Patent Application
20110077731
This invention relates generally to catheters, and more particularly to catheter systems for percutaneous transluminal procedures, such as delivery and deployment of expandable prostheses.
In the treatment of vascular and biliary disease, expandable endoprosthesis devices, generally called stents, are commonly implanted into a patient's body lumen to maintain the patency thereof. Stents are particularly useful in the treatment and repair of body lumens after a stenosis has been compressed by percutaneous transluminal coronary angioplasty (PTCA) or percutaneous transluminal angioplasty (PTA), or removed by atherectomy or other means, to help improve the results of the procedure and reduce the possibility of restenosis. Stents are generally cylindrically shaped devices which function to hold open a segment of a blood vessel such as a coronary artery, peripheral artery, or other body lumen such as a bile duct. Stents are usually delivered in a collapsed state on a catheter to the target site and then deployed at that location by expanding to a larger diameter into contact with the body lumen wall. Stents are generally classified into one of two categories related to the expansion of the stent, namely, stents which require application of a radially outward force such as by inflating a catheter balloon on which the stent is mounted, or alternatively, self-expanding stents which will automatically expand from the collapsed state when the stent is advanced out the distal end of a radial restraining member of the delivery catheter.
Prior art stent delivery systems for implanting self-expanding stents typically include an inner lumen around which the collapsed stent is positioned and an outer restraining sheath which is initially placed over the collapsed stent prior to deployment. When the stent is to be deployed in the body vessel, the outer sheath is moved in relation to the inner lumen to uncover the collapsed stent, allowing the stent to expand to its expanded condition. Delivery systems have utilized a push-pull type technique in which the outer sheath is retracted while the inner lumen is pushed forward, or have been designed to retract the outer sheath and deploy the stent while the inner lumen must remain stationary to prevent the stent from moving axially within the body lumen during deployment.
It is important in any typical vascular intervention procedure to have a relatively short intervention duration, and to have uncomplicated steps which are relatively few in number. This results in a lowered potential for complications. For example, an extended intervention time increases the risk of infection or stress on the patient, and a large number of device insertions and removals increase the potential for creation of emboli which can cause stroke or small vessel occlusions distal to the intervention site. However, one difficulty has been providing a device which facilitates accurately delivering multiple stents within a patient quickly and easily, such that the procedural steps required to use the device are relatively simple and straight forward.
The invention is directed to a stent delivery system having multiple stents in a single delivery catheter, configured for delivering and deploying at least some of the stents in a patient's anatomy.
In one aspect of the invention, the stent delivery system generally includes a delivery catheter having an inner tubular member and an outer tubular member adapted for axial movement with respect to each other, a first stent and at least one second proximal stent in a collapsed configuration in a space between the inner tubular member and outer tubular member within the delivery catheter and configured to radially self expand from the collapsed configuration to an expanded configuration upon removal of a radially restraining force of the catheter outer tubular member, and a reversibly collapsible stent stop secured to the inner tubular member. The outer tubular member has an advanced configuration surrounding a distal section of the inner tubular member, and a proximally retracted configuration, and the inner tubular member is configured for proximally withdrawing the distal section of the inner tubular member into the outer tubular member in the retracted configuration and thereby transitioning the outer tubular member from the retracted to the advanced configuration to ready the catheter for deployment of the next stent. The second collapsed stent is longitudinally spaced apart proximally from the first stent, and the stent stop is configured to radially collapse as the inner tubular member is proximally withdrawn into the outer tubular member through the second collapsed stent, and radially self expand along at least a section thereof at a location proximally adjacent to a proximal end of the second collapsed stent. Thus, the stent stop is slidably positionable to different locations relative to the collapsed stents in the delivery catheter, such that the stent stop initially abuts a proximal end of the first collapsed stent to thereby inhibit proximal movement of the first stent in a first locational configuration, and is configured for being slidably positioned to abut the proximal end of the second collapsed stent to thereby inhibit proximal movement of the second stent in a second locational configuration.
In another aspect of the present invention, the delivery catheter of the invention has only one reversibly collapsible stent stop. In alternative embodiments, an additional reversibly collapsible stent stop is provided at the proximal end of the second (next proximal) stent when said (first) stent stop is in the first locational configuration. Similarly, one or more additional reversibly collapsible stent stops can be provided at the proximal ends of any additional proximally spaced stents in the delivery catheter.
In a method of the invention in which a stent is delivered and deployed in a patient's body lumen, after the delivery catheter outer tubular member is proximally retracted to cause the first stent to radially self expand in the patient's body lumen, the delivery catheter inner tubular member is then proximally withdrawn relative to the outer tubular member and remaining collapsed stents, to position the stent stop at the proximal end of the proximally-next collapsed stent, to ready the catheter for deployment thereof. In one aspect of the invention, the method more specifically includes advancing the stent delivery system to position the first collapsed stent at a desired treatment site in the body lumen with the outer tubular member in the advanced configuration, and deploying the first stent by proximally retracting the outer member relative to the inner tubular member and first stent so that the first stent radially self expands to a deployed configuration in the body lumen with the stent stop in the first locational configuration, such that the stent stop inhibits proximal movement of the first stent, and proximally withdrawing the distal section of the inner tubular member into the outer tubular member in the retracted configuration and thereby transitioning the outer tubular member from the retracted to the advanced configuration, and positioning the stent stop in the second locational configuration by collapsing the stent stop by proximally withdrawing the stent stop (and inner tubular member secured thereto) through the collapsed second stent and radially self expanding the stent stop along at least a section thereof at a location proximally adjacent to the proximal end of the second collapsed stent.
The second stent (and any subsequent stents) can be deployed adjacent to the previously deployed stent(s), or, partially overlapping the previously deployed stent (s) so as to provide continuous scaffolding for a section of the vessel that is longer than one stent, or, fully overlapping the previously deployed stent(s) so as to provide additional scaffolding in the same area of the first stent. Alternatively, the stent delivery system can be repositioned in the body lumen or in a different body lumen prior to deployment of the next stent(s). The stents can have different characteristics from each other, to provide a range of treatment options. For example, the stents can have different maximum deployed outer diameters or lengths. Additionally, in one embodiment, only some of the stents are configured for drug delivery (e.g., drug coated), which facilitates keeping the intervention under the body systemic drug limit. Similarly, some stents can be configured to deliver one drug whereas one or more of the other stents deliver one or more other drugs, which would allow tailoring the drug delivery to various different anatomies or disease states.
Alternatively, the second stent can be a covered stent that can be used in situations when the vessel wall may be accidentally ruptured by a previously deployed stent. In this situation, it is critical to quickly deploy the covered stent to stop the bleeding out of the body vessel. Vessel wall rupture most often occurs after a self-expanding stent has been deployed and a catheter having an expansion member (typically an expandable balloon) is used to further expand the vessel lumen at stent site. An expandable balloon portion could be incorporated into the present invention such that the balloon portion is located distal to the stents which are mounted on the catheter. The balloon portion could be initially utilized to pre-dilate the vessel lumen at the lesion site. A stent can then be deployed into the body lumen. The balloon portion can then be retracted proximally to position the balloon within the deployed stent to allow the balloon to be utilized to further expand the lesion at the stent site. In the event that the vessel wall should rupture, then the covered stent could be deployed within the previously deployed stent. The balloon portion can then be inflated within the covered stent for a period of time which allows the pressure exerted by the balloon to stop any bleeding. The balloon portion can then be deflated and removed from the patient after bleeding has stopped. The use of this balloon portion distal to the pre-mounted stents allows the physician to both pre-dilate the area of stenosis before the stent id deployed and to post-dilate the stenosis after the stent is deployed in the body vessel. Subsequent stents could then be deployed and dilated in multiple sites or to form a continuous scaffolding. This combination of pre-mounted stents and an expandable member, such as an expandable balloon, provide a delivery system which allows for fast and efficient intervention. It should be appreciated that a catheter made in accordance with the present invention having multiple pre-mounted stent also could be used to perform a procedure utilizing a separate catheter having an expandable balloon member. In this procedure, the balloon catheter could be used to pre-dilate several sites or one continuous site, as needed, with the multi-stent catheter then being used to deploy several stents as needed. Thereafter, the balloon catheter could be positioned again to post-dilate the deployed stents.
The delivery catheter provides for accurate deployment of multiple stents at desired treatment sites in the patient's anatomy, due at least in part to the stent stop which is configured to radially collapse and expand as it is slidably positioned within the delivery catheter, and which is radially expanded in a longitudinal gap between a distal collapsed stent ready to be deployed and the proximally-next collapsed stent configured for deploying after the distal stent is deployed. Additionally, the length of the inner tubular member extending beyond the outer tubular member is kept from increasing after each stent deployment by proximally withdrawing the inner tubular member back into the outer tubular member after each stent deployment. As a result, the stent delivery catheter system facilitates quick and easy delivery and deployment of multiple stents to adjoining or different desired locations in the patient's anatomy.
In another aspect of the present invention, a stent delivery catheter can include a pair of stent retainers, each having a portion secured to the elongate shaft member forming the stent delivery catheter and a portion which is slidingly disposed on a portion of the expandable member (for example, an inflatable balloon). Each stent retainer is designed to initially engage an end of the collapsed stent to thereby inhibit proximal and distal movement of the stent from its mounted position on the balloon. The stent retainer can engage the stent by abutting against the end of the stent to prevent longitudinal movement. Alternatively, the stent retainer can engage the stent by having the stent contact portion of the retainer placed over the end of the stent. The other portion of the stent retainer can be fixedly attached to the elongate shaft member forming the catheter or it can be frictionally secured to the shaft member.
In another aspect of the invention, each stent retainer can include at least a pair of cylindrical rings attached together which are adapted to expand with the expandable member as it expands the mounted stent. These rings of the stent retainer move with the expandable member as it partially expands to continue to engage the stent and inhibit proximal movement of the stent form its mounted position.
In another aspect of the invention, one or more stent retainer rings can be used to retain the stent on the stent delivery catheter. Such a stent retainer ring can be disposed on a portion of mounted stent such that the stent retainer ring inhibits both proximal and distal movement of the stent from its mounted position. These retainer rings also could be used on self-expanding stents to prevent the stent from expanding to the expanded position. The retainer ring would have a nominal width and a wall thickness and would include a plurality of tear sections each having a width and/or wall thickness which is less that the nominal width and wall thickness of the remaining portion of the ring. The tear sections of the retainer ring are adapted to be placed between struts of the stent as it is mounted to the expandable member (balloon) and are adapted to break when the balloon is expanded. The retainer ring can be made from a bio-absorbable material which dissolves over time. At least a portion of the retainer ring could be secured to the stent by a bioabsorbable material to ensure that pieces of the ring do not enter the patient's vasculature. The ring can be of a simple cylindrical shape and made from a bioabsorbable material so that as the balloon is expanded the rings simply tear and are wedged between the stent and the vessel wall and remain there until they are dissolved.
These and other advantages of the invention will become more apparent from the following Detailed Description and accompanying exemplary drawings.
In the illustrated embodiment, the first mechanism 20 is configured to slide proximally to effect proximal retraction of the outer tubular member. A variety of suitable handles can be used with a catheter of the invention, generally having a thumb wheel and/or slide activated mechanism. Generally, slide mechanisms, such as the one shown, may be preferred for coronary applications while handles utilizing a thumb wheel as the actuating mechanism may be preferred for peripheral applications where the stents may be longer in length and a higher delivery force is needed to retract the other tubular member. In peripheral cases, a thumb wheel mechanism can provide a mechanical advantage to overcome the initial delivery force resulting from longer and multiple stents. Fittings such as luer fitting 21 are typically provided at the proximal end of the catheter handle for making a fluid connection to an inner lumen of the catheter (e.g., for flushing out the lumen), and may also provide access for a guide wire into a guide wire lumen of the catheter. The handle typically has lock mechanisms which can be separately engaged to prevent unwanted longitudinal movement of the inner and outer tubular members individually.
Although illustrated with three stents 14, 15, 16, it should be understood that a stent delivery system of the invention more generally has a first (distal) stent and one or more additional stents longitudinally spaced apart proximally from the first stent and from each other, in a collapsed configuration in the outer tubular member, configured to deploy by radially self expanding from the collapsed configuration to an expanded configuration upon removal of the radially restraining force of the catheter outer tubular member. The stents are configured to deploy in order from the first stent to each successive next proximal one or more additional stents, and the outer tubular member has a first advanced configuration surrounding the distal section 18 of the inner tubular member 13 and the first stent 14, and one or more additional advanced configurations surrounding the distal section 18 of the inner tubular member 13 and each successive next proximal one or more additional stents (e.g., 15, 16) which are in the collapsed configuration in the outer tubular member 12.
The collapsed stents in the delivery catheter are in an annular space 22 between the outer tubular member 12 and the inner tubular member 13, with the outer surface of the stents in contact with the inner surface of outer tubular member radially spaced above the outer surface of the inner tubular member. The outer tubular member 12 is typically formed of multiple tube sections providing tailored performance characteristics along the length of the catheter. For example, in the illustrated embodiment, the outer tubular member has a stent restraining distal tube or distal outer member or sheath 23 which is configured to radially restrain the collapsed stents therein. Its proximal end is bonded to a distal end of a proximally adjacent tube of the outer tubular member, which is typically more flexible than the distally adjacent distal sheath. A lubricious layer or coating (not shown) on the inner surface of the stent restraining tube 23 can be provided to facilitate proximally retracting the outer tubular member during stent deployment. Although not illustrated, an outer-most tubular member may be provided on a proximal end section of the outer tubular member 12 to provide additional stabilization. The inner tubular member 13 may be similarly formed of multiple tubes joined end to end, and/or multiple layer tube(s). Additionally, a stent holder layer can be provided on an outer surface of the sections of the inner tubular member that is surrounded by the collapsed stents 14, 15, 16, which decreases the size of the gap between the inner surface of the collapsed stent and the outer surface of the inner tubular member to improve catheter deliverability.
The inner tubular member 13 has a lumen 24 therein. In the illustrated embodiment, the inner tubular member lumen 24 is configured to slidably receive a guide wire (see
A distal tip member 25 at the distal end of the inner tubular member is configured to preferably reduce trauma to the patient's body lumens as the system 10 is advanced therein. In the illustrated embodiment, the distal member 25 includes a proximal stem fixedly secured to the distal end of the inner tubular member 13, and with a guide wire distal port 26 in a distal end of the distal tip member 25. However, the distal tip member 25 can alternatively be formed as an integral, one-piece extension of the distal end of the catheter shaft. The distal tip member 25 has a radially enlarged (maximum outer diameter) section which in the illustrated embodiment is substantially flush with the distal end of the outer tubular member stent restraining region 23, such that it provides a gradually tapering surface in front of and covering the end of the outer member, to facilitate atraumatically maneuvering the catheter through the patient's tortuous anatomy. Also, the maximum diameter of the tip can have a radiused edge instead of a sharp corner. This will also prevent vessel wall damage, especially when the outer tubular member is moved proximally when deploying a stent and the tip is substantially distal of the distal end of the other tubular member. Also, after the stent is deployed, the tip will be distal of the stent and will need to be pulled through the deployed stent. A radius on the outer edge of this tip 25 will help to prevent the tip 25 from catching behind the distal end of the deployed stent. The maximum outer diameter of the distal tip 25 can be smaller than the inner diameter of the stent restraining region 23 of the outer tubular member 12, or if larger it can be configured to be radially collapsible, to allow the inner tubular member 13 to be proximally withdrawn into the outer tubular member 12 a distance greater than the length of the stent(s), so that the stent stop 17 can thereby reach the proximal end of the next stent to be deployed when the stent has moved proximally with the outer tubular member during the previous stent deployment. This allows the distal tip member to be drawn into the outer tubular member 12 as the inner tubular member 13 is retracted within the outer tubular member 12.
The distal tip member 25 is typically formed of a relatively soft polymeric material having a lower Shore durometer hardness than at least a layer of the inner tubular member 13 proximally adjacent thereto. In one preferred embodiment, the distal tip member 25 is formed of a blend of polymeric material and radiopaque material such that it is radiopaque, although it could be made radiopaque using a variety of suitable methods including being provided with radiopaque material in form of a marker band, to make at least a portion of the distal tip visible under fluoroscopy during use of the system 10. A marker band is a common component used for visualization. Alternatively, a radiopaque tip could be used as well for visualization.
Secured to the inner tubular member 13, the reversibly collapsible stent stop 17 is illustrated in
The particular embodiment of the stent stop 17 of
The stent stop 17 is preferably made from a material which is self-expanding, such as nickel-titanium (Nitinol) or similar materials. Spring steel could also be used. The stent stop 17 also should be radiopaque, as for example by being formed of a radiopaque metal such as a nickel-titanium loaded with platinum, or similar materials, or a blend of polymeric and radiopaque materials, although other suitable methods of providing the stent stop 17 with radiopacity can alternatively be used including adding a radiopaque marker to the stop or using fittings made from a radiopaque material.
The stent stop 17 also can be formed from a moldable polymer, such as Nylon or polypropylene, although it can alternatively be formed of Nitinol and other self-expanding materials, as mentioned above. In the illustrated embodiment, and particularly when the stent stop is made from a metal or polymer, one or more slots 31 or other voids formed in a wall of stent stop 17 along larger outer diameter portion 27 and distal section 29 make the stent stop radially springy. As can be seen in
Alternative embodiments of the stent stop are shown in
Following deployment of the first stent 15, the inner tubular member 13 distal section 18, which is now distally spaced from the distal end of the outer tubular member, is proximally withdrawn into the retracted outer tubular member 12. The inner tubular member 13 is withdrawn a sufficient distance to transition the outer tubular member 12 from the retracted to the advanced configuration (i.e., so that the outer tubular member surrounds the distal section 18 of the inner tubular member 13. Additionally, the stent stop 17 is thereby positioned in the second locational configuration between the second and third stents 15, 16.
With the outer tubular member 12 in the advanced configuration surrounding the distal section 18 of the inner tubular member and the second stent 15 therearound, the second stent 15 can be deployed either with or without repositioning the stent delivery system 10 in the patient after deployment of the first stent 14. If the system is not repositioned or is only slightly moved in the patient's anatomy, the second stent 15 can be deployed at a desired site adjacent to the first expanded stent 14, with the ends of the expanded stents 14, 15 overlapped (as is typically done for lesions that are longer than a single stent), touching or somewhat spaced apart. Alternatively, the system can be advanced or retracted to a desired treatment site in the body lumen 40 or in a different body lumen, to deploy the second stent 15 remotely from the first expanded stent 14. As before, and as is shown in
Following deployment of the second stent 15, the inner tubular member 13 can be again proximally withdrawn as before.
In the embodiment illustrated in
In contrast, in the embodiment of
An alternative embodiment of a multiple stent delivery catheter 60 is shown in
Additionally, stents, such as bio-absorbable stents, are usually susceptible to fracture or radial force degradation from fluctuation of the strain resulting from the crimp. The elimination of the need to crimp such a bio-absorbable stent to the catheter would ultimately help in the final deployment since the bio-absorbable stent would only be expanded from a single application of force caused by the balloon on such a stent. Accordingly, the elimination of the crimping of the bio absorbable stent to the delivery catheter will help to prevent fracture and other deformations which can result from a crimping process.
Referring initially to
The second stent (and any subsequent stents) can be deployed adjacent to the previously deployed stent(s), or, partially overlapping the previously deployed stent (s) so as to provide continuous scaffolding for a section of the vessel that is longer than one stent, or, fully overlapping the previously deployed stent(s) so as to provide additional scaffolding in the same area of the first stent. Alternatively, the stent delivery system can be repositioned in the body lumen or in a different body lumen prior to deployment of the next stent(s).
Alternatively, the second stent can be a covered stent that can be used in situations when the vessel wall may be accidentally ruptured by a previously deployed stent. In this situation, it is critical to quickly deploy the covered stent to stop the bleeding into the body vessel. Vessel wall rupture most often occurs after a self-expanding stent has been deployed and a catheter having an expansion member (typically an expandable balloon) is used to further expand the vessel lumen at stent site. An expandable balloon portion could be incorporated into the present invention such that the balloon portion is located distal to the stents which are mounted on the catheter. The balloon portion could be initially utilized to pre-dilate the vessel lumen at the lesion site. A stent can then be deployed into the body lumen. The balloon portion can then be retracted proximally to position the balloon within the deployed stent to allow the balloon to be utilized to further expand the lesion at the stent site. In the event that the vessel wall should rupture, then the covered stent could be deployed within the previously deployed stent. The balloon portion can then be inflated within the covered stent for a period of time which allows the pressure exerted by the balloon to stop any bleeding. The balloon portion can then be deflated and removed from the patient after bleeding has stopped. The use of this balloon portion distal to the pre-mounted stents allows the physician to both pre-dilate the area of stenosis before the stent is deployed and to post-dilate the stenosis after the stent is deployed in the body vessel. Subsequent stents could then be deployed and dilated in multiple sites or to form a continuous scaffolding. This combination of pre-mounted stents and an expandable member, such as an expandable balloon, provide a delivery system which allows for fast and efficient intervention. It should be appreciated that a catheter made in accordance with the present invention having multiple pre-mounted stents also could be used to perform a procedure utilizing a separate catheter having an expandable balloon member. In this procedure, the balloon catheter could be used to pre-dilate several sites or one continuous site, as needed, with the multi-stent catheter then being used to deploy several stents as needed. Thereafter, the balloon catheter could be positioned again to post-dilate the deployed stents.
In another embodiment, the stent stop 17 can be placed closer to the distal tip member 25 up to even contacting the tip (provided the tip is soft so it can retract inside the stent to be delivered, or it is of a smaller diameter than the collapsed stent or made as part of the tip so in this way the tip is a combination tip and stent stop). A method of use would include the following: 1) track the delivery catheter to stent deployment site, 2) retract the inner tubular member until the stent stop is proximal of the first stent and 3) if desired, multiple stents can be deployed by moving the stent stop back past the multiple stents and pushing them out one after the other. The advantage of this system, whether deploying one stent at a time or multiple stents at a time, is that the distal tip member does not extent significantly distal of the outer tubular member as the outer tubular member is proximally retracted when deploying a stent. The advantage of this system is that the possibility that the distal tip member can get caught in a deployed stent is virtually eliminated. Also the tip is not extended distally in the vessel. This is significant in anatomy where distal vessels are small, delicate or torturous. Examples of this type of anatomy are renal and cerebral arteries.
Referring now to
Referring now to
Referring now to
In another embodiment of the invention, depicted in
In another aspect of the invention, depicted in
The various stents in the delivery catheter can be all the same, or have one or more different characteristics. The stents can have different characteristics from each other, to provide a range of treatment options. For example, the stents can have different maximum deployed outer diameters or lengths. Additionally, in one embodiment, only some of the stents are configured for drug delivery (e.g., drug coated), which facilitates keeping the intervention under the body systemic drug limit. Similarly, some stents can be configured to deliver one drug whereas one or more of the other stents deliver one or more other drugs, which would allow tailoring the drug delivery to various different anatomies or disease states. In one embodiment, two or more of the stents have different lengths. Similarly, two or more of the stents can have different outer diameters. Preferably, the handle 19 would be marked with the stent sizes so that there would be direct communication to the physician of the size of the next stent to be deployed. Also the stent stop could be made from a radiopaque material so that the doctor could visually see when the stent stop was correctly positioned behind the stent being deployed. Additionally, other characteristics such as whether or not the stent has a drug or other agent coated or otherwise applied thereto, the amount of the drug, and the nature of the drugs delivered by the multiple stents can all vary amongst the different stents. By way of example, the maximum expanded diameter of stents useful in a system of the invention typically ranges from of about 2 to about 10 mm, and the maximum expanded length ranges from about 10 to about 200 mm. This size range covers peripheral and coronary applications and self expanding and balloon expandable metal and bioabsorbable stents.
In a presently preferred embodiment, a catheter system of the invention is configured for delivering and deploying one or more of the stents in the patient's superficial femoral and iliac arteries, although it could be configured for use in a variety of body lumens, including other peripheral and coronary vessels and non-vascular body lumens.
The stent retainers disclosed in
The catheter components, such as the inner and outer tubular members, can be formed of materials found useful in catheter construction. For example, the polymeric tubular members can be formed of materials such as polyamides, polyamide copolymers (e.g., polyether block amide), polyolefins (e.g., polyethylene), polyurethanes, polyesters, and the like. Generally speaking, the more proximal portions of the catheter inner and outer tubular members will be stiffer than the distal portions, to provide the catheter sufficient pushability, and the catheter distal section is configured to provide flexibility and trackability to advance through the patient's vascular system by tracking on a wire in the lumen. The distal sheath 23 that covers the stent before it is deployed, and particularly for self-expanding stents that apply an outward force in the radial direction on the distal sheath, needs to have a high resistance to radial expansion. This is typically achieved through thin rigid materials such as polyimide or a more flexible braded material where a metal bead is encapsulated by nylon or other suitable polymer.
A multilayered balloon could be used with the other components of the present invention. Such a multilayered balloon could include a first layer and at least a second layer, and could have noncompliant limited radial expansion beyond the nominal diameter of the balloon. By selecting the polymeric materials forming the balloon layers, and arranging and radially expanding the multiple layers of the balloon, one can create a balloon that has improved low compliance, preferably in combination with high flexibility and softness. Such a multilayered balloon can be formed in whole or in part of coextruded polymeric tubular layers. A multilayered balloon is typically formed by conventional blow-molding in which a multilayered polymeric tube is radially expanded within a balloon mold. The resulting multilayered balloon has an inflated shape which corresponds to the inner surface of the mold and which has a diameter about equal to the inner diameter of the balloon mold, commonly referred to as the balloon's nominal working diameter. The nominal pressure is the inflation pressure required to fill the balloon to the nominal working diameter. The balloon expands a very small amount (i.e., noncompliantly) at pressures above the nominal pressure. As a result, the balloon minimizes injury to a patient's blood vessel, which can otherwise occur if the balloon continues to expand a substantial uncontrolled amount at increasing inflation pressures above nominal.
The blow-up-ratio (BUR) of a balloon formed from a polymer tube should be understood to refer to the ratio of the outer diameter of the blown balloon expanded within the mold (i.e., the mold inner diameter) to the inner diameter of the polymer tube prior to being expanded in the mold. Each individual layer of a multilayered balloon similarly has its own BUR based on the ratio of the inner diameter of the mold and the inner diameter (prior to expansion in the mold) of the layer of the polymeric tube. For a given balloon wall thickness, the rupture strength generally increases and the radial compliance decreases as the balloon BUR increases. For standard pressure driven blow molding of catheter balloons, typical BURs range from about 4.5 to about 8.0 depending on the material and the product application. Specifically, a multilayered balloon can be made with polymeric materials that can be expanded to higher BURs as the inner layer(s) of the balloon, while lower BUR materials are the outer layer(s) of the balloon. The balloon can have a first layer of a first polymeric material and a second layer of a second polymeric material which has a lower Shore durometer hardness than the first polymeric material and which can be expanded during balloon blowing to a higher BUR (without rupturing or tearing) than the higher Shore durometer hardness material of the first layer, and the second layer is an inner layer relative to the first layer. For example, the multilayered balloon inner layer can be formed of a polyether block amide (PEBA) material (e.g., commercially available as PEBAX®) having a Shore durometer hardness of about 60-70D while the outer layer is formed of a PEBA material having a higher Shore durometer hardness of about 70-72D. However, a variety of suitable materials can be used including materials which are of the same material classification/family, or different classes of materials. The multilayered balloon generally includes two or more layers (i.e., layers formed of materials which differ in some respect such as different Shore durometer hardnesses), although it typically does not have more than about five layers.
For example, a suitable multilayered balloon would include a first (outer) layer of a first durometer, and one or more inner layer(s) of successively lower durometers (i.e., increasingly softer materials), has a lower compliance than a balloon having about the same wall thickness but formed of 100% of the highest durometer material (i.e., the material forming the outer-most layer of the balloon). Compared to a balloon formed of 100% of the highest durometer material, a multilayered balloon has effectively replaced a part of the balloon wall thickness with the layer(s) of lower durometer (softer) material(s), which would typically be expected to increase the compliance. While not wishing to be bound by theory, it is believed that the balloon provides the noncompliant behavior through the specific combination of highly oriented layers of the balloon, and particularly by maximizing the orientation of the inner layer(s) of the balloon. The inner layer orientation significantly affects compliance of the balloon. By selecting and arranging different materials that can be blown to different BURs in accordance with the invention, the balloon has layers with successively increasing BURs from the outer to the inner layer(s), such that the BUR of each layer is preferably maximized and the inner layer(s) have particularly high BURs. The layers of the balloon are therefore optimized for compliance purposes. Although additional layers may be added to the balloon, to, for example, increase the total wall thickness to a desired value, the arrangement of the basic layers in accordance with the invention cannot be varied without resulting in a higher compliance balloon.
Another suitable multilayered balloon would include a first (outer) layer of a first durometer material and one or more inner layer(s) of successively lower durometer materials which has a compliance not substantially greater than (e.g., not more than about 10% to about 20% greater than), and preferably about equal to a balloon which is formed of 100% of the highest durometer material but which has a larger wall thickness than the multilayered balloon of the invention. This balloon has a very thin total wall thickness provides an improved low profile and flexibility due to the thinner walls of the balloon, but, in accordance with the invention, nonetheless continues to provide a low compliance despite the thin wall.
The rupture pressure and compliance of a balloon are affected by the strength (e.g., hoop strength) of a balloon. Because a softer material generally has a relatively lower hoop strength, the presence of the lower durometer material forming the inner layer(s) of the balloon is not generally expected to provide a relatively higher modulus balloon. However, a multilayered balloon preferably has a higher modulus than, and a rupture pressure which is not substantially less than, a balloon formed of 100% of the highest durometer material.
The presence of the lower durometer material inner layer(s) does provide layers of increased softness, and therefore preferably provides a balloon that is softer and more flexible than a balloon formed of 100% of the highest durometer material. The multilayered balloon can be made from elastomers, which typically have a lower flexural modulus than nonelastomers. Elastomeric polymers suitable for forming the first and/or second layer of the multilayered balloon typically have a flexural modulus of about 40 kpsi to about 110 kpsi. Thus, unlike nonelastomeric materials such as PET which have been used in the past to provide relatively low compliance catheter balloons, the multilayered noncompliant balloon is preferably formed of one or more elastomers which provide for improved balloon flexibility.
The balloon catheter also can be at least partially loaded with therapeutic agent which is allowed to treat the walls of the body vessel. “Therapeutic agent” as used herein, refers to any compound, mixture of compounds, or composition of matter consisting of a compound, which produces a therapeutic or useful result. The therapeutic agent can be a polymer, a marker, such as a radiopaque dye or particles, or can be a drug, including pharmaceutical and therapeutic agents, or an agent including inorganic or organic drugs without limitation. The agent or drug can be in various forms such as uncharged molecules, components of molecular complexes, pharmacologically acceptable salts such as hydrochloride, hydrobromide, sulfate, laurate, palmitate, phosphate, nitrate, borate, acetate, maleate, tartrate, oleate, and salicylate.
An agent or drug that is water insoluble can be used in a form that is a water-soluble derivative thereof to effectively serve as a solute, and on its release from the device, is converted by enzymes, hydrolyzed by body pH or metabolic processes to a biologically active form. Additionally, the agents or drug formulations can have various known forms such as solutions, dispersions, pastes, particles, granules, emulsions, suspensions and powders. The drug or agent may or may not be mixed with polymer or a liquid as desired.
In an embodiment of the invention, at least one therapeutic agent can be selected from but not limited to anti-proliferative, anti-inflammmatory, antineoplastic, antiplatelet, anti-coagulant, anti-fibrin, antithrombotic, antimitotic, antibiotic, antiallergic and antioxidant compounds. Thus, the therapeutic agent can be, again without limitation, a synthetic inorganic or organic compound, a protein, a peptide, a polysaccharides and other sugars, a lipid, DNA and RNA nucleic acid sequences, an antisense oligonucleotide, an antibodies, a receptor ligands, an enzyme, an adhesion peptide, a blood clot agent including streptokinase and tissue plasminogen activator, an antigen, a hormone, a growth factor, a ribozyme, a retroviral vector, an anti-proliferative agent including rapamycin (sirolimus), 40-O-(2-hydroxyethyl)rapamycin (everolimus), 40-O-(3-hydroxypropyl)rapamycin, 40-O-(2-hydroxyethyoxy)ethylrapamycin, 40-O-tetrazolylrapamycin (zotarolimus, ABT-578), paclitaxel, docetaxel, methotrexate, azathioprine, vincristine, vinblastine, fluorouracil, doxorubicin hydrochloride, and mitomycin, an antiplatelet compound, an anticoagulant, an antifibrin, an antithrombins including sodium heparin, a low molecular weight heparin, a heparinoid, hirudin, argatroban, forskolin, vapiprost, prostacyclin, a prostacyclin analogue, dextran, D-phe-pro-arg-chloromethylketone (synthetic antithrombin), dipyridamole, glycoprotein IIb/IIIa platelet membrane receptor antagonist antibody, recombinant hirudin, a thrombin inhibitor including Angiomax ä, a calcium channel blocker including nifedipine, colchicine, a fibroblast growth factor (FGF) antagonist, fish oil (omega 3-fatty acid), a histamine antagonist, lovastatin, a monoclonal antibodie, nitroprusside, a phosphodiesterase inhibitor, a prostaglandin inhibitor, suramin, a serotonin blocker, a steroid, a thioprotease inhibitor, triazolopyrimidine, a nitric oxide or nitric oxide donor, a super oxide dismutase, a super oxide dismutase mimetic, estradiol, an anticancer agent, a dietary supplement including vitamins, an anti-inflammatory agent including aspirin, tacrolimus, dexamethasone and clobetasol, a cytostatic substance including angiopeptin, an angiotensin converting enzyme inhibitor including captopril, cilazapril or lisinopril, an antiallergic agent including permirolast potassium, alpha-interferon, bioactive RGD, and genetically engineered epithelial cells. Other therapeutic agents which are currently available or that can be developed in the future for use with implantable medical devices can likewise be used and all are within the scope of this invention.
Examples of such antithrombotics, anticoagulants, antiplatelet agents, and thrombolytics include sodium heparin, low molecular weight heparins, heparinoids, hirudin, argatroban, forskolin, vapriprost, prostacyclin and prostacylin analogues, dextran, D-phe-pro-arg-chlorometh-ylketone (synthetic antithrombin), dipyridamole, glycoprotein IIb/IIIa (platelet membrane receptor antagonist antibody), recombinant hirudin, and thrombin inhibitors such as Angiomax™, from Biogen, Inc., Cambridge, Mass.; and thrombolytic agents, such as urokinase, e.g., Abbokinase™ from Abbott Laboratories Inc., North Chicago, Ill., recombinant urokinase and pro-urokinase from Abbott Laboratories Inc., tissue plasminogen activator (Alteplase™ from Genentech, South San Francisco, Calif. and tenecteplase (TNK-tPA).
Examples of such cytostatic or antiproliferative agents include rapamycin and its analogs such as everolimus, ABT-578, i.e., 3S,6R,7E,9R,10R,12R,14S,15E,17E,19E,21S,23S,26R,27R,34aS)-9,10,12,13,14,2-1,22,23,24,25,26,27,32,33,34,34a-Hexadecahydro-9,27-dihydroxy-3-[(1R)-2-[(-1S,3R,4R)-3-methoxy-4-tetrazol-1-yl)cyclohexyl]-1-methylethyl]-10,21-dimet-hoxy-6,8,12,14,20,26-hexamethyl-23,27-epoxy-3H-pyrido[2,1-c][1,4]oxaazacyclohentriacontine-1,5,11,28,29(4H,6H,31H)-pentone; 23,27-Epoxy-3H pyrido[2,1-c][1,4]oxaazacyclohentria-contine-1,5,11,28,29(4H,6H,31H)-pento-ne, which is disclosed in U.S. Pat. No. 6,015,815, U.S. Pat. No. 6,329,386, U.S. Publication 2003/129215, filed on Sep. 6, 2002, and U.S. Publication 2002/123505, filed Sep. 10, 2001, the disclosures of which are each incorporated herein by reference thereto, tacrolimus and pimecrolimus, angiopeptin, angiotensin converting enzyme inhibitors such as captopril, e.g, Capoten® and Capozide® from Bristol-Myers Squibb Co., Stamford, Conn., cilazapril or lisinopril, e.g., Prinivil™ and Prinzide™ from Merck & Co., Inc., Whitehouse Station, N.J.; calcium channel blockers such as nifedipine, amlodipine, cilnidipine, lercanidipine, benidipine, trifluperazine, diltiazem and verapamil, fibroblast growth factor antagonists, fish oil (omega 3-fatty acid), histamine antagonists, lovastatin, e.g. Mevacor™ from Merck & Co., Inc., Whitehouse Station, N.J. In addition, topoisomerase inhibitors such as etoposide and topotecan, as well as antiestrogens such as tamoxifen can be used.
Examples of such anti-inflammatories include colchicine and glucocorticoids such as betamethasone, cortisone, dexamethasone, budesonide, prednisolone, methylprednisolone and hydrocortisone. Non-steroidal anti-inflammatory agents include flurbiprofen, ibuprofen, ketoprofen, fenoprofen, naproxen, diclofenac, diflunisal, acetominophen, indomethacin, sulindac, etodolac, diclofenac, ketorolac, meclofenamic acid, piroxicam and phenylbutazone.
Examples of such antineoplastics include alkylating agents such as altretamine, bendamucine, carboplatin, carmustine, cisplatin, cyclophosphamide, fotemustine, ifosfamide, lomustine, nimustine, prednimustine, and treosulfin, antimitotics such as vincristine, vinblastine, paclitaxel, e.g., TAXOL® by Bristol-Myers Squibb Co., Stamford, Conn., docetaxel, e.g., Taxotere™ from Aventis S. A., Frankfurt, Germany, antimetabolites such as methotrexate, mercaptopurine, pentostatin, trimetrexate, gemcitabine, azathioprine, and fluorouracil, and antibiotics such as doxorubicin hydrochloride, e.g., Adriamycin™ from Pharmacia & Upjohn, Peapack, N.J., and mitomycin, e.g., Mutamycin™ from Bristol-Myers Squibb Co., Stamford, Conn., agents that promote endothelial cell recovery such as estradiol.
Other agents and materials could conceivably be delivered into a patient anatomy. For example, angiogenetic factors could be delivered. This includes growth factors such as isoforms of vasoendothelial growth factor (VEGF), fibroblast growth factor (FGF, e.g. beta-FGF), Del 1, hypoxia inducing factor (HIF 1-alpha), monocyte chemoattractant protein (MCP-1), nicotine, platelet derived growth factor (PDGF), insulin-like growth factor (HGF), estrogens, follistatin, proliferin, prostaglandin E1 and E2, tumor necrosis factor (TNF-alpha), interleukin 8 (Il-8), hematopoietic growth factors, erythropoietin, granulocyte-colony stimulating factors (G-CSF) and platelet-derived endothelial growth factor (PD-ECGF). In some embodiments, angiogenesis promoting factors include, but are not intended to be limited to, peptides, such as PR39, PR11 and angiogenin, small molecules, such as PHD inhibitors, or other agents, such as eNOS enhancers.
While the foregoing therapeutic agents are known for their preventive and treatment properties, the substances or agents are provided by way of example and are not meant to be limiting. Further, other therapeutic agents that are currently available or may be developed are equally applicable for use with the present invention.
If desired or necessary, the therapeutic agent can include a binder to carry, load, or allow sustained release of an agent, such as but not limited to a suitable polymer or similar carrier. The term “polymer” is intended to include a product of a polymerization reaction inclusive of homopolymers, copolymers, terpolymers, etc., whether natural or synthetic, including random, alternating, block, graft, branched, cross-linked, blends, compositions of blends and variations thereof. The polymer can be in true solution, saturated, or suspended as particles or supersaturated in the therapeutic agent. The polymer can be biocompatible, biosolvable, biostable, or biodegradable.
A variety of suitable self expanding stent designs can be used in a stent delivery system of the invention. Details regarding stent structure can be found in U.S. Pat. No. 6,709,454 (Cox et al.), U.S. Pat. No. 6,663,664 (Pacetti), U.S. Pat. No. 6,375,676 (Cox), U.S. Pat. No. 4,830,003 (Wolff et al.), and U.S. Pat. No. 4,580,568 (Gianturco), incorporated by reference herein in their entireties.
While described herein in terms of certain preferred embodiments, various modifications and improvements can be made to the invention without departing from the scope thereof. Additionally, although individual features of one embodiment of the invention may be discussed herein or shown in the drawings of the one embodiment and not in other embodiments, it should be apparent that individual features of one embodiment may be combined with one or more features of another embodiment or features from a plurality of embodiments.
