Patent Application
20110054498
The present invention relates to endoscopic compression clips and a method and system for their use.
Polyps are defined as growths or masses protruding from a mucous membrane of the body. They may occur in the mucous membrane of many different types of organs, such as the nose, mouth, stomach, intestines, rectum, urinary bladder, and uterus. Most polyps are benign and eventually stop growing, but some may ultimately become cancerous tumors. Colorectal or gastric cancers, often beginning as benign or precancerous polyps, can essentially be avoided if detected and treated in their early stages by performing a polypectomy.
Polypectomy is the medical term for removing polyps, particularly small polyps of the colon and stomach. These can be removed by using a biopsy forceps, which removes small pieces of tissue. Larger polyps are usually removed by putting a noose, or snare, around the polyp base or stalk and burning through the tissue with an electric instrument (cauterization). Other devices employ physical or electrical scraping of the lining of an organ, such as the colon, rectum or stomach, to remove the polyp. The severed polyps are usually retrieved for examination by a pathologist.
Complications, however, sometimes occur during polypectomies. Particularly problematic is bleeding induced by the device used to resect the polyp. The bleeding may be immediate or delayed. When bleeding is immediate, the vision of the physician is obscured and this may interfere with the completion of the surgical procedure, often an endoscopic procedure. When bleeding is delayed, additional surgical intervention, even possibly full invasive surgery may be required.
Mechanical surgical clips, particularly compression clips, for use in endoscopic surgery, including endoscopic polypectomies, are known. These clips inter alia are intended to achieve hemostasis as they apply constrictive forces to blood vessels so as to limit or interrupt blood flow. In effect, the bleeding vessel is ligated, or the tissue around the bleed site is compressed, ligating all of the surrounding vessels. However, these clips have drawbacks.
The typical clip is a two legged clip that is passed through an endoscope's working channel via a flexible delivery catheter. Because the clip needs to pass through the endoscope, the clip's size is limited. Size limitations prevent the clip from being able to effectively clamp off all of the blood vessel or vessels in the tissue or polyp's stalk to be resected. Additionally, the clip may be unable to provide sufficient clamping force because of its structural design.
An additional problem with these clips is that when delivering these clips to the wound site, good visualization of a bleeding vessel cannot be obtained. The endoscopist may be required to blindly attach the clip, resulting in an imprecisely performed procedure that requires guess work on the part of the endoscopist. Attaching a clip therefore may be unsuccessful during an initial attempt.
Finally, many clips slip off the tissue to which they have been attached and are compressing during, or subsequent to, a surgical procedure but prior to complete healing of the wound. All this leads to frequent follow-up endoscopic surveillance, adding to patient discomfort and extra costs to the health care system.
Other medical conditions also make use of compressive hemostatic clips. One such condition is peptic ulcer disease (PUD). This condition is associated with bleeding that can be fatal if not treated immediately. Internal hemorrhaging may be intense and a bleeding peptic ulcer can be a critical clinical event.
Suspected bleeding PUD patients can be diagnosed and treated endoscopically in an emergency room, an ICU or the GI suite. Many of the treatments used on PUDs, such as thermal cauterization, are similar to those applied when endoscopically removing polyps. The main goal in this procedure is to achieve rapid and effective hemostasis. As with polyp removal, delayed bleeding is a problem.
Other lesions, such as fistulas and organ perforations, the latter either naturally occurring or surgically produced, are also susceptible to bleeding.
Therefore, there remains a need for an endoscopic compression clip and a system and a method which would facilitate its use, particularly in endoscopically carried out polypectomies. The clip should be reopenable to ensure that if initial positioning is unsuccessful, the clip can be easily repositioned. In general, there is a need for such a clip, system and method that could be applied to stanch bleeding from all types of bodily lesions, naturally occurring or surgically generated.
“Proximal” relates to the side of an endoscope, a clip, a device or an element closest to the user, while “distal” refers to the side of the endoscope, the clip, the device or the element furthest from the user.
“Polyp” as used in the specification and claims herein is not intended to restrict the assembly, system, subsystems, elements and method discussed herein to polyps alone. Other types of suspect lesions may also be treated using the assembly, system, subsystems, elements and method discussed herein.
“Lesion”, in addition to its use herein to refer to many different types of localized pathological changes in a body organ or tissue, may also be used herein in place of the word “polyp” without any intent at differentiating between the two terms except where specifically indicated. Lesion also contemplates fistulas and organ perforations, either naturally occurring perforations or perforations produced during surgical procedures.
“Tissue” includes, but is not limited to, tissue of the gastrointestinal tract, and the vascular system. The assembly, system, subsystems, elements and method discussed herein may be used with tissue of any internal organ.
“Gastrointestinal tract” or its equivalents are used in the specification and claims without the intent of being limiting. Other organ systems, and lesions found therein, are also contemplated as being treatable with the assembly system, subsystems, elements and methods discussed in the present specification.
“Hinge” is a force applier and this latter term may be used herein interchangeably with hinge, hinge spring or clip hinge without any intent at differentiating between any of these terms, except where specifically indicated.
“Endoscope”, as used herein, should be construed as including all types of invasive instruments, flexible or rigid, having scope features. These include, but are not limited to, colonoscopes, gastroscopes, laparoscopes, and rectoscopes. Similarly, the use of “endoscopic” is to be construed as referring to all types of invasive scopes.
“Endoscopist” as used herein refers to any user of the clips and the clip system described herein. Besides a physician, it may refer to any other properly trained medical personnel.
“Applier” as used herein may be used interchangeably with the term “delivery system” without any attempt at differentiating between them. The applier delivers a compression clip assembly constructed according to an embodiment of the present invention, positions it and locks it around tissue of a lesion to be compressed.
It is an object of the present invention to provide an endoscopic compression clip (ECC), often denoted herein as “clip”, for compression of a lesion, typically but without intending to limit the invention, a gastrointestinal (GI) lesion such as a polyp.
It is a further object of the present invention to provide a clip that can inter alia be used for hemostasis for mucosal or sub-mucosal defects, arteries, diverticula in the colon, for endoscopic marking, for anchoring or otherwise affixing jejunal feeding tubes, closing perforations, either naturally occurring or surgically produced, and multiple clip compression uses.
An additional object of the present invention is to provide a compression clip that reduces the incidence of procedure-related bleeding, irrespective of whether the bleeding is immediate or delayed.
Yet another object of the present invention is to provide a compression clip which is deployed in a controlled fashion and where the arms, that is the elongate members, of the clip can be reopened and repositioned any number of times prior to locking the clip into its final position.
Another object of the present invention is to provide a compression clip with a wide-angle opening between its elongate members
It is an object of the present invention to provide a system and method for use with an endoscopic compression clip constructed and operative according to embodiments of the present invention.
In one aspect of the present invention, there is provided a compression clip assembly for compressing tissue and operable by means of a user-operated applier. The assembly includes:
In an embodiment of the compression clip assembly, the assembly further includes one or more third elements in each lock region. The one or more third elements are positioned between the first and second stop elements. Locking of the clip is effected when the one or more third elements are forcibly engaged by and pass within the lock element. This results in a required increase in force for further movement of the clip through the lock element so as to lock the clip with the lock element.
In another embodiment of the assembly, the lock element further includes one or more orientation teeth and one or more male yoke members for disengageably mating with the user-operated applier.
In yet another embodiment of the assembly, the lock element locks the clip after being positioned against the second stop elements.
In still another embodiment of the assembly, the hinge is configured as a substantially closed geometric shape enclosing an area large enough to accommodate a means for mechanical connection of the applier.
In a further embodiment of the assembly, the elongate members of the clip are formed of a superelastic material.
In yet another embodiment of the assembly, when the clip is locked, the ratio of the length of the elongate members of the clip extending past the lock element to the length of the lock element itself is from about 1 to about 7.
In another aspect of the invention, there is provided a system for applying a compression clip for compressing tissue. The system includes:
In another embodiment of the system, the lock element further includes one or more male yoke members and one or more orientation teeth and the housing further includes one or more yoke elements and one or more housing orientation spaces for disengageably mating with the one or more male yoke members and the one or more orientation teeth, respectively.
In yet another embodiment of the system, the resilient material of the force transmitting element arms is a superelastic material. When the force transmitting element is pulled so as to move beyond the preselected distance, the force transmitting element arms, confined in the housing, are operative to disengage from the hinge and to spring open and exit the housing slots after disengaging from the clip.
In still another embodiment of the system, when the force transmitting element is pulled so as to move beyond the preselected distance, the force transmitting element arms disengage from the clip and then are positioned to push against the one or more male yoke members of the lock element, thereby assisting in disengaging the locked clip assembly from the housing of the applier.
In yet another embodiment of the system, the clip includes one or more third elements. The one or more third elements are positioned between the first and second stop elements. The one or more third elements when encountered serve as the means for applying a resistive force, thereby indicating to the user imminent locking of the clip consequent to further application of force to the control means.
In yet another embodiment of the system, the arms of the force transmitting element include a pair of force transmitting element projections and each of the housing slots has a narrow proximal part and a wider distal part. At the junction of the wider and narrower parts, the parts form a step, the step serving as the means for applying a resistive force, thereby indicating to the user imminent locking of the clip consequent to further application of force to the control means.
In another embodiment of the system, the housing includes one or more yoke elements and the housing is constructed of a material that allows spreading of the one or more housing yoke elements when the force transmitting element projections enter the narrower proximal part of the slots so that the locked clip is more easily disengaged.
In still another embodiment of the system, the resilient material of the force transmitting element is a superelastic material.
In a further embodiment of the system, the open position of the clip forms an angle of at least about 45 degrees.
In still another embodiment of the system, the applier further includes an overtube for compressing the elongate members of the compression clip holding them in their closed position while the clip is brought to tissue to be compressed.
In another aspect of the invention there is provided a method for compressing tissue. The method includes the steps of:
In another embodiment of the method, the method further includes a step of drawing an overtube over the compression clip prior to the step of bringing and a step of pulling back the overtube and uncovering the clip, allowing the clip to return to its biased open position after the step of bringing.
In yet another embodiment of the method, the step of locking further includes a step of bringing the compression clip through the lock element so that the lock element passes over one or more projections on the clip after which the clip locks, the act of passing over the one or more projections after which the clip locks requires additional force by a user signaling to the user that passing the one or more projections will irreversibly lock the clip.
In still another embodiment of the method, the step of freeing further includes a step of moving the resilient force transmitting element so as to press against elements on the lock element mateable with elements on the housing of the applier to further assist in disengagement of the locked clip from the applier.
In yet another embodiment of the method, the step of locking further includes a step of bringing projections located on the resilient force transmitting element over a juncture formed by a narrower portion and a wider portion of the housing slots, the juncture requiring additional force by a user signaling to the user that passing the juncture will irreversibly lock the clip.
In still another embodiment of the method, the step of freeing includes a step of pulling the resilient force transmitting element so that the projections thereon enter the narrower part of the housing slots thereby locking the clip and facilitating disengagement of the locked clip from the applier by spreading apart elements of the housing mateably engaged with elements on the lock element.
The present invention will be more fully understood and its features and advantages will become apparent to those skilled in the art by reference to the ensuing description, taken in conjunction with the accompanying drawings, in which:
Similar elements in the Figures are numbered with similar reference numerals.
The present invention provides an endoscopic compression clip (ECC) for use in endoscopic procedures, inter alia for use in inducing hemostasis. The clip allows for being opened and closed by the endoscopist an unlimited number of times until satisfactory positioning of the clip is achieved. The clip may then be locked by a clip lock element disengageably connected to the housing of a deployment assembly. The deployment assembly is part of a clip delivery system herein denoted as an applier. The clip lock element is disengaged together with the clip from the deployment assembly of the applier and holds the clip in its locked closed position while the clip is compressing tissue. The clip and clip lock element together form what herein is denoted as the compression clip assembly.
The deployment assembly of the applier includes a force transmitting element. In what is described herein the force transmitting element will often be denoted and described as a fork element, typically, but without intending to limit the invention, having a forceps shape. It should readily be understood by persons skilled in the art that the fork element is exemplary only; other constructions of a force transmitting element may also be used. The force transmitting element is formed of a resilient material which allows it to remain in a closed configuration when under a compressive force supplied by the housing of the applier's deployment assembly.
The clip lock element is formed to contain one or more male yoke members and one or more orientation teeth which are mateably and disengageably joinable to one or more yoke elements of the housing of the applier's deployment assembly and the one or more housing orientation spaces thereof, respectively. Disengagement is effected by the force of pulling the clip in the proximal direction into the clip lock element until the lock element reaches distal stop projections on the clip. If disengagement does not occur immediately upon locking the clip, in some embodiments of the invention the arms of the fork element can be used to assist in disengaging the locked clip assembly as will be described below.
Disengagement of the clip from the applier's deployment assembly occurs only after the endoscopist is satisfied with the positioning of the clip around the tissue to be compressed and only after the lock element engages and lies entirely within the clip's locking region. The locking region is located on the outer surface of each elongate member of the clip adjacent to its hinge. In some embodiments, locking of the clip occurs only after the lock element passes over one or more projections positioned in the locking region near the hinge of the clip. These projections provide a resistive force that indicates that an increase in force is required for the lock element to be pulled past these one or more projections. They alert the endoscopist that application of an increased force will result in locking of the clip, allowing him to desist from applying such force preventing the clip from being locked unintentionally.
In other embodiments, locking of the clip occurs after one or more projections located on the arms of the force transmitting element pass a resistive step in release slots located in the housing of the deployment assembly. The resistive step provides a resistive force that indicates to the endoscopist that an increase in force is required for the clip to be pulled further into the lock element thereby locking the clip. This increase in resistive force prevents the endoscopist from locking the clip unintentionally.
It should be noted that in all embodiments of the invention, it is the lock element of the compression clip assembly that remains stationary while it is the clip that is pulled or pushed through the lock element.
Disengagement of the clip and clip lock element is effected when the arms of the force transmitting element, e.g. fork element, are brought adjacent to a region of the housing of the applier's deployment assembly having release openings, also denoted herein as release slots. These release openings act to release the compressive force operative on the resilient arms of the fork element. The release of the compressive force allows for the spreading apart of the fork element's arms. Insertion elements on the fork element's arms, also denoted herein as fork arm projections, then move out of the hinge loop region formed by the clip hinge and exit through the release openings, thereby disengaging the fork element from the clip.
Once the fork arm projections are released from the clip's hinge, the locked clip assembly detaches from the housing of the deployment assembly by separation of the lock element's one or more male yoke members from the housing's one or more yoke elements which hold them. In the case that the detachment is incomplete, the freed arms of the fork element may then be maneuvered to push against the one or more male yoke members of the lock element causing the lock element to separate from the housing of the applier's deployment assembly.
The point of attachment between the fork arms' projections, that is the fork element's insertion elements, and the clip has been described above as a hinge loop. It should be understood that the clip's hinge may be constructed to form any closed shape with a hole in it in addition to a loop through which the fork arm insertion elements may be inserted. The closed shape, however, should have a sufficient area to accommodate and retain the fork arm insertion elements when inserted. The insertion elements are just one means for mechanical connection of the applier to the clip. It should be appreciated by persons skilled in the art that other such means are possible.
The clip, generally the clip hinge, is at least partly made of a superelastic material. This may be a shape memory alloy which exhibits superelasticity, such as a nickel-titanium (Ni—Ti) alloy. In some embodiments, the remainder of the clip may also be made of a superelastic material. The clip is biased to be in its open position with its arms spaced apart. In its open position, the arms of the clip form an angle equal to or greater than 45°. However, it should be understood that this angle is not intended to limit the invention. When nitinol is used in the hinge, its superelastic characteristic allows for greater elastic deformation, that is, deformation without plastic deformation, thereby allowing for the wide angle opening.
In some embodiments, the material used in the clip hinge may be a shape-memory material and not necessarily a superelastic material.
Nitinol or other superelastic material may also be used in the elongate members, herein also denoted as clip arms. When used in the clip arms, thicker tissue can be effectively compressed as the arms are superelastic and possesses a spring effect over a greater range of deflection then other materials. When nitinol is used only in the hinge, the clip arms may be made of plastic or any other stiff material and may be attached to the hinge by any of many methods known to those skilled in the art.
The present invention contemplates a working length ratio of the clip arms, that is, the elongate members, of from about 1 to about 7, more preferably from about 2 to about 6, and even more preferably from about 3 to about 5. The working length ratio (D/L) is defined herein as the ratio of the length of the clip from its distal end to the lock element when the lock element is in its locking position (D) to the length of the lock element (L). The large ratio provided by clips of the present invention allows for compression of thicker tissue (e.g. polyps with large stalks) and for closure of larger perforations.
In what is described herein, the use of the term open position and closed position for the clip refers to the position of the clip's elongate members. When the clip is in its open position the elongate members, the clip arms, are spaced apart. When the clip is in its closed position, the elongate members are not spaced apart and may be substantially adjacent to each other.
As shown in
Actuator assembly 100 may be constructed in a manner similar to conventional actuator assemblies of the type generally employed in endoscopic biopsy devices or in assemblies constructed for other similar applications. These are known to persons skilled in the art. Actuator assembly 100 allows the user to move a control wire 201 or other force transmitter, which is also denoted herein as a control means. Control wire 201 extends through shaft 204 (
Shaft 204, typically a flexible coil, is designed to provide structural strength and to transmit a torque from its proximal end P to its distal end D. The flexible coil may be a conventional coil used in other biopsy devices and may, for example, comprise a single, coiled wire. The coiled wire may have a round, square or a rectangular cross section, and may be made of a biocompatible material such as, for example, stainless steel. Additional protective and low friction outer layers may be included on control wire 201 and/or shaft 204, according to known methods of construction. Sliding over the distal end D of shaft 204 is overtube 205 (
A deployment spring 104, best seen in
Spring 104 has a double purpose. First, spring 104 absorbs the relative movement between control wire 201 and shaft 204 produced by the curves of the body lumen into which the endoscope is inserted. This prevents clip 310 from inadvertently being pulled in the proximal direction. Second, deployment spring 104 increases the operating length of knob 102. Deployment spring 104 amplifies the movement of knob 102 since the overall movement of clip 310 and control wire 201 between the clip's open and closed positions is very small. Pulling knob 102 in the proximal direction will not affect wire 201 until deployment spring 104 is fully compressed. Then, any additional movement of knob 102 in the proximal direction will pull wire 201 in that direction.
As shown in
The proximal end of control wire 201 is attached to sliding control knob 102 using any of many methods known to persons skilled in the art. Stainless steel or other high yield biocompatible materials may be used to manufacture control wire 201 so that the structural integrity of the assembly is maintained. A superelastic material, such as nitinol, may also be used to form control wire 201.
Several views of compression clip 310 and clip lock 320 constructed according to an embodiment of the present invention are shown in
Clip 310 is at least partially formed of a superelastic material. This may be a shape memory alloy which exhibits this property such as, but without intending to limit the invention, a nickel-titanium (Ni—Ti) alloy. In particular, but again without intending to limit the invention, clip hinge 314 may be formed at least partially of a superelastic material. The two elongate members or arms 318 of clip 310 contain teeth 311 for better grasping the tissue being held, and for preventing the tissue from slipping out of the arms of the clip when the tissue is grasped and the clip is locked. As best seen in
Clip lock element 320 is shown in various views in
Lock element 320 can not move past projections 313 and 317 because the inner diameter of lock element 320 is smaller than the distance between the projections on opposing clip arms.
As will be discussed further below, middle stop projections 319 allow for the opening and closing of clip 310 without it being locked. When control wire 201 is pushed in the distal direction as discussed below, force transmitting element, here a fork element, 340 (
It should readily be appreciated that while force transmitting element 340 is herein described in terms of a fork element, other force transmitting elements may be designed and used. These function essentially as the fork element discussed herein.
There is a gradual narrowing 315 (best seen in
It should be noted that the present invention contemplates embodiments where the clips may have fewer than three pairs of stop projections but at least a single pair of stop projections. It must have distal stop projections 313 to stop the lock in the distal direction. In some embodiments, the hinge can be designed in a way that allows it to serve as the proximal stop projection.
Connecting clip 310 to the remainder of ECC system 400 discussed in conjunction with
Fork element 340 may be fabricated from any of many different resilient materials including superelastic materials. Accordingly, fork element 340 may at times be denoted herein as a “resilient element 340”. In some embodiments, superelastic materials, such as nitinol, may be used, while in other embodiments, more conventional resilient materials, for example stainless steel, may be used. In general, fork element 340 may be formed from any alloy and mechanically forced into its locked, that is clip holding, configuration once positioned in a housing of the deployment assembly.
In
Housing pin 334, best seen in
It should be noted that
In what herein is called, for reference, step A, fork element 340 of
It should be remembered that in all the pushing and pulling of wire 201, clip lock element 320 is not moved. Clip 310 moves relative to lock element 320 as lock element 320 remains engaged to housing 330.
Repositioning of clip 310 on the tissue to be compressed is effected and the clip is again provisionally brought to its closed position described in step A. If the repositioning is satisfactory, control wire 201 pulls fork element 340 further in the proximal direction to its position in
When repositioning and closing the arms as in step A, the endoscopist readily avoids inadvertently locking clip 310 with clip lock element 320. Before locking, the clip must be brought in the proximal direction so that lock element 320 is brought over middle stop projections 319, best seen in
The embodiment discussed above indicates that fork arms 341, when emerging from release openings 333, may be used to push against and disengage clip lock element 320 from housing 330. However, it is contemplated that other methods may also be used to effect disengagement of lock element 320 from housing 330. It is even contemplated that lock element 320 may by itself disengage from housing 330 after full deployment. This may occur because proximal stop projections 317 of clip 310 slightly separate the two sides of housing yoke elements 331 once they pass lock element 320. This creates a large enough gap for male yoke members 321 of lock element 320 to disengage from housing yoke elements 331. In effect, the proximal end of the clip applies a force on the yoke connection encouraging disengagement of the locked clip.
Reference is now made to
In some versions of clip 1310, clip 1310 may have distal stop projections 1313, proximal stop projections 1317 and middle stop projections 1319 which function as their analogous parts in clip 310. In other versions of clip 1310, some of these projections may be absent as they may not be required. In these latter versions, geometry alone may prevent clip lock element 320 from sliding off clip 1310.
Clip 2310 is constructed as with the clip discussed in conjunction with
Clip 3310 and clip lock element 3320 are constructed as the clip and clip lock described in conjunction with
Applying an increased force allows fork arm protrusions 3390 to slide in the proximal direction into the narrower slot end 3333P. If the endoscopist continues to pull control means, that is control wire, 3201 in the proximal direction, once clip 3310 is locked against distal stop projections 3313 situated on clip 3310, as in previous embodiments, fork element, that is force transmitting element, 3340 detaches from clip 3310 as fork arms 3341 emerge from slot 3333D. If made from a superelastic material, such as nitinol, fork arms 3341 may spring open; if arms 3341 are made from other resilient materials, such as stainless steel, the application of a force will slightly bend the arms leveraging their flexibility, so that fork arm projections 3342 can “exit” the clip's hinge loop.
The movement of protrusions 3390 in the narrow proximal end 3333P of the slots leads to a spreading of housing yoke elements 3331, as indicted by the diverging arrows in
In the above discussion of the present invention, the invention has been described as being used in bowel polyp resections. It should be evident to one skilled in the art that other types of lesions, in other organs in other organ systems, can also be resected using the present invention with little or no modification. Such organs include, but are not limited to, the urinary bladder and other organs of the urinary tract, the uterus, the liver, the esophagus, the gall bladder, the lungs and the rectum.
The ECC and system for employing the clip may also be used in closing perforations, naturally occurring or resulting from surgical procedures, and fistulas. For such types of lesions, the method of use of the system and clip is essentially the same as discussed above and shown in the Figures. The method may be modified slightly as the particular lesion warrants.
Additionally, the ECC and system discussed herein above may be used to effect hemostasis in all bleeding situations, not only those resulting from resected GI polyps or bleeding peptic ulcers. Resection of any organ that leads to bleeding or any blood vessels that have been ruptured or are otherwise leaking may be treated as described herein.
It should be readily apparent to one skilled in the art that the device and method of the present invention can be used to compress animal tissue as well as human tissue, particularly, but without limiting the invention, tissue of other mammalian species.
Although the invention has been described in conjunction with specific embodiments thereof, it is evident that many alternatives, modifications and variations will be apparent to those skilled in the art. Accordingly, the invention is intended to embrace all such alternatives, modifications and variations that fall within the spirit and broad scope of the appended claims. Also, it is to be understood that the phraseology and terminology employed herein is for the purpose of description and should not be regarded as limiting. In addition, citation or identification of any reference in this application shall not be construed as an admission that such reference is available as prior art to the present invention.
It will be appreciated by persons skilled in the art that the present invention is not limited by the drawings and description hereinabove presented. Rather, the invention is defined solely by the claims that follow.
| Filing Document | Filing Date | Country | Kind | 371c Date |
|---|---|---|---|---|
| PCT/IL09/00466 | 5/5/2009 | WO | 00 | 11/3/2010 |
| Number | Date | Country | |
|---|---|---|---|
| 61071539 | May 2008 | US |
