Abstract:
An infusion catheter for delivering drugs or other agents to selected sites in an organism, such as a human. In an alternate embodiment, a catheter system is disclosed having an infusion catheter and a pump that may be implanted or disposed outside the organism. In either embodiment, the free end of the catheter bears a rounded tip that has at least one elution hole for discharging an agent or drug to a selected site. The catheter has a tubular inner liner that is integral with the tip. The inner liner and tip are formed from a drug compatible polymeric material that is relatively nonporous and unreactive with the agent to be infused. A biocompatible flexible elastomeric tubular jacket surrounds the inner liner and a portion of the tip excluding that portion containing the elution hole or holes. Since the agent flowing in the catheter is isolated from the jacket while flowing through the catheter, and since the inner liner is relatively nonporous and unreactive with the agent to be used, the agent is prevented from diffusing out of the catheter, adsorbing to the surface of the biocompatible jacket, reacting adversely with the jacket material or becoming exposed to substances diffusing through the jacket.

Description:
This application is a Continuation of application Ser. No. 08/924,343 filed Sep. 5, 1997 now abandoned, which is a Divisional application of Ser. No. 08/385,498 filed Feb. 8, 1995 now U.S. Pat. No. 5,702,372. 
    
    
     BACKGROUND OF THE INVENTION 
     1. Field of the Invention 
     In general, this invention relates to infusion catheters. More specifically, this invention relates to an infusion catheter for delivering fluid into an organism where the catheter has a non-reactive lining and tip, surrounded partially by a flexible silicone-type material. 
     2. Description of the Related Art 
     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. 
     In applications where the quantity of delivered drug is relatively minute and must be carefully tailored, it may be critical that the delivered drug be non-reactive with the material of the catheter. Non-reactive means that the delivered drug flows from the IIP to the delivery site without adhering to, diffusing through, or otherwise chemically reacting with, the catheter itself. Standard delivery catheters normally comprise a single tubular member and are composed of a flexible elastomeric material, typically silicone, that is biocompatible with the animal body into which the desired agent is delivered. A more recent design includes an internal lining that is more compatible with the agent desired to be delivered while maintaining the biocompatibility of the external catheter sheath. 
     FIG. 1 depicts a portion of a typical prior art implantable catheter  10  with a drug compatible internal lining. Catheter  10  comprises a tubular jacket or sheath  12  that is coupled at one end to the IIP (not shown) and terminates at its other end in a rounded tip  14 . One or more elution holes  16  are disposed in sheath  12  proximate the rounded tip  14 . Sheath  12  is ordinarily tubular and manufactured from a flexible biocompatible elastomeric material such as silicone. It is desirable for sheath  12  to be both flexible and biocompatible. A flexible material makes catheter  10  easier to conform to the various curved passageways in the body during placement and use. The biocompatibility of sheath  12  will enable catheter  10  to remain in the body for prolonged periods of time without prompting an immune system response. The interior of sheath  12  is lined with a tubular lining  18  which is coextensive with sheath  12  from the IIP (not shown) to a sheath/lining seal point  20 . Catheter  10  may not be manufactured solely of this material because the material may often be too rigid to make a usable catheter for actual use. Sheath/lining seal point  20  is ordinarily located a few millimeters from the elution holes  16 . The lining  18  is ordinarily fabricated from a material that will be non-reactive with the delivered agent such as polyethylene, polyurethane or polytetraflouroethylene (PTFE) or TEFLON® as it is commonly known in the trade. 
     If the delivered drug is sensitive to the material of sheath  12 , the delivered drug may either be adsorbed by sheath  12 , diffuse across sheath  12  or react chemically with sheath  12  or with substances diffusing through sheath  12  from outside catheter  10 . For example, if the delivered drug is adsorbed by sheath  12 , the amount of delivered drug may be significantly less than the required dosage. Similarly, if undesirable agents diffuse through sheath  12  and react with the delivered drug, the amount and efficacy of the delivered drug may be compromised. Because the seal point  20  is directly exposed to the delivered drug, there is the potential for undesirable seepage of the drug between sheath  12  and lining  18 . 
     Many drugs or agents exhibit some detrimental sensitivity to silicone or drugs or agents that may diffuse through a silicone sheath. Insulin presents one example. In certain circumstances, carbon dioxide may diffuse through a silicone sheath. If insulin is flowing through catheter  10 , carbon dioxide from outside catheter  10  may diffuse through sheath  12  and react with the buffer in the insulin solution, causing a pH change in the insulin solution. As a result, the insulin buffer breaks down, causing degradation and polymerization of the insulin to occur. In some applications involving the chronic dispensing of insulin, suitable buffers to counteract the pH changes brought on by CO 2  diffusion are simply not feasible. 
     Another example of drugs sensitive to silicone is presented by neurotrophic factors such as nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), ciliary neurotrophic factor (CNTF), or glial-derived neurotrophic factor (GDNF), currently being studied as potential therapies for amyotrophic lateral sclerosis, Parkinson&#39;s Disease, or other neurological disorders. The particular neurotrophic factor may either be adsorbed by the interior surface of the silicone sheath  12 , or alternatively react with the silicone sheath  12  and degrade into secondary components. The dosage levels for such neurotrophic factors may be so small that an appreciable loss or degradation of the delivered agent will adversely effect the agent&#39;s ability to satisfactorily treat the patient. 
     In the prior art catheter  10  shown in FIG. 1, extension of the lining  18  past the elution holes  16  has proved to be impractical, since it has been difficult, if not impossible, to adequately seal the interfaces between sheath  12  and lining  18  that are in fluid communication with the elution holes  16 . The present invention is directed to solving one or more of the above-noted problems. 
     SUMMARY OF THE INVENTION 
     In one aspect of the present invention a catheter is provided. The catheter includes an elongated inner liner that has an open first end, a distal end that has at least one opening, and a first length. An elongated jacket is disposed about the inner liner and has a second length less than the first length whereby fluid flowing in the inner liner is isolated from the jacket. The problems associated with the infused drug or agent being sensitive to the material of the jacket are eliminated by making the inner liner completely coextensive with the interior of the jacket. 
     In another aspect of the present invention, a catheter system for delivering agents, drugs or other fluids to a selected site within an organism is provided. The system has a catheter and a pump coupled to the catheter for delivering the fluid to the catheter. The catheter is the novel catheter described above and in more detail hereafter with the catheter additionally being in fluid communication with the pump. The jacket, disposed about the inner liner, extends from the pump to the distal end of the catheter and is isolated from fluid flowing in the inner liner. 
     The invention will now be described in detail with reference to the accompanying drawings where like elements, wherever referred to, are referred to with like reference numbers. 
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS 
     Advantages of the invention will become apparent upon reading the following detailed description and references to the drawings in which: 
     FIG. 1 is a sectional view of the distal end of a prior art catheter. 
     FIG. 2 is a section view of a preferred embodiment of the distal end of the catheter. 
     FIG. 3 depicts a sectional view of an alternate preferred embodiment of the distal end of the catheter. 
     FIG. 4 depicts a partial sectional view of a preferred embodiment of the catheter of FIG. 2 with a radiographic marker tip. 
     FIG. 5 depicts a preferred embodiment of the catheter system showing one possible implantation in a human body. 
     FIG. 6 is a sectional view of a typical spinal column. 
     FIG. 7 depicts a preferred embodiment of the catheter system showing an alternate implantation in a human body. 
    
    
     DESCRIPTION OF THE PREFERRED EMBODIMENT 
     A catheter system  22  is disclosed that may be understood by reference to the Figures, particularly FIG.  2 . Catheter system  22  includes a catheter  27  and an implantable infusion pump (IIP)  29 . Catheter  27  has a proximal end  28  and a distal end  30 . FIG. 2 depicts a preferred embodiment of catheter system  22  where catheter  27  and distal end  30  are shown in an enlarged sectional view and with IIP  29  shown in a partial cut-away view. The size of catheter  27  and distal end  30  are highly exaggerated for ease of illustration of the structure thereof and the full length of catheter  27  is not shown for simplicity of illustration. Proximal end  28  of catheter  27  is coupled to a pump connector  40  that is in fluid communication with IIP  29 . The connection between catheter  27  and pump connector  40  is shown schematically in FIG.  2 . It should be understood that the actual type of connection between pump connector  40  and catheter  27  will vary depending upon the particular type of IIP utilized. 
     Catheter  27  includes an elongated inner liner  41  that extends from pump coupling  40  and terminates at distal end  30  in a tip  31 . Liner  41  forms a lumen  42  through which the selected agent, drug or other fluid is delivered to the patient at tip  31 . Liner  41  and tip  31  are preferably integrally molded, though, as discussed below, they may be fabricated as separate units and later coupled. Tip  31  has a generally rounded end  44  to minimize tissue disruption during insertion. 
     At least one elution hole  46  is formed through tip  31 . In the preferred embodiment, one to several elution holes  46   a-i  extend from lumen  42  of catheter  27  through the walls of tip  31  to enable fluid to flow from lumen  42  through elution holes  46   a-i  and into the particular site within the body. There are three elution holes that are collinear with holes  46   g-i  that are not shown because distal end  30  is shown in half section. Elution holes  46   a-i  are depicted as being disposed approximately normal to the longitudinal axis  50  of catheter  27 . However, it should be understood that elution holes  46   a-i  may be disposed at other angular geometries as well. It should be further understood that, while tip  31  must have at least one elution hole to deliver an agent to the body, the actual number of holes will depend upon the agent, drug or fluid to be delivered, and the particular delivery site within the body. In a preferred embodiment, elution holes  46   a-i  are cylindrical and have a diameter of approximately 0.016″. Because it is possible to have a difference in external diameters of tip  31  and inner liner  41 , there may be a peripheral shoulder  52  formed at the junction between inner liner  41  and tip  31 . 
     It is desirable that inner liner  41  be relatively flexible, compatible, and generally non-reactive with the particular agent, drug or fluid to be infused. Catheter  27  may not be manufactured solely of this lining material because the material may often be too rigid to make a usable catheter for actual use. Rigidity problems that may be inherent in the material of inner liner  41  are not an issue to the overall stiffness of catheter  27  if only tip  31  and the relatively thin inner liner  41  are made from the rigid material. While the particular material for inner liner  41  used will depend on the agent, drug or other fluid infused, some possible materials are nonporous polyethylene, polytetraflouroethylene (PTFE) or TEFLON® as it is commonly known in the trade, and polyurethane. It is important that the material used to form inner liner  41  be relatively nonporous to avoid the potential of contaminants, such as CO 2 , diffusing from the organism into lumen  42 . 
     An elongated jacket or jacket  54  surrounds inner liner  41 . Jacket  54  extends from coupling  40  to shoulder  52  on tip  31 . There is preferably a relatively tight tolerance between the external diameter of inner liner  41  and the internal diameter of jacket  54 . In a preferred embodiment, the tolerance is approximately 0.005″. 
     Jacket  54  is preferably formed of a flexible biocompatible substance that is relatively non-porous. The biocompatible substance utilized for making up jacket  54  may include silicone, barium loaded silicone, polyurethane, polyether urethane, polyether urethane urea, styrene butadiene rubber and other related flexible biocompatible polymers. Presently, silicone is the preferred material for jacket  54 . 
     Jacket  54  is secured to inner liner  41  by a suitable adhesive applied to the interface  56  between the outer surface of inner liner  41  and the inner surface of jacket  54 . The adhesive is applied along the entire length of interface  56  as well as shoulder  52  and the portion of jacket  54  abutting shoulder  52 . The adhesive is preferably a biocompatible medical silicone adhesive suitable to bond the silicone elastomer to the inner liner. Other types of adhesives are suitable as well such as, for example, medical grade urethane. Ultimately, the particular type of adhesive used will depend upon the materials used to form jacket  54  and inner liner  41 . 
     In the embodiment of the invention shown in FIG. 2, the drug delivered through catheter  27  never contacts the adhesive that binds liner  41  to jacket  54  since the adhesive is “sealed” between inner liner  41  and jacket  54 . Further, in this embodiment, a continuous surface is provided along the entire length of inner lumen  42  of catheter  27 . As a result, there are no crevices, cracks, breaks or discontinuities along inner lumen  42  for the agent, drug or fluid being delivered to invade. If the agent, drug or fluid were to invade a crack or similar break in inner liner  41 , the agent, drug or fluid could be contaminated by either the adhesive that binds inner liner  41  to jacket  54  or by gases or other materials that might diffuse through jacket  54  from outside jacket  54 . The contaminated agent, drug or other fluid would then contaminate the remaining agent, drug or fluid in lumen  42 . 
     The actual thickness of the walls of inner liner  41  and jacket  54  will depend upon the particular environment where the catheter will be used. Ordinarily, the wall thickness of inner liner  41  will be relatively less than the wall thickness of jacket  54 . However, if inner liner  41  is composed of a sufficiently flexible material, it may have a wall thickness relatively larger than the wall thickness of jacket  54 . 
     FIG. 3 depicts an alternate preferred embodiment of distal end  30 . In this embodiment, tip  31  is not molded integrally with inner liner  41 , but rather is formed as a separate piece that is fixed to inner liner  41  and jacket  54  by a suitable biocompatible adhesive. The agent, drug or other fluid still exits tip  31  through orifices  46  located near the distal end  30  of tip  31 . Tip  31  has a cylindrical nipple portion  58  that has an outer peripheral surface  60  with approximately the same external diameter as the external diameter of inner liner  41 . Nipple portion  58  also has a peripheral shoulder  62  with an external diameter greater than the external diameter of outer peripheral surface  60  and a front peripheral surface  64  that extends at a right angle to outer peripheral surface  60 . A tip lumen  76  extends from front peripheral portion  64  through nipple portion  58  to orifices  46 . Tip lumen  76  has an inner diameter equal to the inner diameter of inner liner  41 . 
     When tip  31  is mated with inner liner  41  and jacket  54 , front peripheral surface  64  abuts peripheral surface  66  on inner liner  41  and peripheral shoulder  62  abuts peripheral surface  68  on jacket  54 . A continuous lumen is formed from the proximal end of inner liner  41  to orifices  46 . Because orifices  46  pass through the material of tip  31  that is the same material as inner liner  41  and because this material is non-reactive to the-agent, drug or fluid passing through catheter  27 , the agent, drug or other fluid contacts only the non-reactive material lining of catheter  27 . 
     To secure tip  31  to the rest of catheter  27 , a suitable biocompatible adhesive, such as the type disclosed above, is applied to front peripheral surface  64 , outer surface  60 , and peripheral shoulder  62  before the parts are joined. 
     Because jacket  54  is physically isolated from lumen  42  of catheter  27  by integrally formed or coupled inner liner  41  and tip  31 , agents, drugs or other fluids passing through lumen  42  that may be sensitive to the material of jacket  54  are not exposed to jacket  54  while flowing through lumen  42  and ultimately discharging out of elution holes  46   a-i . As a result, the infused agent, drug or other fluid is exposed only to the agent, drug or other fluid non-reactive material of inner liner  41  and tip  31 . Furthermore, there is no joint or seal point between inner liner  41  and jacket  54  that is exposed to the agent, drug or fluid flowing through catheter  27  that might lead to undesirable seepage through jacket  54 . 
     Catheter  27  is ordinarily fabricated in the following two fashions depending on whether tip  31  is integrally molded with inner liner  41  or not. If tip  31  is integrally molded with inner liner  41 , inner liner  41  is extruded with an integral tip  31 . Next, jacket  54  is extruded. Tip  31  may then be molded or otherwise manipulated to the desired configuration. A suitable biocompatible adhesive is applied to the outer surface of inner liner  41  and jacket  54  is slid over inner liner  41 . 
     If tip  31  is not to be integrally molded with inner liner  41 , inner liner  41  is extruded without an integral tip  31 . Tip  31  is then separately extruded, molded or otherwise formed. If tip  31  is extruded, tip  31  may then be molded to the desired configuration. Next, jacket  54  is extruded. A suitable biocompatible adhesive is applied to the outer surface of inner liner  41  and jacket  54  is slid over inner liner  41 . The final step entails coupling tip  31  to inner liner  41  and jacket  54  using a suitable biocompatible adhesive. The suitable biocompatible adhesive is applied to front peripheral surface  64 , outer surface  60 , and peripheral shoulder  62  before these parts are joined with jacket  54  and inner liner  41 . 
     FIG. 4 depicts an alternate preferred embodiment of distal end  30  of catheter  27  where a radiographic marker  70  is coupled to tip  31 . Radiographic marker  70  renders at least a portion of tip  31  opaque to x-rays, enabling tip  31  to be observed during fluoroscopy or via x-ray to facilitate placement of distal end  30  and tip  31 . In a preferred embodiment, radiographic marker  70  comprises a semispherical portion  72  that has a cylindrical nipple  74  emanating away therefrom. Semispherical portion  72  provides a rounded profile for minimizing tissue disruption during insertion. Cylindrical nipple  74  is sized to fit snugly within lumen  42  and be held in place via a suitable biocompatible adhesive, such as those discussed above. 
     In a preferred embodiment, radiographic marker  70  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 1. Ordinarily, radiographic marker  70  will be premolded prior to insertion into lumen  42 . After radiographic marker  70  has been inserted into lumen  42 , a thin coating of the same biocompatible adhesive is preferably applied to the exterior of semispherical portion  72 . Other materials may also be suitable for the radiographic marker  70 , such as barium or similar materials. 
     Alternatively, radiographic marker  70  may be composed of a material that is sensitive to nuclear magnetic resonance imaging (MRI) to enable tip  31  to be detected during an MRI scan. A preferred material for radiographic marker  70  in this embodiment is platinum, although tantalum, cobalt, and similar materials are also suitable. Regardless of whether radiography or MRI is being utilized, the goal of providing a radiographic marker  70  is to enable the operator to accurately detect the precise location of tip  31  to facilitate placement and later verification of the integrity and position of catheter  27 . 
     FIGS. 5 and 6 depict an application of catheter system  22  for infusing neurological or analgesic agents, drugs or other fluids directly into the spinal column of the body  26 . FIG. 5 shows the general placement of catheter system  22  in relation to the body  26 . FIG. 6 is a cross-sectional view of the spinal column  34  of the body  26  that shows some potential infusion sites. In FIGS. 5 and 6, distal end  30  and tip  31  are obscured by vertebrae  36 . An Implantable Infusion Pump (IIP)  29  is surgically implanted subcutaneously in the abdominal region of the body  26 . Catheter  27  is tunnelled subcutaneously and the distal end  30  and tip  31  are positioned between vertebrae  36  to infuse the agent, drug or other fluid into either the epidural space  37  or the intrathecal space  38 , depending on whether distal end  30  and tip  31  are passed through the arachnoid membrane  39 . It should be understood that the particular placement of distal end  30  and tip  31  along the spinal column will depend on where specifically the agents, drugs or other fluids are desired to be delivered. 
     FIG. 7 depicts a preferred embodiment of the catheter system  22  in another possible medical application, an intracerebroventricular placement, wherein catheter system  22  provides infusion of neurological agents or drugs directly into the brain  24  in a human body  26 . Catheter system  22  comprises a catheter  27  which has a proximal end  28  coupled to an IIP  29  and a free distal end  30  for insertion into an organism, in this case, a human body  26 . It should be understood that catheter system  22  could be also be used on non-human animals. 
     A catheter tip  31  is disposed at the extreme end of distal end  30 . Tip  31  has a rounded leading exterior surface to minimize disruption during insertion. In the medical application portrayed in FIG. 7, distal end  30  is intracerebrally disposed so that tip  31  projects into the cerebral ventricle  32  of the brain  24 . Distal end  30  is surgically implanted in the brain  24  and catheter  27  is subsequently tunnelled subcutaneously through the body  26  to the location in the body  26  where the IIP  29  will be implanted. 
     IIP  29  is ordinarily surgically implanted subcutaneously in the abdominal region of the body  26 . IIP  29  may be any of a number of commercially available implantable infusion pumps such as, for example, the Synchromed pump, Model 8615, manufactured by Medtronic, Inc., Minneapolis, Minn. While an implantable IIP  29  is depicted, it should be understood to those skilled in the art that the device used to deliver agent to catheter  27  may be either implanted or extracorporeal. 
     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. 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.