Abstract:
A venous shunt system and method adapted to shunt cerebral spinal fluid in a patient. A fluid control device having a fluid passage is adapted to be placed allowing cerebral spinal fluid to flow through the fluid passage. A catheter having a lumen, the catheter being in fluid communication with the fluid control device. At least a portion of at least one of the catheter and the fluid control device being subjected to an anti-thrombogenic treatment.

Description:
FIELD OF THE INVENTION  
       [0001]     The present invention relates generally to the field of venous shunt systems and method and, more particularly, to venous shunt systems and methods used for treating hydrocephalus.  
       BACKGROUND OF THE INVENTION  
       [0002]     Ventricles of the brain contain cerebrospinal fluid which cushions the brain against shock. Cerebral spinal fluid is constantly being secreted and absorbed by the body usually in equilibrium. Cerebral spinal fluid is produced in the ventricles of the brain, where under normal conditions, it is circulated in the subarachnoid space and reabsorbed into the bloodstream, predominantly via the arachnoids villi attached to the superior sagittal sinus. However, if blockages in circulation of cerebral spinal fluid, perhaps in the ventricles, cerebral spinal fluid can&#39;t be reabsorbed by the body at the proper rate.  
         [0003]     This can create a condition known as hydrocephalus which is a condition marked by an excessive accumulation of fluid violating the cerebral ventricles, then the brain and causing a separation of the cranial bones. Hydrocephalus is a condition characterized by abnormal flow, absorption or formation of cerebrospinal fluid within the ventricles of the brain which subsequently increases the volume and pressure of the intracranial cavity. If left untreated, the increased intracranial pressure can lead to neurological damage and may result in death.  
         [0004]     A common treatment for hydrocephalus patients has been the cerebrospinal fluid shunt. The standard shunt consists of the ventricular catheter, a valve and a distal catheter. The excess cerebrospinal fluid is typically drained from the ventricles to a suitable cavity, most often the peritoneum or the atrium. The catheter is placed into ventricles to shunt cerebral spinal fluid to other areas of the body, principally the peritoneum or alternatively to the sagittal sinus, where it can be reabsorbed. The presence of the shunt relieves pressure from cerebral spinal fluid on the brain.  
         [0005]     A problem with venous shunt systems and methods is the possible complication of thrombus formation. A thrombus may form, for example, in the lumen of the shunting catheter or on the surface of the catheter. The same is true for a fluid flow device, e.g., a pressure or flow regulator, which may be included in the venous shunt system. Further, thrombus formation may occur near the area of the outlet tip the catheter, the so-called tip zone.  
         [0006]     Formation of thrombus in or near the venous shunt system, whether in or on a component of the venous shunt system, could lead to blockage of flow and compromise the performance of the shunt system.  
       BRIEF SUMMARY OF THE INVENTION  
       [0007]     Clogging or occluding of a venous shunt system may be prevented or corrected through the use of an anti-thrombogenic and/or clot busting agent or agents. The use of such agent or agents can be effective in preventing the formation of a thrombus or in the elimination of a thrombus already formed.  
         [0008]     In a preferred embodiment, the present invention provides a venous shunt system adapted to shunt cerebral spinal fluid in a patient. A catheter, having a lumen, is adapted to be placed allowing cerebral spinal fluid to flow through the lumen. At least a portion of the catheter being subjected to an anti-thrombogenic treatment.  
         [0009]     In another embodiment, the present invention provides a venous shunt system adapted to shunt cerebral spinal fluid in a patient. A fluid control device having a fluid passage is adapted to be placed allowing cerebral spinal fluid to flow through the fluid passage. A catheter having a lumen, the catheter being in fluid communication with the fluid control device. At least a portion of at least one of the catheter and the fluid control device being subjected to an anti-thrombogenic treatment.  
         [0010]     In a preferred embodiment, the anti-thrombogenic treatment comprises an anti-thrombogenic agent delivered to a proximate area of at least one of the catheter and the fluid control device.  
         [0011]     In a preferred embodiment, a bioresorbable matrix holds the anti-thrombogenic agent.  
         [0012]     In a preferred embodiment, the anti-thrombogenic agent is impregnated into at least a portion of at least one of the catheter and the fluid control device.  
         [0013]     In a preferred embodiment, at least one of the catheter and the fluid control device has a chamber for holding the anti-thrombogenic agent.  
         [0014]     In a preferred embodiment, at least one of the catheter and the fluid control device has an anti-thrombogenic treatment surface modification.  
         [0015]     In a preferred embodiment, at least a portion of at least one of the catheter and the fluid control device are treated with a hydrophilic agent.  
         [0016]     In a preferred embodiment, the hydrophilic agent comprises hydrogel.  
         [0017]     In a preferred embodiment, the hydrogel is covalently bonded to at least a portion of at least one of the catheter and the fluid control device.  
         [0018]     In a preferred embodiment, the hydrogel is covalently bonded to at least a portion of at least one the catheter and the fluid control device using ultraviolet light.  
         [0019]     In another embodiment, the present invention provides a method of shunting cerebral spinal fluid in a patient. A catheter is placed to allow cerebral spinal fluid to flow through the lumen. At least a portion of the catheter is subjected to an anti-thrombogenic treatment.  
         [0020]     In another embodiment, the present invention provides a method of shunting cerebral spinal fluid in a patient. A fluid control device is placed to allow cerebral spinal fluid to flow through the fluid passage. A catheter is placed with a lumen in fluid communication with the fluid passage to allow cerebral spinal fluid to flow through the lumen. At least a portion of at least one of the flow control device and the catheter is subjected to an anti-thrombogenic treatment.  
         [0021]     In a preferred embodiment, the subjecting step delivers an anti-thrombogenic agent to at least a portion of at least one of the flow control device and the catheter.  
         [0022]     In a preferred embodiment, the delivering step holds the anti-thrombogenic agent in a bioresorbable matrix.  
         [0023]     In a preferred embodiment, the delivering step impregnates at least a portion of at least one of the flow control device and the catheter with the anti-thrombogenic agent.  
         [0024]     In a preferred embodiment, the subjecting step holds the anti-thrombogenic agent in a chamber separate from the lumen of the catheter.  
         [0025]     In a preferred embodiment, the subjecting step provides at least a portion of at least one of the flow control device and the catheter with an anti-thrombogenic treatment surface modification.  
         [0026]     In a preferred embodiment, the providing step treats at least a portion of at least one of the flow control device and the catheter with a hydrophilic agent.  
         [0027]     In a preferred embodiment, the hydrophilic agent is a hydrogel.  
         [0028]     In a preferred embodiment, the treating step covalently bonds the hydrogel to at least a portion of at least one of the flow control device and the catheter.  
         [0029]     In a preferred embodiment, the treating step is accomplished with ultraviolet light.  
         [0030]     In a preferred embodiment, the subjecting step injects an anti-thrombogenic agent to a proximate area of at least one of the flow control device and the catheter. 
     
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       [0031]      FIG. 1  is a cut-away perspective view of cerebral spinal fluid flow control device implanted into the cranium of a patient;  
         [0032]      FIG. 2  is a cross-sectional side view of a venous shunt system having an anti-thrombogenic agent administered to the system;  
         [0033]      FIG. 3  is a cut-away side view of a catheter useful in a venous shunt system having an anti-thrombogenic agent associated with a bioresorbable matrix;  
         [0034]      FIG. 4  is a cross-sectional side view of a device insertable into a venous shunt system having a dome containing an anti-thrombogenic agent; and  
         [0035]      FIG. 5  is a cross-sectional side view of a device insertable into a venous shunt system having a separate, valve-controlled reservoir containing an anti-thrombogenic agent along-side a clear flow chamber. 
     
    
     DETAILED DESCRIPTION OF THE INVENTION  
       [0036]     Consistent and reliable drainage of cerebral spinal fluid from one area of the body to another, e.g., from a ventricle or ventricles of the brain to another region of the body such as the peritoneum pr sagittal sinus, can be desirable. A consistent and reliable drainage method and system can minimize the expense as well as trauma and inconvenience to the patient associated with cerebral spinal fluid revision surgery and can also lesson risk to the patient due to an inoperative cerebral spinal fluid drainage system.  
         [0037]      FIG. 1  illustrates an embodiment of a cerebral spinal fluid shunt, or drainage, system  10  for draining cerebral spinal fluid from one area, preferably the ventricles of brain, of the body of patient  12  to another area of the body of patient  12 . Cerebral spinal fluid can preferably be drained to the peritoneum and/or atrium and, alternatively, to the sagittal sinus. Shunt system  10  may consist solely of a catheter having a lumen to transport cerebral spinal fluid or may consist, as illustrated in  FIG. 1 , flow control device  14 .  
         [0038]     Flow control device  14  may be located anywhere along the path of cerebral spinal fluid flow. For example, flow control device  14  may be located at or near the inlet for cerebral spinal fluid, e.g., at or near the ventricles, or may be located at or near the outlet for the cerebral spinal fluid, e.g., at or near the peritoneum.  
         [0039]     Alternatively, flow control device  14  may be located as illustrated in  FIG. 1  along the flow path between the inlet and outlet. In particular, by way of example, flow control device  14  may be near the cranium  24 .  
         [0040]     Ventricular catheter  16 , having a lumen, is connects flow control device  14  to inlet location  18  in the ventricle of patient  12 . It is to be recognized and understood that other locations, other than inlet location  18 , can be used. Distal catheter  20  connects flow control device  14  with an outlet for cerebral spinal fluid, not shown, which preferably is in the peritoneum. It is to be recognized and understood that other outlet locations can be used. Examples of other possible outlet locations include the atrium and the sagittal sinus.  
         [0041]     Although not required, flow control device  14  can help alleviate cerebral spinal fluid flow differential due to different positioning of the body. For example, when the body is supine, the difference in elevation between the inlet of ventricular catheter  16  and the outlet of distal catheter  20  may be relatively small. Thus, the pressure differential due to elevation between the inlet and outlet may also be relatively small. This may result in a relatively small flow rate of cerebral spinal fluid through shunt system  10 .  
         [0042]     However, when the body is erect, for example, the difference in elevation between the inlet of ventricular catheter  16  and the outlet of distal catheter  20  may be relatively large. Thus, the pressure differential due to elevation between the inlet and outlet may also be relatively large. This may result in a relatively large flow rate of cerebral spinal fluid through shunt system  10 .  
         [0043]     The presence of a flow control device  14  in shunt system  10  can help to stabilize the rate of flow of cerebral spinal fluid through shunt system  10  by limiting the higher flow rates associated with, for example, an erect position of the body.  
         [0044]     However, it is to be recognized and understood that the present invention has applicability regardless of whether or not a flow control device is actually desired and/or utilized. However, since it is envisioned that a flow control device is generally desirable in most circumstances, the discussion hereinafter will be mostly based upon the inclusion of a flow control device. The use or inclusion of a flow control device, however, is not required.  
         [0045]     Clogging or occluding of venous shunt system  10  may be prevented or corrected through the use of one or more anti-thrombogenic and/or clot busting agent or agents. The use of such agent or agents can be effective in preventing the formation of a thrombus or in the elimination of a thrombus already formed.  
         [0046]     The use of the term anti-thrombogenic agent refers to an agent that is effective in preventing the coagulation or clotting of cerebral spinal fluid or other fluids in or near shunt system  10 . An example of an anti-thrombogenic agent is heparin. The use of the term clot busting agent refers to an agent that is effective in clearing already existing clots or obstructions of cerebral spinal fluid or other fluids in or near shunt system  10 . An example of a clot busting agent is Streptokinase or Urokinase. Although it is recognized that an anti-thrombogenic agent may be different from a clot busting agent, throughout this specification, including the claims, the use of the terms anti-thrombogenic agent, clot busting agent, either or both, is considered to refer to either agents or both agents. For the purposes of this invention, the terms are considered interchangeable since their purpose is to prevent or clear clots and/or obstructions from the path of flow of cerebral spinal fluid in shunt system  10 .  
         [0047]      FIG. 2  illustrates a cross-sectional view of an embodiment of the invention in which an anti-thrombogenic and/or clot busting agent is delivered, or in a preferred embodiment, injected into flow control device  14 . In this schematic embodiment, not drawn to scale, flow control device  14  is implanted underneath scalp  22  exterior of cranium  24 . Ventricular catheter  16  is tunneled between flow control device  14  underneath scalp  22 , through burr hole  26  into ventricular space  28  containing cerebral spinal fluid  30 . Distal catheter  20  is also tunneled subcutaneously between flow control device  14  and venous space  32  providing an outlet for cerebral spinal fluid from ventricular space  28 .  
         [0048]     Hypodermic needle  34  containing an anti-thrombogenic and/or clot busting agent is transcutaneously inserted with tip  36  positioned at a location where the injection of an anti-thrombogenic and/or clot busting agent would be effective in preventing or clearing an obstruction in cerebral spinal fluid shunt system  10 . In a preferred embodiment illustrated in  FIG. 2 , tip  36  of hypodermic needle  34  is positioned within the body of flow control device  14  in order to deliver an anti-thrombogenic and/or clot busting agent to flow control device  14 . The presence of an anti-thrombogenic and/or clot busting agent in flow control device  14  can help avoid or clear obstructions that might otherwise jeopardize the effectiveness and/or reliability of shunt system  10 .  
         [0049]     Alternatively, hypodermic needle  34  may be used to deliver an anti-thrombogenic and/or clot busting agent to other areas in or along the path of cerebral spinal fluid flow in or near shunt system  10 . As examples, an anti-thrombogenic and/or clot busting agent may be delivered by hypodermic needle  34  to a lumen in either of ventricular catheter  16  or distal catheter  20  or both. In another alternative embodiment, an anti-thrombogenic and/or clot busting agent may be delivered by hypodermic needle  34  to an area of ventricular space  28  near the inlet of ventricular catheter  16  or may be delivered by hypodermic needle  34  to an area near the outlet of distal catheter  20  in venous space  32 .  
         [0050]     It is to be recognized and understood that other delivery mechanisms and methods, beyond the use of a hypodermic needle as illustrated in  FIG. 2 , are contemplated as well.  
         [0051]      FIG. 3  illustrates an alternative delivery mechanism and delivery method for the delivery of an anti-thrombogenic and/or clot busting agent to shunt system  10 . Bioresorbable matrix  38  is secured in the fluid flow path of shunt system  10 , for example prior to implantation. Bioresorbable matrix  38  is impregnated with an anti-thrombogenic and/or clot busting agent. Anti-thrombogenic and/or clot busting agent is graduated released from bioresorbable matrix  38  while shunt system  10  is in use thus preventing or clearing clots which would otherwise obstruct the flow of cerebral spinal fluid through shunt system  10 .  
         [0052]     Bioresorbable matrix  38  is degraded biologically and may be constructed from a bioresorbable material such as the polylactic acid and lactic acid copolymers currently used in the MacroPore™ CMF™ products marketed by Medtronic, Inc., Minneapolis, Minn. In an embodiment, bioresorbable matrix  38  may be using a copolymer described in U.S. Pat. No. 4,916,193, Tang et al, Medical Devices Fabricated Totally Or In Part From Copolymers of Recurring Units Derived From Cyclic Carbonates and Lactides, the content of which is hereby incorporated be reference.  
         [0053]     As illustrated in  FIG. 3 , bioresorbable matrix  38  is positioned within a lumen of ventricular catheter  16 . Bioresorbable matrix  38  may also to positioned a lumen of distal catheter  20  or, alternatively, may be positioned within flow control device  14  and illustrated by flow control device  14 A in  FIG. 4 .  
         [0054]      FIG. 4  also illustrates an alternative delivery mechanism and method for an anti-thrombogenic and/or clot busting agent. Flow control device  14 A is similar to flow control device  14  having a flow chamber  40  with an inlet fluidly coupled to ventricular catheter  16  and an outlet fluidly coupled to distal catheter  20 . Also included in flow control device  14 A is a conventional fluid flow control mechanism which is not explicitly shown. Such flow control mechanisms, such as a tortuous path, however, are well know in the art.  
         [0055]     A preferred fluid control mechanism is illustrated in co-pending U.S. Patent Application filed on even date herewith in the names of William J. Bertrand and Bill Sugleris and entitled “Implantable Cerebral Spinal Fluid Flow Device and Method of Controlling Flow of Cerebral Spinal Fluid”, carrying attorney docket number 151P11489US01, the contents of which are hereby incorporated by reference.  
         [0056]     Flow control device  14 A differs from flow control device  14  by having a second chamber  42  that holds a supply of anti-thrombogenic and/or clot busting agent.  
         [0057]     Second chamber  42  has an opening  44  permitting communication of anti-thrombogenic and/or clot busting agent from second chamber  42  into the fluid flow path of shunt system  10 , such as into flow chamber  40  of flow control device  14 A.  
         [0058]     In a preferred embodiment, upper dome  46  may be flexible. Since flow control device  14 A may be implanted subcutaneously just under scalp  22 , pressure applied to scalp  22  can deform upper dome  46  forcing an amount of anti-thrombogenic and/or clot busting agent to flow from second chamber  42  through opening  44  into flow chamber  40  where the agent or agents can operate effectively to prevent or clear clots and obstructions.  
         [0059]     While shown as part of flow control device  14 A, it is to be recognized and understood that second chamber  42  could also be part of a device separate from a device that provides flow control. That is, the flow control function of flow control device  14 A could be separate from the anti-thrombogenic and/or clot busting function of second chamber  42 . Flow control device  14 A could perform only an anti-thrombogenic and/or clot busting agent function and not a flow control function. Flow control could then, optionally, be provided in a separate device along the flow path of shunt system  10 , if desired.  
         [0060]      FIG. 5  is a cross-sectional view of another embodiment of the present invention. Flow control device  14 B is similar to flow control device  14 A by having flow chamber  40  providing a main fluid path for cerebral spinal fluid and second chamber  42  for holding an anti-thrombogenic and/or clot busting agent. Preferably, anti-thrombogenic and/or clot busting agent is held in chamber  42  with a bioresorbable matrix as described above with respect to  FIG. 3 . As with flow control device  14 A, opening  44  provides a path for communication of anti-thrombogenic and/or clot busting agents from second chamber  42  to the main fluid flow path of shunt system  10 .  
         [0061]     Flow control device  14 B also has an opening or a one-way valve  48  positioned between a main fluid flow path of shunt system  10 , in this case either flow chamber  40  or ventricular catheter  16 , that will allow some of the flow of cerebral spinal fluid from ventricular catheter  16  to second chamber  42  forcing some of the anti-thrombogenic and/or clot busting agents from second chamber  42  through opening  44  into the main fluid flow path of shunt system  10 . Thus, a continuing supply of anti-thrombogenic and/or clot busting agent is available to shunt system  10  relying only on the flow of cerebral spinal fluid to dispense the anti-thrombogenic and/or clot busting agents.  
         [0062]     Optionally a low-pressure opening valve  50  may be positioned in the flow path of flow chamber  40 . One-way valve  48  in this embodiment would have a higher, perhaps only slightly higher, opening pressure. Under normal, i.e., unobstructed, flow conditions, most or nearly all of the flow of cerebral spinal fluid would pass through flow chamber  40  with little or none of the flow of cerebral spinal fluid passing through second chamber  42 .  
         [0063]     Upon buildup of back pressure due to downstream clotting or obstruction of cerebral spinal fluid flow in shunt system  10 , one-way valve  48  will either open or open further resulting in a flow or increased flow of cerebral spinal fluid through second chamber  42  allowing the release, or release of greater amounts of, anti-thrombogenic and/or clot busting agents.  
         [0064]     As with flow control device  14 A of  FIG. 4 , it is to be recognized and understood that second chamber  42  could also be part of a device separate from a device that provides flow control. That is, the flow control function of flow control device  14 B could be separate from the anti-thrombogenic and/or clot busting function of second chamber  42 . Flow control device  14 B could perform only an anti-thrombogenic and/or clot busting agent function and not a flow control function. Flow control could then, optionally, be provided in a separate device along the flow path of shunt system  10 , if desired.  
         [0065]     As can be seen, the anti-thrombogenic and/or clot busting agent may be delivered to shunt system  10  in a number of different manners. The anti-thrombogenic and/or clot busting agent may be injected, for example as described above with respect to  FIG. 2 . The anti-thrombogenic and/or clot busting agent may be held in a bioresorbable matrix, for example as described above with respect to  FIG. 3 . The anti-thrombogenic and/or clot busting agent may be held in a second chamber, for example as described with respect to  FIG. 4  and  FIG. 5 .  
         [0066]     An anti-thrombogenic and/or clot busting agent may also be provided through a surface treatment modification of one or more surfaces of any or all of the components of shunt system  10 . In particular, one or more of the surfaces of shunt system may be made hydrophilic through the use of well known techniques and processes. In a preferred embodiment of the present invention, one or more surfaces of shunt system  10  is made hydrophilic through the use of hydrogel. It is preferred that the hydrogel be covalently bonded to surface of an element or elements of shunt system  10  and still more preferably that such covalent bonding be accomplished with ultraviolet light. Other bonding methods may also be employed.  
         [0067]     Suitable hydrogels include those that are 70 to 80 percent water content by weight. In a preferred embodiment, polyvinylpyrrolidone (PVP or Povidone) is utilized. PVP is ionically neutral. In other embodiments, PEG/PEO (polyethylene glycol/polyethylene oxide), PAA (polyacrylamide) and/or PVA (polyvinyl alcohol) hydrogels may be used. Other hydrogels may also be employed.  
         [0068]     Preferably, hydrogel is surface grafted using covalent bonding to the implant surface. Coatings are held in place with Van der Waals forces, hydrogen bonding, ionic bonding or mechanical attachment. Preferably, covalent attachment, which is much stronger, is used and may be accomplished using ultraviolet light or other methods.  
         [0069]     This treatment is similar to ultraviolet linked polyvinylpyrrolidone utilized under the tradename “BioGlide” by Medtronic, Inc., Minneapolis, Minn., for a surface modification of silicone elastomer shunts for the reduction of bacterial adhesion. This technology is described in U.S. Pat. No. 4,722,906, Guire et al, Binding Reagents and Methods; U.S. Pat. No. 4,973,493, Guire et al, Method of Improving the Biocompatibility of Solid Surfaces; U.S. Pat. No. 4,979,959, Guire et al, Biocompatible Coating For Solid Surfaces; U.S. Pat. No. 5,002,582, Guire et al, Preparation of Polymeric Surfaces Via Covalently Attaching Polymers; U.S. Pat. No. 5,217,492, Guire et al, Biomolecule Attachment To Hydrophobic Surfaces; U.S. Pat. No. 5,258,041, Guire et al, Method of Biomolecule Attachment To Hydrophobic Surfaces; U.S. Pat. No. 5,263,992, Guire et al, Biocompatible Device With Covalently Bonded Biocompatible Agent; U.S. Pat. No. 5,512,329, Guire et al, Surface Treatment Preparation, and U.S. Pat. No. 5,741,551, Guire et al, Preparation of Polymeric Surfaces, the contents of all of which are hereby incorporated by reference.  
         [0070]     Thus, embodiments of the anti-thrombogenic venous shunt system and method are disclosed. One skilled in the art will appreciate that the present invention can be practiced with embodiments other than those disclosed. The disclosed embodiments are presented for purposes of illustration and not limitation, and the present invention is limited only by the claims that follow.