Claims:WE CLAIM:
1. A drug eluting stent (100) comprising:
a. a frame including one or more wire crossings, a proximal end (1) and a distal end (2), the proximal end (1) including one or more up-down loops (7a, 7b), the distal end (2) including one or more free ends, the one or more free ends are back braided towards the proximal end (1);
b. at least one sleeve (9), each sleeve (9) including a hole (A), wherein each sleeve (9) is coupled to a respective free end of a back braided wire such that the hole (A) is placed over the free end of the back braided wire, thereby improving coupling strength of the back braided wire to the frame, wherein each sleeve (9) is placed after at least four wire crossings from the distal end (2) facilitating smooth crimping of the frame; and
c. a plurality of layers including a first layer and a second layer, the first layer being composed of a primary coating solution disposed over the frame and at least one sleeve (9) to prevent breakage of the first layer, the second layer being disposed over the first layer to prevent the first layer from cracking.
2. The drug eluting stent (100) as claimed in claim 1 wherein, the at least one sleeve (9) includes six sleeves being attached with the frame via laser welding process.
3. The drug eluting stent (100) as claimed in claim 1 wherein, the at least one sleeve (9) is made of without limitation, stainless steel, cobalt chromium nitinol.
4. The drug eluting stent (100) as claimed in claim 1 wherein, the hole (A) is an oblong-shaped hole.
5. The drug eluting stent (100) as claimed in claim 1 wherein, the primary coating solution includes one or more of therapeutic drugs and/or anti-mitotic agents, one or more bioresorbable polymers and one or more solvents.
6. The drug eluting stent (100) as claimed in claim 5 wherein, the one or more therapeutic drugs and/or anti-mitotic agents include one or more of sirolimus, everolimus, biolimus, zotarolimus, paclitaxel or its derivatives, docetaxel or combinations thereof.
7. The drug eluting stent (100) as claimed in claim 6 wherein, the dosage of one or more therapeutic drugs and/or anti-mitotic agents are in the range of 1.25- 3.0µg/mm2.
8. The drug eluting stent (100) as claimed in claim 5 wherein, the one or more bioresorbable polymers include one or more of poly-D-lactide (PDLA), poly-DL-lactide (PDLLA), poly-L-lactide co-e-caprolactone (PLCL), poly lactide (PLA), polyglycolide (PGA), poly-DL-lactide glycolide (PDLG) or poly-caprolactone (PCL) or combinations thereof.
9. The drug eluting stent (100) as claimed in claim 8 wherein, the concentration of one or more bioresorbable polymers ranges from 0.05% (v/v) to 0.3% (v/v).
10. The drug eluting stent (100) as claimed in claim 5 wherein, the one or more solvents include one or more of DCM (dichloromethane), acetone, methanol, ethanol, 1-propanol, isopropanol or combinations thereof.
11. The drug eluting stent (100) as claimed in claim 1 wherein, the second layer includes polyvinylpyrrolidone (PVP).
, 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:
DRUG-ELUTING STENT

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

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

FIELD OF INVENTION
[001] The present invention relates to a medical device, more specifically the present invention relates to a drug eluting stent.
BACKGROUND
[002] Peripheral artery disease (PAD) is a disease in which plaque builds up in one or more arteries that carry blood to head, organs and limbs. PAD usually affects the arteries of the legs however it can also affect the arteries that carry blood from heart to head, kidneys, arms, and stomach. The treatment of PAD is usually done with the help of drug eluting stents (DES).
[003] A drug eluting stent is a peripheral or coronary stent which is placed in a narrow, diseased artery such that the stent slowly releases a drug to block cell proliferation. The peripheral arteries close to the knee of a patient experience a lot of external compression and mechanical forces. Therefore, it is required that the drug eluting stents should have superior flexibility and sufficient rigidity to maintain patency of the vessel.
[004] The drug eluting stents are either polymer stents or rigid metal stents which may be formed using braiding or laser cutting. The laser cutting technique utilized in fabricating conventional drug eluting stents include fracture, crushing, and kinking of a polymer or a metal tube. The said steps may result in a stent which might pose negative impact on the patients suffering from PAD. Further, the stent formed using laser cutting is expensive and requires relatively high heat and may change the shape memory properties of the stent. Therefore, braiding is the preferred choice for manufacturing drug eluting stents.
[005] The conventional braided drug eluting stents have less uniformity in braiding angles which in turn leads to a bulging effect when the stent undergoes compression. Also many conventional stents are not coated with a therapeutic drug which leads to the risk of thrombosis and restenosis. The conventional drug eluting stents have a deployment system which lacks retrieval options during deploying of stent at treatment site which may sometimes increase risk of procedural errors. The conventional drug eluting stents include sleeves however, the said sleeves are attached to the stents by welding only the surface of the sleeves at both ends. The said sleeves are not welded on the ends points of stent wires which may increase chances of breaking of wire at welded end due to biomechanical forces exerted on the drug eluting stent in a peripheral vasculature.
SUMMARY
[006] The present invention relates to a drug eluting stent which includes a frame. In an embodiment, the frame includes one or more wire crossings, a proximal end and a distal end.
[007] In an embodiment, the proximal end including one or more up-down loops. The one or more up-down loops are provided for easy/smooth loading of the drug eluting stent inside a catheter assembly.
[008] In an embodiment, the distal end includes one or more free ends. The one or more free ends are back braided towards the proximal end.
[009] The drug eluting stent further includes at least one sleeve. The each sleeve includes a hole. In an embodiment, the each sleeve is coupled to a respective free end of a back braided wire such that the hole is placed over the free end of the back braided wire. The said arrangement improves the coupling strength of the back braided wire to the frame. The each sleeve is placed after at least four wire crossings from the distal end in order to facilitate smooth crimping of the frame.
[0010] In an embodiment, the drug eluting stent also includes a plurality of layers. The plurality of layers includes a first layer and a second layer. The first layer is composed of a primary coating solution which is disposed over the frame and at least one sleeve in order to prevent breakage of the first layer. The second layer is disposed over the first layer to prevent the first layer from cracking.

BRIEF DESCRIPTION OF THE DRAWINGS
[0011] 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.
[0012] Fig.1 depicts a drug eluting stent in accordance with an embodiment of the present invention.
[0013] Fig. 1a depicts a sleeve with a single oblong hole in accordance with an embodiment of the present invention.
[0014] Fig. 2 illustrates a flow chart depicting the method to manufacture a drug eluting stent in accordance with an embodiment of the present invention.
[0015] Fig. 2a depicts the braiding of the drug eluting stent in accordance with an embodiment of the present invention.
[0016] Fig. 3 illustrates the process of loading the drug eluting stent on to a delivery sheath in accordance with an embodiment of the present invention.
[0017] Figs. 3a-e depicts the loading system of the drug eluting stent in accordance with an embodiment of the present invention.
DETAILED DESCRIPTION OF THE DRAWINGS
[0018] 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.
[0019] 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.
[0020] In accordance with the present disclosure, a drug eluting stent and a method of manufacture thereof is disclosed. The drug eluting stent is utilized for the treatment of diseases for example, a peripheral artery disease. The drug eluting stent is deployed at a treatment site with the help of a catheter assembly. Subsequently, the drug eluting stent expands at the treatment site thereby releasing a drug once in contact with an arterial wall. The drug eluting stent of the present invention may be balloon expandable or self-expandable. The drug eluting stent may be manufactured using braiding of nitinol wires. The uniform values of braiding angle of the drug eluting stent and the tension of spring used to braid the nitinol wires provides more flexibility to the drug eluting stent. It also provides high tensile and radial strength to the drug eluting stent which reduces the risk of bulging property during compression of the drug eluting stent and the drug eluting stent can survive in highly calcified areas.
[0021] The drug eluting stent of the present invention includes one or more up- down loops at a proximal end of the drug eluting stent. The up-down loops are provided for easy/smooth loading of the drug eluting stent inside the catheter assembly.
[0022] The drug eluting stent further includes one or more sleeves disposed at a distal end of the drug eluting stent. The one or more sleeves are attached to the drug eluting stent via welding. The one or more sleeves may be attached to the drug eluting stent after at least four to five wire crossings formed during the braiding of the stent. The one ore sleeves are placed after at least four to five wire crossings to facilitate smooth crimping of the drug eluting stent while loading the said stent inside the catheter assembly. The attachment of the one or more sleeves to the drug eluting stent provides strength to the drug eluting stent and reduces the possibility of breakage of the drug eluting stent inside the body and punctures in the arteries during the movement of the body.
[0023] The drug eluting stent of the present invention is coated with a primary coating solution. The primary coating solution includes one or more components. In an embodiment, the components of the primary coating solution include one or more therapeutic drugs and/or anti-mitotic agents, one or more bioresorbable polymers and one or more solvents. The primary coating solution is uniformly coated on a surface of a drug eluting stent to ensure minimal drug loss during drug delivery at the treatment site. The primary coating solution as disclosed in the present invention does not break during the loading of the drug eluting stent inside the catheter assembly.
[0024] Now specifically referring to the drawings, Fig.1 depicts an exemplary embodiment of a drug eluting stent 100 of the present invention. The drug eluting stent 100 may be a self-expandable stent or a balloon expandable stent. In an embodiment, the drug eluting stent 100 is a self-expandable stent.
[0025] The drug eluting stent 100 may be made of, without limitation nitinol, cobalt chromium (CoCr), etc. In an embodiment, the drug eluting stent 100 is made from nitinol. Nitinol is utilized for making the drug eluting stent 100 due to its excellent biocompatibility, kink resistance, physiological compatibility, shape-memory deployment, dynamic interference, and fatigue resistance.
[0026] The drug eluting stent 100 may be manufactured using laser cutting technique or braiding technique. In an embodiment, the drug eluting stent 100 is formed using braiding of the nitinol wires (explained in Fig. 2). In an embodiment, the number of nitinol wires used to form the drug eluting stent 100 is 10-18 wires, more preferably 06-08 wires. In an embodiment, the nitinol wire has a diameter in the range of 0.15-0.3mm, more preferably 0.2-0.25mm.
[0027] The drug eluting stent 100 may be formed by using one or more braiding patterns. The one or more braiding patterns may include without limitation, two over two patterns, diamond pattern and diamond half-load pattern. In an embodiment, the drug eluting stent 100 is formed using half-load diamond braiding pattern.
[0028] The drug eluting stent 100 may have open ends (ends having nitinol wires with loose free ends) or closed ends (ends having nitinol wires with sealed free ends). In an embodiment, the drug eluting stent 100 has closed ends.
[0029] The drug eluting stent may include without limitation, a proximal end 1, a distal end 3, an outer surface 5, an inner surface (not shown), one or more up-down loops (7a and 7b) and one or more sleeves 9.
[0030] In an embodiment, the drug eluting stent 100 is a hollow tubular structure having an inner and outer diameter. In an embodiment, the inner diameter of the drug eluting stent 100 ranges from 4mm to 12mm. In an embodiment the outer diameter of the drug eluting stent 100 ranges from 4.6 to 12.8mm. The drug eluting stent 100 has high radial strength and durability. The radial strength of the drug eluting stent 100 may vary depending upon the size of the drug eluting stent 100. For instance, the drug eluting stent 100 having dimensions 6mm x 60mm (D x L) includes a radial strength sufficient to withstand high biomechanical forces of peripheral arteries. In an embodiment, the drug eluting stent 100 has a strut thickness of 200-230micron.
[0031] The outer surface 5 of the drug eluting stent 100 may be coated with a primary coating solution. In an embodiment, the primary coating solution is coated and is solidified to form of a first layer. The primary coating solution may include one or more components. The one or more components may include without limitation, one or more of therapeutic drugs and/or anti-mitotic agents, one or more bioresorbable polymers and one or more solvents. The primary coating solution may be coated on the outer surface 5 of the drug eluting stent 100 by using dip coating or spray coating method (explained in Fig. 2).
[0032] The one or more therapeutic drugs may include without limitation, sirolimus, everolimus, biolimus A9 and zotarolimus. In an embodiment, the therapeutic drug used in the primary coating solution is sirolimus. The amount of therapeutic drug used in the primary coating solution to coat the outer surface 5 of the drug eluting stent 100 may be in the range of 1.25- 3.0µg/mm2. The therapeutic drug used in the present invention offers various advantages such as the said drug provides anti-proliferative effect which reduces the risk of initial thrombosis and prevents restenosis in the arteries. The coating of the therapeutic drug on the outer surface 5 of the drug eluting stent 100 provides controlled release of the therapeutic drug throughout the healing period.
[0033] In an embodiment, an anti-mitotic agent may be used in the primary coating solution. The anti-mitotic agent is a type of drug which blocks the cell growth by stopping mitosis (cell division). The anti-mitotic agent may include without limitation, paclitaxel or its derivatives or docetaxel etc. In an embodiment, the anti-mitotic agent used is paclitaxel. The amount of anti-mitotic agent used in the primary coating solution to coat the outer surface 5 of the drug eluting stent 100 may be in the range of 1.25- 3.0µg/mm2.
[0034] The one or more bioresorbable polymers may include without limitation, poly-D-lactide (PDLA), poly-DL-lactide (PDLLA), poly-L-lactide co-e-caprolactone (PLCL), poly lactide (PLA), polyglycolide (PGA), poly-DL-lactide glycolide (PDLG) or poly-caprolactone (PCL) or their combination. In an embodiment, the bioresorbable polymer used in the primary coating solution is a mixture of poly L-lactide (PDLLA) and poly DL-lactide co-glycolide (PDLG). The amount of the bioresorbable polymer used in the primary coating solution may range from 0.05-0.3% (v/v). The bioresorbable polymer in the primary coating solution prevents restenosis and reduces the risk of initial thrombosis in the arteries.
[0035] The one or more solvents may include without limitation, DCM (dichloromethane), acetone, methanol, ethanol, 1-propanol, isopropanol etc. In an embodiment, the solvent used in the primary coating solution is 100% (v/v) DCM (dichloromethane).
[0036] The first layer of the drug eluting stent 100 does not break during the loading of the drug eluting stent 100 inside the catheter assembly.
[0037] Optionally and/or additionally, the first layer may be coated with a second layer. The second layer may include without limitation, polyvinylpyrrolidone (PVP). PVP adheres well and protects the first layer which includes a therapeutic drug. PVP also has anti-thrombotic properties. The second layer helps to maintain coating integrity and prevents cracks/peeling of the coating surface during loading and deployment of the drug eluting stent 100. Also, the second layer provides lubricious surface which helps in smooth loading of the drug eluting stent 100 inside the catheter assembly.
[0038] The one or more up-down loops (7a and 7b) are disposed on the proximal end 1 of the drug eluting stent 100. In an embodiment, the drug eluting stent 100 includes six up-down loops (three up loops 7a and three down loops 7b). The one or more up-down loops are formed during the braiding process (explained in Fig. 2).
[0039] The one or more up-down loops (7a and 7b) help in smooth and easy loading of the drug eluting stent 100 over a catheter assembly. Due to the presence of the one or more up-down loops (7a and 7b), the primary coating solution coated on the outer surface 5 of the drug eluting stent 100 does not break during the deployment procedure of the drug eluting stent 100. In an embodiment, the one or more up-down loops (7a and 7b) also help in repositioning/ retrieval after 80% deployment of the drug eluting stent 100.
[0040] Each of the one or more sleeves 9 is in the form of a small piece of hollow tube. The one or more sleeves 9 may be made of without limitation, stainless steel, cobalt chromium nitinol, etc. In an embodiment, the one or more sleeves 9 are made of nitinol. The one or more sleeves 9 may include without limitation, tube sleeve, single oblong hole sleeve, double oblong hole sleeve, oblong slot sleeve, etc. In an embodiment, the one or more sleeves 9 include a single oblong hole A (as depicted in Fig. 1a). In an embodiment, the outer diameter of the one or more sleeves 9 ranges from 0.3- 0.4mm and the length of one or more sleeves 9 ranges from 1.5- 3.5 mm.
[0041] The one or more sleeves 9 are disposed towards the distal end 3 around the diameter of each of the back braided wire in the drug eluting stent 100. In an embodiment, once the drug eluting stent 100 is formed by braiding the nitinol wires from the proximal end 1 to the distal end 3, the free ends of the nitinol wires produced at the distal end 3 are back braided towards the proximal end 1. In an embodiment, the one more sleeves 9 are disposed at a point up to which the drug eluting stent 100 is back braided.
[0042] In an embodiment, six sleeves 9a, 9b, 9c, 9d, 9e and 9f are disposed towards the distal end 3. In another embodiment, the first sleeve 9a is disposed after four to five wire crossings (where the nitinol wires cross each other during the braiding process) from the distal end 3. The first sleeve 9a is placed after at least four to five wire crossings to facilitate smooth crimping of the drug eluting stent while loading the said stent inside the catheter assembly. The second sleeve 9b is disposed adjacent to the first sleeve 9a. The third sleeve 9c is disposed adjacent to the second sleeve 9b. The fourth sleeve 9d is placed adjacent to the third sleeve 9c. The fifth sleeve 9e is placed adjacent to the fourth sleeve 9d. The sixth sleeve 9f is placed adjacent to the fifth sleeve 9e.
[0043] In an embodiment, the one or more sleeves 9 to be used in the drug eluting stent 100 is directly related to the number of wires back braided in the drug eluting stent 100. For example, as depicted in Fig. 1, the number of back braided wires in the drug eluting stent 100 are six, hence, the number of one or more sleeves 9 used in the drug eluting stent 100 will also be six. The position of the one or more sleeves 9 may depend on the length of the back braided wire. In an embodiment, the length of the back braiding wire ranges from 30- 90mm.
[0044] In an embodiment, the one or more sleeves 9 are disposed on the surface (inner and outer 5) of the drug eluting stent 100 via laser welding process. The laser welding of the one or more sleeves 9 on the surface (inner and outer 5) of the drug eluting stent 100 provides strength to the drug eluting stent 100. The laser welding of the one or more sleeves 9 also reduces the possibility of the drug eluting stent 100 to break when placed inside the body and reduces the puncture of the arteries during the movement of the patient’s body.
[0045] Fig. 2 illustrates a flowchart depicting the method to manufacture a drug eluting stent 100 of the present invention. The process of manufacturing a drug eluting stent 100 commences at step 201.
[0046] At step 201, nitinol wires are braided to form the drug eluting stent 100. The process of braiding may be carried out in flat braiding machines used to make flat tapes and tubular braiding machines used to make round structures. In an embodiment, the braiding process is carried out in a 24 to 32 carriers tubular braiding machine. The tubular braiding machine may include without limitation, one or more braiding spools (not shown), a mandrel 20 having one or holes 20a and one or more pins 20b.
[0047] The nitinol wires are wound over the one or more braiding spools (manually or with a winding machine). The mandrel 20 is attached to the center of the tubular braiding machine. The mandrel 20 may have without limitation, a polygonal shape for tightness of braid and to avoid slipping of the wires. The mandrel 20 may be made of medical grade teflon, SS304 or SS316. The one or more holes 20a are provided on the mandrel 20 for attachment of the one or more metal pins 20b. The one or more holes 20a at a proximal end of the mandrel 20 are attached to the one or more pins 20b. The one or more pins 20b at the proximal end of the mandrel 20 are positioned in an up-down manner (as shown in FIG. 2a) and the nitinol wires are hooked in each pin 20b to obtain a closed proximal end 1 of the drug eluting stent 100 having up-down loops (7a and 7b).
[0048] The mandrel 20 includes a distal end. The one or more holes 20a at the distal end of the mandrel 20 does not include the one or more pins 20b in up-down configuration. While braiding, the free ends of the nitinol wires at the distal end of the mandrel 20, are looped around the one or more holes 20a and back braided towards the proximal end 1 of the drug eluting stent 100.
[0049] The number of holes depends upon the number of wires to be used to make the drug eluting stent 100. For example, if braiding is done with 12 numbers of wires then 6 numbers of pins 20b are attached to the mandrel 20 so that closed end is achieved at braiding stage only. Similarly, if braiding is done by 16 numbers of wires then 8 numbers of pins 20b are attached to the mandrel 20.
[0050] The parameters which affect the braiding parameters are distance between the one or more braiding spools and the starting point of the braiding, braiding angle, carrier speed. In an embodiment, distance between the one or more braiding spools and the starting point of the braiding ranges from 5-10mm. During the braiding process, the distance between the one or more braiding spools and the starting point of the braiding is maintained in such a manner that when the braiding process starts, accurate and uniform braiding angle is obtained. In an embodiment, the drug eluting stent 100 has a braiding angle in the range of 115° to 155°, more preferably 130° to 145°. In another embodiment, the tension of spring used to braid the nitinol wires ranges from 0.4mm-1.2mm, more preferably from 0.6mm-0.9mm.
[0051] The distance between the one or more braiding spools and the starting point of the braiding and the braiding angles are important parameters for the braided drug eluting stent 100 as it directly affects the radial strength, foreshortening and bulging issues of the braided drug eluting stent 100. The uniform values of braiding angle and the tension of spring used to braid the nitinol wires provides more flexibility to the drug eluting stent 100. It also provides high tensile and radial strength to the drug eluting stent 100 which reduces the risk of bulging property during compression of the drug eluting stent 100 and the drug eluting stent 100 can survive in highly calcified areas.
[0052] In an embodiment, the proximal end 1 of the drug eluting stent 100 is closed during the braiding process. The distal end of the drug eluting stent 100 is closed by a back braiding process. In an embodiment, the free ends of the nitinol wires produced at the distal end 3 are back braided towards the proximal end 1.
[0053] The back braiding is performed in the same pattern as during the braiding process.
[0054] At step 203, shape setting of the drug eluting stent 100 takes place. After the drug eluting stent 100 is braided, the braided drug eluting stent 100 along with the mandrel is placed in a furnace called the fluidized bath. The braided drug eluting stent 100 may be heated at a predefined temperature for a predefined time duration. In an embodiment, the predefined temperature ranges from 470°C to 550°C, more preferably 490°C to 510° and the predefined time duration ranges from 5 min to 10 min according to ASTM F-2063.
[0055] The nitinol material utilized in making the drug eluting stent 100 is heated through a range of characteristic temperatures. The nitinol material changes its crystal form and gets the shape memory properties. After the heat setting process of the drug eluting stent 100 is performed, the drug eluting stent 100 is quenched in water for the rapid cooling and for producing a martensite transformation of the stent which is responsible for the shape memory effect.
[0056] At step 205, laser welding of the one or more sleeves 9 on the drug eluting stent 100 takes place. In an embodiment, the laser welding of the one or more sleeves 9 on the drug eluting stent 100 is performed using sleeve laser welding process. In the said process, the one or more sleeves 9 are used as a connecting medium for the braided and back braided wires.
[0057] First, the one or more sleeves 9 are placed over the free ends of the back braided nitinol wires under a microscope with the help of forceps. Each sleeve 9 is coupled to the respective free end of the back braided wire such that the oblong hole A of the sleeve 9 is placed over the free end of the back braided wire (i.e. at the center/mid-point of the one or more sleeves 9). Such an arrangement improves coupling strength of the back braided wire to the frame. In an embodiment, the one or more sleeves 9 are adjusted such that the oblong hole A of the one or more sleeves 9 is at a front side of the stent (outer surface 5).
[0058] The laser welding of the sleeve with the frame is performed after positioning the sleeves on the frame.
[0059] In an embodiment, the length of the back braided structure depends on the number of sleeves to be used in the drug eluting stent 100 and the position of the sixth sleeve 9f from distal end 3 of the drug eluting stent 100. After the back braiding process, laser welding is performed by making the back braided wires face to face with the braided wires. In the sleeve laser welding, the braided and back braided wires are placed face to face in the center of the one or more sleeves 9 sleeve/oblong hole A and welding is done by impact laser spot on oblong hole A provided on the one or more sleeves 9.
[0060] Alternately, laser welding is performed by placing the back braided wires side by side with respect to the braided wires and subsequently welding the same.
[0061] In an embodiment, the laser welding by single spot is performed using three steps, first braided wire is welded with back braided wire. Secondly, the braided wire end is laser welded with back braided wire and thirdly both the wires (braided and back braided wires) are laser welded with the one or more sleeves 9.
[0062] In an embodiment, the laser welding is done with a spot diameter which ranges from 0.15-0.30mm and pulse width which ranges from 0.4-0.6ms on the roffin laser welding machine. The welding process provides better strength to the drug eluting stent 100, using of the sleeve welding technique provides a suitable flexibility and strength to the drug eluting stent 100.
[0063] At step 207, passivation of the drug eluting stent 100 takes place. The process of chemical passivation is performed after the drug eluting stent 100 undergoes the process of shape setting and quenching. The chemical passivation process is performed to remove the non-protective oxide layer which is formed on the surface (outer surface 5 & inner surface) of the drug eluting stent 100 during the steps 201, 203 and 205. The non-protective oxide layer includes formation of oxides of iron, nickel and titanium on the surface of drug eluting stent 100. The non-protective oxide layer corrodes the drug eluting stent 100 when the drug eluting stent 100 comes in contact with the body fluids after implantation which also leads to the formation of hazards inside the human body.
[0064] The drug eluting stent 100 is immersed in a passivating solution. The passivating solution may include one or more passivating solvents. The one or more passivating solvents may include without limitation, nitric acid, citric acid, etc. The aforementioned passivating solvents act as strong oxidizing agents. The passivating solution is prepared by mixing nitric acid in water. The concentration of the passivating solution may range from 30- 60% (v/v). In an embodiment, the concentration of the passivating solution is 50 % (v/v).
[0065] The drug eluting stent 100 is immersed in a passivating solution for a passivating time duration which may range from 40-80 min, preferably 50-60min at a predefined speed of 580rpm to 620rpm. In an embodiment, two-four passivation cycles are performed to remove the whole oxide layer from the drug eluting stent 100.
[0066] Subsequently, the drug eluting stent 100 may be washed with a saturated solution of sodium bicarbonate (NaHCO3) to make it clean and the drug eluting stent 100 may be sonicated for a time duration which may range from 20-30 minutes in distilled/deionized water.
[0067] At step 209, coating on the drug eluting stent 100 takes place. The drug coating process takes place on the outer surface 5 of the drug eluting stent 100. The drug coating process may be performed either using spray coating or dip coating method. In an embodiment, the drug coating process is performed using spray coating method. In the spray coating method the primary coating solution is sprayed over the outer surface 5 of the drug eluting stent 100. The coating parameters must be accurately controlled like the distance between stent and spray gun tip, the collate rotation, the solution flow rate and the inert gas pressure etc. In an embodiment, the collate-rotation ranges from 15-25 RPM and the distance between the spray gun tip and the drug eluting stent 100 ranges from 3-8 mm. The solution flow rate may be in the range of 0.1- 0.3ml/min and the inert gas pressure may be in the range of 5- 8 psi.
[0068] The amount of therapeutic drug that is to be coated on the drug eluting stent 100 may be controlled by applying number of thin coats of the primary coating solution while allowing it to dry between the coats. The overall coating thickness should be thin so that the primary coating solution does not increase the profile of the drug eluting stent 100 that can create difficulties while loading or deployment of the drug eluting stent 100. In an embodiment, the coating thickness of the primary coating solution ranges from 2-10 micron, more preferably 3-6 micron.
[0069] At step 211, loading of the drug eluting stent 100 takes place. The loading process includes loading of the drug eluting stent 100 onto a delivery system (explained in Figs. 3a-e).
[0070] At step 213, the drug eluting stent 100 is then sterilized. After the drug eluting stent 100 is loaded inside the delivery sheath, the whole assembly is then sterilized. In an embodiment, the drug eluting stent 100 is packed in a HDPE tray and a Tyvek® pouch to achieve desired sterility assurance level of 10-6 as per ISO 11135:2014.
[0071] The drug eluting stent 100 may be sterilized by any techniques known in the art for example, ethylene oxide (EtO), radiation sterilization like gamma or E-beam sterilization. In an embodiment, the drug eluting stent 100 is sterilized using ethylene oxide sterilization process. In an embodiment, the sterilization cycle may have aeration time ranges from 02-05 hours, more preferably from 03-04 hours. The ethylene oxide (EtO) gas exposure time is approximately 160 minutes.
[0072] Other variables/parameters include temperature, humidity, EtO concentration and pressure. In an embodiment, the temperature of the sterilization is maintained between 35-45°C and the humidity is maintained around 40%.
[0073] Fig. 3 illustrates the process of loading the drug eluting stent 100 on to a delivery sheath. The loading process of the drug eluting stent 100 is carried out in a clean environment. The loading assembly may include without limitation, one or more sutures 30, a dog bone type funnel 32, guide wire 34, a stent driver 36, a pusher rod 38 and the delivery sheath (not shown). The process of loading the drug eluting stent 100 on to the delivery sheath commences at step 301.
[0074] At step 301, the three up loops 7a are attached to the one or more sutures 30 (as depicted in Fig. 3a). The one more sutures 30 help in loading the drug eluting stent 100 without damaging the drug coated surface of the drug eluting stent 100. The up-down loops (7a and 7b) also help in repositioning/ retrieval after 80% deployment of the drug eluting stent 100.
[0075] At step 303, the drug eluting stent 100 is then placed inside a funnel 32 (as depicted in Fig. 3b). In an embodiment, the funnel 32 is a hollow tube type structure having two ends and a central portion. The diameter of central portion of the funnel 32 may be less than the diameter of the ends. For example, the funnel 32 is dog bone shaped.
[0076] At step 305, the drug eluting stent 100 is then mounted on a guide wire 34 (as depicted in Fig. 3c).
[0077] At step 307, the one or more sutures 30 attached to the three up loops 7a are then removed manually. The one or more sutures 30 are removed by placing the drug eluting stent 100 over the stent driver 307 with the help of the dog bone type funnel 32 (as depicted in Fig. 3d). The stent driver 36 includes the pusher rod 38.
[0078] At step 309, the drug eluting stent 100 is completely loaded inside a delivery sheath (not shown) by pulling the pusher rod 38 (as depicted in Fig. 3e). In an embodiment, the diameter of the delivery sheath ranges from 5-10 Fr, more preferably 6-8 Fr with a length of 80-120cm. The dog bone type funnel 32 is detached manually from the distal end 3 of the drug eluting stent 100.
[0079] At first, the three up loops 7a move inside the delivery sheath and then the three down loops 7b move inside the delivery sheath to facilitate smoother, quicker and easier to loading of the drug eluting stent 100.
[0080] In an embodiment, the drug eluting stent 100 has no radiopaque markers but has sufficient radiopacity as the drug eluting stent 100 is made of nitinol.
[0081] The present invention is explained with the following examples:
Example 1: There were two drug eluting stents 100 of the same dimensions i.e. of 6mm inner diameter and 60mm length. The first drug eluting stent 100 (present invention) was fabricated using braiding technology and the second drug eluting stent 100 (prior art) was fabricated using laser cutting technology. The radial strength of both the first drug eluting stent 100 and the second drug eluting stent 100 was checked on radial strength test system. The radial strength of braided stent (the first drug eluting stent 100) was obtained to be around 90 N which was higher (minimum 3X to 4X) than the radial strength of the laser cut self-expanding metal stent (the second drug eluting stent 100) which was around 29.9 N.
[0082] Example 2: Three drug eluting braided stents (X, Y and Z) of 6 mm inner diameter and 60 mm length were fabricated. Stent X (prior art) included both open end structure, stent Y (prior art) included one end closed and other end was twisted wire end structure. Stent Z (present invention) had both closed end structure with proximal up-down loops. Radial strength of all stents is check on radial strength test system. The radial strength of first, second and third stent was found to be 53.52 N, 59.51 N and 176.85 N respectively. The stent Z had more strength than stent X and Y which offered better patency in lumen. Further, the stent Z with up-down loops offered easy and quick loading in outer sheath.
[0083] Example 3: One type of sleeve may be where two holes are provided on the one or more sleeves 9. The second type of sleeve may be a sleeve where a single oblong hole A is provided in the center and wire is in face to face manner in center of the one or more sleeves 9. Laser welding is performed on both the sets as describe above. The welding strength of sleeve having double holes ranges from 02- 06 N and more preferably from 03- 5N while the sleeve with the single hole ranges from 06 - 10 N and more preferably from 07- 09 N.
[0084] 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.