Patent Description:
Transarterial embolization therapy, tumor embolization, and transcatheter arterial embolization (TAE), involve administration of embolization material directly to a target tissue (e.g. a tumor), via a microcatheter, thereby blocking or reducing the blood flow to cancer cells.

Radioembolization combines embolization and radiation therapy and has been used in particular for the treatment of liver cancers, where it has been shown to extend the lives of patients with inoperable tumors and improve their quality of life. During the procedure, tiny glass or resin beads loaded with a radioactive isotope, such as yttrium Y-<NUM>, are placed inside the blood vessels that feed the tumor, thereby delivering a high dose of radiation to the tumor, while sparing normal tissue.

A major problem associated with embolization is "non-target embolization", where the embolic material travels to blood vessels, other than those intended, thus damaging healthy tissues, resulting with unpleasant and even hazardous outcomes. Possible scenarios include gastric ulcers caused by liver embolization, as well as cases where embolic material refluxes alongside the microcatheter reaching the wall of the stomach, possibly causing ischemia and ulceration. An additional phenomenon, which is abundant especially in advanced stage liver cancer, is non-target embolization through arterioportal shunts.

Moreover, in order to reach as close as possible to the tumor, the embolization catheter must be advanced into continuously smaller and sometimes tortuous vessels, accessibility to which is difficult, if not precluded, using large and/or stiff catheters. In addition, blood vessels in the body tend to go into spasm when manipulated, causing an ineffective embolic material delivery. Accordingly, flexible micro-sized catheters are an absolute necessity.

Prior art embolization catheters in the field of the invention are inter alia disclosed in <CIT> and <CIT>.

The invention is defined by appended claim <NUM>.

The present disclosure relates to an embolization microcatheter for delivery of micron-sized embolization particles to a target area; the microcatheter including a skeleton, a polymeric layer intercalated into and/or on the skeleton, a distal end opening, sized and shaped to allow delivery of a suspension, the suspension including a suspension fluid and the embolization particles; and a filter having a plurality of side openings formed in the wall of the microcatheter, proximal to and at a predetermined distance from the distal end opening, e.g. <NUM>-<NUM>, <NUM> -<NUM>, <NUM> - <NUM>, <NUM> -<NUM> or <NUM> - <NUM> from the distal end opening. Each possibility is a separate embodiment.

A major challenge associated with trans-catheter embolization is backflow of the embolization material resulting in the embolization material reaching non-target tissue (and causing damage thereto) as well as negatively affecting the delivery of the embolization material to the target tissue, thus impairing treatment effectiveness and its clinical outcome. This problem is particularly profound in radioembolization therapy, in which tiny beads, also referred to as microspheres, measuring one-third the diameter of a human hair, are utilized.

One aspect of the present disclosure provides a microcatheter configured to deliver smaller beads in a higher quantity in a low viscosity liquid. The filter of the herein-disclosed microcatheter, includes tiny openings, optionally in the form of axial slits, in an amount (typically more than <NUM>) allowing sufficient outflow of fluid to generate a fluid barrier that prevents backflow of particles, yet each opening being small enough to prevent passage of the embolization particles. This ensures delivery of optimal treatment doses through the end opening of the microcatheter, prevents non-target embolization and enables an essentially 'reflux free' delivery of embolization particles at much higher injection rates than those achievable using standard microcatheters. An improved treatment outcome is hence provided.

Delivery of small sized beads, such as but not limited to radioembolization beads, poses two main challenges: <NUM>) producing tiny openings without closing them off during production (e.g. during coating); and <NUM>) to form a sufficient amount of openings to ensure that the outflow of suspension fluid suffices to prevent backflow (which is particularly challenging due to the small sized beads being delivered in a large volume of low viscosity liquid), without compromising the structural integrity of the microcatheter. Advantageously, the herein disclosed microcatheter overcomes both these challenges and meets usability requirements (trackability, torqueability, pushability and radioopacity) as well as regulatory requirements (kink resistance and tensile force resistance), as further elaborated hereinbelow.

According to some embodiments, the filter may include one or more filter sections, such as <NUM>, <NUM>, <NUM>, or more filter sections. Each possibility is a separate embodiment.

According to some embodiments, at least some of the openings of the filter, (e.g. the most distal openings) may have a discrete pattern of openings that are strategically placed on the filter to allow for an increased number of filter openings.

According to some embodiments, at least some of the openings in the filter may have a unique, irregular shape. According to some embodiments, the shape of each opening is configured to have at least a first feature that corresponds to a second mating feature of a neighboring opening, such that when the features are positioned near each other, but not touching, the contours of the features are approximately inversely reciprocated.

For example, a portion of the outer perimeter of a first opening may have a first shape, which forms a protruding feature that projects or extends outwardly and a portion of the outer perimeter of a neighboring opening may have a second shape that forms an indented feature, such as a cavity or groove, wherein the contour of the protruding feature complements the contour of the indented feature. The protruding feature of the first opening is positioned approximately to, but not in contact with the indented feature of the second opening.

In one example, the outer perimeter of the shape of the opening may include a concave portion and also a convex portion.

The discrete pattern of openings on the filter may contain openings having a same shape. Optionally, the pattern may be configured with openings each having a distinct shape out of two or more different shape options. According to some embodiments, the combined shape of the openings may be of an irregular shape.

In one aspect, the filter pattern includes two different shapes for the openings. The first opening somewhat resembles a "dog bone" shape and the second shape somewhat resembles a "bead-on-a-wire" shape. Optionally, the dog bone shape may be an hourglass shape, a dumbbell shape or a shape somewhat resembling a stretched version of the letter "H". Optionally, the "bead-on-a-wire" shape may instead be in the shape of an addition sign ("plus" sign") or the letter "t".

The distinct shape of opening is configured so as to obtain several advantages. First of all, it enables tight stacking of the openings. In addition, it was unexpectedly found the unique shape of the openings also causes beads, flowing through microcatheter, to be "caught" within openings. This in turn decreases the inner diameter of the filter section and thus increases proximal pressure. Advantageously, as a result thereof, the volume of suspension fluid flowing out through the openings of the filter sections, proximal to the most distal filter section increases and thus further concentrate the beads delivered through the end opening of the microcatheter.

According to some embodiments, the total open area of the filter is at least twice, at least <NUM> times or at least <NUM> times, at least <NUM> times or at least <NUM> times the size of the area of the distal end opening. Each possibility is a separate embodiment. According to some embodiments, this may ensure a sufficient outflow of suspension fluid through the openings of the filter to prevent backflow and to provide a concentrated delivery of the beads through the end opening.

In order to allow the physician to push the microcatheter to its target location, the majority of the microcatheter (starting at its proximal end) must be relatively rigid. The distal end of the microcatheter, including the filter must, on the other hand, be flexible in order to enable the microcatheter to take the twists and turns required during navigation through the convoluted vasculature system, without kinking and/or without harming vessel walls.

Moreover, despite its flexibility and despite the numerous openings formed in the filter, the hereindisclosed microcatheter advantageously has a small kink-free radius and a tensile force which exceeds <NUM> N (Newtons) and thus meets the ISO <NUM> requirement.

According to the invention, there is provided an embolization microcatheter for delivery of embolization beads to a target area, the microcatheter including: a proximal end and a distal end, the distal end comprising an end opening; and a filter located between in proximity to the distal end opening; the filter including at least <NUM> openings distributed circumferentially around a wall thereof.

According to the invention, the proximal end of the microcatheter is sized and shaped to allow delivery of a suspension flowing through the microcatheter. According to the invention, the suspension comprises suspension fluid and the embolization beads. According to the invention, the filter is configured to allow outflow of the suspension fluid, while preventing outflow of the embolization beads.

According to some embodiments, the side-openings are sub-side openings. According to some embodiments, the sub-side openings may be formed by a plurality of incisions made in the polymeric layer, while leaving the skeleton intact (also referred to herein as "selective cutting". According to some embodiments, the incisions may include <NUM>-<NUM> elongated slits having a width of <NUM>-<NUM> microns or <NUM>-<NUM> microns and a length of <NUM> -<NUM> or <NUM> - <NUM>.

According to some embodiments, the at least <NUM> openings distributed in at least <NUM> discrete annular patterns. According to some embodiments, each annular pattern comprises at least <NUM> openings.

According to some embodiments, the length of the filter is defined by the distance between the distal edge of the distal most annular ring to the proximal edge of the proximal most annular ring. According to some embodiments, the total area of the filter refers to the area of the part of the microcatheter extending between the distal edge of the distal most annular ring to the proximal edge of the proximal most annular ring.

According to some embodiments, the filter comprises at least <NUM>% open area, i.e. the openings formed in the wall constitute at least <NUM>% of total area of the filter. According to some embodiments, the total open area of the filter is at least <NUM> times larger than an area of the distal end opening. According to some embodiments, the total open area of the filter is at least <NUM><NUM> in size.

According to some embodiments, the at least <NUM> openings are sized and shaped to allow a flow of the embolization beads downstream the filter at a volume flow rate which allows delivery of essentially all particles in the suspension through the distal end opening, while preventing their backflow.

According to some embodiments, the embolization microcatheter has a tensile strength of at least 5N.

According to some embodiments, the at least <NUM> openings are axially distributed.

According to some embodiments, the embolization microcatheter includes a skeleton formed of braided or coiled wires; and a polymeric layer intercalated into and/or overlaying the skeleton. According to some embodiments, the skeleton has a thickness of <NUM>-<NUM> microns or <NUM>-<NUM> microns. As a non-limiting example, the skeleton may have a thickness of about <NUM> microns. According to some embodiments, the microcatheter further includes a hydrophilic coating overlaying the outer surface of the microcatheter. According to some embodiments, the at least <NUM> openings are formed through the outer surface and the hydrophilic coating. According to some embodiments, the microcatheter further includes an inner layer lining the inner surface of the microcatheter. According to some embodiments, the inner coating includes or is made of polytetrafluoroethylene (PTFE). According to some embodiments, the filter is devoid of the inner layer.

According to some embodiments, the openings may be conical. According to some embodiments, the openings may have a smaller cross section at the inner surface of the microcatheter than at the outer surface of the microcatheter. According to some embodiments, the width of each of the at least <NUM> openings is in the range of about <NUM>-<NUM> microns, <NUM>-<NUM> microns, or <NUM>-<NUM> microns, as measured on the inner surface of the microcatheter. Each possibility is a separate embodiment. According to some embodiments, the length of each of the at least <NUM> openings is in the range of about <NUM>-<NUM> microns, as measured on the inner surface of the microcatheter. According to some embodiments, the length of each of the plurality openings/incisions is in the range of about <NUM> - <NUM> or <NUM> - <NUM>, as measured on the inner surface of the microcatheter. Each possibility is a separate embodiment.

According to some embodiments, the at least <NUM> openings may be formed by virtue of forming a plurality of incisions (also referred to herein as side openings) in the polymeric layer, while leaving the skeleton intact, such that the resulting number of side openings (also referred to herein "sub-side openings) is greater than the number of incisions made in the polymeric layer. According to some embodiments, the resulting number of (sub)-side-openings is at least twice the number of side openings made in the polymeric layer. According to some embodiments, the resulting number of (sub)-side-openings is at least four times the number of side openings made in the polymeric layer. According to some embodiments, the resulting number of (sub)-side-openings is at least <NUM> times the number of side openings made in the polymeric layer. According to some embodiments, the resulting number of (sub)-side-openings is at least <NUM> times the number of side openings made in the polymeric layer. According to some embodiments, the resulting number of (sub)-side-openings is at least <NUM> times the number of side openings made in the polymeric layer.

According to some embodiments, the filter includes at least <NUM> openings. According to some embodiments, the filter includes at least <NUM> openings. According to some embodiments, the filter includes at least <NUM>,<NUM> openings. According to some embodiments, the filter includes at least <NUM>,<NUM> openings. According to some embodiments, the filter includes at least <NUM>,<NUM> openings. According to some embodiments, the filter includes at least <NUM>,<NUM> openings.

According to the invention, the at least <NUM> openings are essentially bone shaped or bead-on-string shaped.

According to some embodiments, the microcatheter includes at least two longitudinally spaced-a-part filter sections. According to some embodiments, the microcatheter includes a first distal most filter section comprising at least <NUM> openings, a second middle filter section comprising at least <NUM> openings and a third proximal most filter section comprising at least <NUM> openings. According to some embodiments, the first, second and third filter sections are spaced apart by <NUM>-<NUM>. According to some embodiments, the second filter section is longer than the first and third filter sections. According to some embodiments, the length of the openings of the third filter section is larger than a length of the openings of the first and second filter sections. According to some embodiments, the shape of the openings in the first filter section is different from the shape of the openings in the second and third filter sections.

According to some aspects, there is provided an embolization microcatheter for delivery of embolization beads to a target area, the microcatheter including a proximal end and a distal end, the distal end comprising an end opening; and a filter located between in proximity to the distal end opening; the filter including a plurality of openings distributed circumferentially/annularly around a wall thereof, wherein each of the plurality of openings is essentially bone shaped or bead-on-string shaped.

According to some embodiments, the proximal end is sized and shaped to allow delivery of a suspension flowing through the microcatheter. According to some embodiments, the suspension comprises suspension fluid and the embolization beads. According to some embodiments, the filter is configured to allow outflow of the suspension fluid, while preventing outflow of the embolization beads.

According to some embodiments, the plurality of openings is axially distributed.

According to some embodiments, the embolization microcatheter includes a skeleton formed of braided or coiled wires; and a polymeric layer intercalated into and/or overlaying the skeleton. According to some embodiments, the skeleton has a thickness of <NUM>-<NUM> microns or <NUM>-<NUM> microns. As a non-limiting example, the skeleton may have a thickness of about <NUM> microns. According to some embodiments, the microcatheter further includes a hydrophilic coating overlaying the outer surface of the microcatheter. According to some embodiments, the at least <NUM> openings are formed through the surface and the hydrophilic coating.

According to some embodiments, the microcatheter further includes an inner liner lining the inner surface of the microcatheter. According to some embodiments, the inner coating includes or is made of polytetrafluoroethylene (PTFE). According to some embodiments, the filter is devoid of the inner liner. According to some embodiments, the part of the microcatheter extending between the proximal end of the filter and the distal end opening is devoid of the inner liner.

According to some embodiments, the openings may be conical. According to some embodiments, the openings may have a smaller cross section at the inner surface of the microcatheter than at the outer surface of the microcatheter. According to some embodiments, the width of each of the plurality openings is in the range of about <NUM>-<NUM> microns, <NUM>-<NUM> microns, or <NUM>-<NUM> microns, as measured on the inner surface of the microcatheter. Each possibility is a separate embodiment. According to some embodiments, the length of each of the plurality openings is in the range of about <NUM>-<NUM> microns, as measured on the inner surface of the microcatheter. According to some embodiments, the length of each of the plurality openings/incisions is in the range of about <NUM> -<NUM> or <NUM> - <NUM>, as measured on the inner surface of the microcatheter. Each possibility is a separate embodiment.

According to some embodiments, the filter comprises at least <NUM> openings. According to some embodiments, the filter comprises at least <NUM> openings. According to some embodiments, the filter comprises at least <NUM>,<NUM> openings.

According to some embodiments, the microcatheter includes at least two longitudinally spaced-a-part filter sections. According to some embodiments, microcatheter includes a first distal most filter section including at least <NUM> openings, a second middle filter section including at least <NUM> openings and a third proximal most filter section including at least <NUM> openings.

According to some embodiments, the first, second and third filter sections are spaced apart by <NUM>-<NUM>. According to some embodiments, the second filter section is longer than the first and third filter sections. According to some embodiments, the length of the openings of the third filter section is larger than a length of the openings of the first and second filter sections. According to some embodiments, the shape of the openings in the first filter section is different from the shape of the openings in the second and third filter sections.

According to some aspects, there is provided an embolization microcatheter for delivery of embolization beads to a target area, the microcatheter including a proximal end and a distal end, the distal end comprising an end opening sized and shaped to allow delivery of a suspension flowing through the microcatheter; and a filter located between in proximity to the distal end opening; the filter including a plurality of openings distributed circumferentially around a wall thereof, wherein the width of each of the plurality openings is in the range of about <NUM>-<NUM> microns, as measured at the inner surface of the microcatheter.

According to some embodiments, the proximal end is sized and shaped to allow delivery of a suspension flowing through the microcatheter. According to some embodiments, the suspension comprises suspension fluid and the embolization beads. According to some embodiments, the filter is configured to allow outflow of the suspension fluid while preventing outflow of the embolization beads.

According to some embodiments, the embolization microcatheter includes a skeleton formed of braided or coiled wires; and a polymeric layer intercalated into and/or overlaying the skeleton. According to some embodiments, the skeleton has a thickness of <NUM>-<NUM> microns or <NUM>-<NUM> microns. As a non-limiting example, the skeleton may have a thickness of about <NUM> microns. According to some embodiments, the microcatheter further includes a hydrophilic coating overlaying the outer surface of the microcatheter, and wherein the at least <NUM> openings are formed through the hydrophilic coating.

According to some embodiments, the microcatheter further includes an inner liner lining the inner surface of the microcatheter. According to some embodiments, the inner liner includes or is made of polytetrafluoroethylene (PTFE). According to some embodiments, the filter is devoid of the inner liner.

According to some embodiments, the filter includes at least <NUM> openings. According to some embodiments, the filter includes at least <NUM> openings. According to some embodiments, the filter includes at least <NUM>,<NUM> openings.

According to some embodiments, the microcatheter includes at least two longitudinally spaced-a-part filter sections. According to some embodiments, the microcatheter includes a first distal most filter section including at least <NUM> openings, a second middle filter section including at least <NUM> openings and a third proximal most filter section including at least <NUM> openings. According to some embodiments, the first, second and third filter sections are spaced apart by <NUM>-<NUM>. According to some embodiments, the second filter section is longer than the first and third filter sections. According to some embodiments, the length of the openings of the third filter section is larger than the length of the openings of the first and second filter sections. According to some embodiments, the shape of the openings in the first filter section is different from the shape of the openings in the second and third filter sections.

According to some aspects, there is provided an embolization microcatheter for delivery of embolization beads to a target area, the microcatheter including a proximal end and a distal end, the distal end comprising an end opening sized and shaped to allow delivery of a suspension flowing through the microcatheter; and a filter located between in proximity to the distal end opening; the filter including a plurality of openings distributed circumferentially around a wall thereof, wherein the total open area of the filter is at least <NUM> times larger than an area of the distal end opening.

According to some embodiments, the total open area of the filter is at least <NUM> times larger than an area of the distal end opening. According to some embodiments, the total open area of the filter is at least <NUM><NUM> in size.

According to some embodiments, the plurality of openings are axial openings.

According to some embodiments, the embolization microcatheter includes a skeleton formed of braided or coiled wires; and a polymeric layer intercalated into and/or overlaying the skeleton. According to some embodiments, the skeleton has a thickness of <NUM>-<NUM> microns or <NUM>-<NUM> microns. As a non-limiting example, the skeleton may have a thickness of about <NUM> microns. According to some embodiments, the microcatheter further includes a hydrophilic coating overlaying the outer surface of the microcatheter, wherein the at least <NUM> openings are formed through the outer surface and the hydrophilic coating.

According to some embodiments, the microcatheter includes at least two longitudinally spaced-a-part filter sections.

According to some aspects, there is provided an embolization microcatheter for delivery of embolization beads to a target area, the microcatheter including a proximal end and a distal end, the distal end including an end opening sized and shaped to allow delivery of a suspension flowing through the microcatheter; and at filter located in proximity to the distal end opening; the filter including a plurality of irregularly distributed openings formed circumferentially around a wall thereof.

According to some embodiments, the total open area of the filter section is at least <NUM> times larger than an area of the distal end opening. According to some embodiments, the total open area of the filter section is at least <NUM> times larger than an area of the distal end opening. According to some embodiments, the total open area of the filter is at least <NUM> times larger than an area of the distal end opening. According to some embodiments, the total open area of the filter is at least <NUM><NUM> in size.

Certain embodiments of the present disclosure may include some, all, or none of the above characteristics. One or more technical advantages may be readily apparent to those skilled in the art from the figures, descriptions and claims included herein. Moreover, while specific characteristics have been enumerated above, various embodiments may include all, some or none of the enumerated characteristics.

In addition to the exemplary aspects and embodiments described above, further aspects and embodiments will be further expanded upon in the figures and the following detailed descriptions.

Examples illustrative of embodiments are described below with reference to figures attached hereto. Identical structures elements or parts that appear in more than one figure are generally labeled with the same number in all the figures in which they appear. Alternatively, elements or parts that appear in more than one figure may be labeled with different numbers in the different figures in which they appear. The dimensions of the components and features in the figures were chosen for convenience and clarity of presentation and are not necessarily shown to scale. The figures are listed below:.

In the following description, various aspects of the disclosure will be described. For the purpose of explanation, specific configurations and details are set forth in order to provide a thorough understanding of the different aspects of the disclosure. However, it will also be apparent to one skilled in the art that the disclosure may be practiced without specific details being presented herein. Furthermore, well-known features may be omitted or simplified in order not to obscure the disclosure.

Reference is now made to <FIG> and <FIG>, which schematically illustrate an embolization microcatheter <NUM> and an enlarged view of its distal end <NUM>, according to some aspects of the present disclosure. The embolization microcatheter includes an elongated body <NUM> having an outer diameter of <NUM> or less. Elongated body <NUM> includes a navigation section <NUM>, a filter <NUM>, and a delivery section <NUM>, the latter terminating in an end opening <NUM>. According to some embodiments, the polymeric layer forming the wall of filter <NUM> and/or delivery section <NUM> may be more flexible than the polymeric layer forming the wall of navigation section <NUM>.

The navigation section <NUM> is configured for navigating the microcatheter. As used herein, the term "navigation section" may refer to the part of the microcatheter required for pushing and/or steering the microcatheter through the vasculature to the target region. The navigation section <NUM> extends over the majority of the length of elongated body <NUM>. The navigation section <NUM> may be relatively rigid as compared to the relatively flexible filter <NUM> and delivery section <NUM> of the microcatheter. According to some embodiments, the navigation section <NUM> enables efficient delivery of the microcatheter <NUM> to a target region (not shown) e.g. by using a pusher mechanism (not shown) of a handle. Microcatheter <NUM> further includes a hub <NUM> which is molded on or otherwise attached to the proximal end of navigation section <NUM>. The hub is configured to allow access to the lumen of microcatheter <NUM> for a variety of functions, such as the injection of fluids or drugs, or the introduction of guidewires. Hub <NUM> includes a strain relief <NUM>, preferably mechanically coupled to hub <NUM>. Strain relief <NUM> may be made of a polymeric material and may, as illustrated, be tapered at its distal end. Strain relief <NUM> and be configured to provide structural support to navigation section <NUM>, to prevent it from kinking.

As used herein, the term "filter ", refers to the part of microcatheter configured to allow lateral outflow of a suspension fluid while blocking passage of beads/particles (i.e. embolization particles) flowing therein. The filter is formed at a pre-determined distance from distal outlet (also referred to herein as the "distal end opening"), e.g. <NUM>-<NUM>, <NUM> -<NUM>, <NUM> - <NUM>, <NUM> -<NUM> or <NUM> - <NUM> from the distal outlet. Each possibility is a separate embodiment. According to some embodiments, <NUM>-<NUM>% of the fluid injected into the catheter exits through the filter. The filter <NUM> is here illustrated as including two filter regions/sections, however other configurations of the filter section(s) are also possible, as for example illustrated in <FIG>-<FIG> (which include <NUM> filter sections) and <FIG>, <FIG> and <FIG> (which include a single filter section).

According to some embodiments, the total area of the filter refers to the area of the part of the microcatheter extending between the distal edge of the distal most annular ring to the proximal edge of the proximal most annular ring.

According to some embodiments, the filter <NUM> may be integrally formed with the delivery section <NUM> and the navigation section <NUM>. According to some embodiments, the part of the filter <NUM>, including the plurality of openings, may extend along a length of <NUM>-<NUM>, such as <NUM> -<NUM>, <NUM>- <NUM>, <NUM> - <NUM>, <NUM>-<NUM> or any other in-between suitable length. Each possibility is a separate embodiment.

As used herein, the term "delivery section" may refer to the distal end of the microcatheter extending between the distal end of filter <NUM> and distal end opening <NUM>. The delivery section <NUM> may be configured to restrict and/or impede flow and/or to modify the flow of the suspension so as to decrease the horizontal velocity of the particles along the longitudinal axis of the microcatheter.

According to some embodiments, the delivery section <NUM> may have a tapered inner surface. According to some embodiments, the delivery section may have tapered inner and outer surfaces. According to some embodiments, the delivery section may have an essentially non-tapered inner surface. Each possibility is a separate embodiment. According to some embodiments, the length of the delivery section may be in the range of <NUM>-<NUM>, <NUM>-<NUM>, <NUM>-<NUM>, <NUM>-<NUM> or any other suitable length within the range of <NUM>-<NUM>. Each possibility is a separate embodiment. According to some embodiments, the length of the delivery section may be approximately <NUM>. As used herein, the term "approximately" with regards to the length of the delivery section may refer to +/-<NUM>%, or +/-<NUM>%, or +-/<NUM>%. Each possibility is a separate embodiment.

As used herein, the term "distal end opening" refers to the end opening of the microcatheter leading into the lumen thereof. According to some embodiments, the distal end opening defines the termination of the microcatheter at the distal end thereof. According to some embodiments, the distal end opening may have an inner diameter essentially equal to the inner diameter of the microcatheter lumen. According to some embodiments, the distal end opening may have an inner diameter, which is smaller than the inner diameter of the microcatheter lumen leading to a narrowing of the lumen toward the end thereof.

According to some embodiments, the filter <NUM> of the microcatheter includes three sections, which may be formed integrally, as one piece. Such configuration advantageously eases the production of the microcatheter and may ensure that no attachment and/or assembly, which typically constitutes a weak link and, is required and as such, may result in detachment/dismantling of the microcatheter. However, the sections can also be formed as separate elements co-assembled to form the microcatheter.

According to some embodiments, the navigation section <NUM> of the microcatheter may be made from or include a thermoplastic elastomer, such as, but not limited to, thermoplastic polyurethane (such as Pellethane™ TPU by The Lubrizol Corporation, OH, USA) or polyether block amide (such as Pebax™ TPE by Arkema Group, Colombes, France), Nylon, Polyimide, Silicone or any combination thereof. Each possibility is a separate embodiment.

According to some embodiments, the wall of the filter and/or of the delivery section of the microcatheter may be made from thermoplastic elastomer, such as, but not limited to, thermoplastic polyurethane (such as Pellethane™ TPU by The Lubrizol Corporation, OH, USA) or polyether block amide (such as Pebax™ TPE by Arkema Group, Colombes, France), Nylon, Polyimide, Silicone or any combination thereof. Each possibility is a separate embodiment.

Reference is now made to <FIG>, which schematically illustrates a perspective, cutaway view of the distal end of a microcatheter <NUM>, according to some embodiments. Microcatheter <NUM> includes an outer polymeric layer <NUM> embedded into which is a skeleton <NUM>. According to some embodiments, skeleton <NUM> may be braided. Microcatheter <NUM> further includes an inner liner <NUM>. According to some embodiments, inner liner <NUM> may include or be made of polytetrafluoroethylene (PTFE).

According to some embodiments, and as shown in <FIG>, inner liner <NUM> extends only along a part of the microcatheter <NUM> e.g. only the part of microcatheter <NUM> proximal to its filter (here shown with elongated incisions <NUM> formed in the polymeric layer but not in skeleton <NUM>. Advantageously, the absence of line <NUM> may obviate the need to penetrate inner liner <NUM> when forming the incisions <NUM> of the filter or the need to remove inner liner material from the incisions <NUM>, if applied after the formation thereof.

According to some embodiments, microcatheter <NUM> may include a first marker <NUM> at the proximal end of the filter and a second marker <NUM> at the distal end of the filter. According to some embodiments, first marker <NUM> may be a polymeric marker. According to some embodiments, second marker <NUM> may be a metallic marker. According to some embodiments, such distribution of the markers, on the one hand ensure that microcatheter <NUM> withstands the force of at least <NUM> N and, on the other hand, prevent unraveling of the braid. Advantageously, due to the difference in radio-opaqueness, the markers may serve as indications of the proximal/distal end of the filter, when traveling through curved vasculature.

Reference is now made to <FIG> and <FIG>, which schematically illustrate a spread-out view and enlarged views (<FIG>) of a microcatheter <NUM> in which the filter includes three filter sections 310a-310c, according to some embodiments, each of filter sections 310a-310c including a plurality if side openings <NUM>, <NUM> and <NUM>, arranged in annular rings <NUM>, <NUM> and <NUM>, respectively. Microcatheter <NUM> is here shown to be a <NUM> French microcatheter; however, those skilled in the art will appreciate the microcatheter may be of another suitable size, for example, but not limited to <NUM> French or <NUM> French. Microcatheter <NUM> is suitable for controlled delivery of small (<NUM>-<NUM> microns) embolization beads (also referred to as "microspheres"). In one example, the small embolization beads may be in the size range of <NUM>-<NUM> microns. Microcatheter <NUM> is not limited to radioembolization beads but may also be utilized for the delivery of larger beads. According to some embodiments, microcatheter <NUM> is suitable for use in the treatment of arteriovenous malformations and hypervascular tumors, such as but not limited to uterine fibroids (UFE) and hepatoma, embolization of prostatic arteries (PAE) and for symptomatic benign prostatic hyperplasia (BPH).

Filter section 310a is the most proximal of filter sections 310a-310c and is positioned approximately L1 mm (wherein L1 is in the range of <NUM> - <NUM>) proximally to distal end opening <NUM>. In one example, filter section 310a is positioned about <NUM> proximally to the distal end opening <NUM>. The number of openings (collectively referred to as <NUM>, also referred to herein as slits, included in filter section 310a may be at least <NUM>, or at least <NUM>, or at least <NUM>,<NUM>, or at least <NUM>,<NUM>, or more. By way of example, <FIG>, illustrates the filter section 310a as having about <NUM>,<NUM> openings (<NUM> rows x <NUM> columns). Those skilled in the art will appreciate the number of openings is not limited to this value. According to some embodiments, filter section 310a may have a total length L2 of <NUM> to <NUM>. By way of example, filter section 310a may have a length of about <NUM>.

As best seen in <FIG>, openings <NUM> are relatively long (longer than openings <NUM> and <NUM> of filter sections 310b and 310c respectively), and may have a length, for example of <NUM> microns - <NUM> microns, as measured on the inner surface of the microcatheter. By way of example, <FIG>, illustrates the openings <NUM> as having a length of <NUM> microns, as measured on the inner surface of the microcatheter. Openings <NUM> are narrow and may have a width of <NUM> microns - <NUM> microns. By way of example, and as illustrated in <FIG>, openings <NUM> may have a width of <NUM> microns. Each annular ring of openings is spaced apart from its neighboring ring of openings by approximately <NUM> microns - <NUM> microns. For example, in <FIG>, each annular ring <NUM> is spaced apart from its neighboring annular ring by about <NUM> microns. The size and shape of openings <NUM> serve to ensure that even the smallest embolization beads are prevented from flowing out through openings <NUM> even when microcatheter <NUM> is being bent, while outflow of suspension fluid, in which the embolization beads are suspended, is relatively unhindered. According to some embodiments, slits <NUM> may be separated from its neighboring slit in a same annular ring by approximately <NUM>-<NUM> degrees. According to one embodiment, slits <NUM> may be separated from its neighboring slit in a same ring by approximately <NUM> degrees.

Filter section 310b is the middle filter section located between filter section 310a and 310c and is located L3 (approximately <NUM> - <NUM>) proximally to distal end opening <NUM>. According to one embodiment, filter section 310b is positioned about <NUM> proximally to distal end opening <NUM>. The number of openings included in filter section 310b may be at least <NUM>, or at least <NUM>, or at least <NUM>,<NUM>, or at least <NUM>,<NUM> or, at least <NUM>,<NUM> or more. By way of example, <FIG> illustrates middle filter section 310b as having about <NUM>,<NUM> openings (<NUM> rows x <NUM> columns - collectively referred to as <NUM>). Those skilled in the art will appreciate that the number of openings <NUM> are not limited to this value. As best seen in <FIG>, openings <NUM> are relatively short (shorter than openings <NUM> and <NUM> of filter sections 310a and 310c respectively). The openings <NUM> have an approximate length in the range of <NUM> microns - <NUM> microns, as measured on the inner surface of the microcatheter. By way of example, openings <NUM> illustrated in <FIG> may have a length of about <NUM> microns, as measured on the inner surface of the microcatheter. Openings <NUM> may be narrow e.g. having a width of <NUM> microns - <NUM> microns, as measured on the inner surface of the microcatheter. By way of example, openings <NUM> illustrated in <FIG> may have a width of <NUM> microns. Each annular ring of openings is spaced apart from its neighboring ring of openings by <NUM> microns - <NUM> microns. By way of example, as illustrated in <FIG>, each of annular rings <NUM> may be spaced apart by approximately <NUM> microns. The size and shape of openings <NUM> serve to ensure that even the smallest embolization beads are prevented from flowing out through openings <NUM> even when microcatheter <NUM> is being bent, while outflow of suspension fluid, in which the embolization beads are suspended, is allowed, albeit with higher flow restriction than the outflow of fluid through openings <NUM>. The smaller size of openings <NUM> as compared to openings <NUM> accommodates the lower flow rate downstream of filter section 310a caused by outflow of fluid through openings <NUM>.

According to some embodiments, filter section 310b may have a total length L4 of <NUM> to <NUM> or <NUM> to <NUM>. By way of example, filter section 310b may have a length of about <NUM>.

According to some embodiments, slits <NUM> may be separated from its neighboring slit in a same annular ring by approximately <NUM>-<NUM> degrees. According to one embodiment, slits <NUM> may be separated from its neighboring slit in a same annular ring by approximately <NUM> degrees.

Filter section 310c is the most distal of filter sections 310a-310c and is located L5 (about <NUM>-<NUM>) from distal end opening <NUM> of microcatheter <NUM>. According to one embodiment, filter section 310c is positioned about <NUM> proximally to distal end opening <NUM>. The number of openings included in filter section 310c may be at least <NUM>, or at least <NUM>, or at least <NUM> or at least <NUM>,<NUM> openings or more. By way of example, <FIG> illustrates filter section 310c having about <NUM>,<NUM> openings, collectively referred to as <NUM> (<NUM> rows x <NUM>), distributed circumferentially around the wall of microcatheter <NUM>. Those skilled in the art will appreciate that the number of openings <NUM> are not limited to this value. Openings <NUM> are configured to prevent outflow of the embolization beads, while allowing outflow of the suspension fluid in which the embolization beads are suspended.

According to some embodiments, filter section 310c may have a total length L6 of <NUM> to <NUM> or <NUM> to <NUM>. By way of example, filter section 310b may have a length of about <NUM>.

Each annular ring of openings is spaced apart from its neighboring ring of openings by <NUM> microns - <NUM> microns. By way of example, as illustrated in <FIG> each of annular rings <NUM> may be spaced apart by approximately <NUM> microns.

According to some embodiments, slits <NUM> may be separated from its neighboring slit in a same column by approximately <NUM>-<NUM> degrees. According to one embodiment, slits <NUM> may be separated from its neighboring slit in a same column by approximately <NUM> degrees.

According to some embodiments, openings <NUM> may be irregularly shaped. By way of example and as illustrated in <FIG>, openings <NUM> may have either a "dog bone shaped" 316a or a "bead-on-a-string shaped" 316b, as best seen in <FIG>. The irregular shape of openings <NUM> cause beads flowing through microcatheter <NUM> to be caught within openings <NUM>, which in turn decreases the inner diameter of filter section 310c and thus increases proximal pressure. Advantageously, as a result thereof, the volume of suspension fluid injected through openings <NUM> and <NUM> of filter sections 310a and 310b, proximal to filter section 310a increases further concentrating the beads delivered through end opening <NUM>. Openings <NUM> are preferably arranged such that each opening is neighbored by an opening having a different, but complementary shape, as shown in <FIG>. This arrangement ensures an optimal stacking of the openings enabling a large number of openings being formed in each circumferential column despite their irregular shape.

It is understood that other "irregularly shaped openings such as openings <NUM> illustrated in <FIG> may also be envisaged. According to some embodiments, the openings include a protruding feature that projects or extends outwardly and a portion of the outer perimeter of a neighboring opening may have a second shape that includes an indented feature, such as a cavity or groove, wherein the contour of the protruding feature complements the contour of the indented feature. For example, the protruding feature of the first opening 505a is positioned approximately to, but not in contact with the indented feature of the second opening 505b.

It is also understood that other that the distribution of the openings may be irregular, as for example illustrated by the distribution of openings <NUM> in <FIG>.

In another aspect, the pattern of openings on the filter, includes at least two different shapes of openings as illustrated in <FIG>. In this example, the shape <NUM> includes two concave features that complement the convex features of shape <NUM>. Those skilled in the art will appreciate other shapes, including irregular shapes, may be utilized for the shape of the openings.

According to some embodiments, openings <NUM>, <NUM>, <NUM> and <NUM> may have a smaller cross section at the inner surface of the microcatheter than at the outer surface of the microcatheter.

According to some embodiments, at least <NUM>% of each of the filter sections is open area. Optionally, the open area may be at least <NUM>%, or at least <NUM>% or at least <NUM>% of each of filter sections 310a-310c. Each possibility is a separate embodiment. According to some embodiments, the total open area of each of filter sections 310a-310c is at least <NUM> times, at least <NUM> times, at least <NUM> times, at least <NUM> times, or at least <NUM> times larger than an area of distal end opening <NUM>. This ensures a sufficient outflow of suspension fluid through openings <NUM>, <NUM> and <NUM> to prevent backflow and to provide a concentrated delivery of the beads through end opening <NUM>. Each possibility is a separate embodiment. According to some embodiments, the total open area of filter sections 310a-310c is at least <NUM><NUM>, at least <NUM><NUM>, at least <NUM><NUM>, at least <NUM><NUM> or at least <NUM><NUM> in size. Each possibility is a separate embodiment.

According to some embodiments, the open area of each openings of filter section 310a may be about <NUM>-<NUM><NUM> or about <NUM>-<NUM><NUM>. By way of example, the open area of each openings of filter section 310a (best seen in <FIG>) is <NUM> *<NUM>, which is <NUM><NUM>. Those skilled in the art will appreciate that the open area of each opening in filter section 310a is not limited to this specific value.

According to some embodiments, the total open area of filter section 310a may be about <NUM>-<NUM><NUM>, about <NUM>-<NUM><NUM>, or about <NUM>-<NUM><NUM>. By way of example, the total open area of filter section 310a is <NUM> (number of openings in filter section 310a) x <NUM><NUM> (open area of each openings in filter section 310a) which is <NUM><NUM>. Those skilled in the art will appreciate that the total open area of filter section 310a is not limited to this specific value.

According to some embodiments, the open area of each opening of filter section 310b may be about <NUM>-<NUM><NUM> or about <NUM>-<NUM><NUM>. By way of example, the open area of each openings of filter section 310b (best seen in <FIG>) is <NUM> x <NUM>, which is <NUM><NUM>. Those skilled in the art will appreciate that the open area of each openings in filter section 310b is not limited to this specific value.

According to some embodiments, the total open area of filter section 310b may be about <NUM>-<NUM><NUM>, about <NUM>-<NUM><NUM>, or about <NUM>-<NUM><NUM>. By way of example, the total open area of filter section 310b is <NUM> (number of openings in filter section 310b) x <NUM><NUM> (open area of each opening in filter section 310b) which is <NUM><NUM>. Those skilled in the art will appreciate that the total open area of filter section 310b is not limited to this specific value.

According to some embodiments, the open area of each "dog bone" shaped opening 316a of filter section 310c may be about <NUM>-<NUM><NUM> or about <NUM>-<NUM><NUM>. By way of example, the open area of each "dog bone" shaped opening of filter section 310c (best seen in <FIG>) is <NUM><NUM>. Those skilled in the art will appreciate that the open area of each "dog bone" shaped opening in filter section 310c is not limited to this specific value.

According to some embodiments, the open area of each "beads-on-a-string" shaped opening 316b of filter section 310c may be about <NUM>-<NUM><NUM> or about <NUM>-<NUM><NUM>. By way of example, the open area of each "beads-on-a-string" shaped opening of filter section 310c (best seen in <FIG>) is <NUM><NUM>. Those skilled in the art will appreciate that the open area of each "dog bone" shaped opening in filter section 310c is not limited to this specific value.

According to some embodiments, the total open area of the "dog bone" shaped openings 316a of filter section 310c may be about <NUM>-<NUM><NUM>, about <NUM>-<NUM><NUM>, or about <NUM>-<NUM><NUM>. By way of example, the total open area of "dog bone" shaped openings 316a of filter section is <NUM> (number of "dog bone" shaped openings in filter section 310c) x <NUM><NUM> (open area of each opening in filter section 310c) which is <NUM><NUM>. Those skilled in the art will appreciate that the total open area of the "dog bone" shaped openings 316a of filter section 310c is not limited to this specific value.

According to some embodiments, the total open area of the "beads-on-a-string" shaped openings 316b of filter section 310c may be about <NUM>-<NUM><NUM>, about <NUM>-<NUM><NUM>, or about <NUM>-<NUM><NUM>. By way of example, the total open area of "dog bone" shaped openings 316b of filter section is <NUM> (number of "beads-on-a-string" shaped openings in filter section 310c) x <NUM><NUM> (open area of each opening in filter section 310c) which is <NUM><NUM>. Those skilled in the art will appreciate that the total open area of the "beads-on-a-string" shaped openings 316b of filter section 310c is not limited to this specific value.

According to some embodiments, microcatheter <NUM> has a tensile strength of at least at least 3N, at least 4N, or at least 5N. Each possibility is a separate embodiment.

According to some embodiments, openings <NUM>, <NUM> and/or <NUM> are axially distributed.

According to some embodiments, the wall of microcatheter <NUM> includes/ is made of a skeleton (not shown) formed of braided or coiled wires; and a polymeric layer (not shown) intercalated into and/or overlaying the skeleton. According to some embodiments, openings <NUM>, <NUM> and/or <NUM> are formed such that the braid/coil remains intact (not cut). This advantageously ensures the structural integrity (at least about 5N tension force, kink resistance, flexibility and torqueability) of microcatheter <NUM>.

According to some embodiments, the polymeric layer may include or be made of a thermoplastic elastomer, such as, but not limited to, thermoplastic polyurethane (such as Pellethane™ TPU by The Lubrizol Corporation, OH, USA) or polyether block amide (such as Pebax™ TPE by Arkema Group, Colombes, France), Nylon, Polyimide, Silicone or any combination thereof. Each possibility is a separate embodiment.

According to some embodiments, the skeleton has a thickness of <NUM>-<NUM> microns or <NUM>-<NUM> microns. As a non-limiting example, the skeleton may have a thickness of about <NUM> microns. According to some embodiments, the skeleton may be a tungsten braid. According to some embodiments, the braid/coil may be made of Nickel titanium (Nitinol). According to some embodiments, the braid/coil may be made from or include stainless steel, cobalt chrome, platinum iridium, nylon or any combination thereof. Each possibility is a separate embodiment. Advantageously, the such relatively thick wires enable selective cutting of the polymer of the microcatheter wall (e.g. using a femtosecond laser, with a Galvo scanning head and complementary optics, while causing minimal impact/damage to the braid.

According to some embodiments, the wall of microcatheter <NUM> further includes a hydrophilic liner (not shown) overlaying the polymeric layer of microcatheter <NUM>. According to some embodiments, filter sections 310a, 310b and/or 310c may be devoid of the liner. This may advantageously help conserve the integrity of the braid during laser cutting and increase the kink resistance of the microcatheter. Alternatively, openings <NUM>, <NUM> and/or <NUM> are formed through the polymeric layer and the hydrophilic liner.

According to some embodiments, the polymeric layer of microcatheter <NUM> may be made of a different polymeric material along its length. According to some embodiments, the polymeric layer of the part of microcatheter <NUM>, which is proximal to filter section 310a, has a higher shore than the part of microcatheter <NUM>, which is proximal to filter section 310a. According to some embodiments, the polymeric layer of the part of microcatheter <NUM>, which is proximal to filter section 310c, has a higher shore than the part of microcatheter <NUM>, which is distal to filter section 310c.

According to some embodiments, microcatheter <NUM> further includes an inner layer (also referred to herein as an inner liner) lining the inner surface of the wall of microcatheter <NUM>. According to some embodiments, the layer may include or be made of polytetrafluoroethylene (PTFE). According to some embodiments, openings <NUM>, <NUM> and/or <NUM> are formed through the inner layer. According to some embodiments, the inner layer extends only along part of the microcatheter <NUM> proximal to filter section 310a, thereby obviating the need to penetrate the inner layer when forming the openings or the need to remove inner layer material from the openings if applied after openings <NUM>, <NUM> and/or <NUM> are formed.

Microcatheter <NUM> is here illustrated as having three filter sections; however, any number (e.g. <NUM>, <NUM>, <NUM>, <NUM> or more) of filter sections may be envisaged and is thus within the scope of this disclosure. Each possibility is a separate embodiment. According to some embodiments, the filter sections may be spaced apart by <NUM>-<NUM>, here filter section 310a is spaced apart from filter section 310b by about <NUM>, and filter section 310b is spaced apart from filter section 310c by about <NUM>.

According to some embodiments, the filter sections may have a length of <NUM> -<NUM>. According to some embodiments, the filter sections may be of a same or different length. Here, filter section 310a has a length of about <NUM>, filter section 310b a length of about <NUM> and filter section 310c a length of about <NUM>.

According to some embodiments, microcatheter <NUM> may further include one or more radiopaque markers (not shown). According to some embodiments, microcatheter <NUM> may include a proximal marker positioned proximally to at least filter section 310c and a distal marker positioned distally to filter section 310c and in proximity filter section 310c. According to some embodiments, the proximal marker may be made from a polymeric material configured to retain the tensile strength of microcatheter <NUM>. According to some embodiments, the distal marker may be a metallic marker, this to prevent unraveling of the braid/coil of the skeleton. Advantageously, due to the difference in radio-opaqueness, the markers may serve as indications of the proximal/distal end of the filter section, when traveling through curved vasculature.

Microcatheter <NUM> further includes a hub (not shown) which is molded on or otherwise attached to the proximal end of microcatheter <NUM>. The hub is configured to allow access to the lumen of microcatheter <NUM> for a variety of functions, such as the injection of fluids or drugs, or the introduction of guidewires.

Reference is now made to <FIG>, which schematically shows another optional structure of a filter <NUM> of an embolization microcatheter, such as microcatheter <NUM> of <FIG>. According to some embodiments, filter <NUM> may include a single filter section <NUM> including a plurality of circumferential/annular rings (collectively referred to as <NUM>), such as <NUM>-<NUM> or <NUM>-<NUM> rings (e.g. <NUM> rings), each ring comprising a plurality of side openings, collectively referred to as <NUM>, such as <NUM>-<NUM>, or <NUM>-<NUM> or <NUM>-<NUM> slits (e.g. <NUM> side openings as illustrated here). According to some embodiments, filter <NUM> may have a length of L7, wherein L7 is in the range of <NUM> to <NUM>, e.g. about <NUM>.

According to some embodiments, side openings <NUM> may be in the form of slits. According to some embodiments, each of side opening <NUM> may have a width of <NUM> microns - <NUM> microns or <NUM> microns -<NUM> microns, (e.g. <NUM> microns), as measured on the inner surface of the microcatheter. According to some embodiments, side openings <NUM> may have a length of <NUM>-<NUM> microns or <NUM>-<NUM> microns, (e.g. <NUM> microns), as measured on the inner surface of the microcatheter. According to some embodiments, the distal most of the rings of filter may be positioned L8 mm from the distal end opening, wherein L8 is in the range of about <NUM>-<NUM> or <NUM>-<NUM>, such as but not limited to about <NUM>. According to some embodiments, each ring may be spaced apart from a neighboring ring by a length L9, wherein L9 is in the range of <NUM>-<NUM> microns or <NUM>-<NUM> microns, e.g. <NUM> microns.

According to some embodiments, side openings <NUM> may be formed by selective cutting (e.g. selective laser cutting), that is, without cutting the wires forming skeleton <NUM>. According to some embodiments, the polymeric layer positioned between the wires of braid skeleton <NUM> are penetrated when forming the slits. Advantageously, the selective cutting of the polymeric layer (leaving braid skeleton <NUM> essentially intact may provide subdivision of at least some of the side-openings into two or more sub-side-openings separated by the braid but not by the polymeric outer layer.

Reference is now made to <FIG>, which schematically shows yet another optional structure of a filter <NUM> of an embolization microcatheter, such as microcatheter <NUM> of <FIG>. According to some embodiments, filter <NUM> may include a single filter section <NUM> including a plurality of side openings, collectively referred to as side openings <NUM>. According to some embodiments, the openings may be in the form of axial slits. According to some embodiments, the slits may be annularly distributed, (i.e. distributed circumferentially around the wall of the microcatheter). According to some embodiments, filter section <NUM> includes <NUM>-<NUM>, or <NUM>-<NUM> or <NUM>-<NUM> slits (e.g. <NUM> side openings). According to some embodiments, each of side opening <NUM> may have a width of <NUM> microns -<NUM> microns or <NUM> microns -<NUM> microns, (e.g. <NUM> microns), as measured on the inner surface of the microcatheter. According to some embodiments, each of side opening <NUM> may have a length of <NUM>-<NUM> (e.g. <NUM>), as measured on the inner surface of the microcatheter.

According to some embodiments, side openings <NUM> may be in the form of slits. According to some embodiments, each of side openings <NUM> may have a width of <NUM> microns - <NUM> microns or <NUM> microns -<NUM> microns (e.g. <NUM> microns), as measured on the inner surface of the microcatheter. According to some embodiments, each of side opening <NUM> may have a length of <NUM> to <NUM>, <NUM>-<NUM>, or <NUM>-<NUM> (e.g. <NUM>), as measured on the inner surface of the microcatheter. According to some embodiments, the filter <NUM> may be positioned about <NUM>-<NUM> or <NUM>-<NUM>, such as but not limited to about <NUM> from the distal end opening.

According to some embodiments, side openings <NUM> may be formed by selective cutting (e.g. selective laser cutting), that is, without cutting the wires forming skeleton <NUM>. According to some embodiments, the polymeric layer positioned between the wires of braid skeleton <NUM> are penetrated when forming the slits. Advantageously, the selective cutting of the polymeric layer (leaving braid <NUM> essentially intact) may provide subdivision of at least some of the side-openings into a plurality of sub-side-openings <NUM> separated by skeleton <NUM>, but not by the polymeric outer layer. By way of example, as illustrated in FIG. 7B approximately <NUM> side openings <NUM> formed in the polymeric layer may result in more than <NUM> and even more than <NUM> sub-side-openings.

According to some embodiments, the resulting number of sub-side-openings is greater than the number of side openings made in the polymeric layer. According to some embodiments, the resulting number of sub-side-openings is at least twice the number of side openings made in the polymeric layer. According to some embodiments, the resulting number of sub-side-openings is at least <NUM> times the number of side openings made in the polymeric layer.

As illustrated in <FIG> which show frontal and side detailed views of a filter <NUM> which may be essentially similar to any of the filters disclosed herein (e.g. filters <NUM>, <NUM> and <NUM>). As illustrated in <FIG>, side openings <NUM> may be essentially trapeze shaped, such that the cross section if each side opening at the inner surface of the filter is smaller than the cross section of the opening at the outer surface of the filter. According to some embodiments, the side openings may be formed by selective cutting (e.g. selective laser cutting), that is, without cutting the wires forming braid <NUM> as illustrated in <FIG>. According to some embodiments, the part of the liner positioned below the wires remains intact. According to some embodiments, both the polymeric layer and the inner liner positioned between the wires of braid <NUM> are penetrated when forming the slits. According to some embodiments, the resulting number of side-openings is greater than the number of side openings made in the polymeric layer. According to some embodiments, the resulting number of sub-side-openings is at least twice the number of side openings made in the polymeric layer. According to some embodiments, the resulting number of sub-side-openings is at least <NUM> times the number of side openings made in the polymeric layer.

Reference is now made to <FIG>, which schematically shows yet another optional structure of a filter <NUM> of an embolization microcatheter, such as microcatheter <NUM> of <FIG>. According to some embodiments, filter <NUM> may include a single filter section <NUM> including a plurality of side openings, collectively referred to as side openings <NUM>. According to some embodiments, filter section <NUM> includes <NUM>-<NUM>, or <NUM>-<NUM> or <NUM>-<NUM> side openings (e.g. <NUM> side openings). According to some embodiments, the slits are axial slits. According to some embodiments, the slits are distributed in an annular ring. According to some embodiments, each of side opening <NUM> may have a width of <NUM> microns -<NUM> microns or <NUM> microns -<NUM> microns (e.g. <NUM> microns), as measured on the inner surface of the microcatheter. and a length L10 of <NUM>-<NUM>, <NUM>-<NUM> or <NUM>-<NUM> (e.g. <NUM>), as measured on the inner surface of the microcatheter.

According to some embodiments, the filter <NUM> may be positioned L9 mm i.e. about <NUM>-<NUM> or <NUM>-<NUM>, such as but not limited to about <NUM> from the distal end opening.

According to some embodiments, side openings <NUM> may be formed by selective cutting (e.g. selective laser cutting), that is, without cutting the wires forming skeleton <NUM>. According to some embodiments, the polymeric layer positioned between the wires of skeleton <NUM> are penetrated when forming the slits. Advantageously, the selective cutting of the polymeric layer (leaving braid <NUM> essentially intact) may provide subdivision of at least some of the side-openings into two or more sub-side-openings separated by the braid but not by the polymeric outer layer, thereby de facto providing more than <NUM> side openings, more than <NUM> side openings or more than <NUM> side openings.

It will be further understood that the terms "comprises" or "comprising", when used in this specification, specify the presence of stated features, integers, steps, operations, elements, or components, but do not preclude or rule out the presence or addition of one or more other features, integers, steps, operations, elements, components, or groups thereof. According to some embodiments, the term "comprising" may be replaced by the term "consisting essentially of" or "consisting of".

The term "about" refers to a reasonable variation from a stated amount that retains the ability to achieve one or more functional effect to substantially the same extent as the stated amount. The term may also refer herein to a value of plus or minus <NUM>% of the stated value; or plus or minus <NUM>%, or plus or minus <NUM>%, or plus or minus <NUM>%, or plus or minus <NUM>%, or any percentage in between.

Reflux of beads using a microcatheter as disclosed in <FIG>-<FIG>, was compared to the reflux using a standard microcatheter, under the same test conditions.

Each microcatheter was inserted into a tube connected in its distal end to a filter consisting of a large mesh for collecting the injected beads and a flow regulator that maintained a constant flow rate of <NUM> cc/min in the tube. Sirtex Y90 (<NUM> micron) beads (Sir-Sphere®) were injected in a constant flow rate of <NUM>-<NUM> cc/min using a syringe pump and the injection was recorded and reflux of beads monitored.

When using a standard microcatheter, the reflux began at an injection flow rate just higher than <NUM> cc/min, while when using the herein disclosed microcatheter, no reflux was observed even at an injection flow rate as high as <NUM> cc/min.

<FIG> shows representative images captured at various time points when monitoring reflux of Sirtex Y90 beads using the herein disclosed embolization microcatheter (herein disclosed MC - lower panel) and a standard microcatheters (standard MC - upper panel). It may be clearly seen that reflux is significantly prevented when using the herein disclosed microcatheter, as compared to standard microcatheters (refluxed beads are indicated by arrow <NUM>) As further seen from <FIG> when using the hereindisclosed microcatheter, reflux of Sirtex Y90 beads (Sir-Sphere®) occurs only at an injection rate x1. <NUM> times higher than with a standard microcatheter (~<NUM>/min as compared to ~ <NUM>/min).

Each microcatheter was inserted into a tube connected in its distal end to a filter consisting of a large mesh for collecting the injected beads and a flow regulator that maintained a constant flow rate of <NUM> cc/min in the tube. Embozene® <NUM> microns beads were injected in a constant flow rate of <NUM>-<NUM> cc/min using a syringe pump and the injection was recorded and reflux of beads monitored.

When using a standard microcatheter, the reflux began at an injection flow rate just higher than <NUM> cc/min, while when using the herein disclosed microcatheter, no reflux was observed in injection flow rate of up to <NUM> cc/min.

Claim 1:
An embolization microcatheter (<NUM>) for delivery of embolization beads to a target area, the microcatheter comprising:
a proximal end and a distal end (<NUM>), the distal end (<NUM>) comprising an end opening (<NUM>); and
a skeleton (<NUM>) formed of braided or coiled wires (<NUM>);
a polymeric layer (<NUM>) intercalated into and/or overlaying the skeleton (<NUM>); and
a filter (<NUM>) located in proximity to the distal end opening (<NUM>); the filter (<NUM>) comprising at least <NUM> openings distributed circumferentially around a wall thereof;
wherein
a total open area of the filter (<NUM>) is at least <NUM> times larger than an area of the distal end opening; wherein
the proximal end is sized and
shaped to allow delivery of a suspension flowing through the microcatheter (<NUM>), wherein the suspension comprises a suspension fluid and the embolization beads, and
wherein
the filter (<NUM>) is configured to allow outflow of the suspension fluid while preventing outflow of the embolization beads; characterised in that the at least <NUM> openings are essentially bone shaped or bead-on-string shaped.