Therapeutic delivery devices, systems, and methods

Devices, systems, and methods for delivery of therapeutics, in particular thrombolytic agents, in particular plasmin, are provided. The devices, systems, and methods also provide for occlusion of a vessel or graft distal and/or proximal to a treatment zone. Also provided are devices, systems, and methods that trap emboli.

FIELD OF THE INVENTION

The present invention relates to devices, systems, and methods for delivery of therapeutics, in particular thrombolytic agents, wherein the devices, systems, and methods provide for occlusion of a vessel or graft distal and/or proximal to a treatment zone.

BACKGROUND OF THE INVENTION

The current standard of care for use of thrombolytic in clinical treatment of acute peripheral arterial occlusion (aPAO) is intrathrombus administration of tissue plasminogen activator (t-PA). In approximately 20% of patients administered t-PA via intrathrombus delivery, dissolution of clot is heralded by temporary worsening of the lower leg ischemia prior to improvement. This temporary worsening corresponds to fragmentation of the clot and showering of emboli into distal circulation. Over the next 6-12 hours, the systemic activity of t-PA is known to slowly dissolve these clots, after which symptoms of worsening ischemia generally abate. The condition of the patient subsequently improves slowly to ameliorate the aPAO symptoms that represent native artery or graft occlusion.

One of the safety advantages of a thrombolytic agent such as plasmin is its ability to be neutralized rapidly in the blood by circulating inhibitors. However, there is evidence to suggest that the flow dynamics of a treatment zone can be such that plasmin may escape into the bloodstream prior to contacting its fibrin substrate on the clot and also that blood along with its contained inhibitors can enter the treatment zone during plasmin application and interfere with thrombolysis by inactivating the plasmin.

A need remains for thrombolytic agent delivery devices, systems, and methods that also provide for effective occlusion of a vessel or graft distal and/or proximal to an occlusion.

SUMMARY OF THE INVENTION

In one aspect, the present invention provides a coaxial infusion catheter system comprising:

a) an occlusion catheter component; and

b) an infusion catheter component, wherein at least a portion of the occlusion catheter is coaxially positioned within the infusion catheter, wherein the occlusion catheter provides for occlusion of a vessel or graft distal to an occlusion, wherein a composition comprising a thrombolytic agent can be infused into an annular fluid passageway between the outer wall of the occlusion catheter and the inner wall of the infusion catheter thereby providing the agent to a treatment zone.

In another aspect, the present invention provides an infusion catheter for delivering a thrombolytic agent to an occlusion in a vessel or graft, wherein the catheter comprises:

(a) an infusion zone; and

(b) an occlusion chamber disposed about an outer surface of its shaft about a region proximal to the infusion zone.

In some aspects, the present invention provides an infusion catheter for delivering a thrombolytic agent to an occlusion in a vessel or graft, wherein the catheter comprises:

(a) an infusion zone; and

(b) an occlusion chamber disposed about an outer surface of its shaft about a region distal to the infusion zone.

In other aspects, the present invention provides a coaxial infusion catheter system comprising:

(a) an infusion catheter component having a infusion zone for infusing a thrombolytic agent to an occlusion in a vessel or a graft; and

(b) an occluding catheter component having an elongate body, wherein an expandable occluding element is coupled to a distal end of the elongate body, wherein the element when expanded and in a closed configuration is capable of occluding a vessel or graft distal to a treatment zone, wherein the element when expanded and in an open position is capable of allowing blood flow through the treatment zone.

DETAILED DESCRIPTION

The devices, systems, and methods of the present invention can provide for delivery of a composition, preferably a solution, comprising any therapeutic. In the preferred embodiment, the therapeutic is a thrombolytic agent. Thrombolytic agents include, but are not limited to, plasmin and derivatives thereof. For example, plasmin and truncated variants thereof (e.g., plasmin, mini-plasmin, micro-plasmin, etc.) can be delivered to a treatment zone for contact with an occlusion (e.g., a clot) in a vessel (e.g., peripheral artery) or graft. In some embodiments, the system, devices, and methods of the present invention provide for acute peripheral arterial occlusion (aPAO) indications.

In one aspect, the present invention is based on a coaxial infusion catheter system1depicted inFIG. 1.

In one embodiment, the system comprises: a) an occlusion catheter2component; and b) an infusion catheter3component, wherein at least a portion of the occlusion catheter is coaxially positioned within the infusion catheter. Fluid can be infused into an annular fluid passageway between the outer wall of the occlusion catheter2and the inner wall of infusion catheter3. For example, a syringe containing a thrombolytic agent can be used to inject a solution comprising the agent whereby the solution advances through the annular fluid passageway exiting through side port slits of the infusion catheter3into a vessel (e.g., artery), graft, and/or occlusion (e.g., thrombus).

Preferably, the system components are dimensioned such that an infusion zone is maximized and the device length outside the patient is minimized. In one embodiment, the infusion zone length corresponds to the subject's overall treatment zone (e.g., clot mass inside an artery) in order to ensure uniform drug delivery throughout the treatment zone. Preferably, the portion of the system external to the patient is kept as short as possible so as to at least avoid or minimize complications arising from patient movement during treatment.

Occlusion Catheter

In one embodiment, the occlusion catheter2ofFIG. 1comprises a tubular occlusion catheter shaft4and an inflatable occlusion chamber5. In some embodiments, catheter2is made of nylon or other similar material. Preferably, the occlusion catheter2has a three French outer diameter with a central inflation lumen6that is continuous from the proximal tip end7to the distal tip end8thus providing a direct path from the proximal tip end7to the inflatable occlusion chamber5. When assembled with the infusion catheter3as shown inFIG. 1, the distal tip8extends beyond the infusion catheter's distal tip9such that the inflatable occlusion chamber5also lies distal to the infusion catheter's distal tip9thereby capable of providing occlusion of a vessel or graft distal to the infusion zone10. In some embodiments, the inflatable occlusion chamber5lies distal to the infusion catheter's distal tip9by at least about 0.1 cm, illustratively, by at least about: 0.1, 0.5, 1, and 2 centimeters.

In one embodiment, the inflatable occlusion chamber5is formed of a urethane polymer or a thermoplastic rubber elastomer. In another embodiment, the chamber5is a Latex balloon. The inflatable occlusion chamber5is expandable between a collapsed configuration and an inflated configuration. Upon inflation, the occlusion chamber conforms to the shape of the interior of the body lumen in which the system1is disposed, such as a blood vessel. In the collapsed configuration (not shown), the inflatable occlusion chamber5has the same general diameter (or less) as the distal end of the shaft8.

In another embodiment, the occlusion chamber5can be sized as appropriate to substantially or completely occlude a particular vessel or graft in which the system will be used. In some embodiments, the occlusion catheter2has a length that is at least about 0.5 cm, illustratively, about 0.5 cm to about 2 cm. In another embodiment, the inflatable occlusion chamber5has a collapsed diameter of at most about 0.039 inches; and an expanded diameter up to about 1.5 cm.

The inflatable occlusion chamber5can be inflated to various diameters, depending on the volume of the material (e.g., air, gas, fluid) inserted into the inflatable occlusion chamber5. In some embodiments, a single size occlusion catheter2is used. In order to facilitate inflation to a desired balloon diameter and avoid over-inflation, a chart can be provided listing various balloon diameters and the volume of inflation fluid generally required to achieve each diameter. In other embodiments, one or more occlusion catheter2sare sequentially used with the infusion catheter, wherein the one or more occlusion catheter2sare of different sizes and/or configurations relative to each other.

The inflatable occlusion chamber5can be inflated via inflation lumen6, which is in communication with the interior of the inflatable occlusion chamber5. When an inflation material (e.g., air, gas, fluid) is inserted through the inflation lumen6into the inflatable occlusion chamber5, at least the intermediate portion11of the occlusion chamber5moves radially outward.

In one embodiment, the occlusion catheter2is a balloon catheter comprising an inflatable balloon (i.e., the inflatable occlusion chamber).

Referring toFIG. 2, in some embodiments, a hub assembly provides for connecting an inflation source, directly or indirectly, to the inflation lumen6. In the illustrated embodiment shown inFIG. 2, the occlusion catheter2further comprises an occlusion catheter hub12. In some embodiments, the hub12comprises a rotating male luer thread collar (not shown). The hub can be made of plastic, for example. When the system1is assembled, the rotating male luer thread collar engages a hub connector assembly13, which is engaged with hub14of the infusion catheter, to provide communication between the inflation source15and the inflation lumen6as well as to provide a sealed connection between infusion catheter3and occlusion catheter2. In some embodiments, the rotating capability of the collar16can allow for disengagement of occlusion catheter2from the infusion catheter3without causing movement and possible misalignment of the infusion catheter3within the native artery or graft.

Infusion Catheter

Referring toFIG. 1, the outer infusion catheter3has a nylon (or other suitable material) tubular body. In one embodiment, the catheter3is of a 3 French inner diameter and 4, 5, 6, or 7 French outer diameter having a central lumen17that is continuous from the proximal18to the distal9end of the catheter3.

In one embodiment, the tubular shaft portion of the catheter3includes an infusion zone10with a plurality of slits Sn(wherein n is an integer greater than 0) that serve as pressure responsive valves, e.g. as described in U.S. Pat. Nos. 5,205,034 and 5,267,979, which are herein incorporated by reference in their entirety. For example, in some embodiments, the infusion zone has Sn, wherein n is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 30, 40, or more. The pressure responsive slits Snpermit fluid to exit from the catheter lumen17in response to a pressure level created by introduction of fluid into the lumen by a syringe. In other embodiments, the outer infusion catheter3comprises a plurality of side holes rather than pressure responsive slits. In some embodiments, the infusion catheter is a UNIFUSE™ catheter (Angiodynamics, Queensbury, N.Y.) (e.g., 4F UNI*FUSE™ infusion catheter) or similar device.

As shown inFIG. 1, the infusion zone10of the infusion catheter3is defined as the shaft portion between the optional distal infusion zone marker Mdistaland the optional proximal infusion zone marker Mproximal. Thrombolytic agent injected through the straight through port20into the annular space defined by lumen17will exit from the slits Snon the shaft portion between the two optional markers Mdistaland Mproximal. In one embodiment, marker Mproximalis positioned about 1 cm proximal to the proximal most pressure responsive slit Snand marker Mdistalis positioned on the catheter3about 1 cm or so distal to the distal most pressure responsive slit Sn. The infusion catheter3optionally may also have one or more additional markers to assist the operator in accurately positioning the infusion zone10within the graft. For example, in one embodiment, the optional positioning marker can be positioned on the catheter3shaft proximal to infusion zone marker Mproximal. Optional positioning marker can provide another visual indication of location and depth of the infusion zone10segment of the catheter3, thus ensuring that lytic agent, e.g., is not infused into a non-target area outside of the graft. In some embodiments, markers (e.g., Mdistal, Mproximal) are each optional.

As depicted inFIG. 2, the catheter2fits within infusion catheter3and is sealably connected to the catheter hub14by engaging a side port22of hub connector assembly13. In the preferred embodiment, the infusion catheter3has a 3 French inner diameter and 4, 5, 6, or 7 French outer diameter. For example, in some embodiments, the annular passageway for fluid flow can be created between a three French occlusion catheter (e.g., a balloon catheter) and a 4, 5, 6, or 7 French infusion catheter when assembled together. The dimensions of the annular space are sufficient to allow the desired fluid flow into the treatment zone (e.g., the clot).

In other embodiments, the catheter2also performs the function of occluding the infusion catheter's opening at end9when fully inserted into the catheter lumen17. The catheter2and catheter3components can be dimensioned such that the catheter2fits snugly within and occludes the opening at end9. In one embodiment, the outer diameter of the balloon catheter2and the opening at end9of the outer infusion catheter3are both approximately 0.040″ thus providing occlusion of the opening at end9. In another embodiment, the lumen17of the infusion catheter3is approximately 0.048″ in diameter transitioning down to a 0.040″ diameter at the infusion catheter tip at end9. Thus, in some embodiments, a separate occlusion element such as an occlusion ball or wire is not required with the current invention.

Fluid can be infused through a hub into the annular fluid passageway between the outer wall of the occlusion catheter2and the inner wall of infusion catheter3. For example, a syringe (not shown) containing a thrombolytic agent can be connected to the straight through port20. When injected through the straight through port20, the fluid advances through the annular fluid passageway defined by lumen17and exits through the side port slits Snof the infusion catheter3into the vessel, graft, and/or clot therein. Because the inner diameter of the infusion catheter3is typically larger than the outer diameter of occlusion catheter2, there is sufficient space within the infusion catheter for the passage of a liquid out of the infusion holes.

Preferably, the system components are dimensioned such that the infusion zone10is maximized and the device length outside the patient is minimized. In one embodiment, the infusion zone10length corresponds to the subject's overall treatment zone (e.g., clot mass) length in order to ensure uniform agent (e.g., thrombolytic agent) delivery throughout the treatment zone.

Sheath

In still further embodiments, the coaxial infusion catheter system1comprises: a) the occlusion catheter2component; b) the infusion catheter3component; and (c) a sheath24component.

Referring toFIG. 3, the sheath24comprises a tubular shaft25defining a central lumen26. The sheath can be made of nylon or other similar material. The sheath further comprises an open proximal end27, preferably fixedly secured to a hub28, and a free open and unobstructed distal end29. Preferably, in order to accommodate the infusion catheter, the sheath24has an inner diameter of at least 4, 5, 6, or 7 French with the central lumen26that is continuous from proximal end27to the open distal tip end29thus providing a direct path from the hub28to the inside of a vessel. In one embodiment, in the assembled state, optional markers Mdistaland Mproximalof the infusion catheter extend beyond the sheath distal tip29. In some embodiments, the sheath24has a length that is at least about 10 cm, illustratively, about 10 cm to about 90 cm.

In other aspects, the present invention is based on a coaxial infusion catheter system40depicted inFIG. 4. In one embodiment, the system40comprises a) the occlusion catheter2component; b) the infusion catheter3component; and c) a sheath41comprising an occlusion chamber42, wherein the occlusion chamber42is preferably disposed about the outer surface of tubular sheath shaft25about the distal region of shaft25. The sheath41component of system40can provide for occlusion of a vessel or graft proximal to a treatment zone (e.g., proximal to a clot in an artery).

In one embodiment, the tubular sheath shaft25ofFIG. 4defines central lumen26. The sheath further comprises open proximal end27, preferably fixedly secured to hub28, and a free open and unobstructed distal end29. Preferably, sheath41has an inner diameter of at least 4, 5, 6, or 7 French with the central lumen26that is continuous from hub proximal end30to the open distal tip end29thus providing a direct path from the hub28to the inside of a vessel. In one embodiment, in the assembled state, optional markers Mdistaland Mproximalof the infusion catheter3extends beyond the sheath41distal tip29. In some embodiments, the sheath41has a length that is at least about 10 cm, illustratively, about 10 cm to about 90 cm.

In one embodiment, the inflatable occlusion chamber42is formed of a urethane polymer or a thermoplastic rubber elastomer. In other embodiments, the chamber42is an inflatable balloon. In another embodiment, the chamber42is a Latex balloon. The inflatable occlusion chamber42is expandable between a collapsed configuration and an inflated configuration. Upon inflation, the occlusion chamber occludes the vessel or graft by conforming to the shape of the space between the outer wall of the sheath shaft25and the inner wall of the vessel or graft in which the system40is disposed, such as a blood vessel. The occlusion chamber42can be sized as appropriate to substantially or completely occlude a particular vasculature in which the system will be used.

In one embodiment, the inflatable occlusion chamber42can be inflated to various sizes, depending on the volume of the material (e.g., air, gas, fluid) inserted into the inflatable occlusion chamber42. In order to facilitate inflation to a desired size and avoid over-inflation, a chart can be provided listing various chamber sizes and the volume of inflation material generally required to achieve each size. In other embodiments, the inflatable occlusion chamber42expands to a pre-determined maximum size.

The inflatable occlusion chamber42can be inflated via inflation lumen44, which is in communication with the interior of the inflatable occlusion chamber42. When an inflation material (e.g., air, gas, fluid) is inserted through the inflation lumen44into the inflatable occlusion chamber42, at least the intermediate portion45of chamber42moves radially outward.

In some embodiments, an inflation lumen44is disposed longitudinally along the inner wall of the sheath shaft25and is in communication with the occlusion chamber42disposed about the outer surface of the sheath shaft25about the distal region43.

In one embodiment, the proximal end27of the sheath41is sealingly secured to a sheath hub28. In the illustrated embodiment, sheath41also is provided with a side port structure46to provide a secured sealed fluid communication between an inflation source47and the interior of the inflation lumen44. Side port structure46can be used to inject a suitable material (e.g., air, fluid) to inflate the occlusion chamber42thereby providing occlusion of a vessel proximal to infusion zone10.

Thus, in other embodiments, system40can provide for occlusion of a vessel or graft at a position proximal to and/or distal to a treatment zone. Fluid can be infused into an annular fluid passageway between the outer wall of the occlusion catheter2and the inner wall of infusion catheter3. For example, a syringe containing a thrombolytic agent can be used to inject a solution comprising the agent whereby the solution advances through the annular fluid passageway exiting through side port slits of the infusion catheter3into a vessel (e.g., artery), graft, and/or occlusion (e.g., thrombus). The inflatable occlusion chamber5of the occlusion catheter2can be inflated before, after, or along with injection of the thrombolytic agent, preferably before injection of the thrombolytic agent, to provide occlusion of the vessel or graft distal to the treatment zone. And, the inflatable occlusion chamber42of the sheath41can be inflated before, after, or along with injection of the thrombolytic agent, preferably before injection of the thrombolytic agent, to provide occlusion of the vessel or graft proximal to the treatment zone.

In other aspects, the present invention provides a sheath having an occlusion chamber for occluding a vessel, graft, and/or clot proximal to the treatment zone. The sheath, when employed at least in conjuction with an infusion catheter slideably inserted therein, is capable of providing for occlusion of a vessel or graft proximal to a treatment zone (e.g., proximal to a clot in an artery). In some embodiments, the sheath is sheath41.

In another aspect, the present invention is based on an infusion catheter50depicted inFIG. 5. The infusion catheter50comprises an occlusion chamber51disposed about the outer surface of the catheter shaft52about a region proximal to infusion zone53.

In some embodiments, the infusion catheter50has a nylon (or other suitable material) tubular body. In one embodiment, the catheter50is of 4, 5, 6, or 7 French diameter with a central lumen54that is continuous from the proximal55to the distal56end of the catheter50.

In one embodiment, the tubular shaft portion of the catheter50includes an infusion zone53with a plurality of slits Snthat serve as pressure responsive valves. For example, in some embodiments, the infusion zone has Sn, wherein n is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 30, 40, or more. The pressure responsive slits Snpermit fluid to exit from the catheter lumen54in response to a pressure level created by introduction of fluid into the lumen. Alternatively, infusion catheter50may include a plurality of side holes rather than pressure responsive slits.

The device is dimensioned such that the infusion zone is maximized and the device length outside the patient is minimized. Specifically, the infusion zone53length preferably corresponds to the patient's overall treatment zone (e.g., clot mass length) in order to ensure uniform drug delivery throughout the treatment zone. The portion of the device external to the patient is kept as short as possible to avoid complications arising from patient movement during lyse time. In other embodiments, the infusion catheter50may also have one or more markers to assist the operator in accurately positioning the infusion zone53. For example, in one embodiment, one or more markers are positioned on the catheter shaft52about 1 cm proximal, distal, or both, to infusion zone53.

In some embodiments, an occlusion lumen58is disposed longitudinally along the inner wall of the infusion catheter shaft52and is in communication with occlusion chamber51disposed at the outer surface of the catheter shaft52proximal to the infusion zone53. In the illustrated embodiment, the occlusion lumen58corresponds to an inflation lumen in communication with the occlusion member51, wherein the occlusion chamber51is an inflatable balloon.

In some embodiments, a separate occlusion element such as an occluding wire or ball is used to occlude the opening at end56.

In one embodiment, occlusion of the distal opening of the catheter assembly may be accomplished by inserting an occluding wire59through a valve (e.g., a hemostasis valve coupled to a proximal end of the catheter which substantially prevents fluid from flowing out a proximal end of the catheter assembly during use), then inserting the wire further along the length of the catheter to or beyond the distal end56.

The occluding wire can be configured to substantially seal the distal end56of the infusion catheter50during use in order to facilitate spray distribution through the holes. In some embodiments, the occluding wire comprises a wire body portion and a distal sealing ball portion. The sealing ball portion can form a substantially liquid-tight seal at the distal end of the catheter, thereby forcing liquid located proximal to the seal out of the infusion slits or holes of the catheter. Because the inner diameter of the catheter is typically larger than the diameter of the wire body portion of the occluding wire, there is ample space within the infusion catheter for the passage of a liquid out of the infusion holes.

In other embodiments, the inner diameter of the catheter50is reduced to a narrow neck at the distal end of the catheter. The sealing ball portion of the occluding wire can seat against the inner, narrow neck wall portion of the catheter when inserted into the distal end and thereby substantially occludes the distal opening of the catheter. Consequently, substantially any liquid forced through the catheter is caused to exit through the infusion holes rather than through the opening.

In another embodiment, the inner diameter of catheter50is constant throughout the catheter, but the diameter of the occluding ball is configured to substantially match the inner diameter of the catheter. Thus, the occluding ball can be slid to the distal tip, thereby substantially occluding the passageway of the catheter and forcing fluid to flow out of the side perfusion holes or slits proximal to the occluding ball.

In still further embodiments, a hub coupled to a proximal end of the elongate wire body of the occluding wire can be provided. The hub of the occluding wire can be configured to be coupled to the catheter50. The hub of the occluding wire thus prevents the occluding tip from moving in a longitudinal direction with respect to the catheter once the occluding tip has been placed in a desired position with respect to the catheter50.

In another aspect, the present invention is based on an infusion catheter60depicted inFIG. 6. The infusion catheter60comprises an occlusion chamber61disposed about the outer surface of the catheter shaft62about a region distal to infusion zone63.

In some embodiments, the infusion catheter60has a nylon (or other suitable material) tubular body. In one embodiment, the catheter60is of 4, 5, 6, or 7 French outer diameter with a central lumen64that is continuous from the proximal65to the distal66end of the catheter60. In one embodiment, the tubular shaft portion of the catheter60includes an infusion zone63with a plurality of slits Snthat serve as pressure responsive valves. For example, in some embodiments, the infusion zone has Sn, wherein n is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 30, 40, or more. The pressure responsive slits Snpermit fluid to exit from the catheter lumen64in response to a pressure level created by introduction of fluid into the lumen. Alternatively, infusion catheter60may include a plurality of side holes rather than pressure responsive slits.

The device is dimensioned such that the infusion zone is maximized and the device length outside the patient is minimized. Specifically, the infusion zone63length preferably corresponds to the patient's overall treatment zone (e.g., clot mass length) in order to ensure uniform drug delivery throughout the treatment zone. The portion of the device external to the patient is kept as short as possible to avoid complications arising from patient movement during lyse time. In other embodiments, the infusion catheter60may also have one or more markers to assist the operator in accurately positioning the infusion zone63. For example, in one embodiment, one or more markers are positioned on the catheter shaft62about 1 cm proximal, distal, or both, to infusion zone63.

In some embodiments, an occlusion lumen68is disposed longitudinally along the inner wall of the infusion catheter shaft62and is in communication with occlusion chamber61disposed at the outer surface of the catheter shaft62proximal to the infusion zone63. In the illustrated embodiment, the occlusion lumen68corresponds to an inflation lumen in communication with the occlusion member61, wherein the occlusion chamber61is an inflatable balloon.

In some embodiments, a separate occlusion element such as an occluding wire or ball is used to occlude opening at end66.

In one embodiment, occlusion of the distal opening of the catheter assembly may be accomplished by inserting an occluding wire70through a valve (e.g., a hemostasis valve coupled to a proximal end of the catheter which substantially prevents fluid from flowing out a proximal end of the catheter assembly during use), then inserting the wire further along the length of the catheter to or beyond the distal end66.

The occluding wire can be configured to substantially seal the distal end66of the infusion catheter60during use in order to facilitate spray distribution through the holes. In some embodiments, the occluding wire comprises a wire body portion and a distal sealing ball portion. The sealing ball portion can form a substantially liquid-tight seal at the distal end of the catheter, thereby forcing liquid located proximal to the seal out of the infusion slits or holes of the catheter. Because the inner diameter of the catheter is typically larger than the diameter of the wire body portion of the occluding wire, there is ample space within the infusion catheter for the passage of a liquid out of the infusion holes.

In other embodiments, the inner diameter of the catheter60is reduced to a narrow neck at the distal end of the catheter. The sealing ball portion of the occluding wire can seat against the inner, narrow neck wall portion of the catheter when inserted into the distal end and thereby substantially occludes the distal opening of the catheter. Consequently, substantially any liquid forced through the catheter is caused to exit through the infusion holes rather than through the opening.

In another embodiment, the inner diameter of catheter60is constant throughout the catheter, but the diameter of the occluding ball is configured to substantially match the inner diameter of the catheter. Thus, the occluding ball can be slid to the distal tip, thereby substantially occluding the passageway of the catheter and forcing fluid to flow out of the side perfusion holes or slits proximal to the occluding ball.

In still further embodiments, a hub coupled to a proximal end of the elongate wire body of the occluding wire can be provided. The hub of the occluding wire can be configured to be coupled to the catheter60. The hub of the occluding wire thus prevents the occluding tip from moving in a longitudinal direction with respect to the catheter once the occluding tip has been placed in a desired position with respect to the catheter60.

In one aspect, the present invention is based on a coaxial infusion catheter system70depicted inFIG. 7.

In one embodiment, the system comprises: a) an infusion catheter71component; and b) an occluding catheter72component having an elongate body73, wherein an expandable occluding element74is coupled to a distal end75of the elongate body73.

In some embodiments, the infusion catheter71has a nylon (or other suitable material) tubular body. In one embodiment, the catheter71is of 4, 5, 6, or 7 French outer diameter with a central lumen that is continuous from the proximal76to the distal79end of the infusion catheter71. In some embodiments, the infusion catheter is a UNIFUSE™ catheter (Angiodynamics, Queensbury, N.Y.) (e.g., 4F UNI*FUSE™ infusion catheter) or similar device.

In one embodiment, the tubular shaft portion of the infusion catheter71includes an infusion zone77with a plurality of slits SNthat serve as pressure responsive valves. For example, in some embodiments, the infusion zone has Sn, wherein n is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 30, 40, or more. The pressure responsive slits Snpermit fluid to exit from the catheter lumen in response to a pressure level created by introduction of fluid into the lumen. Alternatively, infusion catheter71may include a plurality of side holes rather than pressure responsive slits.

The device is dimensioned such that the infusion zone is maximized and the device length outside the patient is minimized. Specifically, the infusion zone77length preferably corresponds to the patient's overall treatment zone (e.g., clot mass length) in order to ensure uniform drug delivery throughout the treatment zone. The portion of the device external to the patient is kept as short as possible to avoid complications arising from patient movement during lyse time. In other embodiments, the infusion catheter71may also have one or more markers to assist the operator in accurately positioning the infusion zone77. For example, in one embodiment, one or more markers are positioned on the catheter shaft78about 1 cm proximal, distal, or both, to infusion zone77.

In some embodiments, the inner diameter of the infusion catheter71is larger than the diameter of the body73portion of the occluding catheter72, therefore, there is ample space within the infusion catheter for the passage of a liquid out of the infusion holes as well as through infusion catheter at end79.

In one embodiment, the expandable occluding element74, when used in an open configuration in the expanded position, functions as a filter to filter blood; and, wherein element74, when used in a closed configuration in the expanded position, functions to occlude the lumen of a vessel or graft at a position distal to end hole79. Accordingly, in some embodiments, when the expandable occluding element74is in the closed configuration, system70can provide for completely blocking the lumen of a vessel or graft in order to increase the saturation of the thrombolytic agent into a clot during treatment, wherein when the expandable occluding element74is in the open configuration, blood flow can occur following the treatment in order to allow blood flow to be restored (e.g., restored in the leg) while also trapping emboli, if present.

Referring toFIG. 8, in one embodiment, the expandable occluding element74is configured as a dischargeable umbrella comprising two overlapping components with staggered shutters or overlapping slits. Depending on the degree of rotation, rotation of one of the components over the other allows for blood flow (the open configuration) or vessel/graft lumen occlusion (the closed configuration).

In some embodiments, the expandable occluding element can be configured to have an inherent tension that converts the element from a collapsed to an expanded/unfolded state, or it can be expanded/unfolded using a folding system. For example, the folding system can comprise a plurality of folding arms roughly similar to a typical umbrella.

In other embodiments, the expandable occluding element is a dischargeable umbrella comprising a mesh or net material for trapping emboli. Suitable mesh include those known in the art. For example, polyurethane meshes may be used, such as Saati and Tetko meshes. These are available in sheet form and can be easily cut and formed into a desired shape. Preferably, the mesh is capable of entrapping embolic material without unduly disrupting blood flow when the system is employed with the expandable occluding element in the open configuration.

In one embodiment, the occluding catheter72can be inserted through a valve (e.g., a hemostasis valve coupled to a proximal end of the catheter which substantially prevents fluid from flowing out a proximal end of the catheter assembly during use), then inserting the occluding catheter72further along the length of infusion catheter71through the end hole79.

In other aspects, a kit is provided which comprises the systems and/or one or more of the devices/components of the present invention. In some embodiments, the kit further comprises a therapeutic, for example a thrombolytic agent such as plasmin, etc.