Method for Coating a Glass Syringe Body for a Hypodermic Pre-Filled Glass Syringe, Hypodermic Pre-Filled Glass Syringe and Plasma Treatment Device for Glass Syringe Bodies of Hypodermic Pre-Filled Glass Syringes

Abstract

Method for coating a glass syringe body for a hypodermic pre-filled glass syringe, wherein at least one emulsion and/or one solution containing at least one layer-forming substance is applied to at least one inner surface of the hypodermic pre-filled glass syringe, which defines an axial direction, wherein at least a partial surface of the inner surface in a syringe cone of the pre-filled glass syringe is subsequently exposed to a plasma, wherein a negative pressure source is arranged in relation to the syringe cone in the axial direction opposite the atmospheric-pressure plasma source, wherein a negative pressure of less than atmospheric pressure is provided by means of the negative pressure source.

Claims

1-18. (canceled)

19. A method for forming a coating on a glass syringe body for a hypodermic pre-filled glass syringe, comprising the steps of: applying at least one emulsion and/or one solution containing at least one layer-forming substance to at least one inner surface of the hypodermic pre-filled glass syringe, which defines an axial direction (A), and subsequently exposing at least a partial surface of the inner surface in a syringe cone of the pre-filled glass syringe to a plasma, wherein a negative pressure source is arranged in relation to the syringe cone in the axial direction (A) opposite an atmospheric-pressure plasma source, and wherein a negative pressure of less than atmospheric pressure is provided by means of the negative pressure source.

20. The method according to claim 19, wherein a suction mandrel of the negative pressure source is introduced into a plunger chamber of the glass syringe body.

21. The method according to claim 20, wherein the suction mandrel is brought into a sealing contact with an inner side and/or a bottom surface of the plunger chamber.

22. Then method according to claim 19, wherein the coating comprises a carbon content which decreases to less than about 80% of the initial value before the plasma treatment.

23. The method according to claim 19, wherein the layer thickness of the coating in at least the partial surface of the inner surface before the action of the plasma is between about 20 nm and about 100 nm and decreases in the partial surface by more than about 20% as a result of the plasma treatment.

24. The method according to claim 19, wherein a layer thickness of more than about 70% remains after the plasma treatment in the partial surface.

25. The method according to claim 19, wherein the emulsion and/or the solution comprises at least one silicone oil and optionally water, and/or the coating contains at least carbon and oxygen and hydrogen and silicon, and/or the coating contains at least one poly(-organo)-siloxane.

26. The method according to claim 19, wherein the partial surface of the inner surface of the syringe cone is hydrophobic before the plasma treatment and hydrophilic after the plasma treatment.

27. The method according to claim 19, wherein the plasma comprises an active gas, wherein the active gas optionally comprises oxygen or synthetic air or atmospheric air.

28. The method according to claim 19, wherein the plasma acts for about 0.4 to about 5 seconds, and/or an atmospheric-pressure plasma generated with a dielectrically impeded discharge is used, and/or the plasma comprises an inert gas, and/or that the plasma is formed as a plasma beam or plasma jet which acts at least on the partial surface of the inner surface of the syringe cone, and/or the plasma acts while the negative pressure is provided.

29. A method for producing a hypodermic pre-filled glass syringe comprising a glass syringe body, which is coated using a method according to claim 1, and an injection needle which are joined to one another, wherein the injection needle is connected to the glass syringe body along a joint by means of an adhesive, wherein the joint comprises the partial surface in the syringe cone of the pre-filled glass syringe.

30. The method according to claim 29, wherein the adhesive is selected from an acrylate and/or a polyurethane and/or an epoxy resin and/or a cyanoacrylate.

31. A hypodermic pre-filled glass syringe comprising a glass syringe body and an injection needle, which are connected to each other along a joint by an adhesive layer, wherein the joint comprises at least a partial surface of an inner surface of a syringe cone of the glass syringe body, wherein the partial surface provides a needle holding force in the axial direction (A), wherein at least one atmospheric-plasma-treated coating is applied at least on the inner surface of the syringe cone, whereby the needle holding force is at least: (a) 11 N for needle diameters less than 0.33 mm, (b) 22 N for needle diameters less than 0.55 mm, (c) 34 N for needle diameters less than 0.7 mm, (d) 40 N for needle diameters less than 0.8 mm, (e) 44 N for needle diameters less than 0.9 mm, (f) 54 N for needle diameters less than 1.1 mm, and/or (g) 44 N for needle diameters greater than or equal to 1.1 mm.

32. The pre-filled glass syringe according to claim 31, wherein the layer thickness of the coating in at least the partial surface before the action of the plasma is between about 20 nm and about 100 nm, and decreases in the partial surface by more than about 20% as a result of the plasma treatment, and/or a layer thickness of more than about 70% remains after the plasma treatment in the partial surface.

33. The pre-filled glass syringe according to claim 31, wherein the coating contains at least carbon and oxygen and hydrogen and silicon, and/or the coating contains at least one poly(-organo)-siloxane, and/or the carbon content of the coating is reduced to less than about 80% of the initial value prior to the plasma treatment.

34. The pre-filled glass syringe according to claim 31, wherein the adhesive is selected from an acrylate and/or a polyurethane and/or an epoxy resin and/or a cyanoacrylate.

35. A plasma treatment device for glass syringe bodies of hypodermic pre-filled glass syringes, comprising: an atmospheric-pressure plasma source for providing plasma for treating an inner surface of a syringe cone of the glass syringe body, and a negative pressure source for providing a negative pressure of less than atmospheric pressure, wherein the atmosphere-pressure plasma source and the negative pressure source are arranged opposite each other in relation to the syringe cone.

36. The plasma treatment device according to claim 35, wherein the negative pressure source comprises a suction mandrel having an outer diameter of less than or equal to a plunger chamber inner diameter of the glass syringe body, in particular of the plunger chamber.

37. The plasma treatment device according to claim 36, wherein the suction mandrel has an insertion length along which the outer diameter is less than the plunger chamber inner diameter of the glass syringe body, wherein the insertion length is at least as long as the cylinder height of the plunger chamber, wherein the plasma treatment device is designed to introduce the suction mandrel into the plunger chamber of the glass syringe body.

38. The plasma treatment device according to claim 36, wherein the suction mandrel comprises a sealing means, which is arranged at least on the front end of the suction mandrel in order to be brought into contact with an inner side and/or a bottom surface of the plunger chamber.

Description

[0049] Other properties, features and advantages of the invention become apparent below from the description of preferred embodiments of the invention with reference to the accompanying exemplary drawings, which show:

[0050] FIG. 1 a cross-sectional view of a hypodermic pre-filled glass syringe according to the invention;

[0051] FIG. 2 a partial cross-sectional view of a hypodermic pre-filled glass syringe according to the invention with plasma source and negative pressure source;

[0052] FIG. 3 a section of a plasma treatment device according to the invention;

[0053] FIG. 4 an exemplary embodiment of a plasma treatment device according to the invention;

[0054] FIG. 5 an exemplary embodiment of a plasma source;

[0055] FIG. 6 a diagram of an exemplary layer thickness reduction over the treatment time;

[0056] FIG. 7 a further embodiment of a hypodermic pre-filled glass syringe according to the invention; and

[0057] FIG. 8 a further embodiment of a hypodermic pre-filled glass syringe according to the invention.

[0058] In the following illustrations of preferred embodiments, the same or similar reference numerals are used for the same or similar components. A hypodermic pre-filled glass syringe according to the invention is generally provided with reference numeral 7. A plasma treatment device according to the invention for glass syringe bodies of hypodermic production syringes is generally provided with reference numeral 100.

[0059] FIG. 1 schematically shows a hypodermic pre-filled glass syringe 7 according to the invention in a sectional view, wherein a glass syringe body 70 of the pre-filled glass syringe 7 is shown hatched. The glass syringe 7 or the glass syringe body 70 substantially comprises a flange section 171 at an end 173 when viewed in the axial direction A, an elongated plunger section 175 which has a substantially constant cross-section and a constant wall thickness and which adjoins the flange section 171 when viewed in the axial direction A, and a syringe cone 72 which has a tapering cross-section and is formed with a thicker wall thickness and into which the plunger section 175 opens in the axial direction A. On the inside, the plunger section 175 limits or defines a plunger chamber 107. The syringe cone 72 is adjoined by a funnel section 177 of the plunger section 175 in the interior of which the plunger volume 107 tapers in a funnel-like manner. Through the syringe cone 72, a passage 179 extends substantially in the axial direction A from a syringe cone end 181 opposite the flange end 173 to the plunger chamber 107. The passage or end channel 179 has a substantially constant cross-section during its course. At the syringe cone end 181, the passage 179 may be chamfered, for example with a chamfer at an angle of 45 with respect to the axial direction A in order to facilitate later insertion of a cannula or injection needle and/or an atmospheric-pressure plasma source 101 described in detail below. FIG. 1 indicates a center line or line of symmetry M by a dash-dot line oriented substantially in parallel to the axial direction A. It can be seen that the pre-filled glass syringe 7 is designed to be symmetrical with respect to the center line M. On the inside, i.e. on an inner surface 21 of the pre-filled glass syringe 7, a coating 3 which is preferably designed as a bake-on siliconization is applied. This in particular ensures that a plunger 71, which is to be inserted and is described in more detail below, can be pushed with respect to the inner surface 21 of the glass syringe 7 with as little friction as possible and thus in an easily sliding manner. A partial surface 22 of the inner surface 21, which, as can be seen in particular in FIG. 1, forms at least a part of the syringe cone inner surface or the inner surface of the passage 179, is provided frontally as a later adhesive surface for the injection needle 73 or cannula 76 to be glued in. It is clear that the partial surface 22 is also treated with the coating 3 by the atmospheric-pressure plasma source 101. Furthermore, it is preferably the partial surface 22 which is treated with the negative pressure source 103 using the coating method according to the invention in order to treat the partial surface 22 in such a way that an increased adhesion of the adhesive used for gluing is achieved. The treatment of the syringe interior with the atmospheric-pressure plasma source 101 and the negative pressure source 103 is described in more detail with reference to FIGS. 2 to 4.

[0060] The flange section 171 has at least one flange web 183 which extends at least partially in the circumferential direction and extends away from the center axis M perpendicularly to the axial direction and which is provided for actuation with the fingers by a user.

[0061] FIG. 2 schematically illustrates a section of a pre-filled glass syringe 7 according to the invention, wherein an atmospheric-pressure plasma source 101 is arranged on the syringe-cone-side end 181 and a negative pressure source 103 is located on the plunger-section side in the interior of the plunger chamber 107. With regard to the details regarding a preferred embodiment of the atmospheric-pressure plasma source 101, reference is made to FIG. 5. In FIG. 2, this source is shown merely as a block, which schematically indicates that a plasma beam 4 is introduced via the syringe-cone-side end 181 into the end channel 179 in the syringe cone 72 in order to treat the inner surface 21 and the partial surface 22 with the plasma beam 4. The plasma treatment of the inner surfaces of the pre-filled glass syringe 7 is combined according to the invention with the application of a negative pressure source 103 preferably in the syringe interior. Of the negative pressure source 103, only a suction mandrel 105 introduced into the plunger chamber 107 of the glass syringe body 70 is shown in FIG. 2. In the illustrated position of the suction mandrel 105 with respect to the glass syringe body 70, the suction mandrel 105 is in contact with an inner side 109 of the glass syringe body 70, which contact is a sliding contact in this case, and a rudimentarily funnel-shaped bottom surface 111 of the plunger chamber 107 which prevents further insertion of the suction mandrel 105 into the plunger chamber 107. According to the embodiment in FIG. 2, a sealing ring 119 is arranged on a front end 123 of the suction mandrel 105 facing in the axial direction A in the direction of the bottom surface 111 in order to in particular provide a sealing contact with the bottom surface 111. Alternatively or in addition to the sealing ring 119, a sealing hose (not shown) for providing an additional sealing effect can also be attached to the suction mandrel. It can be seen that negative pressure of less than atmospheric pressure is generated by the negative pressure source 103 or by the suction mandrel 105 of the negative pressure source 103 in the region of the syringe cone 72, i.e. substantially in the passage 179, in order to apply both atmospheric-pressure plasma and negative pressure to the partial surface 22 of the inner surface 21 of the pre-filled glass syringe 7. As a result, the advantageous property change according to the invention arises on the partial surface 22 in order to facilitate or enhance the subsequent gluing-in of the injection needle 73 or of the cannula 76 and to increase the holding force with respect to the glass body inner side 22 in the axial direction A.

[0062] FIG. 3 shows a section of a plasma treatment device 100 for glass syringe bodies 70 of hypodermic pre-filled glass syringes 7 in a side view. The plasma treatment device 100 comprises a support frame 185 on which at least one gripper 187 for gripping or holding a glass syringe body 70 of a hypodermic pre-filled glass syringe 7 is arranged. When viewed in the axial direction A, the gripper 187 extends approximately over three quarters of the complete longitudinal extent of the glass syringe body 70. However, the gripper 187 may also extend, for example, over 15%, 30%, 45%, 60% or even between 80% or 100% of the complete longitudinal extent of the glass syringe body 70 in the axial direction A. The gripper has a substantially constant cross-sectional shape, wherein an elongated chamfer 189 is formed over the entire circumference of the gripper 187 at the end facing away from the support frame 185. The gripper 187 has a substantially cylindrical shape, wherein a slot 191 for laterally inserting a glass syringe body 70 is provided substantially along the entire longitudinal extent of the gripper, i.e. in the axial direction A in FIG. 3. In the assembled state of the glass syringe body 70 in the gripper 187, the latter grips the glass syringe body 70 in a clamp-like manner, wherein an inner diameter of the gripper 187 approximately corresponds to the outer diameter of the glass syringe body 70, it being clear that the inner diameter of the gripper 187 should not be smaller than the outer diameter of the glass syringe body 70. It is however possible to provide an interference fit between the glass syringe body 70 and the gripper 187. Furthermore, the gripper 187 has, near the support frame 185, two grooves 193 which extend perpendicularly to the axial direction A and into which the flange section 177 of the glass syringe body 70 is to be inserted. As can be seen in particular in FIG. 3, the dimensioning of the slots 193 is selected such that the flange section 171 is suitably accommodated. One slot 193 each is introduced into the gripper 187 on both sides with respect to the glass syringe body 70.

[0063] Arranged below the glass syringe body 70 is an atmospheric-plasma pressure source 101 of the plasma treatment device 100 for providing plasma for treating an inner surface 21 of the glass syringe body 70, wherein a plasma beam directed into the syringe interior is indicated by reference numeral 4. The atmospheric-pressure plasma source 101 is explained in more detail (below) with reference to FIG. 5.

[0064] A negative pressure source 103 for providing a negative pressure of less than atmospheric pressure may be arranged on the support frame 185 itself. The atmospheric pressure source 101 and the negative pressure source 103 can be arranged opposite each other in relation to the syringe cone 72 of the glass syringe body 70 so that the negative pressure for the treatment according to the invention of at least a partial surface 22 of the inner surface 21 of the glass syringe body 70 can be carried out in the syringe cone 72. The negative pressure source 103 can also be mounted, for example, at a position other than on the support frame 185, wherein at least one applicator, such as a suction mandrel 105 of the negative pressure source 103, must be arranged according to the invention opposite the atmospheric-pressure plasma source 101 in relation to the syringe cone 72. As shown in FIG. 3, the negative pressure source 103 has a suction mandrel 105 with an outer diameter less than or equal to a plunger chamber inner diameter 113 of the glass syringe body 70 so that it can be brought into the treatment position according to the invention. It can also be seen in FIG. 3 that the suction mandrel 105 has an insertion length 115 along which the outer diameter is smaller than the plunger chamber inner diameter 113 of the glass syringe body 70. In FIG. 3, the suction mandrel 105 is inserted up to contact with a bottom surface 111 of the plunger chamber 107. In other words, a front end 123 of the suction mandrel 105 is pushed into the plunger chamber to such an extent that the front end 123 rests on the bottom surface 111 of the plunger chamber 107. The presence of a sealing means, such as a sealing ring 119 and/or a sealing hose (not shown), which is to be arranged, for example, at the front end 123 of the suction mandrel 105, may be advantageous in order to be brought into sealing contact with the inner side 109 and/or the bottom surface 111 of the plunger chamber 107.

[0065] FIG. 4 shows an exemplary embodiment of a plasma treatment device 100 according to the invention. The following description explains only the components that were not already explained with reference to the previous FIGS. 1 to 3. The exemplary plasma treatment device 100 has a plasma source assembly 195 of four atmospheric-pressure plasma sources 101 for simultaneously or sequentially treating glass syringe bodies 70 of hypodermic pre-filled glass syringes 7. For example, at least five and, for example, at most 30 glass syringe bodies 70 of hypodermic glass syringes 7 can be attached in a holding manner to the support frame 185 which can consist, for example, of three longitudinal struts 197 mounted to one another, in order to treat them by means of the plasma treatment device 100. The plasma treatment device 100 is moreover designed such that negative pressure sources 103 or suction mandrels 105 of a common or separate negative pressure sources 103 corresponding to the number of accommodatable glass syringe bodies 70 are provided.

[0066] At least one or three identically designed (FIG. 4) sensor devices 201 are attached to a stand 199, which may, for example, be designed like a door frame or archway, and are used to detect whether a glass syringe body 70 is located in a gripper 187 of the support frame 185. Based on this knowledge, the atmospheric-pressure plasma source 101 and the negative pressure source 103 by means of which the respective glass syringe body 70 can be treated can then be controlled. For example, the sensor device 201 is designed as a laser device 203 and has a laser beam generator 205 attached to the stand 199 and a reflection device 207, for example a mirror device, for reflecting a laser beam 209 generated by the laser device 205. It is clear that other sensor devices 201 which are capable of detecting whether a glass syringe body 70 is in a respective holder 187 of the support frame 185 are conceivable.

[0067] Explained in more detail with reference to FIG. 5 is a plasma source which is suitable for carrying out the above-described coating method and is designed as an atmospheric-pressure plasma source 101 by way of example. The atmospheric-pressure plasma source 101 comprises a high-voltage electrode 52 surrounded by an insulator 53. The high-voltage electrode 52 is designed as a hollow body and may, for example, be cylindrical or conical. The insulating body 53 is spaced apart from the high-voltage electrode 52. In this way, a working gas, which can be supplied via a gas supply 54, can be introduced into the intermediate space 155 between the high-voltage electrode 52 and the insulating body 53. The working gas leaves the high-voltage electrode 52 via its substrate-side orifice 157, which is designed to be funnel-like and has a longitudinally decreasing cross-section and defines an outlet opening 159 via which the working gas can leave the orifice 157.

[0068] Opposite the orifice 157 is arranged a counter electrode 51, which can optionally be provided with a dielectric coating. This ensures that a dielectrically impeded discharge is triggered between the high-voltage electrode 52 and the counter electrode 51 in every case. If the substrate itself contains or consists of a dielectric or an insulator, the dielectric coating of the counter electrode 51 can also be omitted.

[0069] During operation of the device, a working gas, for example argon, is supplied via the gas supply 54. A high-frequency alternating voltage, which is generated with a high-voltage source 55, is applied to the high-voltage electrode 52. In some embodiments of the invention, the amplitude of the applied high voltage may be between about 2 kV to about 10 kV or between about 5 kV and about 8 kV. The high voltage can be applied as a sinusoidal alternating voltage or in the form of individual high-voltage pulses. The pulse repetition frequency or alternating voltage frequency may be between about 10 Hz and about 30 kHz. The power converted in the plasma 4 can be determined by means of a measuring capacitor which integrates the transferred charge carriers of a discharge cycle. The power thus determined may be between about 0.5 watts and about 5 watts or between about 1 watt and about 3 watts.

[0070] The plasma beam produced in this way has a diameter of about 0.15 mm to about 0.5 mm. When impinging on an exemplary component 2, the root point expands so that the partial surface 22 can be larger than the diameter of the plasma beam 4. If the partial surface 22 is larger than the beam spot resulting from the geometry of the plasma source, a larger partial surface 22 can be treated by sequential treatment with the plasma 4 by displacing the component 2 or the counter electrode 51 with the component 2 arranged thereon. The distance of the beam outlet from the surface to be treated may be between about 3 mm and about 8 mm.

[0071] The elipsometrically determined layer thickness reduction of the partial surface 22 by the plasma treatment is explained with reference to FIG. 6. The treatment time with the plasma beam 4 explained with reference to FIG. 5 is plotted on the abscissa and the elipsometrically determined layer thickness is plotted on the ordinate.

[0072] As FIG. 6 shows, the layer thickness before the action of the plasma is 110 nm. After an exposure time of approximately 10 seconds, the layer thickness is already reduced to about 75 nm. After 30's, the layer thickness is about 57 nm. With a very long treatment time of 300 seconds, the layer thickness decreases to about 50 nm. The layer thickness shows an asymptotic curve with the treatment time. The measured values shown in FIG. 6 suggest that the layer thickness does not fall below 50 nm even with a longer treatment time.

[0073] FIG. 6 thus shows that the plasma treatment of the coating according to the invention does not achieve a complete removal of the coating. Nevertheless, the chemical composition and/or the bonding conditions of the constituents within the coating changes as explained in more detail below. This is accompanied by a change in wetting behavior. The second partial surface 22 treated with the plasma is no longer hydrophobic as originally but hydrophilic, so that the partial surface 22 is suitable after the action of the plasma 4 for being joined by means of an adhesive connection or coated again with another coating material.

[0074] The measured values shown in FIG. 6 were determined on the basis of a coating 3 obtained by bake-on siliconization. For this purpose, an emulsion of silicone oil and water is applied and subsequently baked onto the surface of the component 2 by a heat treatment. The table below shows the element inventory of the coating 3 before the action of the plasma after 1 second, 10 seconds, 30 seconds, 60 seconds and after 300 seconds. All measured values were obtained by photoelectron spectroscopy. Monochromatic x-radiation is irradiated onto the surface of the coating 3 and the kinetic energy of the photoelectrons is determined. The respective element can be determined from the kinetic energy, and the intensity of the photoelectrons indicates the relative proportions in the coating 3.

TABLE-US-00001 TABLE 1 Elemental inventory of the coating 0 s 1 s 10 s 30 s 60 s 300 s Element [Atomic %] [Atomic %] [Atomic %] [Atomic %] [Atomic %] [Atomic %] Oxygen (O) 39.1 56.2 60.4 67 66.96 66.96 Carbon (C) 35.8 18.93 13.9 5.6 4.14 3.63 Silicon 25.1 24.85 25.7 27.4 28.68 29.28 (Si) Remainder 0.27 0.13

[0075] The measurements were obtained after the action of an atmospheric-pressure plasma beam 4, which is obtainable, for example, with the device according to FIG. 5, with atmospheric air as working gas. As the measured values shown above show, the carbon content of the coating decreases rapidly as the exposure time to the plasma increases. This is attributable to the fact that the methyl groups contained in the silicone separate and are transported away by the gas stream of the working gas of the plasma 4.

[0076] In order to increase the needle holding force between the injection needle 73 and the pre-filled glass syringe 7, in particular in order to ensure strength values within the scope of DIN ISO 7864, the method step according to the invention of placing a negative pressure source 103 opposite the atmospheric-pressure plasma source 101 in relation to the syringe cone 72 is used. After being treated with plasma 4 with simultaneous application of negative pressure by the negative pressure source 103, the coating of a partial surface 22 is treated in such a way that subsequent adhesion of an adhesive to be applied to the partial surface 22 is significantly enhanced in order to thus increase the holding force between the cannula 76 or the injection needle 73 and the pre-filled glass syringe 7.

[0077] FIG. 7 shows a pre-filled syringe, which is designed as a pre-filled glass syringe 7 by way of example as a further exemplary embodiment of the invention. The pre-filled glass syringe 7 has an approximately cylindrical syringe body 70. Pre-filled glass syringes 7 of the type shown serve as packaging of the medicine contained therein in the production plant so that the medicine can be given to the doctor or patient in an immediately ready-for-use form.

[0078] In order to produce (not shown) the pre-filled glass syringe 7 illustrated in FIG. 7, the syringe body 70 is first produced from a glass tube. For this purpose, the glass tube is cut, heated and shaped in accordance with the desired shape.

[0079] In the next method step, at least the inner side is treated, for example sprayed, with an emulsion of a solvent and layer-forming substances and subsequently treated in an oven or heating cabinet. This causes a majority of the solvent present in the emulsion to evaporate. At the same time, the silicone contained as a layer-forming substance is covalently bonded to the glass so that a coating 3 which contains or consists of polysiloxane is formed on the inner side. The heat treatment prevents the silicone from undesirably transferring into the medicine during later filling, storage and use of the pre-filled glass syringe 7. At the same time, the siliconization allows easy sliding of the plunger 7 so that the handling of the pre-filled glass syringe 7 is facilitated.

[0080] In the illustrated embodiment, a cone 72, which is provided for receiving the injection needle 73, is glued to the end of the syringe body 70 opposite the plunger 71. In other embodiments of the invention, the injection needle 73 can also be glued directly into the syringe body 70 so that the cone 72 can also be omitted, or the cone 72 is alternatively made of one piece together with the glass syringe body 70.

[0081] Since the coating 3 also covers the partial surface 22 provided for receiving the cone 72, the adhesive strength of an adhesive connection 6 is reduced. This can go so far that the cone 72 already falls out of the syringe body 70 during transport or storage and the contents of the pre-filled glass syringe 7 leaks out.

[0082] According to the invention, it is therefore proposed to treat the partial surface 22 with an atmospheric-pressure plasma in the manner described above and to thereby not completely remove the coating 3 but to inactivate it to such an extent that the adhesive connection 6 can be reliably filled. This is done according to the invention by the application of a negative pressure source 103 which is arranged in relation to the syringe cone 72 in the axial direction A opposite the atmospheric-pressure plasma source 101 and provides a negative pressure of less than atmospheric pressure. By changing the element inventory and/or the bonding conditions of the constituents, the hydrophobic coating 3 in the partial surface 22 can become hydrophilic in order to significantly improve the adhesive strength of the adhesive bond 6 or to provide needle holding forces in the axial direction A which satisfy the requirements of DIN ISO 7864.

[0083] FIG. 8 shows a pre-filled syringe, which can, for example, also be designed as a pre-filled glass syringe 7, and the principal function of which was already explained with reference to the previous embodiments. The same components are provided with the same reference numerals so that the description below is limited to the essential differences.

[0084] In order to produce the pre-filled glass syringe 7 (staked-in-needle syringe) illustrated in FIG. 8, the syringe body 70 is first produced from a glass tube. For this purpose, the glass tube is cut, heated and shaped in accordance with the desired shape. However, the syringe body 70 may also be made of plastic (not shown). Plastic syringes are produced by known production methods, e.g. injection molding.

[0085] In the next method step, at least the inner side of the syringe body 70 is sprayed with an emulsion of a solvent and layer-forming substances and subsequently treated in an oven, for example a tunnel furnace, or heating cabinet. This causes a majority of the solvent present in the emulsion to evaporate. At the same time, the silicone contained as a layer-forming substance is for the most part covalently bonded to the glass so that a coating 3 which contains or consists of polysiloxane and/or polydimethylsiloxane is formed on the inner side, i.e. on the inner surface 21 including the partial surface 22. The heat treatment prevents the silicone from undesirably transferring into the medicine during later filling, storage and use of the pre-filled glass syringe 7. At the same time, the siliconization allows easy sliding of the plunger plug 75 so that the handling of the pre-filled glass syringe 7 or application of the medicine is facilitated or made possible in the first place.

[0086] In the embodiment shown, a cannula 76 is glued to the end of the syringe body 70 opposite the plunger plug 75. Since the coating 3 also covers the partial surface 22 provided for receiving the cannula 76, the adhesive strength of an adhesive connection 6 is reduced. This can go so far that the cannula 76 already falls out of the syringe body 70 during transport or storage and the content of the pre-filled glass syringe 7 leaks out.

[0087] According to the invention, it is therefore proposed to treat the partial surface 22 according to the above-described coating method according to the invention with an atmospheric-pressure plasma source 101 and a negative pressure source 103 which are arranged according to the invention opposite each other in the axial direction A with respect to the syringe cone 72, and wherein the negative pressure source 103 provides a negative pressure of less than atmospheric pressure in particular in the syringe cone 72 in order to enhance the adhesion capability of adhesive on the partial surface 22 of the inner surface 21 of the pre-filled glass syringe 7 so that a holding force between the cannula or injection needle 73 and the glass syringe 7 according to DIN ISO 7864 is achieved. By changing the element inventory and/or the bonding conditions of the constituents, the hydrophobic coating 3 in the second partial surface can become hydrophilic and thus improve the adhesive strength of the adhesive connection 6.

[0088] After the cannula 76 has been glued into the syringe body 70, the pre-filled glass syringe 7 is prepared for filling in a manner known per se, i.e. cleaned, sterilized and packaged. The needle protection part 74 is also seated on the cannula 76 in the process. The syringe prepared in this way for filling is then delivered to the manufacturer of the medicine in order to be filled.

[0089] The features disclosed in the above description, the figures and the claims may be important both individually and in any combination for realizing the invention in the various embodiments.

LIST OF REFERENCE NUMERALS

[0090] 2 Component [0091] 3 Coating [0092] 4 Plasma [0093] 6 Adhesive connection [0094] 7 Pre-filled glass syringe [0095] 21 Inner surface [0096] 22 Partial surface [0097] 51 Counter electrode [0098] 52 High-voltage electrode [0099] 53 Insulator [0100] 54 Gas supply [0101] 55 High-voltage source [0102] 70 Glass syringe body [0103] 71 Plunger [0104] 72 Syringe cone [0105] 73 Injection needle [0106] 74 Needle protection part [0107] 75 Plunger plug [0108] 76 Cannula [0109] 100 Plasma treatment device [0110] 101 Atmospheric-pressure plasma source [0111] 103 Negative pressure source [0112] 105 Suction mandrel [0113] 107 Plunger chamber [0114] 109 Inner side [0115] 111 Bottom surface [0116] 113 Plunger chamber inner diameter [0117] 115 Insertion length [0118] 119 Sealing ring [0119] 123 Front end [0120] 155 Intermediate space [0121] 157 Orifice [0122] 159 Outlet opening [0123] 171 Flange section [0124] 173 Flange end [0125] 175 Plunger section [0126] 177 Funnel section [0127] 179 Passage or end channel [0128] 181 Syringe cone end [0129] 183 Flange web [0130] 185 Support frame [0131] 187 Gripper [0132] 189 Chamfer [0133] 191, 193 Slot [0134] 197 Longitudinal strut [0135] 199 Stand [0136] 201 Sensor device [0137] 203 Laser device [0138] 205 Laser beam generator [0139] 207 Reflection device [0140] 209 Laser beam [0141] A Axial direction [0142] M Center axis