Claims:WE CLAIM
1. An occluder assembly comprising:
an occluder including
a frame having a plurality of portions, the portions including a proximal end, a middle portion, a distal end, at least two of the plurality of portions includes at least one ring of strand loops each for securing the occluder at a defect site, the distal portion is devoid of any loose strands and includes a compressed portion;
a jacket including a proximal end and a distal end, the distal end being coupled to the proximal end of the frame for accurate deployment of the occluder, the jacket including a conical portion at its proximal end; and
a delivery cable coupled to the conical portion of the jacket, wherein the diameter of the delivery cable is aligned with the diameter of the conical portion.
2. The occluder assembly as claimed in claim 1 wherein the strands loops are made of one of nitinol, cobalt-chromium, or copper-aluminum-nickel.
3. The occluder assembly as claimed in claim 1 wherein the strand loops are of rectangular, conical, or triangular shape.
4. The occluder assembly as claimed in claim 1 wherein the strand loops are inclined with respect to a longitudinal axis of the occluder.
5. The occluder assembly as claimed in claim 4 wherein the strand loops are inclined at an angle of 45° with respect to the longitudinal axis of the occluder.
6. The occluder assembly as claimed in claim 1 wherein the proximal end of the jacket includes a threaded hole for screwing a screw of a delivery cable.
7. The occluder assembly as claimed in claim 1 wherein the distal end includes a cavity for encapsulating a ball shaped structure of strands.
8. A method of manufacturing an occluder, the method comprising:
a. braiding of strands over a dome shaped mandrel to form a frame;
b. annealing the frame at a predefined temperature for a predefined time duration to form a primary annealed frame;
c. shape setting the primary annealed frame at a predefined temperature for a predefined time duration to form a secondary annealed frame;
d. welding loose strands of the secondary annealed frame to form a ball shaped structure at a proximal end of the secondary annealed frame;
e. mounting a jacket over the ball shaped structure at the proximal end of the secondary annealed frame;
f. passivating the secondary annealed frame to form a corrosion resistant frame;
g. coating the corrosion resistant frame to form a coated frame; and
h. packaging the coated frame.
9. The method of manufacturing an occluder as claimed in claim 8 wherein the predefined temperature is 500°C to 600°C.
10. The method of manufacturing an occluder as claimed in claim 8 wherein the predefined time duration is 5 minutes to 20 minutes.
11. The method of manufacturing an occluder as claimed in claim 8 wherein the shape setting includes compression.
12. The method of manufacturing an occluder as claimed in claim 11 wherein the shape setting is performed with the help of mold.
13. The method of manufacturing an occluder as claimed in claim 8 wherein the passivating includes treating the secondary annealed frame with nitric acid solution.
14. The method of manufacturing an occluder as claimed in claim 8 wherein the passivating includes treating the secondary annealed frame with titanium nitride.
15. The method of manufacturing an occluder as claimed in claim 8 wherein the coating includes applying a coating of polyurethane diol solution over the corrosion resistant frame. , Description:FORM 2
THE PATENTS ACT, 1970
(39 of 1970)
&
THE PATENTS RULES, 2003
COMPLETE SPECIFICATION
(Section 10 and Rule 13)

1. TITLE OF THE INVENTION:
OCCLUDER AND METHOD OF MANUFACTURING THEREOF

2. APPLICANTS:
Meril Life Sciences Pvt. Ltd., an Indian Company of the address, Survey No. 135/139 Bilakhia House, Muktanand Marg, Chala, Vapi-Gujarat 396191, India

3. The following specification particularly describes the invention and the manner in which it is to be performed:

FIELD OF INVENTION
[1] The present invention relates to an occluder, more specifically the present invention relates to the LAA occluder and a method of manufacturing thereof.

BACKGROUND
[2] Heart-related diseases have become very common nowadays. The heart diseases can be caused due to various reasons, for example, dilated cardiomyopathy, congestive heart failure, congenital, heart blockages, etc. The problem of heart blockages is most common amongst all heart related diseases. The heart blockages may eventually lead to a heart stroke. The heart blockages can be caused due to various reasons for example atherosclerosis, the formation of blot clot due to atrial fibrillation, etc.
[3] When a patient suffers from atrial fibrillation, the electrical impulses that control the heartbeat do not travel in an orderly fashion through the heart. The uncontrolled electrical impulses will lead to generating many pulses at the same time and spread through the atria. The fast and chaotic impulses do not give the atria time to contract and/or effectively squeeze the blood into the ventricles. Due to inefficient contraction and/or squeezing of the atria, blood may collect in the left atrial appendage (LAA) and may form a clot in the LAA. When the blood clots are pumped out of the heart, they can cause the heart stroke.
[4] Approximately, 90% of the stroke-causing clots are formed at left atrial appendage (LAA). To mitigate the aforesaid condition, an opening in the LAA may be closed with the help of a prosthetic occluder. The occluder may be placed inside the opening/left atrial wall to occlude and/or seal the hole which may block the entrance of blood into the LAA, hence eliminate the risk of clot formation.
[5] The most common problem of the conventional LAA occluder is it may not get fixed properly to walls around the LAA, and therefore may lead to bouncing back of the occluder. Further, the conventional occluders may have loose strands at an end which may damage a vessel wall. Thus, there exists a need for an improved LAA occluder that overcomes the deficiencies of the conventional occluder.

SUMMARY
The present invention discloses an occluder and a method of manufacturing thereof. The occluder includes a frame having a plurality of portions, the portions including a proximal end, a middle portion, a distal end, at least two of the plurality of portions includes at least one ring of strand loops. The strand loops help in securing the occluder at a defect site. The distal portion is devoid of any loose strands and includes a compressed portion. Further, the occluder includes a jacket having a proximal end and a distal end, the distal end being coupled to the proximal end of the frame for accurate deployment of the occluder, and the proximal end includes a conical portion coupled to a delivery cable. The diameter of the delivery cable is aligned with the diameter of the conical portion.

BRIEF DESCRIPTION OF THE DRAWINGS
[001] 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.
[002] Figure 1 illustrates a lateral view of an occluder in accordance with an embodiment of the present invention.
[003] Figure 2 illustrates a top view of an occluder in accordance with an embodiment of the present invention.
[004] Figure 3 illustrates a cross-sectional lateral view of a jacket in accordance with an embodiment of the present invention.
[005] Figure 4 illustrates a screw attached on a tip of a delivery cable in accordance with an embodiment of the present invention.
[006] Figure 5 illustrates flowchart representing a process of manufacturing the occluder in accordance with an embodiment of the present invention.
[007] Figure 6 illustrates a dome shaped mandrel in accordance with an embodiment of the present invention.
[008] Figure 7 illustrates a braiding machine in accordance with an embodiment of the present invention.
[009] Figure 8a illustrates a dome shaped frame fitted with a mold in accordance with an embodiment of the present invention.
[0010] FIG 8b illustrates a compressed frame in accordance with an embodiment of the present invention.
[0011] FIG 8c illustrates a jacket attached to the frame in accordance with an embodiment of the present invention.
DETAILED DESCRIPTION OF THE DRAWINGS
[0012] 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.
[0013] 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.
[0014] In accordance with the present disclosure, an occluder and its method of manufacturing are disclosed. The occluder may be used to treat all types of left atrial appendage (LAA) defects. In an embodiment, the occluder is used to treat an atrial septal defect in a patient. The occluder of the present invention includes a plurality of strand loops. The strand loops may secure the occluder to a wall of LAA defect more firmly and/or accurately. The strand loops may be formed at one of the ends as well as in the center of the occluder. In another embodiment, the occluder includes at least one jacket at one of the ends of the occluder. The jacket may hold one or more free ends of the occluder at a first end and may be coupled to a delivery cable at a second end at the time of deployment. The jacket of the present invention is conical at the second end and includes a diameter which is aligned with the diameter of the delivery cable. The shape of the jacket helps in the smooth, accurate and hassle-free deployment of the occluder. Further, the jacket allows repeat procedure for better placement of the occluder in case of any complication (or resheathing).
[0015] The method of manufacturing the occluder includes braiding of the monofilament/multifilament strands over a mandrel using a braiding machine. The braiding is performed in such a way that it does not require sealing of a portion of the occluder previously attached to the mandrel at the time of braiding. Hence, the method of the present invention is simple, time efficient and economically better than the conventional methods.
[0016] Now referring specifically to drawings, FIG. 1 represents a lateral view of the occluder 100. The occluder 100 may include a frame 10, a plurality of strand loops and a jacket 20. The occluder 100 may be self-expandable in the radial direction and/or may be delivered via a catheter. The profile of the catheter may be in a range of 10Fr to 16Fr.
[0017] The frame 10 of the occluder 100 may be manufactured by braiding of a plurality of monofilament and/or multifilament strands. The strands may be made of a material having shape memory properties and/or flexibility such as metallic alloy(s) and/or biodegradable polymer(s). The metallic alloys may include without limitation nitinol, CoCr, copper-aluminum-nickel, etc. The biodegradable polymers may include, without limitation, poly-L-lactic acid (PLLA), poly lactic-co-glycolic acid (PLGA), poly-D, l-lactic acid (PDLA), Polydioxanone (PDO) or combinations thereof. In an embodiment, the strands are made of nitinol. The nitinol strands used in the present invention may be hard tempered and/or oxide free, having a thickness in a range of 100µm-200µm. In an embodiment, the thickness of the strands is in a range of 120µm to 150µm.
[0018] In an exemplary embodiment, the frame 10 of the occluder 100 includes a plurality of portions. The plurality of portions includes a distal end 16, a proximal end 18 and a middle portion 17. The occluder 100 may include at least two rings of strand loops. The strand loops may be located around the circumference of the frame 10. In an embodiment, the frame 10 includes two rings of strand loops each at one of the ends and/or in the middle portion of the frame 10. A first ring of strand loops 12 may be located near the distal end 16 and a second ring of strand loops 14 may be located in the middle portion 17 of the frame 10 of the occluder 100 as depicted in FIG.1.
[0019] The strand loops 12, 14 may firmly secure the occluder 100 to a defect and/or prevent the occluder 100 from slipping and/or moving from the position once implanted. The strand loops are loops made from the strands. The strand loops may secure the occluder 100 firmly to the wall of LAA defect post implantation and/or may lessen the risk of bouncing of the occluder 100 out of the defect in an arterial wall.
[0020] The shape of the strand loops 12, 14 may be predefined. The shape of the strand loops 12, 14 may be for example a triangular shape, oval shape, a circular shape, etc. In an embodiment, the shape of the strand loops 12 and 14 is triangular. FIG. 2 represents a top view of the occluder 100 including the strand loops 12. In an embodiment, the strand loops 12 are triangular. The strand loops 12 may be angled with respect to the longitudinal axis of the occluder 100. The strand loops may be angled in an angular range of 30° to 60°. In an embodiment, the angular range is 45° from the longitudinal axis of the occluder 100.
[0021] The angled strand loops may provide improved holding, and thus the occluder 100 is further prevented from slipping and/or bouncing off from the treatment site once implanted. Also, the angled strand loops may prevent piercing thereby mitigate the risk of damage to the defect site and/or nearby tissue.
[0022] The proximal end 18 of the frame 10 includes a jacket 20 as depicted in FIG. 1. The jacket 20 may be mounted by means of without limitation laser welding, crimping, etc. In an embodiment, the jacket 20 is mounted by means of laser welding. The jacket 20 may act as a housing for a bunch of free ends of the strands as well as facilitate effective deployment of the occluder 100.
[0023] The jacket 20 may be made of radiopaque material. The radiopacity of the jacket 20 may further enhance the visibility of the occluder 100 during the process of deployment. The radiopaque material used for manufacturing of the jacket 20 may include but not limited to stainless Steel, CoCr, gold, platinum, etc. In an embodiment, the jacket 20 is made of Stainless Steel.
[0024] The jacket 20 (as depicted in FIG. 3) may include a distal end 21 and a proximal end 23. In an embodiment, the distal end 21 has a circular shape and the proximal end 23 has a conical portion. The aforesaid shape of the jacket 20 at the distal end 21 and the proximal end 23 facilitate smooth movement of the jacket 20 through a delivery sheath. The diameter of the distal end 21 may be in a range of 02mm to 04mm. The diameter of the proximal end 23 of the jacket 20 may be in a range of 01mm to 03mm. The distal end 21 of the jacket 20 may include a cavity 25. The cavity 25 may be used to encapsulate a ball-shaped structure (not shown) of the strands. The diameter of the cavity 25 may be varied as per the size of the ball-shaped structure. The ball-shaped structure may be formed after welding of the free ends of the strands. In an embodiment, the diameter of the cavity 25 is in a range of 1.5mm to 2.5mm.
[0025] In another embodiment, the jacket 20 includes a threaded hole 27 towards the proximal end 23 of the jacket 20 as depicted in FIG.3. The threaded hole 27 may be employed for screwing the jacket 20 of the occluder 100 with a screw 30 of a delivery cable 40 (as depicted in FIG.4) to form an occluder assembly. The occluder assembly includes the occluder 100 and the delivery cable 40. In an embodiment, the diameter of the threaded hole 27 is aligned with the diameter of the conical portion of the proximal end 23 of the delivery cable 40. In an embodiment, the screwing of the jacket 20 with the screw 30 of the delivery cable 40 facilitates easy and/or accurate deployment of the occluder 100. Such an arrangement may be referred to as a jacket screw mechanism. Coupling of the occluder 100 with the delivery cable 40 by means of screwing may completely eradicate risk of detachment of the occluder 100 during deployment.
[0026] The occluder 100 may be deployed through the femoral artery in a patient. During the deployment process, the screw 30 may engage with the threaded hole 27 of the jacket 20 of the occluder 100. Following engagement of the jacket 20 and the screw 30, the delivery cable 40 may be loaded in a delivery sheath (not shown) in order to deploy the occluder 100 at the treatment site. The diameter of the delivery sheath may be in a range of 10Fr to 16Fr.
[0027] In yet another embodiment, the jacket 20 and the screw 30 facilitates re-sheathing of the occluder 100. Re-sheathing may be performed by retracting and subsequently re-positioning the occluder 100 without unscrewing the jacket 20 and the delivery cable 40. After placement of the occluder 100 at the desired treatment site, the occluder 100 is released from the delivery cable 40 at the treatment site by unscrewing the jacket 20 and the screw 30.
[0028] The process of manufacturing of the occluder 100 is now explained with the help of a flow chart. Fig. 5 illustrates an exemplary process involved in manufacturing of the occluder 100. The occluder 100 may be manufactured by braiding over a mandrel 200 (as depicted in FIG.6) using a braiding machine 300 (as depicted in FIG.8).
[0029] The process of manufacturing of the occluder 100 commences at step 301. At the said step, the strands are braided over the mandrel 200 using the braiding machine 300. The mandrel 200 may be a dome-shaped mandrel (as depicted in FIG.6). In an exemplary embodiment, the mandrel 200 has a distal end 203, a proximal end 205 and at least two rings 207, 209 of circular holes and a stylet 201. The circular holes may be located horizontally around the circumference of the mandrel 200. In another embodiment, each hole of each of the rings 207, 209 includes at least one pin 211. The pin 211 may help to form loops 12, 14 of the occluder 100.
[0030] In an embodiment, the braiding machine 300 includes at least two flairs of spools (an inner flair 215 and an outer flair 217) having a plurality of spools as depicted in FIG.7. For example, each of the inner flair 215 and the outer flair 217 includes 36 spools.
[0031] The braiding may be a continuous and/or non-continuous process. In an embodiment, the braiding is performed in two rounds. The braiding may be interrupted twice along the length of the mandrel 200. The interruption may occur during formation of the strand loops 12, 14.
[0032] At step 301, the braiding may commence from the distal end 203 of the mandrel 200 and is continued till the proximal end 205 of the mandrel 200. The process of braiding begins by winding a strand on one spool of the braiding machine (for example 211) of the inner flair 215 followed by passing the same strand around the slender probe 201 of the mandrel 200 towards the diametrically opposite spool (for example 213) of the outer flair 217 of the braiding machine 300 as depicted in FIG.7. Such a manner of braiding eliminates the formation of any free ends in the frame 10 at the end attached to the mandrel and/or provides support to the strand loops 12, 14. Further, no opening/hole is formed on the frame thereby eliminating any requirement of sealing/welding of the same.
[0033] The braiding may be performed at a take-up speed of 1.0V/Hz to 5.0 V/Hz and a rotation speed of 20V/Hz to 50V/Hz. The braiding is continued from the distal end 203 of the mandrel till the first ring of holes 207 of the mandrel 200. At the first ring of holes 207, the strands are twisted around the pin 211 in each hole of the first ring 207 to form the first ring of strand loops 12 (depicted in FIG.1).
[0034] Further, the braiding is continued till the second ring of holes 209 of the mandrel 200. In an embodiment, alternate single strands are mounted over the pin 211 of each hole of the second ring of holes 209 of the mandrel 200. The said process leads to the formation of the second ring of strand loop 14 (depicted in FIG.1). Lastly, the process of braiding is continued until the proximal end 205 of the mandrel 200.
[0035] In an embodiment, the braiding of the strands in an aforesaid manner leads to the formation of a dome-shaped frame 50 (as depicted in FIG.8a). The dome-shaped frame 50 includes a top portion 52, a middle portion 53 and a bottom portion 54. The top portion 52 of the frame 50 is a dome-shaped structure, the middle portion 53 is a wedge shape structure, and the bottom portion 54 may include free strands.
[0036] The middle portion 53 may include an upper end 53a, a transition 53b and a lower end 53c. The upper end 53a and the transition 53b of the middle portion 53 may include at least one ring of strand loops 12, 14 respectively. The strand loops 12, 14 may be disposed on outer peripheries of the upper end 53a and the transition 53b.
[0037] In next step 303, the dome-shaped frame 50 over the mandrel 200 is heat treated (primary annealing). The process of primary annealing may change mechanical properties of nitinol strands and/or provide shape memory to the frame 50.
[0038] The primary annealing may be performed by means of a fluidized bath and/or a vacuum oven. The fluidized bath provides heat through a continuous circulation of aluminum powder at a high temperature and pressure. The primary annealing maybe performed at a predefined temperature of 500°C to 600°C and pressure of 10 psi-20 psi for a predefined time duration of 5 minutes to 20 minutes. In an embodiment, the predefined temperature and the pressure are maintained at 515°C and 15psi respectively. In an embodiment, the predefined time duration is 15 minutes. Subsequently, the frame 50 is allowed to cool by quenching process at room temperature and/or is removed from the mandrel 200 for further processing.
[0039] At step 305, the dome-shaped frame 50 is further shape set to yield the frame 10 having a desired anatomy (for example as depicted in FIG.1). The shape setting may be performed by means of appropriate molds resembling LAA defect site. The material used for manufacturing of mold may include stainless steel (grade 316L). In an embodiment, the mold is made of medical grade stainless steel.
[0040] Secondary annealing using a vacuum unit may perform the shape setting. The secondary annealing may be carried out at a predefined temperature of 500°C to 600°C for a predefined time duration of 5 minutes to 20 minutes. In an embodiment, the predefined temperature and the time duration is 515°C and 15 minutes respectively. The process of secondary annealing may be performed in order to provide the desired strength and/or shape memory to the frame 10 of the occluder 100.
[0041] In an exemplary embodiment, the dome-shaped frame 50 is fitted inside a mold 60 as depicted in FIG.8a. The mold 60 may include at least two flairs of grooves 62, 64 for hooking the rings of strand loops 12, 14 of the frame 50.
[0042] Such an arrangement may impart a predefined angle of inclination to the strand loops 12, 14. The strand loops 12, 14 may project outwards with respect to a longitudinal axis of the dome-shaped frame 50. In an embodiment, the strand loops 12, 14 are inclined towards a distal end of the frame 50. The angle of inclination of the strand loops 12, 14 may be in a range of 40° to 60°. In an embodiment, the angle of inclination formed by the strand loops 12, 14 of the frame 50 is 45°.
[0043] The angle of inclination of the strand loops 12, 14 may enhance holding capacity and/or reduces the chance of bouncing off the occluder 100 from the LAA defect. The appropriate angle of inclination avoids piercing and/or harming the wall of LAA defects.
[0044] Further, the top portion 52 of the dome-shaped frame 50 may be compressed towards the middle portion 53 to form a compressed portion 11 (as depicted in FIG.1). In an embodiment, the top portion 52 may be compressed till the upper end 53a of the middle portion 53 of the dome shaped frame 50 (as depicted in FIG.8b). The compression may be performed by means of the mold 60. The compression of the frame 50 may provide pressure towards the distal end 16 which may facilitate adequate gripping of the strand loops 12 at the implantation site.
[0045] In next step 307, free ends of the distal end 54 of the dome shaped frame 50 are cut to the desired length. The free strands may pose a risk of damaging the nearby tissues due to their brittle nature. Therefore, the free ends of the strands may be merged by means of laser welding. The laser welding of the free ends may lead to the formation of a ball-shaped structure.
[0046] Subsequently, at step 309, the jacket 20 is mounted over the ball-shaped structure (not shown) of the frame 50 (as depicted in FIG.8c). The jacket 20 may be mounted by means of without limitation to laser welding, crimping. In an embodiment, the jacket 20 is mounted by means of laser welding. The aforesaid steps of 305, 307 and 309 yield the frame 10 as shown in FIG. 1.
[0047] In step 311, a process of passivation is performed. The process of passivation may increase the corrosion resistance of the occluder 100. The process of passivation may be performed by treatment with nitric acid solution at a temperature in a range of 30° to 70°C. In an embodiment, the temperature is maintained approximately 50°C. The frame 10 may be placed in the beaker filled with the nitric acid solution and allowed to stir at around 550-650 rpm for a period of 45-70 minutes. In an embodiment the stirring may be done at 600rpm for 60 minutes.
[0048] After stirring for 60 minutes, the frame 10 may be taken out from the nitric acid solution and is washed with a solution of sodium bi-carbonate. Subsequently, the frame 10 is placed in a beaker filled with distilled water for ultra-sonication for about 30 minutes. The whole aforesaid process of passivation may be repeated until the non-protective oxide layer is removed from the frame 10.
[0049] In another embodiment, the frame 10 is coated with titanium nitride. Coating with titanium nitride may reduce nickel leaching, increase biocompatibility and/or makes the frame 10 corrosion resistant. The coating may be performed by means of filtered multi-arc vacuum ion plating technique at a temperature of around 300°C. The coating thickness may be in a range of 0.4µm-1.0µm
[0050] In the next step 313, the frame 10 is subjected to a coating of polyurethane diol solution to yield the occluder 100. The coating with the polyurethane diol solution may facilitate tissue growth over the occluder 100 for enhanced occlusion at treatment site. The coating is performed by means of electro spin coating. The thickness of coating may be in a range of 50µm to 200µm.
[0051] Lastly, at the step 315, the occluder 100 is packed in an aluminum pouch. The packed occluder 100 may be subjected to sterilization by EtO process.
[0052] 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.