Abstract:
The disclosure pertains to a vessel for holding replacement heart valves and associated positioning and installation apparatus which is configured and adapted to contain a biocidal sterilization fluid during and following exposure of a delivery system for the replacement heart valve to sterilization by ionizing radiation and methods of use therefor. The vessel includes a shield which limits exposure of biologically derived material therein to radiation. The vessel also provides a storage and shipping container for the replacement heart valve in which the biologically derived material is maintained in a sterile fluid environment.

Description:
RELATED APPLICATIONS 
     This application is a continuation of U.S. application Ser. No. 13/676,695 filed Nov. 14, 2012, which claims priority to U.S. Application Ser. No. 61/559,914 filed Nov. 15, 2011. 
    
    
     TECHNICAL FIELD 
     The present disclosure pertains to medical devices, and methods for manufacturing medical devices. More particularly, the present disclosure pertains to medical devices for delivering a replacement heart valve. 
     BACKGROUND 
     A wide variety of intracorporeal medical devices have been developed for medical use, for example, intravascular use. Some of these devices include guidewires, catheters, medical device delivery systems (e.g., for stents, grafts, replacement valves, etc.), and the like. These devices are manufactured by any one of a variety of different manufacturing methods and may be used according to any one of a variety of methods. Of the known medical devices and methods, each has certain advantages and disadvantages. There is an ongoing need to provide alternative medical devices as well as alternative methods for manufacturing and using medical devices. 
     SUMMARY 
     This disclosure pertains to a sealable dual sterilization containment vessel for biologically derived medical components comprising a hollow element having a wall, a proximal end, a distal end, and a lumen therebetween, said lumen configured and adapted to contain a biologically derived medical component and at least a portion of an apparatus configured and adapted to implant the biologically derived medical component in a living body; a distal end cap; a proximal end cap; and a radiopaque sleeve, wherein the proximal end cap has a secondary proximal end cap and ferrule sized and adapted to and capable of reversibly sealing the proximal end cap to a delivery catheter passing therethrough, further wherein the combination of the hollow element, the distal end cap, the proximal end cap, the secondary proximal end cap, the ferrule, and the delivery catheter form a fluid tight system providing a continuous fluid connection between the interior of the hollow element and the lumen of the delivery catheter. 
     In another embodiment, the disclosure relates to a sealed system for delivering a replacement heart valve comprising a replacement heart valve; a delivery catheter; and elements configured and adapted to position and install the replacement heart valve; the system further comprising a storage and shipping container, wherein at least the replacement heart valve and a portion of the elements configured and adapted to position and install the replacement heart valve are initially contained within a fluid filled removable dual sterilization containment vessel. The biologically derived component(s) of the replacement heart valve may be maintained in a hydrated state within the provided sterile system environment during storage and shipping. 
    
    
     
       BRIEF DESCRIPTION OF DRAWINGS 
         FIG. 1  illustrates an exemplary replacement heart valve delivery system and associated packaging. 
         FIG. 2  illustrates a replacement heart valve and associated components which may be used with the dual sterilization containment vessel disclosed herein 
         FIG. 3  illustrates embodiments of a dual sterilization containment vessel of the disclosure. 
         FIGS. 4A and 4B  illustrate partially exploded views of the dual sterilization containment vessel of  FIG. 3 . 
         FIG. 5  illustrates embodiments of a hollow element of the disclosure. 
     
    
    
     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 drawings, which are not necessarily to scale, are not intended to limit the scope of the claimed invention. The detailed description and drawings illustrate example embodiments of the claimed invention. 
     All numbers are herein assumed to be modified by the term “about.” The recitation of numerical ranges by endpoints includes all numbers subsumed within that range (e.g., 1 to 5 includes 1, 1.5, 2, 2.75, 3, 3.80, 4, and 5). 
     As used in this specification and the appended claims, the singular forms “a”, “an”, and “the” include the plural referents unless the content clearly dictates otherwise. As used in this specification and the appended claims, the term “or” is generally employed in its sense including “and/or” unless the content clearly dictates otherwise. 
     It is noted that references in the specification to “an embodiment”, “some embodiments”, “other embodiments”, etc., indicate that the embodiment described may include a particular feature, structure, or characteristic, but every embodiment may not necessarily include the particular feature, structure, or characteristic. Moreover, such phrases are not necessarily referring to the same embodiment. Further, when a particular feature, structure, or characteristic is described in connection with an embodiment, it would be within the knowledge of one skilled in the art to effect such feature, structure, or characteristic in connection with other embodiments whether or not explicitly described unless clearly stated to the contrary. 
       FIG. 1  illustrates a system  10  for delivering a replacement heart valve and packaging  40  associated therewith. The heart valve replacement system  10  may comprise a replacement heart valve  12 , having a biologically derived component  16 , and associated components  14  ( FIG. 2 ) configured and adapted to position and install the replacement heart valve  12 . These components may be any of the replacement heart valves and associated components known in the art and the specifics thereof need not be discussed in detail to understand the operation of the system. The non-limiting exemplary replacement heart valve  12  may be a valve including one or more biologically derived components and may, for example, be derived from treated human, bovine, or porcine tissue. The system  10  for delivering a replacement heart valve also may include additional components such as a control handle  20 , a delivery catheter  30  and a dual sterilization containment vessel  50  which is configured and adapted to contain at least one biocidal fluid (not shown), which biocidal fluid may also be contained within the delivery catheter  20  and in fluid contact therewith. The biocidal fluid may contain, for example, gluteraldehyde which serves to sterilize the contacted surfaces of the system and which optionally may tend to cross-link biologically derived components of the replacement heart valve. 
       FIGS. 3, 4A, and 4B  illustrate various components of a dual sterilization containment vessel  50  which is configured and adapted to contain at least one biocidal fluid. A dual sterilization containment vessel  50  will be understood to encompass a vessel which is configured and adapted to contain at least one sterilizing biocidal fluid as well as to allow ionizing radiation sterilization of the contents of the vessel and other components of a replacement heart valve delivery system without undue damage to the biologically derived components  16  of the replacement heart valve  12 . 
     In some embodiments, this may be accomplished by selecting construction materials which are substantially unreactive with the contacting biocide(s) and further by including as a component the dual sterilization containment vessel  50  a radiopaque sleeve  90  which prevents excessive levels of ionizing radiation which may be applied to the remaining components of the system  10  for delivering a replacement heart valve from reaching and damaging the biologically derived components. The radiopaque sleeve  90  may be removable or may be permanently attached to one or more other components of the dual sterilization containment vessel  50 . In certain embodiments, the radiopaque sleeve  90  may be contained within the sterilization containment vessel  50  to ensure that the space between an external radiopaque sleeve  90  and the sterilization containment vessel  50  remains sterile. In certain other embodiments, the joins between an external radiopaque sleeve  90  and the sterilization containment vessel  50  may be sealed, for example by an O-ring, gasket, sealant, or the like to isolate the space between an external radiopaque sleeve  90  and the sterilization containment vessel  50  and maintain a sterile environment therebetween. In yet other embodiments, the external radiopaque sleeve  90  and the sterilization containment vessel  50  may be integrally formed to eliminate an exposed interface which might harbor contamination. 
     The use of a dual sterilization containment vessel  50  is particularly desirable when other components of the system  10  for delivering a replacement heart valve  12  require exposure of the system as a whole to high levels of ionizing radiation to ensure that biocidal dosage levels are delivered to all internal parts of the system. Further, the use of two separate sterilization methods, enabled by the presence of a dual sterilization containment vessel  50  within the system is believed to substantially reduce the risk of bioactive contamination. 
       FIGS. 3, 4A, and 4B  illustrate a hollow element  80  having a wall, a proximal end, a distal end, and a lumen  81  therebetween, said lumen  81  configured and adapted to contain a biologically derived medical component  16  and at least a portion of an apparatus  14  configured and adapted to position and implant the biologically derived medical component  16  in a living body; a distal end cap  60 ; a proximal end cap  70  wherein the proximal end cap  70  has a secondary proximal end cap  72  and ferrule  74  sized and adapted to and capable of reversibly sealing the proximal end cap  70  to a delivery catheter  30  passing therethrough. Further, the combination of the hollow element  80 , the distal end cap  60 , the proximal end cap  70 , the secondary proximal end cap  72 , the ferrule  74 , delivery catheter  30 , and handle  20  form a fluid tight system providing a continuous fluid connection between the interior of the hollow element  80  and the lumen of the delivery catheter  30 . In some embodiments, the hollow element  80 , and/or the distal end cap  60 , may include a stopcock  82  to facilitate filling and draining biocide (s) from the system prior to removal of the dual sterilization containment vessel  50 . 
     Hollow element  80 , illustrated in greater detail in  FIG. 5 , comprises a hollow body having sufficient internal volume to contain the replacement heart valve and at least a portion of the associated components  14  configured and adapted to position and install the replacement heart valve  12 . In some embodiments, the replacement heart valve  12  and associated components  14  configured and adapted to position and install the replacement heart valve  12  are stored in at least a somewhat expanded configuration which may more fully expose their components to the biocidal fluid contained therein. Although illustrated as generally cylindrical, it will be appreciated the hollow element  80  may have a rectangular or other cross-section if desired. Hollow element  80  is depicted as having a unitary construction, however in some embodiments the hollow body may optionally be fabricated in two or more segments which are suitably sealed when joined. For example, the hollow body may be formed from two half-cylindrical walls  80   a / 80   b  joined along a separable longitudinal seam  81 , such as a clam-shell arrangement, with an appropriate gasket therebetween. In some embodiments, hollow body  80  may include stopcock  82 . 
     As noted herein, construction materials which are substantially unreactive with the contacting biocide(s), such as polycarbonate, may be used for the hollow element  80  and other components of the dual sterilization containment vessel  50 . Such materials may be selected to be partially or fully transparent to visible light thereby allowing visual inspection of the contents. For example, at least a portion of at least one of the hollow element  80 , the distal cap  60 , and the proximal cap  70  may include a region  100  transparent to visible light, as shown in  FIG. 4A . In addition, the materials should remain substantially unchanged chemically and mechanically upon absorption of ionizing radiation at levels of 30, 40, 50 gray, or in some embodiments more whether empty or filled with a biocidal fluid. In certain embodiments, at least a portion of the interior of at least one of the hollow element  80 , the distal cap  60 , and the proximal cap  70  may include a polished surface in fluid communication with the interior of the hollow element which is believed to facilitate removal of bubbles from the biocidal fluid within the dual sterilization containment vessel  50 . In addition, hollow element  80  may include one or more features configured and adapted to direct the motion of any bubbles which may be present within the dual sterilization containment vessel  50  when it is filled with fluid and subject to changes in orientation. Such features may include ridges, grooves, and/or tapers. 
     As illustrated, distal cap  60  and proximal cap  70  may be secured to hollow element  80  by mating threaded sections. Other means of reversible attachment may also be used. Although the illustrated embodiment depicts male threads  84 ,  86  on the hollow body  80  and corresponding female threads on the end caps  60 ,  70 , it will be appreciated that a cap may be provided with male threads and the hollow body with female threads at one or both ends of the dual sterilization containment vessel  50 . 
     Proximal end cap  70  may include a secondary proximal end cap  72  which together with ferrule  74  acts to seal the dual sterilization containment vessel  50  to other parts, indicated by reference numeral  30 , of the illustrated system  10  for delivering a replacement heart valve  12  while maintaining a fluid connection with the lumen or lumens thereof 
     Removable radiopaque sleeve  90  will typically have an internal lumen which substantially matches the exterior shape and dimension of the hollow element  80 . The radiopaque sleeve  90  may comprise a radiopaque solid or a radiopaque fluid or gel. Radiopaque sleeve  90  optionally may be secured to the hollow element  80  by, for example, set screw  92  during a portion of the sterilization process. In the alternative, the radiopaque sleeve may optionally be formed from several pieces  90   a / 90   b  and held in place by a clamping element  94 , as seen in  FIG. 3  for example. In such embodiments, the pieces  90   a / 90   b  may include overlapping regions along the joint to ensure that higher than desirable ionizing radiation does not reach biologically derived components  16 . In yet other embodiments, the radiopaque sleeve  90  may be permanently attached to one or more of the other components of dual sterilization containment vessel  50 . The radiopacity of the combined radiopaque sleeve  90  may be selected such that in combination with hollow body  80 , the biologically derived medical component  16  absorbs no more than 4 gray when the dual sterilization containment vessel  50  absorbs 30, 40, 50 gray, or in some embodiments more whether the dual sterilization containment vessel  50  is empty or filled with a biocidal fluid. 
     Although one or both of distal cap  60  and proximal cap  70  may be sized and configured to retain radiopaque sleeve  90  in position about hollow element  80 , it will be appreciated that in some embodiments, the radiopaque sleeve  90  may be configured to be removable from the hollow element  80  without removing one or both of the end caps. In such embodiments, a set screw  94  or other retaining device may be employed. 
     One possible, non-limiting, use sequence for a dual sterilization containment vessel  50  may be described as follows. Replacement heart valve  12  and associated components  14  configured and adapted to position and install the replacement heart valve  12  may be withdrawn within delivery catheter  30 , whereupon an assembled dual sterilization containment vessel  50  may be positioned to partially encompass the distal end of the delivery catheter  30 . Once proximal end cap  70  is secured to the distal end of delivery catheter  30  by secondary proximal end cap  72  and ferrule  74 , replacement heart valve  10  and associated components  14  configured and adapted to position and install the replacement heart valve  12  may be advanced from the distal end of delivery catheter  30  until it achieves an expanded configuration such as that of  FIG. 2 . Continuous lumen(s) joining handle  20 , delivery catheter  30 , and dual sterilization containment vessel  50  may then be filled with a biocidal fluid, such as an alcoholic gluteraldehyde solution, and flushed to remove bubbles and any incidentally introduced debris. Following flushing, stopcock  82  and a corresponding stopcock associated with handle  20  may be closed to seal and contain the biocidal fluid within the now closed system. 
     The closed system may be placed in packaging  40  and exposed to a source of ionizing radiation of sufficient penetrating power and for a sufficient time to sterilize the contents of packaging  40 . Radiopaque sleeve  90  serves to limit the radiation absorbed by the biologically derived component(s)  16 . In some embodiments, the radiation absorbed by biologically derived component(s)  16  will be less than 4 gray when the system as a whole has absorbed 30, 40, 50 gray, or in some embodiments more. At this point, it will be appreciated that the contents of the system have been sterilized by two independent methods and is ready for storage and distribution prior to use in a heart valve replacement procedure. The dual sterilization containment vessel  50  is configured and adapted to maintain the biologically derived medical component(s) in a hydrating and sterile environment prior to use. 
     Although the illustrative examples described herein relate to replacement heart valves, use of the dual sterilization containment vessel with other biologically derived medical components is also contemplated. In such an embodiment, the biologically derived medical component may be present in the form of a different valve structure, stent graft, or the like. Dual sterilization containment vessels for such applications may require modifications in size, shape and/or materials. 
     Various modifications and alterations of this invention will become apparent to those skilled in the art without departing from the scope and principles of this invention, and it should be understood that this invention is not to be unduly limited to the illustrative embodiments set forth hereinabove. All publications and patents are herein incorporated by reference to the same extent as if each individual publication or patent was specifically and individually indicated to be incorporated by reference.