Abstract:
A guiding catheter for placement in a patient&#39;s vessel. The catheter includes an elongate hollow shaft with open proximal and distal ends and a bore extending there through. The catheter shaft includes an inner liner, a metallic reinforcement layer overlying the inner liner, and a unitary outer jacket covering the reinforcement layer. A distal portion of the outer jacket of the catheter shaft is chemically softened to be more flexible than a proximal portion of the outer jacket. A connector fitting is mounted at the proximal end of the shaft in communication with the bore and a distal tip is attached to the distal end of the shaft. A method of manufacturing the guiding catheter is also disclosed.

Description:
FIELD OF THE INVENTION  
       [0001]     The present invention relates generally to an intraluminal guiding catheter used in a medical procedure, and more particularly, to a guiding catheter with a chemically softened distal portion and a method of making same.  
       BACKGROUND OF THE INVENTION  
       [0002]     A stenosis, or narrowing of a blood vessel such as a coronary artery may comprise a hard, calcified substance and/or a softer thrombus material. There have been numerous therapeutic procedures developed for the treatment of stenosis in a coronary artery. One of the better-known procedures is percutaneous transluminal coronary angioplasty (PTCA). According to this procedure, the narrowing in the artery can be reduced by positioning a dilatation balloon across the stenosis and inflating the balloon to re-establish acceptable blood flow through the artery. Additional therapeutic procedures may include stent deployment, atherectomy, and thrombectomy, which are well known and have proven effective in the treatment of such stenotic lesions.  
         [0003]     The therapeutic procedure starts with the introduction of a guiding catheter into the cardiovascular system from a convenient vascular access location, such as through the femoral artery in the groin area or other locations in the arm or neck. The guiding catheter is advanced through the arteries until its distal end is located near the stenosis that is targeted for treatment. During PTCA, for example, the distal end of the guiding catheter is typically inserted only into the ostium, or origin of the coronary artery. A guidewire is advanced through a central bore in the guiding catheter and positioned across the stenosis. An interventional therapy device, such as balloon dilatation catheter, is then slid over the guidewire until the dilatation balloon is properly positioned across the stenosis. The balloon is inflated to dilate the artery. To help prevent the artery from re-closing, a physician can implant a stent inside the artery. The stent is usually delivered to the artery in a compressed shape on a stent delivery catheter and expanded by a balloon to a larger diameter for implantation against the arterial wall.  
         [0004]     In order for the physician to place the guiding catheter at the correct location in the vessel, the physician must apply longitudinal and rotational forces. In order for the guiding catheter to transmit these forces from the proximal end to the distal end, the catheter must be rigid enough to push through the blood vessel, a property sometimes called pushability, but yet flexible enough to navigate the bends in the blood vessel. The guiding catheter must also have sufficient torsional stiffness to transmit the applied torque, a property sometimes called torqueability. To accomplish this balance between longitudinal rigidity, torsional stiffness, and flexibility, there is often a support member added to the catheter shaft. This support member is often comprised of a reinforcing braid or coil embedded in the shaft. This support wire is often embedded in the shaft between the two layers of tubing that comprise the shaft.  
         [0005]     Using the femoral artery approach in a PTCA procedure, a guiding catheter is passed upward through the aorta, over the aortic arch, and down to the ostium of the coronary artery to be treated. It is preferable the catheter have a soft tip or flexible section for engaging the ostium of the selected branch vessel. Therefore, it is advantageous to have the proximal section be rigid to transmit the forces applied, but to have the distal end more flexible to allow for better placement of the guiding catheter. The need for this combination of performance features makes it desirable for a guiding catheter shaft to have variable flexibility along the length of the catheter. More specifically, it is desirable for a guiding catheter to have increased flexibility near the distal end of the catheter shaft and greater stiffness near the proximal end.  
         [0006]     One approach used to balance the need for pushability and torqueability while maintaining adequate flexibility has been to manufacture a guiding catheter that has two or more discrete tubular portions over its length, each having different performance characteristics. For example, a relatively flexible distal section may be connected to a relatively rigid proximal section. When a guiding catheter is formed from two or more discrete tubular members, it is often necessary to form a bond between the distal end of one tubular member and the proximal end of another tubular member. This method requires substantial manufacturing steps to assemble the various sections and makes it difficult to manufacture the entire shaft utilizing coextrusion technology. Further, the shaft design may include relatively abrupt changes in flexibility at material changes.  
         [0007]     Various approaches for achieving variable stiffness of the guiding catheter shaft include varying the braid pitch of the reinforcing layer and/or by varying the properties of materials used in construction, such as by removing a selected distal portion of an outer tubular layer of the catheter shaft and replacing that distal portion with one or more sections of more flexible tubing. A unitary catheter shaft arrangement with variable stiffness is also known that incorporates one or more layers of a material that is selectively curable by ultraviolet light, wherein selected portions of the catheter shaft are subjected to radiation to cure the material and thereby increase the stiffness of the shaft in the treated area.  
         [0008]     However a need still exists for guiding catheter shafts that can be easily manufactured, such as by extrusion, and yet are capable of having a variable stiffness without assembling multiple components of the shaft or attending to difficulties inherent in irradiated variable-stiffness catheters, such as the limitations in the choice of catheter materials and in the control of the final catheter properties.  
       BRIEF SUMMARY OF THE INVENTION  
       [0009]     An embodiment of the present invention is a guiding catheter for placement in a patient&#39;s vessels, such as the vasculature. The catheter includes an elongate hollow shaft with open proximal and distal ends and a bore extending there through. The shaft includes an inner liner, a reinforcement layer overlying the inner liner, and a unitary outer jacket covering the reinforcement layer. In various embodiments, a distal portion of the outer jacket and/or inner liner of the shaft are chemically softened to be more flexible than a proximal portion of the outer jacket and/or inner liner. In various embodiments of the present invention, a connector fitting is mounted at the proximal end of the shaft in communication with the bore, and/or a soft distal tip is attached to the distal end of the shaft.  
         [0010]     In another embodiment, the chemically softened distal portion of the outer jacket of the catheter shaft includes a first softened segment with a first flexibility and a second softened segment with a second flexibility greater than the first flexibility to provide the catheter shaft distal portion with an increase in flexibility as it extends distally.  
         [0011]     Another embodiment of the present invention is a method of manufacturing a guiding catheter with variable flexibility along a length of the catheter shaft. The method includes forming a catheter shaft subassembly by extruding a first material to form a tubular liner, braiding a reinforcement layer over the tubular liner, and extruding a second material over the reinforcement layer to form an outer jacket. A distal portion of the catheter shaft subassembly is then submerged into a softening agent to chemically soften the outer jacket and/or the inner liner to thereby increase the flexibility of the distal portion. After a suitable amount of time, the distal portion of the catheter shaft is removed from the softening agent, and, optionally, wiped or cleaned of any remaining softening agent. In various embodiments of the present invention, a connector fitting is mounted at the proximal end of the shaft in communication with the bore, and/or a soft distal tip is attached to the distal end of the shaft to construct the guiding catheter.  
         [0012]     In another embodiment, the step of removing the distal portion from the softening agent includes removal of a first segment of the distal portion after a first time period, such that a second segment of the distal portion remains submerged until expiration of a second time period. 
     
    
     BRIEF DESCRIPTION OF DRAWINGS  
       [0013]     The foregoing and other features and advantages of the invention will be apparent from the following description of the invention as illustrated in the accompanying drawings. The accompanying drawings, which are incorporated herein and form a part of the specification, further serve to explain the principles of the invention and to enable a person skilled in the pertinent art to make and use the invention. The drawings are not to scale.  
         [0014]      FIG. 1  illustrates a guiding catheter according to an embodiment of the present invention positioned within a patient&#39;s vascular system.  
         [0015]      FIG. 2  illustrates a side view of the guiding catheter of  FIG. 1 .  
         [0016]      FIG. 3  is a transverse cross-sectional view of the guiding catheter of  FIG. 2  taken along line  3 - 3 .  
         [0017]      FIG. 4  is a longitudinal sectional view of a distal portion of the guiding catheter of  FIG. 2 .  
         [0018]      FIG. 5  schematically illustrates a method of manufacturing a guiding catheter in accordance with an embodiment of the present invention.  
         [0019]      FIG. 6  is a graph of load as a function of degrees of deflection for catheter shafts softened in accordance with various embodiments of the present invention.  
         [0020]      FIG. 7  illustrates a distal portion of a catheter shaft softened in accordance with an embodiment of the present invention.  
         [0021]      FIGS. 7A and 7B  illustrate a process of chemically softening the distal portion of the catheter shaft of  FIG. 7 .  
         [0022]      FIG. 8  illustrates the variation in flexibility of the chemically softened distal portion of the catheter shaft of  FIG. 7 . 
     
    
     DETAILED DESCRIPTION OF THE INVENTION  
       [0023]     Specific embodiments of the present invention are now described with reference to the figures, wherein like reference numbers indicate identical or functionally similar elements. The terms “distal” and “proximal” are used in the following description with respect to a position or direction relative to the treating clinician. “Distal” or “distally” are a position distant from or in a direction away from the clinician. “Proximal” and “proximally” are a position near or in a direction toward the clinician.  
         [0024]     The following detailed description is merely exemplary in nature and is not intended to limit the invention or the application and uses of the invention. Although the description of the invention is in the context of treatment of blood vessels such as the coronary, carotid and renal arteries, the invention may also be used in any other body passageways where it is deemed useful. Furthermore, there is no intention to be bound by any expressed or implied theory presented in the preceding technical field, background, brief summary or the following detailed description.  
         [0025]      FIG. 1  illustrates guiding catheter  100  for use with a therapeutic device (not shown) positioned within a patient&#39;s vascular system  150 . In a representative use of the catheter, the clinician inserts a distal end of guiding catheter  100  through introducer sheath  160  into vascular system  150 , typically through a femoral artery in the groin area. Guiding catheter  100  is then advanced through aorta  165  until the distal end of the catheter is located in the ostium of a targeted branch artery  170 . In the example shown, branch artery  170  is a patient&#39;s left coronary artery, and the distal end of guiding catheter  100  is positioned proximal of a stenosis  175 . Once positioned, a therapeutic device, such as a balloon dilatation catheter including a dilatation balloon, may be advanced through guiding catheter  100  to provide treatment to stenosis  175 . Upon completion of the interventional procedure and removal of any therapeutic device, guiding catheter  100  is withdrawn from the patient&#39;s vascular system  150 .  
         [0026]      FIG. 2  illustrates a side view of an embodiment of guiding catheter  100 , including an elongate shaft  204  with a distal end  206  having an optional soft tip. As shown in  FIGS. 3 and 4 , a bore or lumen  210  extends through shaft  204  between an open proximal end  208  and an open distal end. In an embodiment of the present invention, bore  210  has a low-friction surface  240  and is sized and shaped to receive and direct there through a variety of treatment devices, such as guidewires and/or therapeutic devices including, but not limited to balloon catheters or stent delivery systems. In another embodiment, bore surface  240  may provide a slippery interior surface for reducing frictional forces between the interior surface of guiding catheter  100  and devices that may be moved through bore  210 .  
         [0027]     A connector fitting  102  is coupled to, and provides a functional access port at the proximal end of guiding catheter  100 . Fitting  102  is attached to catheter shaft  204  and has a central opening in communication with open proximal end  208  and bore  210  to allow passage of various therapeutic devices there through. Connector fitting  102  may be made of metal or of a hard polymer, e.g. medical grade polycarbonate, polyvinyl chloride, acrylic, acrylonitrile butadiene styrene (ABS), or polyamide, that possesses the requisite structural integrity, as is well known to those of ordinary skill in the art.  
         [0028]     Catheter shaft  204  is a single lumen tubular structure that is designed to advance through a patient&#39;s vasculature to remote arterial locations without buckling or undesirable bending. In an embodiment of the present invention, catheter shaft  204  also has variable flexibility within at least distal portion  104  with its greatest flexibility proximate distal tip  206 . In various other embodiments, as known to those of ordinary skill in the art, catheter shaft  204  may include a pre-formed distal curve that can provide backup support as therapeutic catheters are advanced through bore  210  of guiding catheter  100  and across stenosis  175 . As shown in  FIG. 2 , any one of a number of pre-formed curve shapes may be incorporated into guiding catheter  100 , such as Judkins-type or Amplatz-type curves, as non-limiting examples.  
         [0029]     In the embodiment illustrated in  FIGS. 2, 3  and  4 , catheter shaft  204  includes an inner liner or tube  215 , a reinforcing layer  220 , and a continuous outer jacket or tube  230 . Inner liner  215  is tubular and defines bore  210 , which is sized and shaped as described above. In an embodiment of the present invention, inner liner  215  is manufactured of a high density polyethylene (HDPE) that provides good flexibility and movement of catheter  100  over a guidewire and/or movement of a therapeutic device within catheter  100 . In another embodiment, inner liner  215  is manufactured of a nylon with a coating (not shown) applied to the surface of bore  210  to provide low-friction surface  240  that facilitates movement of guiding catheter  100  over a guidewire and/or movement of a therapeutic device within catheter  100 . In one exemplary embodiment, the interior surface is provided with a slippery coating, such as a silicone compound or a hydrophilic polymer. Those of ordinary skill in the art may appreciate that any one of numerous low-friction, biocompatible materials such as, for example, fluoropolymers (e.g. PTFE, FEP), polyolefins (e.g. polypropylene, high-density polyethylene), or polyamides, may be used as inner liner  215  or as a coating on the surface of bore  210 .  
         [0030]     Reinforcing layer  220  enhances the torsional strength and inhibits kinking of catheter shaft  204  during advancement of guiding catheter  100  within the patient&#39;s vasculature. Reinforcing layer  220  is positioned between inner liner  215  and outer jacket  230  and is substantially coaxial with inner liner  215  and outer jacket  230 . In various embodiments, reinforcing layer  220  may be formed by braiding multiple filaments or winding at least one filament over inner liner  215  or by applying a metal mesh over inner layer  215 , such as a wire or mesh made from  304  stainless steel or nitinol. Braided or wound filaments may comprise high-modulus thermoplastic or thermo-set plastic materials, e.g., liquid crystal polymer (LCP), polyester, or aramid polymer e.g. poly-paraphenylene terephthalamide (Kevlar® from E.I. du Pont de Nemours and Company, Wilmington, Del., U.S.A.). Alternatively, braided or wound filaments may comprise metal wires of stainless steel, superelastic alloys, such as nitinol (TiNi), refractory metals, such as tantalum, or a work-hardenable super alloy comprising nickel, cobalt, chromium and molybdenum.  
         [0031]     Outer jacket  230  provides support to catheter shaft  204  and coverage of reinforcing layer  220 . Outer jacket  230  is coaxial with inner liner  215  and reinforcing layer  220 , and is a single or unitary tube that continuously extends from proximal end  208  to distal end  206  of catheter shaft  204 . In an embodiment of the present invention, outer jacket  230  is manufactured of a polyamide, such as a polyether block amide copolymer or nylon  6 , 6 . In order to provide distal portion  104  of catheter shaft  204  with variable flexibility, at least a first distal length of outer jacket  230  is chemically softened in a softening agent for a set period of time. In another embodiment, a second distal length of outer jacket  230  may be chemically softened in the softening agent for a second period of time, which is longer than the first period of time, to achieve a greater flexibility in the second distal length versus at least a portion of the first distal length. Additional variations in flexibility of outer jacket  230  within distal portion  104  may be achieved by varying softening agent exposure time of selected distal lengths thereof, as described further below.  
         [0032]     An embodiment of the present invention includes a method of manufacturing catheter shaft  204  that is selectively made more flexible by treatment with a chemical solvent. In one embodiment, as schematically illustrated in the flow chart depicted in  FIG. 5 , elongate reinforced layered tubing to be used for catheter shaft  204  is manufactured by first extruding an inner liner material, such as HDPE, optionally over a suitable mandrel, to form inner liner  215 , which is wound continuously on a reel. Flat stainless steel wires are then selected and braided over inner liner  215  to form reinforcing layer  220 , passing the long subassembly from reel to reel. An outer jacket material, such as polyethylene block amide copolymer, is then thermoplastically extruded over reinforcing layer  220  to form outer jacket  230 . Outer jacket  230  may extend through the interstices of braided reinforcing layer  220  to form a bond with inner liner  215 . Alternatively, an adhesive or other type of tie layer material may be incorporated to bond together inner liner  215 , reinforcing layer  220 , and outer jacket  230 , as would be well known to those of skill in the art. The elongate reinforced layered tubing is then cut in appropriate lengths, e.g. approximately 100 cm for use in PTCA procedures performed via the femoral artery, to form a number of catheter shafts  204 . If a mandrel was used during manufacturing, then it is removed from catheter shaft  204  to provide open bore  210 .  
         [0033]     At least a distal segment of distal portion  104  of each catheter shaft  204  is then chemically treated, or softened, by dipping catheter shaft distal portion  104  in a softening agent. In one embodiment, catheter shaft  204  is suspended from a rack so that a distal length/segment of approximately 20 cm of distal portion  104  is submerged in a chemical softening agent appropriate for softening the material of outer jacket  230 . In an embodiment where outer jacket  230  is formed from polyethylene block amide copolymer or nylon, a dimethyl sulfoxide (DMSO) liquid has been found to be an effective and benign chemical softening agent for this purpose. Another chemical softening agent that is effective for such a catheter shaft arrangement is N,N-dimethylformamide (DMF), which may be used if the catheter shaft is properly treated after softening to neutralize any toxicity that may remain after exposure to the solvent. In another embodiment, the distal end of catheter shaft  204  may be temporarily plugged prior to the dipping process to prevent the softening agent from coming into contact with the surface of bore  210  formed by catheter shaft inner layer  215 .  
         [0034]     In an embodiment of the invention, the material(s) of inner layer  215  and outer jacket  230  may be chosen such that both are susceptible to softening with the same softening agent. In this embodiment, catheter shaft distal end  206  may remain open during the dipping process such that inner layer  215  and outer jacket  230  are both exposed to, and softened by the chemical softening agent.  
         [0035]     Catheter shaft distal portion  104  may be allowed to soak in the softening agent for a time period ranging from less than an hour to about 89 hours. As shown in  FIG. 6 , which depicts stiffness test results in a graph of load as a function of degrees of deflection for catheter shafts softened in accordance with various embodiments of the present invention, a direct correlation exists between the duration of exposure to the softening agent and a subsequent decrease in stiffness, with longer exposures correlating to increased softening of the outer jacket. During the soaking process when DMSO is used to soften an outer jacket  230  formed of a polyamide material, it is theorized that the DMSO replaces at least a portion of the hydrogen-oxygen bonds between chains of amide groups with hydrogen-oxygen bonding between amide groups and DMSO molecules. This replacement prohibits hydrogen bonding between carbonyl oxygen of one amide chain and amide hydrogen of another amide chain thus decreasing the stiffness of the material. As such, the chemical composition of the chemically softened distal portion of the catheter shaft is likely altered from that of the untreated proximal portion.  
         [0036]     After soaking for a predetermined time period sufficient for softening outer jacket  230 , catheter shaft distal portion  104  is removed from the softening agent and, optionally, wiped and/or cleaned to remove any excess softening agent. In an embodiment of the present invention, a cleaning agent, such as water, or other agent may be used that not only removes excess softening agent but also stops the softening process. A connector fitting  102  and, optionally a soft distal tip are then bonded to the proximal and distal ends  208 ,  206 , respectively, of catheter shaft  204  to form guiding catheter  100 . In a further embodiment, as shown in  FIG. 2 , a pre-formed curved region may be set in catheter shaft  204  by various means known to one of ordinary skill in the art.  
         [0037]     In another embodiment, as illustrated in  FIGS. 7, 7A , and  7 B, a first distal length  503  of distal portion  104  of catheter shaft  204 , such as a first distal length up to and including 20 cm, is submerged in the softening agent for a first period of time. After soaking for the first period of time, a portion of the submerged length of catheter shaft distal portion  104  is withdrawn from the softening agent while still leaving a second distal length  501 , which is a portion of first distal length  503 , submerged in the softening agent for a second period of time. Upon expiration of the second period of time, second distal length  501  is removed from the softening agent, as previously discussed. A catheter shaft  204  made according to this embodiment will have three different hardnesses or stiffnesses, or described conversely, three different flexibilities. The un-submerged proximal portion of catheter shaft  204  retains its original stiffness; while a first segment  505  submerged for only the first period of time and a second segment  507  submerged for the first and second periods of time have a measurable flexibility change due to chemical softening. Because of the different time periods during which the first and second segments  505 ,  507  of distal portion  104  are in contact with the softening agent, each segment will have a different flexibility. As illustrated in  FIG. 8 , second segment  507  of catheter shaft distal portion  104  experiences the greatest change in flexibility from the untreated proximal portion of catheter shaft  204  because it was submerged in the softening agent for the longest period of time.  
         [0038]     In further embodiments, a greater number of consecutively shorter distal lengths of distal portion  104  may be submerged for selected periods of time to create a catheter shaft distal portion  104  with more gradations in flexibility. In a still further embodiment, catheter shaft distal portion  104  may be submerged in the softening agent for a set period of time and then gradually lifted out of the softening agent at a fixed or variable rate, e.g., 1 cm/hr, or over a period of time ranging from 1 to 89 hours, until distal portion  104  is fully withdrawn from the softening agent. A distal portion  104  made according to this embodiment would have a more gradual change in flexibility along its length rather than marked or stepped changes in flexibility.  
         [0039]     It would be understood by one of ordinary skill in the art that the variation in flexibility may also be achieved by a process in which a first distalmost length of the catheter shaft is brought into contact with a softening agent for a first period of time and then a second length of the catheter shaft, proximal to the first distalmost length, is brought into contact with the softening agent for a second period of time. In this process, the first distalmost length of the catheter shaft remains exposed to the softening agent during the first and second periods to be made more flexible than the second, more proximal, length of the catheter shaft exposed only for the second period of time. If contact in this embodiment is achieved by dipping or submerging the distal portion of the catheter in the softening agent, the depth of the dipped/submerged portion of the catheter shaft would increase over one or more periods of time until sufficient softening has occurred at which time the entire shaft would be removed from the solvent.  
         [0040]     Those of ordinary skill in the art will recognize alternate ways to manufacture inner liner  215 , reinforcing layer  220  and outer jacket  230  and that alternate materials can be utilized for each component, where the selection of a softening agent will depend on the material chosen for outer jacket  230  and/or inner liner  215 . Besides the dipping processes described, selected portions of inner liner  215  and/or outer jacket  230  can be exposed to a softening agent by other processes, such as surrounding the selected portions with a sealed chamber (not shown) that can be filled with the softening agent. Such a sealed softening chamber does not expose other portions of catheter shaft  204  to the softening agent. Unlike the dipping process, a sealed chamber can be used to create segments of different flexibility wherein the segments are not necessarily arranged to provide sequentially increasing flexibility towards the distal end of catheter  100 . In another embodiment, inner liner  215  may be chemically softened by aspirating a softening agent through open distal end  206  into a distal portion of bore  210 , with or without exposing outer jacket  230  to the softening agent. Thus, the terms dipping or submerging are used herein to broadly describe any process wherein inner liner  215  and/or outer jacket  230  are in contact with, or exposed to a softening agent.  
         [0041]     While various embodiments of the present invention have been described above, it should be understood that they have been presented by way of illustration and example only, and not limitation. It will be apparent to persons skilled in the relevant art that various changes in form and detail can be made therein without departing from the spirit and scope of the invention. Thus, the breadth and scope of the present invention should not be limited by any of the above-described exemplary embodiments, but should be defined only in accordance with the appended claims and their equivalents. It will also be understood that each feature of each embodiment discussed herein, and of each reference cited herein, can be used in combination with the features of any other embodiment. All patents and publications discussed herein are incorporated by reference herein in their entirety.