Abstract:
A method ( 112 ) of loading an expandable medical device in a low vapor environment. The method includes placing the device in a loading chamber ( 114 ) at, for example, room temperature and removing ( 116 ) from the chamber any undesirable contaminants such as water vapor that can form condensation on the device when the device is cooled for compression into a transfer tube or delivery catheter. The temperature in the chamber is lowered ( 118 ) to a temperature below the transition temperature (martensitic finish) of the device. The device is compressed ( 120 ) below its&#39; transition temperature and loaded ( 122 ) into a delivery or transfer device.

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
     This application claims priority of provisional application Ser. No. 60/652,314, filed Feb. 11, 2005. 
    
    
     TECHNICAL FIELD 
     This invention relates generally to medical devices, and, in particular, to a method of loading an expandable medical device. 
     BACKGROUND OF THE INVENTION 
     Various expandable implantable medical devices such as stents, bone clips, vena cava filters, etc., are most easily and safely inserted into a passageway of the body such as the vascular system if they are first compressed into a small diameter configuration, then inserted into the body and expanded. Stents, for example, are compressed to fit onto or into a delivery catheter, which is then inserted into the body vessel such as a coronary artery, then expanded and released or released and expanded. 
     Because the catheter and stent must travel through the patient&#39;s vasculature, the stent must have a small delivery diameter and must be firmly secured within a delivery catheter until the physician is ready to implant it. Thus, the stent must be loaded onto or into the delivery catheter so that it does not interfere with delivery, and it must not come off the catheter until it is implanted. 
     In procedures where a self-expanding medical device such as a stent is utilized, the stent is placed within a protective delivery sleeve of the delivery catheter. It is necessary to properly collapse or compress the stent for loading it into the protective delivery sleeve. This collapsing or compressing of the stent has proven to be a particular challenge where it is necessary to load the stent into a small diameter delivery catheter. 
     In one loading procedure, a self-expanding stent is compressed to a small diameter and then inserted into a transfer tube. The compressed self-expanding stent is then loaded into a delivery sleeve of the delivery catheter by pushing the compressed self-expanding stent from the transfer tube into the protective delivery sleeve. This loading procedure is completed by connecting a tapered dilator head to the distal end of the delivery catheter by, for example, positioning the distal tip on a central rod or tube that extends through the longitudinal passageway of the loaded stent. 
     Several commercially available stent crimping or compression devices are available, which uniformly compress a self-expanding stent from a fully expanded state to a much smaller diameter compressed state for insertion into a transfer tube or delivery catheter. 
     Many vascular medical procedures further require the placement of a coated implantable medical device into the body of the patient. The placement of a metal or polymeric device however, gives rise to numerous complications. In particular, the placement of a bare expandable, implantable medical device such as a stent causes trauma to the vascular wall resulting often times in hyperplasia and restenosis of the vessel with the proliferation of smooth muscle cells at the implantation site. 
     One approach to reducing the potential harmful effects of such an introduction is to provide a coated, expandable, implantable medical device such as a stent having a coating of a bioactive material such as an antiproliferative that is delivered with the stent at the implantation site. By so doing, the harmful effects associated with implantation can be diminished. In particular, bioactive compounds such as paclitaxel and other antiproliferative materials are applied to the surface of the stent. These antiproliferative materials come in contact with the vessel wall and inhibit, among others, hyperplasia and restenosis of the vessel. 
     This bioactive coating material along with the stent must be reduced to a small diameter for loading onto a delivery catheter. This loading procedure is often further complicated when the stent such as a nitinol stent must be cooled to temperatures below the martensitic start and final temperatures of the nitinol material prior to compression and insertion into the delivery catheter. This is done to reduce the force necessary to load nitinol stents into an insertion or delivery catheter. Because the nitinol stent is completely martensitic, it is pliable and ductile, and easily compressed for loading into a delivery catheter. However, cooling a nitinol stent with a bioactive material coating thereon presents additional loading problems. 
     Nitinol stents are typically placed in a cooling chamber or container in which the temperature of the stent is reduced to below its martensitic final temperature such as, for example, below −40 degrees C. After the fully expanded nitinol stent is cooled to below its martensitic final temperature, it is then positioned in a stent crimper or compression apparatus and uniformly compressed to a much smaller diameter size for loading into the delivery sheath of a delivery catheter. However, the stent compression apparatus is typically at a temperature below the austenitic start temperature of the nitinol stent. Depending upon the environmental conditions of the cooling chamber, water or ice as well as other condensates or sublimates, often form on the compression apparatus as well as the coated nitinol stent. This condensation or sublimates can adversely affect the operation of the compression device as well as form an additional layer or thickness on the surface of the coated nitinol stent. The condensate or sublimate can significantly affect the compression of the stent so that the coated stent cannot be easily pushed into a transfer tube or a delivery sheath of the delivery catheter. The condensate or sublimate can be water or ice crystals formed from water vapor or crystals formed from the sublimation of carbon dioxide gas. Other condensates and sublimates such as oxygen and other contaminants found, in, for example, the air, are contemplated. 
     SUMMARY OF THE INVENTION 
     The foregoing problems are solved and a technical advance is achieved in an illustrative method of loading an expandable, implantable medical device such as a coated, self-expanding nitinol stent into a delivery or transfer device such as a delivery catheter or transfer tube. The method includes the steps of placing the expandable medical device in a loading chamber at for example room temperature and removing from the chamber any undesirable contaminants including water vapor and carbon dioxide gas that are purged from the loading chamber during the removal step to minimize, if not eliminate, condensation or sublimates in the chamber and on the device when the coated nitinol stent is, for example, cooled for the purpose of compression into a transfer tube or delivery catheter. The temperature in the chamber is then lowered to a temperature at least below the transition temperature of the device such as the martensitic start temperature or more preferably the martensitic finish temperature of the nitinol. At the lowered temperature, the medical device is compressed and then loaded into the transfer tube or delivery catheter. 
     The step of removing the undesirable contaminants includes purging the chamber with a gas such as nitrogen gas for a minimum amount of time. 
     The step of lowering the temperature in the chamber includes the step of lowering the temperature at a rate slow enough to remove the contaminants before condensation or sublimination can occur. 
     The step of lowering the temperature in the chamber can also advantageously include introducing liquid nitrogen into the chamber, heating the liquid nitrogen to form nitrogen gas and then lowering the temperature in the chamber with the nitrogen gas. 
     The method also includes inserting the medical device in compression fixture. The step of compression includes inserting the medical device at a temperature below its&#39; transition temperature into the compression fixture and then compressing the medical device from a first diameter to a second smaller diameter without advantageously any contaminants having formed on the medical device. 
     Without any contaminants having formed on the medical device, the device is advantageously loaded or transferred to a transfer tube or delivery catheter without the contaminants interfering with the loading step. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWING 
         FIG. 1A  depicts a block diagram flow chart of the present invention of a method of loading an expandable medical device in a low vapor environment; 
         FIG. 1B  is a photograph of a loading chamber of the present invention in which an expandable medical device is inserted therein and its temperature lowered for loading into a delivery or transfer device; 
         FIG. 1C  depicts a schematic diagram of the loading chamber into which an expandable medical device is loaded into a delivery or transfer device; 
         FIG. 2A  depicts a simplified pictorial schematic of the loading chamber apparatus of the present invention of  FIG. 1C ; 
         FIG. 2B  is an end photographic view of the loading chamber of  FIG. 1B ; 
         FIG. 2C  is a back photographic view of the loading chamber of  FIG. 1B ; 
         FIG. 3A  is a photograph of the interior of the loading chamber of  FIG. 1B ; 
         FIG. 3B  is a partial diagram of the interior of the loading chamber of  FIG. 1C ; 
         FIG. 3C  is an enlarged photograph of the interior of the loading chamber of  FIG. 3A ; 
         FIG. 4  is an enlarged pictorial view of the Dewar vessel of  FIG. 3B  in which the expandable medical device is placed therein for cooling; 
         FIG. 5  is a pictorial diagram of the loading apparatus (support mandril) of  FIG. 1C  of which the expandable medical device is positioned thereon for insertion into the compressor; 
         FIG. 6  is a pictorial assembly diagram of the components of the mandril for the positioning and compressing of the expandable medical device into the compressor of  FIG. 1C ; 
         FIG. 7  depicts a diagram of an expanded medical device of the present invention inserted into a radial compressor with the mandril of  FIGS. 5 and 6 . 
         FIG. 8  depicts a diagram of a compressed expandable stent in the radial compressor compressing the stent on a support mandril inserted through the lumen of the medical device; 
         FIG. 9  depicts a partially sectioned diagram of the expandable medical device of the present invention on the support mandril being inserted into the aperture of the compressor of  FIGS. 7 and 8 ; 
         FIG. 10  depicts a section diagram showing removal of the support mandril from the insertion assembly. 
     
    
    
     DETAILED DESCRIPTION 
       FIG. 1A  depicts a block diagram flow chart  110  of the present invention including a method  112  of loading an expandable medical device in a low vapor environment. The method  112  includes the step of placing an expandable medical device in a cooling chamber at a first room temperature as depicted in block  114 . Another step as depicted in block  116  includes removing from the chamber at least one of a vapor and any other gaseous impurity that can form at least one of a liquid and a solid on the medical device at a second temperature lower than the first temperature. Still another step as depicted in block  118  includes lowering the temperature in the chamber to a temperature below at least one of the second temperature and a transition temperature such as the martensitic start temperature of for example a nitinol medical device. The method further includes the step as depicted in block  120  of compressing the medical device at a temperature below the transition temperature of the medical device. Lastly as depicted in block  122  of the flow chart diagram, the method includes the step of loading the compressed medical device into the delivery device or a transfer tube. 
       FIG. 1B  is a photograph of a commercially available loading chamber  12  with a commercially available liquid nitrogen source  16  attached thereto. Nitrogen gas evacuater  52  is positioned on one side of the chamber next to the nitrogen source while a temperature read out gauge  26  measures the temperature inside the loading chamber and in particular the Dewar vessel  40 . Also shown in the photograph is a flow meter, a viewing window, a stent delivery tube, a stent access tube on the front of the chamber, and an air cylinder and an adjustment knob for controlling the flow of air into the chamber. 
       FIG. 1C  depicts a schematic diagram of the loading chamber  12  of the present invention in which an expandable medical device  66  is inserted into the chamber and the temperature of the chamber and device is lowered for loading into a delivery or transfer device  94 . 
       FIG. 2A  depicts a simplified schematic diagram of the loading chamber  12  of the present invention of  FIG. 1C . Connected to the loading chamber is a liquid nitrogen source  16  which supplies liquid nitrogen to the chamber via line  22 . A cannula pusher device  32  is positioned at one end of the loading chamber for pushing the expandable medical device into a transfer tube from a compressor which will be described hereinafter. An access door  14  is provided at the front of the cooling chamber for viewing and gaining access into the interior of the chamber. A stent container access tube  46  and stent delivery tube  48  are positioned on the front and back of the cooling chamber. Manipulation of the device is provided by manipulator device  76  such as a insulated sleeve and glove which is inverted for access into the chamber. 
       FIG. 2B  is an end photographic view of the loading chamber of  FIG. 1B  in which a force gauge  124  is shown positioned on one end of loading chamber  12  with a seal  126  around the cannula pusher  32 . 
       FIG. 2C  is a photographic view of the back of the loading chamber of  FIG. 1B  with access tube  48  for inserting stents into the chamber. 
       FIG. 3A  is a photographic view of the interior of the loading chamber  12  with stent delivery tube  48  extending therein. Air lock caps  128  and  130  are respectively positioned on outlet tube  46  and inlet access tube  48 . Glove access port  58  is shown at the front of the interior chamber. Compression fixture  38  is shown in the interior of the loading chamber next to liquid nitrogen container  40  known commonly as a Dewar vessel. 
       FIG. 3B  is an enlarged partial diagram of the interior of the loading chamber of  FIG. 1C  that further depicts the photograph of  FIG. 3A . In addition to stent compressor  38  as previously described, stent compressor actuator cylinder  34  and actuator arm  36  open and close collet opening  80  in which the expandable medical device is inserted therein for compression into a smaller diameter size. A directed light source  78  is positioned near the collet opening allows the operator to easily view placement of the stent in the chamber. Liquid nitrogen is poured into the Dewar vessel  40  via liquid nitrogen line  22  whereas nitrogen gas line  24  can be used for evacuating the liquid nitrogen gas. 
       FIG. 3C  is an enlarged photograph of the interior of the loading chamber of  FIG. 3A  with a Leister heat gun  132  positioned near the DeWar jar  40  for heating the liquid nitrogen contained therein. 
     Set Up of Cooling Chamber  12   
     The set up of the cooling chamber is facilitated by the following: 
     
         
         1. Turn off all power to the box by shutting off the power strip at back of box and unplugging the Leister heat gun. 
         2. Remove tape from around viewing window access port and remove from box.
 
NOTE: Nitrile gloves, smock &amp; facemask must be worn when cleaning cooling box.
 
         3. Remove all tools and liquid nitrogen vessel making sure to wipe down with lint-free cloth and ethyl alcohol as removed. Be sure to remove the pusher cannula with force gauge adapter assembly from the force gauge and the box. 
         4. Wipe off access tubes, glove access cap and air lock caps and install all air lock caps. 
         5. Clean box as follows: cooling box must be cleaned with a lint-free cloth and ethyl alcohol. Use overlapping motions, start with the furthest point away from your body and wipe in one direction towards your body. Change wipes when starting with a new wall. 
         6. Wrap a cleaning wipe around the 5 GRW cannula so the wipe extends past the end of the cannula slightly, open fixture and using ethyl alcohol wipe out the inside of the fixture. Make sure the end of the cannula does not dig into the fixture when cleaning. 
         7. Change nitrile gloves. 
         8. Insert pusher cannula with force gauge adapter assembly, threaded end first into the fixture until the threaded end contacts the force gauge. Screw the assembly into the force gauge until a slight resistance is felt. Replace seal around pusher cannula.
 
NOTE: Take care that the pusher cannula with force gauge adapter assembly does not scratch the fixture.
 
         9. Wipe down all loading tools, glove and appropriate container for liquid nitrogen and put back in cooling box. 
         10. Plug in Leister heat gun and start airflow by turning on bottom button. Do not turn on heat. 
         11. Turn on power strip that starts fan. 
         12. Turn on microscope light and camera. Adjust light focusing onto compression fixture orifice. 
         13. Wipe down inside surface of viewing window access panels, install in opening and tape edges to seal. 
         14. Turn on nitrogen gas and flow meter, adjust flow to between 0.1 and 0.3 MPH. 
         15. Purge environment inside box with nitrogen gas for 5 minutes. 
         16. Turn on temperature read-out gauge. Confirm gauge is set on k setting for thermocouple. If temperature is unstable, change battery. 
         17. After purging box, turn on liquid nitrogen approx. ½ turn. 
         18. Increase or decrease flow of liquid nitrogen to maintain liquid in the containment vessel without overflow until the temperature has reached 5 Degrees F.
 
NOTE: Flow meter will read at a higher MPH after turning on liquid nitrogen.
 
         19. Remove cap and fill the access tube with stents in test tubes and appropriate length inner support cannula assemblies. Place cap back on the tube outside of the box. 
         20. Remove cap outside of box and position loaded stent catch bag on outlet tube exit. Make sure bag is sealed and has label with: stent size, batch no., and quantity. Order number must be on the bag if applied directly to an order. 
         21. Turn off liquid nitrogen. 
         22. Turn on force gauge and set indicator at 0. Confirm force gauge is in starting position. 
       
    
       FIG. 1A  depicts the method steps  110 - 122  of loading a coated nitinol stent  66  into a transfer tube  94 . The individual steps including each of these method steps is detailed as follows:
     1. Verify temperature in cooling box is between −15 degrees and +5 degrees.   2. If temperature starts to warm up or liquid nitrogen gets low, refill liquid nitrogen Dewar vessel as required.   3. Put on non-latex glove.   4. Place hand with non-latex glove into inverted glove sleeve at access port and pull the cuff of the non-latex glove over the cuff of the glove sleeve. Hand may now be placed in box.   5. Remove air lock cap from glove access port and place on top of stent compression fixture.   6. Remove cap from access tube and remove test tubes with stents from access tube. Replace cap of access tube.   7. Remove cap from test tube and partially expose stent. Place test tube with partially exposed stent into holding rack. IMPORTANT—Only remove one stent from a test tube at a time to insure trackability. Each test tube is numbered.   8. With 0.040″ stylet wire dip stent in liquid nitrogen. After dipping of stent, be careful not to bump stent as this could cause stent deformity.   9. With 0.040″ stylet wire place stent completely in stent compression fixture. There should be approx. ¼″ from end of stent to opening in fixture.   10. Close stent compression fixture with air cylinder and remove 0.040″ stylet wire.   11. Insert inner support cannula assembly or support mandril in stent with cannula end first. Cannula of assembly should be located between gold rivets at both ends of the stent.   12. To insure proper positioning of inner support cannula, adjust the fixture hole size. Turning the adjustment knob counter clockwise while moving the support cannula back and forth does this. Continue this until the support cannula stops against the gold rivets at both ends. Adjustment knob is located with air cylinder on the outside bottom of cooling box.   13. Adjust a medium drag on support cannula by turning the adjust knob Counter clockwise. After sufficient drag is determined position support cannula by rivets farthest from exit opening.
 
NOTE: Transfer tube must be smooth on distal end to enable advancement of transfer tube assist tool.
   14. Place transfer tube alignment cannula on inner support cannula. Transfer tube alignment cannula must butt up to stent. Place transfer tube onto transfer tube alignment cannula up to stent compression fixture opening. Advance large end of transfer tube assist tool over transfer tube.   15. Hold transfer tube assist tool against stent compression fixture and push stent into transfer tube by advancing force gauge.   16. Remove stent in transfer tube, transfer tube alignment cannula, transfer tube assist tool and inner support cannula from stent compression fixture.   17. Remove transfer tube assist tool from transfer tube.   18. Remove transfer tube alignment cannula from transfer tube.   19. Remove inner support cannula assembly by holding it against inside bottom of box (opposite end of flare on transfer tube) and push slightly until gold rivets slightly release from transfer tube. Remove inner support cannula assembly from stent.   20. Put stent in transfer tube back into test tube and replace cap. Place test tube into access tube with stent catch bag attached.   21. Turn adjustment knob on air cylinder clockwise to loosen fixture and release pressure on pusher cannula with force gauge adapter.   22. Open stent compression fixture using air cylinder and retrace force gauge and pusher cannula with force gauge adapter.   23. Send stents in sealed bag to area where they will be Quality Controlled and transferred into delivery systems.   
       FIG. 4  is an enlarged pictorial view of Dewar vessel  40  of  FIG. 3B  in which the expandable medical device or stent  66  is placed in liquid nitrogen  82  for cooling thereof. 
       FIG. 5  is a pictorial diagram of the apparatus such as support mandril  84  for positioning stent  66  about enlarged end  88  of the main body  86  of the mandril. The handle end  92  of the support mandril  84  is depicted at the opposite end thereof. Gold dot markers  90  are shown depicted on each end of the expandable stent  66 . 
       FIG. 6  is a pictorial assembly diagram of the components of support mandril  84  for positioning in transfer tube  94  with lumen  100  extending longitudinally therethrough. One end  96  of transfer tube  94  is flared with a chamfer  98  on the flared loading end of the tube. A push bushing  102  slides over the other end of the transfer tube and an extraction support rod  104  is positioned inside transfer tube  94 . 
       FIG. 7  depicts an expanded medical device  66  of the present invention inserted into collet opening  80  of the stent compressor  38  with the use of support mandril  84 . The support mandril  84  is inserted into the lumen of the expanded stent  66  for compression around the expanded end  88  of the support mandril. When the enlarged end  88  of the support mandril is positioned in the lumen of stent  66 , the stent compressor  38  is actuated by movement of stent compressor actuator  36 . Stent compressor  38  is commercially available from Machine Solutions of Flagstaff, Ariz. 
       FIG. 8  depicts the compression of the stent by stent compressor  38  with support mandril  84  extending from collet compressed opening  106 . 
       FIG. 9  depicts a partially sectioned diagram of the expandable medical device  66  of the present invention positioned on the enlarged end  88  of the support mandril with pusher cannula  30  inside compressor  38  engaging one end of the stent with the other end of the stent for positioning against extraction support rod  104 . The transfer tube  94  has a flared end  96  with chamfer  98  thereon for the loading of the flared end into the compressor. Push bushing  102  is utilized as shown for centering the support mandril and loaded stent  88 . Pusher cannula  30  pushes the stent  66  into transfer tube  94 . Extraction support rod  104  engages the other end of the stent when enlarged end  88  of the mandril is withdrawn from the lumen of the stent  66  just barely making contact with gold markers  90 . 
       FIG. 10  depicts a section detail showing removal of the mandril from the insertion assembly. 
     Instructions for Shutting Cooling Box Off 
     
         
         1. Turn off liquid nitrogen. 
         2. Turn on heat from Leister heat gun, top button. 
         3. Let cooling box heat up to 70 degrees F. 
         4. Shut off heat. Let fan run approx. 5 minutes, then shut off. 
         5. Shut off gas flow from liquid nitrogen tank. 
         6. Turn off temperature read out gauge and flow meter. 
         7. Turn off power strip. 
       
    
     Provided is a listing of assembly components for loading an expandable medical device into a transfer tube. 
     
       
         
               
             
               
               
             
           
               
                   
               
               
                 LISTING OF ASSEMBLY COMPONENTS FOR LOADING 
               
               
                 AN EXPANDABLE MEDICAL DEVICE INTO A TRANSFER TUBE 
               
               
                   
               
             
             
               
                   
               
             
          
           
               
                 10 
                 device 
               
               
                 12 
                 cooling chamber 
               
               
                 14 
                 access door 
               
               
                 16 
                 nitrogen source 
               
               
                 18 
                 nitrogen gas valve 
               
               
                 20 
                 nitrogen liquid valve 
               
               
                 22 
                 liquid N line 
               
               
                 24 
                 N gas line 
               
               
                 26 
                 thermometer 
               
               
                 28 
                 thermometer lead 
               
               
                 30 
                 pusher cannula 
               
               
                 32 
                 cannula pusher device 
               
               
                 34 
                 stent compressor 
               
               
                   
                 actuater cyl. 
               
               
                 36 
                 stent compressor 
               
               
                   
                 actuater 
               
               
                 38 
                 stent compressor 
               
               
                 40 
                 Dewar Vessel 
               
               
                 42 
                 light generator 
               
               
                 44 
                 fiber optic 
               
               
                 46 
                 stent container access 
               
               
                   
                 tube 
               
               
                 48 
                 stent container 
               
               
                   
                 delivery tube 
               
               
                 50 
                 gas evacuation access 
               
               
                 52 
                 gas evacuator 
               
               
                 54 
                 heated air port 
               
               
                 56 
                 air heater 
               
               
                 58 
                 manipulator access 
               
               
                 60 
                 actuating control 
               
               
                   
                 valve 
               
               
                 62 
                 actuator valve lever 
               
               
                 64 
                 pusher valve lever 
               
               
                 66 
                 stent 
               
               
                 68 
                 pusher valve 
               
               
                 70 
                 pusher valve line 
               
               
                 72 
                 actuator valve line 
               
               
                 74 
                 actuating operating 
               
               
                   
                 controls 
               
               
                 76 
                 manipulator device 
               
               
                 78 
                 directed light 
               
               
                   
                 source 
               
               
                 80 
                 collet opening 
               
               
                 82 
                 liquid N 
               
               
                 84 
                 support mandril 
               
               
                 86 
                 body of mandril 
               
               
                 88 
                 enlarged end of 
               
               
                   
                 mandril 
               
               
                 90 
                 gold dot markers 
               
               
                 92 
                 handle end of 84 
               
               
                 94 
                 transfer tube 
               
               
                 96 
                 flared end of 94 
               
               
                 98 
                 chamfer on loading 
               
               
                   
                 end of 96 
               
               
                 100 
                 lumen of 94 
               
               
                 102 
                 push bushing 
               
               
                 104 
                 extraction support rod 
               
               
                 106 
                 collet compressed 
               
               
                   
                 opening 
               
               
                 108 
                 comp. To retain 104 in 94 
               
               
                 110 
                 method block diagram 
               
               
                 112 
                 method of loading 
               
               
                 114 
                 placing in chamber 
               
               
                 116 
                 removing impurities 
               
               
                 118 
                 lowering temperature 
               
               
                 120 
                 compressing the stent 
               
               
                 122 
                 loading the stent 
               
               
                 124 
                 force gauge 
               
               
                 126 
                 seal 
               
               
                 128 
                 end cap 
               
               
                 130 
                 end cap 
               
               
                 132 
                 Leister heat gun