Patent Abstract:
An intraparenchymal infusion catheter system for delivering drugs or other agents to selected sites in an organism, such as a human, includes a pump that may be implanted or disposed outside the organism. A catheter is coupled to the pump. The catheter comprises a flexible biocompatible tubular portion terminating in a free distal end. The distal end of the catheter bears a rounded tip, a portion of which is slidably disposed within the lumen of the tubular portion. The tip is porous for discharging an agent or drug to a selected site. The tip has a microporosity of less than or equal to 0.22 microns. The tubular portion is composed from a material that will expand from its nominal size when exposed to a stimulus such as heat or a solvent and return to its nominal size when the stimulus is withdrawn. By expanding the tubular portion, a physician can select the amount of the tip that is exposed to the organism, thereby customizing the catheter to the structural size of the selected site within the body.

Full Description:
BACKGROUND OF THE INVENTION  
         [0001]    1. Field of the Invention  
           [0002]    In general, this invention relates to infusion catheters. More specifically, this invention relates to an intraparenchymal infusion catheter system for delivering a therapeutic agent into an organism where the catheter has a porous tip which has a perfusion surface area that may be matched to the target volume.  
           [0003]    2. Description of the Related Art  
           [0004]    When chronic administration of a pharmaceutically active agent is required, internal delivery by an external infusion pump or an implantable infusion pump (“IIP”), in combination with a catheter, may be the desired delivery means. For example, IIP-catheter delivery may be preferred when, for example, the site specific delivery of the drug is critical, or the drug must be administered in tightly controlled, yet minute dosages.  
           [0005]    In current catheter designs, the delivered agent ordinarily flows out of the catheter via a fixed number of elution holes. Most catheter designs utilize either a single elution hole or a few elution holes. The current designs suffer from at least two notable disadvantages. To begin with, the fixed number of elution holes may make it difficult to tailor the catheter to the drug flow rates dictated for a particular drug and a particular parenchymal target. In many neurological applications, the quantity of delivered drug is relatively minute and must be carefully tailored. Some flexibility in flow rate is achieved by calibrating the IIP, although it is still desirable to be able to more carefully tailor the number of elution holes to the desired flow rate. In addition, current catheter designs present a fixed external perfusion surface area to a selected parenchymal target volume. Since the perfusion area is fixed, it may be difficult to match the perfusion area to the parenchymal target volume. For example, if the parenchymal target volume consists of a five centimeter long malignant mass, and the perfusion area of the catheter is only three centimeters in length, it may be very difficult to achieve infusion of a cytostatic agent through the entire length of the mass. Furthermore, there may be applications where it is desirable to minimize the volume displacement of the catheter tip into the selected parenchymal target in order to minimize tissue trauma. If the perfusion area of the catheter tip is fixed, no such tailoring is possible.  
           [0006]    The present invention is directed at solving one or more of the above-noted problems.  
         SUMMARY OF THE INVENTION  
         [0007]    A catheter system for delivering fluid to a selected site within an organism comprises a pump for delivering the fluid and a catheter coupled to the pump. The catheter comprises a first tubular portion that has a generally cylindrical lumen of a first internal diameter and is composed of a relatively impermeable material. A second tubular portion that has an open end is disposed within the lumen and a closed distal end is disposed without the lumen. The second tubular portion is composed of a flexible, porous material having a preselected microporosity that is operable to permit fluid to flow from the catheter into the organism. The second tubular portion is selectively moveable with respect to the first tubular portion.  
           [0008]    Alternatively, a catheter for delivering fluid to a selected site within an organism comprises a first tubular portion that has a generally cylindrical lumen of a first internal diameter and is composed of a relatively impermeable material. A second tubular portion that has an open end is disposed within the lumen and a closed distal end is disposed without the lumen. The second tubular portion is composed of a flexible, porous material that has a preselected microporosity that is operable to permit fluid to flow from the catheter into the organism. The second tubular portion is selectively moveable with respect to the first tubular portion. 
       
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       [0009]    Advantages of the invention will become apparent upon reading the following detailed description and references to the drawings in which:  
         [0010]    [0010]FIG. 1 depicts a preferred embodiment of the catheter system showing one possible implantation in a human body.  
         [0011]    [0011]FIG. 1A depicts a schematic representation of a human brain showing placement of the tip of the catheter of the catheter system in the putamen.  
         [0012]    [0012]FIG. 2 is a schematic depiction of the putamen region of the human brain.  
         [0013]    [0013]FIG. 3 depicts a preferred embodiment of the catheter system with the catheter and catheter tip illustrated in a sectional view.  
         [0014]    [0014]FIG. 4 depicts an alternate embodiment of the catheter system wherein the distal end of the catheter contains a radiographic marker, illustrated in partial sectional view.  
         [0015]    [0015]FIG. 5 depicts a portion of a preferred embodiment of the catheter system showing an alternate implantation in a human body, illustrated in a partial sectional view. 
     
    
     DESCRIPTION OF THE PREFERRED EMBODIMENTS  
       [0016]    [0016]FIG. 1 depicts a preferred embodiment of the catheter system  10  in one possible medical application, an intracerebral placement, wherein the system  10  provides infusion of a neurological agent directly into the brain  12  in a human body  14 . The catheter system  10  comprises a catheter  16  which has one end  18  coupled to an implanted infusion pump (IIP)  20  and a free distal end  22  for insertion into an organism, in this case, a human body  14 . It should be understood that the system  10  could also be used on non-human animals. A catheter tip  24  is disposed at the extreme end of the distal end  22 . The tip  24  has a rounded leading exterior surface to minimize tissue disruption during insertion.  
         [0017]    In the medical application portrayed in FIGS. 1 and 1A, the distal end  22  is intracerebrally disposed so that the tip  24  projects into the putamen  26  of the brain  12 . FIG. 2 is an enlarged schematic view of a portion of the interior of the brain  12 , showing the putamen  26  in relation to the pallidum  28  the caudate  30  the thalamus  32 , and the insula  34 , and showing schematically the placement of the tip  24 . In the medical application depicted in FIGS. 1 and 2, the catheter tip  24  is positioned into the putamen  26  for retrograde access to the dopaminergic neurons contained within the retrorubral nucleus, substantia nigra, and ventral tegmentum.  
         [0018]    The distal end  22  is surgically implanted in the brain  12  using well known stereotactic placement techniques and the catheter  16  is subsequently tunneled subcutaneously through the body  14  to the location in the body  14  where the IIP  20  will be implanted. The IIP  20  is ordinarily surgically implanted subcutaneously in the pectoral or abdominal region of the body  14 . The IIP  20  may be any of a number of commercially available implantable infusion pumps such as, for example, the Syncromed pump, model 8611H, manufactured by Medtronic, Inc., Minneapolis, Minn. While an implantable IIP  20  is depicted, it should be understood to those skilled in the art that the device used to deliver agent to the catheter  16  may be either implanted or extracorporeal.  
         [0019]    The detailed structure of the catheter system  10  may be understood by reference to FIG. 3, which depicts a preferred embodiment of the catheter system  10  with the catheter  16  and the distal end  22  shown in an enlarged half section. The size of the catheter  16  and the distal end  22  are highly exaggerated for ease of illustration of the structure thereof and the full length of the catheter  16  is not shown for simplicity of illustration. The end  18  of the catheter  16  is coupled to the pump connector  36 . The connection between the catheter  16  and the pump connector  36  is shown schematically in FIG. 3. It should be understood that the actual type of connection between the pump connector  36  and the catheter  16  will vary depending upon the particular type of IIP  20  utilized.  
         [0020]    The catheter  16  comprises an elongated tubular portion  38  that extends from the pump coupling  36  and terminates in the distal end  22  and the tip  24 . As noted above, the catheter tip  24  has a generally rounded leading exterior surface  40  to minimize tissue disruption during insertion. The tubular portion  38  has an externally tapered end surface  42  to again minimize tissue disruption during insertion.  
         [0021]    The catheter tip  24  has a generally tubular shape and is designed to fit snugly within the lumen  44  of the tubular portion  30 . The catheter tip  24  has a lumen  45  to receive agent from the catheter lumen  44 . The catheter lumen  44  and the external diameter of the catheter tip  24  should be sized so that there is a zero tolerance therebetween. A snug fit is desirable to both maintain the position of the catheter tip  24  in relation to the tubular portion  38  and to discourage seepage of agent between the interface of the exterior of the catheter tip  24  and the interior surface of the tubular portion  38 . However, as discussed more fully below, under certain conditions, the catheter  16  may be customized by moving the catheter tip  24  in relation to the tubular portion  38 .  
         [0022]    The catheter tip  24  is preferably composed of a porous material such as polysulfone hollow fiber, manufactured by Amicon, although polyethylene, polyamides, polypropylene and expanded polytetrafluorethylene (ePTFE) are also suitable. The catheter tip  24  is preferably porous along its entire length to enable agent to flow into the body  14 . The preferred pore size is approximately less than or equal to 0.22 microns. It is preferred that the maximum pore size be less than or equal to approximately 0.22 microns to prevent any derelict bacterial agents that may be present inside the catheter  16  from entering into the body  14 . Furthermore, at larger pore sizes, there is the potential for tissue in-growth that may restrict the flow of agents out of the catheter tip  24 . By making the entire length of the catheter tip  24  porous, a more uniform volume distribution of agent is provided. Unlike an existing catheter tip that has a single elution hole or a few elution holes, the catheter tip  24  dispenses agent in a nearly 360 degree pattern along the entire length of the catheter tip  24  that is exposed to the parenchymal target, represented in FIG. 3 by the length X. Throughout this disclosure, the length of the portion of catheter tip  24  that is exposed to the parenchymal target is represented by X.  
         [0023]    Length X may be custom selected by the physician at the time of insertion. To enable the physician to customize length X, the tubular portion  38  is composed of a material that will expand in response to an external stimulus such as heat or a chemical solvent. When the tubular portion  38  expands in response to the external stimulus, the snug fit between the catheter tip  24  and the tubular portion  38  is relieved, and the physician may slide the catheter tip  24  with respect to the tubular portion  38  by hand to achieve the desired length X. The material from which the tubular portion  38  is composed, is selected so that when the external stimulus is removed, the tubular portion  38  returns to its ordinary shape, thereby reestablishing the near zero tolerance fit between the tubular portion  38  and the catheter tip  24 .  
         [0024]    In one preferred embodiment, the tubular portion  38  is composed of a relatively impermeable material such as polyacrylonitrile. Polyacrylonitrile will expand in response to an external stimuli such as heat, and will return to its original shape upon cooling.  
         [0025]    In an alternate preferred embodiment, the tubular portion  38  is composed of enhanced tear resistant silicone elastomer or polyurethane, which, when exposed to an external stimulus such as a chemical solvent like freon, will expand. When the solvent evaporates, the silicone elastomer or polyurethane will return to its original shape.  
         [0026]    Whether a heat sensitive or solvent sensitive material is used, the tubular portion  38  should be biocompatible and sufficiently flexible to facilitate insertion. A durometer shore value of 80 is preferred.  
         [0027]    In an alternate embodiment of the invention, length X may be set at the time of manufacture. In this embodiment, catheters  16  are manufactured having a variety of lengths X for the portion of catheter tip  24  that will be exposed to the parenchymal target. Lengths X are preselected to produce catheters  16  for predetermined applications. Once the length X has been determined for a catheter  16 , the length X may be established on catheter tip  24  and catheter tip  24  may be attached to tubular portion  38  as described above.  
         [0028]    The catheter system  10  is suitable for delivering a variety of agents such as the cytostatic drugs Methotrexate and Cytosine Arabinosibe and the antiseizure drug Felbamate, nerve growth factors such as glial derived neurotrophic factor (GDNF), neurotransmitters such as dopamine, acetylcholine, and antisense oligomcleotides. In selecting the catheter system  10  for use with a particular drug or agent, care should be taken to ensure that the particular agent will be compatible with the material from which the tubular portion  38  is composed.  
         [0029]    [0029]FIG. 4 depicts an alternate preferred embodiment of the distal end  22  of the catheter  16 , wherein a radiographic marker  46  is coupled to the tip  24 . The radiographic marker  46  renders at least a portion of the tip  24  opaque to x-rays, enabling the tip  24  to be observed during fluoroscopy or via x-ray to facilitate placement of the distal end  22  and the tip  24 . In a preferred embodiment, the radiographic marker  46  comprises a semispherical portion  48  that has a cylindrical nipple  50  emanating away therefrom. The semispherical portion  48  provides a rounded profile for minimizing tissue disruption during insertion. The cylindrical nipple  50  is sized to fit snugly within the lumen  45  and be held in place via a suitable biocompatible adhesive, such as a biocompatible medical silicone adhesive or a medical urethane adhesive. In a preferred embodiment, the radiographic marker  46  comprises tantalum powder dispersed in a matrix composed of a biocompatible adhesive, such as the ones discussed above. The preferred ratio of tantalum to adhesive is 3 to 2. Ordinarily, the radiographic marker  46  will be premolded prior to insertion into the lumen  45 . After the radiographic marker  46  has been inserted into the lumen  45 , a thin coating of the same biocompatible adhesive is preferably applied to the exterior of the semispherical portion  48 . Other materials may also be suitable for the radiographic marker  46 , such as barium or platinum materials.  
         [0030]    Alternatively, the radiographic marker  46  may be composed of a material that is compatible to nuclear magnetic resonance imaging (MRI) to enable the tip  24  to be detected during an MRI scan. A preferred material for the radiographic marker  46  in an MRI context is platinum, though barium, tantalum, and similar materials are also suitable. Regardless of whether radiography or MRI is being utilized, the goal of providing a radiographic marker  46  is to enable the operator to accurately detect the precise location of the tip  24  to facilitate placement and later verification of the integrity and position of the catheter system  10 .  
         [0031]    Alternatively, the radiographic marker  46  may be composed of a material that has sufficient radio density for visualization during radiologic procedures, but in powdered form that is dispersed in the catheter tip  24  at the time the catheter tip  24  is molded.  
         [0032]    The following example illustrates the customization feature of the catheter system  10 . Assume, for the purposes of this illustration, that in the medical application depicted in FIGS. 1 and 2, the patient is suffering from Parkinson&#39;s disease and it is desired to place the catheter tip  24  in the putamen  26  of the brain  12  to deliver GDNF in a dosage of approximately 1.0 μl/h. As an initial step, the structural size of the putamen  26  can be determined by MRI. Once the structural size of the putamen  26  is determined, the physician can stimulate the tubular portion  38  to expand using the techniques discussed above and, by hand, slide the catheter tip  24  relative to the tubular portion  38  to achieve a length X that will provide maximal diffusion of the agent throughout the putamen  26  for accessing the different dopaminergic pathways. The distal end  22  and the catheter tip  24  are then positioned using known stereotactic techniques and the remainder of the catheter system  10  is placed as discussed above.  
         [0033]    An alternate medical application is depicted in FIG. 5. FIG. 5 shows the catheter tip  24  inserted into a malignant mass  52 . Assume for the purposes of this illustration that the length of the mass  52 , represented by Y, is determined via a preoperative MRI. To increase the chances that a cytostatic drug such as Methotrexate will successfully destroy the malignant mass  52 , it is desirable that the cytostatic agent be diffused to as much of the structure of the malignant mass  52  as possible. Therefore, it is desirable for the physician to be able to select the length of the catheter tip  24 , represented by the length X, to approximate the length Y as closely as possible. As noted above, the structural size of the malignant mass  52  may be determined by a preoperative MRI. Once the structural size of the mass  52  is known, the physician can then adjust the length X using the above discussed techniques to match the length X to the length Y as closely as possible, thereby maximizing the area of the mass  52  exposed to the cytostatic agent.  
         [0034]    Many modifications and variations may be made in the techniques and structures described and illustrated herein without departing from the spirit and scope of the present invention. For example, the system could be used to infuse a cytostatic agent into a malignant mass located in a variety of places in the body or infuse into a nerve growth factor into the intrathecal space of the spinal column. Accordingly, the techniques and structures described and illustrated herein should be understood to be illustrative only and not limiting upon the scope of the present invention.

Technology Classification (CPC): 8