, toxin fragments such as pseudomonas, exotoxin (PE) or Ricin A (RA) Toxin, and radioactive isotopes  112  such as  111 Indium,  90 Yttrium,  67 Gallium,  99m Tc (Technetium 99),  205 Thallium, and  32 P (Phosphorous 32) radiopharmaceutical. It is believed that the present method is uniquely suited to safely deliver toxic fluid medicaments  13  into the wall  23  of the blood vessel  11  while minimizing the amount of fluid medicament  13  which is washed away into the blood stream. 
         [0087]    Alternatively, for example, a fluid medicament  13  which stimulates the production of collateral vessels can be delivered by the present method. These fluid medicaments  13  provide preventative treatment for the patient  12  by creating new collateral vessels in the event the original blood vessel  11  develops a stenosis. A fluid medicament  13  which includes an angiogenis factor can be utilized for this purpose. 
         [0088]      FIGS. 13A and 13B , illustrate the delivery and dispersion of a fluid medicament  13  that includes a radioactive isotope  112  which can reduce and inhibit tissue and/or cell growth of the wall  23  of the blood vessel  11 . Because the radioactive isotopes  112  are injected directly in the wall  23  of the blood vessel  11  and are symmetrically injected around the circumference of the wall  23  of the blood vessel  11 , relatively low energy radioactive isotopes  112  having a relatively short half life can be utilized. These relatively low energy radioactive isotopes  112  should cause minimal trauma to the patient  12 . The present method provided herein is uniquely suited to safely deliver a radioactive isotope  112  to only the treatment area  54  of the wall  23  of the blood vessel  11 , while minimizing the amount of radioactive isotope  112  which is washed away into the blood stream. Additionally, the radioactive isotope  112  can be encapsulated within a suitable carrier such as amino- mannose modified liposome, which is rapidly absorbed into the smooth muscle cells of the intima layer  35 . 
         [0089]    The exact dose of radiation to be delivered to the wall  23  of the blood vessel  11  can be varied to suit the needs of the patient  12 . It is presently believed that a tissue absorbed dose of between approximately 8-40 Gray will be utilized to inhibit restenosis. The exact amount of fluid medicament  13  and type of fluid medicament  13  injected into the wall  23  of the blood vessel  11 , can be varied to account for fluid medicament  13  washed into the blood stream and/or account for the active life of the fluid medicament  13 . 
         [0090]    Referring to  FIGS. 14A and 14B , it is shown that a precipitation process can be used to minimize the amount of fluid medicament  13  which is washed away into the blood stream. Specifically, a portion of the fluid medicament  13  can be precipitated at approximately the pH level of the wall  23  of the blood vessel  11 . Typically, the vessel pH is approximately 7. A fluid medicament  13  containing a precipitator  114 , and having a fluid pH level of less than approximately 6 or greater than approximately 8 can be utilized. After the fluid medicament  13  and precipitator  114  are dispensed into the wall  23  of the blood vessel  11 , the fluid medicament pH level will approach  7 , and a portion of the fluid medicament  13  may precipitate. For this embodiment, the fluid medicament  13  could include a precipitator  114 , an active component  115  attached to or incorporated within the precipitator  114  and a carrier component  117  which carries the precipitator  114  and the active component  115 . The active component  115  is the portion of the fluid medicament  13  which is designed to treat the patient  12 . In this example, the precipitator  114  could precipitate in the wall  23  of the blood vessel  11  while the carrier component  117  gets washed away into the blood stream. 
         [0091]    Because the active component  115  is attached to or incorporated within the precipitator  114 , this ensures that the bulk of the active component  115  of the fluid medicament  13  remains in the wall  23  of the blood vessel  11  and minimizes the amount of the active component  115  of the fluid medicament  13  which is washed away into the blood stream. In this embodiment, the active component  115  of the fluid medicament  13 , for example, can include an anti-proliferative agent as outlined above. Alternatively, the precipitator  114  and the active component  115  can be a radionuclide or radiopharmaceutical precipitate, such as gold colloidal, i.e.  198 Au and  199 Au, and/or an inorganic precipitate such as organo-metallic precipitate. 
         [0092]    Additionally, the active component  115  of the fluid medicament  13  can be designed to have a slow, time-release formulation so that active component  115  is released to the wall  23  of the blood vessel  11  over an extended period of time. Stated another way, the active component  115  can biodegrade slowly over a period of time to release the active component of fluid medicament  13  into the wall  23  of the blood vessel  11  over an extended period of time. A biodegradable polymer may be used to provide a control release formulation to the active component  115 . 
         [0093]    Alternatively, referring to  FIGS. 15A and 15B , the fluid medicament  13  may include a binder  116 , the active component  115  and the carrier component  117 . The binder  116  is secured to the active component  115  of the fluid medicament  13 . The binder  116  is adapted to bind, attach and/or crosslink to at least a portion of the wall  23  of the blood vessel  11 . For example, the binder  116  could include a ligand which binds to a portion of the wall  23  of the blood vessel  11  such as collagen or the smooth muscle cell component of the wall  23  of the blood vessel  11 . Because the binder  116  is secured to the active component  115 , this ensures that the bulk of the active component  115  of the fluid medicament  13  remains in the wall  23  of the blood vessel  11  and minimizes the amount of the active component  115  of the fluid medicament  13  which is washed away into the blood stream. Examples of ligands capable of binding to the arterial wall components include PDGF receptors, adhesive molecules including, but not limited to certain molecules of the integrin family, and receptors on activated platelets such as thrombin receptors. Another suitable type of ligand is sold under the name CERETEC® by Amersham located in Arlington Heights, Ill. Alternatively, for example, phosphorous tridentate which binds to collagen can be utilized. In yet an alternative embodiment, the binder  116  can have a direct affinity to form ionic bonds, covalent bonds or Van der Waal attractions with the wall  23  of the blood vessel  11  or some component thereof. 
         [0094]    Alternatively, as illustrated in  FIGS. 16A-16C , the fluid medicament  13  can be used for gene therapy on the wall  23  of the blood vessel  11  In this embodiment, the fluid medicament  13  can include a suitable viral vector  118  which is adapted to infect a cell  120  and replace, modulate, inhibit or enhance one of the cell genes  122  within the cell  120 . For example, the fluid medicament  13  could include a retroviral, adenoviral vectors or Adenovirus Associated Vectors (AAV) carrying the appropriate DNA payload for appropriate gene switching. Alternatively, for example, naked DNA or polycation-condensed DNA could be utilized for gene therapy. The method of the present invention allows for the use of fluid medicaments  13  which genetically alter the treatment area  54  of the wall  23  of the blood vessel  11  without effecting the rest of the body. 
         [0095]    Still other fluid medicaments  13  which could be utilized with the method of the present invention include antibodies such as receptor site monoclonal antibodies, a toxic agent such as saponin, a genetic material such as DNA, a cellular material such as endothelial cells and/or medicaments such as heparin. The examples provided herein are merely examples of fluid medicaments  13  which may be useful with the present invention. Those skilled in the art will recognize that additional fluid medicaments  13  will be developed as medical technology improves. Additionally, those skilled in the art will recognize that the present invention can be utilized for applications other than inhibiting a restenosis. For example, with extended dispensers  20 , the method of the present invention could deliver fluid medicaments  13  from the blood vessel  11  to specific organs. 
       Operation 
       [0096]    An example of the operation of the balloon  16  version of the expanding member  15  can best be visualized with initial reference to  FIGS. 1-3 . First, the guidewire  38  is positioned into the blood vessel  11  of the patient  12 . This is done to establish a mechanical pathway through the blood vessel  11  to the treatment area  54  where the fluid medicament  13  is to be released. 
         [0097]    Next, the balloon  16 , which is attached to the catheter  14 , is moved over the guidewire  38  to the treatment area  54 . The balloon  16  is at its first configuration during movement over the guidewire  38  in the blood vessel  11 . Once the balloon  16  is properly positioned proximate the treatment area  54 , an inflator  56  is activated to inflate the balloon  16  to its second configuration. As shown in  FIG. 2 , the inflator  56  is connected to the proximal (extracorporeal) end  29  of the catheter  14 . 
         [0098]    Referring back to  FIGS. 3A and 3B , it will be appreciated that, as the balloon  16  is inflated, the expanding balloon  16  urges against the tubular sleeve  18  and causes the tubular sleeve  18  to likewise expand. Consequently, the dispensers  20  mounted on the tubular sleeve  18  move radially from the longitudinal axis  17  and embed into the treatment area  54 . Further, the balloon  16  can be used to simultaneously dilate the lumen  21  of the blood vessel  11 . 
         [0099]    With the dispensers  20  embedded into the treatment area  54 , the fluid pump  58  shown in  FIG. 2  is activated to pump a fluid medicament  13  from the fluid medicament source  60  into the fluid passageway  26 . Importantly, this pumping action also causes any fluid medicament  13  which has already been pumped into the fluid passageway  26  to be expelled through the fluid channels  48  of dispensers  20  and into the tissue of treatment area  54 . 
         [0100]    Alternatively, the fluid pump  58  could be activated prior to embedding the dispensers  20  into the wall  23  of the blood vessel  11  and a valve  62  could be used to prevent the flow of fluid medicament  13  until the dispensers  20  are embedded in the treatment area  54 . The valve  62  can then be opened when the dispensers  20  penetrate into the treatment area  54  so that injection occurs substantially simultaneously with the embedding of the dispensers  20  in the treatment area  54 . Alternatively, the injection of the fluid medicament  13  could happen after a time delay by waiting to open the valve  62  for at least about one second to about twenty seconds. Further, one or more fluid medicaments  13  can be released at different time intervals in the wall  23  of the blood vessel  11 . 
         [0101]    After the fluid medicament  13  from the fluid medicament source  60  has been dispensed into the treatment area  54 , the balloon  16  can be deflated to the first configuration by reversing the inflator  56 . This action will cause the balloon  16  to collapse and withdraw the dispensers  20  from the treatment area  54 . The entire device  10  can then be withdrawn from the patient  12  over the guidewire  38 . 
         [0102]    The embodiment shown in  FIG. 6  utilizes a plurality of individual, tubular channels  64 . With this embodiment, it is possible to either maintain fluid communication with, or fluid isolation between, each tubular channel  64 . For example, fluid communication between each tubular channel  64  can be established by fluidly connecting each tubular channel  64  together within one outer lumen  27  of the catheter  14  so that each tubular channel  64  is supplied fluid medicament  13  from the same fluid pump  58 . Alternatively, fluid isolation may be maintained between each tubular channel  64  by providing each tubular channel  64  with a corresponding and independent outer lumen  27  and establishing its own fluid connection to a corresponding and independent fluid pump  58 . Consequently, it is possible to inject a variety of alternate fluid medicaments  13  simultaneously by using a plurality of tubular channels  64  which are each connected to a separate fluid pump  58 . 
         [0103]    While the particular Method for Delivering Medication Into an Arterial Wall for Prevention of Restenosis as herein shown and disclosed in detail is fully capable of obtaining the objects and providing the advantages herein before stated, it is to be understood that it is merely illustrative of the presently preferred embodiments of the invention and that no limitations are intended to the details of the constructions or design herein shown other than as defined in the appended claims. 
         [0104]    The present invention is not limited to all dispensers being located on a single plane. In some embodiments, a device of the present invention has multiple dispensers that are located at different points along the length of the medical device, such as on different planes. 
         [0105]    For example,  FIG. 17  shows a device  100  that is similar to device  10  of  FIG. 2  except that there are multiple dispensers  20  located along the length of tubular sleeve  18  (e.g., on multiple planes). The cross-sectional view of device  100  along line  103 - 103  would appear similar to  FIGS. 3A and 3B  except that there would be multiple dispensers  20 . 
         [0106]    For example,  FIG. 18  shows a device  110  that is similar to device  10  of  FIG. 6  except that there are multiple dispensers  20  located along the length of tubular sleeve  18  (e.g., on multiple planes). The cross-sectional view of device  110  along line  107 - 107  would appear similar to  FIG. 7  except that there would be multiple dispensers  20 . 
         [0107]    For example,  FIG. 19  shows a device  120  that is similar to device  10  of  FIG. 8  except that there are multiple dispensers  20  located along the length of flexible tubes  86  (e.g., on multiple planes). The cross-sectional view of device  120  along line  109 — 109  would appear similar to  FIGS. 9 ,  10 , and  11  except that there would be multiple dispensers  20 .