Abstract:
A solid embolic material that is capable of filling irregularly shaped and asymmetrical vascular defects in a controlled and predictable manner, without the difficulties associated with delivery of the embolic material through a microcatheter and containment of the embolic material in a defect. A detachable embolic balloon with optional check valve for maintaining liquid in the balloon prior to curing and optional multi-leaflet covering to prevent the balloon from expanding into the native vascular lumen.

Description:
FIELD OF THE INVENTION 
     The present invention generally pertains to embolic balloons and delivery systems. In particular, the present invention relates to embolic balloons delivered by intravascular microcatheters to vascular defects. 
     BACKGROUND OF THE INVENTION 
     In treating vascular defects such as aneurysms and fistulas, which commonly occur in the neurovasculature, a microcatheter is navigated through the patient&#39;s vasculature until a distal end of the microcatheter is adjacent the defect. An embolic material is then delivered through the microcatheter and into the vascular defect, to thereby fill and seal-off the defect. However, because vascular defects like aneurysms and fistulas often have irregularly shaped and asymmetrical volumes, it is difficult to accurately and completely fill the defect with embolic coils, balloons or other embolic devices, which are typically symmetrically shaped. Although liquid embolic materials tend to fill irregularly shaped and asymmetrical volumes more precisely and completely, liquid embolic materials are often difficult to deliver through a microcatheter and are often difficult to contain within the defect. Accordingly, there is a substantial need for an embolic material and delivery system that is capable of filling an asymmetrical and irregularly shaped vascular defect, that is easy to deliver with a microcatheter, and that is easy to contain within the defect. 
     There is also an ongoing need for improved embolic balloons and associated delivery systems. In particular, there is a need for detachable embolic balloons that may be easily delivered and maintained in the vascular defect so as to not protrude into the native vascular lumen. 
     SUMMARY OF THE INVENTION 
     To address this substantial unmet need, the present invention provides, in an exemplary non-limiting embodiment, a solid embolic material that is capable of filling irregularly shaped and asymmetrical vascular defects in a controlled and predictable manner, without the difficulties associated with delivery of embolic material through a microcatheter and containment of embolic material in a defect. The solid embolic material of the present invention may be inflated with a liquid (e.g., liquid embolic material) to further engage the internal walls of the defect and to more completely fill the irregularly shaped volume of the defect. 
     The present invention also provides, in another exemplary non-limiting embodiment, a detachable embolic balloon and associated delivery system. The detachable embolic balloon in this embodiment may be filled with a curable liquid wherein the curing process may be aided by thermal means. The detachable embolic balloon may optionally incorporate a check valve for maintaining the liquid in the balloon prior to curing and/or a multi-leaflet covering to prevent the balloon from expanding into the native or parent vascular lumen. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1  illustrates a microcatheter, a syringe containing a solid embolic material therein for placement into a distal end of the microcatheter, and a syringe containing a fluid for injection into a proximal end of the catheter; 
         FIGS. 2A and 2B  illustrate alternative methods of containing the solid embolic material, and loading the solid embolic material into the distal end of the microcatheter; 
         FIGS. 3A-3C  schematically illustrate the delivery of the solid embolic material into an aneurysm having an irregular shape; 
         FIGS. 4A-4D  schematically illustrate a first embodiment of a detachable embolic balloon and delivery system; and 
         FIGS. 5A-5D  schematically illustrate a second embodiment of a detachable embolic balloon and delivery system. 
     
    
    
     DETAILED DESCRIPTION 
     The following description should be read with reference to the drawings wherein like reference numerals indicate like elements throughout the several views. The detailed description and drawings illustrate embodiments by way of example, not limitation. 
     Refer now to  FIG. 1  which illustrates a microcatheter  10 , a syringe  40 , and a syringe  70 . Syringe  40  contains a solid embolic material  50  which may be disposed or injected into the catheter  10  as indicated by arrow  60 . Syringe  70  contains a fluid  80  (e.g., radiopaque saline solution or liquid embolic agent) for injection into the catheter  10  as indicated by arrow  90 . 
     Microcatheter  10  may be used to deliver the solid embolic material  50  to a vascular defect such as an aneurysm or fistula having an internal wall defining an internal volume therein. The solid embolic material  50  is particularly suitable for filling internal volumes that are irregular in shape and eccentric relative to the neck or opening to the native vascular lumen. 
     Intravascular catheter  10  is sized (length and diameter) and designed (pushability and trackability) to navigate a patient&#39;s vascular system to access vascular defects in the neurovasculature, coronary vasculature and/or peripheral vasculature. Intravascular catheter  10  may include one or more lumens and may be designed to accommodate a guide wire (not shown) and/or to incorporate a distally disposed inflatable balloon (not shown). Although a single lumen intravascular microcatheter  10  is illustrated, those skilled in the art will recognize that a wide variety of intravascular catheters may be used to deliver solid embolic material  50  to a vascular defect. 
     The basic design and construction of microcatheter  10  is conventional in the art, and is provided by way of example, not limitation. Intravascular microcatheter  10  includes an elongate shaft  12  having proximal end  14  and a distal end  16 . A hub assembly  18  is connected to the proximal end  14  of the elongate shaft  12 . A lumen (not visible) extends through the hub assembly  18  and through the length of the shaft  12  to a distal-facing opening (not visible) in the distal end  16  of the shaft  12 . Hub assembly  18  facilitates connection to ancillary devices such as syringe  70  for the injection or infusion of fluids  80  such as contrast media (e.g., radiopaque dye and saline solution) and liquid embolic agents (e.g., cyanoacrylate) into the lumen and out the opening at the distal end  16 . The distal end  16  may be rendered radiopaque by utilizing radiopaque loading in the polymers of the distal end  16  of the shaft  12  or by utilizing a radiopaque marker band  20  disposed thereon. Rendering the distal end  16  radiopaque allows the tip to be precisely navigated utilizing x-ray radiographic techniques. 
     Solid embolic material  50  defines an initially solid volume when disposed in syringe  40  and when disposed in the lumen at the distal end  16  of the shaft  12 . Sufficient solid embolic material is disposed in the lumen of the catheter  10  to fill the internal volume or lining of the targeted vascular defect. Solid embolic material  50  is readily stretchable, viscid and self-sealing such that the material is able to expand upon injection of a fluid into the solid volume thereof. Upon injection of a fluid into the solid volume, the solid embolic material  50  expands to create an internal volume which self-seals and retains the fluid therein. Upon expansion, the solid embolic material  50  is not elastically biased to its original state, but rather tends to assume and hold its expanded state with little or no pressure maintained in the volume created therein. To this end, the solid embolic material  50  is much like bubble-gum in its behavior, albeit for substantially different applications requiring substantially different compositions and designs. 
     The fluid  80  used to inflate the solid embolic material  50  may comprise a radiopaque liquid or a liquid embolic material (e.g., cyanoacrylate), for example. The solid embolic material  50  facilitates containment of the liquid embolic material in the vascular defect, and the liquid embolic material may be selected to solidify after injection into the solid embolic material  50 , in order to assist in sealing the inflated internal volume of the solid embolic material  50 . To facilitate injection of fluid  80  into the solid embolic material, a pressurized fluid source such as a syringe  70  may be connected to the hub assembly  18  of the catheter  10 . Such a device  70  may also be used to pressurize the lumen in the catheter  10  to urge the solid embolic material  50  out of the distal end  16  of the catheter  10  and into the vascular defect. 
     The solid embolic material  50  preferably has relatively high cohesivity and simultaneously is in a state capable of plastic deformation at low pressures. In addition, the solid embolic material  50  preferably has little or no elastic restoring force that will cause the material  50  to contract after pressure is released subsequent to inflation within the defect  100 . Further, in order to facilitate delivery in a compact size and subsequent inflation to a relatively large size, the solid embolic material  50  will preferably withstand 1000% elongation or more, for example, during inflation. Polymer based materials are probably the best candidates for this application. However there are a number of material classes that might be used, and within each class, there are a large number of possible formulations that may have suitable properties. Accordingly, although specific examples are given, the examples are illustrative only. 
     In one embodiment, for example, the solid embolic material  50  may comprise a medium to high molecular weight polymer in a semi-swollen or highly plasticized state. An example of such a polymer comprises poly(vinyl acetate) dissolved in ethanol/ethyl lactate. Another example of such a polymer comprises alkyl methacrylate (the alkyl side-chain being greater than C4) dissolved in a plasticizer (e.g., fatty acid ester, di-alkyl citrate, or triglyceride). Many other combinations of polymers with molecular weights greater than 100 KDa and blended with solvents and/or plasticizers may be applicable in this embodiment as well. The types and concentrations of the polymer/solvent mixture may be selected to optimize the desired characteristics. As an alternative, one of the components of the polymer solution/mixture may melt at a temperature slightly above body temperature and act as a plasticizer for the other component. In this alternative embodiment, a localized heat source may be used to heat the first component to a temperature above body temperature (37C). 
     Other embodiments of polymers suitable for the solid embolic material  50  include polymers that can be transformed to a low modulus state in-situ by small localized temperature changes. Examples of such polymers include non-cross linked polymers having semi-crystalline and amorphous phases (or possessing discrete liquid-crystalline phases) which have first or second order thermal transitions slightly above maximum body temperature (42C), such as long hydrocarbon side-chain acrylic copolymers. Such a polymer may utilize localized heating preferably during inflation and may incorporate tissue adhesive properties when heated. 
     Other examples of polymers that can be transformed to a low modulus state in situ by small localized environment (e.g. temperature) changes include high molecular weight linear polymers, copolymers or blends in a swollen gel or dissolved state which have a sharp decrease in solubility/swelling within the incorporated solvent in response to changes in temperature, ionic strength, or pH, such as poly(n-isopropyl acrylamide) copolymer/blend hyrogels. Such polymers may utilize localized cooling during inflation which causes the polymer to change from a solid or dense gel at body temperature to a swollen or loose hydrogel material capable of deformation at lower temperatures. 
     If a mixture of a polymer and a solvent is used, it may be important to ensure that the polymer remains mixed with the solvent until the time of use, in order for the solid embolic material  50  to retain its desired characteristics. For example, the polymer and solvent may be kept in separate containers and manually mixed just prior to use, using a syringe  40  to inject the mixture into the distal end  16  of the catheter  10  as shown in  FIG. 1 . 
     Alternatively, a container  110  may contain a pre-mix of the polymer/solvent which may then be directly injected into the distal end  16  of the catheter  10  as shown in  FIG. 2A . In this particular embodiment, the container  110  may be rolled, squeezed or shaken to ensure a homogenous mix, opened by removal of a cap (not shown), placed over the distal end  16  of the catheter  10 , and manually squeezed (as indicated by arrows  112 ) to inject the mixture therein (as indicated by arrow  114 ). 
     As a further alternative, a short tubular container  120  containing a premix of the polymer/solvent may be attached to the distal end  16  of the catheter  10  as shown in  FIG. 2B . In this particular embodiment, the container  120  has a sealed distal end  122  that may be cut to provide an opening, and a proximal end  124  sealed by cover  126 . The proximal end  124  is sized to snuggly fit over and attach to the distal end  16  of the catheter  10 . The container  120  may be rolled, squeezed or shaken to ensure a homogenous mix, opened by removal of the cover  126  (as indicated by arrow  125 ), attached to the distal end  16  of the catheter  10  by sliding the proximal end  124  thereon (as indicated by arrow  127 ), and the distal end  122  cut (as indicated by arrow and dashed line  129 ) to provide a distal opening. 
     With reference to  FIGS. 3A-3C , the solid embolic material  50  may be used to treat a vascular defect  100  such as an aneurysm or fistula. The vascular defect  100  includes an internal wall  102  defining an internal volume  104 . Although described herein with reference to the treatment of a vascular defect  100 , the solid embolic material  50  may also be used to occlude vessels for therapeutic purposes. 
     After preparing the catheter  10  with the solid embolic material  50  disposed in the distal end  16  thereof as described above, the catheter  10  may be navigated through a patient&#39;s vascular system until the distal end  16  is disposed adjacent the opening  106  to the vascular defect  100  as seen in  FIG. 3A . 
     The solid embolic material  50  may then be urged from the lumen at the distal end  16  of the catheter  10  and into the vascular defect  100  as seen in  FIG. 3B . This may be accomplished by applying fluid pressure in the catheter lumen proximal of the solid embolic material  50  using syringe  70  connected to the hub assembly  18 . 
     The solid embolic material  50  may then be further urged into the vascular defect until the solid embolic material substantially conforms to the internal wall  102  and substantially fills the internal volume  104  as seen in  FIG. 3C , despite the irregular shape of the wall  102  and volume  104 . This may be accomplished by applying more fluid pressure in the catheter lumen proximal of the solid embolic material  50  using syringe  70  connected to the hub assembly  18 , to cause the fluid  80  to be injected into the solid embolic material  50  and to inflate the same. The solid embolic material  50  may be inflated to varying degrees to conform to vascular defects  100  of varying size and shape. 
     After the defect  100  is substantially filled as confirmed by x-ray fluoroscopy, the solid embolic material  50  in the defect  100  may be detached from the distal end  16  of the catheter  10  (and any solid embolic material  50  remaining in the distal end  16 ) by rotating the catheter  10  and/or by pulling the catheter  10  proximally. 
     Refer now to  FIGS. 4A-4D  which schematically illustrate a distal portion of a detachable embolic balloon catheter  200 . With specific reference to  FIG. 4A , catheter  200  includes an elongate shaft  212  having a proximal end (not visible) and a distal end. Catheter  200  also includes a detachable balloon  214  having a proximal end thereof releasably connected to the distal end of the shaft  212 . The detachable balloon  214  may comprise, for example, any of the materials discussed previously with reference to solid embolic material  50 . 
     The shaft  212  may include a guide wire lumen lateral attachment  216  which defines a guide wire lumen (not visible) extending therethrough to slidably accommodate conventional guide wire  400 . The side attachment  216  may comprise, for example, a short tube connected to the shaft  212  by adhesive, thermal bond, and/or a heat shrink sleeve. The shaft  212  may also include a radiopaque marker band  218  connected to its distal end. Radiopaque marker band  218  may comprise, for example, a band of dense metal such as platinum, gold, iridium, or an alloy thereof. 
     With reference to  FIG. 4B , the elongate shaft may comprise an outer tubular layer  222  surrounding an inner tubular layer  224  which extends distally beyond the outer layer  222 . A reinforcement layer (not shown) such as a metallic or polymeric coil or braid may be disposed between the inner layer  224  and the outer layer  22  to enhance navigational performance of the shaft  212 . The marker band  218  may be disposed on the inner layer  224  distal of the outer layer  22  such that the outside diameter of the marker band  218  is flush with or does not exceed the outside diameter of the outer layer  222 . 
     The proximal end of the balloon may include a radiopaque marker coil  226  molded into the wall of the proximal end of the balloon  214  or connected thereto by other means (e.g., adhesive, thermal bonding, etc.) The radiopaque marker  226  may comprise, for example, a wound wire coil of a dense metal such as platinum, gold, iridium, or an alloy thereof. Together with radiopaque marker band  218 , radiopaque marker coil  226  facilitates radiographic visualization during deployment of the detachable balloon  214 . 
     The inner tubular layer  224  defines a lumen  211  which extends through the full length of the shaft  212  and is in fluid communication with the interior  213  of the balloon  214  via optional check valve  228 . Check valve  228  may comprise a duck-bill type or flapper type valve that permits fluid flow in only the distal direction. As will be described in more detail hereinafter, check valve  228  helps retain the inflation liquid in the interior  213  of the balloon  214  to allow the inflation liquid to cure or to otherwise permit detachment of the balloon  214  from the distal end of the shaft  212  after filling the balloon  214  with a liquid. Detachment of the balloon  214  from the distal end of the shaft  212  may be accomplished with an electrolytic detachment system or with a break-away bond as described in more detail below. 
     Because, the balloon  214  may comprise a material that is highly compliant and flexible at low inflation pressures to permit low pressure expansion (e.g., less than 2 ATM), the connection between the distal end of the shaft  212  and the proximal end of the balloon  214  does not necessarily need to withstand high inflation pressures (e.g., greater than 15 ATM). Thus, the connection between the distal end of the shaft  212  and the proximal end of the balloon  214  may be made detachable by a weak chemical and/or mechanical bond, for example, that may be broken upon the application of torsional and/or longitudinal forces. For example, after the balloon  214  has been deployed, twisting and pulling the proximal end of the shaft  212  may be utilized as a means to break the bond and detach the balloon  214  from the shaft  212 . A relatively weak bond may be provided, for example, by utilizing a relatively lubricious polymer (e.g., PTFE or HDPE without surface activation) for the inner tubular layer  224  and a conventional biocompatible adhesive such as cyanoacrylate to bond the inner tube  224  to the proximal end of the balloon  214 . 
     As mentioned above, the interior  213  of the balloon  214  may be inflated or otherwise filled with a curable liquid such as acrylic monomers, urethane prepolymers, epoxy resins, cyanoacrylates, silicones, or similar material. The polymerization or curing process of such materials or a thermal transition of such materials may be accelerated or induced by heat. Accordingly, a heating device  230  may be introduced through the lumen  211  of the shaft  212  and into the interior  213  of the balloon  214  to supply thermal energy to the curable liquid disposed in the interior  213  of the balloon  214  as shown in  FIG. 4C . The heating device  230  may also be used to heat the balloon  214  if the balloon  214  is formed of a thermally responsive material. The heating device  230  may comprise, for example, a hollow guide wire type shaft  234  having a distally disposed heating element  232 . By way of example, not limitation, the heating element  232  may comprise an electrical resistive heating coil powered via leads (not shown) extending through the shaft  234  to a power source (not shown). 
     Alternatively, the polymerization or curing process may be induced or accelerated by contact with an initiating chemical component or catalyst which may be present within the balloon  214  as a coating on the inside surface of the balloon  214  or as a blend contained in the balloon material. Alternatively, the initiating chemical component or catalyst may be delivered into the balloon  214  via a separate lumen in the shaft  212  or via a separate tube (e.g. hypotube) advanced through the shaft  212 . 
     In use, the catheter  200  is navigated through the patient&#39;s vascular system utilizing radiographic visualization or other visualization techniques until the balloon  214  is disposed adjacent the vascular defect. The balloon  214  is then advanced or otherwise urged into the vascular defect. The interior  213  of the balloon  214  is then inflated with a curable liquid via lumen  211  of the shaft  212 . As the balloon  214  is being inflated, the check valve  228  permits the liquid to enter the interior  213  of the balloon  214  but prevents substantial egress of the liquid thereout. The balloon  214  may then be inflated until the perimeter of the balloon  214  substantially conforms to the contours of the defect. After inflation of the balloon  214 , the liquid in the balloon is allowed to cure, with or without the use of a catalyst or an accelerator. If desired, after or during inflation of the balloon  214 , a heating device  230  may be advanced into the interior  213  of the balloon  214  and activated to initiate and/or accelerate the solidification process of the curable liquid, or to heat the balloon material. Once the inflation liquid has cured or otherwise substantially solidified, the catheter shaft  212  may be released from the balloon  214  by an externally activated detachment mechanism or by twisting and pulling, for example, thus leaving the detachable balloon  214  and associated components  226 / 228  in the vascular defect. 
     Refer now to  FIGS. 5A-5D  which schematically illustrate a distal portion of a detachable embolic balloon catheter  210 , which is substantially the same in design and function as catheter  200  except as described herein and illustrated in the drawings. As seen in  FIGS. 5A and 5B , a plurality of leaflets  242  (e.g., 2, 3, 4, or more) are uniformly disposed about the balloon  214  and extend along the balloon  214  to a distal apex thereof. The proximal ends of the leaflets  242  may be hinged and are attached to the proximal end of the balloon  214 . The distal ends of the leaflets  242  collectively meet adjacent the distal apex of the balloon  214 . The leaflets  242  may be formed of a flexible polymeric or metallic material which is generally more rigid than the material of the balloon  214 . The leaflets  242  may have a rectangular cross-section with a convex exterior surface, a concave interior surface, and a distal inward taper to conform to the profile of the balloon  214 . 
     After the balloon  214  has been disposed in the vascular defect as described previously, and as the balloon  214  is being inflated, the leaflets  242  separate and expand about hinge points at their respective proximal ends as shown in  FIG. 5C . Upon further expansion, the leaflets  242  and the balloon  214  conform to the inside surface of the defect as shown in  FIG. 5D . Because the leaflets  242  are relatively more rigid than the balloon  214 , and because the leaflets  242  extend across the opening to the vascular defect, the leaflets  242  prevent the balloon  214  from expanding into the native vascular lumen to thereby confine the balloon  214  within the interior of the vascular defect. The use of catheter  210  is otherwise the same as catheter  200  described previously. 
     It should be understood that this disclosure is, in many respects, only illustrative. Changes may be made in details, particularly in matters of shape, size, arrangement of parts and order of steps without departing from the scope of the invention. The invention&#39;s scope is, of course, defined in the language in which the appended claims are expressed.