Glass cylinder for a piston-cylinder assembly with reduced friction and method for treating a glass cylinder for a piston-cylinder assembly

Description

[0001] The invention relates generally to arrangements with a cylinder and a piston running therein. More specifically, the invention relates to such arrangements with a glass cylinder.

[0002] Piston-cylinder designs are widespread in mechanical engineering. Typically, metal is used as the material for both the piston and the cylinder. Lubricants are used to allow the piston to slide smoothly and create a seal within the cylinder.

[0003] Plastics are also used in specific areas of technology. Some plastics have the advantage of generating very little friction, making lubricant-free applications possible. Plastic syringes for administering medication are one example.

[0004] In addition to plastic syringes, glass syringes are also used, often in the form of pre-filled syringes. Pre-filled syringes offer several advantages in pharmaceutical packaging compared to the conventional combination of vials and disposable syringes, such as precise drug dosing, guaranteed sterility, time savings in emergency situations, ease of use, and, last but not least, less waste and reduced environmental impact. A pre-filled syringe is typically defined as a three-part device consisting of the following components: (a) a syringe barrel with a suitable needle or a Luer adapter, (b) a rubber stopper that provides or ensures the integrity of the container closure, and (c) a plastic plunger rod used to advance the stopper through the glass barrel and thus administer the medication.Prefillable glass syringes are washed, siliconized, sterilized, and packaged by the primary packaging manufacturer. Therefore, all syringes also contain a fourth, often overlooked, component: the lubricant, which can significantly impact syringe function and drug stability.

[0005] Glass syringes offer the advantage of high heat resistance, making them easy to sterilize. Furthermore, their permeability to gases is very low compared to plastics. This allows medications to be stored in the syringe for extended periods. On the other hand, glass is a brittle material that can quickly seize or jam, leading to the shedding of glass particles, if not adequately lubricated. Therefore, it is common practice to coat the inside of glass syringes with a friction-reducing coating or lubricant. Today, the required lubricity is ensured through a controlled siliconization process, which allows the silicone profile to be individually tailored to specific customer requirements. Silicone oils are typically used for this purpose.

[0006] Several aspects of this syringe silicone coating pose a challenge for its use as pre-filled syringes: In specific cases, even small amounts of unbound silicone oil or silicone particles can significantly affect the medication and thus reduce its efficacy. This is particularly important to avoid with regard to biotech pharmaceuticals, as it can lead to the aggregation of specific proteins. For the reasons mentioned (avoiding silicone particles in medications and completely eliminating silicone for highly sensitive drugs), it is desirable to at least significantly reduce the silicone content or eliminate silicone entirely while maintaining the same friction properties and container closure integrity.

[0007] The siliconization of the pharmaceutical primary packaging, specifically the syringe barrel, is an extremely important aspect of the production of sterile, prefillable glass syringes today, as the functional interaction between the glass body and the stopper is crucial for the efficiency of the overall system. Both insufficient and excessive siliconization can cause problems in this context, as previously described. Therefore, a trend—through the use of modern application technologies—is to achieve an extremely uniform distribution of silicone oil in glass syringes, along with drastically reduced amounts of silicone oil. Another way to minimize the amount of free silicone oil in a syringe is the thermal fixation of the silicone oil to the glass surface in a process known as baked-on silicone. Silicone oil-free or lubricant-free glass bodies (e.g.,Syringes or cartridges are of great interest in light of the aforementioned disadvantages and the steadily growing market for highly sensitive biotech pharmaceuticals. Biotech pharmaceuticals are an important class of drugs (e.g., insulin, vaccines, antibodies, blood products, hormones, cytokines) that are manufactured with considerable technological effort and complex development and production methods, and are very sensitive to lubricants (e.g., silicone oil), which is why the challenges for conventional syringe technology are increasing.

[0008] For plastic syringes (COC or COP), the lubricity of special fluoropolymer coatings on specially developed plunger plugs is already being used to completely eliminate the need for siliconizing these syringes. However, this approach is only partially transferable to glass surfaces, as the material properties of plastics and glass differ significantly. Compared to plastic surfaces, glass surfaces are subject to greater dynamics and interaction with the surrounding atmosphere in the form of surface reactions. From this perspective, special considerations must be taken for pre-filled glass syringe devices and similar devices (e.g., cartridges) to keep their components sterile and to ensure their stability and optical clarity during transport and storage for up to several years.In particular, the friction between the stopper material and the syringe body can be considerable, which is why there is a need to reduce the friction between the stopper and the glass cylinder stably over the period of storage until use, without the use of oils or other lubricants.

[0009] US Patent 4767414 A describes a method for reducing static and dynamic friction between sliding surfaces by applying a lubricating film to at least one of the surfaces. A low-molecular-weight silicone oil is applied to one of the surfaces. The silicone oil and the surface are then plasma-treated.

[0010] US Patent 2004 / 0231926 A1 describes a process for producing a sliding layer in which the layer is cured at atmospheric pressure, using, among other things, an atmospheric pressure plasma. In addition to silicone oil-based layers, perfluoropolyether-based sliding layers can also be produced. However, the breakaway force, or static friction, of the latter layers proves to be higher compared to cured silicone oil layers. Furthermore, atmospheric pressure treatment, especially atmospheric pressure plasma treatment, can lead to an increased ingress of gases, particularly plasma reaction products, into the layer.

[0011] From WO 2011 / 029628 A1 it is also known to create a silicone-free sliding layer for a glass syringe with particularly low friction by crosslinking a silicone-free organic fluid in a low-pressure glow discharge.

[0012] Silicone sliding layers are also used in plastic syringes. Such sliding layers are known, for example, from US 2012 / 277686 A1 or US 2008 / 071228 A1. Another method for reducing piston friction in glass syringes is described in US 2008 / 044588.

[0013] For certain active ingredients, it would be desirable to use a glass syringe without a lubricating layer on the glass cylinder, while still maintaining good lubricating properties. This would also be advantageous for other piston-cylinder arrangements with glass cylinders.

[0014] The invention is therefore based on the objective of providing a corresponding piston-cylinder arrangement and a glass cylinder for such an arrangement.

[0015] This problem is solved by the subject matter of the independent claims. Advantageous embodiments of the invention are specified in the respective dependent claims.

[0016] To solve this problem, the invention provides a method for treating a glass cylinder for a piston-cylinder arrangement to reduce the friction of the piston on the cylinder's inner wall, in which the surface energy of the glass is increased in the interior space bounded by the cylinder's inner wall, thereby lowering the contact angle of the glass with water. a gas discharge acting on the glass at the inner wall of the cylinder and generated by an electric or electromagnetic field, or by the action of ozone on the glass surface, wherein After the action of the gas discharge, plasma or ozone, the glass on the inside of the cylinder is exposed to water, wherein the surface of the inside of the cylinder is formed by the glass of the glass cylinder, and wherein the contact angle of this surface with water is less than 15° and the variation of the contact angle of the glass with water in the longitudinal direction from end to end of the glass cylinder is less than 5°.

[0017] The invention is particularly preferred for use in glass syringes.

[0018] To achieve a sliding effect that allows for easy movement of the piston within the glass cylinder, the coefficient of friction is currently modified to create larger water contact angles. This makes the surface of the glass cylinder hydrophobic. The equally hydrophobic sliding partner, in this case the stopper or piston, can then slide easily across the surface with minimal force. In the prior art, this is achieved, for example, by siliconizing the glass surface.

[0019] The invention takes the opposite approach by creating a hydrophilic glass surface. Due to the surface's wetting properties, a film of water forms, and the stopper slides on this film with minimal force.

[0020] According to one embodiment, the water is not water from an active ingredient preparation contained in the piston-cylinder assembly. Rather, the water loading is only temporary. Typically, after being loaded with water, the glass cylinder is stored empty until it is filled with the active ingredient preparation to be administered, which is often also water-based or at least contains water. According to another embodiment, however, the water loading can also be achieved by filling the cylinder with a water-containing active ingredient preparation.

[0021] If the increase in the surface energy of the glass is caused by the action of ozone on the glass surface, the ozone is preferably produced by at least one of the following processes: a gas discharge in an oxygen-containing gas, irradiation with ionizing rays, UV irradiation generated.

[0022] In a preferred embodiment of the invention, the gas discharge takes place in an oxygen-containing gas, in particular pure oxygen or a gas mixture, such as an oxygen-nitrogen mixture or an oxygen-noble gas mixture. It has been shown that air is also suitable as a process gas to produce the reduction of the contact angle with water provided for in the invention.

[0023] In a particular embodiment, no low-pressure gas discharge is performed. Instead, the gas discharge can occur at a gas pressure of at least 100 millibars. A gas discharge at atmospheric pressure is particularly preferred. In this way, sealing the glass cylinder and evacuation are unnecessary. According to yet another embodiment, the gas discharge takes place at a low pressure of at most 10 mbars. A suitable pressure is, for example, 0.3 millibars.

[0024] A corona discharge is particularly suitable for this purpose. This type of discharge allows the treatment to be carried out even at atmospheric pressure, while ensuring a homogeneous surface energy level on the inside of the glass cylinder. Ozone can also be generated using a corona treatment variant. Ozone can also be produced in a gas discharge, such as a plasma discharge, or by irradiation with UV light.

[0025] According to yet another preferred embodiment, the gas discharge comprises plasma treatment, or the generation of a plasma.

[0026] Plasma treatment, as defined in this invention, is a special form of gas discharge in which the discharge leads to the formation of a plasma. Alternating electromagnetic fields can be used to generate the gas discharge in the form of a plasma for plasma treatment. Suitable alternating fields include RF, HF, or microwave fields. The term "gas discharge" as used in this disclosure is not limited to discharges in DC fields.

[0027] Several methods exist for loading the glass cylinder with water. For example, the cylinder could be rinsed with water or immersed in a water bath. Spraying or ultrasonic nebulization are further possibilities. According to a preferred embodiment of the method, loading with water involves introducing water vapor into the interior of the glass cylinder. This offers the advantage that a drying step to remove residual water after emptying can be omitted. Furthermore, the introduction of water vapor prevents contamination of the glass surface with substances dissolved in the water. Particularly preferably, the water vapor is introduced in the form of water-enriched air.

[0028] After their manufacture and storage under normal atmospheric conditions, glass surfaces, particularly after some time in air, exhibit a surface energy that is associated with a contact angle of typically 20° to 60°. This contact angle is significantly reduced by the method according to the invention, thereby hydrophilizing the surface.

[0029] In addition to the low contact angle between the glass and water achievable with the invention, a homogeneous distribution of surface energy on the inner wall of the cylinder is also advantageous. If the surface energy changes, the frictional resistance to the friction partner also varies. This can even lead to the piston becoming blocked at a given applied thrust force. Even a merely changing resistance when moving the piston can be very disadvantageous, for example, if it makes precise dosing of medication with a glass syringe difficult. According to the invention, therefore, the gas discharge, plasma, UV, or ozone treatment not only reduces the contact angle with water, but also causes the contact angle of the glass with water to vary along the axial direction of the glass cylinder, the magnitude of which is reduced by the gas discharge, plasma, UV, or ozone treatment.A glass cylinder according to the invention is generally characterized by the fact that the variation of the contact angle in the longitudinal direction from end to end of the glass cylinder is less than 5°.

[0030] The invention enables the production of a glass cylinder for a piston-cylinder arrangement, in which the surface of the cylinder's inner surface is formed by the glass of the cylinder itself, and the contact angle of this surface with water is less than 15°. Since the surface is formed by the glass itself, the glass cylinder is therefore not coated, unlike known glass syringes.

[0031] In principle, all types of glass can be used, such as soda-lime glass, aluminosilicate glass, borosilicate glass, quartz glass, various glass ceramics, and others. Borosilicate glasses are particularly suitable.

[0032] The hydrophilization effect, as induced by the gas discharge according to the invention, is stabilized by loading with water. The reaction of the glass surface with water molecules following the gas discharge evidently leads to the reactive centers on the surface reacting with water and thus becoming saturated. This prevents or significantly hinders a reaction with other reactants. Preferably, the loading process is to begin within 60 minutes after the gas discharge has ceased. This loading process can, in particular, also include filling with the active ingredient preparation.

[0033] The investigations published by J. Abenojar et al., International Journal of Adhesion & Adhesives 44 (2013) 1-8, show that plasma treatment of a glass surface using a plasma torch results in an increase in bridging oxygen relative to non-bridging oxygen. A corresponding effect can also be observed with gas discharge, plasma, UV, or ozone treatment induced inside the glass cylinder. Additionally, carbon-containing compounds that have deposited on the glass surface from the atmosphere are broken down or fragmented, or their bonds to the silanol groups on the glass surface are broken and subsequently carried away via airflow / convection.

[0034] When glass surfaces are activated with UV light or ozone, the following occurs: Due to their high energy, UV photons are able to break chemical bonds in the molecular network of the glass. The opened bonds strive to return to a chemically stable state as quickly as possible. Oxygen from the atmosphere or ozone, which can be formed from ambient oxygen, especially when exposed to UV radiation, serve as reactants. The open bonds are saturated by the atoms and radicals formed, and new compounds are created on the glass surface. This gives the surface a higher polarity, which also affects the surface energy and thus the contact angle with water.

[0035] According to one embodiment of the invention, the ratio of bridging oxygen to non-bridging oxygen on the inner surface of the cylinder is increased compared to this ratio inside the glass. According to another embodiment of the invention, the ratio of oxygen to silicon on the inner surface of the cylinder is increased compared to this ratio inside the glass. This effect, which increases the polar component of the surface energy, is also described in the aforementioned article.

[0036] From T. Ishibe et al., "Absorption of nitrogen dioxide and nitric oxide by soda lime", British Journal of Anaesthesia 1995; 75:330-333, it is further known that nitric oxide, NO, and nitrogen dioxide, NO₂, are absorbed by glass, with the absorption of NO occurring only in the simultaneous presence of NO₂. Both substances are generated during a gas discharge in a gas containing nitrogen and oxygen, and thus particularly also during a gas discharge in the presence of air. Therefore, according to another embodiment of the invention, the glass on the inner surface of the cylinder contains nitrogen oxides or, more generally, nitrogen compounds on or near the surface.

[0037] Using a glass cylinder as described above and as can be manufactured according to the invention, a piston-cylinder arrangement can now be produced comprising the glass cylinder and a piston inserted into the glass cylinder, which is also referred to as a plug. The piston runs directly on the glass of the glass cylinder, and at least the running surface of the piston is formed by a plastic material. The plastic of the running surface has a larger contact angle with water than the surface of the cylinder's inner wall formed by the glass of the glass cylinder. Typically, the difference is so large that the running surface of the piston can be characterized as hydrophobic and the glass as the friction partner as hydrophilic.

[0038] In particular, the contact angles between the plastic running surface and the cylinder inner wall with water can have a difference of at least 60°, preferably at least 70°. This large difference allows for good sliding properties without the need for a lubricant, such as the silicone oil otherwise used. According to a further development of the invention, the invention can also be used to selectively adjust a specific, predetermined difference in the contact angles between the piston running surface and the cylinder inner wall by performing gas discharge, plasma, or ozone treatment until the contact angle of the glass surface has decreased sufficiently to achieve the predetermined difference. This also results in a homogeneous contact angle along the entire length of the cylinder.

[0039] In general, the described method can be used whenever hydrophilic glass surfaces need to be produced. This is not limited to cylindrical shapes, but in special embodiments can also include flat shapes, which in certain embodiments can subsequently be shaped, for example by rolling a thin glass sheet.

[0040] A liquid active ingredient preparation can then be drawn into and stored in the piston-cylinder assembly, preferably designed in the form of a glass syringe, when the piston is retracted. In this way, a pre-filled syringe is provided.

[0041] Especially with complex active pharmaceutical ingredients (APIs) with high molecular weight, such as insulin, vaccines, antibodies, blood products, hormones, cytokines, and generally protein-based APIs, the use of silicone to reduce friction between the piston and cylinder poses a risk of agglomeration of the respective API on the siliconized surface or the formation of dissolved silicone particles within the pharmaceutical. The same applies to other organic lubricants. The glass syringe according to the invention, which is particularly free of silicone or lubricants, eliminates this problem or at least significantly reduces the risk of agglomeration. According to an advantageous embodiment of the invention, a piston-cylinder arrangement in the form of a glass syringe is provided, in which a liquid API preparation containing an API with a molecular weight of at least 1000 grams / mol is contained.

[0042] The invention is explained in more detail below with reference to exemplary embodiments and the enclosed figures. Brief description of the characters

[0043] Fig. 1 shows a device for treating a glass cylinder by means of a corona discharge. Fig. 2 shows another device for treating a glass cylinder by means of a corona discharge or another form of plasma. Fig. 3 is a diagram showing measured values ​​of the contact angle at various longitudinal positions of an untreated glass syringe and a syringe treated by means of a gas discharge. Fig. 4 shows a filled glass syringe. Fig. 5 shows a device for treating a glass cylinder by means of a radiation source for ionizing radiation. Fig. 6 is a diagram showing measured values ​​of the contact angle at various longitudinal positions of an untreated glass syringe (reference) and of syringes treated according to the invention. Fig. 7 is a diagram showing measured values ​​of the static-static friction forces for an untreated glass syringe (reference) and for syringes treated according to the invention.Figure 8 is a bar chart showing contact angle measurements for glass syringes treated by corona discharge over various storage times.

[0044] Generally, without limitation to the in Fig. 1 The illustrated example, according to one aspect of the invention, is a device 7 for treating a glass cylinder 3 for a piston-cylinder assembly to reduce the friction of the piston against the inner wall of the cylinder, wherein the device 7 is configured to generate a corona discharge in the glass cylinder 3. The device 7 comprises a high-frequency generator 13, a high-voltage transformer 14, and an electrode station 15.

[0045] The high-frequency generator 13 produces an output signal whose frequency preferably adjusts automatically within the range of 15–25 kHz depending on the resistance, thereby optimizing the treatment performance. The electrode station 15 of the device 7 comprises at least one electrode 150 and one counter electrode 151. The electrodes can be specially adapted for each application or to different shapes of glass cylinders 3. The functionalizing corona discharge can be generated with air at atmospheric pressure. The electrode 150 is elongated and inserted axially into the glass cylinder 3. The counter electrode 150 is tubular and surrounds the glass cylinder 3. This ensures an almost homogeneous field distribution, so that the glass 2 surface of the inner 30 is uniformly exposed to the corona discharge.To ensure that the effect of the corona discharge is particularly uniform, a relative movement of glass cylinder 3 and the arrangement of electrodes 150, 151 can also be carried out during the corona discharge.

[0046] In the example shown, the glass cylinder 3 is the cylinder for a glass syringe 1. The glass cylinder 3 includes an inner cylinder wall 30 as a sliding surface for a piston 5, which defines a cylinder interior 31, as well as a retaining element for a syringe needle, typically designed as a Luer cone 32. Such glass cylinders 3 also typically have a flange 33 at the piston insertion opening 34. If the electrical discharge is not performed in air and / or at atmospheric pressure, the glass cylinder 3 can also be sealed at this flange 33 to at least partially evacuate the interior 31.

[0047] Corona discharge is a preferred embodiment of the invention. Besides gas discharges, such as plasma treatment and specifically corona discharges, there are other methods that modify the surface of the glass 2 according to the invention. In particular, these can generally be methods that generate radicals which then react with the glass 2. For example, ozone can be generated by a gas discharge in an oxygen-containing gas or by irradiation with ionizing radiation, such as UV radiation, for example from ambient oxygen. According to one embodiment, the device 7 comprises a loading device 8 for loading the inner surface 30 of the glass cylinder 3, which has been previously treated with the gas discharge, with water. Preferably, a device 10 for enriching air with water is provided to supply air with a high humidity level.Air is then introduced into the interior 31 of the glass cylinder by means of a feed device 10. Unlike in . Fig. 1 The loading device 8 can also include a separate loading station. In this embodiment of the invention, the glass cylinders are successively fed first to a treatment station for treating the inner surface 30 with the gas discharge and then to a loading station for loading with water.

[0048] However, it has also been shown that the hydrophilic properties of the glass surface remain stable after treatment with gas discharge according to the invention, such as plasma or corona discharge, even without temporary charging. According to one embodiment, the charging device can therefore be omitted.

[0049] According to another, in Fig. 2In the illustrated embodiment, a device 7 according to the invention can be used, which is a modification of the arrangement known from WO 2012 / 097972 A1. The device 7 comprises at least one glass cylinder receptacle 15 with one, preferably several, receiving chambers 16, which have at least one open end 17 through which a glass cylinder 3 to be treated can be inserted, such that an opening of the glass cylinder 3 faces the open end of the receiving chamber 16. Furthermore, the device 7 comprises a slidable closing element 18, which can be brought together with the glass cylinder receptacle 15 via a lifting device 19, so that when closing by means of the lifting device 19 by moving the closing element 18 onto the glass cylinder receptacle 15, a received glass cylinder 3 is sealed at an opening of the glass cylinder, preferably at its piston insertion opening 34, against the external atmospheric pressure.Furthermore, the device 7 comprises a device 6 for generating a gas discharge, in this embodiment sealed from the external atmospheric pressure, in particular a corona discharge or another form of plasma with two electrodes, via which an electric or electromagnetic field can be generated inside a contained and sealed glass cylinder 3. Similar to the one described in . Fig. 1 In the illustrated example, one of the electrodes 150 is an inner electrode that is inserted axially into the glass cylinder 3 through the piston insertion opening 34. The glass cylinder receptacle 15 can then form or contain the counter electrode.

[0050] The device 6 for generating a gas discharge, in particular a corona discharge or a plasma, for example in an O₂, O₂ / Ar or O₂ / N₂ atmosphere, comprises a device 20 for evacuating the interior 31 via a gas-tight connection at the closing element 18 and at least one treatment tool which can be joined with the open end 17 of the glass cylinder receptacle 15 for at least one partial step of the surface treatment of the containers. In a particular embodiment, the evacuation is not carried out completely, or a desired process gas is supplied from a process gas container 23 after evacuation, so that the gas pressure during the gas discharge is at least 100 millibar.

[0051] In a further preferred embodiment, the evacuation is carried out down to the low-pressure range, so that the gas pressure during the surface treatment is at most 10 mbar, but preferably at least 0.3 mbar.

[0052] The device 7 further comprises a loading device 8, spatially separate from the device 6 for generating the gas discharge, in particular a corona discharge or another form of plasma, with which a specific quantity of water can be applied to the inner wall 30 of the glass cylinder. A transport device 24 moves the glass cylinder receptacle with the glass cylinders it contains from the device 6 for generating a gas discharge, in particular a corona discharge or another form of plasma, to an optional loading device 8. As shown, a lifting device 19 can also be provided for the loading device 8 to bring the loading tool together with the glass cylinder receptacle 15 and the glass cylinders 3 contained therein. The loading device 8 comprises, as in the embodiment of the Fig. 1A device 9 for enriching air with water. The enriched air is introduced into the glass cylinders via gas lances 91.

[0053] The device 6 can be configured to generate both a corona discharge and another form of plasma, for example a glow discharge.

[0054] The process step of treatment with gas discharge, plasma, or ozone, and the associated activation of the inner surface of the glass 30, can be repeated as often as desired to potentially improve the result. According to the invention, water loading is performed, with the activation and subsequent loading, preferably in the form of purified air enriched with water (WFI), being carried out at least twice in succession. It is also conceivable to perform the process steps independently of one another as a single-step process in certain applications.

[0055] The gas discharge can be controlled and, if necessary, readjusted with regard to power and treatment duration. The sliding coefficient on the surface can be specifically adjusted to the respective container via the power of the source and the residence time in this process step. This allows the surface properties to be specifically adapted to the properties of the stopper to be inserted later. The treatment according to the invention eliminates the risk of layer delamination or particle formation, thereby minimizing any interaction with the pharmaceutical and the risk of contamination for the patient.

[0056] A further advantage of the invention is the universal applicability of the method and the device for a wide variety of packaging materials. The method according to the invention can also be used as a cost-effective and safe alternative to standard or baked-on silicone coating. In a first step, the sliding surface, in the form of a glass surface, is cleaned and activated by means of a high-frequency, high-voltage discharge. In a second process step, the first sliding surface is brought into contact with or loaded with water, preferably WFI water in the form of vapor. When loading with enriched air, the amount of water is so small that an additional drying step can be omitted. However, the contact with water can also be achieved by filling the surface with an active ingredient preparation.

[0057] In addition to the low contact angle of the glass 2 with water achievable according to the invention, a homogeneous distribution of surface energy on the inner wall of the cylinder 30 is also advantageous. If the surface energy changes, the frictional resistance to the friction partner also varies. This can even lead to the piston locking up at a given applied thrust force. Even a merely changing resistance when moving the piston 5 can be very disadvantageous, for example, if it prevents precise dosing of medication with a glass syringe 1, as is the case, for instance, in Fig. 4As depicted, this is more difficult. According to the invention, therefore, the gas discharge, plasma, UV, or ozone treatment not only reduces the contact angle with water, but also causes the contact angle of the glass 2 with water to vary along the axial direction of the glass cylinder, the magnitude of which is reduced by the gas discharge, plasma, UV, or ozone treatment. A glass cylinder 3 according to the invention is generally characterized in that the variation of the contact angle in the longitudinal direction from end to end of the glass cylinder 3 is less than 5°.

[0058] An example of this is shown in the diagram of the Fig. 3This diagram shows the measured values ​​of the contact angle between the glass 2 and water at four longitudinal positions of an untreated glass syringe 1 and a glass syringe 1 treated by means of a gas discharge. Position 1 is located at the piston insertion opening 34 of the glass syringe 1, as for example in Fig. 4 shown. The other positions 2, 3 and 4 are spaced from position 1 by 1.3 cm, 2.3 cm, 3.3 cm and 4.3 cm respectively.

[0059] The measured values, represented as squares, were measured on an untreated glass syringe 1. The measured values ​​represented as circles are those measured on a syringe treated internally by means of a gas discharge according to the invention. Filled symbols represent the measured values ​​at the beginning of the experiment. After this first measurement, the glass syringes 1 were stored in a protective gas atmosphere for four days, after which a further measurement was carried out. These measured values ​​for the untreated and the syringe 1 according to the invention are each represented by open symbols, i.e., open squares (untreated syringe) and open circles (treated syringe).

[0060] The contact angle measurements were performed using the sessile drop method according to DIN 55660, with the following minor deviations from the standard: The measurements were taken at room temperature (22°C) and 37% relative humidity (the standard is 23°C, 50% RH). Due to the curvature of the surface, drops with a volume of 1.5 microliters were used instead of the specified 2 microliters.

[0061] As is evident from the measured values, the treatment according to the invention with a gas discharge leads to a reduction of the contact angle with water to below 10°. It is also particularly advantageous that the effect is maintained over the storage period of 4 days. Unlike the untreated syringe, the fluctuation of the contact angle along the longitudinal direction of the glass cylinder 3 is very small. In the untreated syringe, the contact angle is greatest at the piston insertion opening 34 and decreases towards the other end, i.e., towards the Luer cone. The difference between both the delivered syringe and the one stored for 4 days is approximately 15°. Thus, the variation of the angle is already greater than the contact angle of the glass cylinder 3 treated according to the invention. This variation is less than 5° in the illustrated example. A variation of less than 3° is also generally possible, as the example also shows.

[0062] The low contact angle of the example according to the invention was achieved with a single treatment. In general, according to another embodiment of the invention, it is also possible to repeat the steps of generating a gas discharge and loading with water at least once.

[0063] Fig. 4Figure 1 shows a preferred application of a piston-cylinder arrangement 4 according to the invention in the form of a glass syringe 1. In particular, the glass syringe 1 can be provided as a pre-filled syringe, wherein, when the piston 5 is retracted, a liquid active ingredient preparation 11 is contained in the interior 31 of the glass cylinder 3. The glass syringe 1 can also already be equipped with a cannula 35 attached to the Luer cone. For example, the cannula 35 can be glued in place. The attachment of the cannula 35 can also be carried out, for example, using a method as described in WO 2012 / 034648 A1. In this method, the cannula is melted into the Luer cone, thus eliminating the need for plastics by avoiding adhesive bonding. The disclosure of the aforementioned document, with respect to the method of radiation-assisted heating of the glass and melting the cannula, is also fully incorporated into the present application.

[0064] The special feature of the glass syringe 1 according to the invention is that the running surface 50 of the piston 5 runs directly on the glass 2 of the glass cylinder 3, meaning that no lubricant layer, in particular no silicone-based lubricant, is present. Due to the low contact angle of the treated glass 2, the liquid active ingredient preparation forms a liquid film on the surface on which the running surface 50 glides. The running surface 50 of the piston 5 is preferably made of a plastic, in particular a plastic that has a larger contact angle with water than the glass surface treated according to the invention. The contact angles of the plastic of the running surface 50 and the inner wall of the cylinder 30 with water differ by at least 60°, preferably at least 70°. According to one embodiment of the invention, the plastic of the running surface is selected such that its contact angle with water is at least 70°, preferably at least 80°.

[0065] As mentioned, for a given material of the running surface 50, a specific contact angle difference can also be deliberately set by lowering the contact angle of the glass 2 by the duration and / or intensity of the gas discharge, plasma, UV or ozone treatment until the desired difference is achieved.

[0066] The running surface 50 can be integral with the remaining part of the piston 5 and the push rod 33. Optionally, a different plastic can be used for the running surface, for example, by using a plug or piston 5 in which at least the surface of the seal has a halogenated polymer, preferably a fluoropolymer. Such plugs, which are desirable, for example, for certain active ingredients to be administered, prove to be particularly advantageous in conjunction with the syringe according to the invention and with regard to the sliding and sealing properties.

[0067] Since there is no risk of coagulation of more complex active ingredients under the influence of silicone, as is the case with silicone-containing lubricating films, the invention is particularly suitable for such active ingredients. This advantage is especially true for active ingredients with molecular weights of 1000 grams per mole.

[0068] It is evident to those skilled in the art that the invention is not limited to the specific examples shown in the figures, but rather can be varied in many different ways. For example, in the example of the Fig. 4 A syringe with a permanently attached cannula 35 is shown. The cannula 35 can also be attached only when needed. Cartridges are also considered syringes within the meaning of the invention. Fig. 5Figure 7 shows parts of a device 7 for treating a glass cylinder 3 using a radiation source 26 for ionizing radiation, in particular a UV lamp 27. In the exemplary embodiment, the device 7 comprises a UV lamp 27, for example, in the form of a low-pressure UV lamp with a tube having a wavelength of 185 / 254 nanometers. By irradiating the glass cylinder 3, in particular the glass syringe 1, ozone is generated inside the glass cylinder, which is then exposed to the inner wall of the glass cylinder 3 for a desired time. The treatment can be arranged inside or outside the surface of the glass 2. The process of activating the surface via ozone can also be repeated as desired to improve the result. The coefficient of friction on the surface can be adjusted by the residence time in this process step on the respective container, the glass 2, the stopper, or the...Piston 5 and the other object are adjusted precisely. The treatment according to the invention does not pose a risk of layer detachment or particle formation, thereby minimizing any interaction with the pharmaceutical and the risk of contamination for the patient.

[0069] A further advantage of the invention is the universal applicability of the method and the device for a wide variety of packaging materials. The method according to the invention can also be used as a cost-effective and safe alternative to standard or baked-on silicone coating.

[0070] Ozone can also be produced by ionizing oxygen-containing gas, for example by irradiation in a reaction chamber separate from piston 5, and the ozone-containing gas from the reaction chamber can then be directed into piston 5.

[0071] As in the embodiment with treatment by a gas discharge, the hydrophilization is stabilized by the action of ozone through reloading with water, for example by water vapor.

[0072] The methods according to the invention allow for long-term stable surface treatment including transport and storage for up to several years.

[0073] Three treatments of the cylinder inner walls 30 of glass syringes 1 according to the invention are described below. According to In embodiment 1, the surface of the inner wall 30 of a glass syringe 1 is modified by means of a corona discharge in air. For this purpose, the glass syringe 1 is placed in a device 7 according to Fig. 1The counter electrode 151, made of brass, is mounted, and the electrode 150, made of aluminum, is inserted into the glass cylinder 3. The corona discharge takes place at an effective voltage of 3 kV and a frequency of 15 kHz. The duration can be varied and is 1 second in this example (tested from 0.1 to 30 seconds). According to embodiment 2 The surface of the inner wall of the cylinder 30 of a glass syringe 1 is modified using UV / ozone. For this purpose, the glass syringe 1 is placed in a device 7 according to Fig. 5 The patient was exposed to UV radiation from UV lamp 26 and ozone for a period of time between 1 second and 10 minutes. In this specific example, the treatment duration was 15 seconds. According to embodiment 3 The surface of the inner wall of the cylinder 30 of a glass syringe 1 is modified using oxygen / plasma. For this purpose, the glass syringe 1 is placed in a device 7 according to Fig. 2The electrode 150 is positioned within the cavity of the glass cylinder 3, and the glass syringe 1 is sealed. The reactive gas is introduced through the electrode 150 itself. The oxygen pressure is set to 0.3 mbar, and the plasma is ignited for 10 seconds at a frequency of 60 kHz and a current of 10 mA.

[0074] In Fig. 6The measured values ​​of the contact angle at four different longitudinal positions of an untreated glass syringe (reference), a glass syringe 1 treated for 1 second by corona discharge in air (according to embodiment 1), a glass syringe 1 treated for 15 seconds by UV / ozone (according to embodiment 2), and a glass syringe 1 treated for 10 seconds by oxygen / argon (according to embodiment 3) are shown. The distance from the flange (also referred to as the collar) at the piston insertion opening 34 of the respective glass syringe 1 is indicated. The first position is located 2 mm from the flange 33. The further positions are indicated at distances of 10 mm, 18 mm, and 26 mm from the flange 33 at the piston insertion opening 34. The contact angle measurements were performed using the instrument described above. Fig. 3 The described procedure was carried out.

[0075] As in Fig. 6As can be seen, the contact angle of the cylinder inner wall 30 of the glass syringe 1 treated by corona discharge is less than 10°.

[0076] The contact angle of the cylinder inner wall 30 of the glass syringe 1 treated with UV / ozone is according to Fig. 6 also dropped to a value of less than 10°, homogeneously over the length of the syringe.

[0077] As in Fig. 6 As shown, the contact angle of the cylinder inner wall 30 of the glass syringe 1 treated with oxygen / plasma is also homogeneously less than 10° over the length of the syringe.

[0078] Fig. 7 Figure 1 is a diagram showing measured values ​​of the static-static friction forces for an untreated glass syringe (reference) and for glass syringes treated according to the invention. 1. As in Fig. 7As can be seen, the static friction force measured on the glass syringe 1 treated in air for 1 second by means of corona discharge (according to embodiment 1) is significantly lower than for the untreated reference glass syringe, which is due to a homogeneous, superhydrophilic surface.

[0079] After corona discharge, the glass syringes were stored for 12 weeks at room temperature and the static friction was measured again. The values ​​are comparable to those of freshly treated syringes, as in Fig. 7 depicted.

[0080] The static friction force of the glass syringes 1 treated with UV / ozone for 15 seconds (according to embodiment 2) is according to Fig. 7 also significantly lower than for the untreated reference glass syringe.

[0081] The same applies to the glass syringes 1 treated with oxygen / argon for 10 seconds (according to embodiment 3), as in Fig. 7depicted.

[0082] To test the long-term stability of the treatment, glass syringes 1 were treated by Korana discharge (according to embodiment 1) and subsequently stored at room temperature, and the contact angle was measured after storage intervals of 1 day, 7 days, 28 days, 6 weeks, 9 weeks, 12 weeks, 17 weeks, 21 weeks and 29 weeks. Fig. 8 A bar chart showing the mean values ​​of the contact angle measurements for 10 glass syringes treated by corona discharge per group at 4 positions each over the specified storage times is given.

[0083] As from Fig. 8 As can be seen, the contact angle remains stable over the storage period of up to 29 weeks. This is significantly longer than described in the literature (S. Takeda, J. Non Cryst Solids, (249) 199, 41-46), where the contact angle of various glass types rose again to a constant value after approximately 8 days. Reference symbol list 1 glass syringe 2 Glass 3 Glass cylinder 4 Piston-cylinder arrangement 5 Pistons 6 Device for generating a gas discharge 7 Device for treating a glass cylinder 3 8 Loading device 9 Device for enriching air with water 10 Feeding device 11 Active ingredient preparation 13 High-frequency generator 14 high-voltage transformer 15 Glass cylinder mount 16 Admissions chamber 17 Open ending of 16 18 Locking element 19 Lifting device 20 Evacuation facility for 31 23 Process gas container 24 Transport equipment 26 Radiation source for ionizing radiation 27 UV lamps 30 Cylinder inner wall 31 Interior of 3 32 Luer taper 33 flange 34 Piston insertion opening 35 cannula 37 Push rod 50 Running surface of 5 91 Gas lances 150 electrode 151 Counter electrode

Claims

1. A method for treating a glass cylinder (3) for a plunger-cylinder assembly (4) for reducing friction of the plunger (5) on the cylinder inner wall (30), wherein in the interior space (31) bounded by the cylinder inner wall (30) the surface energy of the glass (2) is increased and thereby the contact angle of the glass (2) with water is lowered by - subjecting the glass (2) at the cylinder inner wall (30) to a gas discharge generated by an electrical or electromagnetic field; or - subjecting the glass surface (2) to ozone, wherein after the subjecting to the gas discharge, the plasma or the ozone, the glass (2) on the inner surface (30) of the cylinder is exposed to water; wherein the surface of the cylinder inner side (30) is defined by the glass (2) of the glass cylinder (3), and wherein the contact angle of this surface with water is less than 15°, and wherein the variation of the contact angle of the glass with water in the longitudinal direction from end to end of the glass cylinder is less than 5°.

2. The method according to the preceding claim, characterised in that the exposure to water is achieved by filling with a water-containing active-substance preparation.

3. The method according to any one of the preceding claims, characterised in that the gas discharge is performed in an oxygen-containing gas, in particular in pure oxygen or in an oxygen-nitrogen mixture or in a mixture of oxygen and noble gas or in air.

4. The method according to any one of the preceding claims, characterised in that the ozone is generated by at least one of the following processes: - a gas discharge in an oxygen-containing gas; - an irradiation with ionizing radiation; - a UV irradiation.

5. The method according to any one of the preceding claims, characterised by at least one of the following features: - the gas discharge is performed at a gas pressure of at least 100 millibar or at a gas pressure of at most 10 millibar; - the gas discharge comprises a corona discharge or a plasma treatment.

6. The method according to any one of the preceding claims, characterised by at least one of the following features: - the contact angle of the glass with water along the axial direction of the glass cylinder exhibits a variation, the magnitude of which is reduced by the gas discharge or by the subjecting to ozone; - a differential between the contact angles of a sliding surface (50) of the plunger (5) and of the cylinder inner surface (30) is predefined, and the gas discharge or the subjecting to ozone is continued until the contact angle of the glass is reduced such that the predefined differential is achieved.

7. The method according to any one of the preceding claims, characterised in that the steps of generating a gas discharge or of subjecting to ozone and of exposing to water are repeated at least once.

8. A glass cylinder (3) for a plunger-cylinder assembly (4), producible by a method according to any one of the preceding claims, wherein the surface of the cylinder inner side (30) is defined by the glass (2) of the glass cylinder (3), and wherein the contact angle of said surface with water is less than 15°, and wherein the variation of the contact angle of the glass with water in the longitudinal direction from end to end of the glass cylinder is less than 5°, characterised by at least one of the following features: - at the surface of the cylinder inner side (30), the ratio of bridging oxygen to non-bridging oxygen is increased relative to the value of this ratio in the interior of the glass (2); - at the surface of the cylinder inner side (30), the ratio of oxygen to silicon is increased relative to the value of this ratio in the interior of the glass (2); - the glass (23) of the glass cylinder (3) at the cylinder inner surface contains at least one nitrogen compound.

9. A plunger-cylinder assembly (4) comprising a glass cylinder (3) according to the preceding claim, and a plunger (5) inserted into the glass cylinder (3), wherein the plunger (5) slides directly on the glass (2) of the glass cylinder (3); wherein at least a sliding surface (50) of the plunger (5) is made of a plastic material; wherein the plastic material of the sliding surface (50) exhibits a larger contact angle with water than the surface of the cylinder inner wall (30) defined by the glass (2) of the glass cylinder (3).

10. The plunger-cylinder assembly (4) according to the preceding claim, characterised by at least one of the following features: - the contact angles with water of the plastic material of the sliding surface (50) and of the cylinder inner wall (30) exhibit a differential of at least 60°, preferably at least 70°; - at least the surface of the seal comprises a halogenated polymer, preferably a fluoropolymer.

11. The plunger-cylinder assembly (4) according to any one of the two preceding claims, in the form of a glass syringe (1).

12. The plunger-cylinder assembly (4) according to the preceding claim, characterised by a liquid active-substance preparation (11) received in the glass syringe (1) when the plunger (5) is retracted, preferably including an active substance having a molecular weight of at least 1000 g / mol.