Apparatus and method for treating vasospasm

Abstract

The present invention relates to a method and a corresponding device for treating vasospasm using a stent structure, the stent structure having an expanded state in contact with the inner wall of a blood vessel and a compressed state movable through the blood vessel within a catheter, the stent structure being preferably connected to a delivery wire at its proximal end, the stent structure being introduced into the catheter at a position within the blood vessel where vasospasm is present or predicted, the stent structure being released from the catheter, and the stent structure being longitudinally moved through the blood vessel in the expanded state. Optionally, after being released from the catheter, the stent structure is left in a predetermined position in the expanded state for a limited period of time, after which longitudinal movement through the blood vessel continues.

Description

Technical Field

[0001] The present invention relates to an apparatus having a stent structure intended for insertion into a blood vessel of a human or animal body, and a method of using the stent structure for treating vasospasm.

Background Art

[0002] Vasospasm is a spastic contraction of blood vessels. This results in insufficient blood supply to subsequent blood vessels (ischemia), with the risk that the tissues supplied by those blood vessels will become necrotic. Particularly in the cerebral region, vasospasm may occur several days after subarachnoid hemorrhage (SAB), many of which are due to rupture of aneurysms. Other causes of subarachnoid hemorrhage include traumatic brain injury and bleeding from vascular malformations or tumors. Blood leaked into the subarachnoid space surrounds the blood vessels running there and is considered the most important inducer of vasospasm. Approximately 60% of all SAB patients experience more or less vasospasm between the 5th and 20th days after bleeding. When arterial blood vessels contract strongly, the supply to the dependent brain tissue is insufficient, and as a result, the brain tissue may be irreversibly damaged. Approximately 15 - 20% of primary SAB survivors experience permanent neurological disorders, resulting in residual disabilities. Approximately 5% of primary SAB survivors die later as a result of cerebral vasospasm. In this regard, vasospasm is one of the main causes of stroke and even death that occur after rupture of aneurysms and / or bleeding from aneurysms or surgery in this region.

[0003] Normally, vasospasm is treated with drugs, particularly calcium antagonists or drugs that increase the NO level in the blood. An example of a calcium antagonist is nimodipine, which is often used after subarachnoid hemorrhage to prevent vasospasm. However, drug treatment is accompanied by quite a few side effects and is costly and time-consuming.

[0004] As other options for treating vasospasm, intensive medical measures such as increasing arterial blood pressure and circulating blood volume, dilating constricted blood vessels using a balloon, blocking the stellate ganglion, and surgically destroying sympathetic nerve fibers (sympathectomy) can be mentioned. These treatments are not individually consistent in their effects, some are very costly, and many do not last sufficiently. Since sympathetic nerve fibers in the cerebral artery wall are greatly involved in the onset of cerebral vasospasm, blocking the stellate ganglion and surgical sympathectomy are effective. However, blocking the stellate ganglion lasts only for a few hours, and surgical sympathectomy is limited to a very narrow segment of the blood vessels that must be surgically incised for this purpose, so these techniques are insufficient for the complete prevention and treatment of cerebral vasospasm.

[0005] Endovascular prostheses, i.e., stents, are commonly used to treat vascular stenosis and are permanently implanted at the site of vascular stenosis to keep the blood vessel open. Typically, a stent has a tubular structure. The stent is delivered to the target site through a catheter and can be expanded. In the case of a self-expanding stent made of a shape memory material, this expansion and attachment to the inner wall of the blood vessel are performed autonomously. Alternatively, the stent can be expanded using a balloon on which the stent is crimped or other mechanical methods. After the final placement, only the stent body remains at the target site, and the catheter, guide wire, and other devices are removed from the vascular system.

[0006] Basically, a similar implant is also used to close an aneurysm by placing it in front of the neck of the aneurysm. However, such a flow diverter generally has a higher surface density than a stent for stenosis removal. An example of a flow diverter is described in PCT Patent Application Publication No. WO2008 / 107172 A1. A flow diverter is not used as a stent in the strict sense, but a flow diverter can be described as a stent structure. Similarly, in the context of the present invention, a structure of basically the same design is understood regardless of whether it is actually used as a stent.

[0007] The stent structure is typically either a surface of struts that are laser cut and have openings between the struts or is composed of a wire mesh. Other manufacturing techniques such as 3D printing are also conceivable.

[0008] International Publication No. WO 2017 / 207689 A1 discloses a stent structure for use in treating vasospasm. In particular, it has a uniform radial force over its effective length, i.e., the entire length where the stent structure is in contact with the inner wall of the blood vessel. The stent structure is released from a catheter at the location of the vasospasm, thereby expanding, and after a certain period, typically 1 to 10 minutes later, is reinserted into the catheter. It has been found that temporarily expanding the stent structure with a uniform radial force is an effective way to treat vasospasm. The aforementioned patent application also describes a method for determining the radial force referred to in the context of the present invention.

[0009] Another device for the treatment of vasospasm can be found in International Publication No. WO 2018 / 046592 A1. The stent structure described herein is characterized by an electrical conductor that can apply a pulse to nerve fibers running within the blood vessel wall, thereby preventing or treating vasospasm.

[0010] Based on this prior art, it was an object to provide a method as well as a device for further improving the treatment and prevention of vasospasm. BRIEF DESCRIPTION OF THE DRAWINGS

[0011]

Figure 1

[0012]

Figure 1A

[0013]

Figure 1B

Figure 1C

Figure 1D

Figure 1E

Figure 1F

Figure 1G

[0014]

Figure 2

[0015]

Figure 2A

[0016]

Figure 3

Mode for Carrying Out the Invention

[0017] The present invention relates to a method for treating vasospasm by means of a stent structure. The stent structure mentioned above has an expanded state in contact with the inner wall of a blood vessel and a compressed state that can move through the blood vessel within a catheter. The stent structure is preferably connected to a delivery wire at its proximal end. The treatment method comprises the following steps: (1) inserting the stent structure within the catheter into a treatment site of a 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) optionally, leaving the stent structure in an expanded state in its radial direction for a limited period at a predetermined position; and (4) moving the expanded stent structure longitudinally through the blood vessel.

[0018] Vasospasm occurs as a result of sudden spastic contraction of a blood vessel as a result of stimulation. This is a (presumed) body reaction to injury aimed at suppressing bleeding by contracting the blood vessel. Therefore, it has previously been considered that damage or stimulation of the blood vessel wall should be avoided in the treatment of vasospasm.

[0019] It has been found that the movement of an expanded stent structure that stimulates the blood vessel wall in the region of vasospasm is beneficial for the treatment of vasospasm. Such stimulation is brought about by slowly moving the expanded stent structure longitudinally and causing friction between the stent structure and the blood vessel wall. The movement of the stent structure is thought to cause to some extent the detachment of the intima-media (inner membrane), i.e., the inner layer of the blood vessel. This is the thin endothelial layer that provides the smooth inner surface of the blood vessel.

[0020] According to the present invention, by moving the expanded device longitudinally, at least partially peeling the intima of the diseased blood vessel plays a role in successfully treating vasospasm. Specifically, according to one embodiment of the present teaching, when the stent structure moves longitudinally along the blood vessel, it exerts a certain radial force on the surrounding blood vessel wall. The radial force exerted by the stent-like device on the blood vessel wall is a function of the compression relative to the uncompressed state. That is, the more the device is compressed, the greater the radial force on the surroundings, and similarly, the less the device is compressed, the smaller the radial force on the surroundings.

[0021] Different from a device as described in International Publication No. WO 2017 / 207689 A1, which mainly has the function of expanding a blood vessel, i.e., widening its width, and thus will exert a relatively large radial force on the surrounding blood vessel wall to stabilize the device at the treatment site, the stent structure of the present invention is intended to move longitudinally in the region of vasospasm. Therefore, the radial force acting on the surrounding blood vessel wall is generally smaller than that of a device intended to be implanted without being moved.

[0022] In addition to the above radial force, how the device applies the radial force to the blood vessel wall is another important factor for the treatment of vasospasm. According to one embodiment of the present teaching, the cross-sectional configuration of the strut / wire also plays a role in the treatment effect. The cross-sectional shape of the strut / wire can be a general shape such as a triangle or a partial triangle, a trapezoid, a blade, or a rhombus. And according to one embodiment of the present teaching, as the device expands radially, the edges of the strut / wire formed along the vertices of such a cross-sectional shape contact the surrounding blood vessel wall. Due to this special configuration, the stent structure having such a design exerts a higher radial force on the blood vessel wall than a stent structure made of circular struts / wires.

[0023] According to another embodiment of the present invention, the radial force acting on the blood vessel wall acts not only statically but also dynamically, specifically in a manner that moves longitudinally during the treatment of vasospasm. According to one embodiment, the stent structure is configured to move longitudinally over a length of about 5 - 50 mm over a period of about 30 - 60 seconds. Typically, the longitudinal movement is induced by the clinician pulling the proximal end of the delivery wire proximally. According to one embodiment of the present teachings, the distal end of the delivery wire is joined to the proximal end of the stent structure. Such movement is a continuous and steady movement, and its speed is generally slower than when retracting an implant into a delivery catheter, for example, when pulling a thrombectomy device into a suction catheter.

[0024] According to one embodiment of the present invention, the treatment of vasospasm includes at least two steps. First, the stent structure is deployed in its radially expanded profile at a treatment site where vasospasm is occurring or may occur, for example. Second, the stent structure is moved longitudinally to induce additional stimulation to the blood vessel wall. In one embodiment, the deployed stent structure is positioned at the treatment site for a limited period after its deployment and before being subjected to longitudinal movement. In another embodiment, the stent structure is subjected to longitudinal movement immediately after its deployment.

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

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

[0027] According to one embodiment of the present invention, when the first longitudinal movement to induce additional stimulation to the blood vessel wall is completed, the stent structure is again retracted proximally into the catheter and then released again at the treatment site, i.e., the site where vasospasm occurs or may occur, and thereafter, a second deployment and a second longitudinal movement follow. The described treatment can be repeated multiple times. In one embodiment, the longitudinal movement is repeated at least once on the same day. In another embodiment, such longitudinal movement is repeated at least once continuously for several days. In yet another embodiment, such longitudinal movement is repeated several weeks later, for example, after 6 weeks, 12 weeks, and 24 weeks, to induce a lasting effect.

[0028] According to one embodiment of the present invention, the repetition of the procedure, i.e., the longitudinal movement of the deployed stent structure, significantly improves the result of vasospasm treatment. In some cases, repeating the procedure only twice is sufficient. In one embodiment, the treatment procedure is performed at the site where vasospasm has occurred or may occur. In another embodiment, the above treatment procedure is performed on one branch of the bifurcation to treat vasospasm in adjacent blood vessels. For example, the treatment procedure in the region of the middle cerebral artery (MCA) and the distal internal carotid artery (ICA) of the sphenoid joint M1 also led to the dilation of the proximal anterior cerebral artery (ACA). That is, when treating vasospasm by the above method using the stent structure disclosed in the present invention, vasospasm in adjacent blood vessels or adjacent blood vessel portions is also relieved.

[0029] In some embodiments, when treating vasospasm by the above method, no lesion remains even when the blood vessel wall is examined using an imaging diagnosis of the blood vessel wall, such as magnetic resonance angiography (MRA), several days after the treatment. Therefore, the above procedure according to the present invention affects the intima as desired, but does not affect the media or adventitia.

[0030] In some embodiments, additional drug treatment, such as with nimodipine, can be performed together with the procedure using the device according to the present invention. In particular, it can be applied intra-arterially at the site of vasospasm.

[0031] According to one embodiment of the present invention, the connection between the insertion wire and the stent structure can be non-detachable or detachable. The delivery wire is typically a type of wire that is also used for implants. In embodiments where the stent structure is intended to remain permanently within the vasculature, the delivery wire is detachably connected to the stent structure. According to one embodiment, the detachment mechanism between the delivery wire and the stent structure can be mechanical separation, thermal ablation, or electrolytic ablation. Since the stent structure is intended for temporary deployment at the site of vasospasm, such a detachable connection to the stent structure is also possible according to the present invention. A stent structure detachably connected to the delivery wire provides the physician with options to release the stent structure inside the blood vessel as the situation demands, for example, if there are problems with retraction and it is found to be infeasible, or if it induces the application of a permanent radial force. The delivery wire is preferably made of stainless steel, nitinol, or a cobalt-chromium alloy. According to the present invention, a wire having an internal cavity or lumen is also considered a delivery wire.

[0032] According to one embodiment of the present invention, the delivery wire is preferably attached to the proximal end of the stent structure while being radially biased. In other words, the connection between the delivery wire and the stent structure is eccentrically located not at the center of the stent structure but at or near the inner wall of the blood vessel. This is done to minimize interference with blood flow as much as possible. Furthermore, the eccentric placement of the delivery wire facilitates the retraction of the stent structure into the catheter.

[0033] According to another embodiment of the present teachings, the delivery wire is connected to the stent structure at a plurality of locations including the proximal end of the stent structure. The plurality of connections between the delivery wire and the stent structure provide, on the one hand, a slightly stronger connection and, on the other hand, a greater occlusion of blood flow due to additional struts or wires running through the center of the blood vessel. Thus, according to some embodiments, the proximal end of the stent structure that tapers towards the delivery wire and thus no longer fully contacts the blood vessel wall and cannot substantially exert a radial force on the blood vessel can be kept shorter. In the case of a delivery wire connected to the stent structure at a plurality of positions, the insertion wire generally extends more centrally.

[0034] The stent structure is delivered through a catheter, which can in particular be a microcatheter. When used in particular in the neurovascular region, it is usually necessary to use a microcatheter. The stent structure can be advanced through the catheter to the treatment site. Alternatively, the stent structure is housed within the catheter and the catheter is advanced to the treatment site with the stent structure therein.

[0035] Often, before the stent structure is delivered to the treatment site by a catheter, a guide catheter with a relatively large lumen is first inserted, and through that guide catheter, a catheter with a small lumen is then advanced distally beyond the distal end of the guide catheter. In neurovascular applications, for example, the guide catheter is advanced from the groin to the carotid artery, and then the catheter advances through the guide catheter beyond the distal end of the guide catheter.

[0036] According to one embodiment of the present teachings, 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 expands radially. In another embodiment, the stent structure is deployed by advancing 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 disclosure, the stent structure is configured to self-expand radially when released from the catheter. For this purpose, a stent structure made of a material having shape memory characteristics, such as the use of a nickel-titanium alloy known as nitinol, or a material having superelastic characteristics. Those skilled in the art should recognize that any other alloy or polymer having the ability to self-expand to 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 stent structure can also be at least partially manufactured from a cobalt-chromium alloy, a cobalt-chromium-nickel alloy, or a cobalt-chromium-nickel-molybdenum alloy. In one embodiment, these materials are mostly titanium-free, thereby further improving the properties. An example of a material option is known as 35N LT (registered trademark).

[0039] The alloys described above in the context of the present invention are merely illustrative. It will be apparent that just because a metal is listed as a component of the alloy does not preclude the alloy from containing additional 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 does not need to have only platinum and iridium as its components. It will also be apparent that the above exemplary alloys may also contain non-metals such as carbon or nitrogen in addition to the metals. Given examples include certain superelastic / pseudoelastic alloys, radiopaque alloys, cobalt-chromium alloys, and the like. All other alloys suitable for the treatment methods disclosed in the present invention should be considered to be within the scope of the present invention.

[0040] According to another embodiment of the present teachings, the stent structure is constructed of DFT (drawn filled tubing) wires or struts. The DFT wire has an inner core of one metal and a sheath of another metal, so that the wire combines the properties of both metals. In particular, the DFT wire can have a radiopaque inner core and a pseudoelastic sheath. Suitable materials include those described above, in particular platinum alloys for inducing X-ray visibility and nickel-titanium alloys for pseudoelasticity.

[0041] When the treatment of vasospasm is completed, the stent structure is typically withdrawn into the catheter. The catheter carrying the folded stent structure is then removed from the blood vessel. According to one embodiment, the catheter is pushed distally onto the stably positioned stent structure so that as the catheter slides over the entire length of the stent structure, the stent structure is radially folded into its compressed state. According to another embodiment, the stent structure is pulled proximally within a fixedly positioned catheter. In yet another embodiment, a combination of the distal movement of the catheter and the proximal movement of the stent structure causes the stent structure to be radially folded and fit back inside the catheter. Once the stent structure is inside the catheter, the clinician can withdraw the entire system proximally outside the blood vessel.

[0042] The stent structure typically consists of interconnected struts or wires that form a mesh structure. In one embodiment, the stent structure is fabricated by laser cutting a tube using techniques known to those skilled in the art. The laser-cut stent structure has a plurality of openings, i.e., a mesh structure, distributed circumferentially around the stent structure. The advantage of the laser-cut stent structure is that almost any shape of the openings can be designed. Those skilled in the art should understand that other forms of manufacturing processes, such as electrolytic or lithographic manufacturing, 3D printing, or rapid prototyping, can also be employed to fabricate the stent structure. Therefore, the above exemplary embodiments should not be considered limiting.

[0043] In another embodiment, the stent structure can be made of braided wire. In this case, typically, a plurality of wires run spirally along the longitudinal axis, and another plurality of wires run spirally in the opposite direction. These wires cross each other vertically and form honeycomb-shaped openings between the wires. The total number of wires used to make the stent structure can be from 8 to 64, and each wire can be a single wire or a stranded wire (a filament formed by twisting several small-diameter wires together). The advantage of the braided stent structure is that the wires can have any preformed cross-section, such as triangular, trapezoidal, blade-shaped, or diamond-shaped.

[0044] In one embodiment, the stent structure has interconnected struts, such as a laser-cut stent structure. Such a stent structure tends to have less length contraction during expansion. The stent structure with interconnected struts exerts a relatively larger radial force than the braided stent structure, considering other equivalent structures such as strut / wire density and strut / wire thickness. This is because the interconnected struts are fixedly connected at the intersections, while the wires of the braided stent structure generally slide relative to each other during the radial expansion of the stent structure.

[0045] The present invention further provides an exemplary strut / wire configuration for the purpose of enhancing the treatment of the blood vessel wall at the vasospastic site. Specifically, according to one embodiment of the present teachings, the cross-section of the strut / wire forming the stent structure decreases radially outward when viewed radially. When the stent structure is deployed, the stent structure expands radially, and the outermost radially portion of the strut / wire contacts the surrounding blood vessel wall. In one embodiment, the portion of the strut / wire that contacts the blood vessel wall is relatively narrower than the radially inner portion of the strut / wire that does not contact the blood vessel wall, that is, the cross-section of the strut / wire tapers outward in the radial direction and the cross-sectional area decreases. Such a strut / wire design increases the temporal pressure on the blood vessel wall, and thus, even with the same radial force of the stent structure, the stimulation to the blood vessel wall is enhanced. According to one embodiment of the present teachings, a strut / wire having a triangular, wedge-shaped, trapezoidal, blade-shaped or rhombic cross-sectional shape exerts a higher piercing force on the blood vessel wall than a stent structure made of struts / wires having a circular cross-sectional shape.

[0046] A properly configured strut or wire can also effect a certain degree of ablation (exfoliation) of the intimal layer. By tapering the strut / wire outward in the radial direction, the strut / wire has a blade-like effect, thus promoting exfoliation. This requirement is somewhat contrary to the requirement for thrombectomy, i.e., the removal of thrombus. For thrombectomy, it is desirable that the stent structure be non-traumatic, but in the treatment of vasospasm according to the present invention, it is desirable to have a certain impact on the blood vessel wall. Therefore, the specific configuration of the strut / wire as disclosed herein is advantageous.

[0047] According to one embodiment of the present teachings, the strut / wire can have a cross-section, for example, in the shape of a triangle, wedge, trapezoid, blade or rhombus. When a stent structure is fabricated with such a strut / wire in a fully expanded state, the strut / wire is oriented such that in the cross-sectional view of the stent structure, the corners of the formed wire are at the outermost radially portion of the stent structure and contact the blood vessel wall.

[0048] According to another embodiment of the present teachings, at least one strut / wire of the stent structure has a cross-sectional shape that is a quadrilateral including any modified quadrilateral such as a parallelogram, rectangle, rhombus, or rectangle having one slanted side. Considering one possible embodiment, when viewed in the cross-sectional direction, one of the acute angles of the quadrilateral is at the outermost radially portion of the deployed stent structure. In other words, the outermost edge of the strut / wire formed along this corner is the outermost radially portion of the stent structure and contacts the vessel wall.

[0049] In an embodiment where the strut or wire extends obliquely and is not perpendicular to the longitudinal axis, the edge of the strut / wire at the outermost radially portion of the stent structure faces in the proximal direction. In this design, when the stent structure moves in the proximal direction, the strut / wire can act on the vessel wall like a scraper or the blade of a razor, causing exfoliation there.

[0050] According to another embodiment of the present teachings, in order to provide a sufficiently strong effect on the vessel wall, the stent structure is configured such that when the stent structure is in a deployed configuration expanded radially, the strut / wire faces in a direction generally perpendicular to the longitudinal axis of the stent structure. For example, the strut / wire and the longitudinal axis of the stent structure form an angle of at least 60°. In a preferred embodiment, the angle between the strut / wire and the longitudinal axis of the stent structure is greater than 70°. In another embodiment, the angle between the strut / wire and the longitudinal axis of the stent structure is greater than 80°. Thus, when the stent structure moves longitudinally, a wider range of the vessel wall is affected.

[0051] The terms "proximal" and "distal" are to be understood to mean that when the device is inserted, the part of the device closer to the treating physician is called proximal and the part farther from the treating physician is called distal. Thus, the device is typically advanced distally through a catheter. The term "axial" refers to the longitudinal axis of the device running 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 individual struts / wires have an inscribed diameter of 0.1 to 6 mm, where the inscribed diameter is understood to be the diameter of the largest possible circle that can be placed within the opening. The maximum inscribed diameter refers to the stent structure in a state where it is not fully constrained, i.e., in a state of maximum radial expansion. However, depending on the diameter of the blood vessel in which the implant is placed, the implant may not be able to assume a fully expanded state, and the inscribed diameter may be different from the state of maximum expansion.

[0053] According to one embodiment, the stent structure has openings formed between individual struts / wires with an inscribed diameter greater than 1 mm. Such a stent structure with a relatively coarse mesh is configured to exert a radial force of an appropriate magnitude to treat vasospasm. For example, a stent structure with an expanded diameter of 3 to 5 mm may have mesh openings with an inscribed diameter of 2 to 4.5 mm.

[0054] According to one embodiment, the stent structure of the present invention has closed-cell mesh openings, i.e., each cell opening is in a closed shape completely surrounded by struts / wires without interruption.

[0055] In one embodiment, the stent structure of the present invention is composed of struts / wires having a relatively large cross-sectional area or diameter, that is, relatively solid struts / wires, and serves the purpose of generating a radial force of a specific magnitude. In one embodiment, the cross-section may be round or angled. In order to generate a specific amount of radial force, the height and width of the strut / wire are 30 to 300 μm, preferably 40 to 200 μm, and most preferably 40 to 120 μm.

[0056] According to one embodiment of the present teachings, the stent structure has a generally longitudinally extending tubular opening that extends from an open proximal end to an open distal end. Such a designed stent structure has the advantage of not disturbing the blood flow as much as possible and preventing insufficient blood supply to the surrounding tissues. In another embodiment of the present teachings, the stent structure has a generally longitudinally extending tubular opening that extends from an open proximal end to a closed distal end. The stent structure with a closed distal end is less invasive. In this context, an open end means that there are no struts / wires at each end of the stent structure, and the struts / wires are limited to the outer periphery of the stent structure. On the other hand, a closed end is defined by the presence of struts / wires in the center of the longitudinally extending tubular opening of the stent structure. Since the stent structure has mesh openings between the struts / wires along its outer periphery, even if the distal end is closed, blood can still pass through the stent structure through the mesh openings. Therefore, although the blood flow will be restricted, it will not be completely blocked.

[0057] Figures 1 to 3 show exemplary embodiments of the present invention. In all figures, the proximal is on the left and the distal is on the right.

[0058] FIG. 1 shows a vasospasm treatment device according to a first exemplary embodiment of the present invention. The device 1 comprises a laser cut stent structure 2 which is connected to a delivery wire 3 at its proximal end. The stent structure 2 is shown in a radially expanded state outside the catheter 4 and inside the vascular region c (constricted region). According to one embodiment, the deployed stent structure 2 is positioned against the inner wall of the blood vessel constricted by vasospasm. According to one embodiment, the stent structure 2 is delivered via a catheter (not shown). During delivery, the stent structure 2 is radially compressed and disposed inside the distal portion of the catheter 4. The catheter 4 carrying the stent structure 2 is inserted through the blood vessel v to the vasospasm site c.

[0059] FIG. 1 further shows an apparatus and method for treating vasospasm using the apparatus 1 according to the present invention according to one embodiment of the present teachings. When the stent structure 2 is released from the catheter 4, the stent structure 2 radially expands and abuts against the inner wall of the blood vessel v at the vasospasm site c. The stent structure is then positioned at the vasospasm site c for a limited period of time, after which the stent structure 2 moves longitudinally through the stenosis region c of the blood vessel v in its radially expanded state. Preferably, the movement of the radially expanded stent structure 2 is in the proximal longitudinal direction as indicated by the first arrow ar1. In this context, the combination of the longitudinal movement and the radial force of the apparatus acting on the blood vessel wall of the stenosis c, as indicated by the second arrow ar2, results in at least partial exfoliation of the inner layer, i.e., the intima, of the blood vessel in the stenosis c.

[0060] FIG. 1A is a detailed cross-sectional view of the stent structure, with the outermost radially portion of the stent structure in contact with the blood vessel wall. As can be seen from FIG. 1A, the outer radial surface of the stent strut 2' is in contact with the blood vessel wall v.

[0061] Figures 1B to 1G show various embodiments of the cross-sectional configuration of the stent strut 2'. In one embodiment, as shown in Figure 1C, the cross-sectional shape of the strut 2' has at least a partially trapezoidal shape. In one embodiment, the shorter parallel side is on the radially outer surface of the stent structure and contacts the blood vessel wall when the stent structure is in its radially expanded state. In another embodiment, the corner of the shorter parallel side is at the outermost radially edge of the stent structure and contacts the blood vessel wall when the stent structure is in its radially expanded state.

[0062] In another embodiment as shown in Figure 1D, the cross-sectional shape of the strut 2' has at least a partially triangular shape. In one embodiment, one corner of the triangle is at the outermost radially edge of the stent structure and contacts the blood vessel wall when the stent structure is in its radially expanded state.

[0063] In another embodiment as shown in Figure 1E, the cross-sectional shape of the strut 2' has at least a partially wedge-shaped, i.e., acute triangular shape. In one embodiment, one corner of the triangle is at the outermost radially edge of the stent structure and contacts the blood vessel wall when the stent structure is in its radially expanded state.

[0064] In another embodiment as shown in Figure 1F, the cross-sectional configuration of the strut 2' has at least a partially parallelogram shape. In one embodiment, one side of the parallelogram is on the radially outer surface of the stent structure and contacts the blood vessel wall when the stent structure is in its radially expanded state. In another embodiment, the corner of the parallelogram is at the outermost radially edge of the stent structure and contacts the blood vessel wall when the stent structure is in its radially expanded state.

[0065] As shown in FIG. 1G, in yet another embodiment, the cross-sectional configuration of the strut 2' has at least a partially rectangular shape. In one embodiment, one side of the rectangle is on the radially outer surface of the stent structure and contacts the blood vessel wall when the stent structure is in its radially expanded state. In another embodiment, the corner of the rectangle is at the outermost radially edge of the stent structure and contacts the blood vessel wall when the stent structure is in its radially expanded state. In yet another embodiment, the corners of the rectangle forming the outermost radially edge of the stent structure are acute angles.

[0066] One of ordinary skill in the art should understand that the term "strut" as used herein can also be a wire, and these two terms can be used interchangeably. Accordingly, the various embodiments described with reference to FIGS. 1B-1G are also applicable to wires, such as the various embodiments described with reference to FIGS. 2 and 2A, for example.

[0067] FIG. 2 shows an apparatus 101 for treating vasospasm, which is a second exemplary embodiment of the present invention. The apparatus 101 includes a braided stent structure 201 made of wires having a proximal end connected to a delivery wire 301. The stent structure 201 is shown in a radially expanded state outside the catheter 401 and inside the blood vessel region c (stenosis). According to one embodiment, the deployed stent structure 2 is positioned against the inner wall of the blood vessel constricted by vasospasm. According to one embodiment, the stent structure 201 is delivered via a catheter (not shown). During delivery, the stent structure 201 is radially compressed and disposed inside the distal portion of the catheter 401. The catheter 401 carrying the stent structure 201 is inserted through the blood vessel v to the vasospasm site c.

[0068] FIG. 2A shows a perspective cross-sectional configuration through the stenosis region c according to FIG. 2. As can be seen from FIG. 2A, the radially outer surface of the wire 201' is in contact with the blood vessel wall vc.

[0069] Figure 3 shows the blood vessel v successfully treated by the apparatus 1 according to an embodiment of the present disclosure. As shown in the figure, the region c that had been constricted until then is fully dilated, and the stent structure 2 further expands radially as compared to the expanded state shown in FIG. 1. Now, the stent structure 2 can be retracted into the catheter 4 and removed from the blood vessel v.

[0070] In one embodiment of the present disclosure, an antithrombotic coating inside the stent structure is useful because it must remain in the blood vessel for a certain period of time and avoid the formation of thrombi in the blood vessels that have already constricted due to the occurrence of vasospasm during that time. Outside the stent structure, a vasodilator coating having a calcium antagonist such as nimodipine is advantageous.

[0071] In another embodiment, a coating that prevents platelet adhesion and aggregation, such as the coating described in International Publication No. WO 2018 / 210989 A1, can also be incorporated into the stent structure. Here, a coating having a functional layer is applied to the medical device, and the functional layer is formed by oligomerization or polymerization of monosaccharides functionalized with at least one sugar alcohol and / or polymerizable groups. This coating can mimic the natural glycocalyx.

[0072] The antithrombotic coating is particularly useful inside the stent structure, and the vasodilatory coating is particularly useful outside the stent structure. However, the antithrombotic coating or the vasodilatory coating can also be applied to the entire stent structure, or the struts / wires can have the corresponding coating on the entire surface. In this case, the coating is not limited to the inside or outside of the stent structure.

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

[0074] In one embodiment, the force exerted radially outward on the vascular inner wall by the expanded stent structure should be 2 to 30 N / m, preferably 5 to 10 N / m, based on a stent structure with a general diameter of 2.00 mm. The specification of the radial force refers to the force acting radially per unit length, i.e., the relative radial force. Only the portion (effective length) of the stent structure that contacts the vascular inner wall and can thus exert a force on the blood vessel is considered.

[0075] According to one embodiment of the present teachings, the radial force exerted by the expanded stent structure is essentially constant along its effective working length, i.e., the radial forces applied to both the proximal section, the intermediate section, and the distal section of the stent structure of the effective working length are the same. In another embodiment, the stent structure can exert a weak radial force at the proximal and distal sections of the effective working length and a relatively strong radial force at the intermediate section of the effective working length. In one embodiment, the proximal and distal sections of the stent structure are selectively modified to generate a uniform radial force over the entire effective working length from the proximal end to the distal end of the stent structure. 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 portion that is located most proximally and is no longer part of the effective working length, where the struts / wires converge towards 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 about 8 to 10 mm.

[0076] According to one embodiment of the present disclosure, in order to increase the radial forces in the proximal and distal sections of the effective working length of the stent structure, the struts / wires used in these two sections can have a larger cross-sectional area than those used in the intermediate section. In other words, the struts / wires used in these two sections have a greater mass. By doing so, the basic tendency of the stent structure for the intermediate section to exert a larger radial force can be at least partially offset.

[0077] In an alternative embodiment, the struts / wires used in the proximal and distal sections of the effective working length of the stent structure can have a higher density than those used in the intermediate section of the effective working length of the stent structure. Therefore, the natural tendency for the radial forces exerted by the proximal and distal sections of the stent structure to be weak is at least partially offset.

[0078] According to another embodiment of the present disclosure, it is possible to provide the stent structure with slots that extend helically across the side surface of the stent structure or slots that extend longitudinally along the side surface of the stent structure. In some embodiments, when the stent structure is in its radially expanded configuration, at least one strut / wire can be incorporated across the slot to adjust the longitudinal distribution of the radial force along the effective working length of the stent structure.

[0079] In one embodiment, the diameter of the stent structure in its radially expanded state is typically 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 typically 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 that actually exerts a radial force on the blood vessel inner wall in its radially expanded state, is usually about 8 to 10 mm shorter than the total length of the stent structure, preferably having a length of 20 to 40 mm.

[0080] This device has one or more radiopaque markers for providing visualization to 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, an X - ray opaque filament can be used for visualization purposes and can be placed at various positions of the device. The radiopaque marker / filament can be incorporated at the distal end of the stent structure, the proximal end of the stent structure, and / or anywhere between the distal and proximal ends of the stent structure. The stent structure, particularly the struts / wires of the stent structure, can also be coated with a coating of a radiopaque material, such as a gold coating. The thickness of the radiopaque coating can be, for example, 1 - 6 μm. The radiopaque coating may also cover only important regions of the stent structure, i.e., the effective length of the stent structure, or the cylindrical portion of the stent structure where it contacts tissue. The stent structure can incorporate both a radiopaque coating and one or more radiopaque markers.

[0081] In one embodiment, the stent structure can be manufactured by laser cutting technology or other techniques known to those skilled in the art from a tube. Such a tube can have a wall thickness of 30 - 300 μm, preferably 40 - 200 μm, and most preferably 40 - 120 μm. In another embodiment, the stent structure can be made of woven wires by braiding technology or other techniques known to those skilled in the art. Such wires can have a thickness of 30 - 300 μm, preferably 40 - 200 μm, and most preferably 40 - 120 μm. A catheter is used to deliver the stent structure to the vasculature. During delivery, the stent structure is radially compressed and placed inside the catheter. Such a catheter can have an inner diameter of 0.4 - 0.9 mm.

[0082] In the radially expanded state, part or all of the stent structure is generally cylindrical, and the openings are distributed on the outer cylindrical surface. In other words, the stent structure has a lattice or mesh-like surface structure with a number of openings between the struts / wires on the outer cylindrical surface.

[0083] In one embodiment, the stent structure is permeable to the outside. In another embodiment, the stent structure may have one or more membranes on the circumference. The term "orifice" refers to a lattice or mesh structure regardless of whether the orifice is isolated from the environment by a membrane, that is, even an orifice covered by a membrane is also called an orifice. If necessary, a membrane can be applied outside or inside the mesh structure. It is also possible to embed the grid and / or mesh structure in the membrane. The membrane can be made of a polymeric material such as polytetrafluoroethylene, polyester, polyamide, polyurethane, polyolefin or polysulfone. Polycarbonate urethane (PCU) is particularly preferred.

[0084] The present invention relates to both a method for treating vasospasm and a corresponding device, as well as the use of the device. The present invention can be used for the treatment of acute vasospasm, but prophylactic use is also possible. The device according to the present invention can be used particularly in the neurovascular field, but can also be used in the cardiovascular or peripheral fields. All descriptions regarding this device apply equally to this method, and vice versa.

[0085] Hereinafter, with reference to the drawings, the present invention and its technical field will be described in more detail. It should be noted that although particularly preferred embodiments of the present invention are shown in the drawings, the present invention is not limited to the illustrated embodiments. In particular, the present invention includes any combination of technical or methodological features described in the claims or the specification related to the present invention, as long as they are technically or methodologically useful.

Claims

1. A method for treating vasospasm using a stent structure, the method comprising: placing the stent structure inside a catheter, the stent structure having a radially expanded state in which the stent structure is positioned against the inner wall of the blood vessel and a radially compressed state in which the stent structure is movable within the catheter, and connecting a delivery wire to the proximal end of the stent structure; inserting the catheter into a treatment site inside the blood vessel; deploying the stent structure by releasing the stent structure from the catheter and transitioning the stent structure from a radially compressed state to a radially expanded state; moving the stent structure longitudinally through the blood vessel, the method.

2. The method according to claim 1, wherein the stent structure is fixed and maintained in its radially expanded state for 1 to 10 minutes before moving longitudinally through the blood vessel.

3. The method according to claim 1 or 2, wherein the stent structure is withdrawn into the catheter after moving longitudinally through the blood vessel and then removed from the blood vessel within the catheter.

4. The method according to any one of claims 1 to 3, wherein the movement of the stent structure in the expanded state is in the proximal direction.

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

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

7. The method according to any one of claims 1 to 5, wherein the struts or wires have a cross-section that is at least partially quadrilateral, and the acute angle portion on the radially outer side of the quadrilateral is the outermost radially portion of the stent structure.

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

9. An apparatus for treating vasospasm, comprising a stent structure formed of struts or wires, the stent structure having a radially expanded state in which the stent structure is positioned against the inner wall of a blood vessel and a radially compressed state in which the stent structure is movable within a catheter, and a stent structure, a delivery wire connected to the proximal end of the stent structure, wherein the cross-section of the strut or wire decreases radially outward, wherein the cross-section of the strut or wire has a radially outwardly acute angle at the outermost radially portion of the stent structure, apparatus.

10. The apparatus according to claim 9, characterized in that the strut or wire has at least partially a cross-section in the shape of a quadrilateral, triangle, blade, or rhombus.

11. The apparatus according to claim 9 or 10, characterized in that the strut or wire in the expanded state forms an angle of at least 60° with the longitudinal axis of the stent structure.

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

13. The apparatus according to claim 12, characterized in that the strut or wire has a larger cross-section in the proximal and distal sections of the effective working length of the stent structure than in the middle portion of the effective working length of the stent structure.

14. The apparatus according to claim 12 or 13, characterized in that the density of the strut or wire is higher in the proximal and distal sections of the effective working length of the stent structure than in the middle portion of the effective working length of the stent structure.

Images