Vascular device loading

Abstract

Vascular device loading can be provided by loading a first liquid having a first density into a vascular device hub having an internal volume that is fluidly connected between a syringe port and a cannula port, connecting a first syringe filled with a second liquid to the syringe port, wherein the second liquid has a second density different from the first density, orienting the first syringe at a first elevation relative to the vascular device hub and placing the higher density of the first liquid and the second liquid below the lower density of the first liquid and the second liquid, injecting the second liquid from the first syringe into the vascular device hub, and discharging the first liquid from the vascular device hub via the cannula port.

Description

Technical Field

[0001] (Cross - Reference to Related Applications) This disclosure claims the benefit of U.S. Provisional Patent Application No. 63 / 356,970, filed Jun. 29, 2022, and titled "PROCESSES FOR LOADING VASCULAR DEVICES", which is hereby incorporated by reference in its entirety.

[0002] This disclosure generally relates to the use of devices for delivering fluids into the vasculature of a biological subject. More specifically, this disclosure describes improved processes or methods for delivering multiple fluids while avoiding or reducing mixing between those fluids through a single catheter and syringe assembly for the improved treatment of various medical conditions in a biological subject.

Summary of the Invention

Means for Solving the Problems

[0003] The present disclosure provides vascular device loading for the treatment or prevention of medical conditions, etc., by targeted delivery of multiple distinct fluids. For example, during a liquid embolization procedure, five flushes of liquid may be used (e.g., a first saline injection to prepare the catheter, an injection of contrast agent to confirm the catheter location and visualize the vasculature of a biological subject, a second saline injection to flush out the contrast agent, a DMSO injection to prepare the target location for injection of a liquid embolizing substance, and an injection of a liquid embolizing substance to treat an AVM or aneurysm). Since it is known that liquid embolic solutions harden prematurely (e.g., at locations other than the target site) when the embolic substance comes into contact with blood, contrast agent, saline, or combinations thereof, it is important to avoid mixing of fluids within the catheter and syringe in order to reduce the risk of premature hardening. Thus, as described herein, proper loading of the vascular device improves delivery of fluids to the target site, reduces the risk of imposing excess pressure on the device or biological subject, reduces operator stress or fatigue, reduces the amount of fluid that needs to be injected (e.g., via improved target up - delivery), and can provide various other benefits that will be apparent to those skilled in the art upon detailed perusal.

[0004] Additional features and advantages of the disclosed methods and apparatuses will be described in, and will be apparent from, the following detailed description and figures. The features and advantages described herein are not exhaustive, and in particular, many additional features and advantages will be apparent to those skilled in the art in light of the figures and description. Also, note that the language used herein has been primarily selected for readability and instructional purposes and has not been selected to limit the scope of the subject matter of the invention.

Brief Description of the Drawings

[0005]

Figure 1

[0006]

Figure 2

[0007]

Figure 3

[0008]

Figure 4

[0009]

Figure 5

[0010]

Figure 6

[0011]

Figure 7

[0012]

Figure 8

[0013]

Figure 9

[0014]

Figure 10A

Figure 10B

Figure 10C

[0015] As will be appreciated, various fluid levels and devices are simplified for purposes of illustration and to avoid confusion from the features discussed within the present disclosure.

DETAILED DESCRIPTION

[0016] DETAILED DESCRIPTION A variety of embolization materials are available for addressing occlusion of fluid flow paths within a lumen or vasculature and include liquid or non-liquid materials. A number of disease states, including but not limited to arteriovenous malformations (AVMs) or aneurysms, can be treated by filling with one or more embolization materials. Some aneurysm treatment techniques involve the use of a catheter (e.g., a microcatheter) in combination with a series of fluid volumes pushed through the catheter, including contrast fluid, flush fluid, preloaded fluid, and embolic fluid, and combinations thereof. Certain liquid embolic polymers may be designed to coagulate, precipitate, or otherwise release themselves from a flowable organic solution at the interface of contact with an aqueous liquid. Subsequent leaching or diffusion of the organic solvent from the liquid embolization material allows the embolic polymer to further solidify.

[0017] Such treatment techniques present various risks, including, for example, fouling of devices used to deliver embolization materials due to premature loading, coagulation, or precipitation of the embolization material within the device or components used to deliver the embolization material to the present device. It has been found that a density difference of the liquids sequentially flowed through the vascular device is required for one or more specific features of the process to reduce the risk of a contaminated device when preparing to administer an occluding material such as a liquid embolization material through the present device or when administering the same.

[0018] Accordingly, provided herein is a method or process for loading a vascular device with an embolization material. Also provided herein is a method for reducing the risk of premature solidification or unfavorable flow characteristics of a liquid embolization material that results in catheter rupture or embolization behavior during treatment of an aneurysm within a biological subject in need thereof using a vascular device (e.g., a microcatheter). Also provided herein is a method for treating or preventing an AVM or aneurysm within a biological subject.

[0019] In some embodiments, the process features referred to above include the maximum angle of the syringe from vertical, the density or viscosity of the liquid flushing agent, the density or viscosity of the liquid resident within the lumen of the vascular device, or combinations thereof, to prevent the settling of one liquid within another, or the channeling of one liquid through or around another.

[0020] As discussed herein, the present disclosure refers to the angles and positions of various components. Unless explicitly stated otherwise, the orientation of these components and elements refers to the longitudinal axis of that component or element relative to the environment in which the component or element is found. As used herein, the vertically upward position corresponds to 0 degrees of rotation, the horizontal position corresponds to 90 degrees of rotation from the vertically upward position, and the vertically downward position corresponds to 180 degrees of rotation from the vertically upward position (90 degrees from the horizontal line towards the floor). For example, a hypothetical fluid would settle to have a surface that is horizontal within a reference frame (ignoring the effect of the meniscus). A buoy positioned within this hypothetical fluid would have a portion that is positioned vertically upward relative to the fluid (e.g., floating above the fluid surface within the reference frame) and a portion that is positioned downward relative to the fluid (e.g., immersed below the fluid surface within the reference frame).

[0021] In some embodiments, when loading a vascular device with a liquid polymer plugging substance that would be released from a flowable organic solution in response to contact with an aqueous liquid, it is important to flush all or substantially all of the aqueous liquid that may be resident within the vascular device prior to the plugging substance being loaded into the vascular device (e.g., due to a previous preloading step). Doing so reduces the risk of premature release of the polymer plugging substance out of the solution within the vascular device, which would require increased force to flow the liquid plugging substance from the syringe through the vascular device to the target within the biological subject and increased stress on the biological subject.

[0022] In some embodiments, the processes provided herein include loading a vascular device with a liquid embolic material and may further include the preloading processes described herein.

[0023] In some embodiments, the process for preloading a vascular device may include: 1) pushing a volume of liquid contrast agent through the device at a specific flow rate; 2) pushing a volume of normal saline through the device at a specific flow rate; and 3) pushing a volume of flush liquid through the device at a specific flow rate and preloading the device for loading with a liquid embolic material. The liquid contrast agent, saline, flush liquid, and liquid embolic material may each have different densities or viscosities, or both. Further, in some embodiments, the liquid contrast agent, saline, flush liquid, and liquid embolic material may each have a different base carrier solvent. That is, in some embodiments, the liquid embolic material may be in an organic solvent such as dimethyl sulfoxide (DMSO) or the like, while saline is an aqueous solution of salt and water. Similarly, in some embodiments, the flush liquid may be in an organic solvent such as DMSO or the like. Additionally, in some embodiments, the liquid contrast agent may be water-based, or in an organic carrier, or a combination thereof.

[0024] The vascular device preloading sequence includes one or more steps in which a second liquid volume is pushed through a vascular device containing a first liquid volume. In some embodiments, the liquid contrast agent, normal saline, flush liquid, and liquid embolic material may each independently be the first liquid volume or the second liquid volume.

[0025] In some embodiments, when the first liquid volume is of a lower density than the second liquid volume and the first liquid volume and the second liquid volume are to be fluidly connected, the syringe containing the second liquid volume is operably connected to the vascular device and is oriented between about 60 degrees from vertical and substantially vertical, and the syringe tip is oriented upward when pushing the second liquid volume through the vascular device.

[0026] Figures 1 - 8 illustrate various interactions between different fluids according to various embodiments of the present disclosure. Figures 1 - 8 each illustrate a portion of a syringe 120 that is connected for use in delivering liquid to a vascular hub device 110. The vascular hub device 110 includes a syringe port 112 provided to establish fluid communication with the syringe 120. Shown on another end of the vascular hub device 110 at the first syringe port 112a is a cannula port 114 with the first end of a catheter 140 attached thereto. The opposite end of the catheter 140 (not shown) is inserted into a biological subject to deliver various fluids or devices to a target location within the biological subject (e.g., the site of an AVM or aneurysm). In some embodiments, the vascular hub device 110 also includes a device port 116 through which an embolization portion 130 is shown that blocks fluid communication between the internal volume of the vascular device hub and the external environment. The embolization portion 130 enables selective access for various instruments, dilators, guidewires, or other devices to the biological subject, or the application of additional syringes, negative pressure sources, or the like.

[0027] In each of Figures 1 - 8, various liquids 150a - c (generally or collectively, liquid 150) are shown. As described in more detail with respect to the individual Figures 1 - 8, the liquids 150 can separate, mix, or permeate through each other based on their individual densities and establish equilibrium according to density flow through the shared space.

[0028] In various embodiments, the catheter 140 through which the aforementioned liquid 150 flows may or may not be coated. In some embodiments, the inner surface of the catheter 140 may be hydrophobic, hydrophilic, or amphiphilic.

[0029] Some examples of density separation are shown in FIGS. 1 and 2 where a first liquid 150a of physiological saline is present within the vascular device hub 110 and catheter 140, and a second liquid 150b of DMSO solution is present within the syringe 120. In some embodiments, to avoid introduction of air bubbles into the liquid 150 being pushed through the vascular device 110, the syringe 120 containing the second liquid 150b, when connected to the vascular device hub 110 (e.g., as shown in FIG. 3), is oriented with its tip downward, and the syringe 120 is then oriented to be substantially vertical (as in FIG. 2). In some embodiments, the syringe 120 is substantially vertical when connected to the syringe port 112 when the longitudinal axis of the syringe 120 is 45 degrees or less from vertical, more preferably 30 degrees or less from vertical, and even more preferably 15 degrees or less from vertical. In some embodiments, such a sequence of tilting between vertically upward and vertically downward reduces an undesirable mixing of the two liquids 150 in a final state where the more dense liquid 150 is below the less dense liquid 150 when the liquids 150 have different densities.

[0030] FIG. 4 illustrates an example of undesirable channeling of two immiscible liquids 150 with different densities that the present disclosure seeks to mitigate. For example, by leaving the syringe 120 above the less dense first liquid 150a with the more dense second liquid 150b present for an overly long period of time, the two liquids 150 may channel through each other such that the less dense liquid 150 forms a layer on top of the more dense liquid 150.

[0031] The second liquid 150b is injected through the vascular device hub 110, but due to the horizontal orientation of the device, instead of being injected through the catheter 140, another undesirable channeling of the two liquids occurs that results in backflow of the first liquid 150a from the vascular device hub 110, as shown in FIG. 5.

[0032] Another undesirable channeling of the two liquids can occur as shown in FIG. 6, which shows undesirable channeling or foaming of the first liquid 150a (e.g., saline) through the higher density second liquid 150b (e.g., contrast agent) through the vascular device hub 110 when the syringe 120 is held in a substantially vertical orientation while pushing the first liquid 150a from the syringe 120 into the vascular device hub 110.

[0033] FIG. 7 shows the orientation of the syringe 120 relative to the vascular device hub 110, with the syringe 120 operably connected to the vascular device hub 110. As shown, the syringe 120 is oriented between about 30 degrees from vertical, but may be oriented at other angles between 0 and 45 degrees from vertical with the syringe tip pointing downward. In the illustrated embodiment, since the first liquid 150a is of higher density than the second liquid 150b, when the first liquid 150a and the second liquid 150b are placed in fluid communication (e.g., fluidly connected), the second liquid 150b floats on top of the first liquid 150a and does not channel or mix with the first liquid 150a, in contrast to the opposing or horizontal orientation behavior discussed in relation to FIGS. 4 - 6.

[0034] In some embodiments, the liquid embolization material has a viscosity of about 12 centipoise or greater. In some embodiments, the liquid embolization material is denser than a typical saline solution. In some embodiments, the liquid contrast agent is denser than a typical saline solution. In some embodiments, the liquid embolization material is denser than the liquid contrast agent. Thus, care should be taken with respect to the orientation of the syringe 120 when sequentially loading and injecting various fluid volumes such as saline solution, liquid embolization material, liquid contrast agent, etc. with different densities, to introduce a new liquid 150 into the vascular device hub 110 that holds the previously introduced liquid 150.

[0035] For example, to prevent channeling of a second liquid 150b in DMSO in the syringe 120 through a first liquid 150a in the vascular device hub 110 consisting of saline solution, or to prevent backflow of the first liquid 150a into the syringe 120, a bolus of a third liquid 150c (such as a liquid contrast agent) may be positioned to flow between the interfaces of the first liquid 150a and the second liquid 150b. In various embodiments, the volume of the bolus will vary based on the volume of the vascular device hub 110, but in some embodiments, the volume of the bolus is up to about 500 microliters (μL).

[0036] FIG. 8 shows such a bolus of the third liquid 150c that can be obtained by first loading the vascular device hub 110 with the first liquid 150a (as in FIG. 2) with the syringe 120 oriented upward, and then loading the third liquid 150c into the vascular device hub 110. For example, a sufficient amount (e.g., 0.2 milliliters (mL)) of the third liquid 150c is injected to fill the vascular device hub 110, and the catheter 140 still contains the first liquid 150a. Once the bolus is loaded into the vascular device hub 110, the operator may remove the syringe 120 that carried the third liquid 150c and attach another syringe 120 carrying the second liquid 150b to the syringe port 112 with the new syringe 120 oriented downward (as in FIG. 8). Thus, using different orientations for the introduction of the various liquids 150 reduces the chance of mixing or channeling occurring. Note that the physiological saline is less dense than DMSO, which is less dense than the contrast liquid.

[0037] One challenge in understanding the hydrodynamics of how these various liquids 150 flow through the system is visualization. Many of the liquids 150 are difficult to visually distinguish through similar or the same colored, or opaque, colored, or translucent components (catheters, microcatheters, syringes, etc.). Generating "real-world" conditions in a laboratory setting may typically require creating a transparent version of a product purchased as an "off-the-shelf" product as opaque or colored. Once a transparent component is generated, a colored dye or other distinguishing characteristic may be added to the various liquids 150 to distinguish the liquids 150 from one another, which may require tests to confirm that the addition of the dye or other factor did not modify or alter the relevant chemical or fluid properties. Once the chemical and fluid properties are confirmed, the modified fluid is used in combination with the modified (transparent) component to visualize in real time the hydrodynamics within the implantable system, and various angles, flash techniques, and sequences of operation can be tested.

[0038] FIG. 9 is a flowchart of an exemplary method 900 for vascular device loading, according to an embodiment of the present disclosure. Method 900 may be repeated across several iterations of blocks 910 - 950 and may load various liquids 150 in turn through a vascular device used for delivery of the liquids 150 to a target site within a biological subject. Thus, while the examples provided herein enumerate three liquids 150a - c, the present disclosure contemplates that two liquids 150a - b or more than three liquids 150 may also be loaded according to method 900.

[0039] For example, during a liquid embolization procedure, five flushes of liquid may be used (e.g., a first saline injection to prepare the catheter, to confirm the catheter location, an injection of a contrast agent to visualize the vasculature of a biological subject, a second saline injection to flush out the contrast agent, a DMSO injection to prepare the target location for injection of a liquid embolizing substance, and an injection of a liquid embolizing substance to treat an AVM or aneurysm). Since it is known that the liquid embolizing solution hardens prematurely (e.g., at a location other than the target site) when the embolizing substance comes into contact with blood, a contrast agent, saline, or a combination thereof, it is important to avoid mixing of fluids within the catheter and syringe to reduce the risk of premature hardening.

[0040] Liquid embolization procedures often require the operator to manually inject various liquids into a target site over an extended period of time (e.g., via depressing the plunger of a syringe), and thus method 900 defines various positions and orientations for the syringe relative to a vascular device hub at a given time to reduce the risk of mixing of fluids of different densities, thereby reducing the risk (or amount) of a liquid embolizing substance that hardens prior to delivery to the target site.

[0041] In block 910, the operator loads a liquid into the vascular device hub. In various embodiments, the liquid may be loaded via injection from a syringe (e.g., according to block 950), aspiration or backflow from a source, or during the manufacture of the vascular device hub.

[0042] In block 920, the operator connects a cannula port of the vascular device hub to a blood vessel within a biological subject via a catheter. In various embodiments, the catheter may be inserted into the blood vessel before or after being connected to the cannula port. The operator may also pass the opposite end of the catheter therethrough.

[0043] In various embodiments, block 920 may be performed before block 910 or may be omitted in the iteration of blocks 910-950. For example, an operator may attach a cannula report to a catheter only once, even though loading multiple fluids into a medical device for injection via catheter 140 into a target site within a biological subject, and the initial connection can be maintained across multiple loadings and injections of different fluids.

[0044] In block 930, the operator connects a syringe to the vascular device hub. In various embodiments, the syringe may be screwed directly into, snap-fitted onto, or held in place relative to the vascular device hub using pressure. In some embodiments, tubing may be connected between the tip of the syringe and the syringe port, allowing additional ergonomic options for the operator to hold the syringe in hand while positioning two fluids at different heights. In various embodiments, various needles, gaskets, or equivalents may be used to establish a pressure seal for delivery of the fluid held by the syringe to the vascular device hub. In some embodiments, to avoid introducing air bubbles into the fluid already loaded in the vascular device hub, the syringe is connected to the vascular device hub with the tip of the syringe facing downward while the syringe is oriented substantially vertically (e.g., as in FIG. 3).

[0045] In block 940, the operator orients the syringe relative to the vascular device hub such that the syringe is at a certain height relative to the vascular device hub, based on the density of the liquids within the syringe and the vascular hub device, respectively, so that the operator can place the denser of the liquids below the less dense of the liquids.

[0046] For example, a first liquid comprising a physiological saline solution (loaded according to the first iteration of block 910), and a second liquid in a syringe (connected according to the first iteration of block 930) comprising an aqueous contrast agent solution, which is denser than the physiological saline solution, are accompanied such that the physiological saline solution (and the vascular device hub) is positioned above the aqueous contrast agent solution (and the syringe). Continuing with the example, when flushing the contrast agent with physiological saline (e.g., in the second iteration of blocks 910 - 950), the orientation of the device is reversed such that the physiological saline solution (currently in the syringe) is positioned above the aqueous contrast agent solution (already loaded in the vascular device hub).

[0047] For example, a first liquid comprising a DMSO solution (loaded according to the current iteration of block 910), and a second liquid in a syringe (connected according to the current iteration of block 930) comprising a liquid plugging substance that is less dense than the DMSO solution, are accompanied such that the DMSO solution (and the vascular device hub) is positioned below the liquid plugging substance (and the syringe).

[0048] At block 950, the operator injects the liquid from the syringe into the vascular device hub, which discharges some or all of the previously loaded liquid in the vascular device hub out of the cannula port and towards the biological subject. In various embodiments, depending on the volume of liquid held in the syringe and the volume of liquid held in the vascular device hub, the injection from the syringe can flush out the vascular device hub and move at least 50% of the volume of the vascular device hub out through the cannula port. In some embodiments, the injection can load a bolus of liquid into the vascular device hub (e.g., as part of a subsequent iteration of block 910) and act as a buffer with the next liquid to be injected (e.g., according to subsequent iterations of blocks 910 - 950).

[0049] Method 900 may be repeated through several iterations to provide a continuous volume of fluid to a target area of a biological subject for treating an AVM or aneurysm or other condition that is treatable via targeted delivery of a plurality of different fluids. Method 900 may be provided as a set of instructions for a medical device (such as a syringe, vascular device hub, catheter, or kit / assembly thereof).

[0050] FIGS. 10A - 10C are flowcharts of exemplary usage methods 1000a - c according to embodiments of the present disclosure.

[0051] FIG. 10A is a flowchart for a first exemplary usage method 1000a when performing liquid embolic substance injection for a liquid embolic substance such as cyanoacrylate adhesive paste (such as Histoacryl (n - butyl cyanoacrylate), Glubran (n - butyl cyanoacrylate and methacryloxy sulfolan), Magic adhesive paste or Purefill (n - hexyl cyanoacrylate), TruFill (n - butyl cyanoacrylate), or Fuaile (n - butyl cyanoacrylate and 2 - octyl cyanoacrylate)), Onyx (a pre - mixed radiopaque injectable embolic fluid liquid embolic system (LES) consisting of the following components, namely, EVOH (ethylene - vinyl alcohol copolymer), DMSO (dimethyl sulfoxide), and TA (micronized tantalum powder)), Squid (EVOH, DMSO, TA), Menox (EVOH, TA, DMSO), or precipitated hydrophobic injectable liquid (PHIL; polyactide - co - glycolide, polyhydroxyethyl - methacrylate, triiodophenol, DMSO).

[0052] In block 1010, the operator flushes the catheter with saline to prepare the catheter. In various embodiments, since the catheter is initially empty, the operator may orient the saline - containing syringe in any direction (e.g., upward, downward, horizontally).

[0053] In block 1020, the operator injects a contrast agent (e.g., to confirm the catheter location within the vasculature). Since the contrast agent is of a higher density than normal saline, when injecting the contrast agent, the operator orients the contrast agent-containing syringe with the syringe facing upward.

[0054] In block 1030, the operator flushes the catheter with normal saline to flush out the contrast agent. Since normal saline is of a lower density than the contrast agent, the operator orients the normal saline-containing syringe with the syringe facing downward.

[0055] In block 1040a, the operator injects DMSO into the catheter in preparation for injecting a liquid embolic substance (e.g., according to block 1050). Since DMSO is of a higher density than the normal saline injected in block 1030, the operator orients the DMSO-containing syringe with the syringe facing upward.

[0056] In block 1050, the operator injects a liquid embolic substance (e.g., Onyx) and performs a procedure on the vasculature of the biological subject within the catheter. Since the liquid embolic substance is of a higher density than the DMSO injected in block 1040a, the operator orients the embolic substance-containing syringe with the syringe facing upward.

[0057] FIG. 10B is a flowchart for a second exemplary method 1000b in which a contrast agent flush (e.g., about 0.2 mL) is performed to fill the catheter hub and act as a bolus (e.g., a liquid “plug”) prior to DMSO injection.

[0058] In block 1010, the operator flushes the catheter with saline to prepare the catheter. In various embodiments, since the catheter is initially empty, the operator may orient the saline-containing syringe in any direction (e.g., upward, downward, horizontally).

[0059] In block 1020, the operator injects a contrast agent (e.g., to confirm the location of the catheter within the vasculature). Since the contrast agent is denser than saline, when injecting the contrast agent, the operator orients the contrast-agent-containing syringe so that the syringe faces upward.

[0060] In block 1030, the operator flushes the catheter with saline to flush out the contrast agent. Since saline is less dense than the contrast agent, the operator orients the saline-containing syringe so that the syringe faces downward.

[0061] In block 1035b, the operator fills the catheter with a liquid bolus or "plug" to separate the saline injected in block 1030 from the DMSO that will be injected in block 1040b. The liquid used for the bolus (e.g., a contrast agent such as that used in block 1020) is denser than saline, so the operator orients the bolus-liquid-containing syringe so that the syringe faces upward.

[0062] In block 1040b, the operator injects DMSO into the catheter in preparation for injecting a liquid embolic substance (e.g., according to block 1050). Since the DMSO is separated from the saline injected in block 1030 by the bolus injected according to block 1035b, which may be a liquid denser than the DMSO, the operator orients the DMSO-containing syringe so that the syringe faces downward.

[0063] In block 1050, the operator injects a liquid embolization substance (e.g., Onyx) and performs a procedure on the vascular system of the biological subject within the catheter. Since the liquid embolization substance is denser than the DMSO injected for block 1040b, the operator orients the embolization substance-containing syringe to face upward.

[0064] FIG. 10C is a flowchart for a third exemplary method 1000c in which an additional pharmaceutically acceptable liquid matching the density of DMSO is used as a saline purge prior to DMSO injection.

[0065] In block 1010, the operator flushes the catheter with saline to prepare the catheter. In various embodiments, since the catheter is initially empty, the operator may orient the saline-containing syringe in any direction (e.g., upward, downward, horizontally).

[0066] In block 1020, the operator injects a contrast agent (e.g., to confirm the location of the catheter within the vascular system). Since the contrast agent is denser than saline, when injecting the contrast agent, the operator orients the contrast agent-containing syringe to face upward.

[0067] In block 1030, the operator flushes the catheter with saline to flush out the contrast agent. Since saline is less dense than the contrast agent, the operator orients the saline-containing syringe to face downward.

[0068] In block 1035c, the operator fills the catheter with a pharmaceutically acceptable liquid that matches the density of DMSO. Since DMSO (and thus the pharmaceutically acceptable liquid) is denser than physiological saline, the operator orients the liquid-containing syringe with the syringe facing upward. One of ordinary skill in the art will be able to identify a pharmaceutically acceptable liquid based on the metabolism of the biological subject and its known density as compared to DMSO.

[0069] In block 1040c, the operator injects DMSO into the catheter in preparation for injecting (e.g., according to block 1050) a liquid embolization substance. Since the DMSO is separated from the physiological saline injected according to block 1035c by the pharmaceutically acceptable liquid in block 1030, the operator may orient the DMSO-containing syringe with the syringe facing in any direction, but most preferably downward, to reduce the risk of introducing air bubbles.

[0070] In block 1050, the operator injects a liquid embolization substance (e.g., Onyx) and performs a procedure on the vasculature of the biological subject within the catheter. Since the liquid embolization substance is denser than the DMSO injected in block 1040c, the operator orients the embolization-substance-containing syringe with the syringe facing upward.

[0071] Based on the density (i.e., specific gravity) of the liquids within the catheter and the liquids that will be injected from the filled syringes as described in FIGS. 10A-1C, there is a significant benefit in holding each liquid-filled syringe in a different orientation such that the denser liquid is maintained in a lower orientation than the less dense liquid. Following the liquid flush / push sequence described in relation to FIGS. 10A-10C, it has been found that the risk of premature solidification of the liquid embolization substance or rupture of the catheter is reduced by up to 50%.

[0072] Although the present disclosure has been described in detail and with reference to its specific illustrative embodiments, it will be apparent to those skilled in the art that various changes and modifications can be made without departing from the spirit and scope of the present disclosure. Accordingly, the present disclosure is not limited to what has been shown and described in detail.

[0073] In addition to the embodiments described above, many examples of specific combinations are also within the scope of the present disclosure, some of which are detailed below.

[0074] Appendix 1: A method, comprising loading a first liquid having a first density into a vascular device hub having an internal volume that is fluidly connected between a syringe port and a cannula port; connecting a first syringe filled with a second liquid to the syringe port, wherein the second liquid has a second density different from the first density; orienting the first syringe at a first height relative to the vascular device hub and placing the higher density of the first liquid and the second liquid below the lower density of the first liquid and the second liquid; injecting the second liquid from the first syringe into the vascular device hub; and discharging the first liquid from the vascular device hub through the cannula port.

[0075] Appendix 2: The method according to Appendix 1 or 3 - 12, wherein the first liquid consists of a physiological saline solution and the second liquid consists of an aqueous contrast agent solution.

[0076] Appendix 3: The method according to Appendix 1 - 2 or 4 - 12, wherein the first liquid consists of an aqueous contrast agent solution and the second liquid consists of a physiological saline solution.

[0077] Appendix 4: The method according to Appendix 1 - 3 or 5 - 12, wherein the first liquid consists of a physiological saline solution and the second liquid consists of a dimethyl sulfoxide solution.

[0078] Supplementary Note 5: The first liquid consists of a dimethyl sulfoxide solution, and the second liquid consists of a liquid plugging solution that is soluble in dimethyl sulfoxide but insoluble in an aqueous solution, according to the method described in any of Supplementary Notes 1-4 or 6-12.

[0079] Supplementary Note 6: Connecting a second syringe filled with a third liquid to a syringe port, where the third liquid has a third density different from the second density, and orienting the second syringe at a second altitude with respect to the blood vessel device hub and placing the higher density of the second liquid and the third liquid below the lower density of the second liquid and the third liquid, where the second altitude is opposite to the first altitude, and further including injecting the third liquid from the second syringe into the blood vessel device hub and discharging the second liquid from the blood vessel device hub via a cannula report, according to the method described in any of Supplementary Notes 1-5 or 7-12.

[0080] Supplementary Note 7: When the second syringe is connected to the syringe port and oriented at an altitude higher than the blood vessel device hub, the third liquid is positioned above the second liquid, and the second liquid is positioned above the first liquid, according to the method described in any of Supplementary Notes 1-6 or 8-12.

[0081] Supplementary Note 8: The first liquid consists of a physiological saline solution, the second liquid consists of a dimethyl sulfoxide solution, and the third liquid contains a liquid plugging substance that is soluble in dimethyl sulfoxide but insoluble in an aqueous solution, according to the method described in any of Supplementary Notes 1-7 or 9-12.

[0082] Supplementary Note 9: The first syringe and the second syringe have a longitudinal axis, and the longitudinal axis is at 45 degrees or less from the vertical when injecting the second liquid and the third liquid, respectively, according to the method described in any of Supplementary Notes 1-8 or 10-12.

[0083] Supplementary Note 10: The method according to any one of Supplementary Notes 1-9 or 11-12, wherein when the first syringe is connected to the vascular device hub, it is oriented in the opposite orientation to when the second liquid is injected into the vascular device hub with respect to the vertical reference axis.

[0084] Supplementary Note 11: The method according to any one of Supplementary Notes 1-10 or 12, wherein the volume of the second liquid is at most 500 microliters.

[0085] Supplementary Note 12: The method according to any one of Supplementary Notes 1-11, further comprising attaching a cannula report to a blood vessel of a biological subject via a catheter (920), and discharging the first liquid via the cannula is injecting the first liquid into the blood vessel via the catheter.

[0086] Supplementary Note 13: A treatment process for arteriovenous malformation (AVM) or aneurysm, comprising the method according to any one of Supplementary Notes 1-12.

[0087] Supplementary Note 14: The treatment process according to Supplementary Note 13, wherein the third liquid contains a liquid embolizing substance that is soluble in dimethyl sulfoxide but insoluble in an aqueous solution, and releases substantially all of the liquid embolizing substance after injection of the third liquid into the target area within the biological subject.

[0088] Supplementary Note 15: A medical device including instructions for use, wherein the instructions for use include the method according to any one of Supplementary Notes 1-12.

[0089] A certain term is used throughout the description and claims to refer to a particular feature or component. As those skilled in the art will understand, different people may refer to the same feature or component by different names. This document is not intended to distinguish components or features that have different names but the same function.

[0090] As used herein, "about", "approximately", and "substantially" are understood to refer to a number within a range of the referenced number, e.g., within -10% to +10% of the referenced number, preferably within -5% to +5% of the referenced number, more preferably within -1% to +1% of the referenced number, and most preferably within -0.1% to +0.1% of the referenced number.

[0091] Furthermore, all numerical ranges herein should be understood to include all integers, zero, and natural numbers, or fractions within that range. Also, these numerical ranges should be construed as providing support for claims directed to any number or subset of numbers within that range. For example, the disclosure of 1 to 10 should be construed as supporting ranges such as 1 to 8, 3 to 7, 1 to 9, 3.6 to 4.6, 3.5 to 9.9, etc.

[0092] As used in this disclosure, the phrase "at least one of" in a list of items refers to any set of those items and all their potential combinations, including a set with a single component. For example, when referring to "at least one of A, B, or C" or "at least one of A, B, and C," the phrase is intended to cover the set of "A, B, C, A - B, B - C, and A - B - C," and the set can include one or more instances of a given component (e.g., A - A, A - A - A, A - A - B, A - A - B - B - C - C - C, etc.) and any of their ordered arrangements. For the avoidance of doubt, the phrase "at least one of A, B, and C" is not to be construed as meaning "at least one of A, at least one of B, and at least one of C."

[0093] As used in this disclosure, the term "determining" encompasses various operations that can include calculating, computing, processing, deriving, investigating, looking up (e.g., via a table, database, or other data structure), ascertaining, receiving (e.g., receiving information), accessing (e.g., accessing data in memory), reading, resolving, selecting, choosing, establishing, and the like.

[0094] Without further elaboration, it is believed that one of ordinary skill in the art can, using the foregoing description, utilize the claimed inventions to their fullest extent. The examples and aspects disclosed herein are to be construed as illustrative only and not as limitations in any way of the scope of the present disclosure. It will be apparent to those skilled in the art that changes can be made to the details of the embodiments described above without departing from the underlying principles discussed. In other words, various modifications and improvements of the embodiments specifically disclosed within the above description are within the scope of the appended claims. For example, any suitable combination of the features of the various embodiments described is also contemplated.

[0095] In the claims, reference to an element in the singular is not intended to mean "one and only one" unless specifically so recited, but rather "one or more" or "at least one." Unless specifically stated otherwise, the term "some" refers to "one or more." No claim element is to be construed under 35 U.S.C. Section 112, paragraph (f), unless the element is expressly recited using the phrase "means for" or "step for." All structural and functional equivalents of the various elements of the embodiments described within the present disclosure that are known or later become known to those of ordinary skill in the art are hereby expressly incorporated herein by reference and are intended to be encompassed by the present claims. Also, nothing disclosed within the present disclosure is intended to be dedicated to the public, whether or not such disclosure is explicitly recited in the claims.

Claims

1. A method (900) comprising: loading (910) a first liquid (150a) having a first density into a vascular device hub (110) having an internal volume that is fluidly connected between a syringe port (112) and a cannula port (114); connecting (930) a first syringe (120) filled with a second liquid (150a) to the syringe port, the second liquid having a second density different from the first density; orienting the first syringe at a first elevation relative to the vascular device hub and positioning the higher density of the first liquid and the second liquid below the lower density of the first liquid and the second liquid (940); injecting the second liquid from the first syringe into the vascular device hub and discharging the first liquid from the vascular device hub via the cannula port (950). The method (900).

2. The method according to claim 1, wherein the first liquid consists of a physiological saline solution and the second liquid consists of an aqueous contrast agent solution.

3. The method according to claim 1, wherein the first liquid consists of an aqueous contrast agent solution and the second liquid consists of a physiological saline solution.

4. The method according to claim 1, wherein the first liquid consists of a physiological saline solution and the second liquid consists of a dimethyl sulfoxide solution.

5. The method according to claim 1, wherein the first liquid consists of a dimethyl sulfoxide solution and the second liquid consists of a liquid embolization solution that is soluble in dimethyl sulfoxide but insoluble in an aqueous solution.

6. connecting (940) a second syringe (120) filled with a third liquid (150c) to the syringe port, the third liquid having a third density different from the second density; orienting the second syringe at a second elevation relative to the vascular device hub and positioning the higher density of the second liquid and the third liquid below the lower density of the second liquid and the third liquid (940), the second elevation being opposite to the first elevation. Injecting the third liquid from the second syringe into the vascular device hub and discharging the second liquid from the vascular device hub via the cannula report (960); The method according to claim 1, further comprising.

7. The method according to claim 6, wherein when the second syringe is connected to the syringe port and oriented at a higher altitude than the vascular device hub, the third liquid is positioned above the second liquid, and the second liquid is positioned above the first liquid.

8. The method according to claim 6, wherein the first liquid consists of a physiological saline solution, the second liquid consists of a dimethyl sulfoxide solution, and the third liquid contains a liquid plugging substance that is soluble in dimethyl sulfoxide but insoluble in an aqueous solution.

9. The method according to claim 6, wherein the first syringe and the second syringe have a longitudinal axis, and the longitudinal axis is 45 degrees or less from the vertical when injecting the second liquid and the third liquid, respectively.

10. The method according to claim 1, wherein when the first syringe is connected to the vascular device hub, it is oriented in the opposite direction to when the second liquid is injected into the vascular device hub with respect to the vertical reference axis.

11. The method according to claim 1, wherein the volume of the second liquid is at most 500 microliters.

12. Further comprising attaching the cannula report to a blood vessel of a biological subject via a catheter (920), The method according to claim 1, wherein discharging the first liquid via the cannula injects the first liquid into the blood vessel via the catheter.

13. A treatment process for arteriovenous malformation (AVM) or aneurysm, the treatment process comprising the method according to any one of claims 1-12.

14. The treatment process according to claim 13, wherein the third liquid contains a liquid plugging substance that is soluble in dimethyl sulfoxide but insoluble in an aqueous solution, and substantially all of the liquid plugging substance is released after injecting the third liquid into the target area within the biological subject.

15. A medical device including an instruction manual, the instruction manual including the method according to any one of claims 1-12.

Images