WO2024035378A1

WO2024035378A1 - Implantable intraluminal blood flow modulator

Info

Publication number: WO2024035378A1
Application number: PCT/TR2023/050807
Authority: WO
Inventors: Rasit DINC
Original assignee: Invamed Sağlik İlaç Sanayi̇ Ve Ti̇caret Anoni̇m Şi̇rketi̇
Priority date: 2022-08-12
Filing date: 2023-08-14
Publication date: 2024-02-15

Abstract

This invention is about an implantable intraluminal prosthesis. The invention is essentially a modulator used as an endoprosthesis, which acts as a lumen blood flow modulator for the treatment of non-linear blood flow in branched defective vascular structures and the treatment of aneurysms containing branches, especially for the treatment of aneurysms located in the aortic arch, abdominal and thoracic aorta, intracranial vessels and peripheral vessels and a transmission system used for the placement of the modulator.

Description

IMPLANTABLE INTRALUMINAL BLOOD FLOW MODULATOR

TECHNICAL FIELD

BACKGROUND

Vascular aneurysms are the result of abnormal enlargement of a blood vessel, usually caused by disease and/or genetic predisposition, which can weaken the artery wall and allow it to enlarge. While aneurysms can occur in any blood vessel, most occur in the aorta and peripheral arteries. The majority of aortic aneurysms occur in the abdominal aorta; it usually begins below the renal arteries and often extends distally to one or both of the iliac arteries.

Aortic aneurysms are most commonly treated with open surgical procedures in which the diseased vessel segment is bypassed and repaired with an artificial vessel graft. While considered an effective surgical technique, traditional vascular graft surgery suffers from a number of disadvantages, especially when considering the alternative, the often fatal ruptured abdominal aortic aneurysm. The surgical procedure is complex and requires experienced surgeons and well-equipped surgical facilities. However, even with the best surgeons and equipment, patients who are often treated become debilitated by cardiovascular and other diseases, reducing the number of eligible patients. Even for eligible patients prior to rupture, conventional aneurysm repair has a relatively high mortality rate, usually 3% to 10%. Morbidity associated with conventional surgery includes myocardial infarction, kidney failure, impotence, paralysis and other conditions. In addition, even with successful surgery, recovery takes several weeks and often requires a long hospital stay. In the background art, endovascular graft placement has been proposed for the treatment of aneurysms to overcome some or all of these disadvantages. Although very promising, many of the proposed methods and apparatus suffer from other problems. For example, while endovascular grafts act as an artificial vessel in the area where they are placed, they do not allow the passage of blood flow through the graft wall. Thus, feeding of the branches is prevented. In such conditions, the use of endovascular grafts is restricted in areas where branch-vessel patency needs to be ensured. In addition, transmission and placement of the endovascular graft within the vasculature may be problematic. Proper positioning and sizing of the endovascular graft are critical to successful treatment of an aneurysm. Grafts are generally flexible, tending to expand and anchor the graft in the body lumen. These flexibly expanding grafts are tightly compressed within the catheter and exert significant forces against the surrounding catheter bodies, often causing excessive friction between the graft and the catheter wall. These forces make it difficult to place the graft into the catheter, in addition to the correct release of the graft and stents in the body lumens. Also, the catheters must move the graft within the vascular system. Therefore, catheters must have flexible, elongated stems that are particularly susceptible to enlarged graft, which often results in graft invagination in the soft material of the catheter wall.

For these reasons, it is desirable to provide improved apparatus and methods for the endovascular placement of intraluminal prostheses, including grafts, stents, and stent-grafts to treat aneurysms and other conditions. It would be particularly desirable to provide delivery catheters and methods for placement of endoluminal tubular prostheses that would facilitate controlled release of flexible tubular prostheses. It is particularly desirable to provide delivery catheters and methods that reduce frictional forces created by flexible expansion against the catheter during the placement and release of prostheses.

Thoracoabdominal aortic aneurysm (TAAA) is a complicated aortic disease involving portions of both the thoracic and abdominal aorta. Although traditional open surgery is still considered the gold standard approach in the treatment of TAAA, some alternative techniques such as endovascular techniques and hybrid surgery have emerged in recent years, especially for patients who are not suitable for an invasive procedure. Total endovascular repair of TAAA is particularly difficult when the aneurysmal site covers the ostia of some secondary branched vessels. In this case, patient-specific, custom-designed grafts are required to protect the associated secondary branches, causing several weeks of delay before surgery can be performed. As an alternative to custom-made stent-grafts, the 5 hybrid technique involves separating the extra-anatomical branches of the secondary branches with the endovascular procedure.

BRIEF SUMMARY AND THE OBJECT OF THE INVENTION

The object of the invention is to provide a blood flow modulator that acts as a luminal endoprosthesis suitable for aneurysm occlusion in the arterial fork and that is easy to position.

Another object of the invention is to provide a modulator that is also simple to manufacture.

The stress created by the turbulent flow applied to the artery wall damages the intima, causing the aneurysm to grow larger. Thanks to the flow modulator with magnetic content developed with the invention, the blood flow in the vessel with aneurysm can be adjusted, turbulent flow is eliminated by converting it to laminar flow. Stabilization and/or reduction of the aneurysm size is ensured, since blood flow to the aneurysm will not be provided and/or be provided in smaller amounts after the blood flow in the vessel passes to laminar flow. The developed flow modulator prevents the formation of new aneurysms due to stress applied to the intima.

The implantable intraluminal blood flow modulator developed with the invention has a self-expanding, biocompatible braided mesh structure that represents a new paradigm for treating aneurysms. The innovative idea of such a device is to overcome the exclusion of the aneurysm site from the circulation by restoring physiological blood flow within the aneurysm sac, converting turbulent flow to laminar flow and promoting organized and stable thrombus formation.

BRIEF DESCRIPTION OF THE DRAWINGS

Drawing 1; This is an exploded view of the transmission system developed with the invention.

Drawing 2; This is a detailed view of the modulator and the layered structure developed with the invention.

Drawing 3; This is a schematic drawing showing the placement of the modulator in the vessel. References in the Drawings

1. Modulator

2. Layer

3. Magnet

4. Transmission system

5. Catheter

6. Distal tip

7. Connector

8. Transmission part

A. Aneurysm

D. Vessel

Y. Branch

DETAILED DESCRIPTION OF THE INVENTION

With this invention, an implantable intraluminal blood flow modulator (1) has been developed. Said blood flow modulator (1) is in a self-expanding, braided-network structure containing magnets (3), formed in multiple interconnected layers, which preferably have three-dimensional geometrical structures, and consisting of metallic stainless steel and nickel-titanium alloy wire. The three- dimensional multilayered structure modulates the hemodynamic flow within the affected arterial segment. Through its three-dimensional geometry and the magnets (3) it contains, the turbulent flow rate in the aneurysm is reduced, while laminar flow in the main artery and surrounding vital branches is improved.

The blood flow modulator (1) developed with the invention, in its most basic form, is made of shape memory material, which is placed intraluminally in the vessel where the aneurysm is located, configured to regulate the turbulent blood flow in the vessel to convert it to laminar flow, sized in accordance with the vessel to be placed, preferably in a cylindrical structure and contains at least one layer (2) in the three-dimensional spiral, porous lattice structure, and at least two magnets (3) located at predetermined positions on the layer (2), positioned with opposite poles facing each other and changing the pore size through their movements in such a way that they approach and move away from each other with the help of the force acting on each other. Here, what is meant by lattice structure is that the layer is formed of a mesh structure. First of all, in the invention, a detailed examination of the branch and the vein with the aneurysm, whose blood flow will be regulated is made and the structure of the vein, the location of the branch/branches, the aneurysm and its properties are examined. This provides a modulator specific to the patient and aneurysm. For example, before the modulator (1) is developed, an image of the vascular structure can be taken with imaging technologies and a modulator (1) suitable for the vascular structure can be designed.

In the modulator (1), the layer (2) is formed by braiding a large number of wires made of shape memory, biocompatible alloy material. The structure of the modulator is preferably cylindrical and the vessel ends are curved. Thus, when placed in the vein, its curved ends prevent it from sticking to the vein and displacing the modulator. A self-expanding lattice structure is formed thanks to the fact that the modulator (1) is made of helical porous mesh structure and shape memory material.

In order to create the modulator (1) developed with the invention, wires made of shape memory material, preferably in micron size, are intertwined on a mandrel to form a mesh structure, and shape memory is given to the obtained mesh structure by applying heat treatment.

In the invention, the mesh structure means that the modulator (1) is porous. Here, the pore sizes in the layer (2) or layers (2) are adjusted by the magnets (3). Thanks to the magnets (3) in the sections where blood flow is expected in the branches of the vessels, these pores expand to allow blood flow. In sections without branches, it creates a narrow pore space and laminates the blood flow. Therefore, while the modulator (1) is being designed, the position of the magnets (3) in the layer (2) is determined according to the position of the aneurysm and branches. In the invention, more than one layer (2) can be utilized and there are preferably 5 layers (2). The magnets (3) can be positioned between these layers (2) and/or on the layer (2) surfaces. The modulator (1) is inserted into the vessel with aneurysm by means of a transmission system (4). The transmission system (4), in its most basic form, includes at least two interlocking catheters (5), at least one transmission piece (13) placed between the two catheters (5), at least one connector (7), at least one distal tip (6) for the placement of the modulator (1) and at least one transmission part (8) controlling the distal tip. The catheters (5) in the transmission system (4) preferably have 2 lower, 2 upper row mesh structures and are hydrophilic coated.

In the process of placing the modulator (1) into the vessel, the position of the tip and end parts of the modulator (1) are adjusted (verification is made) so as to completely cover the part where the aneurysm is located. The blood flow modulator (1) to be implanted through the transmission system (4) is placed in the vessel. Thanks to the magnets (3) on the 3D surface of the modulator (1), the high- pressure blood flow regions that cause the aneurysm in the vessel are located, and these magnets (3) converge on each other and narrow the pore spaces, thanks to the magnetic field they create in the bulging parts of the aneurysm with no angled blood flow (without branches). In locations with branch feeding, the magnets (3) move away from each other, weakening the magnetic field and increasing the pore sizes, thanks to the opposite vertical force created by the blood flow. Here, while the blood flow to the branches continues, the vein with aneurysm is laminated at the same time. In other words, the modulator (1) adjusts the passage of blood to the aneurysm by adjusting the pore sizes thanks to the magnets (3) it contains, and the turbulent flow is laminated thanks to the force applied by the blood flowing to the vessel and branches after the modulator (1) placement, allowing the magnets (3) to converge or move away.

The implantable intraluminal blood flow modulator (1) is described as a self-expanding, preferably platinum wire-supported, biocompatible braided mesh structure that represents a new paradigm for treating aneurysms.

The invention overcomes the exclusion of the aneurysm site from the circulation by re-establishing the physiological blood flow in the aneurysm sac, transforming the turbulent flow in the vessel into laminar flow, supporting the formation of organized, stable thrombus. In this way, after the placement of the implantable intraluminal blood flow modulator, the stress applied to the intima by the irregular flow (WSS) is reduced and the vessel is protected against rupture due to vessel diameter expansion. Another important feature is the ability to maintain perfusion of the branches thanks to the porous structure of the invention, avoiding all the problems associated with the branching procedure that occur in conventional endovascular treatments. Thanks to its special design, the invention changes the pore sizes in its structure by adjusting the blood flow to be fed to the branches and the flow to be laminated in the vessel according to the diameter of the said vessel and aneurysm. Thanks to the magnets it contains, the blood flow modulator (1) can be expanded or contracted without the need for surgery. With its adjustable porous structure, it modulates blood flow at different rates in different vessel diameters. The invention can also increase or decrease blood flow with its magnets (3). It is used in aortic aneurysms, peripheral artery aneurysms and intracranial aneurysms.

The implantable intraluminal blood flow modulator (1) has high bending and fatigue resistance thanks to its small pored structure.

Peak velocities of up to 500 cm/sec may be possible in the aortic valve. The ascending aorta has the highest average peak velocity of the main vessels, with typical velocity values of 150-175 cm/sec. While the flow in the distal aorta and iliac arteries ranges between 100-150 cm/sec, the peak velocities in the proximal carotid, brachial and superficial femoral arteries average 80-110 cm/sec. Within the skull, the peak velocities of the middle and anterior cerebral arteries average 40-70 cm/sec, and the velocity in the vertebrobasilar system is 30-50 cm/sec. Venous velocities are usually less than 20 cm/sec; in certain pathological conditions, such as arteriovenous fistulas, up to 400 cm/sec may be measured.

When the implantable intraluminal blood flow modulator (1) is compared with the wall thickness of a conventional prosthesis, it can be observed that the intraluminal modulator (1) exhibits a three- dimensional (3D) porous structure due to the wall thickness of the intraluminal modulator (1), each layer of which (2) has a mesh structure. The 3D porosity increases in direct proportion to the wall thickness of the modulator (1). One of the technical benefits of the 3D porosity of the intraluminal prosthesis is that the intraluminal prosthesis has mechanically/physically arterial blood flow, as in conventional stent-graft techniques. With its unique structure, the implantable intraluminal blood flow modulator (1) laminates the flow by preventing the passage of turbulent flow into the aneurysm, and thanks to its permeable layers, open bypass procedures and personalized design are not required to maintain blood flow.

Studies and experiments conducted by current researchers have led to unexpected and surprising results. "Perfusion" is the biological process of delivering blood to the capillary bed. The terms "hypoperfusion" and "hyperfusion" refer to the under- or over-circulation of tissue. For example, the intraluminal prosthesis of the invention increases perfusion in the ascending aortic branch while covering it, resulting in improved function of the organ to which the ascending aortic branch supplies blood.

The healthy individual values for the invention planned to be used for intracranial aneurysm were calculated as 82 ml/min in the anterior cerebral artery, 54 ml/min in the posterior cerebral artery, 110 ml/min in the external carotid artery and 257 ml/min in the internal carotid artery. The implantable intraluminal blood flow modulator suitable for peripheral use was researched and it was observed that the iliac arterial blood flow was 119 cm/sec and the popliteal artery blood flow was 69 cm/sec in healthy individuals.

A more characteristic improvement in "perfusion" was observed in the branches covered by the implantable intraluminal blood flow modulator (1), each layer (2) of which was covered by a networked wire composition.

The implantable intraluminal blood flow modulator (1) is preferably constructed from a maximum of 216 wires, preferably by knitting a minimum of 72 and a maximum of 144 wires. The diameter of the wire preferably ranges from a minimum of 100 pm to a maximum of 250 pm. Each wire forming a multiple layer acts to laminate the blood flow through the periphery of the luminal implantable intraluminal blood flow modulator (1). The implantable intraluminal blood flow modulator (1) preferably has a diameter ranging from 5 mm to 45 mm and a length ranging from 20 mm to 200 mm. It is 10 to 30 percent larger in comparison to the outer diameter of the normal arterial wall in the proximal and distal landing zones of the implantable intraluminal blood flow modulator (1).

Table 1. Aortic blood flow values

Table 2. Anterior cerebral artery blood flow values

Table 3. Posterior cerebral artery blood flow values

Table 4. External carotid artery blood flow values

Table 5. Internal carotid artery blood flow values

Table 6. Iliac artery blood flow values

Table 7. Popliteal artery blood flow values

In all the contexts described above for the treatment of aneurysms, and especially in highly complicated cases, surgeons are involved in the evaluation of some important geometric and morphological features such as maximum diameter, volume, area in given positions, and overall surface transformations. Additionally, in the case of implantable intraluminal blood flow modulator treatment, the insertion of the invention into an aneurysm sac causes blood flow changes, resulting in significant geometric changes that are difficult to predict in advance and need to be carefully monitored in a timely manner.

Claims

1. A self-expanding blood flow modulator that is placed intraluminally in the vessel containing the aneurysm, configured to regulate the conversion of turbulent blood flow in the vessel to laminar flow, sized in accordance with the vessel to be placed (1) comprising: at least one layer of three-dimensional spiral, porous lattice structure made of shape memory material (2), at least two magnets located at predetermined positions on the layer (2), positioned with opposite poles facing each other and changing the pore size through their movement in such a way that they approach and move away from each other with the help of the force acting on each other.

2. A modulator (1) as recited in claim 1, wherein the modulator is cylindrical in shape.

3. A modulator (1) as recited in claim 1 or 2, wherein the ends of the modulator are curved.

4. A modulator (1) as recited in any one of the preceding claims, wherein it is made of a biocompatible material.

5. A modulator (1) as recited in any one of the preceding claims, wherein it includes multiple layers (2).

6. A modulator (1) as recited in claim 5, wherein the magnets (3) are positioned between the layers (2) and/or on the surfaces of the layers (2).

7. A kit comprising: a modulator (1) as recited in any one of the preceding claims, at least two interconnecting catheters (5), at least one connector (7) inserted between the two catheters (5), at least one distal tip (6) for insertion of the modulator (1), and at least one transmission part (8) controlling the distal tip.

8. A kit as recited in claim 7, wherein the catheters (5) are comprised of 2 lower and 2 upper rows of mesh structure.

9. A kit as recited in claims 7 or 8, wherein the catheters (5) are hydrophilic coated.