BACKGROUND

[0001] Liver cancer is the second largest killer of cancer patients, right after lung cancer. Whether the cancer originated in the liver itself or in another organ, it is a difficult disease to treat, often due to location and resistance to treatments (such as chemotherapy). Radiation has shown to be effective, however the treatment risks damage to healthy liver tissue. Because cancer patients usually already have compromised liver function, this could delay their treatment significantly or even indefinitely.

[0002] Currently, the most effective treatment is a surgical resection of the cancerous tissue. However, this only works if the cancer originated from the liver and if it is in an isolated location. Next steps normally involve chemotherapy and radiation treatments. Chemotherapy is not only hard on the body, but the cancer can also be resistant, making treatment ineffective. Radiation has similar effects, and although the cancer is not as resistant, damage to healthy liver tissue is inevitable.

SUMMARY

[0003] In a first aspect, an infusion catheter is disclosed. The infusion catheter includes a floppy distal tip having a solid core, an infusion section attached at a first end to the distal tip, the infusion section including at least one hole, and a channel attached to a second end of the infusion section, the channel having a lumen in communication with the at least one hole.

[0004] In some embodiments, the channel comprises a braid, a laser cut hypotube, or an electroplated braid. In some embodiments, the infusion section comprises a braid, a laser cut hypotube, or an electroplated braid. In some embodiments, the distal tip comprises a braid, a laser cut hypotube, or an electroplated braid. In some embodiments, the infusion section and the channel are integrally formed. In some embodiments, the distal tip and the infusion section are integrally formed. In some embodiments, the channel is pushable. In some embodiments, the channel is torqueabie. In some embodiments, the distal tip is a hand shapeable tip. In some embodiments, the distal tip comprises a tapered shape. In some embodiments, the distal tip comprises a conical shape. In some embodiments, the distal tip comprises a hydrophilic coating. In some embodiments, the infusion section comprises a hydrophilic coating. In some embodiments, the channel comprises a hydrophilic coating. In some embodiments, a transition section at the attachment of the distal tip to the first end of the infusion section is smooth. In some embodiments, the at least one hole is configured to control a direction of flow therethrough. In some embodiments, the at least one hole is configured to control a velocity of a flow therethrough. In some embodiments, the at least one hole is configured to control a flow rate of a flow therethrough. In some embodiments, the at least one hole comprises a plurality of holes. In some embodiments, the plurality of holes are configured to control a direction of flow therethrough. In some embodiments, the plurality of holes are configured to control a velocity of a flow therethrough. In some embodiments, the plurality of holes are configured to control a flow rate of a flow therethrough. In some embodiments, the plurality of holes comprises a pattern of holes distributed around a circumference of the infusion secti on. In some embodiments, the pattern of holes is configured to achieve a desired flow pattern, a desired flow direction, and/or a desired flow characteristic. In some embodiments, the at least one hole is configured for delivery of chemicals, beads, fluids, and/or devices. In some embodiments, the infusion catheter further comprises a first radiopaque marker positioned on a first side of the infusion section. In some embodiments, the first side of the infusion section is opposite the distal tip. In some embodiments, the first side of the infusion section is the same side as the distal tip. In some embodiments, the infusion catheter further comprises a second radiopaque marker on a second side of the infusion section, the second side of the infusion section opposite the first side of the infusion section. In some embodiments, the infusion catheter further comprises a curve. In some embodiments, the curve is a cobra, SOS 2, or Chuang B type curve.

[0005] In a second aspect, an infusion catheter is disclosed. The infusion catheter includes a floppy distal tip having a solid core, an infusion section attached at a first end to the distal tip, the infusion section including at least one hole, a channel attached to a second end of the infusion section, the channel having a lumen in communication with the at least one hole, and a balloon positioned on the second side of the infusion section, wherein the distal tip is positioned on a first side of the infusion section.

[0006] In some embodiments, the balloon is compliant, semi-compliant, or non- compliant. In some embodiments, the infusion catheter further includes a first radiopaque marker on a first side of the compliant balloon. In some embodiments, the infusion catheter further includes a second radiopaque marker on a second side of the compliant balloon. In some embodiments, the infusion catheter further includes a radiopaque marker positioned within the balloon. In some embodiments, the infusion catheter further includes a second lumen in fluid connection with the compliant balloon, the second lumen configured for inflating the compliant balloon. In some embodiments, the channel comprises a first channel, the second lumen is formed in a second channel, and the first channel extends through the second channel. In some embodiments, the first channel is configured to telescope relative to the second channel. In some embodiments, the second channel comprises a braid, a laser cut hypotube, or an electroplated braid. In some embodiments, the second channel is pushabie. In some embodiments, the second channel is torqueabie. In some embodiments, in a deflated configuration, the balloon has an outer diameter of approximately 1 mm or less, and the balloon can be inflated to an inflated configuration of approximately 5 mm or more. In some embodiments, the channel extends through the balloon, and the channel, infusion section, and distal tip are configured to telescope together relative to the balloon. In some embodiments, the infusion catheter further includes, a locking hub configured to control the telescoping of the channel, infusion section, and distal tip. In some embodiments, the channel comprises a braid, a laser cut hypotube, or an electroplated braid. In some embodiments, the infusion section comprises a braid, a laser cut hypotube, or an electroplated braid. In some embodiments, the distal tip comprises a braid, a laser cut hypotube, or an electroplated braid. In some embodiments, the infusion section and the channel are integrally formed. In some embodiments, the distal tip and the infusion section are integrally formed. In some embodiments, the channel is pushabie. In some embodiments, the channel is torqueabie. In some embodiments, the distal tip is a hand shapeable tip. In some embodiments, the distal tip comprises a tapered shape. In some embodiments, the distal tip comprises a conical shape. In some embodiments, the distal tip comprises a hydrophilic coating. In some embodiments, the infusion section comprises a hydrophilic coating. In some embodiments, the channel

-J- comprises a hydrophilic coating. In some embodiments, a transition section at the attachment of the distal tip to the first end of the infusion section is smooth. In some embodiments, the at least one hole is configured to control a direction of flow therethrough. In some embodiments, the at least one hole is configured to control a velocity of a flow therethrough. In some embodiments, the at least one hole is configured to control a flow rate of a flow therethrough. In some embodiments, the at least one hole comprises a plurality of holes. In some embodiments, the plurality of holes are configured to control a direction of flow therethrough. In some embodiments, the plurality of holes are configured to control a velocity of a flow therethrough. In some embodiments, the plurality of holes are configured to control a flow rate of a flow therethrough. In some embodiments, the plurality of holes comprises a pattern of holes distributed around a circumference of the infusion section. In some embodiments, the pattern of holes is configured to achieve a desired flow pattern, a desired flow direction, and/or a desired flow characteristic. In some embodiments, the at least one hole is configured for delivery of chemicals, beads, fluids, and/or devices. In some embodiments, the infusion catheter also includes an additional radiopaque marker positioned on a first side of the infusion section. In some embodiments, the first side of the infusion section is opposite the distal tip. In some embodiments, the first side of the infusion section is the same side as the distal tip. In some embodiments the infusion catheter also includes an additional radiopaque marker on a second side of the infusion section, the second side of the infusion section opposite the first side of the infusion section. In some embodiments the infusion catheter also includes a curve. In some embodiments, the curve is a cobra, SOS 2, or Chuang B type curve.

[0007] In a third aspect, an infusion catheter is disclosed. The infusion catheter includes a channel including a lumen in communication with an open end of the channel, and a balloon positioned proximal the open end of the channel. In some embodiments, the infusion catheter includes a curve. In some embodiments, the curve is a cobra, SOS 2, or Chuang B type curve. In some embodiments, the curve is a baked curve. In some embodiments, the curve is positioned on an opposite side of the balloon than the open end of the channel. In some embodiments, the balloon is compliant, semi-compliant, or non- compliant. In some embodiments, the infusion catheter includes a first radiopaque marker on a first side of the compliant balloon. In some embodiments, the infusion catheter further includes a second radiopaque marker on a second side of the compliant balloon, the second side opposite the first side. In some embodiments, the infusion catheter includes a radiopaque marker positioned within the balloon. In some embodiments, the infusion catheter includes a second lumen in fluid connection with the balloon and a port, the second lumen and the port configured for inflating the balloon. In some embodiments, the channel comprises a braid, a laser cut hypotube, or an electroplated braid. In some embodiments, the channel is pushable. In some embodiments, the channel is torqueable. In some embodiments, in a deflated configuration, the balloon has an outer diameter of approximately 1 mm or less, and the balloon can be inflated to an inflated configuration of approximately 5 mm or more. In some embodiments, the channel extends through the balloon. In some embodiments the infusion catheter includes a luer hub positioned at a second end of the channel, the second end opposite the open end. In some embodiments, the channel comprises a hydrophiiic coating. In some embodiments, the open end of the channel is configured to control a velocity of a flow therethrough. In some embodiments, the open end of the channel configured to control a flow rate of a flow therethrough. In some embodiments, the open end of the channel is configured for deliver}' of chemicals, beads, fluids, and/or devices. In some embodiments, the channel is configured to receive a guide wire or catheter therein.

[0008] In another aspect, a method is disclosed. The method includes advancing the infusion catheter of the first aspect through a vessel to a deliver}' location, and delivering a substance through the at least one hole of the infusion section to the delivery location. In some embodiments, said advancing further comprises advancing the infusion catheter along a guide wire. In some embodiments, said advancing further does not require use of a guide wire. In some embodiments, the vessel is the common hepatic artery. In some embodiments, the substance comprises a fluid, beads, a chemical, or a device.

[0009] In another aspect, a method is disclosed. The method includes advancing the infusion catheter of the second aspect through a vessel to a delivery location, and delivering a substance through the at least one hole of the infusion section to the deliver}' location. In some embodiments, the substance comprises a fluid, beads, a chemical, or a device. In some embodiments, the method includes inflating the balloon. In some embodiments, inflating the balloon occludes blood flow within the vessel. In some embodiments, inflating the balloon temporarily reverses blood flow in one or more collateral vessels. In some embodiments, said delivering occurs after said inflating. In some embodiments, said advancing further comprises advancing the infusion catheter through a guide catheter. In some embodiments, the method includes positioning the infusion section relative to the balloon. In some embodiments, the method includes positioning the infusion section relative to the collateral vessel flow reversal. In some embodiments, said positioning comprises telescoping the first channel relative to the second channel. In some embodiments, said positioning comprises telescoping the first channel relative to the balloon. In some embodiments, the vessel is the common hepatic artery. In some embodiments, the deliver}' site is the liver. In some embodiments, the method includes deflating the balloon after deliver}- of the chemical or beads.

[0010] In another aspect, a method is disclosed. The method includes advancing the infusion catheter of the third aspect, through a vessel to a deliver}' location, and delivering a substance through the through the open end of the channel to the delivery location. In some embodiments, the substance comprises a fluid, beads, a chemical, device, guide wire or catheter. In some embodiments, the method further includes inflating the balloon. In some embodiments, inflating the balloon occludes blood flow within the vessel. In some embodiments, inflating the balloon temporarily reverses blood flow in one or more collateral vessels. In some embodiments, said delivering occurs after said inflating. In some embodiments, the vessel is the common hepatic artery. In some embodiments, the delivery site is the liver. In some embodiments, the method also includes deflating the balloon after delivery of the substance.

BRIEF DESCRIPTION OF THE DRAWINGS

[0011] FIG. 1 illustrates a perspective view of a Surefire™ infusion catheter.

[0012] FIG. 2 illustrates a perspective view of a Renegade HI-FLO™ Fathom Kit including a Renegade HI-FLO Microcatheter and Fathom- 16 Steerable Guidewire.

[0013] FIG. 3 illustrates a perspective view of a ProStream™ Multiple Sidehole

Infusion Wire.

[0014] FIG. 4 illustrates use of an IsoFlow™ Infusion Catheter with a dual- balloon design. 15] FIG. 5 illustrates an embodiment of using an infusion catheter within an arterial system.

[0016] FIG. 6 illustrates an embodiment of an infusion catheter having a solid core, floppy distal tip.

[0017] FIG. 7 illustrates an embodiment of an infusion catheter having a telescoping feature.

[0018] FIG. 8 illustrates an embodiment of an infusion catheter disposed within an arterial system.

[0019] FIG. 9 illustrates a perspective view of an embodiment of the infusion catheter shown in FIG. 7.

[0020] FIG. 10 illustrates a perspective view of an embodiment of the infusion catheter shown in FIG. 9.

DETAILED DESCRIPTION OF CERTAIN INVENTIVE EMBODIMENTS

[0021] One promising method of treatment of cancers is radioemboiization. Radioactive microspheres are injected into the hepatic arteries, where they lodge themselves into the cancerous tissue. Here they starve the tumor of nutrient and oxygen-rich blood, and deliver radiation directly to the cancerous cells with minimal risk to the surrounding, healthy tissue.

[0022] Radioemboiization currently uses a basic infusion catheter and yttrium 90 (Y-90) microspheres. Although the liver derives blood supply from both the hepatic arteries and the portal vein, growing tumors obtain most their blood supply from the hepatic arteries. Usually the Y-90 radioemboiization procedure has at least two outpatient sessions: a diagnostic session followed by a treatment session. During both sessions, a small angiographic catheter is inserted into the femoral artery and advanced under x-ray fluoroscopy guidance through the body into the hepatic artery. The vascular anatomy is adequately mapped, and embolizing coils are placed if deemed necessary by the physician.

[0023] Yttrium-90 resin microsphere radioemboiization using an antireflux catheter can be used as an alternative to traditional coil embolization for nontarget protection. Serious complications can result from nontarget embolization during yttrium-90 (Y-90) transarterial radioemboiization. Hepatoenteric artery coil embolization has been traditionally performed to prevent non target radioembolization. This catheter results in a reduction in procedure time, fluoroscopy time, and contrast material dose and may be an attractive cost-effective alternative to detachable coil embolization for prevention of nontarget radioembolization.

[0024] During the treatment session, radioactive Y-90 microspheres are injected in the hepatic arteries that perfuse the tumor. The downside to this treatment occurs only when the radioactive microspheres do not reach the tumor, and instead are refluxed to the intestines or shunted to the lungs. In order to avoid this, two methods can be used. The first is coil embolization, where coils are inserted into surrounding blood vessels in a procedure prior to the microsphere infusion. This helps to prevent microspheres from traveling down the wrong blood vessel.

[0025] Another method (which can be used in addition to coiling) uses a balloon infusion catheter placed strategically in the common hepatic artery. This ensures that blood flow travels through the correct blood vessels, carrying the microspheres directly to the tumor.

[0026] Certain catheters are used, in addition to coiling, to try and direct the microspheres to the correct blood vessels. The SureFire™ catheter employs a mesh net (illustrated in FIG. 1), which helps prevent reflux, but does not fix the problem entirely. Similarly, there are catheters which use balloons and infusion wires to help direct the flow, but the location of the infusion of the microspheres are based on the whim of the physician performing the procedure. When the proper balloon and infusion cannula are combined with the perfect placement of the catheter, more patients will have a successful procedure. This means that they will potentially be able to tolerate higher doses and shorter times between doses, and it will also make the procedure significantly more effective and save lives.

[0027] In some embodiments, general dimensions are: outer diameter: 0.038"; balloon expansion from .038" folded profile to approximately 5mm+ made from a compliant material such as urethane. Other suitable materials may also be employed for this purpose.

[0028] During use, the operator would transverse the device through a guiding catheter that was placed into the celiac trunk and into the common hepatic artery. In one embodiment, an integrated guidewire, infusion catheter would be advanced into position to facilitate the delivery of particles, or fluids, or treatments, for example, delivery of radioembolization beads for the treatment of cancers. In another embodiment a combination system, containing the integrated guidewire, infusion catheter and a balloon catheter would be advanced through a guiding catheter placed into the celiac trunk, the balloon would be deployed in the common hepatic artery to block all blood flow coming from the aorta to the liver. This balloon occlusion technique temporarily reverses the blood flow in branch vessels supplying the stomach and small intestine during transarterial embolization. It ensures that blood flow in constantly supplying the liver tumors to be addressed and will serve as a way to ensure that radioembolization does not reflux into un desired locations. In another embodiment, a guiding catheter with compliant balloon would be placed distal to the celiac trunk, in the common hepatic artery and would embody a compliant balloon. Then the compliant balloon would be expanded to occlude the arterial flow to reverse flow back through the gastroduodenai artery. The integrated guidewire, infusion embodiment of which would then be passed through the guiding catheter with compliant balloon and advanced into position for the delivery of medicines, beads, etc.

[0029] Once the desired blood flow reversal has been confirmed the radioembolization would be delivered through the infusion lumen and out the infusion section of the catheter. This serves to perfuse the liver tumor cells.

[0030] Once the adequate amount of active beads have been infused, the balloon would be deflated, restoring normal flow. An embodiment of use is illustrated in FIG. 5,

Existing Devices

[0031] A Surefire ¹¹ " ⁴ infusion catheter delivers embolic agents directly to the blood vessel using an expandable tip, which collapses in forward flow and expands to the size of the vessel wall in reverse flow. This design increases target deliver and minimizes reflux that might otherwise cause damage to healthy tissue. An example is shown in FIG. 1.

[0032] A Renegade HI-FLO ^IM Fathom Kit includes the Renegade HI-FLO Microcatheter and Fathom- 16 Steerabie Guidewire. The microcatheter has a large diameter, is made of a kink-resistant material, and is available in multiple lengths. The guidewire is designed for visibility and customization. It has a variety of stiffness along the wire to allow for flexibility without compromising control. An example is shown in FIG. 2. [0033] A ProStream ¹ Multiple Sidehole Infusion Wire allows for quick and easy infusion by eliminating the need for a separate core wire. An example of this is shown in FIG. 3.

[0034] An IsoFlow ^1M Infusion Catheter uses a dual-balloon design in order to keep the blood flow intact during treatment. It allows the physician to increase drug concentrations while reducing systemic exposure by enabling sideways perfusion. The IsoFlow™ catheter requires a guide wire for precise placement. An example is shown in FIG. 4.

[0035] FIG. 6 illustrates an embodiment of an infusion catheter 200. The infusion catheter 200 includes a solid core, floppy distal tip 202. The solid core, floppy distal tip 202 may function in a similar manner to a lead or guidewire. Thus, in contrast to some systems requiring both a guidewire and a catheter, the infusion catheter 200 does not require a separate guidewire,

[0036] In some embodiments, the solid core, floppy distal ti 202 has a tapered, conical shape attached to a smooth transition to a larger profile 204, This larger profile 204 is connected to an infusion section 206. The infusion section 206 includes at least one hole 208 for infusion of one or more chemicals or beads from the infusion section 206 to the vessel in proximity to a biological target in vivo. In some embodiments, the biological target is a cancer tumor. In some embodiments, the cancer tumor is in the liver. The at least one hole 208 could include a pattern of holes distributed around the outer circumference of the infusion section 206. In some embodiments, the pattern provides a uniform distribution of holes around the infusion section 206. The infusion section 206 is attached to a pushable channel 210. The pushable channel 210 is formed of a stiffer material than the solid core, floppy distal tip 202. The pushable channel 210 includes a single interior lumen in fluid communication with the at least one hole 208 in the infusion section 206.

[0037] FIGS. 7 and 9 illustrate an embodiment of an infusion catheter 400. The infusion catheter 400 includes an inner infusion catheter 402. In some embodiments, the inner infusion catheter 402 has a telescoping feature allowing extension or retraction. The infusion catheter 400 includes a compliant balloon 404 designed to occlude fonvard flow within the vessel when the compliant balloon 404 is in an expanded position. On either side of the compliant balloon is a radiopaque marker 406 used to identify the position of the infusion catheter 400 within the vessel. The infusion catheter 400 further includes a lumen 408 fluidly connected to the compliant balloon 404. The lumen 408 can be used for expanding the compliant balloon 404 to the expanded position.

[0038] A locking hub 410 is positioned to control the advancement or retraction of the telescoping feature of the inner infusion catheter 402.

[0039] On the end of the infusion catheter 400 is a solid core, floppy distal tip 412. The solid core, floppy distal tip 12 may function in a similar manner to a lead or guidewire. Thus, in contrast to some systems requiring both a guidewire and a catheter, the infusion catheter 412 does not require a separate guidewire. In some embodiments, the solid core, floppy distal tip 412 has a tapered, conical shape attached to a smooth transition to a larger profile.

[0040] The infusion section 414 of the infusion catheter 400 includes at least one hole 416 for infusion of one or more chemicals or beads to the vessel in proximity to a biological target in vivo. In some embodiments, the biological target is a cancer tumor. In some embodiments, the cancer tumor is in the liver. The at least one hole 416 could include a pattern of holes distributed around the outer circumference of the infusion section 414. In some embodiments, the pattern provides a uniform distribution of holes around the infusion section 414.

[0041] FIGS. 8 and 10 illustrate an embodiment of an infusion catheter 600 disposed within an arterial system including the common hepatic artery ("CHA"), which supplies oxygenated blood to the liver. The infusion catheter 600 includes a catheter 602. The catheter 602 includes a curve 604 similar to, for example, a cobra, an SOS 2 or a Chuang B type curve.

[0042] As illustrated in FIG. 8, a compliant balloon 606 is positioned within the CHA, On either side of the compliant balloon 606 along the infusion catheter 600 is radiopaque marker 608. A luer hub 610 is illustrated on an opposite end of the infusion catheter 600 from the compliant balloon 606. In some embodiments, the luer hub 610 is used to accept catheters or guidewires. In some embodiments, the luer hub 610 is used to accept radioactive beads, drugs or other devices or medicines for pushing through the infusion catheter 600. Near the luer hub 610 is a port 612 in fluid communication with the compliant balloon 606. The port 612 can, therefore, be used for inflating the compliant balloon 606 to an expanded position.

[0043] The disclosure above encompasses multiple distinct inventions with independent utility. While each of these inventions has been disclosed in a particular form, the specific embodiments disclosed and illustrated above are not to be considered in a limiting sense as numerous variations are possible. The subject matter of the inventions includes ail novel and nonobvious combinations and subcombinations of the various elements, features, functions and/or properties disclosed above and inherent to those skilled in the art pertaining to such inventions.

[0044] Where the disclosure or subsequently filed claims recite "a" element, "a first" element, or any such equivalent term, the disclosure or claims should be understood to incorporate one or more such elements, neither requiring nor excluding two or more such elements.

[0045] Applicant reserves the right to submit claims directed to combinations and subcombinations of the disclosed inventions that are believed to be novel and non-obvious. Inventions embodied in other combinations and subcombinations of features, functions, elements and/or properties may be claimed through amendment of those claims or presentation of new claims in the present application or in a related application. Such amended or new claims, whether they are directed to the same invention or a different invention and whether they are different, broader, narrower or equal in scope to the original claims, are to be considered within the subject matter of the inventions described herein.