Patent ID: 12246150

DETAILED DESCRIPTION OF THE INVENTION

Exemplary apparatus and methods are described herein. It should be understood that the word “exemplary” is used herein to mean “serving as an example, instance, or illustration.” Any embodiment or feature described herein as “exemplary” is not necessarily to be construed as preferred or advantageous over other embodiments or features. The exemplary embodiments described herein are not meant to be limiting. It will be readily understood that certain aspects of the apparatus and methods can be arranged and combined in a wide variety of different configurations, all of which are contemplated herein.

Furthermore, the particular arrangements shown in the figures should not be viewed as limiting. It should be understood that other embodiments may include more or less of each element shown in a given figure. Further, some of the illustrated elements may be combined or omitted. Yet further, an exemplary embodiment may include elements that are not illustrated in the figures.

As used herein, with respect to measurements, “about” means+/−5%.

As used herein, “coupled” means associated directly, as well as indirectly. For example, a member A may be directly associated with a member B, or may be indirectly associated therewith, e.g., via another member C. It will be understood that not all relationships among the various disclosed elements are necessarily represented.

Unless otherwise indicated, the terms “first,” “second,” etc. are used herein merely as labels, and are not intended to impose ordinal, positional, or hierarchical requirements on the items to which these terms refer. Moreover, reference to, e.g., a “second” item does not require or preclude the existence of, e.g., a “first” or lower-numbered item, and/or, e.g., a “third” or higher-numbered item.

Reference herein to “one embodiment” or “one example” means that one or more feature, structure, or characteristic described in connection with the example is included in at least one implementation. The phrases “one embodiment” or “one example” in various places in the specification may or may not be referring to the same example.

As used herein, apparatus, element and method “configured to” perform a specified function is indeed capable of performing the specified function without any alteration, rather than merely having potential to perform the specified function after further modification. In other words, the apparatus, element, and method “configured to” perform a specified function is specifically selected, created, implemented, utilized, programmed, and/or designed for the purpose of performing the specified function. As used herein, “configured to” denotes existing characteristics of an apparatus, element, and method which enable the apparatus, element, and method to perform the specified function without further modification. For purposes of this disclosure, an apparatus, element, and method described as being “configured to” perform a particular function may additionally or alternatively be described as being “adapted to” and/or as being “operative to” perform that function.

As used herein, an “inflated diameter of the infusion balloon” refers to a diameter measured midway between the first end and the second of the frame.

As used herein, “capillary-action” material is the ability of a liquid to flow in narrow spaces without the assistance of, or even in opposition to, external forces like gravity (e.g., wicking action).

As used herein, “treatment site” refers to the blood vessel or artery in which the drug delivery balloon is deployed to effectively administer a drug solution. The treatment site may further include artificial lumens used, for example, as teaching aids.

As used herein, “drug solution” refers to any flowable material that may be administered into a treatment site. When the drug solution comprises a therapeutic to be administered to a subject, any suitable drug that can be administered in solution can be used. In various non-limiting embodiments, the therapeutic may comprise sirolimus, heparin, and cell-based therapies; and antineoplastic, anti-inflammatory, antiplatelet, anticoagulant, antifibrin, antithrombin, antimitotic, antibiotic, antiallergic and antioxidant substances. Examples of such antineoplastics and/or antimitotics include paclitaxel, (e.g., TAXOL® by Bristol-Myers Squibb Co., Stamford, Conn.), docetaxel (e.g., Taxotere®, from Aventis S. A., Frankfurt, Germany), methotrexate, azathioprine, vincristine, vinblastine, fluorouracil, doxorubicin hydrochloride (e.g., Adriamycin® from Pharmacia & Upjohn, Peapack N.J.), and mitomycin (e.g., Mutamycin® from Bristol-Myers Squibb Co., Stamford, Conn.).

Examples of such antiplatelets, anticoagulants, antifibrin, and antithrombins include aspirin, sodium heparin, low molecular weight heparins, heparinoids, hirudin, argatroban, forskolin, vapiprost, prostacyclin and prostacyclin analogues, dextran, D-phe-pro-arg-chloromethylketone (synthetic antithrombin), dipyridamole, glycoprotein IIb/IIIa platelet infusion balloon receptor antagonist antibody, recombinant hirudin, and thrombin inhibitors such as Angiomax a (Biogen, Inc., Cambridge, Mass.). Examples of such cytostatic or antiproliferative agents include angiopeptin, angiotensin converting enzyme inhibitors such as captopril (e.g., Capoten® and Capozide® from Bristol-Myers Squibb Co., Stamford, Conn.), cilazapril or lisinopril (e.g., Prinivil® and Prinzide® from Merck & Co., Inc., Whitehouse Station, N.J.), calcium channel blockers (such as nifedipine), colchicine, proteins, peptides, fibroblast growth factor (FGF) antagonists, fish oil (omega 3-fatty acid), histamine antagonists, lovastatin (an inhibitor of HMG-CoA reductase, a cholesterol lowering drug, brand name Mevacor® from Merck & Co., Inc., Whitehouse Station, N.J.), monoclonal antibodies (such as those specific for Platelet-Derived Growth Factor (PDGF) receptors), nitroprusside, phosphodiesterase inhibitors, prostaglandin inhibitors, suramin, serotonin blockers, steroids, thioprotease inhibitors, triazolopyrimidine (a PDGF antagonist), and nitric oxide. An example of an antiallergic agent is permirolast potassium. Other therapeutic substances or agents which may be appropriate agents include cisplatin, insulin sensitizers, receptor tyrosine kinase inhibitors, carboplatin, alpha-interferon, genetically engineered epithelial cells, steroidal anti-inflammatory agents, non-steroidal anti-inflammatory agents, antivirals, anticancer drugs, anticoagulant agents, free radical scavengers, estradiol, antibiotics, nitric oxide donors, super oxide dismutases, super oxide dismutases mimics, 4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl (4-amino-TEMPO), tacrolimus, dexamethasone, ABT-578, clobetasol, cytostatic agents, prodrugs thereof, co-drugs thereof, and a combination thereof. Other therapeutic substances or agents may include rapamycin and structural derivatives or functional analogs thereof, such as 40-O-(2-hydroxy)ethyl-rapamycin (known by the trade name of EVEROLIMUS), 40-O-(3-hydroxy)propyl-rapamycin, 40-O-[2-(2-hydroxy)ethoxy]ethyl-rapamycin, methyl rapamycin, and 40-O-tetrazole-rapamycin. In addition, non-therapeutic fluids, such as water, may be used, if the apparatus is being used in a teaching model or training demonstration, for example.

In the following description, numerous specific details are set forth to provide a thorough understanding of the disclosed concepts, which may be practiced without some or all of these particulars. In other instances, details of known apparatus and/or methods have been omitted to avoid unnecessarily obscuring the disclosure. While some concepts will be described in conjunction with specific examples, it will be understood that these examples are not intended to be limiting.

With respect to the figures,FIG.1illustrates a top view of an apparatus100, according to an example embodiment. The apparatus100includes a frame102having a first end104and a second end106. The frame102may range in length from about 50 mm to about 200 mm. In various embodiments, the length of the frame102ranges from about 80 mm to about 200 mm, from about 100 mm to about 200 mm, from about 120 mm to about 200 mm, from about 140 mm to about 200 mm, from about 160 mm to about 200 mm, from about 180 mm to about 200 mm, from about 60 mm to about 120 mm, from about 60 mm to about 100 mm, and from about 10 mm to about 80 mm.

The frame102includes a plurality of struts108arranged between the first end104and the second end106of the frame102. The frame102and corresponding struts108may be made of nitinol or various biocompatible polymers. In optional embodiments, the plurality of struts108have an arrangement that is at least helical, longitudinal, sinusoidal, cross-hatched, or latticed, as non-limiting examples. In one example, the frame102comprises two to eight struts108. The plurality of struts108may be substantially straight from the first end104of the frame102to the second end106of the frame102, or the plurality of struts108may be curved from the first end104of the frame102to the second end106of the frame102. Such a curve may be helical, longitudinal, sinusoidal, for example. In one example, the plurality of struts108comprises at least one strut arranged longitudinally and at least one strut arranged circumferentially. In such an example, the at least one strut arranged circumferentially may be cross-hatched, or latticed, as non-limiting examples. The apparatus100also includes a plurality of channels110disposed within the plurality of struts108of the frame102. In one example, the plurality of channels110form an interconnected network within the plurality of struts108, as illustrated in the front cross-sectional view of the apparatus100inFIG.2. In one example, the plurality of struts108are hollow thereby defining the plurality of channels110.

The apparatus100also includes an infusion balloon112coupled to the frame102. In various examples, the infusion balloon112may be either coupled to an interior of the frame102, coupled to an exterior of the frame102, or embedded within the frame102. The infusion balloon112may be made of compliant materials such as polyurethane, latex, or silicone that results in a low burst pressure of about 5 atm, for example. The infusion balloon112may be configured to transition from a compressed condition (i.e., during delivery of the apparatus100to a treatment site) to an expanded condition. The infusion balloon112may be arranged such that, in the expanded condition, the frame102provides a plurality of openings114that the infusion balloon112is configured to expand through and extend radially outward from the frame102, thereby defining a plurality of grooves116. The plurality of grooves116are defined by the space between adjacent portions of the infusion balloon112that expend through and extend radially outward from adjacent openings114in the frame102, as shown inFIG.2.

The plurality of grooves116may serve to (1) guide the flow of a drug solution and (2) slow the flow of the drug solution to increase the time of contact of the drug with the vessel wall115of the treatment site. The plurality of grooves116are preferably axially aligned with a central axis of the infusion balloon112and may be spiraled, helical, sinusoidal or substantially straight, among other possibilities, in various embodiments. In one particular example, as shown inFIG.4, the infusion balloon112itself may include helical, longitudinal, sinusoidal, cross-hatched, or latticed sections. In another example, as discussed above, the plurality of struts108of the frame are helical, longitudinal, sinusoidal, cross-hatched, or latticed. Spiraled, helical or sinusoidal grooves may be preferred over straight grooves, because the more tortuous grooves provide more surface area to contact the target vessel wall115and further extend the amount of time that the drug solution contacts the target vessel wall115. Further, any pattern of grooves is contemplated including a cross-hatched or waffle pattern, for example. The shape of the plurality of grooves116may mirror the shape of the plurality of openings114in the frame102.

In one example, the frame102includes the plurality of openings114when the infusion balloon112is in both the compressed condition and the expanded condition. In another example, the plurality of openings114in the frame102are only present when the infusion balloon112is in the expanded condition. In such an example, the frame102may have a higher Young's modulus than that of the infusion balloon112such that the frame102and infusion balloon112expand at different rates in response to the same pressure.

The apparatus100also includes a plurality of holes118defined in the frame102. The plurality of holes118are configured to permit fluid communication between the plurality of channels110and the plurality of grooves116. In one example, the plurality of holes118are open when the infusion balloon112is in both the compressed condition and the expanded condition. In another example, the plurality of holes118are closed when the infusion balloon112is in the compressed condition, and the plurality of holes118are open when the infusion balloon112is in the expanded condition. In such an example, each of the plurality of holes118may include valves that open in response to the pressure applied by the infusion balloon112as the infusion balloon112inflates. The apparatus100also includes an infusion hub120arranged at the first end104or the second end106of the frame102. The infusion hub120includes a reservoir122in fluid communication with the plurality of channels110. The reservoir122of the infusion hub120may be configured to receive a drug solution to more evenly distribute the drug solution through the plurality of channels110, out of the plurality of holes118, and into the plurality of grooves116. The reservoir122of the infusion hub120may be circumferential.

In one embodiment, the apparatus100also includes a capillary-action material123coupled to the struts108of the frame102, as shown inFIG.3. Example materials for the capillary-action material123may include biological, bio-synthetic and synthetic microtubules, thin tubes, or porous materials. Capillary-action may result from intermolecular forces between a liquid and surrounding solid surfaces. For example, a diameter of a thin tube is sufficiently small, then the combination of surface tension, caused by cohesion within the liquid, and adhesive forces between the liquid and tubular wall act to propel the liquid along the length of the tube. In operation, the capillary-action material123is configured to transport a fluid along the plurality of struts108of the frame102thereby placing the fluid in contact with a treatment site. In various embodiments, the capillary-action material123is configured to expand with the frame102. In some embodiments, the microtubules and thin tubes may be arranged with their first ends adjacent to the infusion hub120and their second ends arranged in a staggered configuration along the length of the plurality of struts108to evenly distribute the fluid along the length of the plurality of grooves116.

In one embodiment, the apparatus100also includes a catheter124having at least one lumen. In such an example, the apparatus100may also include a balloon inflation port126in communication with the at least one lumen, a drug delivery port128in communication with the at least one lumen through which a drug solution is administered, and a guidewire port130in communication with the at least one lumen for receiving a guidewire. The apparatus100may also include an occlusion balloon132arranged adjacent to the first end104of the frame102. The occlusion balloon132and the infusion balloon112are configured to be in fluid communication with the balloon inflation port126such that the balloon inflation port126is used to inflate both the occlusion balloon132and the infusion balloon112. In one example embodiment, the drug delivery port128may be bifurcated, as shown inFIG.1, such that two, three, four or more different drug solutions or other solutions may be introduced into the drug delivery port108as deemed appropriate for treatment.

The occlusion balloon132may be composed of atraumatic compliant materials such as polyurethane, latex, or silicone, among other possibilities, that results in a low burst pressure of about 5 atm, for example. However, the occlusion balloon132may be configured to withstand greater pressures, for example up to about 20 atm. The occlusion balloon132may be configured to conform to the shape and size of the treatment site via low pressure inflation, about 1 to 2 atm. Once inflated, the occlusion balloon132may provide occlusion in the treatment site to allow for drug delivery into the treatment site downstream from the occlusion balloon132to minimize dilution of the drug solution from blood flow. The inflated diameter of both the infusion balloon112and the occlusion balloon132may range from about 2.5 mm to about 24 mm. The length of the occlusion balloon132may range from about 20 mm to about 40 mm. In one embodiment, the inflated diameter of the occlusion balloon132ranges from about the same as the inflated diameter of the infusion balloon112to about 2 mm to about 6 mm larger than the inflated diameter of the infusion balloon112. The occlusion balloon132and the frame102may be separated from each other by a distance ranging from about 2 mm to about 20 mm. This distance allows adequate pressure to be maintained in the system such that the drug solution may be effectively advanced into and along the plurality of grooves116. In operation, the occlusion balloon132may be inflated prior to the introduction of the drug solution into the infusion hub120.

In one example, the at least one lumen of the catheter124comprises two parallel lumens133.FIG.5illustrates a front cross-sectional view of the two lumens133. In particular, the apparatus100may include an infusion lumen134in communication with the balloon inflation port126and may be configured to receive a saline contrast mixture, or any other suitable fluid medium, to inflate the occlusion balloon132and the infusion balloon112. Further, the apparatus100may include a guidewire lumen136in communication with the drug delivery port128and the guidewire port130. In one embodiment, the second lumen116may be sized and shaped to receive a drug solution. In one embodiment, the second lumen116may also be sized and shaped to receive a guidewire having a diameter in the range from about 0.25 mm to about 1 mm, and preferably in a range from about 0.254 mm to about 0.9652 mm. The guidewire lumen136may include one or more drug delivery channels138extending the length of the guidewire lumen136. These drug delivery channels138may be used to transport the drug solution from the drug delivery port128to a treatment site. The guidewire lumen136may also include a guidewire channel140extending the length of the guidewire lumen136. In another example, the guidewire lumen136may include a single channel for both the guidewire and drug solution.

In such a configuration, the guidewire may be removed after use so that the drug solution can pass through the guidewire lumen136. In operation, the apparatus100may be configured to infuse the drug solution while the guidewire is in the guidewire lumen136. In such a configuration, the guidewire lumen136may have a larger diameter than the guidewire from a location between the guidewire port130and the drug delivery port128until just distal to the infusion hub120. The guidewire lumen136would shrink down to about the diameter of the guidewire just distal to the infusion hub120to the distal end of the frame102. Further, the guidewire lumen136would shrink down to about the diameter of the guidewire proximal to the infusion hub120, so as to prevent the drug solution from exiting the guidewire port130. In another example, a flange or one-way valve may be used to prevent the drug solution from exiting the guidewire port130. In yet another example, a portion of the catheter124surrounded by the frame102has a chamber142in fluid communication with the infusion port120. In such an example, when the infusion balloon112is in the expanded condition, the chamber142configured to inflate radially inward within the at least one lumen to thereby form a seal with a guidewire distal to the infusion hub120. Other configurations are possible as well.

In another embodiment, the balloon inflation port126, the drug delivery port128, and the guidewire port130may be coupled to three concentrically aligned lumens144. For example,FIG.6illustrates a front cross-sectional view of the three lumens144. As shown inFIG.6, the three concentrically aligned lumens144comprise a guidewire lumen136, a drug delivery lumen146, and an infusion lumen134. The guidewire lumen136may be in communication with the guidewire port130and may be sized and shaped to receive a guidewire having a diameter in the range from about 0.25 mm to about 1 mm, and preferably in a range from about 0.254 mm to about 0.9652 mm. The drug delivery lumen146may be in communication with the drug delivery port128. The drug delivery lumen146may include a plurality of flexible spacers148that extend between the guidewire lumen136and the infusion lumen134to maintain the structural integrity of the drug delivery lumen146. These spacers148, in combination with the drug delivery lumen146and the guidewire lumen136, may further define one or more drug delivery channels138extending the length of the drug delivery lumen146. As discussed above, these drug delivery channels134may be used to transport the drug solution from the drug delivery port128to a treatment site. The infusion lumen134may be in communication with the balloon inflation port126. The infusion lumen134may also include a plurality of flexible spacers150to help maintain the structural integrity of the infusion lumen134. These spacers150, in combination with the infusion lumen134and drug delivery lumen146, may also define a plurality of fluid delivery channels152extending the length of the infusion lumen134. These fluid delivery channels152may be in fluid communication with the occlusion balloon132, the infusion balloon112, and the reservoir122of the infusion hub120.

In use, the apparatus100of any one of embodiments described above is delivered via a catheter over a guidewire to a treatment site. Once positioned in the treatment site, the occlusion balloon132is inflated to provide occlusion in the treatment site to allow for drug delivery into the treatment site downstream from the occlusion balloon132to minimize dilution of the drug solution from blood flow. The infusion balloon112is then inflated, such that the frame102provides a plurality of openings114that the infusion balloon112is configured to expand through and extend radially outward from the frame102, thereby defining a plurality of grooves116. A drug solution is then provided to the drug delivery port126and into the reservoir122of the infusion hub120. From there, the drug solution transitions through the plurality of channels110, out of the plurality of holes118, and into the plurality of grooves116and contacts the vessel wall115at the treatment site. The drug solution advances downstream into and along the plurality of grooves116defined in the outer surface of the infusion balloon112. Once the drug solution exits the plurality of grooves116at the second end106of the frame102, the drug solution may be cleared via normal arterial blood flow and ultimate physiological function.

FIG.7illustrates another example apparatus200, according to an example embodiment. The apparatus200may include one or more features of the apparatus100described above. As shown inFIG.7, the apparatus200includes a frame202having a first end204and a second end206. The frame202includes a plurality of struts208arranged between the first end204and the second end206of the frame202. The apparatus200also includes a capillary-action material223coupled to the plurality of struts208of the frame202. The apparatus200also includes an infusion balloon212coupled to the frame202. The infusion balloon212may be configured to transition from a compressed condition (i.e., during delivery of the apparatus200to a treatment site) to an expanded condition. The infusion balloon212may be arranged such that, in the expanded condition, the frame202provides a plurality of openings214that the infusion balloon212is configured to expand through and extend radially outward from the frame202, thereby defining a plurality of grooves216. The plurality of grooves116are defined by the space between adjacent portions of the infusion balloon112that expend through and extend radially outward from adjacent openings114in the frame102, as shown inFIG.8. The apparatus200also includes an infusion hub220arranged at the first end204or the second end206of the frame202. The infusion hub220includes a reservoir222and a plurality of openings219to permit fluid communication with the capillary-action material.

As discussed above, example materials for the capillary-action material223may include biological, bio-synthetic and synthetic microtubules, thin tubes, or porous materials. Capillary-action may result from intermolecular forces between a liquid and surrounding solid surfaces. For example, a diameter of a thin tube is sufficiently small, then the combination of surface tension, caused by cohesion within the liquid, and adhesive forces between the liquid and tubular wall act to propel the liquid along the length of the tube. In operation, the capillary-action material223is configured to transport a fluid along the plurality of struts208of the frame202thereby placing the fluid in contact with a treatment site. In various embodiments, the capillary-action material223is configured to expand with the frame202. In some embodiments, the microtubules and thin tubes may be arranged with their first ends adjacent to the infusion hub220and their second ends arranged in a staggered configuration along the length of the plurality of struts208to evenly distribute the fluid along the length of the plurality of grooves216.

In one embodiment, the apparatus200further includes a plurality of channels210disposed within the plurality of struts208of the frame202. In such an example, the apparatus200further includes a plurality of holes218defined in the plurality of struts208, as shown inFIG.8. The plurality of holes218are configured to permit fluid communication between the plurality of channels210and the capillary-action material223.

FIG.9illustrates yet another example apparatus300, according to an example embodiment. The apparatus300may include one or more features of the apparatus100and/or the apparatus200described above. As shown inFIG.9, the apparatus300includes a frame302having a first end304and a second end306. The frame302includes a plurality of struts308arranged between the first end304and the second end306of the frame302. The apparatus300further includes an infusion balloon312coupled to the frame302. The infusion balloon312may be configured to transition from a compressed condition (i.e., during delivery of the apparatus300to a treatment site) to an expanded condition. The infusion balloon312may be arranged such that, in the expanded condition, the frame302provides a plurality of openings314that the infusion balloon312is configured to expand through and extend radially outward from the frame302, thereby defining a plurality of grooves316. The apparatus300further includes an occlusion balloon332arranged adjacent to the first end304of the frame302. The occlusion balloon332and the infusion balloon312are configured to be in fluid communication with a balloon inflation port. The apparatus300further includes one or more drug delivery ducts313disposed between the occlusion balloon332and the infusion balloon312. In other words, these drug delivery ducts313may be downstream from the occlusion balloon132in operation. The number of drug delivery ducts313may depend upon the distance between the occlusion balloon132and the infusion balloon312and/or the diameter of the drug delivery ducts313, among other possibilities. In one particular example, there are between 2 and 24 drug delivery ducts313.

FIG.10is a simplified flow chart illustrating a method400according to an exemplary embodiment. Although the blocks are illustrated in a sequential order, these blocks may also be performed in parallel, and/or in a different order than those described herein. Also, the various blocks may be combined into fewer blocks, divided into additional blocks, and/or removed based upon the desired implementation.

At block402, the method400involves delivering the apparatus of any one of embodiments described above via a catheter over a guidewire to a treatment site. The drug delivery balloon apparatus may be introduced and delivered in a standard coaxial manner, via over-the-wire or rapid exchange techniques, as examples.

At block404, the method400involves inflating the occlusion balloon and the drug delivery balloon, thereby causing the frame to expand and the infusion balloon to expand through the plurality of openings and extend radially outward thereby defining a plurality of grooves. In one embodiment, the occlusion balloon and the drug delivery balloon may be inflated by injecting a saline contrast mixture, for example, into a balloon inflation port. The saline contrast mixture may then be advanced through an infusion lumen of the catheter to the occlusion balloon and the drug delivery balloon until both balloons are inflated. The occlusion balloon may inflate at a slightly faster rate, since the occlusion balloon and the drug delivery balloon are connected in series such that the occlusion balloon receives the saline contrast inflation mixture first. In another embodiment, the occlusion balloon and drug delivery balloon may be inflated using any other suitable fluid medium.

After both the occlusion balloon and the drug delivery balloon have been inflated, the method400continues at block406with injecting a drug solution into a drug delivery lumen of the catheter in fluid communication with the infusion hub. In one embodiment, the drug delivery lumen is in fluid communication with a drug delivery port of the catheter. In one particular example, the drug delivery port is bifurcated, such that two, three, four or more different drug solutions or other solutions may be introduced into the drug delivery port as deemed appropriate.

At block408, the method400involves advancing the drug solution through the drug delivery lumen to the infusion hub into the plurality of channels of the frame through the plurality of holes to the plurality of grooves and into the treatment site. At this stage, the space between the occlusion balloon and the drug delivery balloon acts as a reservoir storing the drug solution as the drug solution is delivered via the drug delivery ducts. Due to the pressure at which the drug solution is being introduced to the drug delivery lumen, the drug solution advances downstream into and along the plurality of grooves defined in the outer surface of the infusion balloon. The injection of the drug solution is performed at a fluid pressure at or below about 1 atm to about 4 atm. Once the drug solution exits the plurality of grooves at the second end of the frame, the drug solution may be cleared via normal arterial blood flow and ultimate physiological function. In one example, the inflated diameter of the occlusion balloon ranges from about the same as the inflated diameter of the infusion balloon to about 2 mm to about 6 mm larger than the inflated diameter of the infusion balloon.

In one example, a common lumen is used for the drug delivery lumen and the guidewire lumen, and a portion of the catheter surrounded by the frame has a chamber in fluid communication with the infusion port. In such an example, the method200may further include inflating the chamber of the catheter to thereby expand a portion of an interior wall of the catheter to form a seal with the guidewire distal to the infusion hub.

While various aspects and embodiments have been disclosed herein, other aspects and embodiments will be apparent to those skilled in the art. All embodiments within and between different aspects of the invention can be combined unless the context clearly dictates otherwise. The various aspects and embodiments disclosed herein are for purposes of illustration and are not intended to be limiting, with the true scope and spirit being indicated by the claims.