WO2020021559A1

WO2020021559A1 - Flow diverter and method of chemically passivating thereof

Info

Publication number: WO2020021559A1
Application number: PCT/IN2018/050573
Authority: WO
Inventors: Deveshkumar Mahendralal KOTHWALA; Rajnikant Gandalal Vyas; Dr. Pramod Kumar MINOCHA
Original assignee: Meril Life Sciences Pvt Ltd
Priority date: 2018-07-23
Filing date: 2018-09-05
Publication date: 2020-01-30
Also published as: WO2020021559A9; EP3826580A1; EP3826580A4

Abstract

A flow diverter and method of chemically passivating thereof. The process includes immersing the flow diverter in a passivating solution at a passivating temperature for passivating time duration. The flow diverter is then rinsed with an alkalizing solution followed by sonicating the rinsed flow diverter in deionized water at sonicating time duration. The aforesaid steps are repeated till color of the sonicated flow diverter changes. Further, the sonicated flow diverter is soaked in a soaking solution and then the soaked flow diverter is rinsed in a rinsing solution. The present invention also discloses a method for manufacturing the flow diverter which includes braiding, annealing, quenching and chemically passivating the flow diverter. The flow diverter is deployed with the help of a delivery system.

Description

FLOW DIVERTER AND METHOD OF CHEMICALLY PASSIVATING THEREOF

FIELD OF INVENTION

The present invention relates to a process for passivating a medical device. More specifically, the present invention relates to chemically passivating a flow diverter.

BACKGROUND

[001] Intracranial aneurysm refers to a bulge or ballooning in a blood vessel in the brain. Intracranial aneurysm can leak or rupture causing bleeding inside the brain. Intracranial aneurysm occurs in the neurovasculature and is developed at vessel branch points. Aneurysms of anterior neurovasculature can include ICA (Internal Carotid Artery) aneurysms, superior hypophysial artery aneurysms, ophthalmic artery aneurysms, anterior choroidal aneurysms, etc. Aneurysms of posterior neurovasculature can include anterior inferior cerebellar artery (AICA) aneurysms, posterior inferior cerebellar artery (PICA) aneurysms, superior cerebellar artery (SCA) aneurysms, etc.

[002] There are several known methods for the treatment of aneurysms for example, surgical clipping across the artery which feeds the aneurysm, coiling method, flow diversion, etc. The method of flow diversion is safe as compared to other techniques as it does not involve placement of an implant within the aneurysm sac and the method avoids risk associated with coil bulging out of the parent artery. Therefore, this method reduces rupturing of the aneurysm during surgery.

[003] The conventional flow diverters are manufactured using a series of processes for example, laser cutting/braiding, heat setting, quenching, etc. Generally, the heat-setting and quenching processes involved in the manufacturing of metal based flow diverters causes oxidation of the flow diverters to form a small "non-protective" surface oxide layer. The said layer when not removed leads to corrosion of the surface of the metal flow diverter when it comes in contact with body fluids after implantation in the body lumen. In order to overcome the same, chemical passivation of a flow diverter post heat setting and quenching process is suggested. However, the conventional processes of chemical passivation have certain drawbacks.

[004] The conventional processes of chemical passivation are time consuming and involve long exposures of the flow diverter to chemical solutions leading to leaching of important elements, thus resulting in brittleness of ultrathin nitinol wire. SUMMARY

[005] A flow diverter and method of chemically passivating thereof. The process includes immersing the flow diverter in a passivating solution at a passivating temperature for passivating time duration. The flow diverter is then rinsed with an alkalizing solution followed by sonicating the rinsed flow diverter in deionized water at sonicating time duration. The aforesaid steps are repeated till color of the sonicated flow diverter changes. Further, the sonicated flow diverter is soaked in a soaking solution and then the soaked flow diverter is rinsed in a rinsing solution. The present invention also discloses a method for manufacturing the flow diverter. The method includes braiding monofilaments and/or multifilaments in a braiding pattern to form a flow diverter of a radial strength, annealing the flow diverter, quenching the flow diverter at a quenching temperature for quenching time duration and chemically passivating the flow diverter.

BRIEF DESCRIPTION OF THE DRAWINGS

[006] The summary above, as well as the following detailed description of illustrative embodiments, is better understood when read in conjunction with the appended drawings. For the purpose of illustrating the present disclosure, exemplary constructions of the disclosure are shown in the drawings. However, the disclosure is not limited to specific methods and instrumentalities disclosed herein. Moreover, those in the art will understand that the drawings are not to scale. [007] FIG.l depicts a schematic view of the flow diverter in accordance with an embodiment of the present invention.

[008] FIG. la depicts a schematic view of one over one braiding pattern in accordance with an embodiment of the present invention.

[009] FIG. lb depicts a schematic view of two over two braiding pattern in accordance with an embodiment of the present invention.

[0010] FIG.lc depicts a schematic view of one over two braiding pattern design in accordance with an embodiment of the present invention.

[0011] FiG.2 illustrates a flow chart depicting the process of manufacturing of the flow diverter in accordance with an embodiment of the present invention. [0012] FIG.3 depicts a flow chart of chemical passivation procedure of the flow diverter in accordance with an embodiment of the present invention.

[0013] FIG.3a depicts a schematic view of chemical passivation set-up for a flow diverter in accordance with an embodiment of the present invention.

[0014] FIG.4 depicts a schematic view of the delivery system of the flow diverter in accordance with an embodiment of the present invention.

DETAILED DESCRIPTION OF THE DRAWINGS

[0015] Prior to describing the invention in detail, definitions of certain words or phrases used throughout this patent document will be defined: the terms "include" and "comprise", as well as derivatives thereof, mean inclusion without limitation; the term "or" is inclusive, meaning and/or; the phrases "coupled with" and "associated therewith", as well as derivatives thereof, may mean to include, be included within, interconnect with, contain, be contained within, connect to or with, couple to or with, be communicable with, cooperate with, interleave, juxtapose, be proximate to, be bound to or with, have a property of, or the like; Definitions of certain words and phrases are provided throughout this patent document, and those of ordinary skill in the art will understand that such definitions apply in many, if not most, instances to prior as well as future uses of such defined words and phrases.

[0016] Particular embodiments of the present disclosure are described herein below with reference to the accompanying drawings, however, it is to be understood that the disclosed embodiments are merely examples of the disclosure, which may be embodied in various forms. Well-known functions or constructions are not described in detail to avoid obscuring the present disclosure in unnecessary detail. Therefore, specific structural and functional details disclosed herein are not to be interpreted as limiting, but merely as a basis for the claims and as a representative basis for teaching one skilled in the art to variously employ the present disclosure in virtually any appropriately detailed structure.

[0017] It must be noted that "surface of the flow diverter" in the following description corresponds to inner and outer surfaces of the flow diverter.

[0018] In accordance with the present disclosure, the process for chemical passivation of a flow diverter is disclosed. The flow diverter of the present invention overcomes the disadvantages of the conventional systems. The chemical passivation of flow diverter involves treatment of the flow diverter with a passivating solution for example, 35 % nitric acid (v/v). In order to enhance the efficiency of chemical passivation, the flow diverter is treated with a neutralizing agent such as 0.1N sodium bicarbonate to remove excess passivating solution remaining on an inner and/or outer surface of the flow diverter. Further, the flow diverter is then sonicated in de ionized water to remove oxide layers present on the surface of the flow diverter which may be formed during treatment of the flow diverter with the passivating solution (or weak oxide layer).

[0019] The present invention also relates to the process of manufacturing the flow diverter. The process of manufacturing includes, without limitation, braiding of the flow diverter, heat treatment of the flow diverter and chemical passivation of the flow diverter (as mentioned aforesaid), etc. The flow diverter manufactured using said processes is then loaded onto a delivery system.

[0020] The flow diverter of the present invention has uniform wire thickness and braiding angle which provides the flow diverter excellent radial stiffness and crush resistance properties. The flow diverter of the present invention can be used for a number of applications which include without limitation, intracranial, peripheral, carotid, pulmonary, biliary, esophageal, or tapered blood vessels. In an embodiment, the flow diverter is used for the treatment of intracranial aneurysm.

[0021] The flow diverter of the present invention is a braided tube with high strength, high elasticity, high flexibility and reduced pore size. The flow diverter may be braided with one by two braiding pattern which leads to minimal deformation and high recovery during deployment procedure. The reduced pore size of the flow diverter redirects the blood flow in order to restrict the flow of blood inside an aneurysm sac. The reduced pore size of the flow diverter results in greater metal surface area. The reduced pore size also helps in better flow diversion resulting in early formation of an endothelial layer over the metal surface which in turn, enhances the endothelialization process. The flow diverter of the present invention illustrates super elastic behavior.

[0022] FIG. 1 depicts a schematic view of the flow diverter of the present invention. The shape of the flow diverter 100 may be without limitation circular, cylindrical or any shape known in the art. In an embodiment, the flow diverter 100 is cylindrical in shape. As represented, the flow diverter 100 may have without limitation an outer surface 1, an inner surface (not shown), a distal end 3 and a proximal end 5. [0023] In an embodiment, the flow diverter 100 is fabricated by braiding of one or more ultrathin monofilaments and/or multifilaments (or wires) in a predefined braiding pattern. The multi/monofilaments may be made of, without limitation, a radiopaque (radiopaque wires) and a non-radiopaque material. The radiopaque materials may include without limitation nitinol- platinum, nitinol-platinum alloys, nitinol-titanium alloys, nitinol-tungsten, platinum, platinum tungsten, platinum iridium, stainless steel or combinations thereof. In an embodiment, the radiopaque material is a nitinol-platinum core wire. The nitinol-platinum core wire is used to provide better radiopacity to the flow diverter 100. The nitinol-platinum core wire also enhances elasticity of the flow diverter 100, flexibility of the flow diverter 100 and provides strength to the configuration of the flow diverter 100.

[0024] The nitinol-platinum core wire imparts strength to the flow diverter 100. The nitinol- platinum core wire helps in locating the position of the flow diverter 100 after the implantation of the flow diverter 100 due to its radiopaque property.

[0025] In another embodiment, the platinum-tungsten wire is used for radiopacity to the flow diverter 100. The platinum-tungsten wire uses in the ratio of 92% platinum and 8% tungsten. The platinum-tungsten material is used in such application due to its relatively high degree biocompatibility.

[0026] The diameter of the radiopaque wires may be in the range of 20-50 micron, more preferably 30-40 micron.

[0027] The non-radiopaque materials may include without limitation nitinol, stainless steel, cobalt chromium, cobalt-chromium-tungsten-nickel alloy. In an embodiment, the non radiopaque material is a nitinol straight annealed wire. In an embodiment, nitinol is selected for the fabrication of the flow diverter 100 as it shows shape memory effect, super elastic behavior, high tensile strength, good corrosion resistance and biocompatibility.

[0028] In an embodiment, the number of radiopaque wires used for the formation of the flow diverter 100 is four and the number of non-radiopaque wires used for the formation of the flow diverter 100 is forty four. The flow diverter 100 is formed in such a way that one radiopaque wire is present in between each set of eleven non-radiopaque wires.

[0029] In another embodiment, the number of radiopaque wires used for the formation of the flow diverter 100 is twelve and the number of non-radiopaque wires used for the formation of the flow diverter 100 is thirty six. The flow diverter 100 is formed in such a way that one radiopaque wire is present in between each set of three non-radiopaque wires.

[0030] In another embodiment, the flow diverter 100 is fabricated from forty eight wires which comprises of forty six non-radiopaque nitinol wires and two radiopaque nitinol-platinum core wires.

[0031] In another embodiment, the flow diverter 100 is fabricated from forty eight wires which comprises of forty two non-radiopaque nitinol wires with six radiopaque nitinol-platinum core wires.

[0032] In another embodiment, the flow diverter 100 is fabricated from forty eight wires which comprises of forty non-radiopaque nitinol wires with eight radiopaque nitinol-platinum core wires.

[0033] In another embodiment, the flow diverter 100 is fabricated from forty eight wires which comprises of thirty eight non-radiopaque nitinol wires with ten radiopaque nitinol-platinum core wires.

[0034] Also, in another embodiment the flow diverter 100 is fabricated only from the radiopaque nitinol-platinum core wire material.

[0035] The braided configuration helps to reroute the blood flow by reducing pore size that restricts penetration of blood inside the aneurysm sac. The braided configuration may have various porosities which are dependent on braiding angle set during braiding process to manufacture the flow diverter 100. In an embodiment, the braiding angle is inversely proportional to the pore size of the flow diverter 100 i.e. as the braiding angles decreases, the pore size of the flow diverter 100 increases which further reduces radial stiffness, integrity and mechanical properties of flow diverter 100. The pore size and the radial stiffness are important parameters which affect the ability of the flow diverter 100 to maintain its integrity and structure after placement of the flow diverter 100 into the body lumen.

[0036] In an embodiment, the flow diverter 100 is formed using one over one braiding pattern (shown in Fig. la). The one over one braiding pattern is able to resist distortion to wire spacing. The flow diverter 100 formed using the one over one braiding pattern has a stiffer sidewall.

[0037] In another embodiment, the flow diverter 100 is formed using two over two braiding pattern (shown in Fig. lb). The two over two braiding pattern is also referred to as the diamond pattern. The two over two braiding pattern is the most flexible braiding pattern in bending the stiffness of the flow diverter 100.

[00B8] In yet another embodiment, the flow diverter 100 is formed using one over two braiding pattern (shown in Fig. lc). The one over two braiding pattern is used in the formation of the flow diverter 100 to obtain reduced pore size and high flexibility. The one over two braiding pattern also helps in achieving higher pick counts and small pore sizes. The flow diverter 100 formed using the one over two braiding pattern is less likely to kink when bent around tight radii and provides higher tensile strength or bulb burst strength. The flow diverter 100 formed using one over two braiding pattern has an average pore size in the range of 0.02 to 0.04 mm². [0039] In an embodiment, the flow diverter 100 formed using the one over two braiding pattern has braiding angle in the range of 120°-160°, more specifically 125°-155°. The change in the braiding angle can change the axial density of the braid.

[0040] The selection of the braiding angle may also influence the mechanical properties of the flow diverter 100, more specifically, radial strength and crush recovery of the flow diverter 100. The radial strength of the flow diverter 100 defines the strength of the flow diverter 100 to withstand the arterial wall pressure in order to prevent the relocation/migration of the flow diverter 100 from its deployed position. In an embodiment, the radial strength of the flow diverter 100 is approximately in the range of 10-60 N. The crush recovery of the flow diverter 100 defines the self-expanding property of the flow diverter 100. In an embodiment, the flow diverter 100 may have a percentage crush recovery of greater than 95%.

[0041] For example, in a 3.25 mm flow diverter implant having braiding angles between 120° and 160° and made as per braiding process parameters defined above, resulted in radial strength of 10-60 N of the flow diverter implant.

[0042] An exemplary table depicting results of radial strength value obtained relative to the braiding angle of flow diverter braided mesh are shown below:

135-160 10-60

[0043] Fig. 2 illustrates a flow chart depicting the manufacturing process of the flow diverter 100. The manufacturing process of the flow diverter 100 commences at step 201.

[0044] At step 201, the braiding process of the flow diverter 100 takes place. The braiding process is performed at predefined braiding parameters. The braiding patterns used in the formation of the flow diverter 100 are generated with the help of a braiding machine. The braiding machine may include without limitation a spindle, a mandrel and a winding machine. The spindle is designed to roll the wires (radiopaque and non-radiopaque) in a way that extra pressure is reduced on the wires and breakage of the wires is avoided during the braiding process. The wires wind up around the spindle with the help of the winding machine. The mandrel is used to hold the braided structure during the braiding process. The braided structure of the flow diverter 100 is formed over the mandrel to create a hollow lumen with a specific cross-sectional shape and size. The braiding patterns are illustrated in FIGs. la, lb and lc.

[0045] At step 203, the heat setting/annealing process is carried out after the braiding of the flow diverter 100. The flow diverter 100 placed over the mandrel of the braiding machine (step 201) is exposed to an annealing environment. The flow diverter 100 is annealed for an annealing temperature and for annealing time duration. In an embodiment, the exposing of the flow diverter 100 to the annealing environment refers to placing the flow diverter 100 inside a fluidized sand bath for 1-20 minutes, (more preferably 5-10 minutes) at 450-550°C (more preferably 500-510°C). The flow diverter 100 gains the shape retention properties during the heat setting/annealing process.

[0046] At step 205, the process of quenching takes place. After the heat setting/annealing step, the material is immediately quenched in water for a quenching time duration of about 1-20 minutes, more preferably 5-10 minutes. In an embodiment, the quenching process takes place at a quenching temperature of approximately 20°C. The process of quenching is carried out to induce relaxation of the material (radiopaque and non-radiopaque wires) for achieving the desired stable shape of the flow diverter 100. Further, the moderate temperatures and the short time durations are used to prevent the permanent deformation of flow diverter 100 and to maintain the super elastic behavior of the flow diverter 100. [0047] Post steps 203 & 205, the nitinol braided flow diverter 100 gains its shape retention properties. However, as a result of oxidized fluidization environment during steps 203 & 205, a non-protective layer of free ions and oxides of nickel and titanium (also referred as non- protective oxide layer) is generated on the surface (outer surface 1 & inner surface) of the flow diverter 100. The said layer leads to corrosion of the metal when the flow diverter 100 comes in contact with body fluids after implantation in the body lumen.

[0048] At step 207, the flow diverter 100 undergoes the chemical passivation process (explained in Fig. 3) to remove the non-protective oxide layer from the surface (outer surface 1 & inner surface) of the flow diverter 100.

[0049] Optionally/additionally at step 209, the flow diverter 100 is coated with an antithrombogenic, anti-inflammatory and/or any hormonal coating. In an embodiment, the flow diverter 100 is coated with an antithrombogenic coating. The coating is done to reduce the formation of thrombus on the outer surface 1 of the flow diverter 100. The antithrombogenic materials used for coating the flow diverter 100 may include without limitation phosphorylcholine, polyethylene oxide, hyaluronic acid, heparin, plasminogen activating factors such as streptokinase and urokinase, hydrophobic materials, etc.

[0050] In another embodiment, the flow diverter 100 is coated with a hormonal coating. The hormonal coating involves the use of specific growth hormones that enhances the endothelial layer formation and has a rapid healing process for intracranial aneurysm. The hormonal coating has the ability of cell growing and increasing myofibroblast separations enhancing wound healing of the endothelial layer of the blood vessel and helps in minimizing the inner arterial wall damage after the deployment of the flow diverter 100. The hormonal coating can also incorporate specific hormones like some cytokines that attracts the monocytes and lymphocytes from blood to the outer surface 1 of the flow diverter 100 that leads to vessel reconstruction aids in endothelial layer formation over aneurysm neck.

[0051] The coating process may be performed by various methods known in the art for example, spray coating, dipping technique etc. In an embodiment the thickness of the coating layer may be less than 5 micron, more preferably in the range of 0.1-3 micron.

[0052] FIG. 3 depicts a flow chart for chemical passivation procedure of the flow diverter 100. The process of chemical passivation is performed after the flow diverter 100 undergoes the process of heat setting/annealing. The process of chemical passivation commences at step 301. At step 301, preparation of passivating solution takes place. The passivating solution is prepared by diluting one or more passivating solvents in water.

[0053] During the chemical passivation process, the passivating solvents react with oxides of metals present on the non-protective oxide layer. The reaction of the passivating solvents with oxides of metals causes dissolution of free ions present on the surface 1 of the flow diverter 100 and underneath of the flow diverter 100. The passivating solvents penetrate in the radial space between the non-protective oxide layer and the surface of the flow diverter 100 which produces a pressure between the radial space created. This leads to separation of dissolved ions and metal oxides from the surface (outer surface 1 & inner surface) of the flow diverter 100. Post separation of the metal oxides, the passivating solvents form a protective oxide layer that prevents further formation of the non-protective oxide layer on the surface (outer surface 1 & inner surface) of the flow diverter 100. This results in prevention of the nitinol material from corrosion when it comes in contact with body fluid.

[0054] The passivating solvents may include without limitation, nitric acid, citric acid, etc. The aforementioned passivating solvents act as strong oxidizing agents. In an embodiment, nitric acid is used as the passivating solvent to carry out the process of chemical passivation. The passivating solution is prepared by mixing nitric acid in water. The concentration of the passivating solution may range from 10-50% (v/v). In an embodiment, the concentration of the passivating solution is 35% (v/v).

[0055] At step 303, the flow diverter 100 is treated with the passivating solution prepared at step 301. The flow diverter 100 is immersed in a beaker which contains the passivating solution of nitric acid and water. The beaker is placed on a magnetic stirrer (as shown in Fig. 3a). The magnetic stirrer may stir the passivating solution containing the flow diverter 100 at a speed ranging from 200-500 RPM, more preferably 350-400 RPM. In an embodiment, the stirring speed of the magnetic stirrer is 360 RPM. The passivating temperature of the passivating solution may range from 20-60°C, more preferably 40-45°C. In an embodiment, the passivating temperature of the passivating solution is 43 ± 3°C. The passivation is process may be carried out for a passivating time duration of 10-60 minutes, more preferably 20-40 minutes. In an embodiment, the process of passivation is carried out for 30 minutes.

[0056] The chemical passivation process is performed to remove the non-protective oxide layer which is formed on the surface (outer surface 1 & inner surface) of the flow diverter 100 during the heat setting/annealing process and/or quenching process. The non-protective oxide layer includes formation of oxides of iron, nickel and titanium on the surface of the flow diverter 100. The non-protective oxide layer corrodes the flow diverter 100 when the flow diverter 100 comes in contact with the body fluids after implantation which also leads to the formation of hazards inside the human body.

[0057] At step 305, rinsing of the flow diverter 100 takes place. After the flow diverter 100 is exposed in the passivating solution, the flow diverter 100 is rinsed with an alkalizing solution. For example, the alkalizing solution is a saturated solution of 0.1N (Normality: 0.1) sodium bicarbonate (no more solute can be added). The sodium bicarbonate solution neutralizes excess of nitric acid present on the surface of the flow diverter 100. The sodium bicarbonate solution prevents the unnecessary hazards that may be caused by the nitric acid solution.

[0058] At step 307, the sonication of the flow diverter 100 takes place. In an embodiment, the process of sonication is carried out in deionized water. The process of sonication may be carried out for sonicating time duration of 20-30 minutes. In an embodiment, the process of sonication is carried out for 20 minutes. The process of sonication is performed to remove a weak layer of metal oxide formed during the passivation process on the surface (outer surface 1 & inner surface) of the flow diverter 100. The weak layer of metal oxide acts as a barrier for further reaction of passivating solvent with free metals and it leads to saturation of electrochemical reaction during the passivation process. During the sonication process, ultrasonic vibrations are produced which causes the separation and removal of impurities and contaminants which are adhered on the flow diverter 100.

[0059] The aforesaid steps 301-307 relate to one chemical passivation cycle. Each chemical passivation cycle is repeated till the time the non-protective oxide layer is completely removed from the surface (outer surface 1 & inner surface) of the flow diverter 100. In an embodiment, the chemical passivation is performed for about 5-10 cycles. During each chemical passivation cycle, the flow diverter 100 is observed for the visualization and verification of any damage on the surface (outer surface 1 & inner surface) of the flow diverter 100 and for the presence of the non-protective oxide layer on the surface (outer surface 1 & inner surface) of the flow diverter 100. If any sign of the non-protective oxide layer is observed the flow diverter 100 again undergoes the process of chemical passivation. In an embodiment, the change in colour of the flow diverter 100 is observed after each passivation cycle. The shorter passivating time and regular intervals of sonication between the passivation cycles may lead to reduction in the saturation of chemical reaction by the passivating solvent and it results in uniform passivation of metal stent with reduction in time for passivation process.

[0060] The change in the colour of the flow diverter 100 indicates the removal of the non- protective oxide layer. In an embodiment, the flow diverter 100 undergoes chemical passivation till the color of the flow diverter 100 changes from violet blue to polished white.

[0061] At step 309, the flow diverter 100 is soaked in a soaking solution. In an embodiment, the soaking solution is a 30-35% (v/v) solution of nitric acid. The soaking step is performed for a short duration of time, say, 30-35 minutes in the soaking solution. Soaking the flow diverter 100 in nitric acid solution assures that the protective oxide layer fully covers the flow diverter 100. The use of nitric acid solution also helps in reducing surface damage of the flow diverter 100 after the non-protective oxide layer is removed from the surface (outer surface 1 & inner surface) of the flow diverter 100.

[0062] At step 311, the flow diverter 100 may be rinsed with a rinsing solution for a rinsing time. In an embodiment, the rinsing solution is deionized water. The flow diverter is rinsed for 2 minutes to 5 minutes. The rinsing step helps in removing traces of nitric acid solution present on the surface (outer surface 1 and inner surface) of the flow diverter 100 thereby preventing unnecessary hazards that may be caused by the nitric acid solution.

[0063] Fig. 4 depicts the schematic view of the delivery system 400 of the of the flow diverter 100. As represented, the delivery system 400 of the flow diverter 100 includes without limitation an introducer sheath 401, a delivery wire 403, a resheathing pad 405, a one or more markers 407 and a microcatheter 409.

[0064] The introducer sheath 401 places the flow diverter 100 inside the hollow lumen of the microcatheter 409. The introducer sheath 401 may or may not have, without limitation, a dual layer configuration. In an embodiment, the introducer sheath 401 is a transparent tube comprising of an inner layer and an outer layer.

[0065] The introducer sheath 401 may be made of without limitation a polymeric material. The polymeric material may include, without limitation polytetrafluoroethylene (PTFE), polyimide or the mixture of PTFE-polyimide, polyamide or the mixture of nylon-polyamide and nylon. In an embodiment, the inner layer of the introducer sheath 401 is composed of polyimide-PTFE blend or polytetrafluoroethylene (PTFE). The outer layer of the introducer sheath 401 is composed of polyimide and nylon material. The polyimide used for the formation of the outer layer of the introducer sheath 401 provides strength and integrity to the introducer sheath 401. The polyimide used also helps to prevent the deformation and kinking of the introducer sheath 401 during the deployment process. The transparency of the introducer sheath 401 helps to inspect the location of the flow diverter 100 and the configuration of the flow diverter 100 within the introducer sheath 401. The transparency of the introducer sheath 401 also helps to confirm the advancement of the flow diverter 100 within the proximal end of the microcatheter 409.

[0066] In an embodiment, the lumen diameter of the introducer sheath 401 may be in the range of 0.40-0.70mm, more preferably 0.55-0.65mm. The introducer sheath 401 may have a wall thickness in the range of 0.20-0.35mm, more preferably 0.25-0.30mm. The introducer sheath 401 may have a length in the range of 50-100cm, more preferably 60-80cm. The outer diameter of the introducer sheath is lesser than the inner diameter of microcatheter for ease in access through the microcatheter during deployment of flow diverter implant.

[0067] The delivery wire 403 may include without limitation, a distal end (not shown), a proximal end (not shown) and a coil 403a. The delivery wire 403 is placed inside the hollow lumen of the introducer sheath 401. The delivery wire 403 is coupled to the resheathing pad 405 and the one or more markers 407 (distal marker, resheathing marker, proximal marker). The flow diverter 100 is placed over the delivery wire 403. The delivery wire 403 carries the flow diverter 100 which is placed inside the introducer sheath 401 and other components of the delivery system 400 to the hollow lumen of the microcatheter 409. In an embodiment, the delivery wire 403 is of tapered configuration.

[0068] The delivery wire 403 may be made of without limitation, nitinol or platinum-tungsten or stainless steel material. In an embodiment, the delivery wire 403 is made of 304V stainless steel material.

[0069] In an embodiment, the delivery wire 403 includes two visual markers at proximal end (not shown) of delivery wire 403. The visual markers guide to deliver the flow diverter 100 which is placed inside the introducer sheath 401 and other components of the delivery system 400 to the hollow lumen of the microcatheter 409. The length of the microcatheter 409 decides the position of the visual markers on proximal end of the delivery wire 403. Out of the two markers, a first visual marker is emplacing at 330-370mm distance from the proximal end of delivery wire. The second visual marker is emplacing at 530-570mm distance from the proximal end of the delivery wire 403. [0070] In an embodiment, the first visual marker reaches at the microcatheter hub indicates that coil tip of the delivery wire 403 has reached at the microcatheter tip end. The second visual marker reaches at microcatheter hub indicates the flow diverter 100 is completely deployed from the microcatheter 409.

[0071] In an embodiment, the delivery wire 403 has a tapered configuration. The tapered configuration of the delivery wire 403 along with the PTFE coating over the delivery wire 403 enhances the lubricity and makes the delivery wire 403 more flexible for easy movement during deployment through tortuous vasculature.

[0072] The delivery wire 403 may include without limitation, a coil 403a. In an embodiment, the delivery wire 403 has a J-tip coil. The J-tip coil is coupled at the distal end of the delivery wire 403. The J-tip coil is made of without limitation, platinum-tungsten material. In an embodiment, the outer diameter of the J-tip coil may range from 0.30-0.40mm, more preferably 0.34- 0.38mm. The length of the J-tip coil may range from 10-20mm. The J-tip coil has a bending configuration that helps to prevent the damage of the vessel wall by the tip of the delivery wire 403 during deployment of the flow diverter 100 in tortuous vasculature.

[0073] The resheathing pad 405 may include without limitation, a proximal and a distal end (not shown). The resheathing pad 405 is coupled to the delivery wire 403. The length of the resheathing pad 405 may range from about l-5mm, more preferably 2-4mm.

[0074] In an embodiment, the resheathing pad 405 is a tube that includes an outer layer and an inner layer (not shown). The outer layer may be made of without limitation silicone, rubber, thermoplastic polyurethane, poly-ether block amide or pebax. In an embodiment, the outer layer is made of silicone or pebax material. The silicone material maintains strong longitudinal grip with the inner layer of the flow diverter 100 that helps in ease of multiple resheathing of the flow diverter 100 during the deployment procedure. The diameter of the outer layer may range from 0.30-0.60 mm and the thickness of the outer layer may range from 0.050 to 0.105mm, more preferably from 0.070 to 0.100mm.

[0075] The inner layer may be made of without limitation, polyimide tube, nylon, pebax, polyamide. In an embodiment, the inner layer is made of nylon or pebax material. The nylon or pebax material provides support and rigidity to the inner layer of the flow diverter 100 which helps to avoid the deformation of the resheathing pad 405 during movement through the tortuous vasculature. The diameter of the inner layer may range from 0.20-0.30 mm, more preferably about less than or equal to 0.27 mm and the thickness of the inner layer may range from 0.020-0.050mm, more preferably 0.035-0.045mm. As the inner diameter of the resheathing pad 405 changes, the thickness of the outer layer is changed.

[0076] In another embodiment, resheathing pad 405 is a circular wire coil. The coil may be made of without limitation of nitinol, platinum, nitinol-platinum core wire and platinum tungsten wire. The diameter of coil may range from 0.30-0.60 mm.

[0077] The one or more markers may include without limitation, a distal marker, resheathing marker and a proximal marker. The one or more markers may be placed without limitation along the proximal and distal ends of the resheathing pad. The one or more markers may be made of without limitation, stainless steel, platinum-iridium, platinum tungsten material, more preferably from platinum iridium material. In an embodiment, the one or more markers are made of platinum-iridium material. The iridium material in combination with platinum material provides strength to the one or more markers and also aids in radiopacity of the one or more markers under a fluoroscopic examination.

[0078] In an embodiment, the proximal marker is present at the proximal end of the resheathing pad. The proximal marker has an outer diameter in the range of 0.50-0.60mm, more preferably 0.54-0.58mm and inner diameter ranging from 0.18-0.23mm. The tapered diameter of the proximal marker may range from 0.35-0.40mm. The proximal marker acts as a pusher by pushing forward the flow diverter 100 towards a distal end of the microcatheter during deployment process into the body lumen.

[0079] The diameter of the flow diverter 100 decides its in-sheath loaded length and the flow diverter 100 ultimately affects the position of the proximal marker. The change in position of the proximal marker largely affects its internal diameter because of the tapered delivery configuration of the delivery wire that leads to a change in the internal diameter of the proximal marker.

[0080] In an embodiment, the resheathing marker is present at the distal end of resheathing pad. The resheathing marker has an outer diameter in the range of 0.40-0.50mm, more preferably 0.44-0.48mm and inner diameter ranging from 0.15-0.23mm. The tapered diameter of the proximal marker may range from 0.28-0.35mm. The resheathing marker acts as an indicator to repositioning the flow diverter 100 towards a proximal end of the microcatheter during deployment process into the body lumen. [0081] In an embodiment, the distal marker is present at junction of the delivery wire and J-tip coil. The distal marker has an outer diameter in the range of 0.40-0.50mm, more preferably in between 0.45-0.50mm and inner diameter in the range of 0.05-0.15mm, more preferably 0.08- 0.12mm. The distal marker helps to position the flow diverter 100 during the deployment process at the aneurysm neck.

[0082] The microcatheter 409 is used to deliver the flow diverter 100 in an intracranial vessel. The delivery system 400 of the flow diverter 100 may be compatible with a 2.4-2.7F microcatheter with a length of 100-150cm. In an embodiment, the delivery system 400 of the flow diverter 100 is compatible with the microcatheter 409 which contains a guide wire having 0.014"-0.027" size and length of 190-195cm.

[0083] The flow diverter 100 may be loaded inside the lumen of the introducer sheath 401 using a small diameter 5/0 polyester monofilament. The monofilament used may have two ends: a first end and a second end. The loading procedure of the flow diverter 100 is initiated with the alignment of the flow diverter 100 over the distal section of the delivery wire 403 between the proximal marker and the distal marker. After the alignment, the two ends of the monofilament are folded close to each other to form a small diameter loop which is positioned over the proximal end of flow diverter 100 that is to be placed inside the introducer sheath 401.

[0084] After the flow diverter 100 is loaded inside the introducer sheath 401, the whole delivery system 400 is primary packaged into tyvek pouch. The delivery system 400 is then sterilized under ethylene oxide gas followed by storage of the flow diverter 100 under specified storage condition. The procedure for loading the flow diverter 100 using threading mechanism is advantageous in terms of ease in operation and also it helps in loading of the flow diverter 100 without any damage to its surface and configuration. This process also helps in loading of the flow diverter 100 in a shorter period of time that leads to reduction in time required for the loading process.

[0085] The scope of the invention is only limited by the appended patent claims. More generally, those skilled in the art will readily appreciate that all parameters, dimensions, materials, and configurations described herein are meant to be exemplary and that the actual parameters, dimensions, materials, and/or configurations will depend upon the specific application or applications for which the teachings of the present invention is/are used.

Claims

We Claim:

I. A process to chemically passivate a flow diverter, the process comprising: a. immersing a flow diverter in a passivating solution at a passivating temperature for a passivating time duration; b. rinsing the immersed flow diverter with an alkalizing solution; c. sonicating the rinsed flow diverter in deionized water at a sonicating time duration; d. repeating the steps a-c till color of the sonicated flow diverter changes; e. soaking the sonicated flow diverter in a soaking solution; and f. rinsing the soaked flow diverter in a rinsing solution. 2. The process as claimed in claim 1 wherein the rinsing includes rinsing the flow diverter with purified water followed by rinsing with the alkalizing solution.

3. The process as claimed in claim 1 wherein the immersing the flow diverter includes stirring the flow diverter at a speed of 200-500 RPM.

4. The process as claimed in claim 1 wherein the passivating solution includes a solution of nitric acid having a concentration of 10-50% v/v.

5. The process as claimed in claim 1 wherein the alkalizing solution includes a saturated solution of sodium bicarbonate having a normality of 0.1N.

6. The process as claimed in claim 1 wherein the passivating temperature is 20-60°C.

7. The process as claimed in claim 1 wherein the passivating time duration is 10-60 minutes. 8. The process as claimed in claim 1 wherein the sonicating time is 20-30 minutes.

9. The process as claimed in claim 1 wherein the soaking solution is nitric acid solution having a concentration of 30-35%.

10. The process as claimed in claim 1 wherein the rinsing solution is deionized water.

II. The process as claimed in claim 1 wherein the rinsing time is 2-5 minutes. 12. A method for manufacturing a flow diverter, the method comprising: a. braiding one or more monofilaments and/or multifilaments in a predefined braiding pattern to form a flow diverter of a predefined radial strength; b. annealing the flow diverter at an annealing temperature for annealing time duration; c. quenching the flow diverter at a quenching temperature for a quenching time duration; and d. chemically passivating the flow diverter in accordance with the process as claimed in claim 1.

IB. The method as claimed in claim 12, wherein the predefined braiding pattern includes one over one braiding pattern, a two over two braiding pattern and a one over two braiding pattern.

14. The method as claimed in claim 13, wherein the braiding includes braiding at a braiding angle of 120°-160° for one over two braiding pattern.

15. The method as claimed in claim 12, wherein the annealing temperature is 450-550°C.

16. The method as claimed in claim 12, wherein the annealing time duration is 1-20 minutes.

17. The method as claimed in claim 12, wherein the quenching includes quenching the flow diverter in water. 18. The method as claimed in claim 12, wherein the quenching temperature is approximately

20° C.

19. The method as claimed in claim 12, wherein the quenching time duration is 1-20 minutes.

20. The method as claimed in claim 12, wherein the chemically passivating the flow diverter is followed by coating the flow diverter with one of an antithrombogenic, anti-inflammatory and hormonal coating.

21. A flow diverter for the treatment of aneurysm, the flow diverter being made using a process as claimed in claim 12.

22. The flow diverter as claimed in claim 21, wherein the flow diverter is made by braiding one of one or more radiopaque monofilaments/multifilaments and one or more non-radiopaque monofilaments/multifilaments.

23. The flow diverter as claimed in claim 21, wherein the radiopaque monofilaments/multifilaments are nitinol-platinum core wires.

24. The flow diverter as claimed in claim 21, wherein the non-radiopaque monofilaments/multifilaments are nitinol straight annealed wires.

25. The flow diverter as claimed in claim 21, wherein the flow diverter includes a pore size of 0.02-0.04 mm² for a one over two braiding pattern.

26. The flow diverter as claimed in claim 21, wherein the predefined radial strength ranges from 10-60N. 27. The flow diverter as claimed in claim 21, wherein the flow diverter includes a percentage crush recovery greater than 95%.

28. The flow diverter as claimed in claim 21, wherein the flow diverter is deployed with the help of a delivery system, the delivery system comprising;

• a transparent introducer sheath with a hollow lumen, and · a resheathing pad disposed inside the hollow lumen of the transparent introducer sheath, a flow diverter being placed over the resheathing pad.