US010471211B2 United States Patent (10 ) Patent No.: US 10,471,211 B2 Rusch et al. (45 ) Date of Patent: Nov. 12 , 2019 ( 54 ) MEDICAL DELIVERY DEVICE WITH A61M 2005/31506 ; A61M 2205/0216 ; LAMINATED STOPPER A61M 2205/0222 ; A61M 2205/0238 ; A61L 31/048 ( 71 ) Applicant: W.L. Gore & Associates, Inc., Newark , See application file for complete search history. DE (US ) ( 56 ) References Cited ( 72 ) Inventors : Greg Rusch , Newark , DE (US ) ; Robert C. Basham , Forest Hill , MD U.S. PATENT DOCUMENTS (US ) 5,374,473 A 12/1994 Knox et al . 5,708,044 A 1/1998 Branca ( 73 ) Assignee : W. L. Gore & Associates, Inc., 5,792,525 A 8/1998 Fuhr et al. Newark , DE (US ) ( Continued ) ( * ) Notice: Subject to any disclaimer , the term of this patent is extended or adjusted under 35 FOREIGN PATENT DOCUMENTS U.S.C. 154 (b ) by 0 days . WO WO2014 / 196057 12/2014 WO WO2015 /016170 2/2015 ( 21) Appl. No .: 15 /404,892 OTHER PUBLICATIONS ( 22 ) Filed : Jan. 12 , 2017 International Search Report PCT/ US2017 /013297 dated May 16 , (65 ) Prior Publication Data 2017 . US 2017/0203043 A1 Jul. 20 , 2017 Primary Examiner Lauren P Farrar Related U.S. Application Data ( 74 ) Attorney , Agent, or Firm — Amy L. Miller (60 ) Provisional application No.62 / 279,553, filed on Jan. ( 57 ) ABSTRACT 15 , 2016 . The present disclosure relates to a medical delivery device that includes a barrel having an inner surface , a plunger rod ( 51 ) Int. Cl. having a distal end inserted within the barrel , and a stopper A61M 5/315 ( 2006.01) attached to the distal end of the plunger rod and contacting A61L 31/04 ( 2006.01) at least a portion of the inner surface of the barrel . In at least A61M 5/31 ( 2006.01) one embodiment, the inner surface is hydrophilic . The (52 ) U.S. CI. stopper may include an elastomeric body, one or more CPC A61M 5/31505 (2013.01 ) ; A61L 31/048 fluoropolymer layers , and two or more ribs laminated with (2013.01 ) ; A61M 5/31513 ( 2013.01) ; A61M the one or more fluoropolymer layers . In some embodi 2005/3101 ( 2013.01) ; A61M 2005/31506 ments , the contact width between at least one rib having a ( 2013.01 ) ; A61M 2205/0216 (2013.01 ) ; sealing surface and the portion of the inner surface of the ( Continued ) barrel measured at a compressibility of greater than about (58 ) Field of Classification Search 7.9 % of the stopper is less than about 1.0 mm . CPC A61M 5/31511; A61M 5/31513 ; A61M 5/315 ; A61M 5/31505 ; A61M 2005/3101; 27 Claims, 6 Drawing Sheets 100 -125 150 130 US 10,471,211 B2 Page 2 ( 52 ) U.S. CI. CPC A61M 2205/0222 (2013.01 ) ; A61M 2205/0238 ( 2013.01 ) (56 ) References Cited U.S. PATENT DOCUMENTS 6,030,694 A 2/2000 Dolan et al . 6,541,589 B1 4/2003 Baillie 7,521,010 B2 4/2009 Kennedy et al. 7,531,611 B2 5/2009 Sabol et al. 8,637,144 B2 1/2014 Ford 8,658,707 B2 2/2014 Xu et al. 8,722,178 B2 5/2014 Ashmead et al . 9,139,669 B2 9/2015 Xu et al . 2011/0137263 A1 6/2011 Ashmead et al. 2012/0251748 A1 * 10/2012 Ashmead A61M 5/31513 428 / 34.7 2015/0148751 A1 * 5/2015 Yotsutsuji A61M 5/31513 604/218 2016/0015898 A1 * 1/2016 Jones A61M 5/31513 604/230 2016/0022918 Al 1/2016 Gunzel * cited by examiner U.S. Patent Nov. 12 , 2019 Sheet 1 of 6 US 10,471,211 B2 115 -15 130 20 45 40 60 50 30 35 55 95 85 105 100 25 120 FIG . 1 U.S. Patent Nov. 12 , 2019 Sheet 2 of 6 US 10,471,211 B2 21 140 130 125 FIG . 2 100 125 Itt 150 } 145 130 FIG . 3 U.S. Patent Nov. 12 , 2019 Sheet 3 of 6 US 10,471,211 B2 100 125 150 } 145 ???????? 130 160 FIG . 4 100 125 165 150 - 145 130 FIG . 5 U.S. Patent Nov. 12 , 2019 Sheet 4 of 6 US 10,471,211 B2 100 125 175 180 130 FIG . 6 100 -125 175 180 130 FIG . 7 U.S. Patent Nov. 12 , 2019 Sheet 5 of 6 US 10,471,211 B2 100 170 125 130 190 FIG . 8 100 125 170 175 180 130 195 FIG . 9 U.S. Patent Nov. 12 , 2019 Sheet 6 of 6 US 10,471,211 B2 100 225 ( x ) 220 ( c ) 230 (r ) (c ) 220 205 -230 240 220 210 FIG . 10A (c % ) = V x 100 100 215 225 (w ). obs ( ) -220 -230 -220 205 240 -230 130 220 240 210 FIG . 10B US 10,471,211 B2 1 2 MEDICAL DELIVERY DEVICE WITH ably low break loose and slide forces ( i.e. , low - friction LAMINATED STOPPER slidability ) but not so much contact that the fluoropolymer film is distorted to create leak paths that decrease air and FIELD liquid impermeability . 5 The present invention relates to a medical delivery device SUMMARY with a laminated stopper , and in particular , to a medical delivery device with a stopper laminated with a fluoropo One embodiment relates to a medical delivery device that lymer film . includes a barrel , a plunger rod having a distal end inserted 10 within the barrel , a stopper attached to the distal end of the BACKGROUND plunger rod and contacting at least a portion of the inner surface of the barrel. The stopper has an elastomeric body, Medical delivery devices such as syringes typically one or more fluoropolymer layers , and two or more ribs include a barrel, a plunger rod reciprocally movable in the laminated with the one or more fluoropolymer layers . A barrel, and a stopper attached to an end of the plunger rod . 15 contact width between at least one of the two or more ribs The stopper to be used for the syringe is typically air, and having a sealing surface and a portion of the inner surface of liquid impermeable while also possessing low - friction slid the barrel measured at a compressibility of greater than ability . Air and liquid impermeability is important for elimi about 7.9 % of the stopper is less than about 1.0 mm . In at nating liquid leakage within the barrel and the introduction least one embodiment, the barrel has a hydrophilic inner of air between an outer face of the stopper and an inner wall 20 surface . Optionally , the hydrophilic inner surface is bare of the barrel when charging or discharging the liquid inside glass ( e.g., free or substantially free of silicone oil ) . the syringe . Low - friction slidability is important for facili In some embodiments, the medical delivery device further tating the charging and discharging of the liquid inside the includes a sliding surface that is less than about 2.0 mm , syringe. In addition to these requirements , a medical which is calculated based on a sum of the contact widths syringe, in particular, must not, adversely affect any phar- 25 between at least one of the two or more ribs having a sealing maceutical composition such as biopharmaceuticals that surface and the portion of the inner surface of the barrel come in contact with the syringe ( e.g. , a pre - filled syringe measured at a compressibility of greater than about 7.9 % . comprising a pharmaceutical composition ). In some embodiments , at least one of: each rib of the two Stoppers for conventional syringes are commonly made or more ribs having a sealing surface includes a radius of of a rubber material such as natural rubber , isoprene rubber 30 curvature at an apex of each respective rib that is less than or styrene -butadiene rubber which may be vulcanized . about 0.22 mm ; and a ratio of a maximum outer diameter of Although this type of conventional stopper, has satisfactory all the ribs having a sealing surface to an inner diameter of air and liquid impermeability , it does not have good low the inner surface of the barrel is nominally greater than about friction slidability . Accordingly , silicone lubricants are typi 1.08 . cally applied to both the outer face of the stopper and the 35 In some embodiments , a maximum outer diameter of the inner wall of the barrel such that the stopper can slide within ribs having a sealing surface is greater than about 5.0 mm , the barrel. However , syringes comprising silicone lubricants an inner diameter of the inner surface of the barrel is cannot be used for pharmaceutical composition and the like nominally between about 4.65 and about 11.85 mm , and a because the silicone lubricant can cause inactivation or ratio of the maximum outer diameter of the ribs having a otherwise impact the efficacy of these pharmaceutical com- 40 sealing surface to an inner diameter of the inner surface of positions. Therefore , in order to maintain the stability of the the barrel is greater than about 1.08 . pharmaceutical composition , stoppers laminated with a fluo In another embodiment, a plunger rod includes a distal ropolymer film have been used . Since the air and liquid end that is insertable into a barrel and a stopper attached to impermeability of stoppers may also have an impact on the the distal end . In one or more embodiment, the barrel has a quality and stability of the pharmaceutical compositions , the 45 hydrophilic inner surface. The stopper is configured to stoppers laminated with a fluoropolymer film are required to contact at least a portion of the inner surface of the barrel.