Patent Application
20220331555
The present technology generally relates to intravascular catheter systems, and more particularly to intravascular catheter systems for delivery of therapeutic agents, diagnostic agents, and/or other substances into the tissue and wall layers of blood vessels and other body conduits.
Some vascular diseases and clinical conditions can benefit from the delivery of therapeutic drugs, or other agents, into and/or around a blood vessel wall or other body conduit. For example, local drug delivery catheters and implants have been used to deliver anti-restenosis drugs to an inner tissue surface of a blood vessel to prevent or reduce the severity of restenosis after a balloon angioplasty or stent procedure in the blood vessel. Local drug delivery catheters include infusion catheters with or without side-holes, drug-coated balloon catheters, balloon catheters with porous walls or porous outer channels, or double balloon catheters with a porous shaft for drug delivery in between the two balloons. However, there are significant obstacles encountered with these types of devices. For example, the drug delivery catheters must be able to deliver adequate quantities of a drug to the vessel wall without either injuring the wall or compromising flow. Other technologies include local injection catheters with needles that infuse drug into the adventitial space of a vessel wall. An example of such a device is the Bullfrog Catheter (Mercator Medsystems, Emeryville, Calif.) that includes a single needle for drug delivery directed radially outward from the catheter through the vessel wall and into the perivascular space when the balloon is inflated. Another example is the Peregrine System Infusion Catheter (Ablative Solutions, San Jose, Calif.) which is also designed for needle puncture and infusion into the perivascular space of a blood vessel. The Peregrine System has three needles and relies on a pre-shaped spring structure of the needle elements to direct the needles completely through the vessel wall. These devices, as well as other perivalvular space drug delivery systems, puncture through all layers of the vessel wall and are thus limited to delivering drugs to the perivascular space at discreet sites.
Intravascular stents with drug-eluting capabilities, including metallic stents with drug-impregnated coatings or drug-impregnated polymer stents, have also been developed for local drug delivery to reduce the restenosis or re-occlusion rate after implantation of the stent. These devices are used when stent implantation is the primary therapy for treatment of vessel stenosis but suffer from late thrombosis due to delayed or impaired healing of the endothelium around the stent caused by the drug and/or the polymer coating. Additionally, these devices are limited to procedures that already involve stent implantation.
Many aspects of the present disclosure can be better understood with reference to the following drawings. The components in the drawings are not necessarily to scale. Instead, emphasis is placed on clearly illustrating the principles of the present disclosure. Reference numbers/indicators are used consistently throughout the drawings and description for ease in referring to items having similar structures, features, and/or functions. Identical reference numbers/indicators are not indicative that the items are identical.
The present technology generally relates to medical systems, devices and methods for delivery of drugs, other therapeutic agents, diagnostic agents, and/or other fluids or substances (collectively referred to as “infusates”) into the tissue walls, intraluminal tissues, intraluminal spaces, layers of various body conduits, and/or a space adjacent to the body conduits (e.g., perivascular space). Some embodiments of the present technology provide the delivery of the infusates into a space created between the outer and inner boundaries of a blood vessel wall (e.g., the medial layer of the vessel wall and/or to the adventitial layer of the vessel wall, sometimes also referred to as an intramural space) and/or into the perivascular space outside the vessel wall. Some embodiments of the present technology provide the delivery of the infusates into intravascular tissue or other anatomical structures (e.g., atherosclerotic plaque, fibrous tissue, thrombus, other stenotic tissue, and/or other structures/tissue within the vessel), between the intravascular tissue/structure and the natural inner surface of the vessel wall, and/or between an intravascular implant (e.g., a stent, graft, or stent graft) and the inner surface of the vessel wall. Some embodiments of the present technology provide the delivery of the infusates into an intraluminal space to help break down an obstructive material in a vessel lumen, such as thrombus and/or other occlusive material. For example, the infusate can be delivered into an intraluminal space adjacent the obstructive material, into the obstructive material, and/or into a boundary layer between the obstructive material and a vessel wall. Unlike current methods of local drug delivery, the delivery of the infusates into a wall layer (e.g., intramural space) or other anatomical structure is expected to retain the infusates in tissue layers rather than being washed out if delivered superficially to the inner surface, into a wall layer (intramural) or other anatomical structure (e.g., an obstructive tissue such as a partial or total occlusion, thrombotic tissue, artificial vessel-shunts, and/or any other suitable structure). Further, the infusate delivery disclosed herein is more targeted to the vessel wall and/or other anatomical structure than current perivascular infusion devices.
The term “intramural,” which refers to a location within the layers of vessel wall tissue between the innermost and outermost surfaces of a vessel wall, is used frequently throughout the specification to refer to devices, systems, and locations of drug delivery. However, the “intramural” systems, devices, and methods described herein can additionally, or alternatively, be used to deliver infusates to other in a similar manner and using similar mechanisms as described herein with respect to intramural fluid/agent delivery. For example, the intramural systems, devices, and methods described herein can additionally, or alternatively, be used to deliver infusates into the perivascular space just beyond the outer surface of the vessel wall, other intravascular tissue, anatomical structures, a space between intravascular tissue and the natural inner surface (also referred to as an inner layer) of the vessel wall, an intravascular implant and/or other internally positioned devices, and/or a space between an intravascular implant (or other device) and the inner surface of a vessel.
The term “tissue,” as used herein, can include muscle, epithelial, connective and nervous tissue. Further, when discussed with respect to the structures through which the devices herein penetrate and/or deliver infusates, “tissue” can also refer to atherosclerotic plaque, fibrous tissue, thrombus, other stenotic tissue, and/or other structures within or surrounding a vessel.
Infusate delivery systems (sometimes referred to herein as “systems”) disclosed herein include devices for accessing a layer of a vessel wall at one or more sites in a section of a blood vessel (e.g., an artery or vein wall) and a means for infusing infusates into the accessed vessel wall layer and/or the perivascular space. The systems disclosed herein can also include variations in the number of puncture sites per device, controls of the perfusion parameters (e.g., flow rate or pressure), control of the thickness and length of the vessel layer accessed, and/or control of other functional parameters associated with hydrodissection, infusate delivery, and/or vessel layer access. In some embodiments, the systems include a means to provide intravascular imaging, such as an imaging catheter with an imaging element to provide an image of the treatment site. The imaging catheter can be an intravascular ultrasound (“IVUS”) catheter that captures ultrasound images from within the vessel and/or any other suitable imaging device. The devices disclosed herein can deliver the infusates into an intramural space within the layers of a blood vessel wall and/or perivascular space. The intramural and/or perivascular delivery is expected to increase a drug retention period at the target site, reduce the distance from the target site to the endothelial layer (thereby reducing the distance an agent must travel, disperse, be directed, etc. once delivered), and provide the devices disclosed herein with a wide range of infusion pressure, flow rate, and volume when delivering infusates.
In some embodiments, the infusate delivery system includes an infusion device that is able to selectively infuse into an intraluminal space (e.g., adjacent an obstruction and/or stenosis), into an obstruction or partial obstruction, and/or into an intramural tissue layer). Additionally, or alternatively, the infusion device can access layers of variable thickness up to and beyond the thickness of the vessel wall. As a result, the infusion device can access spaces within the vessel wall and/or outside of the vessel. By delivering an infusate selectively into obstructive material located within an intraluminal space, an intramural space, and/or selectively into an extraluminal space, the infusion device is expected to provide multiple clinical benefits. For example, the infusion device can provide localized drug delivery into selective luminal target tissue at higher concentrations than systemic delivery, with a higher dwell period than typically provided by infusion catheters, because the agents are delivered into intraluminal tissue rather than into the blood flow, and/or deliver the drug closer to endothelial and/or or medial layers than existing local injection catheters which deliver fluid only to extraluminal tissue.
As used herein, the term “obstruction” can refer to tissue or other material within a blood vessel that creates either a complete vessel occlusion or a partial vessel occlusion, such as a narrowing of the vessel (i.e., a stenosed vessel).
In some embodiments, the infusion device is capable of delivering anti-inflammatory agents into the vessel wall (e.g., into the wall of a blood vessel), into a residual thrombotic tissue, and/or into a boundary layer between thrombotic tissue and the vessel wall. In such embodiments, the infusion device can help counter the after-effects of a deep vein thrombosis (DVT) event, including venous wall thickening and scarring that can lead to impaired flow and/or failure of native venous valves.
In some embodiments, the infusion device is capable of infusing a thrombolytic agent and/or another enzymatic agent into an occlusive material and/or into a boundary layer between an intraluminal obstructive material and the vessel wall. In such embodiments, the infusion device can help facilitate a natural removal of blockage in the vessel (e.g., via gradual breakdown and removal through blood flow) and/or provide a pre-treatment for a subsequent thrombectomy procedure (e.g., by beginning to break up the obstructive material before a procedure to more fully remove it).
Specific details of several embodiments of the technology are described below with reference to
The accompanying Figures depict embodiments of the present technology and are not intended to be limiting of its scope. The sizes of various depicted elements are not necessarily drawn to scale, and these various elements can be arbitrarily enlarged to improve legibility. Component details can be abstracted in the Figures to exclude details such as position of components and certain precise connections between such components when such details are unnecessary for a complete understanding of how to make and use the present technology. Many of the details, dimensions, angles, and other features shown in the Figures are merely illustrative of particular embodiments of the disclosure. Accordingly, other embodiments can have other details, dimensions, angles, and features without departing from the spirit or scope of the present technology.
With regard to the terms “distal” and “proximal” within this description, unless otherwise specified, the terms can reference a relative position of the portions of a catheter subsystem with reference to an operator and/or a location in the vasculature. Also, as used herein, the designations “rearward,” “forward,” “upward,” “downward,” etc., are not meant to limit the referenced component to use in a specific orientation. It will be appreciated that such designations refer to the orientation of the referenced component as illustrated in the Figures and that the systems of the present technology can be used in any orientation suitable to the user.
As best illustrated in
As discussed in more detail below, the guidewire lumen 221 allows a guidewire and/or an imaging device to move within the length of the device and through the distal portion 110 of the device. For example, a guidewire can extend through the handle 130, the catheter shaft 120 via guidewire lumen 221 and out of the second exit port 113b to guide the distal portion 110 into position adjacent a target site. Once in position, the guidewire can be retracted, and an imaging component (sometimes referred to as a “visualization device”), for example an IVUS catheter, can be advanced through the guidewire lumen 221 to a position within the distal portion 110 proximal to the distalmost end and/or out of the second exit port 113b. The balloon lumens allow an inflation device (not shown) to be fluidly connected to the balloon 111 to inflate and/or deflate the balloon 111, as desired, during a procedure. In various embodiments, the inflation device can be carried by and/or fluidly coupled to the handle 130 (
The needle 140 is slidably positioned in the needle lumen 222 and can extend through the catheter shaft 120 and exit out of first exit port 113a. During a procedure using the device 101, the needle 140 can retract (e.g., in response to movement of the actuating component 150 on the handle 130 (
Referring to
In the illustrated embodiment, the distal portion 110 includes a transition portion 214 (also referred to as a “transition surface”) from the outer surface (e.g., from the housing 112) to the offset surface 215. The transition portion 214 can be a ramp that is angled (e.g., sloping upward, at an obtuse angle relative to the offset surface 215, etc.) or perpendicular with respect to the offset surface 215. Together, the outer surface, the transition portion 214, and the offset surface 215 are configured to conform tissue (e.g., a vessel wall layer) in contact with the distal portion 110 to cover at least a portion of the first exit port 113a. Further, in the illustrated embodiment, the balloon 111 is positioned on the opposite side of the distal portion 110 as the offset surface 215. Accordingly, as the balloon 111 inflates, the balloon 111 can push the outer surface, the transition portion 214, and the offset surface 215 against tissue at and/or adjacent the target site. As a result. the pressure from the balloon 111 can cause the tissue to conform against the distal portion 110. The length of the offset surface 215 can determine the length of the vessel wall that can be accessed by the needle 140, and therefore the length of an intramural space that can created and/or dosed with an infusate therein. The length of the offset surface 215 can vary based on one or more intended uses for the device 101. In various embodiments, for example, the length of the offset surface 215 can be between about 5 millimeters (mm) to about 50 mm, or from about 10 mm to about 30 mm. However, in various embodiments, the length of the offset surface 215 can be shorter than 5 mm, or longer than 50 mm. In some embodiments, the balloon 111 is replaced with another suitable expandable element, such as an expanding cage (e.g.,
Referring back to
Once the distal portion 110 is positioned, the balloon 111 is inflated, as shown in
Once the entirety of the opening in the needle 140 is enclosed in a space S within the vessel wall, as illustrated in
In the embodiments illustrated in
In another example, as illustrated in
In some embodiments, the infusion site can be an intramural site (e.g., a space within the vessel wall W, such as any of the intramural spaces accessed by the device in
For example, as illustrated in
Returning to the description of
In the illustrated embodiment, the tube 242 has a tapered leading edge that defines an atraumatic surface that helps facilitate advancement of the tube 242 and the needle 140 through a puncture point in the vessel wall 404. During a procedure, as seen in
After the needle 140 and tube 542 have advanced into the intramural space, the needle 140 can be pulled back to expose the side holes 544, for example as illustrated in
In the illustrated embodiment, the plug 645 is positioned on a lower portion of the distal opening 648, thereby offsetting the distal opening 648 towards the distal-most tip of the needle 640. Said another way, the plug 645 biases the open space of the distal opening 648 at least partially above a central axis needle of the needle 640 (extending along the longitudinal axis of the needle 640). The offset allows the needle opening 648 to be enclosed within a vessel wall before the needle 640 is fully advanced into the vessel wall. That is, while an upper portion of the distal tip of the needle 640 has penetrated a vessel wall (e.g., corresponding to the open space of the distal opening 648), the lower portion (e.g., corresponding to the space of the distal opening 648n blocked by the plug 645) can still be outside and/or engaging the vessel wall. In this position, the plug 645 can contact the vessel wall while the open space of the needle opening 648 is fully within the vessel wall. Further, the plug 645 can create a fluid tight seal with the vessel wall, allowing a dissection fluid (e.g., saline) to flow out of the needle opening 648 to create the intramural space within a thinner layer of the vessel wall (e.g., less that the full thickness of the needle 640). Additionally, or alternatively, the offset of the needle opening 648 allows an infusate to be delivered to the vessel wall close to the inner endothelial layer of the blood vessel while still enclosed in an intramural space for retention. The offset of the needle opening 648 can be advantageous if the vessel wall is very thin, (e.g., for a vein wall with less than 1 mm wall thickness) and a thin layer is required to stay within an intramural space in the vessel wall rather than exiting into the outer adventitial or perivascular space.
In some embodiments, the device 101 includes features to adjust the needle height H. For example,
In some embodiments, the needle guide 1402 extends from the first exit port 1413a along the shaft 1420 and is operably coupled to a needle height adjustor (not shown) at the handle 130 (
In various other embodiments, the infusion devices disclosed herein can include various additional (or alternative) features to adjust the height of the needle. For example, the tube 542 (
In some embodiments, the user (e.g., a surgeon or other medical care provider) can predetermine a thickness of the intraluminal tissue, vessel wall layer, and/or perivascular space they would like to access and deliver an infusate into, adjust the height of the needle, then puncture the vessel wall. Additionally, or alternatively, the user can perform an infusion in one layer at a first depth (and therefore with a first layer thickness), retract the needle out of the wall, adjust the needle height, then re-puncture to perform an additional infusion at a second layer at a second depth. In some embodiments, the device can access the target site multiple times to perform the infusion at multiple layers with varying depths (e.g., the first and second layers from above). In some embodiments, the user can predetermine two or more target sites in the same vessel (or in varying vessels) and access the multiple target at multiple depths.
In any of the embodiments discussed above, intravascular imaging can help facilitate the infusion procedure. For example, during an infusion procedure, the user can intravascularly image the target site in a vessel before inserting and/or positioning the device 101 (
In some embodiments, once positioned, the guidewire 817 is removed and replaced with the imaging component 816 (e.g., an imaging catheter IC (e.g., including an optional component-specific guidewire)). In some embodiments, the device 801 includes separate lumens for the imaging component 816 and the guidewire 817 (e.g., adjacent to each other and/or spaced apart from on another).
In some embodiments, as illustrated in
As best illustrated in
In some embodiments, the balloon is a non-compliant, or limited compliance, balloon and the needle height is determined by the inflated balloon diameter combined with the dimensions of the rigid offset components 1005. In some embodiments, as the balloon is inflated (e.g., the diameter increases), the needle height can also increase accordingly. In some embodiments, the balloon is a compliant balloon and the needle height is determined by the amount of balloon inflation by the user. For example, in a case where the user wants to infuse into an intraluminal site (e.g., a thrombotic material and/or other obstructive material), the balloon can be inflated to a diameter that is smaller than the diameter of the vessel lumen. In this example, the needle can then advance into the intraluminal site and not puncture the vessel wall W. In various embodiments, a similar type of advancement can be achieved by a device that includes a non-compliant balloon that is smaller than the vessel diameter. Additionally, or alternatively, the dimensions of the offset component 1005 can be configured such that the needle puncture height is more than one vessel wall thickness past the balloon surface. Accordingly, the needle then punctures entirely through the vessel wall to a location outside the vessel (e.g., in the perivascular space around the vessel).
However, in the illustrated embodiment, the needles 1740 can extend distal to the distal portion 1710 of device 1701 in a direction generally parallel (or fully parallel) to a longitudinal axis of the catheter shaft 1720 of device 1701. As a result, the device 1701 can manipulate and/or deliver an infusate into an infusion site (e.g., into intraluminal tissue) distal to the distal end 1710. Further, because the device 1701 includes multiple needles 1740 and corresponding needle-guiding components 1724, the device 1701 can deliver the infusion to multiple infusion sites at one time (or sequentially without relocating the distal portion 1710).
In the illustrated embodiment, each of the needles 1740 extends through a corresponding lumen 1722 (
In some embodiments, the expandable device 1711 is a balloon. The balloon can be compliant, semi-compliant, or non-compliant. The balloon compliance, the balloon size with respect to the vessel, and/or the balloon inflation strategy can all be selected and/or controlled to access specific, predetermined regions of an intraluminal site, an intramural site, and/or an extraluminal site. For example, the balloon can be inflated to target a boundary layer between an obstructive material and the vessel walls. In another example, the balloon can be inflated to a diameter that presses the infusion assemblies 1724 into apposition with the vessel walls, allowing the needles 1740 to access extraluminal sites for infusion.
In some embodiments, as best illustrated in
During advancement of the penetrating member 1240, one or more fluids (e.g., a dissecting fluid and/or an infusate) can be delivered through a lumen in the penetrating member 1240 at a controlled pressure or flow rate. The pressure generated by the fluid flow can separate the layer between the tissue T and the wall W. Once the penetrating member 1240 has advanced a desired distance, an infusate can be delivered into the tissue T and/or between the tissue T and the vessel wall W. In some embodiments, the infusate is at least partially delivered through the penetrating member 1240 during the advancement step (e.g., in a diluted form in the dissection fluid). Although
In some embodiments, the tissue in the vessel wall W can grow around and/or through the implant 1380 over time (not shown). In some such embodiments, the penetrating member 1340 advances along a trajectory substantially parallel to the longitudinal axis of the distal portion 1310 through the tissue ingrowth and/or between the implant 1380 and the vessel wall W to deliver the infusate into the tissue. The infusate can then disperse into the vessel V. In some embodiments, the tissue penetrating member 1340 can deliver the infusate into an implant (not shown) that includes a thickness (e.g., a foam) and/or a cavity (e.g., an expandable member). In such embodiments, the infusate can then dispel from the implant over time (e.g., through porous walls of the implant, through openings in the implant, through valves of the implant, and the like).
All embodiments of an infusion device described above include a proximal handle (e.g., the handle 130 of
As further illustrated in
A procedure utilizing the device 101 can begin with the needle accessing the vessel wall. In some embodiments, the needle's access is at least partially facilitated through a hydrodissection that includes infusing pressurized saline (or other suitable fluid) using inflation device 164. Once the vessel wall layer is accessed and an intramural space is created, the valve 162 can be turned towards the line with the infusion component 166. In some embodiments, the infusate is then automatically delivered in a controllable matter, for example by a pump in the infusion component 166, into the intramural space. In some embodiments, the access is completed without a hydrodissection fluid, for example by directly advancing the needle 140 of the distal portion of the device and into a vessel wall layer. In some embodiments without the hydrodissection, the valve 162 is movable between a closed position and an open position with the infusion component 166. In some embodiments without the hydrodissection, the infusion component 166 includes an internal mechanism (e.g., a valve, switch, and the like) to regulate flow out of the infusion component 166. In some embodiments, the infusion component 166 is manually operated, allowing the infusate to be delivered at a manually controlled rate. In some such embodiments, the infusion component 166 includes an indicator that allows the user access to real time feedback about infusion pressure (e.g., a pressure gauge), a location of the needle and/or the tube (e.g., a location indicator based on the presence or absence of a pressure spike), and/or other relevant information. In some embodiments, delivery of the infusate can be automated such that the device 101 maintains a constant pressure during infusate delivery. In some embodiments, the valve 162 can be turned towards the line with the saline (or other suitable fluid) after delivering the infusate to provide a bolus of liquid. This can help ensure the infusate has been fully flushed from the device and delivered at the target site.
As further illustrated in
In various embodiments, the guidewire lumen 221 exits the shaft 120 at a location distal to the handle 130. This can accommodate various lengths of imaging catheters for use with system 100. For example, some imaging catheters may not be long enough to extend from the distal end 110 of the shaft 120 through the handle 130, but may have a length suitable for extending from the distal end 110 of the shaft 120 to an exit at a port distal to handle 130. This embodiment can also reduce the components extending through the handle 130, thereby allowing for a lower profile handle and/or additional versatility for the system 100.
In some embodiments, the handle 130 has an actuator which can pull back the catheter shaft 120 and/or distal portion 110 while maintaining the position of the needle 140 in the vessel. During a procedure, this allows the distal portion 110 and the balloon 111 to be pulled away from the target site (at or near the puncture location or near the first exit port 113a) while the infusate is delivered. The removal of the distal portion 110 and the balloon 111 can allow a clearer visualization of the infusion, for example by an intravascular imaging catheter extending through the guidewire lumen 221 and/or by an external fluoroscopy component.
In various embodiments, the devices and/or their components discussed above can vary in size depending on the size of the target vessel or body conduit, the size of the target site, and/or the desired maximum flow rate through the device. For example, the needle can have a size of between about 20 gauge and about 35 gauge. In some embodiments, the needle can be smaller at the distal portion to facilitate access to the vessel wall, then step up in size and/or be connected to a larger tube so that flow resistance through the length of the lumen within the needle is reduced. Additionally, or alternatively, the expansion element (either a balloon or mechanical expansion), can expand to provide adequate vessel wall apposition in vessels and have a maximum inner diameter from about 6 mm up to about 22 mm.
In some embodiments, the device is coupled to an energy source that can be used in conjunction with intramural agent delivery to increase diffusion and uptake of the agent into the target site. Examples of energy sources include electric current, magnetic field, ultrasound, pulsed light, or temperature, each of which are expected to improve the efficiency of the infusate delivery and/or absorption by the tissue. The energy source can be carried by and/or incorporated into the distal portion of the device. For example, an electrode can be attached to the distal portion of the device to generate an electric current, magnetic field, and/or an ultrasound pulse. Additionally, or alternatively, a separate tool catheter can be deployed in a central lumen of the device (e.g., within the guidewire lumen 221 (
In some embodiments, the infusion delivery device is coupled with another therapeutic device. For example, the guidewire lumen 221 (
In various embodiments a method of using a device of the type disclosed above with reference to
The balloon (or other expansion element) is then expanded such that the vessel wall is pressed against the transition portion and the offset surface of the distal portion 110. The needle, which is connected to a pressurized fluid source (e.g., saline), is then advanced from the first exit port and pierces the vessel wall, then pressurized fluid is used to further access an intramural space within the vessel wall. That is, once the distal opening of the needle is completely enclosed by the vessel wall, the fluid builds up pressure and creates an intramural space. In various embodiments, the pressure of the fluid may be between about 1 atmosphere (atm) and about 4 atm. The needle continues to advance for a first distance after puncturing the vessel wall (e.g., between about 3 mm and about 6 mm), then the tapered tube is advanced to cover the tip of the needle. The needle and the tube are then advanced together for a second distance (e.g., in a range between about 0.5 cm and about 3 cm) as the pressurized fluid from the needle creates an intramural space in between the vessel wall layers.
The imaging component can then be advanced through the guidewire lumen 221 (or another suitable lumen) and positioned such that the imaging component can provide images and/or measurements related to the puncturing and access into the intramural layers. The imaging component can also provide images that help visualize the intramural space created therein.
Once the position of the needle 140 within the intramural layers is confirmed, the valve 162 can be actuated to deliver an infusate (e.g., a drug or other therapeutic agent) into the intramural space. The infusate can be mixed with a contrasting agent so that infusion can be viewed more easily through fluoroscopy devices. The infusate can additionally, or alternatively, be mixed with an echogenic agent (e.g., gas-filled microbubbles, such as air bubbles, or suspended particles) such that the infusion can be visualized in cross section using the imaging component. The user can control the flow rate and volume of the infusates delivered until an adequate area is treated and/or an adequate infusates volume is delivered and/or absorbed. In some embodiments, the user can use the imaging information to determine an optimal volume, pressure, and/or flow rate, or base the infusion on a pre-determined volume of an infusate. In some embodiments, the infusate can be delivered at a steady flow rate and/or a steady pressure until the desired distribution or volume of the infusate is delivered and/or absorbed.
In some embodiments, the infusion pressure is generally equal to or less than the pressure that was used to access the tissue layer and create the intramural space. In some embodiments, the infusion pressure is higher (e.g., in a range between about 4 atm and about 10 atm) to increase the size of the intramural space and the drug dispersion area. For example, the infusion pressure can be set to achieve a specific circumferential distribution of an infusate, for example encompassing 90, 180, 270, or 360 degrees of vessel wall. In some embodiments, the infusion pressure can be set to achieve a specific longitudinal distribution of the infusate (e.g., about 1 cm, 3 cm, 5 cm, and/or another distance from the puncture site).
In some embodiments, the infusate can be delivered in a pulsed manner, either pulsed pressure or pulsed flow until the desired distribution or volume of the infusate is delivered. A pulsed flow can be paired with real time cross-sectional imaging at a pre-specified target distance from the puncture location (e.g., about 3 cm caudal or cranial to the puncture location), as a means to determine if the hydrodissection fluid or infusate mixture has reached the pre-specified target distance. For example, the analysis can include a real-time imaging interpretation of pulsed or dynamic movement within the appropriate intramural or extra vascular layers at the pre-specified target distance. In some embodiments, the infusion can occur while the balloon 111 is inflated. Alternately, the intramural space can be created while the balloon 111 is inflated, then the balloon 111 can be deflated while (or before) the infusate is being delivered so that the vessel V is not compressed during the delivery. In some embodiments, the distal portion 110 is pulled back during the infusion stage of the procedure. In some embodiments, the needle can deliver at least a portion of the infusate during the needle advancement step (e.g., an initial dose that can be absorbed while the intramural space is created).
In some embodiments, the pressurized fluid used to access the vessel wall W and create the intramural space includes a diluted amount of the infusate. In such embodiments, the needle 140 is advanced to a desired length and the pressurized fluid is delivered until a desired distribution area on the vessel wall receives the infusate and/or a desired volume is delivered.
Various tissue characteristics can affect an ideal infusion pressure to achieve a predetermined distribution area (e.g., corresponding to predetermined target treatment site). For example, a thickened fibrotic vessel wall can require a higher infusion pressure than a normal vessel wall. Accordingly, in various embodiments, the infusion pressure to achieve the predetermined distribution area can be as high as about 10 atm, as low as about 2 atm, and/or dynamically adjusted throughout the procedure (e.g., based on intravascular or fluoroscopic imaging and/or a position of the needle 140), until the predetermined distribution area is achieved. The predetermined distribution area can be of a particular circumferential coverage around the vessel, (e.g., 90, 180, 270 or 360 degrees around the vessel). Additionally, or alternatively, the predetermined distribution area can be of a particular length along the vessel (e.g., about 1 centimeter (cm), about 3 cm, or about 5 cm in one or both directions from the target site). Once the predetermined distribution area is achieved, the infusion pressure can be lowered to deliver a desired total volume of infusate without increasing the size of the distribution area further.
In some embodiments, the device 101 can be configured to penetrate, advance, and deliver an infusate between specific and/or predetermined layers of the vessel wall (e.g., at a predetermined layer, at a predetermined depth, etc.). For example, in various embodiments, the device 101 is configured to specifically access the medial layer of an artery or vein, the adventitial layer of an artery or vein, the perivascular space around the vessel, and/or any other suitable layer or depth. In some embodiments, the device 101 is configured to extend between intravascular tissue, such as between the thrombus or atherosclerotic plaque and the vessel wall, and/or into the intravascular tissue itself. The device 101 can also be configured such that the needle height is dynamically adjustable. In some such embodiments, the user can adjust the needle height to selectively access one or more layers of the vessel wall (e.g., the medial, adventitial, or perivascular layers of the vessel wall) during the procedure. The needle height adjustment can additionally (or alternatively) be used to accommodate vessels with varying wall thicknesses (e.g., to adjust operation of the device 101 to a particular patient anatomy, to selectively access a desired layer in the vessel wall, and the like). In some embodiments, the user can use imaging information (e.g., from an IVUS) of an initial infusion to adjust the needle height for a subsequent infusion.
In some embodiments, after the device 101 is used to deliver an infusate to an intramural layer of a vessel wall (with the balloon either inflated or deflated), the distal portion 110 is re-positioned adjacent the target site (e.g., re-advanced if it was pulled back in a previous step) and the balloon 111 is re-inflated to compress the intramural layer such that the infusate is further dispersed in the layer of the vessel wall, and/or outward from the layer into outer layers (e.g., the adventitial layers or perivascular space surrounding the vessel) to aid in infusate dispersion into the vessel wall layers. Additionally, or alternatively, after the device 101 is used to deliver the infusate to an intramural layer of a vessel wall, the device 101 can be pulled back and a separate expandable catheter (e.g., a separate balloon catheter) can be advanced through the guidewire lumen 221 to the target site. In embodiments in which an imaging component and/or the guidewire 317 were in the guidewire lumen 221 at this stage of the procedure, the imaging component and/or the guidewire 317 are removed prior to introduction of a separate expandable catheter.
The separate expandable catheter size is selected to be larger than the vessel diameter, for example 110% or 120% of the vessel diameter, such that it will compress the vessel wall when expanded and further disperse the infusate in the wall layer, and/or outward from the layer into outer wall layers and/or perivascular space. In some embodiments, the separate expandable catheter does not have a rigid offset surface such that dispersion with the separate expandable catheter more uniformly compresses the vessel wall. For example, the separate expandable catheter can include an inflatable balloon that partially contorts to apply a generally even pressure across the vessel wall. The separate expandable catheter can also have a desired therapeutic effect on the vessel, for example when the procedure is treating a narrowing vessel and/or an occlusion.
In many of the embodiments discussed above, the infusion device can be re-used at multiple locations to deliver the infusate at multiple locations along a vessel, thereby treating more locations than can be accommodated by a single puncture and infusate location. In some embodiments, real-time imaging information gained during the previous puncture can help dictate where the next puncture and infusion should take place.
In some embodiments, the device 101 is used to deliver an infusate to an intramural layer of a vessel wall. After the infusate delivery, the device 101 is pulled back, a separate stent delivery catheter is advanced through the guidewire lumen 221, and a stent is implanted at the target site. The stent delivery procedure can be used, for example, when the target site has a narrowing vessel and/or stenosis compromising flow through the vessel. The stent implantation is the primary therapy for the procedure, but the preliminary infusate delivery from the device 101 is expected to mitigate various undesired negative effects of the stent implantation (e.g., vessel irritation).
In some embodiments, as discussed above with respect to
Types of drugs that can mitigate the effects of restenosis as the infusate in any of the examples above include anti-thrombotic, anti-proliferative, anti-inflammatory drugs, or some combination therein. Examples include paclitaxel, sirolimus, everolimus, heparin, dexamethasone, or the flavonoid family of drugs. Drug mixtures may also be injected as the infusate. Additionally, drug-impregnated microspheres can be delivered by the device 101. Microspheres for controlled release of drugs are typically made from bioabsorbable polymers such as the polylactic acid family of polymers (PLA, PDLA, PLLA) and range in size from about 10 microns (μm) to about 20 μm (e.g., about 0.0004 inches to about 0.0008 inches). Drug-impregnated microspheres injected into an intramural space of a vessel wall can extend the therapeutic effect of an infusate for a desired period. Additionally, or alternatively, a drug-impregnated polymer can be directly injected into the intramural space to prolong the diffusion of an infusate at the target tissue area. Examples of injectable polymers include polylactic acid polymers such as PLLA or PDLA diluted with a biocompatible solvent such as N-methyl-2-pyrrolidone (NMP). Dilutions can vary depending on the required viscosity for injection and the desired final material characteristics. For example, the dilution can be about 50:50 PDLA and NMP.
In yet further embodiments, infusate delivery can be used in conjunction with treatment of thrombosis in the vein to mitigate post-thrombotic syndrome. For example, for patients with deep vein thrombosis (DVT), removal of thrombus either through natural causes or treatment can often lead to thrombotic obstruction, valvular incompetence, or a combination of, thereby causing an array of clinical symptoms such as leg pain, leg heaviness, vein dilation, edema, skin pigmentation, and/or venous ulcers (known collectively as post-thrombotic syndrome (PTS)). In some embodiments, the infusate delivery device is used to deliver infusates that have the potential to reduce the incidence of PTS, such as anti-inflammatory drugs into an intramural layer of the vessel wall. In some embodiments, the infusate delivery device is used to deliver anti-inflammatory drugs into a space between residual thrombus and the vessel wall and/or into the thrombus itself. Examples include corticosteroids such as dexamethasone, anti-thrombotic infusates such as heparin, or some combination. The infusate delivery can occur after a thrombectomy procedure has been performed and the occlusive clot has been removed. Alternately, an infusate delivery procedure can be performed on patients who have previously had a DVT, or who may or may not have been treated for the DVT but are nonetheless at risk for PTS.
In some embodiments, infusate delivery can be used in conjunction with various other treatments of patients at risk for aortic aneurysm or dissection. For example, a breakdown in elastin and collagen can cause an aortic wall to weaken, leading to increased risk of aneurysm dissection or ulcers. An intramural delivery of an infusate (e.g., anti-inflammatory agent such as doxycycline) to the weakened aortic wall can counteract the effects of degradation of elastin and collagen. Additionally, or alternatively, the device can be used to inject collagen or biocompatible or bioabsorbable polymers (such as the injectable polymers described above), or adhesives to strengthen the aortic wall. These treatments are expected to reduce the risk of aortic rupture or dissection, both of which have catastrophic and often fatal consequences.
In some embodiments, infusate delivery is used for a treatment of thrombosis and/or another vessel obstruction to facilitate removal of obstructive material. For example, the infusate can be delivered into an intraluminal location (e.g., into an obstructive material, an intraluminal site, and/or into a boundary layer between obstructive material and vessel wall), an intramural location, and/or another suitable infusion site (e.g., to a location external to a delivery vessel, such as a second vessel adjacent a delivery vessel). In various embodiments, the infusate can be delivered at the distal portion 110 of the device 101 (e.g., as discussed above with respect to
In some such embodiments, the infusion device 101 is used to deliver the agent into a vessel obstruction (e.g., into an intraluminal site such as a thrombotic occlusion) and/or the boundary layer between the obstruction and to facilitate removal of the obstructive material. The infusion drug may be selected based on the nature of the obstructive material. In a specific, non-limiting example of a case of chronic obstruction, the infusate can be selected from a type of MMP such as collagenase or fibrinolytic agent. In the case of a thrombotic obstruction, the agent may be selected from a group of thrombolytic agents or other suitable agents to break down the obstructive material. Additionally, or alternatively, the infusate can include a saline solution. Additionally, or alternatively, the procedure can include a hydrodissection step with saline, followed by an infusion step with an agent that breaks down obstructive material.
The process 1800 begins at block 1802 by positioning an infusion device (e.g., the infusion device 1601 of
At block 1804, the process 1800 includes targeting the infusion site. Targeting the infusion site can include orienting the infusion device, imaging the infusion site, and/or manipulating the vessel to allow the needle to advance out of an exit port and into the infusion site.
In some embodiments, targeting the infusion site includes expanding an expandable component at the distal portion of the infusion device (e.g., the balloon 1611 of
In some embodiments, targeting the infusion site includes rotating the infusion device within the vessel (e.g., to target tissue on other radial walls within the vessel). In some embodiments, targeting the infusion site includes adjusting a height of the needle above the offset surface at the distal portion of the infusion device (e.g., thereby adjusting a distance between the needle and a central longitudinal axis of the catheter shaft of the infusion device). For example, the exit port for the needle can include a rotatable guide component (e.g., the needle guide 1402 of
At block 1806, the process 1800 includes advancing the needle into the infusion site. As discussed above, the infusion site can an intraluminal location, such as longitudinally adjacent an obstructive material (e.g., thrombotic tissue or another occlusion), a space within the obstructive material, and/or a space within boundary layer between the obstructive material and the vessel wall. Accordingly, in some embodiments, advancing the needle includes penetrating intraluminal tissue. Additionally, or alternatively, the infusion site can be at an intramural space (e.g., within the vessel wall, within a pocket created in the vessel wall, and the like). In some such embodiments, advancing the needle includes hydrodissecting the vessel wall to create an intramural space within the wall. Additionally, or alternatively, the infusion site can be external to the vessel (e.g., into an occlusion in an adjacent vessel). Accordingly, in such embodiments, advancing the needle includes penetrating vessel wall to access the external infusion site (e.g., as discussed above with respect to
Further, in some embodiments, the process 1800 includes hydrodissecting the obstructive material to help access the infusion site and/or to aid in breaking down the obstructive material. For example, the process 1800 can partially dissect the boundary layer between the obstructive material and the vessel wall to both access a space between the two and to help aid in separative the obstructive material (e.g., thrombotic tissue) from the vessel wall.
At block 1808, the process 1800 includes delivering the infusate to the infusion site. In some embodiments, the infusate is delivered at a relatively low pressure to avoid dissecting any adjacent tissue. In some embodiments, the infusate is delivered at a pressure sufficient to at least partially dissect adjacent tissue (e.g., tissue in the boundary layer) and/or help ensure the infusate contacts and acts on the obstructive material. Once the infusate is delivered, the drugs in the infusate can act on surrounding tissue. For example, when the infusate includes an MMP (e.g., collagenase and/or a fibrinolytic agent), the MMP can begin breaking down the tissue in the obstructive material.
In some embodiments, the process 1800 energizes the infusate and/or the tissue in and around the infusion site before, during, or after delivery to catalyze the action of a drug in the infusate. For example, the process 1800 can include directing ultrasound energy to the infusion site. In a specific, non-limiting example, the infusion device can include a transmitter directed distal to the distal portion to direct ultrasound energy to the infusion site. Additionally, or alternatively, the ultrasound energy can be directed to the infusion site through an external source (e.g., a transmitter external to the patient's body). In still further examples, additional (or alternative) sources of energy (e.g., heat and/or light) can be applied to the infusate to help accelerate the action and/or increase the overall action performed by the infusate.
In some embodiments, the infusate is delivered in the form of an agent compounded in a slow-release vehicle (e.g., polymer nano-particles or beads, foam from materials such as PVA, PLLA, liposomes, hydrogels, and the like). In such embodiments, the slow release can extend the action of the agent over a longer period of time.
In some embodiments, after delivering the infusate at block 1808, the process 1800 returns to block 1802 or block 1804 to position the infusion device adjacent a second infusion site and/or to target a second infusion site. For example, when the obstructive material is a fully occlusive tissue (e.g., a full thrombotic blockage), the process 1800 can deliver infusate to multiple infusion locations to improve the amount of the obstructive material that is removed. In a specific, non-limiting example, the process 1800 can execute blocks 1802-1808 multiple times to deliver infusate to multiple radial locations of the boundary layer and/or multiple locations in the obstructive material. In some embodiments (e.g., when the process 1800 is executed using the infusion device 1701 of
At optional block 1810, the process 1800 includes removing at least a portion of the obstructive material. In some embodiments, removing a portion of the obstructive material includes hydrodissecting a portion of the obstructive material (e.g., the portion acted on by the infusate) and allowing blood flow to carry away any removed portions. For example, when the infusate was delivered to a boundary layer, the infusate can break down the tissue at the boundary layer, then a hydrodissection process can further excise remaining tissue from the vessel wall. In some embodiments, removing a portion of the obstructive material includes capturing the removed portions (e.g., through a fluid removal lumen).
The process 1800 can be a stand-alone procedure to enhance the natural removal of obstructive material in a vessel of a patient. In such embodiments, the removal at block 1810 (e.g., the hydrodissection) can be executed by the infusion device. Alternately, the process 1800 can be a partially adjunct procedure to a removal of an obstructive material. For example, the removal process at block 1810 can be completed by a separate device, such as a mechanical and/or aspiration thrombectomy device. When the removal process 1800 is completed by a separate device, the removal can occur during the same procedure. For example, an infusion device (e.g., the device 101 of
In some embodiments, the process 1800 includes a dwell period between the infusion step and the removal step. For example, the infusate can be left to act on the obstructive material for about 30-60 minutes. Alternately, the infusion step can be completed in a first procedure; then the removal step can be completed in a second procedure one or more days later. In such embodiments, the infusate is provided a relatively large amount of time to act on (e.g., break down) the obstructive material.
The following examples are included to further describe some aspects of the present technology and should not be used to limit the scope of the invention.
1. A method of delivering a therapeutic agent to an infusion site, the method comprising:
2. The method of example 1 wherein the tissue is an intraluminal tissue that is at least partially occluding the vein beyond a distal end of the catheter, and wherein the method further comprises removing at least a portion of the intraluminal tissue after delivering the infusate to the infusion site.
3. The method of any of examples 1 and 2 wherein the infusion site is a boundary layer between a thrombotic material and a vessel wall, and wherein advancing the needle toward the infusion site includes penetrating the boundary layer to access a space between the thrombotic material and the vessel wall.
4. The method of example 3 wherein the infusate at least partially breaks down a bond between the thrombotic material and the vessel wall, and wherein the method further comprises removing at least a portion of the thrombotic material after delivering the infusate to the infusion site.
5. The method of any of examples 3 and 4, further comprising performing a hydrodissection of tissue at the boundary layer to aid in separation of the thrombotic material from the vessel wall.
6. The method of any of examples 1-6 wherein the tissue is an intraluminal tissue that is at least partially occluding the vein, wherein the infusion site is a space within the intraluminal tissue, and wherein advancing the needle to the infusion site includes advancing the needle into the intraluminal tissue.
7. The method of any of examples 1-6 wherein the infusate includes collagenase.
8. The method of any of examples 1-7, further comprising targeting the infusion site with the distal end of the catheter shaft.
9. The method of example 8 wherein targeting the infusion site includes at least partially expanding an expandable component on the distal end of the catheter shaft, wherein expanding the expandable component at least partially straightens a portion of the vein.
10. The method of any of examples 8 and 9 wherein the exit port includes a rotatable guide component to adjust a distance between the needle and a central longitudinal axis of the catheter shaft before advancing the needle out of the exit port, and wherein targeting the infusion site includes adjusting the distance between needle and the central longitudinal axis of the catheter shaft.
11. The method of any of examples 1-10, further comprising energizing the infusate at the infusion site, wherein energizing the infusate increases and/or accelerates the break down of the intraluminal tissue.
12. The method of any of examples 1-11 wherein energizing the infusate includes directing ultrasound energy into the infusion site.
13. The method of any of examples 1-12, further comprising advancing an imaging component out of a second lumen at the distal portion of the catheter device to image the infusion site.
14. The method of any of examples 1-13 wherein:
15. The method of example 14 wherein the vessel is a first vessel, and wherein the infusion site is in a second vessel adjacent the first vessel.
16. An infusion device, comprising
17. The infusion device of example 16 wherein the infusion site is within a boundary layer of the thrombotic tissue with a vessel wall, and wherein the exit port includes a rotatable guide component to adjust a height of the needle above the offset surface to target the needle toward the boundary layer before advancing the needle out of the exit port.
18. An infusion device, comprising:
19. The infusion device of example 18 wherein the expandable component positions each of the one or more needle guide components a controllable distance away from a central longitudinal axis of the catheter shaft
20. The infusion device of any of examples 18 and 19 wherein the exit ports are each positioned a set distance from the central longitudinal axis of the catheter shaft, and wherein each of the one or more needles transitions between the controllable distance and the set distance.
21. A method of operating the catheter device of claim 16 comprising any of the step of examples 1-15.
22. A method of operating the catheter device of claim 18 comprising any of the step of examples 1-9 and 11-13.
23. An infusion device for delivering an infusate to an infusion site as disclosed herein.
24. A system for infusing a substance into an intraluminal site as disclosed herein.
25. A system as disclosed herein.
26. A method of infusing a substance into an obstructive material as disclosed herein.
27. A method as disclosed herein.
28. The method of example 27 wherein delivering the drug comprises delivering a matrix metalloproteinase to an infusion site within and/or adjacent an obstructive material.
29. A method of intravascularly delivering a therapeutic agent to a patient diagnosed with vessel obstruction, the method comprising:
30. The method example 29 wherein the catheter accesses the boundary layer at the site of the distal portion of the infusion device.
31. The method any of examples 29 and 30 wherein the catheter accesses the boundary layer at the site distal to the distal portion of the infusion device.
32. The method any of examples 29-31, further comprising a hydrodissection step to aid in separation of the obstructive material from the vessel wall.
33. A method of intravascularly delivering a pressurized fluid to a patient diagnosed with vessel obstruction, the method comprising:
The above detailed description of embodiments of the technology are not intended to be exhaustive or to limit the technology to the precise form disclosed above. Although specific embodiments of, and examples for, the technology are described above for illustrative purposes, various equivalent modifications are possible within the scope of the technology as those skilled in the relevant art will recognize. For example, although steps are presented in a given order, alternative embodiments can perform steps in a different order. The various embodiments described herein can also be combined to provide further embodiments.
From the foregoing, it will be appreciated that specific embodiments of the technology have been described herein for purposes of illustration, but well-known structures and functions have not been shown or described in detail to avoid unnecessarily obscuring the description of the embodiments of the technology. Where the context permits, singular or plural terms can also include the plural or singular term, respectively.
Moreover, unless the word “or” is expressly limited to mean only a single item exclusive from the other items in reference to a list of two or more items, then the use of “or” in such a list is to be interpreted as including (a) any single item in the list, (b) all of the items in the list, or (c) any combination of the items in the list. Additionally, the term “comprising” is used throughout to mean including at least the recited feature(s) such that any greater number of the same feature and/or additional types of other features are not precluded. It will also be appreciated that specific embodiments have been described herein for purposes of illustration, but that various modifications can be made without deviating from the technology. Further, while advantages associated with some embodiments of the technology have been described in the context of those embodiments, other embodiments can also exhibit such advantages, and not all embodiments need necessarily exhibit such advantages to fall within the scope of the technology. Accordingly, the disclosure and associated technology can encompass other embodiments not expressly shown or described herein.
This application is a Continuation-In-Part of U.S. patent application Ser. No. 17/378,446, filed Jul. 16, 2021, now pending, which claims priority to U.S. Provisional Patent Application No. 63/052,900, filed on Jul. 16, 2020, U.S. Provisional Patent Application No. 63/061,108, filed Aug. 4, 2020, and U.S. Provisional Patent Application No. 63/167,633, filed on Mar. 29, 2021, the entireties of which are incorporated herein by reference.
| Number | Date | Country | |
|---|---|---|---|
| 63052900 | Jul 2020 | US | |
| 63061108 | Aug 2020 | US | |
| 63167633 | Mar 2021 | US |
| Number | Date | Country | |
|---|---|---|---|
| Parent | 17378446 | Jul 2021 | US |
| Child | 17661507 | US |
