Devices and methods for treating vasospasm

Abstract

The present invention relates to a method and a corresponding device for treating vasospasm with a stent structure, in which the stent structure has an expanded state, in which the stent structure rests against the inner wall of a blood vessel, and a compressed state, in which the stent structure is movable through the blood vessel within a catheter, in which the stent structure is preferably connected to a delivery line at its proximal end, wherein the stent structure is introduced into the catheter to a location in the blood vessel where vasospasm is present or predicted, the stent structure is released from the catheter, and the stent structure is moved longitudinally through the blood vessel in an expanded state. Optionally, the stent structure, after release from the catheter, remains in situ in an expanded state for a limited period of time, and then moves longitudinally through the blood vessel.

Description

Technical Field

[0001] The present invention relates to a device comprising a stent structure for insertion into a blood vessel of a human or animal body, and a method for treating vascular spasm using the stent structure. Background Art

[0002] Vasospasm is a spasmodic constriction of blood vessels. This is associated with the risk that the subsequent blood vessels will no longer have an adequate blood supply (ischemia), which can lead to necrosis of tissues supplied by blood vessels. Particularly in the brain region, vasospasm may occur a few days after a subarachnoid hemorrhage (SAB), often as a result of a ruptured aneurysm. Other causes of subarachnoid hemorrhage include traumatic brain injury and bleeding from vascular malformations or tumors. Bleeding in the subarachnoid space surrounds the blood vessels that flow there and is considered the most important predisposing factor for vasospasm. About 60% of SAB patients experience vasospasm to a greater or lesser extent between the fifth and twentieth day after the hemorrhage. When arterial vessels are highly constricted, the supply to dependent brain tissue is insufficient, which can lead to irreversible damage. About 15-20% of primary SAB survivors suffer permanent neurological damage, which leads to disability. About 5% of primary SAB survivors die from cerebral vasospasm in later life. In this regard, vasospasm is one of the main causes of stroke and even death after a ruptured aneurysm and / or aneurysmal bleeding or surgery in this area.

[0003] Typically, vasospasm is treated with medication, specifically calcium channel blockers or drugs that increase NO levels in the blood. An example of a calcium channel blocker is nimodipine, which is often used to prevent vasospasm after a subarachnoid hemorrhage. However, the side effects of drug treatment are not insignificant, and it is expensive and time-consuming.

[0004] Other options for the treatment of vasospasm include intensive medical measures such as increasing arterial blood pressure and circulating blood volume, dilating constricted blood vessels with the aid of balloons, blocking the stellate ganglion, and surgical destruction of sympathetic nerve fibers (sympathectomy). The effectiveness of these treatments varies, some are very costly, and they often do not last long enough. Stellate ganglion blockade and surgical sympathectomy are effective because the sympathetic nerve fibers in the walls of cerebral arteries are largely involved in the development of cerebral vasospasm. However, these procedures are not sufficient to completely prevent and treat cerebral vasospasm because blockade of the stellate ganglion lasts only a few hours and surgical sympathectomy is limited to narrowed blood vessel loops that must be surgically removed for this purpose.

[0005] Endovascular prostheses, or stents, are commonly used to treat vascular stenosis and are permanently implanted at the site of the stenosis to keep the vessel open. Typically, stents have a tubular structure. The stent can be delivered to the target site via a catheter and expanded; in the case of self-expanding stents made of shape memory materials, this expansion and attachment to the inner wall of the vessel occurs autonomously. Alternatively, the stent can be expanded using a balloon onto which the stent is crimped or other mechanical methods. After final placement, only the stent itself remains at the target site; the catheter, guidewire, and other devices are removed from the vessel.

[0006] Basically, similar implants are also used to close aneurysms by placing them in front of the neck of the aneurysm. However, such flow diverters generally have a higher surface density than stents used to remove stenosis. An example of a flow diverter is described in PCT patent application with publication number WO 2008 / 107172 A1. Even though the flow diverter is not a stent in the strict sense, the flow diverter can also be described as a stent structure. Likewise, in the context of the present invention, structures of basically similar design are understood regardless of whether they are actually used as stents.

[0007] The stent structure is usually made by laser cutting (resulting in a surface consisting of struts with openings between them) or consists of a wire mesh. Other manufacturing techniques, such as 3D printing, are also conceivable.

[0008] WO 2017 / 207689 A1 discloses a stent structure for treating vasospasm. In particular, it has a uniform radial force over its entire effective length (i.e., the length of the stent structure in contact with the inner wall of the blood vessel). The stent structure is released from the catheter at the location of the vasospasm, thereby expanding and reinserting the catheter after a period of time (usually 1 to 10 minutes). It has been found that temporarily expanding the stent structure with a uniform radial force is an effective method for treating vasospasm. The above patent application also describes a method for determining radial force, which is mentioned in the context of the present invention.

[0009] Another device for treating vasospasm is disclosed in WO 2018 / 046592 A1. The stent structure described here is characterized by an electrical conductor, through which pulses can be applied to nerve fibers running in the blood vessel wall, thereby preventing or treating vasospasm.

[0010] Based on this prior art, the object was to provide a method and a device in order to further improve the treatment and prevention of vasospasm. BRIEF DESCRIPTION OF THE DRAWINGS

[0011] Figure 1 is a perspective view of a first exemplary stent structure for treating vasospasm according to the present teachings;

[0012] Figure 1Ais a close-up view of a radially outward portion of a first exemplary stent structure contacting an inner wall of a blood vessel according to the present teachings;

[0013] Figure 1B-1 G is a perspective view of various cross-sectional configurations of struts and / or wires of a stent structure according to the present teachings;

[0014] Figure 2 is a perspective view of a second exemplary stent structure for treating vasospasm according to the present teachings;

[0015] Figure 2A is a close-up view of a radially outward portion of a second exemplary stent structure contacting an inner wall of a blood vessel according to the present teachings;

[0016] Figure 3 is a perspective view of a stent structure in accordance with the present teachings successfully treating vasospasm. DETAILED DESCRIPTION

[0017] The present invention relates to a method for treating vasospasm using a stent structure. The stent structure has an expanded state and a compressed state; in the expanded state, the stent structure is against the inner wall of the blood vessel; in the compressed state, the stent structure is movable through the blood vessel in a catheter. The stent structure is preferably connected to a delivery line at its proximal end. The treatment method includes the following steps: (1) inserting the stent structure in the catheter into a treatment site in the blood vessel where vasospasm exists or may occur, (2) deploying the stent structure at the treatment site by releasing the stent structure from the catheter, (3) if necessary, leaving the stent structure in place for a limited period of time in its radially expanded state, and (4) moving the stent structure in the expanded state in the longitudinal direction through the blood vessel.

[0018] Vasospasm occurs when a stimulus causes a sudden, spasmodic constriction of a blood vessel. This is the body's response to a (presumed) injury, with the goal of limiting blood loss by constricting the blood vessels. Therefore, it was previously thought that damage or irritation of the blood vessel wall should be avoided when treating vasospasm.

[0019] It has been found that the movement of the expanded stent structure stimulates the vessel wall in the area of ​​vasospasm and is beneficial in treating vasospasm. This stimulation is produced by slowly moving the expanded stent structure longitudinally, creating friction between the stent structure and the vessel wall. It is believed that, to some extent, the movement of the stent structure also causes stripping of the intima or endothelium, the inner layer of the blood vessel. This is a thin endothelial layer that provides a smooth inner surface for the blood vessel.

[0020] According to the present invention, at least partially stripping the endothelium in the affected blood vessel by moving the expanded device in the longitudinal direction plays an important role in the successful treatment of vasospasm. Specifically, according to one embodiment of the present teachings, the stent structure applies a certain amount of radial force to the surrounding blood vessel wall when moving longitudinally along the blood vessel. The radial force applied by the stent-like device on the blood vessel wall is a function of compression relative to the uncompressed state. This means that the more the device is compressed, the greater the radial force applied to its surroundings; similarly, the less the device is compressed, the smaller the radial force applied to its surroundings.

[0021] Unlike the devices described in WO 2017 / 207689 A1, the stent structure of the present invention is intended to move longitudinally in the area of ​​vasospasm, and its main function is to dilate the blood vessel, i.e. widen the blood vessel, thereby exerting a relatively large radial force on the surrounding vessel wall to stabilize the device at the treatment site. Therefore, the radial force exerted on the surrounding vessel wall is generally lower than those devices that are intended to be implanted without movement.

[0022] In addition to the radial forces described above, how the device applies radial forces to the vessel wall is another important factor in treating vasospasm. According to one embodiment of the present teachings, the cross-sectional configuration of the struts / wires also plays an important role in the effectiveness of the treatment. The cross-sectional shape of the struts / wires can be a general shape of a triangle or partial triangle, a trapezoid, a blade, or a rhombus. And, according to one embodiment of the present teachings, as the device expands radially, the edges of the struts / wires formed along the vertices of such cross-sectional shape contact the surrounding vessel wall. Due to this particular configuration, a stent structure having such a design applies greater radial forces to the vessel wall than a stent structure made with round struts / wires.

[0023] According to another embodiment of the present invention, the radial force applied to the vessel wall is not only static, but also dynamic, particularly in the form of a longitudinal movement during the treatment of vasospasm. According to one embodiment, the stent structure is configured to move in a longitudinal direction over a length of about 5-50 mm over a period of about 30-60 seconds. Typically, the longitudinal movement is caused by the clinician proximally withdrawing the proximal end of the delivery line. According to one embodiment of the present teachings, the distal end of the delivery line is connected to the proximal end of the stent structure. This movement is performed in a continuous and stable motion, in which the speed is generally slower than retracting the implant into its delivery catheter (for example, when retracting the thrombectomy device into the aspiration catheter).

[0024] According to one embodiment of the present invention, the treatment of vasospasm includes at least two steps. In a first step, the stent structure is deployed to its radially expanded profile at a treatment location (e.g., a location where vasospasm occurs or may occur). In a second step, the stent structure is moved in a longitudinal direction to induce additional stimulation on the vessel wall. In one embodiment, the deployed stent structure is positioned at the treatment location for a limited time after deployment and before longitudinal movement. In another embodiment, the stent structure is longitudinally moved immediately after deployment.

[0025] According to one embodiment of the present invention, the movement of the stent structure in the longitudinal direction is generally in the proximal direction. In other words, the stent structure is pulled proximally over the delivery wire. According to another embodiment of the present invention, the movement of the stent structure in the longitudinal direction is in the distal direction. In other words, the stent structure is pushed distally over the delivery wire.

[0026] According to one embodiment of the invention, the longitudinal movement of the support structure occurs only once. According to another embodiment of the invention, the longitudinal movement of the support structure is repeated at least once. According to yet another embodiment, the longitudinal movement of the support structure is repeated several times.

[0027] According to one embodiment of the present invention, after completing the first longitudinal movement to induce additional stimulation on the vessel wall, the stent structure is re-inserted into the catheter at the proximal end and released again at the treatment location (i.e., the location where vasospasm occurs or may occur), and then a second deployment and a second longitudinal movement are performed. The treatment can be repeated multiple times. In one embodiment, the longitudinal movement is repeated at least once on the same day. In another embodiment, this longitudinal movement is repeated at least once in consecutive days. In yet another embodiment, this longitudinal movement is repeated after a few weeks, for example after 6, 12 and 24 weeks, to produce a lasting effect.

[0028] According to one embodiment of the present invention, repetition of the process, i.e., longitudinal movement of the deployed stent structure, significantly improves the therapeutic effect of vasospasm. In some cases, it is sufficient to repeat the process twice. In one embodiment, the treatment process is performed at a location where vasospasm occurs or may occur. In another embodiment, the above-mentioned treatment process is performed on a branch of the bifurcation to treat vasospasm of adjacent blood vessels. For example, the treatment process in the middle cerebral artery (MCA) region of the sphenoid segment M1 and the distal internal carotid artery (ICA) also leads to dilation of the proximal anterior cerebral artery (ACA). This means that when vasospasm is treated with the above-mentioned method using the stent structure disclosed in the present invention, vasospasm of adjacent blood vessels or portions of adjacent blood vessels will also be released.

[0029] In some embodiments, after treating vasospasm using the above methods, no lesions remain when the vessel wall is examined a few days after treatment using vessel wall imaging, such as magnetic resonance angiography (MRA). Thus, the above process according to the present invention affects the intima as desired, but does not affect the media or adventitia.

[0030] In some embodiments, an additional drug treatment, such as nimodipine, may be administered simultaneously with treatment using the device according to the invention. In particular, this may be administered intra-arterially at the site of vasospasm.

[0031] According to one embodiment of the present invention, the connection between the insertion wire (delivery wire) and the stent structure can be non-detachable or detachable. The delivery wire is typically a wire of a type similar to that used for implants. In embodiments where the stent structure is intended to remain permanently in the vascular system, the delivery wire is detachably connected to the stent structure. According to one embodiment, the separation mechanism between the delivery wire and the stent structure can be a mechanical separation, a thermal separation, or an electrolytic separation. According to the present invention, such a detachable connection to the stent structure is also possible because the stent structure is used for temporary deployment at the site of vasospasm. The stent structure detachably connected to the delivery wire provides the physician with an option to release the stent structure within the blood vessel, depending on the circumstances, for example, if retraction proves to be problematic, unfeasible, or would result in permanent radial force application. The delivery wire is preferably made of stainless steel, nitinol, or cobalt-chromium alloy. According to the present invention, wires having an inner lumen or a lumen are also considered to be delivery wires.

[0032] According to one embodiment of the present invention, the delivery wire is preferably attached to the proximal end of the stent structure in a radially offset manner. In other words, the connection between the delivery wire and the stent structure is not located in the center of the stent structure, but is eccentrically located at or near the inner wall of the blood vessel. In this way, blood flow is obstructed as little as possible. In addition, the eccentric arrangement of the delivery wire helps the stent structure to be retracted into the catheter.

[0033] According to another embodiment of the present teachings, the delivery wire is connected to the stent structure at multiple locations, including the proximal end of the stent structure. The multiple connections between the delivery wire and the stent structure provide a slightly stronger connection on the one hand, and on the other hand, a greater obstruction to blood flow due to the additional struts or wires extending in the center of the vessel. Therefore, according to some embodiments, the proximal end of the stent structure can be kept shorter, and the proximal end of the stent structure gradually tapers toward the delivery wire, so that it no longer completely rests against the inner wall of the vessel and substantially no radial force is applied thereto. In the case where the delivery wire is connected to the stent structure at multiple points, the insertion wire typically extends more centrally.

[0034] The stent structure is delivered via a catheter, which can be a microcatheter in particular. In particular, when used in the neurovascular field, a microcatheter is usually used. The stent structure can be pushed to the treatment site via the catheter. Alternatively, the stent structure is accommodated in a catheter, which is pushed to the treatment site together with the stent structure therein.

[0035] Typically, before the stent structure is delivered to the treatment site via a catheter, a relatively large lumen guide catheter is inserted, and then a small lumen catheter is advanced distally through the relatively large lumen guide catheter beyond the distal end of the guide catheter. For example, for neurovascular applications, a guide catheter is advanced from the groin to the carotid artery, and then the catheter is advanced through the guide catheter beyond the distal end of the guide catheter.

[0036] According to one embodiment of the present teachings, the deployment of the stent structure is achieved by relative movement between the catheter and the stent structure. In one embodiment, the stent structure is held in place and the catheter is withdrawn proximally until the stent structure is exposed and radially expanded. In another embodiment, the stent structure is deployed by pushing the stent structure distally relative to the catheter. In yet another embodiment, the stent structure is deployed by a combination of these movements.

[0037] According to one embodiment of the present teachings, the stent structure is configured to radially self-expand when released from the catheter. To this end, the stent structure is made of a material having shape memory properties (e.g., a nickel-titanium alloy called Nitinol) or superelastic properties. It should be appreciated by those skilled in the art that other alloys or polymers having the ability to self-expand into a predetermined shape can be used for the purposes of the present invention. Therefore, the exemplary embodiments disclosed herein should not be considered limiting.

[0038] According to one embodiment of the present invention, the support structure can also be at least partially made of cobalt-chromium alloy, cobalt-chromium-nickel alloy and cobalt-chromium-nickel-molybdenum alloy. In one embodiment, these materials are substantially free of titanium, which further improves performance. An example of material selection is 35N

[0039] The alloys mentioned in the context of the present invention are merely examples. It should be clear that the mention of a metal as a component of such an alloy does not exclude that the alloy contains other components. For example, a cobalt-chromium alloy may contain other components, such as nickel or molybdenum, in addition to cobalt and chromium. Similarly, a platinum-iridium alloy need not contain platinum and iridium as its only components. It should also be clear that, in addition to metals, the above exemplary alloys may also include non-metals, such as carbon or nitrogen. Examples given include certain superelastic / pseudoelastic alloys, X-ray visible alloys, cobalt-chromium alloys, etc. Other alloys suitable for the treatment methods disclosed in the present invention should be considered within the scope of the present invention.

[0040] According to another embodiment of the present teachings, a stent structure is constructed with a DFT (drawn filling tube) wire or strut. The inner layer of the DFT wire is one metal and the sheath is another metal, so that the wire has the properties of both metals. In particular, the DFT wire may have an inner layer that is not radiopaque and a pseudo-elastic sheath. Suitable materials include the above materials, in particular platinum alloys for inducing X-ray visibility and nickel-titanium alloys for pseudo-elasticity.

[0041] After completing the treatment of the vasospasm, the stent structure is typically withdrawn into the catheter. The catheter carrying the collapsed stent structure is then removed from the blood vessel. According to one embodiment, the catheter is pushed distally onto the stent structure in a stable position so that the stent structure collapses radially to assume its compressed state as the catheter slides over the entire length of the stent structure. According to another embodiment, the stent structure is withdrawn proximally into the stably positioned catheter. In yet another embodiment, a combination of distal movement of the catheter and proximal movement of the stent structure causes the stent structure to collapse radially and be re-sheathed within the catheter. Once the stent structure is within the catheter, the clinician can withdraw the entire system proximally out of the blood vessel.

[0042] The support structure is generally composed of interconnected struts or wires to form a mesh structure. In one embodiment, the support structure is made by laser cutting a tube using a technique known to those skilled in the art. The laser cut support structure has a plurality of openings or a mesh structure distributed around the circumference of the support structure. The advantage of laser cutting the support structure is that almost any form of opening can be designed. It should be understood by those skilled in the art that other forms of manufacturing processes may also be used to manufacture the support structure, such as electroplating or photolithography manufacturing, 3D printing or rapid prototyping. Therefore, the exemplary embodiments described above should not be considered restrictive.

[0043] In another embodiment, the stent structure can be made of braided wires. In this case, multiple wires typically extend spirally along the longitudinal axis, while multiple other wires extend spirally in the opposite direction. The wires cross each other to form honeycomb openings between the wires. The total number of wires used to make the stent structure can be 8 to 64, and each wire can be a single wire or a strand (several small diameter wires twisted together to form a filament). The advantage of a braided stent structure is that the wire can have any pre-formed cross-section, such as a triangle, trapezoid, blade shape, or diamond shape.

[0044] In one embodiment, a stent structure has interconnected struts, such as a laser cut stent structure. Such stent structures tend to shrink less in length during expansion. Stent structures with interconnected struts exert relatively greater radial forces than braided stent structures, taking into account other similar structures (such as strut / wire density and strut / wire thickness). This is because the interconnected struts have fixed connections at the intersections, while the wires of the braided stent structure generally slide over each other during radial expansion of the stent structure.

[0045] The present invention also provides an exemplary support / wire configuration for strengthening the treatment of the vascular wall in the area of ​​vascular spasm. Specifically, according to one embodiment of the present teaching, when viewed from the radial direction, the cross-section of the support / wire forming the stent structure decreases in the radially outward direction. When the stent structure is deployed, the stent structure expands radially, and the most radially outward portion of the support / wire contacts the surrounding vascular wall. In one embodiment, the portion of the support / wire in contact with the vascular wall is relatively narrower than the radially inward portion of the support / wire that does not contact the vascular wall, that is, the cross-section of the support / wire gradually tapers toward the radially outward direction to form a reduced cross-sectional area. This design of the support / wire leads to a greater point pressure (punctual pressure) on the vascular wall, thereby producing a stronger stimulation to the vascular wall under the same radial force of the support structure. According to one embodiment of the present teaching, the support / wire having a triangular, wedge-shaped, trapezoidal, blade or diamond cross-sectional shape exerts a higher point force (punctual force) on the vascular wall than a support structure made of a support / wire having a circular cross-sectional shape.

[0046] Properly configured struts or wires may also provide some ablation (stripping) of the intimal layer. By tapering the struts / wires radially outward, the struts / wires may have a blade-like effect, thereby enhancing the stripping. This requirement is somewhat contrary to the requirements of thrombectomy (i.e., removal of a clot). In thrombectomy, the stent structure is preferably non-invasive, whereas in the treatment of vasospasm, according to the present invention, the vessel wall may be affected to some extent. Therefore, the specific configuration of the struts / wires disclosed herein is advantageous.

[0047] According to one embodiment of the present teachings, the struts / wires may have, for example, a triangular, wedge-shaped, trapezoidal, blade-shaped or diamond-shaped cross-section. When a stent structure is made of such fully expanded struts / wires, the struts / wires are oriented in such a way that, in a cross-sectional view of the stent structure, the corners of the shaped wires are located at the most radially outward portion of the stent structure and contact the vessel wall.

[0048] According to another embodiment of the present teachings, at least one strut / wire of the stent structure has a quadrilateral cross-sectional shape, which may include a parallelogram, a rectangle, a rhombus, or any modified quadrilateral shape, such as a rectangle with one inclined side. Considering one possible embodiment, when viewed from the cross-sectional direction, one of the acute angles of the quadrilateral is located at the most radially outward portion of the deployed stent structure. In other words, the outermost edge of the strut / wire formed along the angle is the most radially outward portion of the stent structure and contacts the vessel wall.

[0049] In embodiments where the struts or wires extend diagonally, i.e., not at right angles to the longitudinal axis, the edges of the struts / wires at the most radially outward portion of the stent structure face in the proximal direction. In such designs, as the stent structure moves in the proximal direction, the orientation of the struts / wires can act on the vessel wall in a manner similar to a scraper or razor blade, thereby causing peeling therefrom.

[0050] According to another embodiment of the present teaching, in order to produce a sufficiently strong effect on the vessel wall, the stent structure is configured so that when the stent structure is in its radially expanded deployment configuration, the struts / wires are oriented in a direction substantially orthogonal to the longitudinal axis of the stent structure. For example, the struts / wires and the longitudinal axis of the stent structure form an angle of at least 60°. In a preferred embodiment, the angle between the struts / wires and the longitudinal axis of the stent structure is greater than 70°. In another embodiment, the angle between the struts / wires and the longitudinal axis of the stent structure is greater than 80°. Therefore, when the stent structure moves in the longitudinal direction, a larger area of ​​the vessel wall is affected.

[0051] The terms "proximal" and "distal" are to be understood as meaning that the portion of the device that is closer to the treating physician when the device is inserted is referred to as proximal, and the portion that is farther from the treating physician is referred to as distal. Thus, the device is typically pushed through the catheter in a distal direction. The term "axial" refers to the longitudinal axis of the device extending from the proximal end to the distal end, and the term "radial" refers to a plane perpendicular to the longitudinal axis.

[0052] In one embodiment, the openings formed in the stent structure between the individual struts / wires have an internal diameter of 0.1 to 6 mm, wherein the internal diameter is understood to be the diameter of the largest possible circle that can be placed in the opening. The maximum internal diameter refers to the stent structure in a completely unconstrained state, i.e., a state of maximum radial expansion. However, depending on the diameter of the vessel in which the implant is placed, the implant may not be able to assume its fully expanded state, resulting in an internal diameter that is different from the maximum expanded state.

[0053] According to one embodiment, the stent structure has openings formed between each strut / wire with an internal diameter greater than 1 mm. Such a relatively coarse mesh stent structure is configured to apply an appropriate amount of radial force to treat vasospasm. For example, a stent structure with an expanded diameter of 3 to 5 mm may have a mesh with an internal diameter of 2 to 4.5 mm.

[0054] According to one embodiment, the stent structure of the present invention has closed unit meshes, ie, each unit mesh is a closed shape completely surrounded by struts / wires without interruptions.

[0055] In one embodiment, the stent structure of the present invention is composed of struts / wires having relatively large cross-sectional areas or diameters (i.e., relatively strong struts / wires) that are used to generate a specified amount of radial force. In one embodiment, where the cross-section may be circular or angled, the height and width of the struts / wires are 30 to 300 μm, preferably 40 to 200 μm, and most preferably 40 to 120 μm to generate a specific amount of radial force.

[0056] According to one embodiment of the present teaching, the stent structure has a generally longitudinal tubular opening extending from an open proximal end to an open distal end. A stent structure of this design has the advantage of interfering with blood flow as little as possible and preventing insufficient blood supply to surrounding tissues. In another embodiment of the present teaching, the stent structure has a generally longitudinal tubular opening extending from an open proximal end to a closed distal end. A stent structure with a closed distal end is more non-invasive. In this case, the open end means that there are no struts / wires at the corresponding ends of the stent structure, and the struts / wires are limited to the periphery of the stent structure. On the other hand, the closed end is defined by the struts / wires at the center of the longitudinal tubular opening of the stent structure. Since the stent structure has meshes between the struts / wires along its periphery, blood can still pass through the stent structure through its meshes even if the distal end is closed, so blood flow will be restricted but not completely blocked.

[0057] Figure 1-3 An exemplary embodiment of the present invention is provided. In all drawings, the proximal end is the left and the distal end is the right.

[0058] Figure 1 A first exemplary embodiment of the present invention is shown, a device for treating vasospasm. The device 1 includes a laser-cut stent structure 2, the proximal end of which is connected to a delivery wire 3. The stent structure 2 is shown in its radially expanded state outside the catheter 4 and within the blood vessel region c (contraction region). According to one embodiment, the deployed stent structure 2 is positioned against the inner wall of the blood vessel that is constricted by the vasospasm. According to one embodiment, the stent structure 2 is delivered by a catheter (not shown). During delivery, the stent structure 2 is radially compressed and placed within the distal portion of the catheter 4. The catheter 4 carrying the stent structure 2 is inserted through the blood vessel v to reach the vasospasm site c.

[0059] Figure 1Further shown is a device and method for treating vasospasm using the device 1 of the present invention according to one embodiment of the present teaching. When the stent structure 2 is released from the catheter 4. It expands radially and abuts against the inner wall of the blood vessel v at the site of vasospasm c. The stent structure is then placed at the site of vasospasm c for a limited period of time, and then the stent structure 2 in its radially expanded state is moved in the longitudinal direction through the contraction region c of the blood vessel v. Preferably, the movement of the radially expanded stent structure 2 is in the proximal longitudinal direction indicated by the first arrow ar1. In this case, as indicated by the second arrow ar2, the combination of the longitudinal movement and the radial force of the device applied to the blood vessel wall in the contraction region c results in at least partial peeling of the inner layer of the blood vessel (i.e., the endothelium or the intima) in the contraction region c.

[0060] Figure 1A A detailed cross-sectional view of a stent structure is shown with the radially outermost portion of the stent structure in contact with the vessel wall. Figure 1A As shown, the radially outer surface of the stent strut 2' is in contact with the vessel wall v.

[0061] Figure 1B to Figure 1 G shows various embodiments of the cross-sectional configuration of the stent strut 2'. In one embodiment, as Figure 1C As shown, the cross-sectional configuration of the struts 2' has at least a partial trapezoidal shape. In one embodiment, the shorter parallel sides are located at the radially outer surface of the stent structure and contact the vessel wall when the stent structure is in its radially expanded state. In another embodiment, the corners of the shorter parallel sides are located at the most radially outward edge of the stent structure, and the corners contact the vessel wall when the stent structure is in its radially expanded state.

[0062] In such Figure 1D In another embodiment shown, the cross-sectional configuration of the struts 2' is at least partially triangular. In one embodiment, one corner of the triangle is located at the radially outermost edge of the stent structure, which corner contacts the vessel wall when the stent structure is in its radially expanded state.

[0063] In such Figure 1E In another embodiment shown, the cross-sectional configuration of the struts 2' is at least partially wedge-shaped, i.e., an acute triangle. In one embodiment, one corner of the triangle is located at the radially outermost edge of the stent structure, which contacts the vessel wall when the stent structure is in its radially expanded state.

[0064] In such Figure 1FIn another embodiment shown, the cross-sectional configuration of the struts 2' is at least partially parallelogram-shaped. In one embodiment, one side of the parallelogram is located at the radially outer surface of the stent structure and contacts the vessel wall when the stent structure is in its radially expanded state. In another embodiment, the corners of the parallelogram are located at the most radially outward edges of the stent structure and contact the vessel wall when the stent structure is in its radially expanded state.

[0065] In such Figure 1 In yet another embodiment shown in G, the cross-sectional configuration of the struts 2' is at least partially rectangular. In one embodiment, one side of the rectangle is located at the radially outer surface of the stent structure and contacts the vessel wall when the stent structure is in its radially expanded state. In another embodiment, the corner of the rectangle is located at the most radially outward edge of the stent structure, and the corner contacts the vessel wall when the stent structure is in its radially expanded state. In yet another embodiment, the corner of the rectangle forming the most radially outward edge of the stent structure is an acute angle.

[0066] It will be understood by those skilled in the art that the term "pillar" as used herein may also be a wire, and the two terms may be used interchangeably. Figure 1B-1 The various embodiments described in G also apply to lines, such as Figure 2 and Figure 2A Various embodiments described.

[0067] Figure 2 A second exemplary embodiment of the present invention, a device 101 for treating vasospasm, is shown. The device 101 includes a braided stent structure 201 made of wire, which is connected to a delivery wire 301 at its proximal end. The stent structure 201 is shown in its radially expanded state outside the catheter 401 and in the blood vessel region c (contraction region). According to one embodiment, the deployed stent structure 2 is positioned against the inner wall of the blood vessel contracted by the vasospasm. According to one embodiment, the stent structure 201 is delivered by a catheter (not shown). During delivery, the stent structure 201 is radially compressed and placed in the distal portion of the catheter 401. The catheter 401 carrying the stent structure 201 is inserted through the blood vessel v to reach the vasospasm site c.

[0068] Figure 2A Shown according to Figure 2 A perspective cross-sectional view of the configuration through the contraction region c. Figure 2A As shown, the radially outer surface of wire 201 ' is in contact with the vessel wall vc.

[0069] Figure 3 A blood vessel v is shown that has been successfully treated using the device 1 according to one embodiment of the present teachings. As shown, the previously contracted region c is fully dilated, and Figure 1Compared to the expanded state shown, the stent structure 2 is radially further expanded (expanded). The stent structure 2 can now be retracted into the catheter 4 and removed from the blood vessel v.

[0070] In one embodiment of the present teachings, an antithrombotic coating on the inside of the stent structure is useful because it resides in the vessel for a period of time during which thrombus formation must be avoided in a vessel that has contracted due to vasospasm. On the outside of the stent structure, a vasodilator coating is advantageous, for example, for use with a calcium channel blocker such as nimodipine.

[0071] In another embodiment, a coating that prevents platelet adhesion and aggregation can also be incorporated into the stent structure, such as the coating described in WO2018 / 210989A1. Here, a coating having a functional layer is applied to the medical device, wherein the functional layer comprises at least one sugar alcohol and / or is formed by oligomerization or polymerization of monosaccharides functionalized with polymerizable groups. Such a coating can mimic the natural glycocalyx.

[0072] Although antithrombotic coatings are particularly useful on the inside of a stent structure and vasopressant coatings are particularly useful on the outside of a stent structure, antithrombotic or vasopressant coatings may be applied to the entire stent structure, or the struts / wires may have corresponding coatings on all sides. In this case, the coatings are not limited to the inside or outside of the stent structure.

[0073] Generally speaking, it should be noted that all coatings can be incorporated into a portion or partial length of the stent structure. In one embodiment, the coating is incorporated into the region of the stent structure that contacts the inner wall of the blood vessel, ie, the cylindrical portion of the stent structure.

[0074] In one embodiment, based on a conventional stent structure with a diameter of 2.00 mm, the force applied radially outwardly by the expanded stent structure on the inner wall of the blood vessel should be between 2 and 30 N / m, preferably between 5 and 10 N / m. The specification of radial force refers to the force applied radially per unit length, that is, it is a relative radial force. Only the portion of the stent structure that is in contact with the inner wall of the blood vessel and is therefore able to apply force thereto (effective length) is considered.

[0075] According to one embodiment of the present teachings, the radial force applied by the stent structure in the expanded state is substantially constant along its effective working length, that is, the radial force on the proximal portion, the middle portion and the distal portion of the effective working length stent structure is the same. In another embodiment, the stent structure can apply a weaker radial force at the proximal and distal portions of its effective working length, and a relatively stronger radial force at the middle portion of its effective working length. In one embodiment, the proximal and distal portions of the stent structure are selectively modified so as to produce a uniform radial force over the entire effective working length of the stent structure from its proximal end to its distal end. The proximal end of the effective working length of the stent structure is different from the proximal end of the stent structure. The proximal end of the stent structure refers to the most proximal portion of the stent structure, which is no longer part of the effective working length, and at the most proximal portion of the stent structure, the struts / wires converge toward the delivery wire. According to one embodiment of the present teachings, the typical length between the proximal end of the stent structure and the proximal end of the effective working length of the stent structure is approximately 8 to 10 mm.

[0076] According to one embodiment of the present teachings, in order to increase the radial forces in the proximal and distal portions of the effective working length of the stent structure, the struts / wires used in these two portions may have a larger cross-sectional area than the struts / wires used in the middle portion. In other words, the mass of the struts / wires used in these two portions is greater. In this way, the basic tendency of the stent structure to exert higher radial forces in the middle portion can be at least partially compensated.

[0077] In an alternative embodiment, the struts / wires used in the proximal and distal portions of the effective working length of the stent structure may have a higher density than the struts / wires used in the middle portion of the working length of the stent structure. Thus, the natural tendency of the proximal and distal portions of the stent structure to exert weaker radial forces is at least partially compensated.

[0078] According to another embodiment of the present teachings, a stent structure may be provided with a slot that extends helically on a lateral surface of the stent structure, or that extends longitudinally along a transverse surface of the stent structure. In some embodiments, at least one strut / wire may be coupled across the slot to longitudinally adjust the radial force distribution along the effective working length of the stent structure when the stent structure is in its radially expanded configuration.

[0079] In one embodiment, the diameter of the stent structure in the radially expanded state is generally in the range of 2 to 8 mm, preferably in the range of 4 to 6 mm. In another embodiment, the total length of the stent structure in its radially expanded state is generally 5 to 50 mm, preferably 10 to 45 mm, more preferably 20 to 40 mm. In yet another embodiment, the effective length, i.e., the length of the stent structure in the radially expanded state (actually applying radial force to the inner wall of the blood vessel) is generally about 8 to 10 mm shorter than the total length of the stent structure, and it (the effective length) is preferably 20 to 40 mm.

[0080] The device has one or more radiopaque markers to provide visualization for the treating physician. For example, the radiopaque marker can be platinum, palladium, platinum iridium, tantalum, gold, tungsten or other types of radiopaque metals. In another example, radiopaque filaments can be used for visualization purposes and are placed at various points on the device. The radiopaque marker / filament can be incorporated into the distal end of the stent structure, the proximal end of the stent structure and / or any position between the distal and proximal ends of the stent structure. The stent structure, in particular the struts / wires of the stent structure, can also be coated with a radiopaque material coating, such as a gold coating. For example, the thickness of the radiopaque coating can be 1 to 6 μm. The radiopaque coating may also cover only important areas of the stent structure, i.e., where it contacts the tissue, such as the effective length of the stent structure or the cylindrical portion of the stent structure. The stent structure can combine a radiopaque coating and one or more radiopaque markers.

[0081] In one embodiment, the stent structure can be made from a tube using laser cutting technology or other techniques known to those skilled in the art. The wall thickness of such a tube can be 30 to 300 μm, preferably 40 to 200 μm, and most preferably 40 to 120 μm. In another embodiment, the stent structure can be made of interwoven wires using braiding technology or other techniques known to those skilled in the art. The thickness of such wires can be 30 to 300 μm, preferably 40 to 200 μm, and most preferably 40 to 120 μm. The catheter is used to deliver the stent structure into the vascular system. During delivery, the stent structure is radially compressed and placed in the catheter. The inner diameter of such a catheter can be 0.4 to 0.9 mm.

[0082] Part or all of the stent structure (in its radially expanded state) has a generally cylindrical shape, with openings distributed on the outer cylindrical surface. In other words, the stent structure has a grid or mesh-like surface structure with a large number of openings between the struts / wires on the outer cylindrical surface.

[0083] In one embodiment, the support structure is permeable to the outside. In another embodiment, the support structure can have one or more membranes on the circumference. The term "pore" refers to a lattice or mesh structure, whether or not the pore is isolated from the environment by a membrane, i.e., even a pore covered by a membrane is referred to as a pore. If necessary, a membrane can be applied to the outside or inside of the mesh structure. The grid and / or mesh structure can also be embedded in the membrane. The membrane can be made of a polymer material such as polytetrafluoroethylene, polyester, polyamide, polyurethane, polyolefin or polysulfone. Polycarbonate (PCU) is particularly preferred.

[0084] The present invention relates to a method and a corresponding device for the treatment of vasospasm, as well as the use of the device. The invention can be used for the treatment of acute vasospasm, but can also be used for prevention. According to the invention, the device can be used in particular in the neurovascular field, but can also be used in the cardiovascular or peripheral field. All statements about the device apply in the same way to the method and vice versa.

[0085] The present invention and the technical field are explained in more detail below with reference to the accompanying drawings. It should be noted that the accompanying drawings show particularly preferred embodiments of the present invention, but the present invention is not limited to the embodiments shown. In particular, the present invention includes any combination of technical features or method features related to the present invention listed in the claims or described in the specification, within the technically or methodologically useful range.

Claims

1. A method for treating vascular spasm using a stent structure, characterized in that: The method comprises: placing a stent structure within the catheter, wherein the stent structure has a radially expanded state and a radially compressed state, the radially expanded state being configured to position the stent structure against an inner wall of a blood vessel; in the radially compressed state, the stent structure is movable within the catheter; and wherein a delivery wire is connected to a proximal end of the stent structure; inserting the catheter into a treatment site within a blood vessel; deploying the stent structure by releasing the stent structure from the catheter and allowing the stent structure to transition from its radially compressed state to its radially expanded state; and The stent structure is moved in a longitudinal direction through the blood vessel.

2. The method according to claim 1, characterized in that The stent structure remains stable in its radially expanded state for 1 to 10 minutes before being moved in the longitudinal direction through the blood vessel.

3. The method according to claim 1 or 2, characterized in that: The stent structure is retracted into the catheter after being moved through the blood vessel in the longitudinal direction and is subsequently removed from the blood vessel in the catheter.

4. The method according to any one of claims 1 to 3, characterized in that The stent structure moves in the proximal direction in the expanded state.

5. The method according to any one of claims 1 to 4, characterized in that The stent structure is composed of struts or wires, wherein the cross-section of the struts or wires decreases radially outwards.

6. The method according to claim 5, characterized in that The struts or wires at least partially have a triangular, wedge-shaped, trapezoidal, blade-shaped or diamond-shaped cross-section, wherein the radially outer acute corner of the quadrilateral is the radially outermost portion of the stent structure.

7. The method according to any one of claims 1 to 5, characterized in that The struts or wires at least partially have a quadrilateral cross-section, the radially outer acute corner of the quadrilateral being the radially outermost portion of the stent structure.

8. The method according to any one of claims 1 to 7, characterized in that The struts or wires of the stent structure in the expanded state form an angle of at least 60° with the longitudinal axis of the stent structure.

9. A device for treating vasospasm, characterized in that: The device comprises: A stent structure formed by struts or wires, wherein the stent structure has a radially expanded state and a radially compressed state; in the radially expanded state, the stent structure is positioned against the inner wall of the blood vessel; in the radially compressed state, the stent structure is movable within the catheter; a delivery wire connected to a proximal end of the stent structure; wherein the cross-section of the struts or wires decreases radially outwardly; and The cross-section of the struts or wires has a radially outward acute angle at the most radially outward portion of the stent structure.

10. The device according to claim 9, characterized in that The struts or wires at least partially have a quadrilateral, triangular, blade-shaped or diamond-shaped cross-section.

11. The device according to claim 9 or 10, characterized in that The struts or wires in the expanded state form an angle of at least 60° with the longitudinal axis of the stent structure.

12. The device according to any one of claims 9 to 11, characterized in that The stent structure has an effective working length, and wherein in the radially expanded state, the stent structure applies a substantially constant radially outward force along the entire effective working length.

13. The device according to claim 12, characterized in that The cross-section of the struts or wires at the proximal and distal portions of the effective working length of the stent structure is larger than the cross-section at the middle portion of the effective working length of the stent structure.

14. The device according to claim 12 or 13, characterized in that The density of the struts or wires in the proximal and distal portions of the effective working length of the stent structure is higher than the density in the middle portion of the effective working length of the stent structure.

Images