Vascular device loading

Abstract

Vascular device loading may be provided by loading a first liquid having a first density into a vasculature hub having an internal volume fluidly connected between a syringe port and a cannula port; connecting a first syringe loaded 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 vasculature hub to place a greater density of the first liquid and the second liquid below a less density of the first liquid and the second liquid; and injecting the second liquid from the first injector into the vasculature hub to expel the first liquid from the vasculature hub via the cannula port.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This disclosure claims the benefit of U.S. Provisional Patent Application No. 63 / 356,970, filed on June 29, 2022, entitled “PROCESSES FOR LOADING VASCULARD EVICES,” the entire contents of which are incorporated herein by reference. Technical Field

[0003] The present disclosure generally relates to the use of devices for delivering fluids into the vasculature of a biological subject. More specifically, the present disclosure describes an improved process or method for delivering multiple fluids through a single catheter and syringe assembly while avoiding or reducing mixing between the fluids to improve the treatment of various medical conditions in a biological subject. Summary of the invention

[0004] The present disclosure provides vascular device loading, for example, for treating or preventing medical conditions by targeted delivery of multiple individual fluids. For example, in the liquid embolization process, five liquid flushes can be used (for example, the first saline injection is to prepare the catheter, the contrast agent injection is to confirm the catheter position and visualize the vascular system of the biological object, the second saline injection is to flush the contrast agent, the DMSO injection is to prepare the target position for injecting the liquid embolism, and the liquid embolism injection is to treat AVM or aneurysm). Because it is known that the liquid embolization solution prematurely hardens (for example, not in the target site) when the embolism contacts with blood, contrast agent, saline or its combination, it is important to avoid mixing the fluid in the catheter and the syringe to reduce the risk of premature hardening. Therefore, the appropriate loading of the vascular device as described in the present invention can improve the delivery of the fluid to the target site, reduce the risk of applying excessive pressure on the device or the biological object, reduce operator strain or fatigue, reduce the amount of the fluid to be injected (for example, via improved delivery of the target), and various other benefits that will be apparent to those of ordinary skill in the art when reading in detail.

[0005] Additional features and advantages of the disclosed methods and apparatus are described in and will become apparent from the following detailed description and accompanying drawings. The features and advantages described herein are not all-inclusive, and in particular, many additional features and advantages will be apparent to one of ordinary skill in the art in view of the drawings and description. Furthermore, it should be noted that the language used in the specification is primarily selected for readability and instructional purposes, and not to limit the scope of the inventive subject matter. BRIEF DESCRIPTION OF THE DRAWINGS

[0006] Figure 1A syringe is shown oriented approximately 60 degrees from vertical with its tip pointing upward, connected to a vascular device hub, the syringe containing a second liquid that is denser than a first liquid in the vascular device hub, in accordance with an embodiment of the present disclosure.

[0007] Figure 2 A syringe is shown oriented substantially vertically with its tip pointing upward, connected to a vascular device hub, the syringe containing a second liquid that is denser than a first liquid in the vascular device hub, in accordance with an embodiment of the present disclosure.

[0008] Figure 3 To illustrate avoiding the introduction of air bubbles into a vascular device system according to an embodiment of the present disclosure, the syringe contains a second liquid that is denser than a first liquid in the vascular device hub.

[0009] Figure 4 Illustrating undesirable channeling or backflow of two liquids through one another, according to an embodiment of the present disclosure, the syringe contains a second liquid that is denser than the first liquid in the hub of the vascular device.

[0010] Figure 5 Undesirable channeling or backflow of two liquids past each other in a vascular device is shown according to an embodiment of the present disclosure, the vascular device comprising a first liquid in a vascular device hub, wherein the first liquid has a density less than a second liquid in a syringe.

[0011] Figure 6 A syringe connected to a vascular device hub is shown oriented approximately 30 degrees from vertical with its tip pointing downward, the syringe containing a second liquid less dense than a first liquid in the vascular device hub in accordance with an embodiment of the present disclosure.

[0012] Figure 7 Undesirable passage or bubbling of a second liquid in a syringe through a first liquid in a vascular device hub is shown, wherein the first liquid is denser than the second liquid in the syringe, in accordance with an embodiment of the present disclosure.

[0013] Figure 8 A syringe is shown according to an embodiment of the present disclosure, oriented substantially vertically with its tip pointing downward and connected to a vascular device hub, wherein the syringe contains a second liquid having a density greater than a first liquid in the vascular device, and the device hub contains a third liquid flowably connected to the first liquid and the second liquid, the third liquid having a density greater than the first liquid and the second liquid.

[0014] Fig. 9 is a flow chart of an example method for vascular device loading according to an embodiment of the present disclosure.

[0015] Fig. 10A - Fig. 10C is a flow chart of an example usage method according to an embodiment of the present disclosure.

[0016] It will be appreciated that the various fluid levels and devices have been simplified for purposes of explanation so as not to distract from the features discussed in the present disclosure. DETAILED DESCRIPTION

[0017] Various embolics can be used to address the interruption of the liquid flow path in the lumen or vascular system, and contain liquid or non-liquid materials. Many disease states, including but not limited to arteriovenous malformations (AVM) or aneurysms, can be treated by filling with one or more embolics. Some aneurysm treatment processes include the use of a catheter (e.g., a microcatheter) and a series of liquid volumes pushed through the catheter, including contrast medium liquid, flushing liquid, preloaded liquid and embolic liquid and combinations thereof. Some liquid embolic polymers can be designed to condense, precipitate or otherwise release themselves from a flowable organic solution at an interface in contact with an aqueous liquid. Subsequently, the organic solvent leaches or diffuses from the liquid embolism to allow the embolic polymer to further solidify.

[0018] Such treatment procedures present a variety of risks, including contamination of the device used to deliver the embolism through, for example, premature clogging, coagulation, or precipitation of the embolism in the device or in a component used to deliver the embolism to the device. It has been discovered that the density differentials of the liquid continuously flowing through the vascular device require one or more specific process features to reduce the risk of device contamination when preparing to administer or administering an occlusive material, such as a liquid embolism, through the device.

[0019] Thus, the present invention provides methods or processes for loading a vascular device with an embolism. The present invention also provides methods for reducing the risk of premature liquid embolism solidification or adverse flow characteristics that lead to catheter rupture or embolic behavior when using a vascular device (e.g., a microcatheter) to treat an aneurysm in a biological subject in need. The present invention also provides methods for treating or preventing an AVM or aneurysm in a biological subject.

[0020] In some embodiments, the above process features include a maximum angle of the syringe from the vertical to prevent one liquid from settling into another liquid or preventing one liquid from channeling through or around another liquid, the density or viscosity of the liquid flush, the density or viscosity of the liquid residing in the lumen of the vascular device, or a combination thereof.

[0021] As discussed herein, the present disclosure relates to the angles and positions of various components. Unless otherwise clearly stated, the orientation of these components and elements is with reference to the longitudinal axis of the environment in which the component or element is located. As used herein, the vertical upward position corresponds to a 0 degree rotation, the horizontal position corresponds to a 90 degree rotation from the vertical upward position, and the vertical downward position corresponds to a 180 degree rotation from the vertical upward position (and 90 degrees from the horizontal line to the floor). For example, an imaginary fluid will settle to have a surface that is horizontal in a reference coordinate system (ignoring the influence of the meniscus). A float positioned in the imaginary fluid will have a portion positioned vertically upward relative to the fluid (e.g., floating above the fluid surface in a reference coordinate system) and a portion positioned downward relative to the fluid (e.g., immersed below the fluid surface in a reference coordinate system).

[0022] In some embodiments, when loading a vascular device with a liquid polymer plug that will be released from the flowable organic solution upon contact with an aqueous liquid, it is important to flush all or substantially all of the aqueous liquid that may be present in the vascular device (e.g., due to a previous pre-loading step) prior to loading the plug into the vascular device. Doing so reduces the risk of premature release of the polymer plug from the solution within the vascular device, which would require increased force to flow the liquid plug from the syringe through the vascular device to the target in the biological object and increase stress on the biological object.

[0023] In some embodiments, the process provided herein comprises loading a vascular device with a liquid embolic agent and may further comprise a pre-loading process as described herein.

[0024] In some embodiments, a process for preloading a vascular device may include 1) pushing a volume of liquid contrast through the device at a specific flow rate, 2) pushing a volume of saline through the device at a specific flow rate, and 3) pushing a volume of flushing fluid through the device at a specific flow rate to preload the device for loading liquid emboli. Each of the liquid contrast, saline, flushing fluid, and liquid emboli may have a different density or viscosity, or a different density and viscosity. In addition, in some embodiments, each of the liquid contrast, saline, flushing fluid, and liquid emboli may have a different base carrier solvent. That is, in some embodiments, the liquid emboli may be in an organic solvent, such as dimethyl sulfoxide (DMSO), etc., while saline is an aqueous solution of salt and water. Similarly, in some embodiments, the flushing fluid may be in an organic solvent, such as DMSO, etc. In addition, in some embodiments, the liquid contrast may be water-based or in an organic carrier, or a combination thereof.

[0025] The vascular device preloading sequence includes one or more steps in which a second liquid volume is pushed through the vascular device containing the first liquid volume. In some embodiments, each of the liquid contrast agent, saline, flushing fluid, and liquid embolization can independently be the first liquid volume or the second liquid volume.

[0026] In some embodiments, when the density of the first liquid volume is less than the second liquid volume and the first liquid volume and the second liquid volume are to be fluidly connected, a syringe containing the second liquid volume is operably connected to the vascular device and oriented between approximately 60 degrees from vertical to substantially vertical, with the syringe tip pointing upward when the second liquid volume is pushed through the vascular device.

[0027] Figure 1 - Figure 8 Various interactions between different fluids according to various embodiments of the present disclosure are shown. Figure 1 - Figure 8 Each of the vascular hub device 110 shows a portion of a syringe 120 that is connected for delivering a liquid to the vascular hub device 110. The vascular hub device 110 includes a syringe port 112 configured to establish fluid communication with the syringe 120. At the other end of the vascular hub device 110 opposite the first syringe port 112a is a cannula port 114, to which the first end of the catheter 140 is shown attached. The opposite end (not shown) of the catheter 140 is inserted into the biological object to deliver various fluids or devices to a target location in the biological object (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 a plug 130 is shown to block fluid communication between the internal volume of the vascular device hub and the external environment. The plug 130 allows various tools, dilators, guides, or other devices to selectively approach the biological object, or allows the application of additional syringes, negative pressure sources, etc.

[0028] exist Figure 1 - Figure 8 In each of the , various liquids 150a-c (generally or collectively, liquid 150) are shown. Figure 1 - Figure 8 As described in more detail, the liquids 150 may separate based on their respective densities, may mix or percolate with each other to establish equilibrium based on density flow through a common space.

[0029] In various embodiments, the conduit 140 through which the aforementioned liquid 150 flows can be coated or uncoated. In some embodiments, the inner surface of the conduit 140 can be hydrophobic, hydrophilic, or amphiphilic.

[0030] Figure 1 and Figure 2140, wherein a first liquid 150a of saline solution is present in the vascular device hub 110 and the catheter 140, and a second liquid 150b of DMSO solution is present in the syringe 120. In some embodiments, to avoid introducing air bubbles into the liquid 150 being pushed through the vascular device 110, the syringe 120 containing the second liquid 150b is oriented with its tip downward when connected to the vascular device hub 110 (e.g., as shown in FIG. 140 ). Figure 3 ), and then the syringe 120 is oriented substantially vertically (as shown Figure 2 ). In some embodiments, the syringe 120 is substantially vertical when connected to the syringe port 112, and the longitudinal axis of the syringe 120 is at an angle of no more than 45 degrees to the vertical direction, more preferably no more than 30 degrees to the vertical direction, and even more preferably no more than 15 degrees to the vertical direction. In some embodiments, when the liquids 150 have different densities, this flipping sequence between vertically upward and vertically downward reduces undesirable mixing of the two liquids 150, and in the final state, the denser liquid 150 is below the less dense liquid 150.

[0031] Figure 4 An example of the undesirable channeling effect of two immiscible liquids 150 having different densities is shown, which the present disclosure seeks to mitigate. For example, by having a syringe 120 of a second liquid 150b having a greater density above a first liquid 150a having a lesser density for a longer period of time, the two liquids 150 may pass through each other such that the less dense liquid 150 forms a layer on top of the more dense liquid 150.

[0032] like Figure 5 As shown, another undesirable channeling of two liquids may occur where the second liquid 150b is injected through the vascular device hub 110, but due to the horizontal orientation of the device, the first liquid 150a flows back from the vascular device hub 110 rather than being injected through the catheter 140.

[0033] like Figure 6 As shown, another undesirable channeling effect of the two liquids may occur, Figure 6 Shown is the undesired passageway or bubbling of a first liquid 150a (e.g., saline) through a denser second liquid 150b (e.g., contrast agent) through the vascular device hub 110 as the syringe 120 is held in a substantially vertical orientation while a first liquid 150a is pushed from the syringe 120 into the vascular device hub 110.

[0034] Figure 7The orientation of the syringe 120 relative to the vascular device hub 110 is shown, wherein the syringe 120 containing the second liquid 150b is operably connected to the vascular device hub 110. As shown, the syringe 120 is oriented between about 30 degrees from vertical, but may also be oriented at other angles between about 45 degrees from substantially vertical, with the syringe tip pointing downward. In the example shown, because the first liquid 150a is denser than the second liquid 150b, when the first liquid 150a and the second liquid 150b are placed in fluid communication (e.g., flowably connected), the second liquid 150b floats on the first liquid 150a and does not interact or mix with the first liquid 150a channel, which is consistent with the embodiment of the present invention. Figure 4 - Figure 6 The relative or horizontal orientation in question behaves in the opposite way.

[0035] In some embodiments, the liquid embolism has a viscosity of about 12 centipoise or greater. In some embodiments, the liquid embolism 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 embolism is denser than a liquid contrast agent. Therefore, when sequentially loading and injecting various fluid volumes of saline solution, liquid embolism, liquid contrast agent, etc. having different densities, attention should be paid to the orientation of the syringe 120 introducing the new liquid 150 relative to the vascular device hub 110 holding the earlier introduced liquid 150.

[0036] For example, a bolus of third liquid 150c (e.g., liquid contrast agent) may be fluidly positioned between the interface between first liquid 150a and second liquid 150b in order to prevent DMSO-based second liquid 150b in syringe 120 from acting through the passage of first liquid 150a comprised of saline solution in vascular device hub 110, or to prevent first liquid 150a from flowing back into syringe 120. In various embodiments, the volume of the bolus will vary based on the volume of vascular device hub 110, but in some embodiments, the volume of the bolus is up to about 500 microliters (μL).

[0037] Figure 8 Such a bolus of third liquid 150c is shown, which may be obtained by first loading the vascular device hub 110 with the first liquid 150a and then injecting the bolus with an upwardly directed syringe 120 (eg, Figure 2150c) into the vascular device hub 110. For example, enough third liquid 150c is injected to fill the vascular device hub 110 (e.g., 0.2 milliliters (mL)), and the catheter 140 still contains the first liquid 150a. Once the bolus is loaded into the vascular device hub 110, the operator can remove the syringe 120 carrying the third liquid 150c and attach another syringe 120 carrying the second liquid 150b to the syringe port 112, with the new syringe 120 pointing downward (e.g., Figure 8 ). Thus, using different orientations to introduce the various liquids 150 reduces the chance of mixing or channeling. Note that saline has a lower density than DMSO, which has a lower density than contrast fluid.

[0038] A challenge to understanding how these various liquids 150 flow through the fluid mechanics of the system is visualization.Many liquids 150 have similar or identical colors, or are difficult to visually distinguish by opaque, colored or translucent parts (catheter, microcatheter, syringe, etc.).Creating "real world" conditions in a laboratory environment may require that a transparent version of the product (usually "off-the-shelf" purchase) be made opaque or colored.Once transparent parts are formed, colored dyes or other distinguishing features may be added to the various liquids 150 to distinguish liquids 150 from each other, which may require testing to confirm that the addition of dyes or other factors will not modify or change the relevant chemistry or fluid properties.Once confirming chemistry and fluid properties, then modified fluids can be used together with modified (transparent) parts to visualize the fluid mechanics in the implantable system in real time, and various angles, flushing techniques and operating sequences can be tested.

[0039] Fig. 9 is a flow chart of an example method 900 for loading a vascular device according to an embodiment of the present disclosure. The method 900 may be repeated in multiple iterations of blocks 910-950 to sequentially load various liquids 150 through a vascular device for delivering the liquid 150 to a target site in a biological subject. Therefore, although the examples given herein describe 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 the method 900.

[0040] For example, during a liquid embolic procedure, five liquid flushes may be used (e.g., a first saline injection to prepare the catheter, a contrast injection to confirm catheter position and visualize the vasculature of the biological subject, a second saline injection to flush the contrast, a DMSO injection to prepare the target site for injection of the liquid embolic, and a liquid embolic injection to treat the AVM or aneurysm). Because liquid embolic solutions are known to prematurely harden (e.g., not at the target site) when the embolization comes into contact with blood, contrast, saline, or a combination thereof, avoiding mixing of fluids in the catheter and syringe is important to reduce the risk of premature hardening.

[0041] Because liquid embolization procedures are often lengthy and require an operator to manually inject various liquids into a target site (e.g., by depressing a plunger of a syringe), method 900 provides for various positions and orientations of the syringe relative to the hub of the vascular device at specific times to reduce the risk of mixing of fluids of different densities, thereby reducing the risk (or amount) of hardening of the liquid embolization prior to delivery to the target site.

[0042] At block 910, an operator loads a liquid into the vascular device hub. In various embodiments, the liquid may be loaded by injection from a syringe (eg, according to block 950), by aspiration or regurgitation from a source, or during manufacture of the vascular device hub.

[0043] At block 920, the operator connects the cannula port of the vascular device hub to a blood vessel in the biological subject via the catheter. In various embodiments, the catheter can be inserted into the blood vessel before or after being connected to the cannula port. The operator can also manipulate the opposite end of the catheter.

[0044] In various embodiments, block 920 may be performed before block 910, or may be omitted in the iteration of blocks 910 to 950. For example, while loading multiple fluids into the medical device for injection into a target site in a biological subject via catheter 140, an operator may only attach the cannula port to the catheter once; the initial connection may be maintained during multiple loadings and injections of different fluids.

[0045] At block 930, the operator connects the syringe to the vascular device hub. In various embodiments, the syringe may be screwed directly to the vascular device hub, snapped into place on the vascular device hub, or held in place on the vascular device hub under pressure. In some embodiments, tubing may be connected between the tip of the syringe and the syringe port; allowing the operator additional ergonomic options for how to hold the syringe in hand when positioning two fluids at different heights. In various embodiments, various needles, washers, etc. may be used to establish a pressure seal for delivering the fluid held by the syringe to the vascular device hub. In some embodiments, to avoid introducing air bubbles into one or more fluids already loaded into the vascular device hub, the syringe is connected to the vascular device hub with the tip of the syringe pointing downward and the syringe oriented substantially vertically (e.g., as in FIG. 1 ). Figure 3 shown).

[0046] At block 940, the operator orients the syringe relative to the vascular device hub based on the densities of the liquids in the syringe and the vascular hub device, respectively, such that the syringe is at a height relative to the vascular device hub to place a denser liquid below a less dense liquid.

[0047] For example, for a first liquid consisting of a saline solution (loaded in the first iteration of block 910) and a second liquid consisting of an aqueous contrast medium solution in a syringe (connected in the first iteration of block 930) that is denser than the saline solution, the saline solution (and the vascular device hub) is placed above the aqueous contrast medium solution (and the syringe). Continuing with this example, when flushing the contrast medium with saline (e.g., in the second iteration of blocks 910-950), the orientation of the device is reversed so that the saline solution (now in the syringe) is placed above the aqueous contrast medium solution (now loaded in the vascular device hub).

[0048] For example, for a first liquid consisting of a DMSO solution (loaded in the current iteration of block 910) and a second liquid consisting of a liquid plug (whose density is less than the DMSO solution) in a syringe (connected in the current iteration of block 930), the DMSO solution (and the vascular device hub) are placed below the liquid plug (and the syringe).

[0049] At block 950, the operator injects liquid from the syringe into the vascular device hub, which expels some or all of the liquid previously loaded into the vascular device hub from the cannula port and toward the biological object. 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 of the syringe may flush the vascular device hub; displacing at least 50% of the volume of the vascular device hub through the cannula port. In some embodiments, the injection may load a bolus of liquid into the vascular device hub (e.g., as part of a subsequent iteration of block 910) to serve as a buffer with the next liquid to be injected (e.g., per a subsequent iteration of blocks 910-950).

[0050] Method 900 can be repeated several times to provide successive volumes of fluid to a target area of ​​a biological subject to treat an AVM or an aneurysm or other condition treatable by targeted delivery of multiple different fluids. Method 900 can be provided in a set of instructions for a medical device (e.g., an injector, a vascular device hub, a catheter, or a kit / assembly thereof).

[0051] Fig. 10A - Fig. 10C is a flow chart of exemplary usage methods 1000a - c according to an embodiment of the present disclosure.

[0052] Fig. 10A is a flow chart of a first exemplary method of use 1000a when performing a liquid embolic injection for a liquid embolic such as a cyanoacrylate glue (e.g., Histoacryl (n-butyl cyanoacrylate), Glubran (n-butyl cyanoacrylate plus metacryloxysulpholane), Magic Glue or Purefill (n-hexyl cyanoacrylate), TruFill (n-butyl cyanoacrylate), or Fuaile (n-butyl cyanoacrylate plus cyanoacrylate), Onyx (a premixed, radiopaque, injectable embolic fluid consisting of EVOH (co-vinyl alcohol), DMSO (dimethyl sulfoxide), and TA (micronized tantalum powder)), Squid (EVOH, DMSO, TA), Menox (EVOH, TA, DMSO), or Precipitated Hydrophobic Injection Solution (PHIL; polylactide-co-glycolide, polyhydroxyethyl-methacrylate, triiodophenol, DMSO), with five liquid flushes.

[0053] At block 1010, the operator primes the catheter by flushing it with saline. In various embodiments, when the catheter is initially empty, the operator can orient the syringe containing saline in any direction (eg, pointing upward, downward, horizontally).

[0054] At block 1020, the operator injects contrast media (eg, to confirm catheter position in the vasculature). Because contrast media is denser than saline, when injecting contrast media, the operator orients the syringe containing the contrast media so that the syringe points upward.

[0055] At block 1030, the operator flushes the catheter with saline to flush the contrast agent. Because the density of saline is less than the density of contrast agent, the operator orients the syringe containing saline to point the syringe downward.

[0056] At block 1040a, the operator injects DMSO into the catheter in preparation for injecting the liquid embolism (eg, per block 1050). Because DMSO is denser than the saline injected at block 1030, the operator orients the syringe containing DMSO so that the syringe points upward.

[0057] At block 1050, the operator injects a liquid embolism (eg, Onyx) into the catheter to perform the procedure on the vasculature of the biological subject. Because the liquid embolism is denser than the DMSO injected at block 1040a, the operator orients the syringe containing the embolism to point upward.

[0058] Fig. 10B is a flow chart of a second exemplary method 1000b in which a contrast flush (eg, of approximately 0.2 mL) is performed to fill the catheter hub and act as a bolus (eg, liquid "plug") prior to DMSO injection.

[0059] At block 1010, the operator primes the catheter by flushing it with saline. In various embodiments, when the catheter is initially empty, the operator can orient the syringe containing saline in any direction (eg, pointing upward, downward, horizontally).

[0060] At block 1020, the operator injects contrast media (eg, to confirm catheter position in the vasculature). Because contrast media is denser than saline, when injecting contrast media, the operator orients the syringe containing the contrast media so that the syringe points upward.

[0061] At block 1030, the operator flushes the catheter with saline to flush out the contrast agent. Because the density of saline is less than the density of the contrast agent, the operator orients the syringe containing saline to point the syringe downward.

[0062] At block 1035b, the operator fills the catheter with a bolus or "plug" of liquid to separate the saline injected in block 1030 and the DMSO to be injected in block 1040b. Because the liquid used as the bolus is denser than saline (e.g., like the contrast agent used in block 1020), the operator orients the syringe containing the bolus liquid to point the syringe upward.

[0063] At block 1040b, the operator injects DMSO into the catheter in preparation for injecting the liquid embolism (e.g., per block 1050). Because the DMSO is separated from the saline injected in block 1030 by the bolus injected at block 1035b (which may be a liquid denser than DMSO), the operator orients the syringe containing DMSO to point the syringe downward.

[0064] At block 1050, the operator injects a liquid embolism (eg, Onyx) into the catheter to perform the procedure on the vasculature of the biological subject. Because the liquid embolism is denser than the DMSO injected in block 1040b, the operator orients the syringe containing the embolism to point upward.

[0065] Fig. 10C is a flow chart of a third example method 1000c in which an additional pharmaceutically acceptable liquid matching the density of DMSO is used as a saline wash prior to DMSO injection.

[0066] At block 1010, the operator primes the catheter by flushing it with saline. In various embodiments, when the catheter is initially empty, the operator can orient the syringe containing saline in any direction (eg, pointing upward, downward, horizontally).

[0067] At block 1020, the operator injects contrast media (eg, to confirm catheter position in the vasculature). Because contrast media is denser than saline, when injecting contrast media, the operator orients the syringe containing the contrast media so that the syringe points upward.

[0068] At block 1030, the operator flushes the catheter with saline to flush out the contrast agent. Because the density of saline is less than the density of the contrast agent, the operator orients the syringe containing saline to point the syringe downward.

[0069] At block 1035c, the operator fills the catheter with a pharmaceutically acceptable liquid that matches the density of DMSO. Because DMSO (and therefore the pharmaceutically acceptable liquid) is denser than saline, the operator orients the syringe containing the liquid to point the syringe 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 compared to DMSO.

[0070] At block 1040c, the operator injects DMSO into the catheter in preparation for injecting the liquid embolism (e.g., per block 1050). Because the DMSO is separated from the saline injected in block 1030 by the pharmaceutically acceptable liquid per block 1035c, the operator can orient the syringe containing DMSO to point the syringe in any direction, although downward is most preferred to reduce the risk of introducing air bubbles.

[0071] At block 1050, the operator injects a liquid embolism (eg, Onyx) into the catheter to perform the procedure on the vasculature of the biological subject. Because the liquid embolism is denser than the DMSO injected in block 1040c, the operator orients the syringe containing the embolism to point upward.

[0072] Based on the density (or specific gravity) of the liquid in the conduit and the Fig. 10A - Fig. 10C In the case of liquids injected by the filled syringes described in , there is a significant benefit in maintaining each liquid-filled syringe in a different orientation; orienting the syringes so that the denser liquid is maintained in a lower orientation than the less dense liquid. Fig. 10A - Fig. 10C Following the described fluid flush / push sequence, the risk of premature solidification of the fluid embolism or catheter rupture has been found to be reduced by up to 50%.

[0073] Although the present invention has been described in detail with reference to specific illustrative embodiments thereof, it will be apparent to those skilled in the art that various changes and modifications may be made without departing from the spirit and scope of the present disclosure. Therefore, the present invention is not limited to the specific contents shown and described.

[0074] In addition to the above embodiments, many examples of specific combinations are within the scope of the present invention, some of which are detailed below:

[0075] Item 1: A method comprising: loading a first liquid having a first density into a vascular device hub, the vascular device hub having an internal volume fluidly connected between a syringe port and a cannula port; connecting a first syringe loaded 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 to place a liquid with a higher density of the first liquid and the second liquid below a liquid with a lower density of the first liquid and the second liquid; and injecting the second liquid from the first syringe into the vascular device hub to discharge the first liquid from the vascular device hub via the cannula port.

[0076] Item 2: The method of any one of Items 1 or 3-12, wherein the first liquid consists of a saline solution and the second liquid consists of an aqueous contrast medium solution.

[0077] Item 3: The method of any one of items 1-2 or 4-12, wherein the first liquid consists of an aqueous contrast medium solution and the second liquid consists of a saline solution.

[0078] Item 4: The method of any one of items 1-3 or 5-12, wherein the first liquid consists of a saline solution and the second liquid consists of a dimethyl sulfoxide solution.

[0079] Item 5: The method of any one of Items 1-4 or 6-12, wherein the first liquid consists of a dimethyl sulfoxide solution, and the second liquid consists of a liquid embolic solution that is soluble in dimethyl sulfoxide but insoluble in an aqueous solution.

[0080] Item 6: The method as described in any of Items 1-5 or 7-12, further comprising: connecting a second syringe loaded with a third liquid to the syringe port, wherein the third liquid has a third density different from the second density; orienting the second syringe at a second height relative to the vascular device hub to place the liquid with a higher density among the second liquid and the third liquid below the liquid with a lower density among the second liquid and the third liquid, wherein the second height is opposite to the first height; and injecting the third liquid from the second syringe into the vascular device hub to discharge the second liquid from the vascular device hub via the cannula port.

[0081] Item 7: The method of any of Items 1-6 or 8-12, wherein when a second syringe is connected to the syringe port and oriented at a higher elevation than the vascular device hub, the third liquid is positioned above the second liquid and the second liquid is positioned above the first liquid.

[0082] Item 8: The method of any one of Items 1-7 or 9-12, wherein the first liquid consists of a saline solution, the second liquid consists of a dimethyl sulfoxide solution, and the third liquid comprises a liquid plug that is soluble in dimethyl sulfoxide but insoluble in aqueous solution.

[0083] Item 9: A method as described in any one of Items 1-8 or 10-12, wherein the first syringe and the second syringe include a longitudinal axis, and when the second liquid and the third liquid are injected respectively, the angle between the longitudinal axis and the vertical direction is no more than 45 degrees.

[0084] Item 10: The method of any of items 1-9 or 11-12, wherein the first syringe, when connected to the vascular device hub, is oriented oppositely relative to a vertical reference axis as compared to when the second liquid is injected into the vascular device hub.

[0085] Item 11: The method of any one of Items 1-10 or 12, wherein the volume of the second liquid is up to 500 microliters.

[0086] Item 12: The method of any one of Items 1-11, further comprising: attaching (920) the cannula port to a blood vessel of a biological object via a catheter; and wherein discharging the first liquid via the cannula will inject the first liquid into the blood vessel via the catheter.

[0087] Item 13: A treatment process for an arteriovenous malformation (AVM) or an aneurysm, comprising a method as described in any one of Items 1-12.

[0088] Item 14: The treatment process as described in Item 13, wherein the third liquid contains a liquid embolism that is soluble in dimethyl sulfoxide but insoluble in an aqueous solution, and after the third liquid is injected into the target area of ​​the biological subject, the aqueous solution releases substantially all of the liquid embolism.

[0089] Item 15: A medical device comprising instructions for use, wherein the instructions for use comprise the method of any one of Items 1-12.

[0090] Certain terms are used throughout the specification and claims to refer to specific features or components. As will be appreciated by those skilled in the art, different people may refer to the same feature or component by different names. This document is not intended to distinguish between components or features that have different names but the same function.

[0091] As used herein, "about", "approximately" and "substantially" should be understood to refer to a number within a range of the referenced number, for example, a range of -10% to +10% of the referenced number, preferably a range of -5% to +5% of the referenced number, more preferably a range of -1% to +1% of the referenced number, and most preferably a range of -0.1% to +0.1% of the referenced number.

[0092] In addition, all numerical ranges in the present invention should be understood to include all integers, non-negative integers or fractions within the range. In addition, these numerical ranges should be interpreted as supporting claims involving any numerical value or numerical subset within the range. For example, the disclosure of 1 to 10 should be interpreted as supporting ranges of 1 to 8, 3 to 7, 1 to 9, 3.6 to 4.6, 3.5 to 9.9, etc.

[0093] As used in this disclosure, a phrase referring to "at least one" of a list of items refers to any set of those items, including sets with single members and every potential combination thereof. 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 including: A, B, C, A-B, B-C, and A-B-C, wherein the set may include one or more instances of a given member (e.g., A-A, A-A-A, A-A-B, A-A-B-B-C-C-C, etc.) and any order thereof. For the avoidance of doubt, the phrase "at least one of A, B, and C" should not be construed to mean "at least one of A, at least one of B, and at least one of C."

[0094] As used in this disclosure, the term "determine" encompasses various actions that may include calculating, computing, processing, deriving, investigating, searching (e.g., via a table, database, or other data structure), ascertaining, receiving (e.g., receiving information), accessing (e.g., accessing data in a memory), retrieving, parsing, selecting, choosing, establishing, and the like.

[0095] Without further detailed description, it is believed that those skilled in the art can use the foregoing description to make the most of the claimed invention. The various examples and aspects disclosed in the present invention should be interpreted as being illustrative only and not limiting the scope of the present invention in any way. It is obvious to those skilled in the art that the details of the above examples may be changed without departing from the basic principles discussed. In other words, various modifications and improvements of the examples specifically disclosed in the above description are within the scope of the appended claims. For example, any suitable combination of the features of the various examples described is contemplated.

[0096] In the claims, unless explicitly stated, referring to an element in the singular does not mean "one and only one", but rather means "one or more" or "at least one". Unless specifically stated otherwise, the term "some" means one or more. A claim element should not be interpreted under the provisions of 35 U.S.C. §112(f) unless the element is explicitly stated using the phrase "means for..." or "step for...". All structural and functional equivalents of the elements of the various embodiments described in this disclosure, which are known or will later be known to a person of ordinary skill in the relevant art, are expressly incorporated into the present invention by reference and are intended to be covered by the claims. In addition, nothing disclosed in this disclosure is intended to be dedicated to the public, regardless of whether such disclosure is explicitly stated 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 interior volume fluidly connected between a syringe port (112) and a cannula port (114); connecting (930) a first syringe (120) loaded with a second liquid (150a) to the syringe port, wherein the second liquid has a second density different from the first density; orienting (940) the first syringe at a first height relative to the vascular device hub to position a denser liquid of the first liquid and the second liquid below a less dense liquid of the first liquid and the second liquid; and The second liquid is injected (950) from the first syringe into the vascular device hub to expel the first liquid from the vascular device hub via the cannula port.

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

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

4. The method according to claim 1, wherein: The first liquid consists of a 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 embolic solution that is soluble in dimethyl sulfoxide but insoluble in an aqueous solution.

6. The method according to claim 1, further comprising: connecting (940) a second syringe (120) loaded with a third liquid (150c) to the syringe port, wherein the third liquid has a third density different from the second density; orienting (940) the second syringe at a second height relative to the vascular device hub to position a denser liquid of the second liquid and the third liquid below a less dense liquid of the second liquid and the third liquid, wherein the second height is opposite the first height; and The third liquid is injected (960) from the second syringe into the vascular device hub to expel the second liquid from the vascular device hub via the cannula port.

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

8. The method according to claim 6, wherein: The first liquid consists of a saline solution, the second liquid consists of a dimethyl sulfoxide solution, and the third liquid comprises a liquid plug that is soluble in dimethyl sulfoxide but insoluble in the aqueous solution.

9. The method according to claim 6, wherein: The first syringe and the second syringe include a longitudinal axis, and when the second liquid and the third liquid are injected respectively, the angle between the longitudinal axis and the vertical direction is no more than 45 degrees.

10. The method according to claim 1, wherein: The first syringe, when connected to the vascular device hub, is oriented in an opposite orientation relative to a vertical reference axis than when the second liquid is injected into the vascular device hub.

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

12. The method according to claim 1, further comprising: attaching (920) the cannula port to a blood vessel of a biological subject via a catheter; as well as Wherein draining the first liquid through the cannula will inject the first liquid into the blood vessel through the catheter.

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

14. The treatment process of claim 13, wherein: The third liquid comprises a liquid embolus that is soluble in dimethyl sulfoxide but insoluble in an aqueous solution, and the aqueous solution releases substantially all of the liquid embolus after the third liquid is injected into a target area of ​​a biological subject.

15. A medical device comprising instructions for use, wherein: The instructions for use include a method according to any one of claims 1-12.

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