EP1060031B1 - Medical article with coated surfaces exhibiting low friction and low protein adsorption - Google Patents

Medical article with coated surfaces exhibiting low friction and low protein adsorption Download PDF

Info

Publication number
EP1060031B1
EP1060031B1 EP99937894A EP99937894A EP1060031B1 EP 1060031 B1 EP1060031 B1 EP 1060031B1 EP 99937894 A EP99937894 A EP 99937894A EP 99937894 A EP99937894 A EP 99937894A EP 1060031 B1 EP1060031 B1 EP 1060031B1
Authority
EP
European Patent Office
Prior art keywords
coating
component
medical article
article according
hydrophilized
Prior art date
Legal status (The legal status 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 status listed.)
Expired - Lifetime
Application number
EP99937894A
Other languages
German (de)
English (en)
French (fr)
Other versions
EP1060031A1 (en
Inventor
Thomas Buch-Rasmussen
Patric Jannasch
Erling Bonne Jorgensen
Ib Johannesen
Sokol Ndoni
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Novo Nordisk AS
Original Assignee
Novo Nordisk AS
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 Novo Nordisk AS filed Critical Novo Nordisk AS
Priority claimed from PCT/DK1999/000093 external-priority patent/WO1999044755A1/en
Publication of EP1060031A1 publication Critical patent/EP1060031A1/en
Application granted granted Critical
Publication of EP1060031B1 publication Critical patent/EP1060031B1/en
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

Links

Images

Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B65—CONVEYING; PACKING; STORING; HANDLING THIN OR FILAMENTARY MATERIAL
    • B65D—CONTAINERS FOR STORAGE OR TRANSPORT OF ARTICLES OR MATERIALS, e.g. BAGS, BARRELS, BOTTLES, BOXES, CANS, CARTONS, CRATES, DRUMS, JARS, TANKS, HOPPERS, FORWARDING CONTAINERS; ACCESSORIES, CLOSURES, OR FITTINGS THEREFOR; PACKAGING ELEMENTS; PACKAGES
    • B65D25/00—Details of other kinds or types of rigid or semi-rigid containers
    • B65D25/14—Linings or internal coatings
    • 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
    • A61J1/05—Containers specially adapted for medical or pharmaceutical purposes for collecting, storing or administering blood, plasma or medical fluids ; Infusion or perfusion containers

Definitions

  • the present invention relates to a medical article for containing a pharmaceutical protein preparation comprising at least a first component and a second component, having at least one surface coated with a coating to reduce the friction between the two components and to reduce the protein adsorption to the coating.
  • the described coatings are particularly useful for coating containers for storage and administration of liquid protein solutions, such as insulin formulations.
  • Protein formulations are mostly dosed from relatively small containers, i.e. up to 5 ml, and many of the containers are designed for multiple dosages, each dosage often being in the range of 0.1 ml or even less.
  • Such containers equipped with stoppers require a smooth sliding movement of one component, e. g. a stopper, in contact with another component, e. g. a container wall, to provide reliable dosages with high precision.
  • a static friction force a certain applied force
  • the phenomenon causes a sudden, rapid relative movement of the two surfaces. Frequently, the movement stops and another resistance is built up. This kind of movement is generally known as the 'slip-stick' phenomenon and is caused by a degree of adhesion between the components.
  • Today large amounts of insulin are sold in dispensing devices.
  • the insulin is filled in glass containers, which are equipped with rubber stoppers, and these containers are then loaded into dispensing devices.
  • both the glass containers and the rubber stoppers are coated with silicon oil, poly(dimethy) siloxane) (PDMS), to reduce the friction between the container wall and the stopper.
  • PDMS poly(dimethy) siloxane)
  • One common method to coat glass containers with silicon oil is to apply a PDMS-in-water emulsion and subsequently evaporate the water in an oven.
  • US 4,767,414 suggests a coating of a medical container having reduced friction between the components wherein a surface is plasma-treated as well as a lubricant at one of the components is plasma-treated to inhibit migration of the lubricant into the content of the container.
  • the lubricant is disclosed to reduce the friction between a container wall and a stopper compared to untreated containers and stoppers.
  • the reference does not discuss adherence of proteins.
  • Another reference US 5,338,312 discloses an article having a coating with two or more layers of lubricant securing a low friction force at different movement velocities, in that one layer may secure low friction at low velocities and the other(s) at other velocities. The adherence of protein molecules to the coating is not disclosed.
  • An aspect, which should be considered, when dispensing protein formulations is the events occurring at the surface between the protein solution and the container material that play a crucial role for the overall performance of biological material.
  • the drug is in contact with a packaging material for a long time during storage which is often the case with protein formulations that are filled into the containers immediately after molding of the containers, the stability and life-time of the drug will be affected.
  • the primary reason for this is that protein may be adsorbed to the surfaces of the container, where it is deactivated or denaturated. In this way, layers of deactivated and inaccessible protein are built up at the container surface. This will lead to a loss in protein activity and an enhanced risk of incorrect dosage, due to lowering of the concentration of soluble protein.
  • adsorbed insulin may desorb and some molecules will associate with other deactivated molecules and form aggregates.
  • Aggregates such as fibrils or gel-like particles, form as a result of lower degree of water solubility and aggregation after denaturation.
  • Aggregation of insulin is thought to be an autocatalyzed process, and leads to an overall destabilization of the insulin formulation. When these aggregates become large enough, they can be seen visually. By blocking the adsorption of insulin at the container surface, the propensity of the insulin molecule to change its conformation is removed. The result is a significant improvement of the drug stability. Furthermore, the presence of protein aggregates may lead to immunological reactions in the patient, which is unacceptable.
  • Addition of glycerol and certain polysaccarides are well known methods to improve the stability. Further, addition of zinc and calcium ions significantly stabilizes the insulin by promoting the formation of more stable species, i. e., dimers and hexamers. It is also known that low concentrations of lecithins or synthetic detergents has a markedly positive effect on the stability of insulin. This effect is thought to be coupled to their ability to cover hydrophobic domains exposed by the insulin molecules. These hydrophobic domains are thought to be involved in the destabilization of insulin.
  • non-ionic surfactants In relation to insulin, different kinds of non-ionic surfactants have been used to stabilize insulin formulation, e. g., ethoxylated fatty acids and Pluronics®. Chawla et al. (Diabetes Vol 34, May 1985, pp 420-424) was able to stabilize insulin in PS and PP containers by adding Pluronic® F68, a non-ionic surfactant containing PEO. These types of molecules are however only loosely adsorbed to the surfaces, and are probably present in the insulin solution which results in injection of the polymer when the protein formulation is injected. It is therefore unclear whether the surfactants cover the hydrophobic domains of the insulin, or the hydrophobic plastic surface. Chawla et al. also found that other types of Pluronics®, 17R8 and 25R5, did not stabilize the insulin formulations.
  • the object of the invention is obtained by a medical article for containing a pharmaceutical protein preparation comprising at least a first component and a second component, which is in frictional engagement with said first component, wherein at least one surface on either the first or the second component or both is coated independently with a hydrophilic coating whereby the hydrophilicity of the surface of the coating as measured by the water contact angle is below 90 °, and the long term static friction forces between the first and the second component are below 14 N.
  • the coatings according to the present invention are especially suited for permanently coating internal surfaces of containers equipped with stoppers for storage and administration of liquid protein preparations, such as insulin preparations.
  • the coating(s) provide low friction between the two components, such as a container wall and a rubber stopper, resulting in high-precision dosing. In addition, they efficiently prevent the adsorption of protein to the container surface, thereby increasing the stability and prolonging the storage time of the protein.
  • Another object of the invention is a process of producing a component of a medical article coated as described above, comprising
  • a third object of the invention is a coating as defined above, for articles having at least a first component and a second component, said second component being in frictional engagement with said first component, wherein at least one surface or either the first or the second component or both is coated independently with a hydrophilic coating.
  • Figure 1 shows an example of the first (figure 1A, injection cylinder) and second (figure 1B, plunger) components according to the invention.
  • the components are shown in longitudinal cross section.
  • the inner diameter of the first component is 9,23 mm and the outer diameter is 11,0 mm.
  • the outer diameter D of the second component is 9,6 mm.
  • Figure 2 and Figure 3 show the result of recordings of friction forces where the maximum static forces are indicated with S and the maximum dynamic friction forces are indicated with D for a medical article coated with two different coatings as described in the examples.
  • the present invention relates to a medical article for containing a pharmaceutical protein preparation
  • a medical article for containing a pharmaceutical protein preparation comprising at least a first component and a second component, such as a container and a stopper, which is in frictional engagement with each other, wherein at least one surface on either the container or the stopper or both is coated independently with a hydrophilic coating whereby the hydrophilicity of the surface of the coating as measured by the water contact angle is below 90 °, and the long term static friction forces between the first and the second component are below 14 N.
  • the coating according to the present invention is hydrophilic, or at least the surface part of the coating exposed to the content is hydrophilic. Without being bound by theory it is believed that hydrophobic domains on the protein molecule is responsible for the protein adsorption, and hence, that a certain hydrophilic surface of the coating reduces the adsorption tendency.
  • the present invention relates to a medical article coated with a coating which is hydrophilic to such an extent that the protein adsorption, in particular the insulin absorption is significantly reduced or substantially eliminated.
  • the hydrophilicity as measured by the water contact angle is below 90 °.
  • the water contact angle is preferably below 60 °, more preferably below 20 °, most preferably below 10 °, in order to secure a low protein adsorption.
  • the amount of protein adsorbed to the coating depends on the concentration of protein solution as well as the surface area of the coating in contact with the protein solution.
  • a measure of the protein adsorption is obtained by measuring by the insulin adsorption in a container with a standard volume of 3,5 ml, and an internal surface area of 14.1 cm 2 by the procedure as described in example 2.
  • the protein adsorption measured under these conditions is preferably less than 0.5 %, such as less than 0.4 %, most preferably less than 0.3 % of the original protein solution.
  • insulin stability may be measured by assembling containers and plungers, and subsequently filling the container with Penmix 30/70®. After closing the container with a bromobutyl plate and an aluminum cap, the containers are stored at 37 degree Centigrade and rotated vertically 4 h every 24 h at 30 rotations per minute. The experiment is stopped at the specified time, and the insulin is acidified by an aqueous HCI solution. The remaining percentage of monoinsulin, as compared to the original amount, may be detected by GPC (gel permeation chromatography), and used as a parameter to describe the remaining insulin activity.
  • GPC gel permeation chromatography
  • any hydrophilic coating exhibiting the low protein adsorption, especially insulin adsorption, may be used for coating the surface of the medical article provided the long-term static friction forces between the first and the second component are below 14 N.
  • the coating according to the present invention has a reduced ability of migrating, because it is preferably essentially a solid material and not an oil or a liquid. Furthermore, the coating is preferably fixed to the component.
  • the coating does not migrate from the interface between the two components during storage hence the slip-stick phenomenon is significantly reduced or eliminated whereby a high-precise dosing is possible, in particular when dosing small volumes, such as when dosing insulin.
  • the reduced migration tendency reduces the risk of having particles of the coating solubilised or suspended in the protein formulation.
  • the coating material is not not capable of forming an emulsion with the solvent of the protein formulation, such as water, and is not soluble in water.
  • the coating is preferably a silicon-containing coating, such as a poly(dialkyl siloxane) oil or copolymer.
  • the poly(dialkyl siloxane) is selected from poly(dimethyl siloxane) (PDMS), poly(dipropyl siloxane) or poly(dihexyl siloxane).
  • the coating comprises a linear or branched hydrophilized poly(dialkyl siloxane) oil.
  • the viscosity of the oil is preferably above 200,000 centistokes, such as above 500,000 centistokes when applied to the component.
  • the coating comprises a crosslinked or gelled silicon oil, such as a hydrophilized poly(dialkyl siloxane) oil, or a mixture of a crosslinked and a non-crosslinked oil.
  • a crosslinked or gelled oil the migration ability of the oil is significantly reduced and the viscosity increased towards infinitely great, i.e. the oil may broadly be looked upon as a solid material.
  • a cross-linked, or cured, silicon oil is typically obtained by applying a linear, or branched, silicon oil with reactive functionalities which are used to cross-link the coating in a subsequent step.
  • a linear, or branched, silicon oil with reactive functionalities which are used to cross-link the coating in a subsequent step.
  • the cross-linkable silicon oil is of medical grade, e. g. MDX® supplied by Dow Coming (MDX4-4159 Fluid).
  • a cross-linked silicon oil may also be obtained by first applying a silicon oil, linear or branched, and secondly irradiating the oil by a high-energy radiation source, e. g. an electron or x-ray source.
  • the coating comprises a hydrophilized poly(dialkyl siloxane) block and graft copolymer.
  • the copolymer may be any block and graft copolymer which comprises polymeric segments of poly(dialkyl siloxane), such as PDMS.
  • the polymeric segments may, for example, be combined with polymeric segments of polystyrene, polyolefins, polyamides, or polyurethane to form the desired copolymer.
  • the copolymer may be prepared by any method available, for example by sequential anionic polymerization, or different grafting procedures.
  • the hydrophilicity of the coating according to the invention may be obtained by any appropriate method.
  • the coating is subjected to an oxidative treatment, such as plasma treatment or corona treatment after having been applied to the component.
  • the coating comprises a copolymer which is made hydrophilic by end-capping the copolymer with hydrophilic group or chain segments.
  • the hydrophilic group may, for example, be a negatively charged chemical group or phosphorylcholine (PC) groups, and the chain segment may, for example, be poly(ethylene oxide) (PEO) or poly(2-hydroxyethyl methacrylate) (pHEMA).
  • PC phosphorylcholine
  • the chain segment may, for example, be poly(ethylene oxide) (PEO) or poly(2-hydroxyethyl methacrylate) (pHEMA).
  • the plasma treated surfaces may be modified in order to further decrease the protein adsorption by coupling of hydrophilic polymer segments or functional groups.
  • These polymer segments or functional groups may be of the same kind as those described above, and may further be coupled to the functional groups generated during the plasma treatment.
  • the hydrophilic groups at the coating will tend to seek into the coating leaving the surface hydrophobic due to the hydrophobicity of the surrounding air. Accordingly, it is of great importance that the coating remains hydrophilic during storage until the medical article is filled with the protein solution. This may be secured by placing the coated article in a hydrophilic environment, such as by filling the medical article with the protein formulation shortly after the coating process.
  • the thickness of the coating depends on the specific coating, and is preferably from 0.005 to 10 ⁇ m, more preferably from 0.01 to 1 ⁇ m.
  • the optimal thickness depends on the dimensions and shape of the components, and it can easily be performed by one skilled in the art. If the coating is too thin the coating may be torn in use, thereby increasing the friction between the two components. When the thickness of the coating has reached a certain plateau value the friction forces are approximately constant even when the thickness is further increased.
  • the coating is preferably as thin as possible to reduce the costs.
  • the thin coating is preferably from 0,005 to 0,4 ⁇ m, such as from 0,015 to 0,25 ⁇ m, more preferably approximately 0,2 ⁇ m.
  • the medical article may be any article wherein two components are in frictional engagement with each other, such as a syringe and plunger, in particular a cartridge with a stopper.
  • the particular form or shape of the components of the article is not crucial for the present inventionen, as long as they fulfill the criteria for their use, e.g. container and fluid-tight stopper in frictional engagement.
  • the first component is preferably a container, such as a cartridge made of a material selected from glass, ceramic, metal and preferably plastic.
  • the plastic may be filled with inorganic or organic filler.
  • the first component is made of plastic material which is an excellent barrier against the contents of the protein solution, e. g. water and preservatives.
  • plastic materials are commercially available, e. g. polypropylene, cyclic polyolefins, polyester resin.
  • the second component is preferably a stopper at least partly made of a flexible material, such as for example a stopper made of any appropriate material with only the contacting surfaces made in a flexible material, such as rubber.
  • a stopper made of any appropriate material with only the contacting surfaces made in a flexible material, such as rubber.
  • An example is a stopper with an O-ring.
  • the stopper may also be made totally of a flexible material, such as rubber.
  • suitable rubber materials are available on the market, such as bromobutyl, Santoprene®, and Trefsin®.
  • the article may further comprise mixing means. It is preferred that the surface of the mixing means is at least partly coated with a coating as defined above. This is especially to reduce the protein adsorption to the mixing means, but it is also of importance that the friction between the mixing means and the other components is reduced.
  • the medical article according to the present invention is preferably a container 1 and a stopper 4 as depicted in Fig 1 A and Fig. 1 B comprising the cylinder wall 2 and a coating 3 on the inner surface of the cylinder wall 2.
  • Fig. 1 B the stopper 4 is depicted with a rubber end 5 to be inserted in the injection cylinder 1.
  • the diameter D of the stopper is slightly greater than the inner diameter of the injection cylinder to obtain a sufficient liquid tight sliding engagement.
  • the medical article is preferably constructed to avoid leakage of the liquid protein formulation, in particular without leakage between the stopper and the container wall. This is a problem in particular encountered with a container for storing and administrating (injecting) the formulation because the container is filled with the formulation and stored for a longer period before use. Accordingly, the pressure of the stopper against the container wall is adjusted to withstand leakage.
  • the coating may be applied either on both the components, in any combination, or on only one of the mentioned surfaces.
  • a coating according to the invention may be applied on one of the surfaces, while the other surface is coated with untreated, i.e. not hydrophilized linear or branched silicon oil.
  • at least the component having the largest surface area in contact with the protein formulation is coated according to the invention.
  • the coating is applied to substantially all the surfaces to be in contact with the protein solution, in order to reduce the risk of destabilisation of the protein solution. Furthermore, in order to maintain the low friction and reduced slip-stick phenomenon at any stage of frictional engagement between the two components the coating should be applied to the all the surfaces of at least one component to be in frictional engagement with the other component.
  • the coating on the first component is different from the coating on the second component, at least at the surfaces to be in frictional engagement with each other.
  • the coating on the first component and the second component may comprise, for example a hydrophilized poly(dialkyl siloxane) oil and a hydrophilized cross-linked poly(dialkyl siloxane) oil. respectively, or hydrophilized block copolymer and hydrophilized poly(dialkyl siloxane) oil.
  • the object of the present invention is also achieved by a medical article according to the invention coated with a hydrophilic coating on one component and on the other component coated with a coating responsible or substantially responsible for the low friction forces.
  • the static friction force between the first component and the second component increases gradually with the storage time from the moment of frictional engagement of the two components to reach a plateau value approximately 14 days after assembling of the components. Thereafter the static friction force is approximately constant. Accordingly, the static friction force measured 14 days after assembling the two components, such as placing a stopper in a container, can be taken as a measure of the long-term static friction forces.
  • the long-term static friction forces between the first and the second component are below 10 N, preferably below 8 N, more preferably below 6 N.
  • the dynamic friction force should preferably be as close to the static friction force as possible to secure an even movement of the second component relative to the first component during an injection.
  • the dynamic friction forces between the first and the second component are below 8 N, such as 6 N, more preferably below 4 N.
  • the long-term static friction forces as well as the dynamic friction forces depend on the dimensions of the two components.
  • the long-term static friction forces are measured with a container as described in the Examples.
  • Another aspect of the present invention is a process of producing a component coated as described above said process comprises adding the coating material to the component material prior to molding and subsequently molding the component from the mixture, or molding the component from the component material and subsequently applying the coating material to the at least one surface of the component, and hydrophilizing the coating material prior to the molding or after the molding.
  • the components of the medical article may be molded by any suitable process, such as injection molding.
  • the coating is applied to the component after the molding of said component.
  • the coating may be applied by any appropriate method, such as dip coating, spray coating or plasma polymerisation.
  • the coating material is preferably applied as a solution and the solvent removed after application, eg. by evaporation.
  • a hydrophilisation step may be accomplised prior to or after molding.
  • the coating comprises a copolymer being hydrophilised by end-capping the hydrophilisation step is preferably carried out prior to the coating step.
  • the hydrophilisation may take place as described above.
  • the component material and the coating material is mixed before molding and molded as a mixture.
  • the coating material preferably comprises a copolymer, such as a polyolefin-PDMS block copolymer endcapped with a hydrophilic segment or group. During the molding process the coating material will make for the surface of the component forming a coating fixed to the component.
  • Polypropylene (PP) containers depicted in Figure 1 A, with a volume of 3,5 ml, and an internal surface area of 14.1 cm 2 , having an inner diameter of 9.44 mm were used in the evaluation of the different coatings.
  • the diameter D of the stopper was 9.6 mm.
  • Polypropylene (PP) and bromobutyl rubber represents model materials for the container and stopper in the examples.
  • the used silicone oils were Dow Corning DC360 fluid® (DC360) and Dow Corning MDX4-4159 fluid® (MDX).
  • the molecular data of the polystyrene-polydimethylsiloxane (PSPDMS) block copolymer used are shown in Table 1 below.
  • Block copolymer designation Molecular weight of the PDMS bloc (kg/mol) Molecular weight of the PS block (kg/mol) PDMS content of the copolymer (wt %) BCP5 250 250 50
  • PP containers and rubber plungers were coated with silicone oil (MDX and DC360) by a dip coating method.
  • the containers were dip coated in heptane solutions of the silicone oils, and the rubber plungers were dip coated in a Dow Coming OS10® fluid solution of the silicone oils.
  • the concentrations were 1 % (w/v) for DC360, and 1 + 1 % (w/v) for the mixture of DC360 and MDX.
  • PP containers were also dip coated in chloroform solutions (1 % w/v) of the polystyrene-polydimethylsiloxane (PSPDMS) block copolymer. The dip coated samples were left to dry in air at ambient temperature.
  • PSPDMS polystyrene-polydimethylsiloxane
  • Coatings containing MDX were cured by storing the coated containers in an oven at 40 °C for 10 days. A cup of water was placed in the oven to maintain a relative humidity above 30 % during the curing.
  • the plasma treatments were performed by using a laboratory set-up.
  • the gas used in the treatment was a mixture consisting of 80 % argon and 20 % oxygen.
  • the equipment was operated at 40 W, at a pressure of 0.5 bar for 1.5 min.
  • the friction measurements were carried out as follows: After coating, drying, and in some cases curing, the plungers and the containers were assembled. The containers were filled with a commercial liquid insulin solution (Actrapid® from Novo Nordisk A/S, Penmix 30/70 ), sealed with aluminum caps, and stored at 37 °C. After the storage period, the aluminum caps were removed and the dynamic and static friction forces between the plungers and the containers were evaluated by using a Lloyds tensile tester at a constant displacement speed of 100 mm/min. The plunger was pushed down through the container by the tensile tester, and the force to do so was recorded as a function of the displacement.
  • a commercial liquid insulin solution Actrapid® from Novo Nordisk A/S, Penmix 30/70
  • the maximum static friction force was taken as the peak friction force reached shortly after the plunger begins to move, and the maximum dynamic friction force was taken as the maximum friction force reached after the maximum static friction force had been recorded.
  • the friction forces were measured immediately after assembling, and after 14 days to evaluate the influence of storage time on the friction forces. The results are shown in Fig. 2 and Fig. 3.
  • Water contact angle measurements were carried out with a Leitz sessile drop contact meter at ambient temperature. A 5 microliter droplet of Milli-Q water were pumped out onto the surface be means of a microsyringe, and the advancing angles were measured. Receding contact angles were measured after the droplet had been in contact with the surface for 60 sec. At least four measurements were made on different positions on each plate.
  • Insulin adsorption was measured by filling coated containers with 125 I-labeled Novo Nordisk Penmix 30/70® insulin with a protein activity of 100 U/ml, and a radio activity of 3.9 microCi/ml. After storage for 14 days at 37 °C the ⁇ -counts per minute (CPM) of the protein solutions in the containers were measured. The containers were subsequently emptied, and washed 5 times with Milli-Q water. The CPM of the washed containers were measured, and the insulin adsorption is reported as percentage of the original insulin solution detected on the ampoules after washing. The average value from measurements on five containers is reported for each given adsorption value. The water contact angle was measured as specified in example 1.
  • the insulin adsorption to the hydrophilic coating is significantly decreased as compared to the coating exhibiting a water contact angle of 105 °.
  • the decrease is more than 30 %.

Landscapes

  • Engineering & Computer Science (AREA)
  • Mechanical Engineering (AREA)
  • Medical Preparation Storing Or Oral Administration Devices (AREA)
  • Materials For Medical Uses (AREA)
  • Paints Or Removers (AREA)
  • Application Of Or Painting With Fluid Materials (AREA)
  • Infusion, Injection, And Reservoir Apparatuses (AREA)
EP99937894A 1998-03-06 1999-02-26 Medical article with coated surfaces exhibiting low friction and low protein adsorption Expired - Lifetime EP1060031B1 (en)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
DK30798 1998-03-06
DK30798 1998-03-06
DK73198 1998-05-28
DK73198 1998-05-28
PCT/DK1999/000093 WO1999044755A1 (en) 1998-03-06 1999-02-26 Medical article with coated surfaces exhibiting low friction and low protein adsorption

Publications (2)

Publication Number Publication Date
EP1060031A1 EP1060031A1 (en) 2000-12-20
EP1060031B1 true EP1060031B1 (en) 2003-09-03

Family

ID=26063739

Family Applications (1)

Application Number Title Priority Date Filing Date
EP99937894A Expired - Lifetime EP1060031B1 (en) 1998-03-06 1999-02-26 Medical article with coated surfaces exhibiting low friction and low protein adsorption

Country Status (4)

Country Link
EP (1) EP1060031B1 (ja)
JP (1) JP2002505177A (ja)
AT (1) ATE248662T1 (ja)
DE (1) DE69910982T2 (ja)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2151253A1 (de) 2008-07-31 2010-02-10 Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. Biokompatibilitätsschicht und beschichtete Gegenstände
US9993597B2 (en) 2012-05-29 2018-06-12 Becton Dickinson France Lubricant coating and medical injection device comprising such a coating
US11266568B2 (en) 2018-09-11 2022-03-08 West Pharmaceutical Services, Inc. Elastomer components containing taggants
US11325367B2 (en) 2017-12-15 2022-05-10 West Pharmaceutical Services, Inc. Smooth film laminated elastomer articles

Families Citing this family (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2006182960A (ja) * 2004-12-28 2006-07-13 Nipro Corp 医療用潤滑剤およびこれを塗布したシリンジ
US8084103B2 (en) * 2006-08-15 2011-12-27 Sakhrani Vinay G Method for treating a hydrophilic surface
DE102006049134A1 (de) * 2006-10-18 2008-04-24 Khs Ag Verfahren und Vorrichtung zur Behandlung von Behältern aus Kunststoff
CA2749354A1 (en) * 2009-03-30 2010-10-14 F. Hoffmann-La Roche Ag A method for avoiding glass fogging
EP2760509B1 (en) * 2011-09-27 2023-04-05 Becton Dickinson France Use of plasma treated silicone oil as a coating in a medical injection device
JP5945071B2 (ja) 2012-05-07 2016-07-05 ベクトン ディキンソン フランス 医療容器用潤滑性コーティング
EP3009354A1 (en) * 2014-10-15 2016-04-20 F. Hoffmann-La Roche AG Method for providing in a primary packaging container a dried solid product containing an active pharmaceutical ingredient
WO2018135228A1 (ja) 2017-01-18 2018-07-26 ダイキン工業株式会社 タンパク質低吸着性を有するタンパク質若しくはタンパク質を含む組成物の投与用、保存用、運搬用、または輸送用の容器及びタンパク質若しくはタンパク質組成物の製造用器材
US10493207B2 (en) 2017-02-27 2019-12-03 W. L. Gore & Associates, Inc. Medical delivery devices having low lubricant syringe barrels
JPWO2021221159A1 (ja) * 2020-05-01 2021-11-04
WO2022202881A1 (ja) 2021-03-25 2022-09-29 テルモ株式会社 持続投与装置

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2151253A1 (de) 2008-07-31 2010-02-10 Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. Biokompatibilitätsschicht und beschichtete Gegenstände
US9993597B2 (en) 2012-05-29 2018-06-12 Becton Dickinson France Lubricant coating and medical injection device comprising such a coating
US11135370B2 (en) 2012-05-29 2021-10-05 Becton Dickinson France Lubricant coating and medical injection device comprising such a coating
US11779706B2 (en) 2012-05-29 2023-10-10 Becton Dickinson France Lubricant coating and medical injection device comprising such a coating
US11325367B2 (en) 2017-12-15 2022-05-10 West Pharmaceutical Services, Inc. Smooth film laminated elastomer articles
US11266568B2 (en) 2018-09-11 2022-03-08 West Pharmaceutical Services, Inc. Elastomer components containing taggants

Also Published As

Publication number Publication date
ATE248662T1 (de) 2003-09-15
DE69910982D1 (de) 2003-10-09
EP1060031A1 (en) 2000-12-20
DE69910982T2 (de) 2004-07-15
JP2002505177A (ja) 2002-02-19

Similar Documents

Publication Publication Date Title
US6461334B1 (en) Medical article with coated surfaces exhibiting low friction and protein adsorption
US6482509B2 (en) Coating system providing low friction
EP1060031B1 (en) Medical article with coated surfaces exhibiting low friction and low protein adsorption
US6296893B2 (en) Pharmaceutical packing device comprising a hollow plastic body having an improved internal lubricant layer and method of making same
US9234118B2 (en) Coating system, articles and assembly using the same and methods of reducing sticktion
WO1999044755A1 (en) Medical article with coated surfaces exhibiting low friction and low protein adsorption
ES2431669T3 (es) Componentes médicos que tienen superficies recubiertas que presentan baja fricción y métodos para reducir la adherencia
US8816022B2 (en) Sealing members, articles using the same and methods of reducing sticktion
RU2590154C2 (ru) Смазочное покрытие для медицинского контейнера
US8802603B2 (en) Medical components having coated surfaces exhibiting low friction and low reactivity
KR101634031B1 (ko) 윤활제 코팅 및 그러한 코팅을 포함하는 의료용 주사 장치
US4822632A (en) Ionizing plasma lubricant method
EP1060030B1 (en) Coating system providing low friction
HU208786B (en) Coated implantate by tetracycline type antibiotic and process for producing it
JP2020040731A (ja) 医薬品および化粧品用の摺動層を有する包装材および方法、およびその製造のための調製物
EP0201915B1 (en) Ionizing plasma lubricant method
CN117163461A (zh) 玻璃容器和玻璃容器系统

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 20000821

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): AT BE CH CY DE DK ES FI FR GB GR IE IT LI LU MC NL PT SE

17Q First examination report despatched

Effective date: 20010911

GRAH Despatch of communication of intention to grant a patent

Free format text: ORIGINAL CODE: EPIDOS IGRA

GRAS Grant fee paid

Free format text: ORIGINAL CODE: EPIDOSNIGR3

GRAA (expected) grant

Free format text: ORIGINAL CODE: 0009210

AK Designated contracting states

Kind code of ref document: B1

Designated state(s): AT BE CH CY DE DK ES FI FR GB GR IE IT LI LU MC NL PT SE

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: NL

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20030903

Ref country code: IT

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT;WARNING: LAPSES OF ITALIAN PATENTS WITH EFFECTIVE DATE BEFORE 2007 MAY HAVE OCCURRED AT ANY TIME BEFORE 2007. THE CORRECT EFFECTIVE DATE MAY BE DIFFERENT FROM THE ONE RECORDED.

Effective date: 20030903

Ref country code: FI

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20030903

Ref country code: CY

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20030903

Ref country code: BE

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20030903

Ref country code: AT

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20030903

REG Reference to a national code

Ref country code: GB

Ref legal event code: FG4D

REG Reference to a national code

Ref country code: CH

Ref legal event code: EP

REF Corresponds to:

Ref document number: 69910982

Country of ref document: DE

Date of ref document: 20031009

Kind code of ref document: P

REG Reference to a national code

Ref country code: IE

Ref legal event code: FG4D

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: SE

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20031203

Ref country code: GR

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20031203

Ref country code: DK

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20031203

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: ES

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20031214

REG Reference to a national code

Ref country code: CH

Ref legal event code: NV

Representative=s name: PATENTS & TECHNOLOGY SURVEYS SA

NLV1 Nl: lapsed or annulled due to failure to fulfill the requirements of art. 29p and 29m of the patents act
PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: PT

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20040203

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: LU

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20040226

Ref country code: IE

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20040226

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: MC

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20040228

ET Fr: translation filed
PLBE No opposition filed within time limit

Free format text: ORIGINAL CODE: 0009261

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: NO OPPOSITION FILED WITHIN TIME LIMIT

26N No opposition filed

Effective date: 20040604

REG Reference to a national code

Ref country code: IE

Ref legal event code: MM4A

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: CH

Payment date: 20080214

Year of fee payment: 10

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: GB

Payment date: 20080220

Year of fee payment: 10

Ref country code: DE

Payment date: 20080221

Year of fee payment: 10

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: FR

Payment date: 20080208

Year of fee payment: 10

REG Reference to a national code

Ref country code: CH

Ref legal event code: PL

GBPC Gb: european patent ceased through non-payment of renewal fee

Effective date: 20090226

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: LI

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20090228

Ref country code: CH

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20090228

REG Reference to a national code

Ref country code: FR

Ref legal event code: ST

Effective date: 20091030

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: DE

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20090901

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: GB

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20090226

Ref country code: FR

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20090302