Abstract:
The present embodiments provide systems and methods for deploying at least one clip device. In a first embodiment, the system comprises a first clip device having first and second arms. The first clip device and an associated sliding ring are configured to be selectively advanced through a lumen of an inner catheter. Selective positioning of an outer catheter over a distal region of the inner catheter causes a distal region of the inner catheter to bow radially inward to form a constriction that securely engages the sliding ring of the first clip device, thereby allowing for partial closure and repositioning of the first clip device. In an alternative embodiment, a delivery system includes a single catheter having a tapered distal region, such that upon ejection of the sliding ring from the distal end of the catheter, the sliding ring is dimensioned to abut the distal end of the catheter. In any of the embodiments, multiple clips may be sequentially loaded and deployed using the delivery systems. Various clip designs and a loading cylinder are also disclosed.

Description:
PRIORITY CLAIM 
       [0001]    This invention claims the benefit of priority of U.S. Provisional Application Ser. No. 61/372,283, entitled “Clip Devices and Methods of Delivery and Deployment,” filed Aug. 10, 2010, the disclosure of which is hereby incorporated by reference in its entirety. 
     
    
     BACKGROUND 
       [0002]    Conventionally, a clip may be introduced into a body cavity through an endoscope to grasp living tissue of a body cavity for hemostasis, marking, and/or ligating. In addition, clips are now being used in a number of applications related to gastrointestinal bleeding such as peptic ulcers, Mallory-Weiss tears, Dieulafoy&#39;s lesions, angiomas, post-papillotomy bleeding, and small varices with active bleeding. 
         [0003]    Gastrointestinal bleeding is a somewhat common and serious condition that is often fatal if left untreated. This problem has prompted the development of a number of endoscopic therapeutic approaches to achieve hemostasis such as the injection of sclerosing agents and contact thermo-coagulation techniques. Although such approaches are often effective, bleeding continues for many patients and corrective surgery therefore becomes necessary. Because surgery is an invasive technique that is associated with a high morbidity rate and many other undesirable side effects, there exists a need for highly effective, less invasive procedures. 
         [0004]    Mechanical hemostatic devices have been used in various parts of the body, including gastrointestinal applications. Such devices are typically in the form of clamps, clips, staples and sutures, which are able to apply sufficient constrictive forces to blood vessels so as to limit or interrupt blood flow. One of the problems associated with conventional hemostatic devices, however, is that many devices are not strong enough to cause permanent hemostasis. Further, typically once such mechanical hemostatic devices are at least partially deployed, they cannot be opened and closed repeatedly before the final release of the device, which may result in possible permanent deployment of the device at an undesirable location. 
         [0005]    Still further, mechanical hemostatic devices typically are loaded, one at a time, within an introducer equipped to deliver and deploy the device. A first hemostatic device may be deployed, but if it becomes desirable to deliver and deploy a second hemostatic device, the introducer typically must be removed from the patient&#39;s body in order to load the second hemostatic device. The introducer then is loaded back into the patient&#39;s body to deploy the second hemostatic device, and the process is repeated for each subsequent device. However, the process of deploying only one hemostatic device at a time may become very time consuming and inconvenient, causing significant delays when it may be imperative to quickly stop bleeding. 
       SUMMARY 
       [0006]    The present embodiments provide systems and methods for deploying at least one clip device. In each embodiment, multiple clips may be sequentially loaded and deployed using the delivery systems. Various clip designs and a loading cylinder are also disclosed. 
         [0007]    In a first embodiment, the system comprises a first clip device having first and second arms. The first clip device and an associated sliding ring are configured to be selectively advanced through a lumen of an inner catheter. Selective positioning of an outer catheter over a distal region of the inner catheter causes a distal region of the inner catheter to bow radially inward to form a constriction that securely engages the sliding ring of the first clip device. When the sliding ring is securely engaged, the first and second arms of the first clip device are movable longitudinally relative to the sliding ring, thereby allowing for partial closure and repositioning of the first clip device. 
         [0008]    Advantageously, in this manner, any number of clip devices may be sequentially loaded into the lumen of the catheter and deployed, one at a time, without the need to remove the inner and outer catheters from the patient&#39;s body and individually re-load clip devices, thereby reducing operating time. Further, each of the clip devices advantageously may move between the open and closed states any number of times before final deployment. 
         [0009]    In an alternative embodiment, a delivery system includes a catheter having proximal and distal ends, a lumen extending therebetween, and a tapered distal region. The catheter comprises a first inner diameter at a location proximal to the tapered distal region, and further has a second inner diameter at the distal end, wherein the second inner diameter is less than the first inner diameter. The sliding ring comprises an outer diameter that is less than the first inner diameter of the catheter and greater than the second inner diameter of the catheter. The tapered distal region of the catheter is flexible such that application of a predetermined distally-oriented forced imposed upon the sliding ring ejects the sliding ring from the distal end of the catheter. Upon ejection of the sliding ring from the distal end of the catheter, the sliding ring is dimensioned to abut the distal end of the catheter. At this time, proximal retraction of the first and second arms of the first clip device relative to the sliding ring moves the clip device between the open and closed states. 
         [0010]    Other systems, methods, features and advantages of the invention will be, or will become, apparent to one with skill in the art upon examination of the following figures and detailed description. It is intended that all such additional systems, methods, features and advantages be within the scope of the invention, and be encompassed by the following claims. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0011]    The invention can be better understood with reference to the following drawings and description. The components in the figures are not necessarily to scale, emphasis instead being placed upon illustrating the principles of the invention. Moreover, in the figures, like referenced numerals designate corresponding parts throughout the different views. 
           [0012]      FIGS. 1-5  are side-sectional views illustrating an exemplary delivery system and sequence of deployment for at least one clip device. 
           [0013]      FIG. 6  is a perspective view illustrating features of a distal region of an inner catheter of the delivery system of  FIGS. 1-5 . 
           [0014]      FIGS. 7-9  are side-sectional views illustrating an alternative delivery system and sequence of deployment for at least one clip device. 
           [0015]      FIG. 10  is a perspective view illustrating features of a distal region of a catheter of the delivery system of  FIGS. 7-9 . 
           [0016]      FIG. 11  is a side-sectional view of a loading cylinder that may be used in conjunction with clip delivery systems. 
           [0017]      FIG. 12  is a perspective view of the clip device of  FIGS. 7-9 . 
           [0018]      FIG. 13  is a perspective view of an alternative clip device. 
           [0019]      FIG. 14  is a perspective view of a further alternative clip device. 
           [0020]      FIG. 15  is a perspective view of yet a further alternative clip device. 
       
    
    
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS 
       [0021]    In the present application, the term “proximal” refers to a direction that is generally towards a physician during a medical procedure, while the term “distal” refers to a direction that is generally towards a target site within a patient&#39;s anatomy during a medical procedure. 
         [0022]    Referring now to  FIGS. 1-6 , a first embodiment of a clip device is shown, along with an exemplary system for delivery and deployment of at least one of the clip devices. In this embodiment, first and second clip devices  20   a  and  20   b  are provided. The first clip device  20   a  comprises a first arm  30   a  and a second arm  40   a . The first arm  30   a  has a proximal end  32   a  and a distal end  34   a , while the second arm  40   a  has a proximal end  42   a  and a distal end  44   a . The proximal end  32   a  of the first arm  30   a  and the proximal end  42   a  of the second arm  40   a  are joined together by a proximal securement member  60   a , which may comprise an adhesive, solder, weld, mechanical attachment device, or any other suitable mechanism, that joins the proximal ends  32   a  and  42   a  of the arms  30   a  and  40   a  together. 
         [0023]    The clip device  20   a  further comprises a sliding ring  50   a , which has an inner diameter that is slightly larger than an outer diameter of the first and second arms  30   a  and  40   a  combined. The proximal securement member  60   a  limits proximal movement of the sliding ring  50   a . In use, the sliding ring  50   a  is dimensioned to slide over the first and second arms  30   a  and  40   a , causing the arms to move to a closed position, as explained further in  FIG. 4  below. 
         [0024]    The distal ends  34   a  and  44   a  of the arms  30   a  and  40   a  are preferably bent in radially inward directions to form tips  38   a  and  48   a , respectively, as best seen in  FIG. 2 . The tips  38   a  and  48   a  are configured to grasp and/or pierce tissue. While two arms  30   a  and  40   a  are depicted in the embodiment of  FIGS. 1-5 , it is contemplated that a greater number of arms may be used. For example, as explained in  FIGS. 13-14  below, alternative clip devices  120   a ′ and  120   a ″ comprise three and four arms, respectively. 
         [0025]    The first clip device  20   a  has a delivery state, an open state, and a closed state. In the delivery state, the first clip device  20   a  is disposed within a lumen  78  of an inner catheter  70 . The lumen  78  of the inner catheter  70  is dimensioned such that the distal ends  34   a  and  44   a  of the arms  30   a  and  40   a  are held adjacent to one another in the delivery state, as depicted in  FIG. 1 . 
         [0026]    In the open state, the distal ends  34   a  and  44   a  of the first and second arms  30   a  and  40   a , respectively, tend to be spaced apart from one another, as shown in  FIGS. 2-3 . The first and second arms  30   a  and  40   a  are biased to assume the open state when the distal ends  34   a  and  44   a  are no longer constrained by the inner catheter  70 . The distal ends  34   a  and  44   a  may be biased to assume the open state either due to the inherent resilient properties of the material forming the first and second arms  30   a  and  40   a , or alternatively, the first and second arms  30   a  and  40   a  may be heat-set to assume the deployed configuration shown. The first and second arms  30   a  and  40   a  may be made from any suitable resilient material such as stainless steel, nitinol, plastic, and the like. Optionally, the arms of the clip may be formed of a resorbable material such as the magnesium alloy WE43, which can dissolve over time instead of needing to pass through a patient&#39;s gastrointestinal system. Further, the first and second arms  30   a  and  40   a  may have a cross-sectional shape that is round, square, rectangular, triangular, pie-shaped, truncated cone, and the like. 
         [0027]    In the closed state, the sliding ring  50   a  is translated distally relative to the first and second arms  30   a  and  40   a , as depicted in  FIGS. 4-5  and explained further below. At this time, the distal ends  34   a  and  44   a  of the first and second arms  30   a  and  40   a , respectively, are closed together and the tips  38   a  and  48   a  are configured to grasp tissue and facilitate tissue closure and hemostasis. The sliding ring  50   a  may lockingly engage the distal ends  34   a  and  44   a  of the first and second arms  30   a  and  40   a , respectively, and may be sized so that it will not slide distally over the ends of the first and second arms  30   a  and  40   a  in the closed state. Optionally, one or more distal stop members, such as a solder or a mechanical member, may be disposed on the first arm  30   a  and/or the second arm  40   a  to limit distal advancement of the sliding ring  50   a.    
         [0028]    Referring still to  FIGS. 1-5 , an exemplary system is described for delivery and deployment of at least one of the clip devices. The delivery system comprises the inner catheter  70  having the lumen  78 , as noted above, and further comprises an outer catheter  80  having a lumen  88 . In the embodiment of  FIGS. 1-5 , first and second clip devices  20   a  and  20   b  are provided for sequential deployment, and the second clip device  20   b  is generally identical to the first clip device  20   a.    
         [0029]    The inner catheter  70  comprises an outer diameter that is less than an inner diameter of the outer catheter  80 , thereby allowing the inner catheter  70  to be longitudinally advanced within the lumen  88  of the outer catheter  80 . The inner catheter  70  further comprises an inner diameter that allows the first and second clip devices  20   a  and  20   b  to be loaded within the lumen  78  of the inner catheter  70 , as shown in  FIG. 1 . 
         [0030]    The inner catheter  70  comprises a distal end  74  and a flexible distal region  75 . The flexible distal region  75  may be selectively moved in a radially inward direction, for purposes described further below. Preferably, a plurality of slits  77  are formed in the distal end  74 , as shown in  FIG. 6 , to permit the radial flexibility along the distal region  75 . 
         [0031]    At least one wedge member  92  may be positioned along the flexible distal region  75  of the inner catheter  70 . In the embodiment shown, a plurality of wedge members  92  having a tapered shape are disposed between the inner catheter  70  and the outer catheter  80 , causing the flexible distal region  75  of the inner catheter  70  to move radially inward to form a constriction  79  when the outer catheter  80  is advanced against the wedge member  92 , as shown in  FIGS. 3-4 . The wedge member  92  may comprise a biocompatible glue, plastic, metal or other suitable material, and may comprise other shapes besides the tapered shape depicted to accomplish the objectives described below. Alternatively, one or more wedge members  92  may be formed as an integral portion of the inner catheter  70  along the distal region  75 . 
         [0032]    The outer catheter  80  may comprise a rigid or substantially rigid material, such as stainless steel or plastic materials, which substantially prohibits radial outward movement of the wedge member  92  and the flexible distal region  75  of the inner catheter  70  when a distal end  84  of the outer catheter  80  covers these regions, as shown in  FIGS. 3-4 . However, when the distal end  84  of the outer catheter  80  is retracted proximally beyond the wedge member  92  and the flexible distal region  75  of the inner catheter  70 , the flexible distal region  75  may move radially outward and the constriction  79  may be removed, as depicted in  FIG. 5  below. 
         [0033]    In one exemplary method, the first and second clip devices  20   a  and  20   b  are loaded sequentially such that the first clip device  20   a  is loaded distal to the second clip device  20   b  within the lumen  78  of the inner catheter  70 , as shown in  FIG. 1 . A stylet  90  may be positioned in the lumen  78  at a location proximal to the second clip device  20   b.    
         [0034]    In one embodiment, the first and second clip devices  20   a  and  20   b  each comprise proximal retainers  64   a  and  64   b , respectively. The proximal retainers  64   a  and  64   b  may be in the form of loop members having outer diameters that are smaller than the inner diameter of the inner catheter  70 . In use, the first and second clip devices  20   a  and  20   b  may be loaded within the inner catheter  70  such that the distal ends  34   b  and  44   b  of the second clip device  20   b  securely engage the proximal retainer  64   a  of the first clip device  20   a  when the inner catheter  70  is positioned over the connection as shown in  FIGS. 1-4 . When the inner catheter  70  is no longer positioned over this connection, as shown in  FIG. 5 , the first and second clip devices  20   a  and  20   b  may disengage from one another, as explained below. 
         [0035]    The stylet  90  may comprise a retainer  92 , such as a hook member, that engages the proximal retainer  64   b  at the proximal end of the second clip device  20   b  when the inner catheter  70  is positioned over this connection, as shown in  FIGS. 1-5 . Accordingly, proximal and distal advancement of the stylet  90  causes a corresponding movement of the first and second clip devices  20   a  and  20   b.    
         [0036]    It should be noted that while two clip devices are shown in this example, any number may be used and sequentially loaded into the inner catheter  70  in an abutting manner distal to the stylet  90 . Moreover, while one exemplary retainer arrangement is shown in the form of a hook and loop connection, various other retainer arrangements are possible. By way of example, alternative retainer arrangements to couple the stylet  90  to the second clip device  20   b , and/or to couple the first and second clip devices  20   a  and  20   b  together, are described in U.S. Pat. Pub. No. 2007/0282355, the disclosure of which is hereby incorporated by reference in its entirety. 
         [0037]    The stylet  90 , the first clip device  20   a  and the second clip device  20   b  are loaded into the inner catheter  70  as shown in  FIG. 1 . Optionally, at this time, the outer catheter  80  may be positioned over the inner catheter  70 , as shown in  FIG. 3 , such that the constriction  79  is formed via the wedge member  92 . The constriction  79  may prevent the first and second arms  30   a  and  40   a  of the first clip device from extending distal to the inner catheter  70  to reduce the likelihood of inadvertent piercing during delivery. 
         [0038]    Referring to  FIG. 2 , the outer catheter  80  is positioned proximally relative to the inner catheter  70 , thereby exposing the distal region  75  of the inner catheter  70 . The stylet  90  is advanced distally, relative to the inner catheter  70  and the outer catheter  80 , to cause distal advancement of the second clip device  20   b  and corresponding distal advancement of the first clip device  20   a  in an abutting manner. The stylet  90  is advanced distally until the sliding ring  50   a  of the first clip device  20   a  is aligned with the distal region  75  of the inner catheter  70 , as shown in  FIG. 2 . At this time, the distal ends  34   a  and  44   a  of the first and second arms  30   a  and  40   a , respectively, of the first clip device  20   a  are advanced distally beyond the distal end  74  of the catheter  70 , and when unconstrained, tend to bow in a radially outward direction spaced apart from one another, as depicted in  FIG. 2 . 
         [0039]    Referring to  FIG. 3 , in a next step, the outer catheter  80  is advanced distally relative to the inner catheter  70 , thereby engaging the wedge members  92  and urging the distal end  74  of the inner catheter  70  into engagement with the sliding ring  50   a . A friction fit is achieved such that the sliding ring  50   a  is held steady. At this time, the stylet  90  may be proximally and distally advanced, thus causing corresponding movement of the first and second arms  30   a  and  40   a  relative to the sliding ring  50   a . Thus, the sliding ring  50   a  is held steady while the first and second arms  30   a  and  40  disposed therein are advanced or retracted as desired. 
         [0040]    In accordance with one aspect, a physician need not deploy the first clip device  20   a  at this time. Rather, the first clip device  20   a  may be moved between the open state of  FIG. 3 , and a state that is at least partially closed, any number of times before final deployment. For example, a physician may at least partially close the first clip device  20   a  by proximally retracting the stylet  90 , and therefore the first and second arms  30   a  and  40   a , relative to the sliding ring  50   a , thus forcing the distal ends  34   a  and  44   a  closer together. However, before the distal ends  34   a  and  44   a  are locked closed within the sliding ring  50   a , the physician may distally advance the stylet  90 , thus distally advancing the first and second arms  30   a  and  40   a  relative to the sliding ring  50   a  and re-opening the first clip device  20   a , e.g., for alternative positioning or grasping. Advantageously, in this manner, the first clip device  20   a  may move between the open and closed states any number of times before final deployment. 
         [0041]    Referring now to  FIG. 4 , if a physician wishes to securely close the first clip device  20   a  with tissue therein, the stylet  90  and the first clip device  20   a  are retracted tightly relative to the inner catheter  70  that is holding the sliding ring  50   a . Alternatively, the inner catheter  70  and outer catheter  80  may be advanced distally in tandem, while the stylet  90  is held steady. The result in either case is that the sliding ring  50   a  is translated distally relative to the first and second arms  30   a  and  40   a  with enough force, as shown in  FIG. 4 , thereby securely closing the first clip device  20   a.    
         [0042]    Referring now to  FIG. 5 , in a next step, the outer catheter  80  is proximally retracted with respect to the inner catheter  70 , such that the distal end  84  of the outer catheter  80  is positioned proximal to the wedge member  92 . At this time, the wedge member  92  is no longer radially constrained and the flexible distal region  75  of the inner catheter  70  may move radially outward to remove the constriction  79 , as depicted in  FIG. 5 . The sliding ring  50   a  is no longer engaged in a friction fit with the inner catheter  70 . 
         [0043]    The stylet  90  is then advanced distally relative to the inner catheter  70  to cause the distal ends  34   b  and  44   b  of the first and second arms  30   b  and  40   b , respectively, of the second clip device  20   b  to extend distal to the inner catheter  70 . At this time, the connection between the first and second arms  30   b  and  40   b  of the second clip device  20   b  and the proximal retainer  64   a  of the first clip device  20   a  is exposed, thereby allowing the first and second clip devices  20   a  and  20   b  to detach from engagement with one another, as shown in  FIG. 5 . 
         [0044]    After deployment of the first clip device  20   a , but before deployment of the second clip device  20   b , the sliding ring  50   b  of the second clip device  20   b  may be aligned with the distal region  75  of the inner catheter  70 , in the manner explained in  FIG. 2  above for the first clip device  20   a . The sequence of deployment described in  FIGS. 2-5  then may be carried out for the second clip device  20   b . Advantageously, in this manner, any number of clip devices may be sequentially loaded into the lumen  78  of the inner catheter  70  and deployed, one at a time, without the need to remove the inner and outer catheters  70  and  80  from the patient&#39;s body and individually re-load clip devices, thereby saving operating time. 
         [0045]    Referring to  FIG. 6 , and as noted above, the flexible distal region  75  of the inner catheter  70  may be selectively moved in a radially inward direction by providing a plurality of slits  77  formed in the flexible distal region  75 . In the embodiment shown, four slits  77  are formed in the distal end  74  of the catheter  70  and extend in tapered manner in a distal to proximal direction. The four slits  77  may be radially spaced apart around the circumference of the catheter  70 . The one or more wedge members  92  may be attached to the flexible distal region  75  at one or more locations between the slits  77 . While four illustrative tapered slits  77  are shown in  FIG. 6 , it will be appreciated that greater or fewer slits may be employed, and they may comprise different shapes and configurations than depicted. 
         [0046]    Referring now to  FIGS. 7-10 , an alternative delivery system and sequence of deployment for at least one clip device is shown. In  FIGS. 7-10 , an alternative first clip device  120   a  is similar to the first clip device  20   a  described above, with a main exception that proximal ends  132   a  and  142   a  of first and second arms  130   a  and  140   a , respectively, are integrally formed into a proximal retainer  164   a  in the shape of a loop member, and therefore the proximal securement member  60   a  of  FIGS. 1-5  is omitted. In this manner, the first clip device  120   a  may be formed from one continuous wire that is looped around at its proximal end, and where the continuous wire is bent to form distal ends  134   a  and  144   a , as shown in  FIG. 7  and described further in  FIG. 12  below. 
         [0047]    The proximal retainer  164   a  in the shape of the loop member has an outer diameter that is larger than the inner diameter of the sliding ring  50   a , thereby limiting proximal movement of the sliding ring  50   a . As in the embodiment of  FIGS. 1-5 , the sliding ring  50   a  is otherwise dimensioned to slide over the first and second arms  130   a  and  140   a , toward the distal ends  134   a  and  134   b  of the first and second arms  130   a  and  140   a , respectively, causing the arms to move to a closed position. The first clip device  120   a  has a delivery state, an open state, and a closed state, similar to the first clip device  20   a  described above. 
         [0048]    The alternative delivery system of  FIGS. 7-10  comprises a catheter  170  having a lumen  178 , and has an inner diameter that is generally larger than an outer diameter of the first and second clip devices  20   a  and  20   b  in the delivery state, thereby allowing the first and second clip devices  20   a  and  20   b  to be loaded within the lumen  78  of the catheter  70  as shown in  FIG. 1 . Notably, in this embodiment, an outer catheter is omitted. 
         [0049]    The catheter  170  comprises a distal end  174  and a tapered distal region  175 . Preferably, at least one slit  177  is formed in the tapered distal region  175 , as shown in  FIG. 10 , to permit the radial flexibility along the distal region  175 . 
         [0050]    In one exemplary method, the first and second clip devices  120   a  and  120   b  may be loaded sequentially such that the first clip device  120   a  is loaded distal to the second clip device  120   b  within the lumen  178  of the catheter  170 , as shown in  FIG. 7 . The stylet  90  may be positioned in the lumen  178  at a location proximal to the second clip device  120   b . In use, the first and second clip devices  120   a  and  120   b  may be loaded within the catheter  170  such that the distal ends  134   b  and  144   b  of the second clip device  120   b  securely engage the proximal retainer  164   a  of the first clip device  120   a . Further, the retainer  92  of the stylet  90  engages the proximal retainer  164   b  at the proximal end of the second clip device  120   b , as shown in  FIG. 7 . Accordingly, proximal and distal advancement of the stylet  90  causes a corresponding movement of the first and second clip devices  120   a  and  120   b.    
         [0051]    Notably, the catheter  170  has a first inner diameter D 1  at a location proximal to the tapered distal region  175 , and has a smaller second inner diameter D 2  at the distal end  174 , as shown in  FIG. 10 , such that the taper reduces the inner diameter from D 1  to D 2 . The sliding ring  50   a  has an outer diameter having a size dimension between the first and second inner diameters D 1  to D 2  of the catheter  170 . In the delivery state shown in  FIG. 7 , absent significant forces imposed thereon, the tapered distal region  175  serves to retain the first clip device  120   a  inside of the catheter  170  and prevents inadvertent piercing by the arms  130   a  and  140   a.    
         [0052]    Referring to  FIG. 8 , in a next step, the stylet  90  is advanced distally, relative to the catheter  170 , to cause distal advancement of the second clip device  120   b  and corresponding distal advancement of the first clip device  120   a  in an abutting manner. The stylet  90  is advanced distally until the sliding ring  50   a  of the first clip device  120   a  abuts the tapered distal region  175  and is ultimately advanced distal to the tapered distal region  175  with a sufficient force. The slit  177  of the tapered distal region  175  allows the distal end  174  of the catheter  170  to flex upon application of the sufficient force imposed by the sliding ring  50   a , and further, the tapered distal region  175  may be formed of a material, such as molded plastic, that facilitates such flexing upon application of the sufficient force by the sliding ring  50   a . At this time, the distal ends  134   a  and  144   a  of the arms  130   a  and  140   a , respectively, of the first clip device  120   a  are advanced distally beyond the distal end  174  of the catheter  170 , and when unconstrained, tend to bow in a radially outward direction spaced apart from one another, as depicted in  FIG. 8 . 
         [0053]    While the sliding ring  50   a  is disposed just distal to the tapered distal region  175  of the catheter  170 , the proximal retainer  164   a  of the first clip device  120   a  is retained within the lumen  178  of the catheter  170 , as shown in  FIG. 8 . The tapered distal region  175  of the catheter  170  may be biased such that it tends to close around the proximal retainer  164   a  of the first clip device  120   a . At this time, the distal end  174  of the catheter  170  abuts a proximal edge of the sliding ring  50   a , as depicted in  FIG. 8 . Since the second inner diameters D 2  of the catheter  70  is less than an outer diameter of the sliding ring  50   a , the sliding ring  50   a  is prevented from being pulled back into the lumen  178  of the catheter  170 . 
         [0054]    The stylet  90  may be proximally retracted to at least partially close the first clip device  120   a . However, before the distal ends  134   a  and  144   a  are locked closed within the sliding ring  50   a , the physician may proximally or distally advance the stylet  90  gently, thus partially closing and re-opening the first and second arms  130   a  and  140   a.    
         [0055]    Referring to  FIG. 9 , if a physician wishes to securely close the first clip device  120   a  with tissue therein, the stylet  90  and the first clip device  120   a  are retracted tightly relative to the catheter  170 . Alternatively, the catheter  170  may be advanced while the stylet  90  is held steady. The result in either case is that the sliding ring  50   a  is translated distally relative to the first and second arms  130   a  and  140   a , as shown in  FIG. 9 , thereby securely closing the first clip device  120   a.    
         [0056]    Subsequently, the stylet  90  is then advanced distally relative to the catheter  170  to cause the distal ends  134   b  and  144   b  of the arms  130   b  and  140   b , respectively, of the second clip device  120   b  to extend distal to the catheter  170 . At this time, the connection between the first and second arms  130   b  and  140   b  of the second clip device  120   b  and the proximal retainer  164   a  of the first clip device  120   a  is exposed, thereby allowing the first and second clip devices  120   a  and  120   b  to detach from engagement with one another in a manner similar to the embodiment of  FIG. 5 . 
         [0057]    The sequence of deployment described in  FIGS. 7-9  then may be carried out for the second clip device  120   b . Advantageously, in this manner, any number of clip devices may be sequentially loaded into the lumen  178  of the catheter  170  and deployed, one at a time, without the need to remove the catheter  170  from the patient&#39;s body and individually re-load clip devices, thereby saving operating time. 
         [0058]    Referring now to  FIG. 11 , a loading cylinder  190  may be used in conjunction with either the embodiment of  FIGS. 1-6  or  FIGS. 7-10  to facilitate fast and efficient loading or reloading of one or more clip devices. In the embodiment of  FIG. 11 , the loading cylinder  190  comprises proximal and distal ends  192  and  194 , respectively, and a lumen  198  extending therebetween. The loading cylinder  190  may comprises inner and outer diameters that are identical to inner and outer diameters of the inner catheter  70  of  FIGS. 1-6  or the catheter  170  of  FIGS. 7-10 . Optionally, an engagement mechanism (not shown) may be provided to selectively couple the distal end  194  of the loading cylinder  190  with the proximal end  172  of the catheter  170 , to thereby ensure a correct alignment between the lumen  198  of the loading cylinder  190  and the lumen  178  of the catheter  170 . 
         [0059]    In the example of  FIG. 11 , two additional clip devices  120   c  and  120   d , which are identical to the clip devices  120   a  and  120   b  of  FIGS. 7-9 , are loaded into the lumen  198  of the loading cylinder  190  as shown. The proximal retainer  164   d  of the clip device  120   d  may extend just outside of the proximal end  192  of the loading cylinder  190 , as shown in  FIG. 11 , for subsequent engagement with a retainer  92 ′ of an alternative stylet  90 ′. The alternative stylet  90 ′ is similar to the stylet  90  described above, with an exception that the retainer  92 ′comprises arms  95  and  96 , which are similar in structure to the distal ends  134   a  and  144   a  of the first clip device  120   a.    
         [0060]    In use, a physician may deploy the clip devices  120   a  and  120   b  in the manner described in  FIGS. 7-9  above. The loading cylinder  190 , carrying additional clip devices  120   c  and  120   d , may be provided in the operating room. If the additional clip devices  120   c  and  120   d  are needed, the stylet  90 ′ is retracted from within the lumen  178  of the catheter  170 , and may be withdrawn towards a sheath  98  as depicted in  FIG. 11 . The distal end  194  of the loading cylinder  190  then is aligned with the proximal end  172  of the catheter  170 , such that the lumen  198  of the loading cylinder  190  is aligned with the lumen  178  of the catheter  170 . The arms  95  and  96  of the retainer  92 ′ of the stylet  90 ′ then are joined to the proximal retainer  164   d  of the clip device  120   d  and urged distally into the loading cylinder  190 . Distal advancement of the stylet  90 ′ causes corresponding distal advancement of the clip devices  120   c  and  120   d  through the lumen  178  of the catheter  170 , and the deployment of the clip devices  120   c  and  120   d  may be carried out in the manner described above. Advantageously, the endoscope and catheters can remain in place within the body of the patient, retaining access to the bleeding site, and facilitating a faster procedure. The catheters  70  and  170  described above can be reloaded as many times as needed using one or more loading cylinders  190 . Moreover, different loading cylinders  190  can be provided with different clip styles. 
         [0061]    Referring now to  FIGS. 12-15 , features of various possible clip designs are shown. In  FIG. 12 , the clip device  120   a  of the embodiment of  FIGS. 7-10  is shown in isolation. In one embodiment, the clip device  120   a  has a length in the delivery state of between about 10 mm to about 25 mm. In the open state, the distance between the distal ends  134   a  and  144   a  of the first and second arms  130   a  and  140   a , respectively, may be between about 6 mm to about 10 mm. The wire forming the clip device  120   a  may comprise a flat wire having a width of about 0.8 mm to about 1.0 mm, and a thickness of about 0.1 mm to about 0.2 mm. When used in conjunction with a delivery system as shown in  FIGS. 1-6  or  FIGS. 7-10 , the clip device  120   a  and associated sliding ring  50   a  can fit down an endoscope channel having a 2.8 mm or 3.2 mm diameter. As noted above, the clip device  120   a  can be formed of any suitable material such as nitinol or another material that may be biased to assume the open state shown in  FIG. 12  upon removal from a delivery catheter, and optionally may be formed of a resorbable material. 
         [0062]    In  FIG. 13 , an alternative clip device  120   a ′ is formed from a wire that is bent to form the first and second arms  130   a  and  140   a , as explained in  FIGS. 7-9  and  FIG. 12  above, however an additional wire segment is provided and forms a third arm  150   a  having a proximal end  152   a  and a distal end  154   a . A three-prong clip device  120   a ′ therefore is provided. The proximal end  152   a  of the third arm  150   a  may be soldered to a portion of the loop formed by the proximal ends  132   a  and  142   a  of the arms  130   a  and  140   a , respectively, thereby forming a proximal retainer  164   a . In a further alternative, a clip device may be similar to the clip device  120   a ′, but may comprise a fourth arm, whereby the four arms may be equally spaced apart about 90 degrees from one another, or variably spaced apart at other distances from one another. 
         [0063]    In  FIG. 14 , an alternative clip device  120   a ″ is substantially identical to the clip device  120   a , with the exception that an additional wire is disposed inward of the wire forming the first and second arms  130   a  and  140   a . The additional wire forms third and fourth arms  130   a ″ and  140   a ″ having proximal ends  132   a ″ and  142   a ″, respectively. The proximal ends  132   a ″ and  142   a ″ form a loop member disposed inside of the loop member formed by the proximal ends  132   a  and  142   a  of the first and second arms  130   a  and  140   a , respectively, as shown in  FIG. 14 , to form a proximal retainer  164   a ″. Further, the third and fourth arms  130   a ″ and  140   a ″ have distal ends  134   a ″ and  144   a ″, which may be slightly offset from the distal ends  134   a  and  144   a  of the first and second arms  130   a  and  140   a , respectively, as shown in  FIG. 14 . 
         [0064]    In  FIG. 15 , an alternative clip device  220  is similar to the clip device  120   a  in that one wire is bent to form first and second arms  230  and  240  having proximal ends  232  and  234 , respectively, which are coupled together to form a proximal retainer  264  in the shape of a loop member. The first and second arms  230  and  240  further comprise distal ends  234  and  244 , respectively. In this embodiment, the wire forming the first and second arms comprises a round cross-sectional shape. In order to provide a larger and sharper surface area to engage tissue, grasping members  250   a  and  250   b  are coupled to exterior surfaces of the distal ends  234  and  244  of the first and second arms  230  and  240 , respectively. The grasping members  250   a  and  250   b  may be coupled to the first and second arms  230  and  240  using a solder, weld, mechanical connection, or other suitable technique. Preferably, the grasping members  250   a  and  250   b  comprise sharpened distal tips  255  that are bent radially inward to securely engage tissue. It will be appreciated that where flat wire cross-sections are depicted herein, round wire cross-sections may be provided, and vice versa. 
         [0065]    While various embodiments of the invention have been described, the invention is not to be restricted except in light of the attached claims and their equivalents. Moreover, the advantages described herein are not necessarily the only advantages of the invention and it is not necessarily expected that every embodiment of the invention will achieve all of the advantages described.