Claims:1. A bioabsorbable mesh-scaffold assembly, comprising:
a bioabsorbable scaffold having an outer surface to be implanted in a human arterial vasculature; and
an expandable bioabsorbable mesh mounted coaxially on the outer surface of the bioabsorbable scaffold, the expandable bioabsorbable mesh made of a single monofilament;
the bioabsorbable mesh-scaffold assembly having a low crimp profile configured for insertion into the human arterial vasculature.
2. The bioabsorbable mesh-scaffold assembly as claimed in claim 1 wherein the low crimp profile ranges from 1.2mm to 1.4mm.
3. The bioabsorbable mesh-scaffold assembly as claimed in claim 1 wherein the bioabsorbable scaffold is barrel shaped.
4. The bioabsorbable mesh-scaffold assembly as claimed in claim 1 wherein the bioabsorbable scaffold is made up of a bioabsorbable polymer.
5. The bioabsorbable mesh-scaffold assembly as claimed in claim 4 wherein the bioabsorbable polymer is Poly-L lactide (PLLA).
6. The bioabsorbable mesh-scaffold assembly as claimed in claim 1 wherein the bioabsorbable scaffold is coated with an antiproliferative drug.
7. The bioabsorbable mesh-scaffold assembly as claimed in claim 6 wherein the antiproliferative drug is Sirolimus.
8. The bioabsorbable mesh-scaffold assembly as claimed in claim 1 wherein the expandable bioabsorbable mesh is barrel shaped.
9. The bioabsorbable mesh-scaffold assembly as claimed in claim 1 wherein the expandable bioabsorbable mesh is coated with at least one therapeutic agent.
10. The bioabsorbable mesh-scaffold assembly as claimed in claim 9 wherein the at least one therapeutic agent comprises one or more of an antiproliferative drug, an antithrombin drug and an antiplatelet drug.
11. The bioabsorbable mesh-scaffold assembly as claimed in claim 1 wherein the expandable bioabsorbable mesh is mounted around the outer surface of the bioabsorbable scaffold by a plurality of stitches and a plurality of mounting means.
12. The bioabsorbable mesh-scaffold assembly as claimed in claim 11 wherein the plurality of mounting means comprises one or more surgeon’s knot by knotting corresponding mounting means present on respective end of the expandable bioabsorbable mesh and bioabsorbable scaffold.
13. The bioabsorbable mesh-scaffold assembly as claimed in claim 1 wherein the monofilament is extruded from a bioabsorbable polymer.
14. The bioabsorbable mesh-scaffold assembly as claimed in claim 1 wherein the monofilament is extruded from a combination of the bioabsorbable polymer and a therapeutic agent.
15. The bioabsorbable mesh-scaffold assembly as claimed in claim 14 wherein the bioabsorbable polymer is polylactic-co-polyglycolic ("PLGA"), the PLGA comprises lactic acid and polyglycolic acid in the ration of 85:15.
16. The bioabsorbable mesh-scaffold assembly as claimed in claim 14 wherein the at least one therapeutic agent comprises one or more of an antiproliferative drug, an antithrombin drug and an antiplatelet drug.
17. The bioabsorbable mesh-scaffold assembly as claimed in claim 1 wherein diameter of the monofilament is in the range of 25-30 µm.
18. The bioabsorbable mesh-scaffold assembly as claimed in claim 1 wherein the monofilament is knitted to form the expandable bioabsorbable mesh using a circular weft knitting machine.
19. The bioabsorbable mesh-scaffold assembly as claimed in claim 1 wherein the circular weft knitting machine is performed by a circular head knitting cam having a plurality of needles ranging from 22 to 110.
20. A method of annealing of an extruded monofilament comprising:
annealing an extruded monofilament under vacuum and with a temperature range of 115° C to 125° C for a duration ranging from 60 minutes to 120 minutes;
purging the vacuum with an inert gas for a predefined time duration;
applying vacuum in a first set of conditions;
repeating the steps of purging and application of vacuum for a predefined number of times; and
applying vacuum in a second set of conditions.
21. The method as claimed in claim 20 wherein the inert gas is nitrogen.
22. A method of manufacturing a bioabsorbable mesh-scaffold assembly comprising:
extruding a monofilament from a bioabsorbable polymer;
annealing the extruded monofilament under vacuum and with a temperature range of 115° C to 125° C for a duration ranging from 60 minutes to 120 minutes;
knitting an expandable bioabsorbable mesh using the annealed monofilament, the knitting is performed by a weft knitting technology;
mounting the expandable bioabsorbable mesh coaxially onto an outer surface of a bioabsorbable scaffold making a bioabsorbable mesh-scaffold assembly; and
crimping the bioabsorbable mesh-scaffold assembly onto an expandable member of a delivery catheter, the bioabsorbable mesh-scaffold assembly having a low crimp profile in the range of 1.2mm to 1.4mm.
23. The method as claimed in claim 22, wherein the extrusion comprising cryogrinding of the bioabsorbable polymer to powdered form.
24. The method as claimed in claim 22, wherein the extrusion comprising the blending of the bioabsorbable polymer with at least one therapeutic agent.
25. The method as claimed in claim 24 wherein the at least one therapeutic agent comprises one or more of an antiproliferative drug, an antithrombin drug and an antiplatelet drug.
26. The method as claimed in claim 22 wherein the annealing comprises purging the vacuum with an inert gas for a predefined time duration.
27. The method as claimed in claim 26 wherein the inert gas is nitrogen.
28. The method as claimed in claim 22, wherein the mounting comprises affixing the expandable bioabsorbable mesh using one or more of a plurality of stitches and a plurality of mounting means.
29. The method as claimed in claim 22, wherein the method comprises sterilizing the bioabsorbable mesh-scaffold assembly via e-beam radiation.
30. The method as claimed in claim 22, wherein the method comprises packaging the crimped bioabsorbable mesh-scaffold assembly on the delivery catheter in a multi-layer pouch.
, 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:
Bioabsorbable mesh-scaffold assembly and method of manufacture 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

The following specification, particularly describes the invention:

FIELD OF INVENTION
[001] This invention relates to embolic protection device. More particularly, the invention relates to a bioabsorbable mesh-scaffold assembly that is suitable for implantation into a human body lumen, such as a blood vessel or a coronary artery.
BACKGROUND
[002] Bioabsorbable drug-eluting stents (DES) or scaffolds are preferred to prevent proliferation of smooth muscle cells (SMCs) present in an arterial wall. These scaffolds prevent the proliferation of SMCs with a controlled release of antiproliferative drugs coated on their outer surfaces. The prevention of proliferation of SMCs in turn drastically reduces the rate of in-stent restenosis.
[003] Despite the above advantages, there are a few challenges/side effects of using these scaffolds in body lumens like coronary arteries, etc. For example, an accidental injury of the arterial walls is possible due to direct contact of scaffold’s struts with an arterial wall. Further, a major safety concern in using these stents is delayed healing of the endothelial wound. A likely reason for the same is inhibition of endothelial cell (EC) proliferation and migration property of the antiproliferative drug used in the stent. Moreover, there are high chances of distal embolization after implantation of such scaffolds due to thrombus fragmentation and protrusion by one or more scaffold struts. The thrombus or emboli from scaffold has resulted in administration of prophylactic drugs i.e. prasugrel, clopidogrel, etc. However, such administration has many side effects including myelotoxicity, syncope, ulcers and skin rashes.
[004] Therefore, a preventive strategy having a preventive approach with pharmacological and/or technical advancement is required to address the complication of stenting of arterial walls.
SUMMARY
[005] In an embodiment of the present disclosure, a bioabsorbable mesh-scaffold assembly is disclosed. The bioabsorbable mesh-scaffold assembly includes a bioabsorbable scaffold having an outer surface to be implanted in a human arterial vasculature and an expandable bioabsorbable mesh mounted coaxially on the outer surface of the bioabsorbable scaffold, the expandable bioabsorbable mesh may be made of a single monofilament. The bioabsorbable mesh-scaffold assembly may have a low crimp profile configured for insertion into the human arterial vasculature. The bioabsorbable mesh-scaffold assembly may have a low crimp profile in ranges of 1.2 mm to 1.4 mm. The expandable bioabsorbable mesh is knitted with a monofilament using a circular weft knitting machine. The monofilament is extruded from a bioabsorbable polymer. In an embodiment the monofilament extrusion include blending of bioabsorbable polymer and at least one therapeutic agent to release the therapeutic agent for long duration. The diameter of the monofilament used may be in a ranges of 25-30µm. In another embodiment, the extruded monofilament is annealed to increase the strength required for knitting process. The annealing of the extruded monofilament includes annealing under vacuum in the range of 115° C to 125° C temperature for a duration ranging from 60-120 minutes.
[006] The disclosed bioabsorbable mesh-scaffold assembly is equipped with at least one of a multiplicity of benefits over a conventional arterial stent. For example, the bioabsorbable mesh is completely absorbable inside the body lumen in 5-6 months. Further, the bioabsorbable mesh-scaffold assembly prevents plaque from getting into the blood stream to cause embolism, since the bioabsorbable mesh includes small openings (sizes indicated below) to hold detached plaque in place. In an embodiment of the arterial invention, use of a bioabsorbable mesh replaces the use of an embolism protection device during scaffold implantation. In an embodiment of the invention, the bioabsorbable mesh-scaffold assembly provides more comprehensive and effective pharmacological assistance to a treated area than conventional stents. In some embodiments of the invention, the bioabsorbable mesh-scaffold assembly is optimized to encourage endothelial cell growth and migration (due to low crimped diameter 1.2mm to 1.4mm) at sufficiently high concentrations to SMCs to prevent restenosis while simultaneously maintaining a sufficiently low drug concentration at the endothelial cell surface to allow sufficiently rapid endothelial wound closure.
BRIEF DESCRIPTION OF THE DRAWINGS
[007] 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.
[008] FIG. 1: illustrates an exemplary embodiment of a bioabsorbable mesh-scaffold assembly.
[009] FIG. 1A: illustrates an exemplary embodiment of an expandable bioabsorbable mesh.
[0010] FIG. 2A: illustrates an exemplary flowchart depicting a process of manufacturing a bioabsorbable mesh-scaffold assembly.
[0011] FIG. 3 illustrates the steps of an exemplary embodiment of the annealing process of an extruded monofilament.
[0012] FIG. 4A illustrates an exemplary embodiment of a knitting head in open mode with needle slotting, used in knitting the expandable bioabsorbable mesh of FIG. 1.
[0013] FIG. 4B illustrates perspective view of an exemplary embodiment of 48-teeth timing pulley in open mode used in a circular weft knitting machine.
[0014] FIG. 5 illustrates an exemplary process of mounting the expandable bioabsorbable mesh of FIG. 1 to the outer surface of a scaffold.
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, 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] Wherever possible, same reference numbers will be used throughout the drawings to refer to same or like parts. Moreover, references to various elements described herein are made collectively or individually when there may be more than one element of the same type. However, such references are merely exemplary in nature. It may be noted that any reference to elements in the singular may also be construed to relate to the plural and vice-versa without limiting the scope of the disclosure to the exact number or type of such elements unless set forth explicitly in the appended claims.
[0017] 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. In the present description and claims, the term proximal end refers to an end of an element that is closer to a user while the distal end refers to an end of the element which is farther from the user.
[0018] The words “bioabsorbable” and “biodegradable” can be interchangeably used and refer to bioabsorbable nature of a stent.
[0019] “Monofilament” refers to a single strand of a bioabsorbable/ biodegradable polymer.
[0020] “Elongation” refers to a fracture strain and is a ratio of initial length (before breakage) to changed length (after breakage) of monofilament.
[0021] ‘Modulus’ refers to the ratio of tensile stress to tensile strain.
[0022] The present invention discloses a bioabsorbable mesh-scaffold assembly. The bioabsorbable mesh-scaffold assembly includes an expandable bioabsorbable mesh and a bioabsorbable scaffold. In an embodiment, the expandable bioabsorbable mesh is constructed by knitting an annealed monofilament. The expandable bioabsorbable mesh of the present invention is mounted on a bioabsorbable scaffold to form a bioabsorbable mesh-scaffold assembly. The bioabsorbable mesh-scaffold assembly of the present invention has a low crimp profile. In case of coronary application, the crimp profile of the biodegradable mesh-scaffold assembly is in the range of 1.2 mm -1.4 mm diameter. In case of peripheral application, the biodegradable mesh-scaffold assembly has a crimp profile of 2.0 mm - 2.2 mm diameter for easy access in body lumen.
[0023] FIG. 1 depicts an exemplary embodiment of a bioabsorbable mesh-scaffold assembly 100. In an embodiment, the bioabsorbable mesh 102 of the present invention may completely degrade inside the body lumen over a period of 5 to 6 months. The bioabsorbable mesh-scaffold assembly 100 may be formed by mounting an expandable bioabsorbable mesh 102 on a bioabsorbable scaffold 104.
[0024] The expandable bioabsorbable mesh 102 may coaxially cover the bioabsorbable scaffold 104 entirely. In another embodiment, the expandable bioabsorbable mesh 102 may coaxially cover only a portion of the bioabsorbable scaffold 104.
[0025] In an embodiment, the expandable bioabsorbable mesh 102 of the bioabsorbable mesh-scaffold assembly 100 has a predetermined shape with predefined dimensions. For example, the expandable bioabsorbable mesh 102 is barrel shaped with an aperture size of 200µ. Alternatively, the expandable bioabsorbable mesh 102 is cylindrical in shape with a uniform diameter. The expandable bioabsorbable mesh 102 may have a stitch length of 350µ. The specified stitch value of the expandable bioabsorbable mesh 102 may be in the range of 30 to 40. The thickness of the expandable bioabsorbable mesh 102 may be in the range of 28µm to 32µm.
[0026] As shown in FIG.1A, the expandable bioabsorbable mesh 102 includes without limitation, a proximal end 102a and a distal end 102b, and a porous body. The proximal end 102a and distal end 102b of the expandable bioabsorbable mesh 102 may have at least one mounting means (not shown) known in the art. The mounting means may aid in mounting the expandable bioabsorbable mesh 102 on the bioabsorbable scaffold 104. In one embodiment, the mounting means is a loose end of a monofilament with which the expandable bioabsorbable mesh 102 is constructed. In another embodiment, the mounting means is externally attached or sewn to the proximal end 102a and/or distal end 102b. Such mounting means may be made up of a material different from the material used in construction of the expandable bioabsorbable mesh 102.
[0027] Additionally, the expandable bioabsorbable mesh 102 has a porous body with a plurality of openings 102c. These openings 102c prevent embolic shower. The dimension of such openings 102c may be altered by changing the parameters of the knitting process. In an embodiment, the width and aperture size of openings 102c range from 100µ to 170µ and 200µ to 350µ respectively. Thus, debris larger than 100 µ and below 300 µ can be trapped.
[0028] In an embodiment, the expandable bioabsorbable mesh 102 is constructed by knitting a monofilament. The monofilament of the expandable bioabsorbable mesh 102 may be derived from granules/billets/pellets of a bioabsorbable polymer selected from a group consisting of poly lactic-co-polyglycolic ("PLGA"), or any other degradable co-polymeric combination, such as polycaprolactone ("PCL"), polygluconate, polylactic acid-polyethylene oxide copolymers, poly(hydroxybutyrate), polyanhydride, poly-phosphoester, poly(amino acids), poly-L-lactide, poly-D- lactide, polyglycolide, poly(alpha-hydroxy acid) and combinations thereof.
[0029] In an embodiment the bioabsorbable mesh 102 may be coated with at least one therapeutic agent including one or more of an antiproliferative drug, an antithrombin drug and an antiplatelet drug. In an exemplary embodiment the bioabsorbable mesh 102 may be coated with the antiproliferative drug - sirolimus.
[0030] In another embodiment, the bioabsorbable scaffold 104 may include an outer surface and an inner surface. The bioabsorbable scaffold 104 may be made up of Co-Cr, steel or bioabsorbable polymer including PDLA, PDLLA, PLCL, PLA, PLLA, PLGA, PGA or PCL and optionally a combination thereof. The bioabsorbable scaffold 104 may be coated with antiproliferative drug for example sirolimus, and elutes the drug from the outer surface.
[0031] FIG. 2A illustrates an exemplary process 200 of manufacturing a bioabsorbable mesh-scaffold assembly 100. In an embodiment, the bioabsorbable mesh-scaffold assembly 100 is a single unit formed by mounting the expandable bioabsorbable mesh 102 onto an outer surface of a bioabsorbable scaffold 104 (elaborated below). The exemplary process 200 broadly includes melting and extruding polymer granules to reduce their cross-section thereby forming a monofilament of said polymer. The said monofilament may then be knitted to form a mesh. The mesh is further mounted onto the scaffold thereby forming a “bioabsorbable mesh-scaffold assembly”.
[0032] In an exemplary embodiment, the process initiates with drying of polymer granules at step 210. The polymer granules may be any bioabsorbable polymer granules known in the art such as PLGA granules. The polymer granules may be dried to reduce and/or maintain the dryness of the polymer granules (prior to extrusion) to a maximum of 20 parts per million (ppm) or 0.002% moisture content. Alternatively, drying may be performed at the end of step 220.
[0033] In an embodiment, white to light tan coloured PLGA granules (85mol% L-lactide and 15mol% Glycolide) with IV range 1.80 dl/g - 2.50 dl/g are dried by using dry air at a dew point of 4°C for 16 hrs at 100°C temperature. The degradation time of 85:15 PLGA granules as used at step 210 is 5-6 months. However, the degradation time varies with variation in molar percentages of PLGA granules say, the degradation times of 50:50 PLGA and 75:25 PLGA, are 1–2 months and 4–5 months respectively.
[0034] At step 220, the polymer granules obtained from step 210 are extruded to form a monofilament. In an embodiment, the polymer granules may be directly employed for extrusion after drying. In an alternate embodiment, the extrusion process may be initiated by converting the PLGA granules obtained at step 210 into its powdered form by cryogenic grinding. The cryogenic grinding may be performed at -150 °C to -200 °C temperature amidst circulation of liquid nitrogen. The circulation of liquid nitrogen may help in keeping the temperature steady. The powdered PLGA may then be blended with an antiproliferative drug. In an embodiment, 1.0 to 1.5 % sirolimus drug powder may be blended with the powdered PLGA granules. Optionally, the powdered PLGA may be blended with at least one therapeutic agent including one or more of an antiproliferative drug, an antithrombin drug and an antiplatelet drug.
[0035] In both the above cases, the PLGA granules or the drug blended polymer granules are forced to flow through a die orifice under high pressure, say 600-700 mmHg to yield PLGA granules with reduced cross-section.
[0036] Extrusion of the polymer granules may be performed by any method known in the art such as in an extruder barrel. In an embodiment, the extruder barrel is composed of three heated zones where the polymer granules are plasticized first and then converted into melted polymer. In an embodiment, the heated zone 1 is maintained at temperature below the polymer melting point. For example, for PLGA granules, the temperature of heated zone 1 is about 210-220° C. The temperature of heated zone 2 and 3 is more than the temperature of heated zone 1. However, the temperature of heated zone 2 and 3 should not be maintained more than 40° C, more preferably, 25° C above the melting point of the polymer.
[0037] The melted polymer may further be processed with the help of for example, fine screen filters and breaker plate in order to maintain consistency of polymer. The melted polymer is then transferred to an apparatus say, a spinneret/die to reduce the cross-section area and finally yield a monofilament. In an embodiment, the spinneret/die has capillaries with 0.028 mm diameter and is maintained at the temperature of 20 °C to 40 °C.
[0038] Optionally, post extrusion, the obtained monofilament may be quenched via say, air quenched. The quenching of monofilament may prevent sudden changes of monofilament properties during cooling process. The temperature employed for quenching may range from 40°C to 60°C. The quenched monofilament is then stretched to obtain monofilament with desired dimensions. The quenched monofilament may be stretched with the help of, godet rolls. Stretching may be performed at a constant speed to form a finished monofilament. The diameter of the finished monofilament obtained from extrusion may have a diameter ranging from 28 µ to 32 µ.
[0039] At step 230, the extruded monofilament is annealed to yield an annealed monofilament. In an embodiment, the annealing temperature of the monofilament may be selected between PLGA polymer melting temperature and the glass transition temperature. The annealing process may aid in defining the lattice of monofilament and increase the strength of monofilament. Annealing also relieves internal stress of the monofilament and results in enhancement of its mechanical properties. Moreover, the annealing process helps in removing residual monomer from the monofilament. An exemplary annealing process in the context of the teachings of the present invention is described below in FIG. 3 description.
[0040] At step 240, the annealed monofilament is knitted to form the expandable bioabsorbable mesh 102. In an exemplary embodiment of the invention, the expandable bioabsorbable mesh 102 may optionally be knitted as closed interlocked design and/or an open interlocked design, or semi open design, or may be similar to the bioabsorbable scaffold 104 (described below).
[0041] In an embodiment, the annealed monofilament may be knitted using a circular weft knitting machine. In an alternate embodiment, the expandable bioabsorbable mesh 102 may be formed by warp knitting technology or by braiding or weaving one or more monofilaments together. The annealed monofilament may be knitted using a high density knitting head (elaborated in the description of FIG. 4). In an embodiment, a plurality of PET filaments may be utilized to initiate the knitting process. The use of PET filaments optimizes knitting set-up with required mesh specifications in terms of shape and design. On optimization of knitting parameters, the PET filaments are replaced with the annealed bioresorbable monofilament, having a diameter of 28 µ.
[0042] In an embodiment, the knitting head speed (RPM) ranges from 15% to 25%; the mesh traction speed (frequency) may be in the range of 15mm/min to 20mm/min. The initial fiber tension on the annealed monofilament may in the range of 25 to 40 grams during the knitting process. The post tension weight on the annealed monofilament during knitting may be in the range of 15 to 50 grams.
[0043] In an embodiment, the knitted expandable bioabsorbable mesh 102 may be further processed by heat treatment under controlled environmental condition to stabilize the knit structure and to relieve internal stress which helps in seamless expansion upon deployment.
[0044] At step 250, the expandable bioabsorbable mesh 102 is mounted on the outer surface of the bioabsorbable scaffold 104. Such mounting results in the formation of the bioabsorbable mesh-scaffold assembly 100. An exemplary mounting process in the context of the teachings of the present invention is described below in FIG. 5 description. At step 260, the bioabsorbable mesh-scaffold assembly 100 is crimped and packed. The bioabsorbable mesh-scaffold assembly 100 may be crimped onto a delivery catheter. The bioabsorbable mesh-scaffold assembly 100 may be crimped to allow easy access in a human body lumen or at specific sites (depending upon site of application inside human body). For example, in case of coronary application, the bioabsorbable mesh-scaffold assembly 100 may be crimped to 1.2 mm -1.4 mm diameter. For peripheral application, the bioabsorbable mesh-scaffold assembly 100 may be crimped to 2.0 mm - 2.2 mm diameter. For intracranial application, the bioabsorbable mesh-scaffold assembly 100 may have low profile compatible with 3F guide catheter.
[0045] For effective crimping, the crimping parameters may vary as per the bioabsorbable scaffold 104 dimensions/ size. In an embodiment, crimping is done in 6 to 8 stages with dwell time between 200 to 310 seconds. The crimping temperature may in the range of 35°C to 40°C. In the last stage of crimping process, a peel away barrier sheath may be placed on the bioabsorbable mesh-scaffold assembly 100. The barrier sheath may be incorporated during the crimping process to avoid the damage to the expandable bioabsorbable mesh 102 due to crimping jaws. After the crimping process, the barrier sheath is discarded. In an embodiment, the bioabsorbable mesh-scaffold assembly 100 mounted on the delivery catheter may again be protected by a second peel away protective sheath to prevent damage during storage and shipping.
[0046] The crimped bioabsorbable mesh-scaffold assembly 100 along with delivery catheter may then be packed and sealed in a multilayer protective pouch. The multilayer protective pouch may be made up of aluminium or a material selected from polyethylene, terephthalate, and peelable foil. In an embodiment, the sealed bioabsorbable mesh-scaffold assembly 100 along with delivery catheter may undergo a heat treatment in vacuum oven at 37°C for 10 to 30 minutes. The heat treatment of sealed bioabsorbable mesh-scaffold assembly 100 helps in setting/aligning expandable bioabsorbable mesh 102 over bioabsorbable scaffold 104 in a uniform manner.
[0047] At step 270, the sealed bioabsorbable mesh-scaffold assembly 100 and delivery catheter may be exposed to a radiation sterilization procedure. In another embodiment, the bioabsorbable mesh-scaffold assembly 100 along with delivery catheter may be sterilized using ethylene oxide gas exposure. In an embodiment, the radiation sterilization applied is e-beam radiation sterilization. The dose of e-beam irradiation may be in the range of 15 kGy to 40 kGy or in the range of 18 kGy and 23 kGy at a temperature between 15° C and 25° C. The e-beam dose affects only on polymeric material of packed device, i.e. bioabsorbable mesh-scaffold assembly 100 and not the delivery catheter.
[0048] In context to the present invention, some exemplary parameter variations before and after sterilization procedure are as follows:
[0049] The reduction in average molecular weight Mw of the expandable bioabsorbable mesh 102 post sterilization may be in the range of 35% to 50% depending upon the dose level. Table 1 depicts a comparative profile of the bioabsorbable mesh 102 prior and post sterilization.
Prior- Sterilization Post-Sterilization
Inherent viscosity (IV) Average molecular weight (Mw) Average Molecular mass (Mn) Inherent viscosity (IV) Average molecular weight (Mw) Average Molecular mass (Mn)
1.8 dl/g - 2.5 dl/g 220000 g/mol- 280000 g/mol 105000 g/mol- 135000 g/mol 1 dl/g-1.5 dl/g 110000 g/mol- 118000 g/mol 50000 g/mol and 65000 g/mol
Table 1
[0050] FIG. 3 depicts an exemplary annealing process 300 of the extruded monofilament. Prior to annealing, the monofilament is first wound onto a spool to form a monofilament spool. The process of annealing is then initiated at step 310 in which the monofilament spool may be pre-heated at 125°C for a period of 60 to 120 minutes in vacuum in an annealing chamber. In an embodiment, the annealing chamber is a closed chamber.
[0051] At step 320, an inert gas is purged for a predefined time duration (for example, 5 mins) to break the vacuum inside the annealing chamber. Inert gas used may be nitrogen gas, argon gas, helium gas, xenon gas etc. The purging of inert gas causes reduction in temperature inside the annealing chamber.
[0052] At step 330, a vacuum is again applied for a predefined time duration (1-8 minutes) and under predefined conditions (for example, at 115°C and 25psi). At step 340, the vacuum is released by opening of a valve in the annealing chamber.
[0053] Thereafter, the steps 320 to 340 are repeated for a predefined number of times sequentially to obtain desired characteristics in the monofilament. In an exemplary embodiment, the steps 320 and 340 may be repeated twice. The sequential and repeated introduction of inert gas followed by application of vacuum removes any trace of moisture that may have been introduced inside the annealing chamber.
[0054] Finally at step 350, 650 - 700mm Hg vacuum is applied in the annealing chamber for a predefined time duration (1-8 minutes) and under predefined conditions (for example, at 115°C and 25psi). In an embodiment, the annealing chamber is programmed to rotate 5 minutes clockwise and 5 minutes anticlockwise throughout the cycle time. At the end of the cycle time (60 minutes), the valve is opened for a predefined time duration (for example, 10 seconds) to release vacuum (corresponding change in internal pressure to atmospheric pressure).
[0055] The exemplary annealing process 300 may considerably enhance the properties of monofilament. For example, table 2 depicts a comparative profile of annealed and a non-annealed monofilament.
Annealed Monofilament Non-annealed Monofilament
Monofilament Diameter (mm) Break Load (lbf) Elongation (%) Modulus (ksi) Monofilament Diameter (mm) Break Load (lbf) Elongation (%) Modulus (ksi)
0.0274 0.097 44.3 771 0.0276 0.080 24.9 1162
0.0281 0.095 44.5 769 0.0279 0.079 24.1 1194
0.0276 0.092 43.0 694 0.0279 0.078 24.5 1299
0.0274 0.094 42.9 601 0.0281 0.077 26.9 1291
0.0276 0.094 42.0 618 0.0279 0.079 24.3 1096
Table 2
[0056] As depicted in Table 2, the annealed monofilament has greater break load and percentage elongation in comparison to non-annealed monofilament. The annealed monofilament has higher tensile strength and flexibility compared to non-annealed monofilament which is suitable for knitting process with high density knitting head.
[0057] FIG. 4A illustrates exemplary embodiments of a high density knitting head 400. The high density knitting head 400 rotates with 48-teeth pulley 450 to knit the monofilament into the bioabsorbable mesh 102. FIG. 4B illustrates exemplary embodiment of a 48-teeth timing pulley 450.
[0058] The high density knitting head 400 may have a plurality of needles ranging from 22-110 with a needle density ranging 0.016” - 0.025”. In an embodiment, the needles of the high density knitting head 400 may be selected from different types of needles. For example, the needle may have slender- straight sticks tapered to a point at one end and a knob at the other end. Alternatively, straight-double pointed knitting needles or double-pointed needles tapered at both ends may also be used. In an embodiment, during knitting the bioabsorbable mesh 102, one needle from a range of needles is active while the other needles hold the remaining active stitches. The needles used in the high density knitting head 400 may be selected on the basis of length, type and material of needles. For example, needles may be selected from plastic, aluminum, steel and nickel-plated brass. In an embodiment, the expandable bioabsorbable mesh 102 may be knitted with Groz-backert needle. The stitched length of the expandable bioabsorbable mesh 102 using the Groz-backert needle is around 350 µm.
[0059] FIG. 5 depicts the exemplary embodiment of mounting the expandable bioabsorbable mesh 102 on the outer surface of the bioabsorbable scaffold 104 to form the bioabsorbable mesh-scaffold assembly 100. In an embodiment, the expandable bioabsorbable mesh 102 may be affixed on the outer surface of the bioabsorbable scaffold 104 by a sewn procedure 500.
[0060] At step 510, the expandable bioabsorbable mesh 102 may be mounted on the outer surface of the bioabsorbable scaffold 104. At step 520, the expandable bioabsorbable mesh 102 may be first aligned coaxially on the outer surface of bioabsorbable scaffold 104. The coaxial alignment of expandable bioabsorbable mesh 102 on the outer surface of the bioabsorbable scaffold 104 may be performed by a plurality of surgeon’s knots. The surgeon’s knot may be formed by knotting the corresponding mounting means present on the respective proximal and distal ends of expandable bioabsorbable mesh 102 and bioabsorbable scaffold 104. The corresponding mounting means of expandable bioabsorbable mesh 102 and bioabsorbable scaffold 104 may be knotted to each other by using specialized instruments like micro-forceps etc.
[0061] At step 530, the coaxially aligned expandable bioabsorbable mesh 102 and bioabsorbable scaffold 104 may then be affixed with each other by using a plurality of stitches. The one or more of plurality of stitches may pass from each opening 102c of expandable bioabsorbable mesh 102 and through each struts of bioabsorbable scaffold 104. The stitching may be performed by a monofilament. The stitching monofilament may pass through the opening 102c of expandable bioabsorbable mesh 102 and may create a plurality of loops to secure it around the outer surface of bioabsorbable scaffold 104.
[0062] The stitching material used in sewn process may be composed of any polymer material including but not limited to the same material used to create the bioabsorbable mesh 102. In one embodiment, tweezers are used to align the expandable bioabsorbable mesh 102 on the bioabsorbable scaffold 104. In another embodiment, the coaxial association of expandable bioabsorbable mesh 102 and bioabsorbable scaffold 104 may include the bioabsorbable mesh100 being adhered, glued to the bioabsorbable scaffold 104.
[0063] The present invention will be further understood by reference to the following non-limiting examples.
EXAMPLE 1:
[0064] White to light tan coloured purasorb PLGA granules with 85mol% L-lactide and 15mol% glycolide having Inherent viscosity range of 1.80 dl/g - 2.5 dl/g were used for extrusion. The melting point ranged between 126 °C to 145 °C. The extruded monofilament was annealed at 125°C for 60 minutes under vacuum condition and then stored at ambient temperature in vacuum condition for half an hour. The monofilament is stored in a refrigerator at 0°C (±15° C) prior to knitting process.
[0065] The annealed monofilament was then used for knitting process. To knit the mesh using a circular weft knitting machine, the machine was first optimized for knitting parameters using 10-20 denier PET multi-filaments. On optimization knitting parameters, PET multifilament was switched over to a 28 µm monofilament to create the expandable bioabsorbable mesh. The expandable bioabsorbable mesh with a stitch length of around 350 µm and diameter of 3.0 mm was created with the following parameters; i) Stitch value ranging from 30 to 45, ii) post monofilament tension weight from 10gms - 45gms, iii) machine speed 10% - 20%. A heat treatment of knitted expandable bioabsorbable mesh between 115 °C and 125 °C for 60 minutes was then performed to stabilize the knit structure and relieve internal stress in monofilament.
[0066] The knitted expandable bioabsorbable mesh was mounted on partially expanded bioabsorbable scaffold. The proximal and distal ends of expandable bioabsorbable mesh were then secured by surgeon’s knot present on the corresponding proximal and distal ends of bioabsorbable scaffold with the help of micro forceps. A PLGA monofilament of same diameter as of monofilament i.e. 28µ was used for knotting process as well. The PLGA monofilament was passed through the holes of expandable bioabsorbable mesh 102 and plurality of loops, for securing the bioabsorbable mesh on bioabsorbable scaffold. The bioabsorbable mesh-scaffold assembly was then crimped to achieve reduced diameter of 1.2 mm to 1.4 mm crimp profile using crimping machine (Make: Machine Solutions, USA & Model SC775S). During crimping process, a barrier sheath was placed on the bioabsorbable mesh-scaffold assembly to avoid damage of bioabsorbable mesh. To pack the bioabsorbable mesh-scaffold assembly along with delivery catheter the barrier sheath was discarded and was again protected by peel-away PTFE sheath. The bioabsorbable mesh-scaffold assembly along with delivery catheter was then packed in aluminium pouch. The device was further subjected to e-beam sterilization. The finished product was then tested for mechanical and analytical aspects. The recoil of bioabsorbable mesh-scaffold assembly was found to be not more than 5% and the dislodgement force was as high as 3N.
EXAMPLE 2:
[0067] The knitting process of the expandable bioabsorbable mesh used in the present example is same as mentioned in Example 1. A bioabsorbable scaffold coated with 1:1 Sirolimus drug and polymer ratio was used.
[0068] The knitted expandable bioabsorbable mesh was mounted on partially expanded bioabsorbable scaffold and secured by a PLGA monofilament with the help of surgeon’s knot using micro forceps. PLGA monofilament of 28µ diameter was used for knotting process. The PLGA monofilament was passed through the pores of knitted bioabsorbable mesh. The bioabsorbable mesh-scaffold assembly was then crimped to achieve a reduced diameter of 1.2 mm to 1.4 mm crimp profile by using crimping machine (Make : Machine Solutions, USA& Model SC775S). During crimping process, barrier sheath was placed on the bioabsorbable mesh-scaffold assembly to avoid damage. To pack the bioabsorbable mesh-scaffold assembly along with delivery catheter the barrier sheath was discarded and was again protected by peel-away PTFE sheath. The bioabsorbable mesh-scaffold assembly along with delivery catheter was then packed in aluminium pouch. The aluminium pouch contacting the bioabsorbable mesh-scaffold assembly along with delivery catheter was then kept for heat treatment at 37°C for 10 minutes in a hot air oven. The packed bioabsorbable mesh-scaffold assembly along with delivery catheter was further subjected to e-beam sterilization.
[0069] The bioabsorbable mesh disclosed in the present invention can be used in various clinical applications which may include by way of non-limitation to coronary, peripheral, intracranial, carotid and renal implants.
[0070] In view of the many possible embodiments to which the principles of the disclosed invention may be applied, it should be recognized that the illustrated embodiments are only preferred examples of the invention and should not be taken as limiting the scope of the invention. Rather, the scope of the invention is defined by the following claims.