US 20170203043A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2017/0203043 A1 Rusch et al. (43) Pub. Date: Jul. 20, 2017 (54) MEDICAL DELIVERY DEVICE WITH (52) U.S. Cl. LAMINATED STOPPER CPC ....... A61M 5/31505 (2013.01); A6IL 31/048 (2013.01); A61M 2005/3101 (2013.01) (71) Applicant: W. L. Gore & Associates, Inc., Newark, DE (US) (72) Inventors: Greg Rusch, Newark, DE (US); (57) ABSTRACT Robert C. Basham, Forest Hill, MD (US) The present disclosure relates to a medical delivery device (21) Appl. No.: 15/404,892 that includes a barrel having an inner Surface, a plunger rod having a distal end inserted within the barrel, and a stopper (22) Filed: Jan. 12, 2017 attached to the distal end of the plunger rod and contacting at least a portion of the inner surface of the barrel. In at least Related U.S. Application Data one embodiment, the inner surface is hydrophilic. The (60) Provisional application No. 62/279,553, filed on Jan. stopper may include an elastomeric body, one or more 15, 2016. fluoropolymer layers, and two or more ribs laminated with the one or more fluoropolymer layers. In some embodi Publication Classification ments, the contact width between at least one rib having a (51) Int. Cl. sealing Surface and the portion of the inner Surface of the A6M 5/35 (2006.01) barrel measured at a compressibility of greater than about A6IL 3L/04 (2006.01) 7.9% of the stopper is less than about 1.0 mm. O y 95 25 85 105 0 Patent Application Publication Jul. 20, 2017 Sheet 1 of 6 US 2017/0203043 A1 1.O. : W. W. 70 95 2s. 85 105 do y 3S 2 FG, Patent Application Publication Jul. 20, 2017 Sheet 2 of 6 US 2017/0203043 A1 FG, 2 FG 3 Patent Application Publication Jul. 20, 2017 Sheet 3 of 6 US 2017/0203043 A1 5 FG, 5 Patent Application Publication Jul. 20, 2017 Sheet 4 of 6 US 2017/0203043 A1 FG, 8 170 Patent Application Publication Jul. 20, 2017 Sheet 5 of 6 US 2017/0203043 A1 Patent Application Publication Jul. 20, 2017 Sheet 6 of 6 US 2017/0203043 A1 FG, OA FG, OB US 2017/0203043 A1 Jul. 20, 2017 MEDICAL DELIVERY DEVICE WITH Surface of a barrel of a glass or resin Syringe to achieve high LAMINATED STOPPER levels of air and liquid impermeability while also maintain ing acceptably low break loose and slide forces (i.e., low FIELD friction slidability) but not so much contact that the fluo ropolymer film is distorted to create leak paths that decrease 0001. The present invention relates to a medical delivery air and liquid impermeability. device with a laminated stopper, and in particular, to a medical delivery device with a stopper laminated with a fluoropolymer film. SUMMARY 0006. One embodiment relates to a medical delivery BACKGROUND device that includes a barrel, a plunger rod having a distal 0002 Medical delivery devices such as syringes typically end inserted within the barrel, a stopper attached to the distal include a barrel, a plunger rod reciprocally movable in the end of the plunger rod and contacting at least a portion of the barrel, and a stopper attached to an end of the plunger rod. inner surface of the barrel. The stopper has an elastomeric The stopper to be used for the Syringe is typically air, and body, one or more fluoropolymer layers, and two or more liquid impermeable while also possessing low-friction slid ribs laminated with the one or more fluoropolymer layers. A ability. Air and liquid impermeability is important for elimi contact width between at least one of the two or more ribs nating liquid leakage within the barrel and the introduction having a sealing Surface and a portion of the inner Surface of of air between an outer face of the stopper and an inner wall the barrel measured at a compressibility of greater than of the barrel when charging or discharging the liquid inside about 7.9% of the stopper is less than about 1.0 mm. In at the syringe. Low-friction slidability is important for facili least one embodiment, the barrel has a hydrophilic inner tating the charging and discharging of the liquid inside the surface. Optionally, the hydrophilic inner surface is bare Syringe. In addition to these requirements, a medical glass (e.g., free or Substantially free of silicone oil). Syringe, in particular, must not, adversely affect any phar 0007. In some embodiments, the medical delivery device maceutical composition Such as biopharmaceuticals that further includes a sliding surface that is less than about 2.0 come in contact with the Syringe (e.g., a pre-filled Syringe mm, which is calculated based on a sum of the contact comprising a pharmaceutical composition). widths between at least one of the two or more ribs having 0003 Stoppers for conventional syringes are commonly a sealing Surface and the portion of the inner Surface of the made of a rubber material such as natural rubber, isoprene barrel measured at a compressibility of greater than about rubber or styrene-butadiene rubber which may be vulca 7.9%. nized. Although this type of conventional stopper, has sat 0008. In some embodiments, at least one of each rib of isfactory air and liquid impermeability, it does not have good the two or more ribs having a sealing Surface includes a low-friction slidability. Accordingly, silicone lubricants are radius of curvature at an apex of each respective rib that is typically applied to both the outerface of the stopper and the less than about 0.22 mm; and a ratio of a maximum outer inner wall of the barrel such that the stopper can slide within diameter of all the ribs having a sealing Surface to an inner the barrel. However, Syringes comprising silicone lubricants diameter of the inner surface of the barrel is nominally cannot be used for pharmaceutical composition and the like greater than about 1.08. because the silicone lubricant can cause inactivation or 0009. In some embodiments, a maximum outer diameter otherwise impact the efficacy of these pharmaceutical com of the ribs having a sealing Surface is greater than about 5.0 positions. Therefore, in order to maintain the stability of the mm, an inner diameter of the inner surface of the barrel is pharmaceutical composition, stoppers laminated with a fluo nominally between about 4.65 and about 11.85 mm, and a ropolymer film have been used. Since the air and liquid ratio of the maximum outer diameter of the ribs having a impermeability of stoppers may also have an impact on the sealing Surface to an inner diameter of the inner Surface of quality and stability of the pharmaceutical compositions, the the barrel is greater than about 1.08. stoppers laminated with a fluoropolymer film are required to 0010. In another embodiment, a plunger rod includes a have high levels of air and liquid impermeability. However, distal end that is insertable into a barrel and a stopper when stoppers laminated with a fluoropolymer film are used attached to the distal end. In one or more embodiment, the with a glass or resin Syringe having a hydrophilic or lubri barrel has a hydrophilic inner Surface. The stopper is con cant free inner surface, the stoppers undesirably exhibit figured to contact at least a portion of the inner Surface of the poorer air and liquid impermeability than conventional, barrel. The stopper includes an elastomeric body, one or non-laminated rubber stoppers. more fluoropolymer layers, and two or more ribs laminated 0004 Another problem associated with some fluoropo with the one or more fluoropolymer layers. Each rib of the lymer laminates is its ability to maintain air and liquid two or more ribs having a sealing Surface includes a radius impermeability while also possessing low-friction slidabil of curvature at an apex of each respective rib that is less than ity. For example, Some fluoropolymer laminates function about 0.22 mm, and a ratio of a maximum outer diameter of inconsistently and can distort during insertion of the plunger all the ribs having a sealing Surface to an inner diameter of rod into the barrel and/or during movement of the plunger the inner surface of the barrel is greater than about 1.08. The rod within the barrel, which can create leak paths for the plunger rod may be configured such that when the plunger liquid. Additional difficulties with some fluoropolymer lami rod is inserted in the barrel having an inner diameter of an nates include poor airtightness due to a rough outer Surface inner surface of the barrel, a contact width between at least especially when manufactured as a skived film. one of the two or more ribs having a sealing Surface and the 0005 Accordingly, the need exists for stoppers laminated portion of the inner surface of the barrel measured at a with a fluoropolymer film that are capable of achieving compressibility of greater than about 7.9% of the stopper is sufficient contact with a hydrophilic or lubricant free inner less than about 1.0 mm. US 2017/0203043 A1 Jul. 20, 2017 0011. In yet another embodiment, a stopper that is insert lymer laminates have good biocompatibility, have good able in a barrel having a hydrophilic inner Surface comprises mechanical integrity, are inert, and are processable. an elastomeric body, one or more fluoropolymer layers, and 0020. In some embodiments, the stopper has a compress two or more ribs. The at least one of the two or more ribs are ibility (C96) that is greater than about 7.9%, between about laminated with the one or more fluoropolymer layers and 9.5 and about 20.0%, between about 11.75 and about 18.5%, configured to contact at least a portion of the inner Surface between about 14.0 and about 14.5.