Device for forming a cone for accommodating a needle in a syringe, method for producing a cone for accommodating a needle in a syringe, and syringe therefor

Abstract

An apparatus for forming (4) a housing cone (8) of a needle in a syringe body (12) of a glass syringe comprises: a forming tool (16) formed to produce a hole (20) for forming the housing cone (8); and a lubricant coolant liquid dispensing device (24), wherein the forming tool (16) comprises a gripping portion (28), a tip (32), and a tip body (36) between the tip (32) and the gripping portion (28), the tip body (36) being adapted to produce the hole (20). The gripping portion (28), the tip body (36) and the tip (32) are integral and aligned along a main extension axis (X-X). The tip body (36) has a non-circular cross section relative to a cross-sectional plane perpendicular to the main extension axis (X-X), the non-circular cross section being inscribed in a maximum circle (40) having as its radius the maximum distance between a point (P) of the cross section and the main extension axis (X-X), the maximum distance being measured on the cross-sectional plane.

Description

Technical Field

[0001] The present invention relates to a device for forming a cone for accommodating a needle in a syringe, a method for manufacturing a cone for accommodating a needle in a syringe, and a syringe obtained thereby. Background Art

[0002] As is well known, glass syringes are widely used in the medical industry, and the glass syringes include a hollow cylindrical syringe body to contain a medical substance to be injected in the form of a solid, a suspension or a solution. The injection is performed through the front delivery end via a needle applied therein, which itself is hollow and in fluid communication with the body cavity.

[0003] The cavity houses a piston or plunger internally therein which is pushed by the user or by an automated or semi-automated system to allow injection of a medical fluid in a known manner.

[0004] The formation of the cone configured to fix the needle on the syringe body is a critical step: in fact, the end of the tool is attached to the syringe body before closing the rollers and shaping the glass with said rollers. It is therefore necessary to keep open (ie permeable) the passage of the part that houses the needle attached to said syringe body, during a phase when the glass is very hot and ductile: obviously, this phase is critical, since there is a risk that the hole intended to house the needle could easily close.

[0005] In practice, this shaping must be carried out in a precise and controlled manner, since this could lead to cracks forming in the particularly fragile glass body and thus to mechanical weakening. Furthermore, the hole for receiving the needle must be formed with extreme precision in order to avoid residual or broken glass and / or sharp-edged portions, which could lead to subsequent cracking due to the subsequent insertion of the needle into the desired position or seat.

[0006] Furthermore, it must be remembered that the operation of forming the cone that houses the needle in the syringe must also be as fast as possible, since batches of tens or hundreds of thousands of pieces must be processed. Obviously, increasing the molding speed carries a greater risk in terms of defects.

[0007] In order to keep the shell hole permeable, a known solution consists in using a forming tip comprising tungsten: tungsten is in fact a particularly hard material and is able to resist the high temperatures and the severe wear and tear that occurs on the tip when in contact with the glass to be formed.

[0008] The problem with tungsten is that while it solves the abrasion / wear / high temperature resistance problem by allowing a fairly rapid forming operation, it can be a contaminant of the syringe glass. In other words, small amounts of tungsten are released from the tip onto the glass due to abrasion and redeposition of salts and oxides generated by the higher glass forming temperatures. These tungsten derivatives may be incompatible with the drugs and formulations contained in the syringe body and may alter their therapeutic effects over time.

[0009] Therefore, during the molding process using a tungsten tip, the tip is used for a limited time (in the range of 2-4 hours) to minimize the release of tungsten compounds on the syringe body. After this time, the tip must be replaced.

[0010] It is also known to use a gas, usually nitrogen, during the shaping phase in order to avoid or limit as far as possible the formation of tungsten oxide due to the oxidizing effect of the oxygen contained in the air.

[0011] However, these solutions are complex and increase the overall processing costs.

[0012] Alternative shaped tips are also known that do not contain tungsten, thereby preventing the problem of the formation of tungsten compounds (such as oxides and salts) upstream. Tips containing silicon nitride are known for this purpose. However, these solutions have some disadvantages and drawbacks.

[0013] In fact, silicon nitride tips, although hard and resistant to moderately high temperatures, do not allow the speeds and operating temperatures achieved by equivalent (in terms of size and geometry) tungsten tips to be achieved.

[0014] In order to at least partially overcome this temperature resistance limitation, it is known to appropriately introduce a flow of lubricant coolant fluid at the contact between the glass and the forming tip in order to reduce the operating temperature thereof.

[0015] In any case, because the absolute size of the tip (ie, the thickness of the tip) is extremely small, the lubricant coolant fluid cannot always effectively penetrate and therefore cannot lubricate and cool the tip.

[0016] As a result, such prior art tips are unable to achieve or exceed the production performance of comparable tungsten tips. Summary of the invention

[0017] Therefore, there is a need to address the above-mentioned shortcomings and limitations of the prior art.

[0018] In particular, there is a need to provide a formed tip for the shell cone of a syringe needle, which allows precise, rapid and reliable forming, whose functional life is not less than that of a tungsten tip and which ensures that the release of compounds on the syringe body is completely eliminated or greatly reduced without the need for expensive and complex controlled atmospheres (for example, using inert gases such as nitrogen). BRIEF DESCRIPTION OF THE DRAWINGS

[0019] Other features and advantages of the present invention will be more readily understood from the following description of preferred and non-limiting embodiments thereof, in which:

[0020] Figure 1a depicts a side view of a molding apparatus according to one embodiment of the present invention;

[0021] Figure 1b depicts a cross-sectional view of a syringe body formed in accordance with the present invention;

[0022] Figure 2a , 2b 2c respectively depict two side views and a plan view viewed from the end side of a molding tool according to a possible embodiment of the present invention;

[0023] Figure 3a , 3b 3c respectively depict two side views and a plan view viewed from the end side of a molding tool according to another possible embodiment of the present invention;

[0024] Figure 4a , 4b 4c respectively depict two side views and a plan view viewed from the end side of a molding tool according to another possible embodiment of the present invention;

[0025] Figure 5a , 5b 5c respectively depict two side views and a plan view viewed from the end side of a molding tool according to another possible embodiment of the present invention;

[0026] Figure 6a , 6b 6c respectively depict two side views and a plan view viewed from the end side of a molding tool according to another possible embodiment of the present invention;

[0027] Figure 7a , 7b 7c respectively depict two side views and a plan view viewed from the end side of a molding tool according to another possible embodiment of the present invention;

[0028] Figure 8a , 8b 8c respectively depict two side views and a plan view viewed from the end side of a molding tool according to another possible embodiment of the present invention;

[0029] Figure 9a , 9b9c respectively depict two side views and a plan view viewed from the end side of a molding tool according to another possible embodiment of the present invention;

[0030] Fig.10a , 10b 10c respectively depict two side views and a plan view viewed from the end side of a molding tool according to another possible embodiment of the present invention;

[0031] Fig.11a , 11b , 11c respectively depict two side views and a plan view viewed from the end side of a molding tool according to another possible embodiment of the present invention;

[0032] Fig.12a , 12b 12c respectively depict two side views and a plan view viewed from the end side of a molding tool according to another possible embodiment of the present invention;

[0033] Fig.13a , 13b 13c respectively depict two side views and a plan view viewed from the end side of a molding tool according to another possible embodiment of the present invention;

[0034] Fig.14a , 14b 14c respectively depict two side views and a plan view viewed from the end side of a molding tool according to another possible embodiment of the present invention.

[0035] Common elements or parts of elements in the embodiments described below will be denoted by the same reference numerals. DETAILED DESCRIPTION

[0036] With reference to the above-mentioned figures, reference numeral 4 is used to generally designate a device for forming a housing cone 8 of a needle in a syringe body 12 of a glass syringe for a medicinal substance. The syringe body 12 has a main extension axis XX.

[0037] The apparatus 4 comprises a forming tool 16 shaped to produce a hole 20 in the glass syringe body 12 for forming said housing cone 8 .

[0038] In other words, the housing cone 8 is obtained in successive stages by forming the wall of the glass syringe body 12, preferably by using a pair of rollers 22, contracting around the forming tool 16. Thus, the forming tool 16 acts as a male plug, while the side wall 23 of the syringe body 12 is contracted thereon by the rollers 22, which move along a radial direction RR perpendicular to the main extension axis XX. When the forming tool 16 is removed, a hole 20 will remain for later receiving the needle of the syringe.

[0039] The molding apparatus 4 further comprises a lubricant coolant liquid dispensing device 24 located on the tip 32 of the molding tool 16 and / or in the contact area between said molding tool 16 and the glass syringe body 12. The dispensing device 24 may comprise one or more dispensing nozzles 25 of the lubricant coolant liquid.

[0040] For purposes of the present invention, the specific type of distribution device 24 and the type of lubricant coolant fluid used are not critical.

[0041] The shaping tool 16 comprises a gripping portion 28, which gripping or handle portion is suitable for gripping by an associated motor device. The motor device can translate, rotate or rotationally translate the shaping tool 16 relative to the syringe body 12 along the main extension axis XX. It is also possible to keep the shaping tool 16 stationary and rotate, translate and / or rotationally translate the syringe body 12 along the main extension axis XX. The shaping tool 16 further comprises a terminal end 32 suitable for forming the syringe body 12 and a terminal end body 36 between the terminal end 32 and the gripping portion 28, which terminal end body is suitable for manufacturing the hole 20 by machining the glass.

[0042] The gripping portion 28 , the tip body 36 and the tip 32 are preferably made integrally with one another and are aligned along the main axis of extension of the forming tool 16 and along the axis of rotation XX.

[0043] Advantageously, the end body 36 has, relative to a cross-sectional plane perpendicular to the main extension axis XX, a non-circular cross-section inscribed in a maximum circle 40 having as its radius the maximum distance between any point P of said cross-section and the main extension axis XX, measured on said cross-section perpendicular to the main extension axis XX.

[0044] In other words, relative to a cross-sectional plane perpendicular to the main extension axis XX, the maximum radius or maximum distance from the main extension axis is considered, which defines the radius and diameter of the hole 20 that can be formed in the syringe body 12 after rotating the forming tool about its main extension and rotation axis XX.

[0045] This means that, relative to a cross-sectional plane perpendicular to the main extension axis XX, the cross section of the end body 36 will always be smaller than the cross section or area of ​​the largest circle 40, i.e. a circle having a radius equal to the radius of the hole 20 to be formed. In other words, the end body 36 has one or more lateral depressions relative to said largest circle 40.

[0046] Preferably, the cross section of the tip body 36 at its maximum cross section along the main extension axis XX is less than 85% of the cross section of said maximum circle 40 .

[0047] According to another embodiment, the cross section of the tip body 36 at its maximum cross section along the main extension axis XX is less than 70% of the cross section of said maximum circle 40 .

[0048] The ratio between the tip body cross section 36 and the largest circle 40 can be further reduced, thereby always ensuring the necessary mechanical torsional (and bending) strength of the tip body 36 .

[0049] In particular, the cross section of the tip body 36 defines, relative to the largest circle 40 , at least one recess 44 suitable for allowing the passage of said lubricant-coolant liquid.

[0050] In other words, with respect to the theoretical maximum dimension of the tip body 36 given by the largest circle 40 , it is envisaged to use a geometry that is not circular but has at least one recess 44 constituting a cavity suitable for forming a passage for a lubricant coolant liquid.

[0051] According to one embodiment, the tip body 36 has, in a cross section along the main extension axis XX, a plurality of recesses 44 fluidly connected to one another so as to create a continuous channel for the passage of said lubricant-coolant liquid.

[0052] Preferably, the recesses 44 of the tip body 36 are fluidly connected to each other along the main extension axis XX so as to create a continuous passage for the passage of said lubricant-coolant liquid along the tip body 36 .

[0053] The cross-section of the end body 36 preferably remains constant along the main extension axis: in other words, the end body 36 is cylindrical, i.e. it is composed of straight lines that are all parallel to the main extension axis, but it has a cross-section that is different from the circular cross-section (in particular, due to the presence of at least one recess 44, its cross-section is smaller than the largest circle 40).

[0054] Obviously, for the purpose of mechanical strength and durability / reliability of the molding tool 16, it is best that the cross-section of the syringe body 36 is as symmetrical as possible.

[0055] The cross section of the tip body 36 may also vary along said main extension axis XX.

[0056] For example, according to one possible embodiment, the cross section of the tip body 36 tapers along said main extension axis XX, moving from the handle portion or grip portion 28 towards the tip 32 .

[0057] There are many possible geometries for the tip body 36 .

[0058] For example, the cross section of the tip body 36 may be a regular polygon inscribed in the largest circle 40 , such as a triangle, a square, a rhombus, a pentagon, a hexagon, or the like.

[0059] The cross-section of the tip body 36 may also be a closed polyline inscribed within the maximum perimeter, such as a rectangle, a trapezoid, or any closed geometric shape.

[0060] It is also possible to make the cross section of the end body 36 curved, inscribed in the maximum circle 40. The cross section may have straight sides and / or curved sides, etc.

[0061] 2-14 depict some of these possible embodiments according to the present invention.

[0062] As examples, FIGS. 2-14 illustrate some possible geometries of the tip body 36 according to alternative embodiments of the present invention.

[0063] For example, in Figure 2a-2c In the drawings, a triangular cross-sectional geometry is envisaged, in particular based on an equilateral triangle inscribed in the largest circle 40 .

[0064] Figure 3a-3c A square cross-sectional geometry is shown; Figure 4a-4c A rectangular cross-sectional geometry is shown; Figure 5a-5c A diamond cross-sectional geometry is shown.

[0065] Figure 6a-6c A pentagonal cross-sectional geometry is envisaged, whereas Figure 7a-7c A hexagonal cross-sectional geometry is envisaged in FIG.

[0066] Figure 8a-8c shows a star-shaped cross-sectional geometry, while Figure 9a-9c A cruciform cross-sectional geometry is contemplated, wherein the arms are perpendicular and equal to one another, with a length equal to the diameter of the largest circle 40 .

[0067] exist Figure 10a-10c In the embodiment, a partially circular cross-sectional geometry is envisaged, provided on one side with a facet 56; preferably, but not exclusively, said facet 56 has an extension that is smaller than the diameter of the remaining circular cross-section.

[0068] exist Figures 11a-11c In FIG. 4 , an elliptical cross-sectional geometry is envisioned, wherein the major axis of the ellipse is equal to the diameter of the largest circle 40 .

[0069] exist Figure 12a-12c In the embodiment, a part-circular cross-sectional geometry is envisaged, provided with a pair of facets 56 arranged on opposite sides (preferably symmetrical sides) with respect to the main extension axis XX.

[0070] Figures 13a-13c A circular cross-sectional geometry is shown, wherein the diameter is equal to the diameter of the largest circle 40, with a pair of recesses 44 having a substantially parabolic geometry arranged on opposite sides relative to the main extension axis XX.

[0071] at last, Figures 14a-14c A circular cross-sectional geometry is shown having a diameter that is smaller than the diameter of the largest circle 40 , with an arc 60 being substantially tangential to the diameter of the largest circle 40 .

[0072] The circular arc corresponds to a thread 64 which spirals around the circular geometry along the main extension axis XX.

[0073] The tip 32 is preferably tapered relative to its attachment to the tip body 36 .

[0074] Preferably, said tip 32 has the same geometry as the tip body 36 relative to a cross-sectional plane perpendicular to the main extension axis XX.

[0075] For example, if the tip body 36 has a square cross-section, the tip 32 will also have a square cross-section, but tapered, ie, with smaller sides.

[0076] The tip 32 need not have a sharp end 48 .

[0077] For example, the tip may have a flat end 48 contained in a plane perpendicular to the main extension axis XX.

[0078] The tip 32 may also be provided with a conical, pyramidal or frustoconical tip 48 .

[0079] According to one embodiment, a step or constriction 52 is provided at the region for attaching the gripping portion 28 to the tip body 36 relative to a cross-sectional plane perpendicular to the main extension axis XX.

[0080] The gripping portion 28 may have any cross section. The gripping portion 28 may even have a circular cross section even equal to said largest circle 40.

[0081] The function of the gripping portion 28 is to allow the shaping tool 16 to be gripped and / or moved about the main extension axis XX, but it does not have the function of removing material from the syringe body 12 .

[0082] Preferably, the gripping portion 28, the tip 32, and the tip body 36 are made of metal, and / or ceramic, and / or non-metallic materials and are free of tungsten.

[0083] Obviously, the invention can also be applied to tips which are made completely or even partially of tungsten.

[0084] As described above, the special geometry of forming tool 16 and tip 32 allows lubrication and temperature control at housing cone 8, thereby reducing contamination of the cone with tungsten compounds (which are prone to form at the high temperatures reached by conventional tips), or allowing the use of ceramic tips with some resistance to fracture.

[0085] However, it has been found that by using a ceramic material doped with yttrium compounds, it is possible to obtain a forming tool 16 having a high-strength tip 32. In particular, the combination of such a ceramic material doped with yttrium compounds with the aforementioned geometry of the forming tool 16 and tip 32 makes it possible to avoid the use of a tungsten tip without losing the high temperature resistance characteristics typical of a tungsten tip.

[0086] In a preferred embodiment, the ceramic material used is doped with yttrium oxide (Y 2 O 3 ) of silicon nitride (Si 3 N 4 ), wherein, more preferably, yttrium oxide is contained in silicon nitride in an amount of 3% to 7% or 4% to 6% (by weight). In certain embodiments, silicon nitride contains yttrium oxide and aluminum oxide (Al 2 O 3 ), the combined amount of which is 7% to 13% or 8% to 12% (by weight).

[0087] In order to assess the residual amount of yttrium present in the cone of the syringe after it has been formed from the ceramic material doped with the yttrium compound using the forming tool 16 , an analytical test method has been developed and is described below.

[0088] The analytical method for detecting yttrium is as follows.

[0089] Measurement: Use 2% nitric acid (2% HNO 3 ) as an extraction solvent, element Y can be removed from the syringe cone by extraction in a heated ultrasonic bath;

[0090] Analytical technique: Inductively coupled plasma mass spectrometry (ICP-MS);

[0091] Test items: Bulk syringes (not assembled with needles, lacking internal coating), made of neutral borosilicate type I glass (as specified by USP <660> Neutral borosilicate type I glass as defined in ), with two cone forms (Staked Needle–SN– and Luer Lock–LLC);

[0092] Quantitative range: 0.1-200 μg / L;

[0093] Extraction method:

[0094] a) Insert each syringe into a test tube with a screw cap.

[0095] b) Use 1 ml of 2% HNO 3 Fill the syringe and close the tube with the cap

[0096] c) Soak in a preheated ultrasonic bath at 75°C for 1 hour

[0097] d) Shake (using a vortex shaker) the test tube with the syringe

[0098] e) Allow to cool to room temperature

[0099] f) Remove the syringe from the test tube and carefully empty all the liquid from the test tube.

[0100] g) Take 0.3 ml of the extraction solution, transfer it to a new clean test tube, and add 2.7 ml of the internal standard solution (iridium 56 μg / L, in 2% HNO 3 The extract was diluted 10-fold.

[0101] h) Shake the solution to make it uniform.

[0102] Instrument settings:

[0103] Volume of sample submitted for analysis: 3 mL (obtained by dilution in step (g))

[0104] Internal standard solution used: Iridium, final concentration 50 μg / L

[0105] Acquisition mode: Standard

[0106] In 2% HNO 3 The instrument was adjusted and calibrated with a calibration line for element Y in the range of 0.1-200 μg / L.

[0107] Atomic mass: 193 iridium, 89 yttrium;

[0108] Calculate the amount of Y extracted per syringe (considering an extraction volume of 1 mL):

[0109] Y(ng / syringe)=C*FD

[0110] Where C = the concentration in the diluted extract returned by the software (expressed in μg / L)

[0111] FD = dilution factor (equal to 10)

[0112] A second method of extracting yttrium from cone 8 is described below.

[0113] Measurement: After total mineralization, the element Y present in the syringe cone can be quantified / digested by digestion of the glass matrix (cone area fragments only) with the help of hydrofluoric acid or other solvents that facilitate mineralization.

[0114] Analytical technique: Inductively coupled plasma mass spectrometry (ICP-MS)

[0115] Test items: Bulk syringes (not assembled with needles, lacking internal coating), made of neutral borosilicate type I glass (such as USP <660> Neutral borosilicate type I glass as defined in ), with two cone forms (Staked Needle–SN– and Luer Lock–LLC);

[0116] A second method of extracting yttrium from cone 8 is described below.

[0117] Measurement: Element Y present in the syringe cone can be identified by fragmentation of the syringe cone region, laser ablated for sampling, and subsequently determined by ICP-MS without pretreatment or derivatization.

[0118] Analytical technique: Laser ablation, inductively coupled plasma mass spectrometry (LA-ICP-MS)

[0119] Test items: Bulk syringes (not assembled with needles, lacking internal coating), made of neutral borosilicate type I glass (such as USP <660> Neutral borosilicate type I glass as defined in ), with two cone forms (Staked Needle–SN– and Luer Lock–LLC);

[0120] Using the above method, it has been determined that the yttrium content in the cone of a syringe formed with a tip according to the method of the present invention is between 0.5 ng and 1 ng.

[0121] The forming device 4 may comprise at least one second forming tool which is shaped for finishing the hole 20 formed by means of the forming tool 16 .

[0122] In other words, the forming device 4 generally comprises a plurality of forming tools 16 having the function of forming the shape of the needle housing cone 8 in successive stages or steps: the first stage comprises finishing or forming the main hole, while the subsequent stages are used to determine the details. The forming tools 16 used may have the characteristics described above. The forming tools 16 may have the same shape but different sizes, or they may also have different shapes / geometry / materials. A plurality of forming tools constitutes a set of forming tools 16.

[0123] The operation or method for forming a cone in a syringe for accommodating a needle according to the present invention will now be described.

[0124] In particular, the forming tool 16 is mounted on a suitable drive means by means of a gripping portion 28 .

[0125] Next, the injector body 12 is rotated about the main extension and rotation axis XX, taking care to also activate the flow of the lubricant-coolant liquid in the region of the tip 32 and / or the tip body 36 .

[0126] Due to the geometry of the tip body 36, which has an assumed cross-section that is smaller than the cross-section of the largest circle 40, the lubricant-coolant liquid allows the glass of the syringe body 12 to be machined to form the hole 20 while allowing sufficient lubricant-coolant liquid to flow therethrough to avoid overheating of the forming tool 16 and thereby avoid premature wear.

[0127] Obviously, the centre of the hole 20 (to be manufactured) in the syringe body 12 must be centred or aligned with said main extension axis XX.

[0128] After the hole 20 is made, the forming tool 16 is removed and finishing of the surface of the hole 20 continues by using at least a second forming tool, as described above.

[0129] As can be seen from what has been described, the device for forming a cone for accommodating a needle in a syringe according to the present invention can overcome the disadvantages existing in the prior art.

[0130] In particular, the invention makes it possible to avoid or otherwise significantly reduce the release of tungsten compounds on the glass syringe body, since it envisages the use of a shaped tip that may be completely free of tungsten.

[0131] Thus, the present invention enables a transition from glass syringes with a lower tungsten content (according to prior art solutions, which utilize a tungsten tip and employ techniques to suppress the release of tungsten from the glass body) to glass syringes that are completely free of tungsten or that otherwise contain a significantly lower and negligible amount of tungsten compounds compared to prior art solutions.

[0132] Although free of tungsten, the forming tip of the present invention allows the same forming accuracy and speed as a tungsten tip to be achieved without the use of any controlled atmosphere.

[0133] Indeed, on the one hand, the absence of tungsten prevents the formation of relevant tungsten compounds, and on the other hand, the particular geometry of the tip body envisaged allows the use of large flows of lubricant-coolant fluids in order to effectively control and suppress the heating temperature of the tip.

[0134] Due to this geometry, the lubricant coolant fluid has a sufficient cross-sectional passage which can effectively reach the areas of greatest stress from a mechanical and thermal point of view, thus avoiding excessive heating and the appearance of processing defects, which could generate future cracks in the glass. For example, due to the suboptimal flow of the coolant, the so-called "screwing in" of the surface of the syringe cone typical of the methods of the prior art can be eliminated; this effect manifests itself as an irregular, in particular wavy, contour of the inner contour of the syringe cone; in the case of conventional tips, this effect can in fact be reduced, but not eliminated, only by slowing down the rotation speed, thus slowing down the process.

[0135] The mechanical wear of the forming tip of the present invention can also be advantageously monitored and kept under control, because the tip is continuously and effectively lubricated and cooled during the machining of the glass body. Therefore, even when using a material with a lower electrical resistance than tungsten (such as silicon nitride), the tip will never reach a critical temperature due to the effective cooling and lubrication during the machining of the glass, so the tip will still have reduced consumption and can ensure high machining accuracy.

[0136] In particular, when using a forming tool 16 made of a ceramic material doped with an yttrium compound, it is possible to obtain a syringe completely free of tungsten (and with an irrelevant residual yttrium content), while optimizing the production process, i.e. providing a tip 32 of greater strength and durability, which is not possible with ceramic tips of conventional shape and composition.

[0137] These syringes are particularly suitable for certain active ingredients that are sensitive to the presence of tungsten, such as, in particular: tocilizumab, daptomycin alfa, bevacizumab, interferon beta 1-alpha, interferon beta 1b, Botox, exenatide, imiglucerase, certolizumab pegol, glatiramer acetate, secukinumab, triptorelin, dupilumab, etanercept, epoetin, cetuximab, aflibercept, follicle-stimulating hormone beta, teriparatide, papillomavirus vaccine, glucagon, FSH-follicle stimulating hormone (FSH)-1, 1-hydroxy-2-hydroxy-2-hydroxy-1 ... stimulants, trastuzumab, insulin lispro, insulin, adalimumab, depotamine alfa, interferon alfa 2a, paliperidone, pembrolizumab, anakinra, factor VIII-antihemophilic factor, insulin glargine, enoxaparin, ranitidine, alemtuzumab, rituximab, tenecteplase, botulinum toxin type A, epoetin beta, pegfilgrastim, filgrastim, growth hormone, insulin aspart, activated heptad alfa eptagon alfa), romiplostim, pegaspargase, nivolumab, abatacept, chorionic gonadotropin alfa, pegylated interferon alfa 2a, pertuzumab, pegylated interferon beta 1a, pneumococcal vaccine, denosumab, infliximab, atiplasmab, golimumab, basiliximab, eculizumab, ustekinumab, palivizumab, atezolizumab, insulin degludec, ibagra, liraglutide, ranibizumab, omalizumab, and pegaspargase.

[0138] Therefore, another subject matter of the present invention is to provide a syringe filled with one of the above-mentioned active substances, characterized in that the syringe contains no tungsten and contains a residual amount of yttrium of 0.5 ng to 1 ng.

[0139] In order to meet accidental and specific needs, those skilled in the art may make various modifications and variations to the above-mentioned molding equipment, all of which are included in the scope of the invention defined by the claims.

Claims

1. A device (4) for forming a housing cone (8) of a needle in a syringe body (12) of a glass syringe for a medicinal substance, comprising: - a forming tool (16) shaped to produce a hole (20) for forming said housing cone (8) in a glass syringe body (12), at least one dispensing device (24) for a lubricant-coolant liquid, said dispensing device being situated in the contact area between said forming tool (16) and said glass syringe body (12), in, The molding tool (16) comprises - a gripping portion (28) adapted to be gripped and moved by means of corresponding motor means, - a tip (32) suitable for forming said hole (20) in said syringe body (12), - a tip body (36) between said tip (32) and said gripping portion (28) suitable for making said hole (20), - the gripping portion (28), the tip body (36) and the tip (32) are integral and aligned along the main axis of extension and rotation (XX) of the syringe body (12) and / or the forming tool (16), Features - relative to a cross-sectional plane perpendicular to the main extension axis (XX), the terminal body (36) has a non-circular cross-section, the non-circular cross-section being inscribed in a maximum circle (40) so as to have a total cross-section that is smaller than the cross-section of the maximum circle (40), the maximum circle having as its radius the maximum distance between a point (P) of the cross-section and the main extension axis (XX), the maximum distance being measured on the cross-sectional plane perpendicular to the main extension axis (XX).

2. The forming device (4) according to claim 1, in, The tip body (36) has a cross section at its maximum cross section along the main extension axis (XX) that is less than 85% of the cross section of the maximum circle (40).

3. The forming device (4) according to claim 1 or 2, in, The tip body (36) has a cross section at its maximum cross section along the main extension axis (XX) that is less than 70% of the cross section of the maximum circle (40).

4. The forming device (4) according to claim 1 or 2, in, Relative to the largest circle (40), a cross section of the tip body (36) defines at least one recess (44) adapted to allow passage of the lubricant-coolant liquid.

5. The forming device (4) according to claim 4, in, The tip body (36) has, in a cross section along the main extension axis (XX), a plurality of recesses (44) which are fluidically connected to one another so as to form a continuous channel for the passage of the lubricant coolant liquid.

6. The forming device (4) according to claim 4, in, The recesses (44) of the tip body (36) are connected to one another along the main extension axis (XX) so as to form a continuous channel for the passage of the lubricant coolant liquid along the tip body (36).

7. The forming device (4) according to claim 1 or 2, in, The cross section of the tip body (36) varies along the main extension axis (XX).

8. The forming device (4) according to claim 1 or 2, in, Moving from the gripping portion (28) to the tip (32), the tip body (36) has a cross-section that tapers along the main extension axis (XX).

9. The forming device (4) according to claim 1 or 2, in, The tip (32) and the tip body (36) are made of metallic, non-metallic and / or ceramic materials and are free of tungsten.

10. The forming device (4) according to claim 1 or 2, in, The tip (32) and the tip body (36) are made entirely or at least partially of tungsten.

11. The forming device (4) according to claim 1 or 2, in, The cross section of the tip body (36) is a regular polygon inscribed inside the largest circle (40).

12. The forming device (4) according to claim 1 or 2, in, The cross section of the tip body (36) is a closed polyline inscribed inside the largest circle (40).

13. The forming device (4) according to claim 1 or 2, in, The cross section of the end body (36) is curved and inscribed inside the largest circle (40).

14. The forming device (4) according to claim 1 or 2, in, The tip (32) is tapered relative to its attachment to the tip body (36).

15. The forming device (4) according to claim 1 or 2, in, With respect to a cross-sectional plane perpendicular to the main extension axis (XX), the tip (32) has the same geometric shape as the tip body (36).

16. A forming tool (16) shaped to produce a hole (20) for forming a housing cone (8) in the body of a glass syringe, in, The forming tool (16) is defined in accordance with any one of claims 1 to 9 or 11 to 15.

17. The forming tool (16) according to claim 16, wherein the tip (32) and the tip body (36) of the forming tool (16) are made of a ceramic material doped with an yttrium compound.

18. The forming tool (16) according to claim 17, in, The ceramic material is doped with yttrium oxide (Y 2 O 3 ) of silicon nitride (Si 3 N 4 ), wherein the yttrium oxide is contained in the silicon nitride in an amount between 3% and 7% by weight, or the ceramic material is a ceramic material containing a combined amount of yttrium oxide and aluminum oxide (Al2O3) between 7% and 13% by weight. 2 O 3 ) of silicon nitride.

19. The forming tool (16) according to claim 17, in, The ceramic material is doped with yttrium oxide (Y 2 O 3 ) of silicon nitride (Si 3 N 4 ), wherein the yttrium oxide is contained in the silicon nitride in an amount between 4% and 6% by weight, or the ceramic material is a ceramic material containing a combined amount of yttrium oxide and aluminum oxide (Al2O3) between 8% and 12% by weight. 2 O 3 ) of silicon nitride.

20. A method for producing a glass syringe for a medicinal substance, the glass syringe being provided with a housing cone (8) of a needle, the method The following steps are involved: - preparing a glass syringe body (12) provided with a side wall (23) intended to delimit the hole (20) in the housing cone (8), - providing a forming device (4) according to any one of claims 1 to 15, - rotating the syringe body (12) and / or the forming tool (16) about a main extension axis (XX), - forming the side wall (23) of the syringe body (12) after aligning the main extension axis (XX) of the forming tool (16) with the axis of symmetry (SS) of the hole (20) to be produced.

21. A syringe manufactured by a molding device (4) according to any one of claims 1 to 15 and / or a syringe manufactured by a method according to claim 20, It is characterized in that The syringe contained no tungsten and contained a residual amount of yttrium between 0.5 ng and 1 ng.

22. The syringe according to claim 21, in, The syringe is filled with: tocilizumab, alfadarboine, bevacizumab, interferon β1-α, interferon β1b, Botox, exenatide, imiglucerase, certolizumab, glatiramer acetate, secukinumab, triptorelin, dupilumab, etanercept, epoetin, cetuximab, aflibercept, follicle-stimulating hormone β, teriparatide, papillomavirus vaccine, glucagon, FSH-follicle-stimulating hormone, trastuzumab, lysine proline insulin, insulin, adalimumab, depotamine alfa, interferon alfa 2a, paliperidone, pembrolizumab, anakinra, factor VIII-antihemophilic factor, insulin glargine, enoxaparin, ranitidine, alemtuzumab, rituximab, tenecteplase, botulinum toxin type A, epoetin beta, pegfilgrastim, filgrastim, growth hormone, insulin aspart, activated heptad alfa heptagon alfa), romiplostim, pegasparaginase, nivolumab, abatacept, chorionic gonadotropin alfa, pegylated interferon alfa 2a, pertuzumab, pegylated interferon beta 1a, pneumococcal vaccine, denosumab, infliximab, atiplasmab, golimumab, basiliximab, eculizumab, ustekinumab, palivizumab, atezolizumab, insulin degludec, ibagra, liraglutide, ranibizumab, omalizumab, and pegaspargase.

Images