Abstract:
A balloon catheter having a multilayer catheter shaft is formed to have an inner layer and an outer layer, where the inner layer and outer layer are selected from materials that enhance the pushability of the catheter while preserving the flexibility. Using a combination of a high Shore D duromater value material and a lower Shore D duromater value material, various combinations of multilayer catheter shafts are disclosed utilizing different glass transition temperatures and block copolyamides to obtain the desired characteristics.

Description:
CROSS-REFERENCES TO RELATED APPLICATIONS 
     This application is a continuation of U.S. patent application Ser. No. 12/478,929, filed Jun. 5, 2009, which is continuation-in-part of U.S. patent application Ser. No. 12/324,425 entitled “Low Compliant Catheter Tubing” filed Nov. 26, 2008, now U.S. Pat. No. 8,070,719, the contents each of which are incorporated by reference in their entirety. 
    
    
     BACKGROUND 
     The invention relates to the field of intravascular catheters, and more particularly to a balloon catheter or other catheter components, such as a guidewire enclosure and catheter tubing, that would benefit from the properties of the materials disclosed herein. 
     In percutaneous transluminal coronary angioplasty (PTCA) procedures, a guiding catheter is advanced until the distal tip of the guiding catheter is seated in the ostium of a desired coronary artery. A guidewire, positioned within an inner lumen of an dilatation catheter, is first advanced out of the distal end of the guiding catheter into the patient&#39;s coronary artery until the distal end of the guidewire crosses a lesion to be dilated. Then the dilatation catheter having an inflatable balloon on the distal portion thereof is advanced into the patient&#39;s coronary anatomy, over the previously introduced guidewire, until the balloon of the dilatation catheter is properly positioned across the lesion. Once properly positioned, the dilatation balloon is inflated with liquid one or more times to a predetermined size at relatively high pressures (e.g. greater than 8 atmospheres) so that the stenosis is compressed against the arterial wall and the wall expanded to open up the passageway. Generally, the inflated diameter of the balloon is approximately the same diameter as the native diameter of the body lumen being dilated so as to complete the dilatation but not overexpand the artery wall. The rate of expansion of the balloon for a given pressure is an important consideration in the design of the dilation catheter, as greater than anticipated expansion of the balloon against the vessel wall can cause trauma to the vessel wall. After the balloon is finally deflated, blood flow resumes through the dilated artery and the dilatation catheter can be removed from the patient&#39;s artery. 
     In such angioplasty procedures, there may be restenosis of the artery, i.e. reformation of the arterial blockage, which necessitates either another angioplasty procedure, or some other method of repairing or strengthening the dilated area. To reduce the restenosis rate and to strengthen the dilated area, physicians frequently implant an intravascular prosthesis, generally called a stent, inside the artery at the site of the lesion. Stents may also be used to repair vessels having an intimal flap or dissection or to generally strengthen a weakened section of a vessel. Stents are usually delivered to a desired location within a coronary artery in a contracted condition on a balloon of a catheter which is similar in many respects to a balloon angioplasty catheter, and expanded to a larger diameter by expansion of the balloon. The balloon is deflated to remove the catheter and the stent left in place within the artery at the site of the dilated lesion. 
     In the design of catheter balloons and catheter tubing, material characteristics such as strength, flexibility and compliance must be tailored to provide optimal performance for a particular application. Angioplasty balloons and catheter tubing preferably have high strength for inflation at relatively high pressure, and high flexibility and softness for improved ability to track the tortuous anatomy. The balloon compliance, for example, is chosen so that the balloon will have a desired amount of expansion during inflation. Compliant balloons, for example balloons made from materials such as polyethylene, exhibit substantial stretching upon the application of tensile force. Noncompliant balloons, for example balloons made from materials such as PET, exhibit relatively little stretching during inflation, and therefore provide controlled radial growth in response to an increase in inflation pressure within the working pressure range. However, noncompliant balloons generally have relatively low flexibility and softness, making it more difficult to maneuver through various body lumens. Heretofore the art has lacked an optimum combination of strength, flexibility, and compliance, and particularly a low to non-compliant balloon with high flexibility and softness for enhanced trackability. Semi-compliant balloons made from semi-crystalline nylon 11, nylon 12, and copolymers of these nylons, such as poly ether block amide (for example, Pebax from Arkema) address these shortcomings and provide low distensibility and good flexibility, thus being used in many balloon dilatation catheters and stent delivery system. 
     For ease of thermal bonding to afore mentioned semi-compliant balloons, it is also preferred that the shaft of the balloon dilatation catheters and stent delivery system are also derived from same materials. Many balloon dilatation catheters and stent delivery systems therefore use shafts derived from these materials. The relative hardness and flexibility of the catheter tubing is also a constant compromise between the need for an agile tubing that can navigate the various body lumens, while having enough stiffness to be able to be pushed from a proximal end outside the body through the patient&#39;s vascular tract. A tubing that is relatively stiff will transmit proximal force more efficiently to the distal end, giving the practitioner more control over the location and position of the catheter balloon. However, stiffer tubing makes it much more difficult to bend or track curvatures in the body, leading to the paradox of the need for stiffer yet more flexible tubing. Moreover, stiffer materials when used to make catheter shafts have a higher tendency to kink, making it more difficult to control or push. Therefore, it is desirable to be able to increase stiffness and thus pushability by incorporating nylons having higher stiffness than semi-crystalline nylons having been used thus far. Some amorphous nylons offer desired higher stiffness than semi-crystalline nylons. However, the higher stiffness amorphous nylons are more susceptible to damage from solvents, such as isopropyl alcohol, used in the manufacturing, cleaning processes, and during clinical use. The present invention is directed to address this issue. 
     SUMMARY OF THE INVENTION 
     The softness and flexibility of a balloon or catheter tubing is a function of the flexural modulus of the polymeric material of the balloon, so that a balloon or tubing material having a higher Shore D durometer hardness, which yields a stronger and stiffer balloon or catheter tubing, has a higher flexural modulus. Conversely, a balloon or catheter tubing material having a lower Shore D durometer hardness, which thus provides a soft and flexible balloon or tubing, has a lower flexural modulus. The present invention is directed to a catheter tubing formed with a combination of at least two polyamides, a high durometer hardness material and a lower durometer hardness material. 
     The tubing can be made from a blend of the two polyamides, or a co-extrusion of the two polyamides with an inner layer and an outer layer. The first inner polyamide has a Shore D durometer hardness of greater than 78 D, more preferably Shore D durometer hardness of greater than 80 D, and can be preferably selected from various transparent amorphous nylons having segment such as an aliphatic segment, an aromatic segment, or a cycloaliphatic segment. The second outer polyamide has a lower durometer hardness than the first polyamide, and preferably less than 76 D, and preferably a block copolymer of nylon and polytetramethylene oxide (i.e. a copolyamide), or Pebax. The second outer polyamide is preferably semi-crystalline polyamide, thus providing enhanced resistance to solvents, such as isopropyl alcohol, used in the manufacturing, cleaning processes, and during clinical use. Both inner and outer polyamides preferably have the same amide block or segment, e.g. nylon 12, nylon 11, or nylon 6,6. 
     The preferred high hardness material is a nylon referred to as transparent amorphous nylon. The transparent amorphous nylon preferably has either an aliphatic segment, an aromatic segment, or a cycloaliphatic segment. 
     The catheter tubing of the invention may be formed by coextruding a tubular product formed from the two polymeric components to create a tubing having an outer layer and an inner layer of the two materials. 
     Various designs for balloon catheters well known in the art may be used in the catheter system of the invention. For example, conventional over-the-wire balloon catheters for angioplasty or stent delivery usually include a guidewire receiving lumen extending the length of the catheter shaft from a guidewire port in the proximal end of the shaft. Rapid exchange balloon catheters for similar procedures generally include a short guidewire lumen extending to the distal end of the shaft from a guidewire port located distal to the proximal end of the shaft. 
     In the case of a robust co-extruded catheter shaft, an inner layer can be comprised of a high modulus or high Shore D durometer nylon, preferably a Shore D durometer value greater than 80, such as Grilamid TR55 LX nylon 12 from EMS—American Grilon Inc., which provides a high modulus for enhanced pushability. Also, it would be beneficial if the glass transition temperature of the high modulus polymer forming the inner layer is greater than 100° C., and more preferably greater than 120° C. However, the TR55 LX or other high modulus amorphous nylon has a greater tendency to kink and is susceptible to attack by solvents. To combat the kink propensity and to protect the catheter shaft from solvents, a thin outer layer of lower modulus material such as Pebax is formed over the TR55 LX inner layer to serve as a protective layer and to resist kinking of the shaft. The outer layer can be selected from semi-crystalline polyamide or more preferably from a copolyamide of lower durometer value such as Pebax 72 D, Pebax 63 D, and the like, where the Shore D durometer value is less than 76. 
     By incorporating an amorphous polyamide such as TR 55 LX as one layer, the dimensional stability is increased for as the shelf life of the catheter increases due to the higher glass transition temperature, as compared with nylon 12 or Pebax which has a glass transition temperature at or below 55° C. Also, a higher tensile strength (approximately 11,000 psi) of amorphous nylon TR 55 LX compared with nylon 12 or Pebax (7,500-8,200) provides a higher rupture limit with the same wall thickness. 
     The co-axial tubing can be formed into a tapered configuration, where the radius of the shaft gradually reduces until the balloon attachment point. This gradual reduction in the radial component of the shaft serves to eliminate the mid-shaft portion of the catheter, which simplifies the manufacturing process by avoiding a laser operation or other mechanism to attach the mid-shaft. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1  is an elevated view partially in section of a balloon catheter which embodies features of the invention, showing the balloon in an expanded state; 
         FIG. 2  is a transverse cross sectional view of the balloon catheter of  FIG. 1  taken along lines  2 - 2 ; 
         FIG. 3  is a transverse cross sectional view of the balloon catheter of  FIG. 1  taken along lines  3 - 3 ; and 
         FIG. 4  is a graph of the compliance of the catheter balloon using a first preferred blend of materials; 
         FIG. 5  is a cross-sectional view of a catheter shaft with an inner layer, an intermediate layer, and an outer layer; 
         FIG. 6  is an enlarged, partially cut-away view of a catheter shaft illustrating multiple layers, including an embedded high strength ribbon or coil in the outer layer; and 
         FIG. 7  is an enlarged, cross-sectional view of another embodiment of a catheter shaft. 
     
    
    
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS 
     In angioplasty balloons, an object is to apply a high pressure to the interior wall of the lumen to compress the plaque and/or to fully expand the stent. This relies on a robust balloon with a sturdy out wall and a high pressure capability. The compliance of the balloon, i.e., the expansion of the balloon as a function of internal pressure, is preferably low or flat to more accurately control the amount of pressure applied to the arterial wall. However, the deliverability of the balloon is also a factor, especially where tortuous body lumens are involved. Stiff balloons (i.e., high modulus materials) tend to have poor flexibility and lack the maneuverability to navigate the various body lumens, and thus make poor choices for catheter balloons. Conversely, flexible balloons (low modulus materials) that have high compliance are poorly suited to apply a precise known pressure on the arterial wall due to a high expansion rate per applied pressure. The goal is thus to increase the rupture strength by adding the high modulus material such as nylon to the softer polyamide material. 
     Soft polyamide materials such as Pebax® are semi-crystalline polymers and usually include an amorphous segment. The amorphous segment has a lower density than the crystalline structure and thus is weaker in general than crystalline segments. If the amorphous segment can be reinforced by adding a small amount of a higher modulus material the response of the amorphous segment can be delayed and the overall strength of the material can be strengthened. The high modulus material preferably has a Shore D durometer hardness of 78 D or more. Suitable materials include transparent amorphous nylon such as nylon 12, and more preferably a nylon 12 with a aliphatic segment, an aromatic segment, or a cycloaliphatic segment. These nylons are transparent amorphous because they are essentially amorphous, lacking the crystalline structure of other more conventional nylon 12. The aliphatic segment, aromatic segment, or cycloaliphatic segment does not crystallize with the main chain, disrupting the formation of longer crystalline chains in the polymer. The amorphous segment of the transparent amorphous nylon 12 combines with the amorphous segment of the Pebax to strengthen the Pebax by enhancing the weakest link in the chain, thereby increasing the overall strength of the polymer. 
       FIG. 1  illustrates a balloon catheter which embodies features of the invention. The catheter  10  of the invention generally comprises an elongated catheter shaft  11  having a proximal section,  12  a distal section  13 , an inflatable balloon  14  formed of a blend of polymeric materials on the distal section  13  of the catheter shaft  11 , and an adapter  17  mounted on the proximal section  12  of shaft  11 . In  FIG. 1 , the catheter  10  is illustrated within a patient&#39;s body lumen  18 , prior to expansion of the balloon  14 . 
     In the embodiment illustrated in  FIG. 1 , the catheter shaft  11  has an outer tubular member  19  and an inner tubular member  20  disposed within the outer tubular member and defining, with the outer tubular member, inflation lumen  21 . Inflation lumen  21  is in fluid communication with the interior chamber  15  of the inflatable balloon  14 . The inner tubular member  20  has an inner lumen  22  extending therein which is configured to slidably receive a guidewire  23  suitable for advancement through a patient&#39;s coronary arteries. The distal extremity of the inflatable balloon  14  is sealingly secured to the distal extremity of the inner tubular member  20  and the proximal extremity of the balloon is sealingly secured to the distal extremity of the outer tubular member  19 . 
       FIGS. 2 and 3  show transverse cross sections of the catheter shaft  11  and balloon  14 , respectively, illustrating the guidewire receiving lumen  22  of the guidewire&#39;s inner tubular member  20  and inflation lumen  21  leading to the balloon interior  15 . The balloon  14  can be inflated by radiopaque fluid introduced at the port in the side arm  24  into inflation lumen  21  contained in the catheter shaft  11 , or by other means, such as from a passageway formed between the outside of the catheter shaft and the member forming the balloon, depending on the particular design of the catheter. The details and mechanics of balloon inflation vary according to the specific design of the catheter, and are well known in the art. 
     Non-compliant or low-compliant balloon  14  and/or the shaft  11  is formed of a blend of a first polyamide having a Shore D durometer hardness greater than 78 D and a copolyamide of lower durometer hardness, preferably less than 76 D. A preferred polyamide having a Shore D durometer hardness greater than 78 D is an amorphous polyamide such as EMS TR 55 (transparent amorphous nylon 12), Arkema Rilsan G110 (transparent amorphous nylon 12), or Cristamid MS 110 (transparent amorphous nylon 12). The polyamide is preferably includes a cycloaliphatic segment, an aromatic segment, or an aliphatic segment. Such polyamides are also referred to as transparent polyamide. The preferred copolyamide material for forming the polymeric blend for the balloon is Pebax, and more preferably Pebax 72 D, Pebax 70 D, Pebax 63 D, or Pebax 55 D. Alternatively, the copolyamide of lower durometer hardness is preferably a block copolymer of nylon 12 and polytetramethylene oxide. 
     The flexural modulus of the polyamide is preferably greater than 1700 MPa (240,000 psi) and the flexural modulus of the copolyamide is less than 850 MPa (120,000 psi). The tensile strength at break of both polyamides is at least 50 MPa, and elongation at break of both polyamides is at least 150%. 
     The catheter shaft will generally have the dimensions of conventional dilatation or stent deploying catheters. The length of the catheter  10  may be about 90 cm to about 150 cm, and is typically about 135 cm. The outer tubular member  19  has a length of about 25 cm to about 40 cm, an outer diameter (OD) of about 0.039 in to about 0.042 in, and an inner diameter (ID) of about 0.032 in. The inner tubular member  20  has a length of about 25 cm to about 40 cm, an OD of about 0.024 in and an ID of about 0.018 in. The inner and outer tubular members may taper in the distal section to a smaller OD or ID. 
     The length of the compliant balloon  14  may be about 1 cm to about 4 cm, preferably about 0.8 cm to about 4.0 cm, and is typically about 2.0 cm. In an expanded state, at nominal pressure of about 8 to about 10 atm, the balloon diameter is generally about 0.06 in (1.5 mm) to about 0.20 in (5.0 mm). and the wall thickness is about 0.0006 in (0.015 mm) to about 0.001 in (0.025 mm), or a dual wall thickness of about 0.025 mm to about 0.056 mm. The burst pressure is typically about 20 to 26 atm, and the rated burst pressure is typically about 18 atm. 
     In a presently preferred embodiment, the balloon  14  may include wings, which may be folded into a low profile configuration (not shown) for introduction into and advancement within the patient&#39;s vasculature. When inflating the balloon to dilate a stenosis, the catheter  10  is inserted into a patient&#39;s vasculature to the desired location, and inflation fluid is delivered through the inflation lumen  21  to the balloon  14  through the inflation port  24 . The semi-compliant or noncompliant balloon  14  expands in a controlled fashion with limited radial expansion, to increase the size of the passageway through the stenosed region. Similarly, the balloon has low axial growth during inflation, to a rated burst pressure of about 14 atm, of about 5 to about 10%. The balloon is then deflated to allow the catheter to be withdrawn. The balloon may be used to deliver a stent (not shown), which may be any of a variety of stent materials and forms designed to be implanted by an expanding member, see for example U.S. Pat. No. 5,514,154 (Lau et al.) and U.S. Pat. No. 5,443,500 (Sigwart), incorporated herein in their entireties by reference. 
     EXAMPLE 1 
     A proximal shaft for the over-the-wire catheter may have a tapered tubing coextruded and tapered with TR55 inner layer and Pebax 72 D outer layer. The proximal wall thickness of TR55 may be approximately 0.005″ and a proximal wall thickness of Pebax 72 D may be approximately 0.001″. A distal wall thickness of TR55 is approximately 0.002″ and a distal wall thickness of Pebax 72 D is approximately 0.001″. In addition to balloons, the blended composition has usefulness as other parts of the catheter, such as the guidewire enclosure  20  of  FIGS. 1-3 . The inner member of the multi-layered tubing can have a lubricious inner layer (HDPE. UHMWPE, and the like) with bonding mid layer and polymer blend outer layer. Like the catheter balloon, the blend is comprised of one polymer having a Shore D durometer greater than 78 and another polymer having lower durometer, preferably less than 76 D. Both polyamides preferably have same amide block or segment, i.e. one type of amide (nylon) block, solely comprised of nylon 12, nylon 11, nylon 6, or nylon 6, 6 but not combination of these. 
     The polyamide having Shore D durometer greater than 78 D is preferably amorphous polyamide selected from polyamide such as EMS TR 55 (transparent amorphous nylon 12), Arkema Rilsan G110 (transparent amorphous nylon 12), or Cristamid MS 110 (transparent amorphous nylon 12). This polyamide is preferably a copolyamide comprising cycloaliphatic, and/or aromatic, and/or aliphatic segment. The other copolyamide of lower durometer is preferably a block copolymer of nylon 12 and polytetramethylene oxide, such as Pebax 72 D, Pebax 70 D or Pebax 63 D. 
     The high durometer polymer serves to increase resistance to collapse of the tubing and provides enhanced pushability while the lower durometer polymer provides flexibility and kink resistance. Although it is preferred to have blends of high miscibility, the blend ratio is such that the lower durometer polymer forms a “virtual” continuous phase while the higher durometer polymer forms “virtual” reinforcement. 
     As shown in  FIG. 5 , an outer layer  60  of the catheter shaft can be comprised of an amorphous polyamide selected from polyamide such as EMS TR 55 (transparent amorphous nylon 12), Arkema Rilsan G110 (transparent amorphous nylon 12), Cristamid MS 110 (transparent amorphous nylon 12), polyamide 11, polyamide 6, or polyamide 6,6. This polyamide is preferably a copolyamide comprising cycloaliphatic, and/or aromatic, and/or aliphatic segment. In one embodiment, the outer layer  60  is blended with a softer polyamide such as a crystalline or semi-crystalline copolymer of nylon 12 and polytetramethylene oxide or polytetramethylene glycol, e.g. Pebax 72 D or Pebax 70 D. This blending offers a higher strength outer layer that offers higher pushability and resists collapse, while the copolymer operates to resist kinking and yield greater flexibility. Although it is preferable to have blends of high miscibility, blend ratios are such that the lower durometer polymer forms a virtual continuous phase and the high durometer polymer forms a virtual reinforcement. The intermediate layer  70  is a bonding layer, such as Primacore, to meld the inner and outer layers together. The inner layer  80  can be a lubricious material that reduces the friction of a guide wire passing through the lumen  90 , such as HDPE or UHMWPE. Other materials are also contemplated, as long as the outer layer has a glass transition or melting temperature that is preferably lower than, or at least approximately equal to, the surface temperature of the mold during the blowing or forming process of the balloon. 
       FIG. 6  shows another embodiment of a catheter shaft  120  having a lumen  125  extending therein, the shaft  120  having an inner layer  130  comprising a low friction material such as high density polyethylene and an intermediate layer  140  serving as a bonding layer. An outer layer comprising a first polymer having a first Shore D durometer value of no greater than 76 D, such as Pebax 72 D or Pebax 63 D is impregnated with a second polymer having a Shore D durometer value that is greater than the first Shore D durometer value, and preferably greater than 78 such as TR55 or the other transparent nylon 12 materials discussed above. The second polymer  160  can be wrapped around the shaft  120  like a helix or coil to reinforce the outer layer  150 . 
       FIG. 7  illustrates another embodiment of a catheter shaft having an inner layer  220  of a high modulus material with a high Shore D durometer value such as amorphous nylon 12. This inner layer material provides a high strength catheter shaft for higher pushability. However, the transparent nylon 12 has a tendency to kink, and it is susceptible to solvents used in cleaning or other manufacturing processes. To resist kinking, and to protect the catheter from solvents, a thin outer layer  240  of Pebax or other soft copolyamide is formed over the inner layer  220 . The two layers  220 ,  240  can be co-extruded in a single operation to create the shaft  200  of  FIG. 7 . The shaft  220  also incorporates a tapered section  250  as the shaft transitions from a main body portion to the portion  260  to the portion  270  where a balloon may be attached. In existing catheter shafts, this section requires a mid shaft section that must be separately attached to the catheter shaft using expensive laser equipment. The tapered transition from the main body portion  260  to the balloon attachment portion  270  eliminates the need for a mid shaft and thus the need for the laser equipment and assembly line personnel required to operate the laser equipment, resulting in a more efficient and cost effective catheter. 
     The shaft of  FIG. 7  preferably has both co-extruded layers  220 ,  240  with a common amide block or segment for better adhesion or compatibility, i.e., one type of amide (nylon) block, comprising one and only one of nylon 12, nylon 11, nylon 6, or nylon 6,6. The inner polymer is preferably a polyamide having a Shore D durometer value of greater than 78, such as amorphous polyamide selected from EMS TR55, Arkema Rilsan G110, or Cristamid MS 110, all commonly referred to as transparent nylon 12. This polyamide preferably comprises cycloaliphatic, aromatic, and/or aliphatic segments. The outer layer  240  may preferably be a copolyamide block copolymer of nylon 12 and polytetramethylene glycol. 
     Various embodiments are described above in effort to illustrate the concepts of the present invention, but these embodiments are not intended to be limiting or exclusive. Rather, the scope of the invention is to be determined by the words of the appended claims, interpreted in the context of the above description but not limited to those examples and embodiments described above and shown in the Figures.