# US 10,478,530 B2 · Thin strut stent from bioabsorbable polymer with high fatigue and radial strength and method to manufacture thereof > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,478,530 B2 - Document ID: US10478530B2 - Status: Granted - Kind: B2 - Application number: 15/031,804 - Filed: 2014-11-20 - Published: 2016-08-25 - Granted: 2019-11-19 - Earliest claimed: 2014-07-07 - Assignees: Meril Life Sciences Pvt Ltd. - Applicants: Meril Life Sciences Pvt. Ltd. - Inventors: Rajnikant Gandalal Vyas; Pramod Kumar Minocha; Deveshkumar Mahendralal Kothwala - Web page: https://patentgrep.com/patent/US10478530B2 ## CPC - A61L 31/06: obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds {(A61L31/041 takes precedence)} - A61F 2/915: with bands having a meander structure, adjacent bands being connected to each other - A61L 31/14: Materials characterised by their function or physical properties {, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials} - A61L 31/148: {Materials at least partially resorbable by the body} - A61L 31/18: Materials at least partially X-ray or laser opaque - B29C 49/18: using several blowing steps (B29C49/16 takes precedence) - B29C 49/4273: {Auxiliary operations after the blow-moulding operation not otherwise provided for} - B29C 49/6472: {in several stages} - B29C 55/22: of tubes {(B29C61/08 takes precedence)} - B29C 65/56: using mechanical means {or mechanical connections, e.g. form-fits} - B29C 66/534: {Joining single elements to open ends of tubular or hollow articles or to the ends of bars} - A61F 2002/91558: {connected peak to peak} - A61F 2002/91575: {connected peak to trough} - B05B 13/00: Machines or plants for applying liquids or other fluent materials to surfaces of objects or other work by spraying, not covered by groups B05B1/00 - B05B11/00 (means for supplying or discharging liquid or other fluent material for this purpose, see the relevant one of groups B05B1/00 - B05B12/00; processes for applying liquids or other fluent materials to surfaces in general B05D) - B29K 2667/046: {PLA, i.e. polylactic acid or polylactide} - B29L 2031/7534: {Cardiovascular protheses} - A61L: METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES (preservation of bodies or disinfecting characterised by the agents employed A01N; preserving, e.g. sterilising, food or foodstuffs A23; preparations for medical, dental or toiletry purposes A61K) - A61F: FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS (dental prosthetics A61C) - B29C: SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING (making preforms B29B11/00; making laminated products by combining previously unconnected layers which become one product whose layers will remain together B32B37/00 - B32B41/00) - B05B: SPRAYING APPARATUS; ATOMISING APPARATUS; NOZZLES (spray-mixers with nozzles B01F25/72; processes for applying liquids or other fluent materials to surfaces by spraying B05D) - B29K: INDEXING SCHEME ASSOCIATED WITH SUBCLASSES B29B, B29C OR B29D, RELATING TO MOULDING MATERIALS OR TO MATERIALS FOR {MOULDS, } REINFORCEMENTS, FILLERS OR PREFORMED PARTS, e.g. INSERTS - B29L: INDEXING SCHEME ASSOCIATED WITH SUBCLASS B29C, RELATING TO PARTICULAR ARTICLES ## Abstract This invention discloses method of manufacture of balloon expandable stent made from bioabsorbable polymer with thin struts (strut thickness 130 μm or less, preferably 100-110 μm) with high fatigue and radial strength. The invention further discloses balloon expandable stent made from bioabsorbable polymer with thin struts (strut thickness 130 μm or less, preferably 100-110 μm) with high fatigue and radial strength. ## Claims ### Claim 1 A process for preparation of a biodegradable polymer stent made of PLLA (poly-L-Lactide) with a strut thickness of less than 130 μm, comprising: (a) Deforming an extruded PLLA tube axially at a temperature of 70° C. to 80° C. by applying an axial force until a desired stretch is achieved; (b) radially expanding the tube at a temperature of 70° C. to 80° C. by pressurizing the tube with inert gas in three stages, including sequentially: i. pressurizing at a pressure of 250-280 psi in a first stage, ii. pressurizing at a pressure of 375-410 psi in a second stage, and iii. pressurizing at a pressure of 500-530 psi in a third stage; (c) heating the tube to a temperature between 100° C. and 110° C. after radial expansion under pressure for up to 2 min, and then cooling the tube to 20° C. in 20-30 sec to get a finished deformed tube; (d) Cutting a scaffold structure pattern on the deformed tube by laser machining to obtain a stent; (e) Annealing the laser machined stent and depositing radio opaque markers on the stent; (f) Cleaning the annealed stent with radio opaque markers using a solvent to remove irregularities and to achieve a smooth surface; (g) optionally coating the cleaned stent with a formulation of an antiproliferative drug and a carrier polymer by spray coating; (h) Crimping the cleaned stent on a balloon of a pre-sterilized delivery catheter in a clean environment to form a crimped stent system; and (i) Sterilizing the crimped stent system by an e-beam method with an e-beam dose less than 20 kGy. ### Claim 2 (depends on 1) The process for preparation of biodegradable polymer stent made of PLLA according to claim 1, wherein the extruded PLLA tube is made of PLLA having a Mw in the range of 590000 to 620000, a Mn in the range of 350000 to 370000, and crystallinity in the range of 7% to 12%. ### Claim 3 (depends on 1) The process according to claim 1, wherein the axial deformation of the tube is carried out at temperature between 74° C. and 76° C. at axial expansion ratio between 1.4 and 1.7 and maintaining the temperature and pressure conditions for 15-20 sec. ### Claim 4 (depends on 1) The process according to claim 1, wherein the radial deformation of the tube is carried out at temperature between 74° C. and 76° C. at radial deformation ratio between 3 and 5 by pressurizing the tube with nitrogen in three stages and maintaining the temperature and pressure conditions for 15-20 sec at each pressurization stage. ### Claim 5 (depends on 1) The process according to claim 1, wherein the tube after radial deformation, while maintaining the pressure, is heated between 100° C. and 110° C. and maintained for 30 sec to 2 min and then cooled to 20° C. in 20-30 sec to get finished deformed tube. ### Claim 6 (depends on 1) The process according to claim 1, wherein the laser cutting operation of the finished deformed tube is done at wave length between 1300 and 1600 nm. ### Claim 7 (depends on 1) The process according to claim 1, wherein the scaffold structure of the stent comprises a pattern with rows of struts with sinusoidal shape wherein the peaks of one row is aligned with valleys of the subsequent row and wherein, the valley of one row is connected by straight crosslinking struts with peak of subsequent row at every third such position in the central portion and at every peak and valley in the end portions. ### Claim 8 (depends on 1) The process according to claim 1, wherein the annealing is done at temperature between 100° C. and 110° C. for a period varying from 3 hours to 4 hours under vacuum of up to 650 to 700 mm Hg followed by cooling the stent to ambient temperature in 25-30 sec. ### Claim 9 (depends on 1) The process according to claim 1, wherein the cleaning of the annealed stent is done by rotation in perchloro ethylene as such or diluted in a suitable solvent or in a mixture of isopropyl alcohol and chloroform. ### Claim 10 (depends on 1) The process according to claim 1, wherein six radio opaque markers made from platinum with triaxial ellipse shape are fixed on the cross linking struts, wherein the said markers are equi-spaced at 120° to each other. ### Claim 11 (depends on 1) The process according to claim 1, wherein the stent is coated with a formulation comprising Sirolimus and a biodegradable polymer in a 50:50 proportion w/w, at a Sirolimus dose of 1.25 μg per mm2 of the stent surface area. ### Claim 12 (depends on 11) The process according to claim 11, wherein the coating is done using spray coating. ### Claim 13 (depends on 1) The process according to claim 1, wherein the cleaned stent is crimped on the pre-sterilized balloon of the delivery catheter under clean atmosphere at 25° C. to 40° C. in 6-8 stages and dwell time of 200-310 sec. ### Claim 14 (depends on 1) The process according to claim 1, wherein the stent is sterilized using process steps as under: a) subjecting the components other than the stent to ETO sterilization process; b) crimping the un-sterilized stent on a balloon of the pre-sterilized catheter in a clean environment; and c) subjecting the crimped stent system to e-beam sterilization at dose between 6 and 12 kGy, preferably between 6 and 10 kGy at temperature between 15° C. and 25° C. ### Claim 15 (depends on 14) The process according to claim 14, wherein the sterilization process results in a bio burden of less than 3 cfu and a Sterility Assurance Level (SAL) of 10−6 with no effect on the optical rotation or crystallinity. ### Claim 16 (depends on 1) The process according to claim 1, wherein the stent has a strut thickness of 100-110 μm and a strength of 20-25N. ### Claim 17 (depends on 1) The process according to claim 1, wherein step (d) comprises annealing the laser machined stent prior to depositing the radio opaque markers on the stent. ### Claim 18 (depends on 1) The process according to claim 1, wherein step (d) comprises annealing the laser machined stent after depositing the radio opaque markers on the stent. ### Claim 19 A process for preparation of a biodegradable polymer stent made of PLLA (poly-L-Lactide) with a strut thickness of less than 130 μm, comprising: (a) deforming an extruded PLLA tube axially at a temperature of 70° C. to 80° C. by applying an axial force until a desired stretch is achieved; (b) radially expanding the tube at a temperature of 70° C. to 80° C. by pressurizing the tube with inert gas in three stages, including sequentially: i. pressurizing at a pressure of 250-280 psi in a first stage, ii. pressurizing at a pressure of 375-410 psi in a second stage, and iii. pressurizing at a pressure of 500-530 psi in a third stage; (c) cutting a scaffold structure pattern on the radially expanded tube by laser machining to obtain a stent; and (d) crimping the stent on a balloon of a delivery catheter. ### Claim 20 (depends on 19) The process according to claim 19, further comprising at least one of: i) after cutting the scaffold structure, annealing the laser machined stent; and coating the annealed stent with a formulation of an antiproliferative drug and a carrier polymer; and ii) after crimping the stent on the balloon, sterilizing the crimped stent system by an e-beam method with an e-beam dose less than 20 kGy.