WO2009030975A1 - Dispositif médical comprenant une chambre siliconée et un moyen de fermeture pourvu d'un revêtement - Google Patents

Dispositif médical comprenant une chambre siliconée et un moyen de fermeture pourvu d'un revêtement Download PDF

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Publication number
WO2009030975A1
WO2009030975A1 PCT/IB2007/003432 IB2007003432W WO2009030975A1 WO 2009030975 A1 WO2009030975 A1 WO 2009030975A1 IB 2007003432 W IB2007003432 W IB 2007003432W WO 2009030975 A1 WO2009030975 A1 WO 2009030975A1
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WO
WIPO (PCT)
Prior art keywords
medical device
coating
closure means
piston
barrel
Prior art date
Application number
PCT/IB2007/003432
Other languages
English (en)
Inventor
Laurence Boulange
Frédérique CROZET
Jean-Bernard Hamel
Florent Charlon
Original Assignee
Becton Dickinson France
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Becton Dickinson France filed Critical Becton Dickinson France
Priority to PCT/IB2007/003432 priority Critical patent/WO2009030975A1/fr
Publication of WO2009030975A1 publication Critical patent/WO2009030975A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/178—Syringes
    • A61M5/31—Details
    • A61M5/315—Pistons; Piston-rods; Guiding, blocking or restricting the movement of the rod or piston; Appliances on the rod for facilitating dosing ; Dosing mechanisms
    • A61M5/31511—Piston or piston-rod constructions, e.g. connection of piston with piston-rod
    • A61M5/31513—Piston constructions to improve sealing or sliding
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
    • A61J1/00—Containers specially adapted for medical or pharmaceutical purposes
    • A61J1/14—Details; Accessories therefor
    • A61J1/1468—Containers characterised by specific material properties
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/178—Syringes
    • A61M5/31—Details
    • A61M5/3129—Syringe barrels
    • A61M2005/3131—Syringe barrels specially adapted for improving sealing or sliding
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M2205/00—General characteristics of the apparatus
    • A61M2205/02—General characteristics of the apparatus characterised by a particular materials
    • A61M2205/0222—Materials for reducing friction
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M2205/00—General characteristics of the apparatus
    • A61M2205/02—General characteristics of the apparatus characterised by a particular materials
    • A61M2205/0238—General characteristics of the apparatus characterised by a particular materials the material being a coating or protective layer

Definitions

  • Medical device comprising a siliconized chamber and a coated closure means
  • the present invention relates in general to a medical device, for example a container or a syringe, comprising a chamber intended to receive a protein containing composition and closure means.
  • a medical device for example a container or a syringe
  • the chamber and the closure means may be able to move one relative to the other, for example translationally and/or rotationally, when the medical device is operated.
  • the chamber is intended to accommodate a protein containing composition in the liquid, gaseous, fluid, pasty or lyophilized phase. This protein containing composition may remain within said chamber for a certain period of time until the medical device is used. In order to be efficient at the time it is used, the protein containing composition should remain stable within said chamber.
  • the proteins interact with the material the chamber is made of.
  • some particles coming from glass chambers may cause aggregation of therapeutic proteins contained in the product stored in the chamber.
  • glass nanoparticles generated during heating of glass chambers for depyrogenation may initiate the nucleation of protein aggregates.
  • the closure means is preferably made at least partially from a viscoelastic material so as to ensure tightness in the region of contact between the chamber and the closure means. It can happen that the proteins interact with the material which the piston is made of, for example rubber. In particular, it is known that some particles coming from rubber pistons may cause aggregation of therapeutic proteins contained in the barrel of an injection device such as a syringe.
  • the closure means is usually a piston which must be able to slide with respect to the internal surface of the chamber, for example the barrel of the syringe, in order to push the product such as the protein containing composition, towards the distal end of the barrel to realize the injection. It is therefore necessary that the piston shows good sliding properties with respect to the internal surface of the barrel.
  • X represents a halogen, for example F, or a hydrogen
  • Yi, Y 2 , Y 3 , Y 4 each independently represent a halogen, for example Cl, or a hydrogen.
  • the polymer material is chosen from the group consisting of poly(p-xylylene) polymers, which may or may not be substituted, and in particular, poly(p-xylylene), poly(p-meta-chloroxylylene), poly(p-ortho- chloro/meta-chloroxylylene) and poly(p-difluoroxylylene).
  • poly(p-xylylene) polymers which may or may not be substituted, and in particular, poly(p-xylylene), poly(p-meta-chloroxylylene), poly(p-ortho- chloro/meta-chloroxylylene) and poly(p-difluoroxylylene).
  • the latter four polymer materials are manufactured and sold by UNION CARBIDE CORPORATION, or by SPECIALTY COATING SYSTEMS, under the names Parylene N, Parylene C, Parylene D and Parylene AF 4 , respectively.
  • a polymer material of the poly(p-xylylene) type is not employed by injection, dissolving or suspending in a solvent, but is used by depositing it onto the part by a direct dry vacuum deposition process using the following protocol:
  • the vaporized dimer is then pyrolized, still under vacuum but at a higher temperature, for example at 650 0 C, in order to obtain the reactive monomer form corresponding to the aforementioned dimer and to the afore- mentioned chemical unit, and
  • the reactive monomer is deposited directly on the entire accessible developed surface of the part, both internal and external, and polymerized at ambient temperature under a low vacuum, in a method akin to the vacuum deposition of a thin metal layer, so as to obtain a continuous coating of (substituted or unsubstituted) poly(p-xylylene) of relatively uniform thickness, completely (with no discontinuity) covering the part of the medical device.
  • the coating thus obtained adheres to the piston directly or indirectly. Because of its slip characteristics, the coating facilitates the relative movement between the two parts of the medical device. In addition, the elastic behaviour of the coating allows it in a resilient manner to accommodate the deformations and stresses imposed on the part provided with it, for example the piston, as it slides in the container. Thus, tightness in the region of contact between the piston and the container can be guaranteed to be maintained.
  • Adhesion between the coating and the part may be direct, particularly by means of chemical bonds formed at the time of deposition and polymerization of the reactive monomer, between the said part and the polymer material, or indirect, by way of a tie layer or primer layer applied beforehand to the surface that is to be coated, if appropriate after that surface has been cleaned or prepared.
  • the polymer material coating of the poly(p-xylylene) type has a thickness ranging from 0.25 ⁇ m to 1 ⁇ m, it being possible for a coating thickness of 0.10 to 76 ⁇ m to be obtained in a single stage.
  • this thickness range seems inappropriate for most medical devices, particularly of the syringe type. This is because with this range of thicknesses, when the two parts of the medical device move relative to one another, the coating breaks, tears or breaks up. This permanently worsens the surface finish of the coated part, at the region of contact between the two moving parts, thus increasing resistance to movement, or friction, between the said two parts.
  • a first aspect of the invention is a medical device comprising :
  • closure means for tightly sealing said inner space, said closure means having at least one face facing said inner space, said face being coated with a coating (8) consisting of at least one polymer material comprising polymer chains having the following repeat unit:
  • X represents a halogen, for example F, or a hydrogen
  • Y-i, Y 2 , Y 3 , Y 4 each independently represent a halogen, for example Cl, or a hydrogen, characterized in that -said inner surface of said chamber is coated with a layer of silicone, and
  • the mean thickness of the coating of said face of said closure means ranges from 3 to 10 ⁇ m.
  • the medical device of the invention allows to store protein containing compositions for a certain period of time, for example over 7 days or over 15 days, while maintaining the stability of the proteins.
  • the medical device of the invention is an injection device provided with a syringe barrel and a piston movable within said barrel
  • the invention allows to have decreased activation, sustainable and final forces for moving the piston within the barrel in which it is lodged, without having to add a lubricant on the piston and while preserving the tightness at the contact region between the piston and the internal surface of the barrel.
  • the piston in a medical device such as a syringe, the piston must be able to be moved relative to the barrel, through a gliding movement, while at the same time ensuring the tightness with said barrel, so that all of the product to be administered escapes only via the distal end of the barrel and does not leak out of said barrel via the piston at the proximal end of the barrel.
  • the medical device of the invention thanks to a first specific coating on the internal surface of the barrel and to a second coating having a specific thickness range on the piston, allows the successful completion of these two relatively incompatible requirements and the preservation of the stability of the proteins contained in the product to be administered.
  • distal end of a component or of a device means the end furthest away from the hand of the user and the proximal end means the end closest to the hand of the user.
  • proximal direction and proximally mean in the direction opposite to the direction of injection.
  • the medical device of the invention it is possible to decrease the total amount of lubricant, for example silicone oil, that is necessary in such a medical device, by eliminating the need to have such a silicone oil on the piston.
  • lubricant for example silicone oil
  • the mean thickness of the said coating of said face of said closure means ranges from 3 to 5 ⁇ m.
  • said closure means consists of a viscoelastic material.
  • the said coating of said face of said closure means is continuous and elastic.
  • the said polymer material is chosen from the group consisting of poly(p-xylylene), poly(p-meta-chloroxylylene), poly(p-ortho- chloro/meta-chloroxylylene) and poly(p-difluoroxylylene). More preferably, the said polymer material consists of poly(p-meta-chloroxylene).
  • the outer surface of said coating of said face of said closure means has a mean roughness Ra of less than 2.5 ⁇ m, preferably less than 2 ⁇ m and, for example, of the order of 1.0 ⁇ m.
  • said layer of a silicone has a mean thickness ranging from 0.05 to 2 ⁇ m.
  • the mean thickness of the layer of silicone is about 0.5 to 1.5 ⁇ m.
  • the silicone is selected from the class of polydimethylsiloxanes of general structure :
  • R and R 1 are alkyl groups of 1 to 20 carbon atoms, preferably 1 to 8 carbon atoms, and n is an integer ranging from 1 to 2000, preferably about 1 to 800.
  • the silicone has a viscosity ranging from 10 to 100,000 centistokes, more preferably from 50 to 1000 centistokes.
  • the silicone has a molecular weight ranging from 100 to 200,000 g/mol, and preferably from 1,000 to 100,000 g/mol.
  • said chamber is the barrel of an injection device and said closure means is a piston movable within said barrel when said injection device is operated.
  • FIG. 1 depicts, schematically and in cross section, a medical device considered by the present invention and according to a first embodiment thereof
  • FIG. 2 depicts, again schematically and in cross section, a portion of a medical device according to a second embodiment of the invention
  • FIG. 3 is a graphic showing the necessary forces to move a piston within a barrel for a medical device according to the invention and for prior art devices.
  • a medical device 1 of the invention under the form of a closed container or a vial is shown.
  • the medical device 1 of figure 1 comprises a chamber under the form of a container 2, having an inner surface 2a delimiting an inner space 3 receiving a protein containing composition 4, under form of a liquid in the example shown.
  • the container 2 may be in plastic or in glass.
  • the inner surface 2a of the container 2 is coated with a layer 5 of silicone oil or a mixture of silicone oils.
  • the silicone may be selected in the class of poiydimethylsiloxanes of general structure:
  • R and R' are alkyl groups of 1 to 20 carbon atoms, preferably 1 to 8 carbon atoms, and n is an integer ranging from 1 to 2000, preferably about 1 to 800.
  • the silicone has preferably a viscosity ranging from 10 to 100,000 centistokes, more preferably from 50 to 1000 centistokes.
  • the silicone has preferably a molecular weight ranging from 100 to 200,000 g/mol, and preferably from 1,000 to 100,000 g/mol.
  • the silicone layer may be applied on the inner surface 2a of the container 2 via spraying. Alternatively, the silicone may be deposited on the inner surface 2a of the container 2 and then baked. Methods of applying a silicone layer on the inner surface of a container are well known from the man skilled in the art.
  • the silicone layer 5 has a mean thickness ranging from 0.05 to 2 ⁇ m. More preferably, said thickness is about 0.5 to 1.5 ⁇ m.
  • the medical device 1 of figure 1 further comprises closure means for tightly sealing said inner space 3, under the form of a plug 6 in the example shown.
  • the plug 6 is preferably made out of a viscoelastic material, for example an elastomer or a rubber, in order to ensure tightness at the contact region 7 defined between the coated inner surface 2a of the container 2 and the plug 6.
  • the plug 6 is provided, at least on its face facing the inner space 3 and in contact with the container 2 with a coating 8.
  • the plug 6 is provided with the coating 8 on its entire outer surface.
  • the coating 8 is preferably continuous, intrinsically elastic and firmly secured to the plug 6.
  • the coating 8 ensures the tightness between the plug 6 and the container 2 by preventing the leakage of the product 4 at the contact region 7 between the plug 6 and the container 2.
  • the coating 8 consists of at least one polymer material comprising polymer chains consisting of the following repeat unit:
  • This coating 8 according to the invention is obtained by dry vacuum deposition/polymerization at ambient temperature, as described above.
  • the coating 8 according to the invention has a thickness ranging from 3 to 10 ⁇ m.
  • the person skilled in the art will know how to deposit and control a predetermined thickness of the polymer material adopted, particularly by varying the time for which the plug that is to be coated is exposed to the reactive monomer form of the poly(p-xylylene) chosen. Furthermore, a person skilled in the art knows that the rate of deposition/ polymerization is directly proportional to the square of the reactive monomer concentration, and inversely proportional to the absolute temperature of the part exposed to the monomer, this information allowing him to modify and control the thickness of the coating deposited on the plug.
  • the present invention considers various substrates or viscoelastic materials to be appropriate to the deposition of a coating 8 as previously defined, these being various natural or synthetic elastomers: silicones, nitrile- based elastomers, natural or synthetic rubber, fluorocarbon elastomers, polyurethanes. As a preference, the invention will devote itself to bromobutyl and chlorobutyl synthetic elastomers.
  • the mean thickness of the coating 8 ranges from 3 to 10 ⁇ m and preferably from 3 to 10 ⁇ m and, more preferably still, from 3 to 5 ⁇ m.
  • Such a specific thickness range allows the protein containing composition 4 to be preserved for contamination from particles coming from the plug 6.
  • the polymer material is preferably chosen from the group consisting of poly(p-xylylene), poly(p-meta-chloroxylylene), poly(p-ortho- chloro/meta-chloroxylylene) and poly(p-difluoroxylylene).
  • the polymer material consists of poly(p-meta-chioroxylylene).
  • FIG 2 With reference to figure 2 is partially shown a variant of a medical device 1 according to the invention, wherein the chamber is the barrel 9 of an injection device and the closure means is a piston 10 movable within said barrel 9.
  • the barrel 9 and the piston 10 are in contact with one another via a contact surface 11.
  • the piston 10 and the barrel 9 are able to move one with respect to the other in a predetermined gliding movement, for example translationally and/or rotationally.
  • Such a translational movement is represented on figure 2 by the arrow F.
  • the inner surface 9a of the barrel 9 delimits an inner space 3 which receives a protein containing product 4 in the liquid, gaseous or fluid phase, the volume of said product varying according to the movement of the piston 10 with respect to the barrel 9.
  • the inner surface 9a of the barrel 9 is coated with a silicone layer 5 applied on said inner surface 9a by any classical method known in the art.
  • the silicone layer 5 has a mean thickness ranging from 0.05 to 2 ⁇ m. More preferably, said thickness ranges from 0.5 to 1.5 ⁇ m.
  • the piston 10 is caused to move distally along arrow F of figure 2 in order to push the product 4 out of the barrel 9.
  • the piston 10 is designed to deform in order to tighten the contact region 11.
  • the face of the piston 10 which faces the product 4 and the contact region 11 is provided with a coating 8 which is continuous, intrinsically elastic and firmly secured to the piston 10.
  • the piston 10 may be made in its entirety of a viscoelastic material, for example an elastomer. According to the embodiment of figure 2, the contact surface 11 between the barrel 9 and the piston 10 determines a region of gliding contact between the piston 10 and the barrel 9.
  • the coating 8 of the piston 10 of the medical device 1 of the invention encourages the gliding of the piston 10 relative to the barrel 9 at the time of administration of the product 4. Moreover, the coating 8 also ensures static and dynamic tightness at the contact surface 11 of the piston 10 and the barrel 9. In particular, before use of the medical device 1 , for example during storage, the coating 8 ensures the static tightness between the piston 10 and the barrel 9 by preventing the leakage of the product 4 at the contact surface 11 between the piston 10 and the barrel 9. When the medical device 1 is in use, the coating 8 ensures the dynamic tightness between the piston 10 and the barrel 9 by preventing the leakage of the product 4 at the contact surface 11 between the piston 10 and the barrel 9 while the piston 10 is moving relative to the barrel 9.
  • the coating 8 consists of at least one polymer material comprising polymer chains consisting of the following repeat unit:
  • This coating 8 according to the invention is obtained by dry vacuum deposition/polymerization at ambient temperature, as described above.
  • the coating 8 according to the invention has a thickness ranging from 2 to 10 ⁇ m.
  • the deposition of the coating 8 is completed as described above for the embodiment of figure 1.
  • the present invention considers various substrates or viscoelastic materials to be appropriate to the deposition of a coating 8 as previously defined, these being various natural or synthetic elastomers: silicones, nitrile-based elastomers, natural or synthetic rubber, fluorocarbon elastomers, polyurethanes. As a preference, the invention will devote itself to bromobutyl and chlorobutyl synthetic elastomers.
  • the mean thickness of the coating 8 ranges from
  • the polymer material is preferably chosen from the group consisting of poly(p-xylylene), poly(p-meta-chloroxylylene), poiy(p-ortho- chloro/meta-chloroxylylene) and poly(p-difluoroxylylene).
  • the polymer material consists of poly(p-meta-chloroxylylene).
  • the roughness, and therefore the surface finish, of the coating 8 of the piston 10 of the medical device 1 in the contact surface 11 of sliding contact with the barrel 9, is important in giving the coating 8 the desired performance and function, and this, independently of the thickness of the coating 8, provided said thickness ranges from 3 to 10 ⁇ m as defined in the present invention.
  • the surface finish of the coating 8, in the contact surface 11 of sliding contact has a mean roughness R a of less than 2.5 ⁇ m and preferably less than 2 ⁇ m and, more preferably still, less than 1.5 ⁇ m, for example of the order of 1.0 ⁇ m.
  • the roughness is measured according the following method : roughness measurements done in triplicate are performed by using a profiler Wyko NT 1100 (Veeco Instruments Inc. Arlington USA) on scans 370 ⁇ m x 240 ⁇ m with a VSI mode (Vertical Scanning Interferometry).
  • the calibration of the apparatus is performed following the procedure Wl 7.6-20 using measuring instruments traceable to the National Institute of Standards and Technology (NIST).
  • a roughness of less than 2.5 ⁇ m, measured as described hereinabove, for the coating 8 of the piston 10 of a medical device 1 of the invention allows a smooth gliding of such a coated piston 10, relative to the barrel 9.
  • Tests were performed in order to compare the ability of medical devices 1 according to the invention to preserve the stability of a product 4 containing proteins with respect to medical devices of the prior art.
  • the tested chambers were glass barrels of prefilled syringes commercially available under the trade name "Hypak 1 mlL" from the company Becton and Dickinson, Company.
  • the syringe barrels were provided with bromobutyl pistons from the Company West.
  • Various systems piston-barrel were tested : the characteristics of the tested systems are collected in the following table 1 :
  • the piston was coated with 150 ⁇ g of silicone according to the following method : the uncoated piston was cleaned for 10 min in distilled water at a temperature of 8O 0 C and then spray siliconized with 150 ⁇ g of a silicone oil of viscosity 1000 Cst (available at company Dow Corning).
  • the piston was coated with poly(p-meta- chloroxylylene) (Parylene C) according to the dry vacuum deposition/polymerization method previously described hereinabove.
  • the mean thickness of the Parylene C coating on each piston was about 3 ⁇ m.
  • the inner surface of each barrel was coated with a silicone layer of 0.05-1 ⁇ m by spraying a silicone oil of viscosity 1000 Cst (available at company Dow Corning) on said surface by means of nozzles.
  • the inner surface of the barrel was coated with a silicone layer of 0.5-1.5 ⁇ m, by first spraying onto said surface an emulsion of water and silicone oil of viscosity 360 Cst (available at company Dow Corning) stabilized with a surfactant ("Triton X100" commercially available at company Union carbide Chemicals and Plastic), and then heating said coated barrel in an oven at a temperature of 300 0 C in order to evaporate the water phase.
  • a surfactant Triton X100
  • compositions containing different proteins were tested prior to the contact with the protein containing composition. Prior to the contact with the protein containing composition, all the barrels to be tested were cleaned by a sequence of soda (1N) during 10 min, wter rinsing during 10 min, chlorhydric acid (1N) during 10 min, water rinsing during 10 min and then sterilized during 20 min at a temperature of 121 0 C.
  • the protein stability was studied at 37 0 C and the hydrodynamic diameter of the protein (nm) was measured by dynamic light scattering (DLS). The measurements were made with a He Ne laser 633 nm at 173° in order to verify the presence of aggregates and to minimize the effects of dust contamination.
  • Each native protein has a specific hydrodynamic diameter that is typically less than 20 nm.
  • a study of the kinetics was performed at 37°C and the hydrodynamic diameter was measured after 7, 15 and 30 days. When proteins formed aggregates, large hydrodynamic diameters were measured. All the experiments were done in isotonic conditions (300 mOsm). The percentage of intensity was recorded as a function of the hydrodynamic diameter. Several peaks can be observed.
  • Peak 1 corresponds to the hydrodynamic diameter of the native protein
  • Peaks 2 and 3 correspond to the protein aggregates.
  • BSA Bovine Serum Albumine Bovine Serum Albumin
  • Peak 1 corresponds to the hydrodynamic diameter of the native protein and peaks 2 and 3 to the protein aggregates. Values in brackets correspond to the percentage of light intensity for each peak.
  • system S5 The most stable system was obtained with system S5 according to the invention. Indeed, for S5, the percentage of native protein is more than 70% after 7, 14 and 30 days of stabilization (72% at 7 days, 77% at 15 days and 80% at 30 days) at 37°C. With comparative systems S1 and S2, the stable protein is only 30% after 15 days of stabilization.
  • Lyzozyme is an enzyme, commonly referred to as the 'body's own antibiotic' since it disintegrates the bacteria walls. It is abundantly present in secretions such as tears or saliva. It is a positive protein, i.e. it has an isoelectric point more than 7 at pH 7.
  • Lyzozyme stabilization was studied for one month in a buffer (sodium phosphate 10 mM, NaC1 130 mM pH 7.2) .
  • the results are collected in the following Table 3 :
  • Peak 1 corresponds to the hydrodynamic diameter of the native protein and peaks 2 and 3 to the protein aggregates. Values in brackets correspond to the percentage of light intensity for each peak.
  • Ribonuclease is a nuclease that catalyzes the breakdown of RNA into smaller components.
  • Peak 1 corresponds to the hydrodynamic diameter of the native protein and peaks 2 and 3 to the protein aggregates. Values in brackets correspond to the percentage of light intensity for each peak
  • systems S4 and S5 according to the invention insure at least 90%, and even 100%, of RNAse stability after 15 and 30 days at 37°C. On the contrary, with comparative system S2, this stability is less than 63% after 30 days.
  • Insulin is a polypeptide hormone that regulates glucose metabolism.
  • Peak 1 corresponds to the hydrodynamic diameter of the native protein and peaks 2 and 3 to the protein aggregates. Values in brackets correspond to the percentage of light intensity for each peak
  • the initial solution (at day 0) remains constant in systems S4 and S5 according to the invention after 15 and/or 30 days of stabilization in comparison with comparative systems S1 and S2 over the same period (15 and 30 days).
  • Pistons C2 and C3 were coated with poly(p-meta-chloroxylylene) (Parylene C) according to the dry vacuum deposition/polymerization method previously described hereinabove.
  • each piston was tested as follows : the piston was inserted in a glass barrel initially filled with a composition of distilled water and ethanol (80/20 V/V). The system was heated at 121 0 C for 20 min and the composition was then analyzed by HPLC (High Performance Liquid Chromatography). A chromatogram with different peaks as a function of time was obtained, in which each peak corresponds to a chemical species coming either from the coating of the piston or from the piston itself.
  • the tested chambers were glass barrels of prefilled syringes commercially available under the trade name "Hypak 1 mlL" from the company Becton and Dickinson, Company.
  • the syringe barrels were provided with chlorobutyl pistons available from the Company West.
  • Tests were performed to determine the necessary forces for moving each piston with respect to the barrel in which it is housed. These tests were performed using a LLOYD-CB190 tensile testing machine dynamometer using NEXYGEN operating software, according to the test protocol outlined briefly below.
  • Activation Gliding Force (AGF) tests were applied on barrels filled with 1 mL of demineralised water and each plugged with one piston to be tested (coated or uncoated). Each barrel-piston system was tested 32 times in order to ensure the reproducibility and to validate the results. To prepare the 32 syringes for a system, and particularly to insert the piston in the barrel, a Groninger machine was used.
  • system S9 according to the. invention necessitates lower values to move the piston within the barrel compared to comparative systems S6-S8.
  • the system S9 according to the invention has improved sliding properties compared to the systems of the prior art S6-S8.

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  • Health & Medical Sciences (AREA)
  • Vascular Medicine (AREA)
  • Engineering & Computer Science (AREA)
  • Anesthesiology (AREA)
  • Biomedical Technology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Hematology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Infusion, Injection, And Reservoir Apparatuses (AREA)

Abstract

L'invention concerne un dispositif médical (1) comprenant au moins une chambre (9) qui présente une surface intérieure (9a) délimitant un espace intérieur (3) destiné à recevoir une composition (4) contenant des protéines, ainsi qu'un moyen de fermeture (10) destiné à assurer l'étanchéité de cet espace intérieur. Ledit moyen de fermeture (10) présente au moins un côté faisant face audit espace intérieur (3), ce côté étant pourvu d'un revêtement (8) composé d'au moins une matière polymère comprenant des chaînes polymères comportant l'unité de répétition (I), dans laquelle X représente un halogène, par exemple F, ou un hydrogène et dans laquelle Y1, Y2, Y3 et Y4 représentent chacun indépendamment un halogène, par exemple Cl, ou un hydrogène. L'invention se caractérise en ce que la surface intérieure (9a) de la chambre (9) est revêtue d'une couche (5) de silicone et en ce que l'épaisseur moyenne du revêtement (8) dudit côté du moyen de fermeture (6; 10) est comprise entre 3 et 10 μm.
PCT/IB2007/003432 2007-09-03 2007-09-03 Dispositif médical comprenant une chambre siliconée et un moyen de fermeture pourvu d'un revêtement WO2009030975A1 (fr)

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US7985188B2 (en) 2009-05-13 2011-07-26 Cv Holdings Llc Vessel, coating, inspection and processing apparatus
WO2012055845A1 (fr) * 2010-10-25 2012-05-03 Sanofi-Aventis Deutschland Gmbh Dispositif d'administration de médicament et procédé pour assembler un dispositif d'administration de médicament
JP2013132349A (ja) * 2011-12-26 2013-07-08 Daikyo Seiko Ltd 二薬混合用シリンジキット
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JP2014530059A (ja) * 2011-09-27 2014-11-17 ベクトン ディキンソン フランス 医療用注射装置においてプラズマ処理したシリコーンオイルのコーティングとしての使用
US9272095B2 (en) 2011-04-01 2016-03-01 Sio2 Medical Products, Inc. Vessels, contact surfaces, and coating and inspection apparatus and methods
US9458536B2 (en) 2009-07-02 2016-10-04 Sio2 Medical Products, Inc. PECVD coating methods for capped syringes, cartridges and other articles
US9545360B2 (en) 2009-05-13 2017-01-17 Sio2 Medical Products, Inc. Saccharide protective coating for pharmaceutical package
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US9764093B2 (en) 2012-11-30 2017-09-19 Sio2 Medical Products, Inc. Controlling the uniformity of PECVD deposition
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US9878101B2 (en) 2010-11-12 2018-01-30 Sio2 Medical Products, Inc. Cyclic olefin polymer vessels and vessel coating methods
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US10189603B2 (en) 2011-11-11 2019-01-29 Sio2 Medical Products, Inc. Passivation, pH protective or lubricity coating for pharmaceutical package, coating process and apparatus
US10201660B2 (en) 2012-11-30 2019-02-12 Sio2 Medical Products, Inc. Controlling the uniformity of PECVD deposition on medical syringes, cartridges, and the like
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EP3381444B1 (fr) 2012-07-03 2021-05-19 Novartis AG Seringue
US11066745B2 (en) 2014-03-28 2021-07-20 Sio2 Medical Products, Inc. Antistatic coatings for plastic vessels
US11077233B2 (en) 2015-08-18 2021-08-03 Sio2 Medical Products, Inc. Pharmaceutical and other packaging with low oxygen transmission rate
US11116695B2 (en) 2011-11-11 2021-09-14 Sio2 Medical Products, Inc. Blood sample collection tube
US11406565B2 (en) 2015-03-10 2022-08-09 Regeneran Pharmaceuticals, Inc. Aseptic piercing system and method
US11547801B2 (en) 2017-05-05 2023-01-10 Regeneron Pharmaceuticals, Inc. Auto-injector
US11624115B2 (en) 2010-05-12 2023-04-11 Sio2 Medical Products, Inc. Syringe with PECVD lubrication
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US11624115B2 (en) 2010-05-12 2023-04-11 Sio2 Medical Products, Inc. Syringe with PECVD lubrication
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WO2012055845A1 (fr) * 2010-10-25 2012-05-03 Sanofi-Aventis Deutschland Gmbh Dispositif d'administration de médicament et procédé pour assembler un dispositif d'administration de médicament
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US11066745B2 (en) 2014-03-28 2021-07-20 Sio2 Medical Products, Inc. Antistatic coatings for plastic vessels
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EP3278829A1 (fr) * 2016-08-03 2018-02-07 Sumitomo Rubber Industries, Ltd. Seringue médicale, joint à utiliser pour la seringue et procédé de production de joint
EP3376076A1 (fr) * 2017-03-14 2018-09-19 Sumitomo Rubber Industries, Ltd. Joint
CN108570162A (zh) * 2017-03-14 2018-09-25 住友橡胶工业株式会社 垫片
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