Abstract:
Systems and methods provide intraluminal delivery of a bandage structure within a body lumen or hollow body organ, e.g., for treating an injured gastrointestinal tract or an esophageal hemorrhage in a non-invasive way using endoscopic visualization. The systems and methods can be sized and configured to apply a chitosan bandage structure within a body lumen or hollow body organ, to take advantage of the mucoadhesive, antimicrobial, hemostatic, and potential accelerated wound healing properties of the chitosan material.

Description:
RELATED APPLICATIONS 
     This application is a continuation of patent application Ser. No. 11/805,543 filed 23 May 2007, now abandoned, which claims the benefit of provisional patent application Ser. No. 60/802,654filed 23 May 2006. 
    
    
     This application is related to U.S. patent application Ser. No. 11/084,688, filed on Mar. 17, 2005, entitled “Systems and Methods for Hemmorrhage Control and/or Tissue Repair.” 
     FIELD OF THE INVENTION 
     The invention is generally directed to systems and methods to introduce and deploy tissue bandage structures within a body lumen or hollow body organ, such, e.g., as within the gastrointestinal tract. 
     BACKGROUND OF THE INVENTION 
     Currently, there exists no overwhelmingly accepted treatment for gastrointestinal, specifically esophageal bleeding with etiology such as; esophageal ulcers, esophagitis, Mallory Weis tears, Booerhave&#39;s syndrome, esophageal varices, anastomosis, fistula, and endoscopic procedures. 
     Electro-cautery and sclerotherapy are two existing treatments for esophageal hemorrhage, however both run a risk of perforation to the esophagus. Electro-cautery requires a large amount of pressure to be applied to the wall of the esophagus and also inherently damages tissue. Sclerotherapy consists of injecting a hardening agent in to the area of the injury with a needle. Clipping is another method of treatment; it consists of a two or three-pronged clip that can be inserted into the mucosa of the esophagus to constrict the area of the bleeding. If applied correctly, clipping is effective in controlling hemorrhage, however clips are difficult to deploy. Often, the clip is not inserted deep enough into the mucosa and sloughs off before the desired time. 
     SUMMARY OF THE INVENTION 
     The invention provides systems and methods for applying a bandage structure within a body lumen or a hollow body organ, e.g., for treating an injured gastrointestinal tract or an esophageal hemorrhage. 
     Another aspect of the invention includes systems and methods for placing a bandage structure within a body lumen or hollow body organ in a non-invasive way using endoscopic visualization. 
     The systems and methods do not involve the use of any sharp edges or points. The systems and methods do not involve the use of a point pressure, as existing treatment options require. Only moderate circumferential pressure is required to apply the bandage structure. The systems and methods adapt well to tools and techniques usable by gastroenterologists. 
     The systems and methods can be sized and configured to apply a chitosan bandage structure within a body lumen or hollow body organ, to take advantage of the mucoadhesive, antimicrobial, hemostatic, and potential accelerated wound healing properties of the chitosan material. Drug delivery and cell therapy with a chitosan bandage structure as a delivery matrix are also made possible. 
     Other features and advantages of the invention shall be apparent based upon the accompanying description, drawings, and claims. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1  is a plane view of an intraluminal delivery system for introducing and applying a bandage structure within a body lumen or hollow body organ. 
         FIG. 2  is perspective view of the bandage structure that is sized and configured for deployment by the system shown in  FIG. 1 . 
         FIGS. 3 to 5  show the rolling of the bandage structure into a low profile condition prior to deployment by the system shown in  FIG. 1 . 
         FIGS. 6 to 9  show the placement of a rolled bandage structure upon the expandable delivery structure that forms a part of the system shown in  FIG. 1 . 
         FIGS. 10 to 13  show the use of the delivery system shown in  FIG. 1  for introducing and applying a bandage structure within a body lumen or hollow body organ. 
         FIG. 14  shows an optional over-tube that can be used in association with the system shown in  FIG. 1 . 
         FIG. 15  shows the system shown in  FIG. 1  back-loaded into the working channel of an endoscope. 
     
    
    
     DESCRIPTION OF THE PREFERRED EMBODIMENT 
     Although the disclosure hereof is detailed and exact to enable those skilled in the art to practice the invention, the physical embodiments herein disclosed merely exemplify the invention, which may be embodied in other specific structure. While the preferred embodiment has been described, the details may be changed without departing from the invention, which is defined by the claims. 
     I. The Intraluminal Delivery System 
       FIG. 1  shows an intraluminal delivery system  10  for introducing and applying a bandage structure  12  within a body lumen or hollow body organ. The delivery system  10  includes a bandage structure  12  and a delivery device  14  that is sized and configured to deliver and deploy the bandage structure  12  at a targeted tissue region within a body lumen or hollow body organ. The delivery device  14  is sized and configured to deploy the bandage structure  12  while preventing it from contacting tissue lining the body lumen or hollow body organ until the desired time of deployment. The delivery device  14  not only provides a barrier between the bandage structure  12  and tissue within the body lumen or hollow body organ during introduction, but also provides a means to deploy the bandage structure  12  into contact with the tissue at the desired time. 
     As shown in  FIG. 1 , the delivery device  14  can be sized and configured to accommodate passage over a guide wire  32 . In this way, the delivery device  14  can be introduced over the guide wire  32  under direct visualization from an endoscope  50 , as  FIG. 10  shows. In this arrangement, the guide wire  32  runs next to the endoscope  50  and therefore leaves the working channel of the endoscope  50  free. In an alternative arrangement (see  FIG. 15 ), the delivery device  14  can be sized and configured to be back-loaded through the working channel  52  of an endoscope  50 . The working channel  52  of the endoscope  50  thereby serves to guide the delivery device  14  while providing direct visualization. 
     A. The Tissue Bandage Structure 
     The size, shape, and configuration of the bandage structure  12  shown in  FIG. 1  can vary according to its intended use, which includes taking into account the topology and morphology of the site to be treated and the age/status of the patient (e.g., adult or child). The tissue bandage structure  12  is desirably flexible and relatively thin so that it can be rolled or folded upon itself for deployment in a low profile condition, as  FIGS. 2 to 5  show. The tissue bandage structure  12  can be rectilinear, elongated, square, round, oval, or a composite or complex combination thereof. The shape, size, and configuration of tissue bandage structure  12  can be specially formed and adapted to the topology and morphology of the site of application, by cutting, bending, or molding in advance of use. 
     The tissue bandage structure  12  desirably includes an active therapeutic surface  36  for contacting tissue. The active surface  36  desirably comprises a biocompatible material that reacts in the presence of blood, body fluid, or moisture to become a strong adhesive or glue. The material of the active surface  36  can, alone or in combination with adhesive features, possess other beneficial attributes, for example, anti-bacterial and/or anti-microbial and/or anti-viral characteristics, and/or characteristics that accelerate or otherwise enhance coagulation and the body&#39;s defensive reaction to injury. 
     In one embodiment, the material of the active surface  36  of the tissue bandage structure  12  comprises a hydrophilic polymer form, such as a polyacrylate, an alginate, chitosan, a hydrophilic polyamine, a chitosan derivative, polylysine, polyethylene imine, xanthan, carrageenan, quaternary ammonium polymer, chondroitin sulfate, a starch, a modified cellulosic polymer, a dextran, hyaluronan or combinations thereof. The starch may be of amylase, amylopectin and a combination of amylopectin and amylase. 
     In a preferred embodiment, the biocompatible material of the active surface  36  comprises a non-mammalian material, which is most preferably poly [β-(1→4)-2-amino-2-deoxy-D-glucopyranose, which is more commonly referred to as chitosan. 
     The chitosan material is preferred because of the special properties of the chitosan. The chitosan active surface  36  is capable of adhering to a site of tissue injury along a body lumen in the presence of blood, or body fluids, or moisture. The presence of the chitosan active surface  36  stanches, seals, and/or stabilizes the site of tissue injury, while establishing conditions conducive to the healing of the site. 
     The chitosan material that is incorporated into the active surface  36  can be produced in conventional ways. The structure or form producing steps for the chitosan material are typically carried out from a chitosan solution employing techniques such as freezing (to cause phase separation), non-solvent die extrusion (to produce a filament), electro-spinning (to produce a filament), phase inversion and precipitation with a non-solvent (as is typically used to produce dialysis and filter membranes) or solution coating onto a preformed sponge-like or woven product. The filament can be formed into a non-woven sponge-like mesh by non-woven spinning processes. Alternately, the filament may be produced into a felted weave by conventional spinning and weaving processes. Improved compliance and flexibility can be achieved by mechanical manipulation during or after manufacture, e.g., by controlled micro-fracturing by rolling, bending, twisting, rotating, vibrating, probing, compressing, extending, shaking and kneading; or controlled macro-texturing (by the formation of deep relief patterns) by thermal compression techniques. The tissue bandage structure  12  can also comprise a sheet of woven or non-woven mesh material enveloped between layers of the chitosan material. 
     The active surface  36  that includes chitosan material presents a robust, permeable, high specific surface area, positively charged surface. The positively charged surface creates a highly reactive surface for red blood cell and platelet interaction. Red blood cell membranes are negatively charged, and they are attracted to the chitosan material. The cellular membranes fuse to chitosan material upon contact. A clot can be formed very quickly, circumventing immediate need for clotting proteins that are normally required for hemostasis. For this reason, the chitosan material is effective for both normal as well as anti-coagulated individuals, and as well as persons having a coagulation disorder like hemophilia. The chitosan material also binds bacteria, endotoxins, and microbes, and can kill bacteria, microbes, and/or viral agents on contact. 
     B. The Delivery Device 
     As  FIG. 1  shows, the delivery device  14  includes a multi-lumen catheter tube  16  having a proximal end  18  and a distal end  20 . The distal end  20  carries an expandable structure  22 , which in the illustrated embodiment takes the form of an inflatable balloon. Other non-inflatable, but nevertheless expandable or enlargeable structures, can be used. The proximal end carries an actuator  30  and a coupling  24  which are manipulated in synchrony during operation of the expandable structure  22 , as will be described in greater detail later. 
     The catheter tube  16  can be formed of conventional polymeric materials and include an interior lumen (not shown) that accommodates passage of a guide wire  32 . The lumen also passes through the center of the expandable structure  22  as well. This makes it possible to guide the intraluminal deployment of the expandable structure  22  to an injury site within a body lumen or hollow body organ targeted for treatment. 
     The catheter tube  16  includes another lumen that communicates with the interior of the balloon  22 . The proximal end  18  of the catheter tube  16  includes a coupling  24  for coupling an inflation device  26 , such as a syringe or the like (see  FIG. 1 ), in communication with the interior of the expandable structure  22 . Operation of the inflation device  26  conveys an appropriate inflation medium (e.g., saline) into the expandable structure  22  to cause it to expand. 
     The catheter tube also includes a movable sheath  28 . The sheath  28  comprises a material that is flexible and impermeable to water. A push-pull wire  30  is coupled to the sheath  28 , which extends through another lumen within the catheter tube  16  and is coupled to an actuator  30  on the proximal end  18  of the catheter tube  16 . Pushing on the actuator  30  advances the sheath  28  distally over the expandable structure  22  (as shown in phantom lines in  FIG. 1 ). Pulling on the actuator  30  withdraws the sheath  28  proximally and free of the expandable structure  22  (as shown in solid lines in  FIG. 1 ). 
     In use, the tissue bandage structure  12  is sized and configured to be carried about the expandable structure  22  in a generally collapsed condition during introduction within the body lumen or hollow body organ (see  FIG. 10 ). The tissue bandage structure is also sized and configured to be enlarged in response to expansion of the expandable structure  22  (see  FIG. 12 ) for placement into contact with tissue in the body lumen or hollow body organ. 
       FIGS. 2 to 5  show a representative embodiment of a flexible chitosan bandage structure  12  that can be readily deployed using the delivery device  14  in the manner just described. The bandage structure  12  includes an inert, non-stick, water impermeable coating  34  on a side opposite to the active chitosan surface  36 . In use, it is the active chitosan surface  36  that is placed into contact with tissue. The inert, non-stick, water impermeable coating  34  makes it possible to roll or fold the chitosan surface  34  about the expandable structure  22  for deployment without sticking or adhering to the expandable structure  22  or itself. 
     Prior to intraluminal introduction of the delivery device  14  (see  FIGS. 6 and 7 ), the sheath  28  is withdrawn, and the chitosan bandage structure  12  is mounted about the expandable structure  22 , with the active chitosan surface  36  facing outward. In the illustrated embodiment, this is accomplished by wrapping the chitosan bandage structure  12  around the expandable structure  22 , with the non-stick coating  34  facing the expandable structure  22 . This corresponds to the generally collapsed condition described above, which provides a low profile condition for intraluminal introduction of the chitosan bandage structure  12 . 
     In this arrangement, the flexible bandage structure  12  (see  FIGS. 2 to 5 ) has a rectangular shape with a tab  40  at one end. To secure the bandage in a rolled position about the expandable structure  22  (as shown in  FIGS. 6 and 7 ), the tab can be inserted into a slit  42  formed in the chitosan bandage structure  12 . The frictional force between the tab  40  and the walls of the slit  42  are sufficient to hold the bandage structure  12  in a rolled position. However, when pressure is applied from within the rolled bandage structure  12  (as is shown in  FIG. 12  and will be described later), the tab  40  slides out of the slit  42  and the bandage structure  12  unfurls. Alternatively, the tab  40  and slit  42  can be replaced by a biodegradable tape with a perforation that will be more reliable in preventing premature deployment or unfurling of the bandage structure  12 . 
     Prior to intraluminal introduction, the sheath  28  is advanced over the bandage structure  12  that has been wrapped about the expandable structure  22  (see  FIGS. 8 and 9 ). As  FIG. 9  shows, the distal end of the sheath  28  is closed by a frangible or otherwise releasable securing device  44 . The securing device  28  holds the distal end of the sheath  28  closed. 
     The securing device  44  can be various constructed. It can, e.g., comprise a removable slip-knot that releases when the sheath is withdrawn, or a tearable perforated tab that tears when the sheath is withdrawn, or a ring that slides off or breaks when sheath is withdrawn. 
     In this position, the sheath  28  prevents contact between the active chitosan surface  36  and the mucosa during introduction until the instance of application. The sheath  28  protects the bandage structure  12  from becoming moist until the sheath  28  is moved proximally to reveal the bandage structure  12 . 
     Prior to insertion into the body lumen (see  FIG. 8 ), the expandable structure  22  is desirably partially enlarged by introduction of the inflating media (e.g., to about 0.25 atm) to create bulbous forms on each side of the bandage structure  12  as shown in  FIG. 8 . This partial expansion prevents the bandage structure  12  from migrating from the center of the expandable structure  22  during the introduction, but does not otherwise unfurl the bandage structure  12 , which remains in the generally collapsed condition. 
     As will also be described later, when it is desired to deploy the bandage structure  12 , the sheath  28  is withdrawn (see  FIG. 11 ) and subsequent expansion of the expandable structure  22  (see  FIG. 12 ) provides enough force to unfurl the bandage structure  12  into contact with an interior wall of the body lumen or hollow body organ. 
     II. Use of the Delivery System 
     The delivery system  10  makes possible the deployment of a chitosan bandage structure  12  within a body lumen or hollow body organ under endoscopic visualization, e.g., to treat an injury of the esophagus or other area of the gastrointestinal tract. 
     As  FIGS. 6 to 9  show, the chitosan bandage structure  12  can be wrapped and secured around the expandable structure  22  and enclosed during introduction with the removable sheath  28 . The delivery device  12  can be deployed either over a guide wire  32  alongside an endoscope  50  (as  FIG. 10  shows) or through the working channel of an endoscope (as  FIG. 15  shows). Once the chitosan bandage structure  12  is positioned correctly over an injury site, the removable sheath  28  is pulled back (see  FIG. 11 ) to uncover the chitosan bandage structure  12  for deployment. Subsequent expansion of the expandable structure  22  (see  FIG. 12 ) expands and unfurls the chitosan bandage structure, holding it against the mucosa circumferentially at the site of injury. After an appropriate holding time (e.g., about three minutes), the expandable structure  22  is collapsed, and the delivery device  14  is withdrawn (see  FIG. 13 ), leaving the chitosan bandage structure  12  at the injury site. During the entire procedure, the endoscope  50  provides direct visualization. 
     As the chitosan bandage structure  12  unfurls, it covers a circumferential section of the body lumen or hollow body organ and adheres to it. The properties of the active chitosan surface  36  serve to moderate bleeding, fluid seepage or weeping, or other forms of fluid loss, while also promoting healing. Due to the properties of the chitosan, the active surface  36  can also form an anti-bacterial and/or anti-microbial and/or anti-viral protective barrier at or surrounding the tissue treatment site within a body lumen or hollow body organ. The active surface  36  (whether or not it contains a chitosan material) can also provide a platform for the delivery of one or more therapeutic agents into the blood stream in a controlled release fashion. Examples of therapeutic agents that can be incorporated into the active surface  36  of the bandage structure  12  include, but are not limited to, drugs or medications, stem cells, antibodies, anti-microbials, anti-virals, collagens, genes, DNA, and other therapeutic agents; hemostatic agents like fibrin; growth factors; Bone Morphogenic Protein (BMP); and similar compounds. 
     The system  10  thereby makes possible an intraluminal delivery method that (i) locates and identifies the site of injury using an endoscope  50  and correlating video monitor; (ii) passes a guide wire  32  into the site of injury; (iii) positions the distal end of the delivery device  14  over the guide wire  32  (see  FIG. 10 ) at the site of injury while viewing the area with the endoscope  50 , which is positioned alongside the catheter tube  14 ; (iv) when positioned over the site of injury, as confirmed by the endoscope  50 , pulls the actuator  30  on the proximal end of the catheter tube  14  (see  FIG. 11 ) to withdraw the sheath  28  (also thereby breaking or otherwise releasing the security device  44 ) to unsheath and expose the chitosan bandage structure  12 ; (v) expands the expandable structure  22  (e.g., inflate the balloon) for a prescribed period (e.g., about three minutes) (see  FIG. 12 ) to unfurl the bandage structure  12  and hold the active surface  36  of the bandage structure  12  against mucosa; (vi) after the prescribed holding period, collapses the expandable structure  22  (e.g. deflate the balloon) and removes the delivery device  12  and guide wire  32  (see  FIG. 13 ), while continuing to monitor with the endoscope  50 , if desired. 
     Various modifications of the above-described method can be made. For example (see  FIG. 14 ), between (ii) and (iii), an over-tube  52  may be inserted in the body lumen to serve as a delivery sheath as well as a further water impermeable barrier between the device and the mucosa. As another example (see  FIG. 15 ), the actuator  30  and coupling  24  can be separated from the proximal end of the catheter tube  14 , and the catheter tube  14  back-loaded (proximal end first) through the working channel  52  of an endoscope  50 . Once back-loaded, the proximal components are re-connected to the catheter tube  14 . This arrangement uses the working channel  52  of the endoscope as a delivery sheath, instead of or in combination with a guide wire and/or an over-tube. 
     The shape, shape, and configuration of the expandable body and the bandage structure  12  can modified to accommodate varying anatomies encountered within a body lumen or hollow body organ, such as the gastrointestinal tract. This expands the possible use of the delivery system  10  greatly. For example, in esophagogastrectomies, an anastomosis between the stomach and the esophagus is created where an asymmetric expandable structure  22  and a bandage structure  12  can be deployed by the system  10  to cover the suture lines of the anastomosis. In addition, the size and shape of the expandable structure  22  can be altered to accommodate deployment of a bandage structure  12  in the duodenum or stomach. 
     The intraluminal delivery method as described utilizes the catheter-based delivery device  12 , as described, to introduce a flexible, relatively thin chitosan bandage structure  12 , as described, in an low profile condition and covered with a water impermeable layer to a targeted treatment site within a body lumen or hollow body organ, e.g. to treat esophageal injury. The delivery method prevents the active chitosan surface  36  of the bandage structure  12  from contacting the mucosa until the bandage structure  12  positioned in a desired position over the injury. 
     III. Conclusion 
     It has been demonstrated that a therapeutic bandage structure can be introduced and deployed within a body lumen or hollow body organ using an intraluminal delivery system  10  under endoscopic guidance. 
     It should be apparent that above-described embodiments of this invention are merely descriptive of its principles and are not to be limited. The scope of this invention instead shall be determined from the scope of the following claims, including their equivalents.