Patent Description:
The delivery of fluid compositions which solidify in vivo is useful for numerous vascular applications including the occlusion of neurovascular aneurysms, arteriovenous malformations ("AVMs"), arteriovenous fistulas ("AVF"), abdominal aortic aneurysm Type <NUM> and Type <NUM> endoleaks, bleeding, tumors (including hypervascular tumors), varicose seals, and portal vein embolization, as well as in the sterilization of mammals and the treatment of urinary incontinence. Some liquid embolic compositions include a water insoluble, biocompatible, non-biodegradable polymer, dissolved in biocompatible solvent. These liquid embolic compositions can include a water insoluble, radiopaque material or contrast agent to permit the clinician to visualize delivery of the composition to the vascular treatment site via conventional techniques such as fluoroscopy.

Liquid embolic compositions may be delivered via a catheter technique that permits the clinician to selectively place the catheter at any desired location within the vasculature. A catheter tip is directed to the desired location by use of a visualization technique, such as fluoroscopy. The liquid embolic composition is delivered to the catheter through a syringe connected to the catheter hub. Some current practices require the liquid embolic composition to be continuously mixed for <NUM> minutes in a vial to achieve adequate suspension of the contrast agent during delivery. Inadequate mixing or delays in delivery after mixing may result in contrast agent settling, causing poor visualization of the liquid embolic composition during injection. Accurate visualization helps ensure that the liquid embolic composition is being delivered to the intended vascular site, to detect undesired reflux of the liquid embolic composition on the catheter tip, or to detect premature solidification of the liquid embolic composition causing catheter or branch vessel occlusion.

<CIT> describes an apparatus for generating foam, where the apparatus includes a syringe type device comprising a syringe barrel having an annular chamber and an inner wall defining an inner chamber.

<CIT> describes an injection device that includes first and second leakproof compartments. Syringe type devices are also known from <CIT>, <CIT> and <CIT>.

The present disclosure describes a mixing syringe comprising a fluid housing defining an internal housing chamber and a fluid outlet in communication with the internal housing chamber. The mixing syringe further comprises an outer plunger disposed within the internal housing chamber of the fluid housing. The outer plunger defines a cavity and comprises an outer plunger head defining a flow passage between the cavity and the internal housing chamber. The outer plunger is configured to move relative to the fluid housing between a proximal position and a distal position. The mixing syringe further comprises an inner plunger at least partially disposed within the cavity defined by the outer plunger. The inner plunger is configured to move between a retracted position and an advanced position relative to the outer plunger. When the outer plunger is in the distal position and fluid is disposed in the cavity of the outer plunger, movement of the inner plunger toward the advanced position causes the inner plunger to force the fluid through the flow passage of the outer plunger head and through the fluid outlet of the fluid housing. The outer plunger head is configured to rotate within the internal housing chamber of the fluid housing. The outer plunger head includes at least one scraper element dimensioned to contact an inner housing wall of the fluid housing during rotational movement thereof.

In some embodiments, the outer plunger comprises an outer barrel defining the cavity, and the outer plunger head is connected to the outer barrel. In addition, in some embodiments, the inner plunger comprises an inner plunger barrel and an inner plunger head connected to the inner plunger barrel.

The at least one scraper element may be dimensioned to extend to an outer periphery of the outer plunger head. In embodiments, the outer plunger head includes a plurality of scraper elements.

In some embodiments, the outer plunger head is dimensioned to establish a substantial fluid tight seal with the inner housing wall of the fluid housing. In certain embodiments, the inner plunger head is dimensioned to establish a substantial fluid tight seal with an inner barrel wall of the outer plunger.

In some embodiments, a fluid is disposed within the internal housing chamber. In some embodiments, the fluid may be a liquid embolic composition including a contrast agent. The contrast agent may be water insoluble. In some embodiments, the contrast agent may be one of tantalum, tantalum oxide, barium sulfate, gold, tungsten, or platinum.

In some embodiments, a clamp retains the outer plunger in the second distal position. The clamp is removable to permit movement of the outer plunger to the first proximal position. The clamp may include first and second end restraints interconnected by a connecting member. The first end restraint can be positioned about a flange of the fluid housing and the second end restraint can be positioned about an outer plunger grip of the outer plunger.

In some embodiments, an end cap is releasably mounted to the fluid housing to enclose the fluid outlet. The end cap may include a cap body which is positionable about a fluid nozzle of the fluid housing and a pin extending from the cap body. The pin is configured to be received within the fluid outlet to close the fluid outlet.

The disclosure also describes a mixing syringe comprising a fluid housing, an outer plunger, and an inner plunger. The fluid housing defines a longitudinal axis and has proximal and distal ends. In addition, the fluid housing defines an internal housing chamber configured to receive a medical agent, and a fluid outlet in communication with the internal housing chamber. The outer plunger is disposed within the internal housing chamber of the fluid housing, and comprises an outer barrel defining a barrel cavity, and an outer plunger head connected to the outer barrel. The outer plunger is configured for longitudinal movement within the internal housing chamber of the fluid housing between a proximal position and a distal position. In addition, the outer plunger head defines a flow passage in communication with the barrel cavity. The outer plunger is configured such that, upon movement of the outer plunger toward the distal position, the medical agent passes from the internal housing chamber through the flow passage into the barrel cavity of the outer plunger. The inner plunger is at least partially disposed within the barrel cavity of the outer plunger, and comprises an inner plunger barrel, and an inner plunger head connected to the inner plunger barrel. The inner plunger is configured for longitudinal movement between a retracted position and an advanced position relative to the outer plunger. With the outer plunger in the distal position and the medical agent disposed in the barrel cavity of the outer plunger, movement of the inner plunger toward the advanced position causes the inner plunger head to force the medical agent through the flow passage of the outer plunger head for disposition through the fluid outlet of the fluid housing.

In some embodiments, the at least one scraper element is dimensioned to scrape an inner housing wall of the fluid housing as the outer plunger head rotates relative to the internal housing chamber.

In some embodiments, the outer plunger head is dimensioned to establish a substantial fluid tight seal with an inner housing wall of the fluid housing and the inner plunger head dimensioned to establish a substantial fluid tight seal with an inner barrel wall of the outer plunger.

The syringe may further comprise an end cap configured to be releasably mounted to the fluid housing to enclose the fluid outlet.

The disclosure also describe a method, e.g., for delivering a medical agent to a subject. The method comprises advancing an outer plunger within an internal housing chamber defined by a fluid housing of a syringe such that a medical agent in the internal housing chamber passes through a flow passage defined by an outer plunger head of the outer plunger and into a cavity defined by the outer plunger, and moving an inner plunger through the cavity of the outer plunger to direct the medical agent back through the flow passage for delivery through a fluid outlet of the fluid housing, the fluid outlet being in communication with the internal housing chamber.

The method may include positioning the outer plunger in a distal position such that a volume of the medical agent is stored within the outer barrel, and, thereafter, retracting the outer plunger to a proximal position such that the volume of the medical agent is disposed within the internal housing chamber of the fluid housing. Advancing the outer plunger within the internal housing chamber may comprise advancing the outer plunger after retracting the outer plunger to the proximal position.

In some embodiments, the method includes releasably securing the outer barrel in the distal position. Releasably securing may include mounting a clamp to the fluid housing and the outer plunger.

In some embodiments, the medical agent is a liquid embolic composition. The liquid embolic composition includes a water insoluble contrast agent, and advancing the outer plunger at least partially mixes the contrast agent within the liquid embolic composition.

In some embodiments, rotating the outer plunger head within the internal housing chamber of the fluid housing facilitates mixing of the contrast agent within the liquid embolic composition. In some embodiments, the outer plunger head includes at least one wiper element and wherein rotating the outer plunger head causes the at least one wiper element to displace the contrast agent relative to a housing wall of the fluid housing.

The present disclosure is also directed a method of making a medical syringe.

The mixing syringe described herein is adapted to uniformly mix a medical agent such as a liquid embolic composition containing a contrast agent and deliver the mixed composition to a catheter or conduit accessing, e.g., the vasculature of a subject. The outer plunger head with scraper elements may help remove any residual contrast agent from the walls of the fluid housing and uniformly mix the components within the apparatus prior to delivery to a catheter. In some examples, the mixing syringe can be pre-filled with the liquid embolic composition, thereby eliminating the need to mix the components prior to the procedure, which helps avoid spills that may occur during the mixing stage and may help reduce treatment time and maximize clinician efficiency.

Particular embodiments of the present disclosure are described below with reference to the accompanying drawings; however, it is to be understood that the disclosed embodiments are merely examples of the disclosure and may be embodied in various forms. Well-known functions or constructions are not described in detail to avoid obscuring the present disclosure in unnecessary detail. Therefore, specific structural and functional details disclosed herein are not to be interpreted as limiting, but merely as a basis for the claims and as a representative basis for teaching one skilled in the art to employ the present disclosure in virtually any appropriately detailed structure. Like reference numerals may refer to similar or identical elements throughout the description of the figures.

<FIG> illustrate an example mixing syringe <NUM>. Although the mixing syringe <NUM> will be discussed in the context of delivering a liquid embolic composition having two or more components, including liquid and/or solid components, to the vasculature of a subject, the mixing syringe <NUM> may deliver any suitable medical agent or composition, such as any suitable medical agent or composition for treatment of blood vessels, aneurysms, arteriovenous malformations ("AVMs"), arteriovenous fistula ("AVF"), abdominal aortic aneurysm Type <NUM> and Type <NUM> endoleaks, portal vein embolization, bleeding, tumors (including hypervascular tumors), or varicose seals, as well as any medical agent or composition for the sterilization of mammals or for the treatment of urinary incontinence.

Referring to <FIG>, the mixing syringe <NUM> includes a fluid housing <NUM>, an outer plunger <NUM> at least partially disposed within the fluid housing <NUM>, and an inner plunger <NUM> which is at least partially disposed within the outer plunger <NUM>. The fluid housing <NUM> includes an internal housing chamber <NUM> that at least partially receives the outer and inner plungers <NUM>, <NUM>, and defines a reservoir configured to receive a liquid embolic composition prior to mixing and injecting. The outer plunger <NUM> includes an outer plunger head <NUM>, which includes a plurality of annular ribs <NUM> configured to establish a sealing relation with inner wall surface 12i of the fluid housing <NUM> and at least one or more scraping elements <NUM> that may extend radially outward to at least the outer perimeter 42p of the outer plunger head <NUM> as best depicted in <FIG>. The plurality of annular ribs <NUM> and the scraping elements <NUM> ensure sufficient mixing of the liquid embolic composition, including the resuspension of any settled contrast agent or contrast agent which has adhered to inner wall surface 12i of the fluid housing <NUM>, to allow immediate injection of a liquid embolic composition with uniformly suspended contrast agent therein.

With reference again to <FIG>, the mixing syringe <NUM> includes a fluid housing <NUM>, an outer plunger <NUM> at least partially disposed within the fluid housing <NUM>, and an inner plunger <NUM> which is at least partially disposed within the outer plunger <NUM>. The fluid housing <NUM> defines a longitudinal axis "k" and has a proximal end <NUM> and a distal end <NUM>. A flange <NUM> is mounted adjacent the proximal end <NUM> for engagement by the clinician. The flange <NUM> may include opposed openings <NUM> which may receive a suture or ligament to secure the fluid housing <NUM> relative to a support, the subject, or the outer plunger <NUM>. The fluid housing <NUM> includes an internal housing chamber <NUM> terminating adjacent the distal end <NUM> of the fluid housing <NUM>. The internal housing chamber <NUM> at least partially receives the outer and inner plungers <NUM>, <NUM>, and also defines a reservoir configured to receive the medical agent during mixing and activation of the outer and inner plungers <NUM>, <NUM>.

With reference to <FIG>, in conjunction with <FIG> and <FIG>, the fluid housing <NUM> further defines a receptacle <NUM> at its distal end for reception and/or coupling to a connector associated with a delivery conduit such as a catheter. In one embodiment, the receptacle <NUM> may have an internal thread <NUM> configured to cooperate with and mate with a corresponding thread of a luer connector, which is in turn coupled to the catheter. A fluid nozzle <NUM> extends through the receptacle <NUM> and defines a fluid outlet <NUM> in fluid communication with the internal housing chamber <NUM> for delivering the medical agent into the catheter.

With reference to <FIG>, <FIG> and <FIG>, an end cap <NUM> is releasably coupled to the fluid nozzle <NUM> to contain the medical agent within the internal housing chamber <NUM> of the fluid housing <NUM> until the clinician is ready to inject the medical agent. In one embodiment, the end cap <NUM> is adapted to establish a friction fit with the fluid nozzle <NUM>, e.g., the inner wall surface <NUM> of the body 36b of the end cap <NUM> may engage the outer wall of the fluid nozzle <NUM> in friction relation therewith. In other embodiments, the end cap <NUM> may include a threaded arrangement that engages the internal thread <NUM> of the receptacle <NUM>. Other releasable coupling arrangements are also envisioned. In the example shown in <FIG>, the end cap <NUM> includes a pin 36i that fills the internal diameter (ID) of the fluid nozzle <NUM>. The pin 36i extends from body 36b and may include an elastomeric material adapted to establish a seal within the fluid nozzle <NUM>. The pin 36i may help prevent settling of contrast agent in the fluid nozzle <NUM>.

Referring again to <FIG>, the outer plunger <NUM> includes an outer plunger grip <NUM>, an outer plunger barrel <NUM>, and an outer plunger head <NUM>. The outer plunger head <NUM> may be monolithically formed with the outer plunger barrel <NUM>, or may be a separate component mounted about the distal end of the outer plunger barrel <NUM>. The outer plunger barrel <NUM> and the outer plunger head <NUM> define a barrel cavity <NUM> extending through these components, which at least partially accommodates or receives the inner plunger <NUM> (see also <FIG>). Further, in some examples, the internal diameter (ID) of the outer plunger barrel <NUM> provides a uniform surface devoid of any areas in which the contrast agent may adhere or settle. The outer plunger <NUM> is adapted for reciprocal movement (e.g., in a direction parallel to longitudinal axis "k") within the internal housing chamber <NUM> of the fluid housing <NUM>. The outer plunger <NUM> also may be configured to rotate within the internal housing chamber <NUM>, such that the outer plunger <NUM> may be adapted for rotational movement within the internal housing chamber <NUM>.

Referring now to <FIG>, <FIG>, the outer plunger head <NUM> may define a plurality of outer annular ribs <NUM>, which are dimensioned to establish a sealing relation with the inner wall surface 12i of the fluid housing <NUM>. In one embodiment, one or more of the ribs <NUM> defines a transverse dimension or diameter generally approximating the internal dimension of the fluid housing <NUM>. The outer plunger head <NUM>, including the annular ribs <NUM>, may be formed of an elastomeric or resilient material such as rubber.

The outer plunger head <NUM> also includes at least one or more scraper elements <NUM> extending from the distal end of the outer plunger head <NUM> dimensioned to contact the inner housing wall 12i of the fluid housing <NUM> to assist in the mixing of the medical agent. In one embodiment, the outer plunger head <NUM> includes a plurality of scraper elements <NUM> arranged in predefined spaced relation about the distal end. For example, the scraper elements <NUM> may extend radially outwardly relative to a central axis "m" of the outer plunger head <NUM> toward the outer perimeter 42p of the outer plunger head <NUM>. As best depicted in <FIG>, the scraper elements <NUM> each may extend radially outward to at least the outer perimeter 42p of the outer plunger head <NUM>. The scraper elements <NUM> may be linear in configuration, or, in the alternative have an arcuate profile. The scraper elements <NUM> may define a height, which increases toward the outer perimeter 42p of the outer plunger head <NUM>. The scraper elements <NUM> may be aligned with the center or central axis "m" of the outer plunger head <NUM>, and may or may not intersect at the central axis "m". In the embodiment shown in <FIG>, the scraper elements <NUM> terminate at locations radially spaced from the center axis "m" and the distal opening <NUM>.

The scraper elements <NUM> are formed of an elastomeric or resilient material sufficiently flexible to not interfere with the sealing relation established between the outer plunger head <NUM> and the inner surface 12i of the fluid housing <NUM>. In an embodiment shown on <FIG>, the scraper elements <NUM> are monolithically formed with the outer plunger head <NUM>. Four scraper elements <NUM> are shown and are equidistantly spaced relative to the central axis "m", e.g., at ninety (<NUM>) degree intervals. More or less than four scraper elements <NUM> may be provided.

Referring again to <FIG>, the inner plunger <NUM> is at least partially disposed within the barrel cavity <NUM> of the outer plunger <NUM>. The inner plunger <NUM> includes an inner plunger grip <NUM>, an inner plunger barrel <NUM>, and an inner plunger head <NUM>. The inner plunger grip <NUM> may have a different configuration than the outer plunger grip <NUM> to assist the clinician in distinguishing between the components. The inner plunger head <NUM> may include a plurality of annular ribs <NUM> each having a cross-sectional dimension approximating the inner dimension or diameter of the barrel cavity <NUM>. The ribs <NUM> establish a substantial sealing relation with the inner barrel wall 40i of the outer barrel <NUM>.

The inner plunger head <NUM> may be fabricated from any suitable elastomeric material and connected to the inner plunger barrel <NUM> through conventional means including mechanical, chemical, or thermal. Alternatively, the inner plunger head <NUM> may be monolithically formed with inner plunger barrel <NUM>. The inner plunger head <NUM> is closed at its distal end.

The inner plunger <NUM> is adapted for reciprocal longitudinal movement relative to the outer plunger <NUM>, i.e., within the barrel cavity <NUM> of the outer plunger <NUM> and in a direction substantially parallel to longitudinal axis "k. " The inner plunger <NUM> may be configured to rotate within the barrel cavity <NUM>.

Referring again to <FIG>, the mixing syringe <NUM> may also include locking mechanisms to prevent undesired movement of the syringe components prior to delivery of the medical agents, such as during transport or storage. For example, the syringe <NUM> may include a lock bar <NUM>, which extends through an opening <NUM> defined by the inner plunger barrel <NUM> of the inner plunger <NUM>. When disposed within the opening <NUM>, the lock bar <NUM> engages the outer plunger grip <NUM> of the outer plunger <NUM> thereby preventing distal movement (toward distal end <NUM> of fluid housing <NUM>) of the inner plunger <NUM> at least relative to the outer plunger <NUM> and/or proximal movement of the outer plunger <NUM> relative to the inner plunger <NUM>. The lock bar <NUM> may be removed during the procedure to permit retracting movement of the outer plunger <NUM> and advancing movement of the inner plunger <NUM>. Other arrangements for restraining movement of the components of the mixing syringe <NUM>, including the outer plunger <NUM> relative to the fluid housing <NUM>, can be used, such as the arrangements discussed below.

As indicated hereinabove, in some examples, the mixing syringe <NUM> may be prefilled with a liquid embolic composition. Suitable liquid embolic compositions to be delivered in the invention are well known. Examples of commonly known liquid embolic compositions are described in <CIT>; <CIT>; <CIT>; and <CIT>. Some liquid embolic compositions, such as the ONYX™ liquid embolic system sold by Covidien LP, Irvine, CA. , include a biocompatible polymer such as EVOH (ethylene vinyl alcohol) copolymer, a biocompatible solvent such as DMSO (dimethyl sulfoxide), and a contrast agent suspended therein to provide contrast for visualization under fluoroscopy. Formulations may vary in viscosity, for example, the lower viscosity compositions capable of travelling more distally in the vasculature and capable of penetrating more deeply into the nidus of an aneurysm or malformation.

The water insoluble contrast agents may be in particle or powder form. During treatment, it can be desirable to have the contrast agent in uniform suspension within the liquid embolic composition. However, during storage, these water insoluble contrast agents may settle and, therefore, require sufficient mixing immediately prior to delivery to achieve adequate suspension and resultant ability to visualize the composition under fluoroscopy once delivered to the desired vascular site.

<FIG> illustrate the mixing syringe <NUM> in a preferred transport or storage condition with the mixing syringe <NUM> pre-filled with the liquid embolic composition <NUM> disposed (or accommodated) within the barrel cavity <NUM> of the outer plunger <NUM>. In the transport condition, the inner plunger <NUM> is in a proximally retracted position to leave open the barrel cavity <NUM> of the outer plunger <NUM> for the liquid embolic composition <NUM> to fill. The inner plunger <NUM> may not move in the distal direction due to the volume of liquid embolic composition <NUM> within the barrel cavity <NUM>. The outer plunger <NUM> is in a distal advanced position. As previously disclosed, the end cap <NUM> and the lock bar <NUM> facilitate the containment of the liquid embolic composition <NUM> and restrain movement of the components within the mixing syringe <NUM> until such time as the clinician is ready to deliver the liquid embolic composition <NUM>. Such a pre-filled configuration can be advantageous to the clinician in reducing procedure preparation time and eliminating spills from the transfer of liquid embolic composition <NUM> from vial to syringe.

As best depicted on <FIG>, the lock bar <NUM> can be removed from the inner plunger barrel <NUM> of the inner plunger <NUM> to allow for movement of the outer plunger <NUM> relative to the inner plunger <NUM>. In one embodiment, the outer plunger <NUM> is retracted or moved in a proximal direction "b" (<FIG>) to displace the outer plunger head <NUM> from the fluid nozzle <NUM> of the fluid housing <NUM> creating a void within the internal housing chamber <NUM> for accommodating a volume of the liquid embolic composition. For example, a volume of the liquid embolic composition <NUM> is displaced from the barrel cavity <NUM> of the outer plunger <NUM> and is accommodated within the internal housing chamber <NUM> (<FIG>). The inner plunger <NUM> may be further retracted in a proximal direction "b" to further open the barrel cavity <NUM> of the outer plunger <NUM> if desired.

With reference to <FIG> and <FIG>, the procedure is continued by advancing the barrel cavity <NUM> from a first proximal position (<FIG>) in the direction of arrow "t" (<FIG>) causing the outer plunger head <NUM> of the outer plunger <NUM> to force the liquid embolic composition <NUM> into the opening <NUM> of the outer plunger head <NUM> for reception within the flow passage <NUM> of the barrel cavity <NUM>. <FIG> illustrates an intermediate position of the outer plunger <NUM>. The mouth of the flow passage <NUM> enables the liquid embolic composition <NUM> to be received within the barrel cavity <NUM> while minimizing flow resistance.

As the outer plunger head <NUM> is advanced distally within the internal housing chamber <NUM>, the scraper elements <NUM> contact the inner wall 12i of the fluid housing <NUM>, and scrape any settled or adhered residual contrast agent from the inner wall 12i. The contents of the liquid embolic composition <NUM> including the contrast agent are directed under pressure along a flow pattern leading through the leading opening <NUM> of the outer plunger head <NUM>, the flow passage <NUM> and into the barrel cavity <NUM> of the outer plunger <NUM> creating sufficient turbulence (identified as arrows "z" in <FIG>) to ensure the suspension of the contrast agent within the liquid embolic composition <NUM>.

In addition to the reciprocal movement of each of the inner plunger <NUM> and the outer plunger <NUM> within the fluid housing <NUM>, the outer plunger <NUM> may be rotated about its axis in either direction "j" (<FIG> and <FIG>) to further facilitate removal via the scraper elements <NUM> of any contrast agent that may have settled or may have adhered to the inner wall 12i of the fluid housing <NUM>. Further, the outer plunger <NUM> also may be rotated when in its second distal or advanced position of <FIG> such that the scraper elements <NUM> engage the forward internal end face <NUM> (<FIG>) within the internal housing chamber <NUM> to remove any contrast agent attached to the forward end face <NUM> (<FIG>). The outer plunger <NUM> may be advanced, retracted and rotated several times to ensure that the scraper elements <NUM> releases all the residual contrast agent particles from the inner wall 12i and the end face <NUM> of the fluid housing <NUM>. Preferably, the clinician repeats advancement and retraction of the outer plunger <NUM> at least three (<NUM>) times prior to delivery of the medical agent.

Referring now to <FIG>, when the clinician is ready to deliver the liquid embolic composition <NUM> from the mixing syringe <NUM>, the end cap <NUM> is removed from the fluid nozzle <NUM>. A luer connector <NUM> is coupled to the receptacle <NUM>. The luer connector <NUM> is coupled to a catheter placed at the desired treatment site within the vasculature.

The process is continued by advancing the inner plunger <NUM> in the direction of arrow "<NUM>" from the retracted position (<FIG>) through the barrel cavity <NUM> to the distal position (<FIG>) such that the inner plunger head <NUM> drives the liquid composition <NUM> through the fluid outlet <NUM> of the fluid nozzle <NUM> under pressure for passage to the catheter, and delivery to the targeted vascular treatment site. Upon passage of the liquid embolic composition <NUM> through the fluid nozzle <NUM> under pressure, the contrast agent is further mixed within the liquid embolic composition <NUM> thereby further uniformly suspending the contrast agent within the liquid embolic composition <NUM>.

<FIG> illustrates another embodiment of the mixing syringe <NUM>. In this embodiment, the mixing syringe <NUM> includes a fastener, such as a clamp <NUM>, which restrains movement of the outer plunger <NUM> relative to the fluid housing <NUM>. The clamp <NUM> may include, opposed end restraints <NUM>, <NUM> interconnected by connecting member <NUM>. The end restraints <NUM>, <NUM> may be generally c-shaped and positioned over the respective plunger grip <NUM> of the outer plunger <NUM> and the flange <NUM> of the fluid housing <NUM>. With this arrangement, the outer plunger <NUM> is restricted from moving, e.g., in the proximal direction, relative to the fluid housing <NUM> thereby maintaining the volume of liquid embolic composition within the barrel cavity <NUM> of the outer plunger <NUM> and preventing preloading of the liquid embolic composition within the internal housing chamber <NUM> of the fluid housing <NUM>. The clamp <NUM> may be removed prior to retraction of the outer plunger <NUM> which movement is shown in <FIG>. Once the outer plunger <NUM> is distally advanced to the distal position of <FIG>, the clamp <NUM> may be reinstalled or mounted about the plunger grip <NUM> of the outer plunger <NUM> and the flange <NUM> of the fluid housing <NUM>. The inner plunger <NUM> is advanced to distribute the liquid embolic composition <NUM>. The clamp <NUM>, when installed, will prevent movement of the outer plunger <NUM> in the proximal direction, which may otherwise occur, in response to the volumetric forces of the liquid embolic composition <NUM> against the outer plunger head <NUM>, i.e., realized during advancing distal movement of the inner plunger <NUM>. Thus, the clinician does not need to hold the outer plunger <NUM> to maintain the outer plunger <NUM> in the distal position during advancement of the inner plunger <NUM>.

In another embodiment, the syringe <NUM> is not prefilled with a liquid embolic composition <NUM>, but may be filled just prior to application to the subject. For example, the end cap <NUM> may be removed from the empty syringe <NUM> and the liquid embolic composition <NUM> delivered through the fluid nozzle <NUM> of the fluid housing <NUM> for reception within the barrel cavity <NUM> of the outer plunger <NUM>. The syringe <NUM> may be used in the aforedescribed manner.

In some examples, a method of making any of the mixing syringes described herein may include positioning the outer plunger <NUM> in the fluid housing <NUM> of the syringe <NUM>, and positioning the inner plunger <NUM> in the outer plunger barrel <NUM>. This may be performed in any suitable order. The method may further comprise introducing the liquid embolic composition <NUM> or another suitable fluid (e.g., another medical agent) in the fluid housing <NUM>. In some examples, the method may further comprise coupling the end cap <NUM> to the fluid nozzle <NUM> to help contain the liquid embolic composition <NUM> within internal housing chamber <NUM>.

In some examples, the method may further comprise fixing a position of the outer plunger <NUM> relative to the fluid housing <NUM>, e.g., using the lock bar <NUM>, the clamp <NUM>, or another suitable technique.

Claim 1:
A mixing syringe (<NUM>) comprising:
a fluid housing (<NUM>) defining an internal housing chamber (<NUM>) and a fluid outlet (<NUM>) in communication with the internal housing chamber (<NUM>);
an outer plunger (<NUM>) disposed within the internal housing chamber of the fluid housing, the outer plunger defining a cavity (<NUM>) and comprising an outer plunger head (<NUM>) defining a flow passage (<NUM>) between the cavity and the internal housing chamber (<NUM>), wherein the outer plunger (<NUM>) is configured to move relative to the fluid housing (<NUM>) between a proximal position and a distal position, wherein the outer plunger head (<NUM>) is configured to rotate within the internal housing chamber (<NUM>) of the fluid housing (<NUM>), and wherein the outer plunger head (<NUM>) includes at least one scraper element (<NUM>) dimensioned to contact an inner housing wall (12i) of the fluid housing (<NUM>) during rotational movement thereof; and
an inner plunger (<NUM>) at least partially disposed within the cavity (<NUM>) defined by the outer plunger (<NUM>), the inner plunger (<NUM>) being configured to move between a retracted position and an advanced position relative to the outer plunger (<NUM>),
whereby, when the outer plunger (<NUM>) is in the distal position and fluid is disposed in the cavity (<NUM>) of the outer plunger (<NUM>), movement of the inner plunger (<NUM>) toward the advanced position causes the inner plunger (<NUM>) to force the fluid through the flow passage of the outer plunger head (<NUM>)and through the fluid outlet of the fluid housing (<NUM>).