TIP COVER HAVING CROSS-LINKED SILICONE LAYER AND METHOD FOR FORMING SUCH TIP COVER - Patent application

Abstract

The present disclosure relates to a method of treating a tip cover (1, 100) of an injection device (20, 120) to reduce the pull-out force of the tip cover (1, 100), the method comprising applying a quantity of a first silicone oil and a quantity of a second silicone oil to an inner surface (10, 110) of the tip cover (1, 100) and treating the silicone oil to form a cross-linked silicone coating on the inner surface (10, 110) of the tip cover (10), the inner surface (10, 110) being configured to engage an outer surface of the tip of the injection device.

Description

[Technical field]

[0001] The present invention relates generally to tip covers, injection devices including tip covers, and methods of forming tip covers. [Background technology]

[0002] An injection device, such as a syringe, is a medical delivery device configured to administer a medical fluid (e.g., a medicine, a drug) to a patient. Syringes are sold in a pre-filled form, where the medical fluid is placed in the syringe, for example, when the syringe is manufactured. Syringes typically include a reservoir for containing the medical fluid and have an end piece with a fluid passageway through which the medical fluid can be discharged from the reservoir.

[0003] In some cases, a needle is attached to the end piece of the syringe to pierce the patient's skin and administer the medicinal fluid to the patient. A needle cover is attached to the end piece to surround the needle. The needle cover includes an inner needle shield made of an elastomeric material and an outer needle shield formed of a rigid material and disposed around the inner needle shield. The needle cover can prevent injury to a person handling the injection device. Furthermore, the inner needle shield can be in sealing contact with the needle and / or the end piece, thereby protecting the needle and the end piece from contamination of the medicinal fluid from the external environment and / or preventing leakage of the medicinal fluid from the syringe. An example of a needle cover having a non-stick surface formed on the inner surface is provided in EP 2974761.

[0004] Alternatively, the syringe is needleless, and when a needle is connected to the end piece of the syringe, the end piece provides a fluid passageway in the end piece for allowing the medicinal fluid to be expelled from the container. Prior to connecting the syringe, a tip cap is attached to the end piece. Similar to a needle cover, the tip cap may provide a sealing contact with the end piece, thereby protecting the end piece from contamination of the medicinal fluid from the outside environment and / or preventing leakage of the medicinal fluid from the syringe.

[0005] In order to use the syringe, the needle cover or tip cap must be removed. To remove the needle cover or tip cap, the user must grasp both the syringe and the needle cover or tip cap and apply a significant pulling force to pull the needle cover or tip cap off.

[0006] The force required to remove a needle cover or tip cap is measured by a physical parameter known as the "pull-out force" or "POF." An injection device needs to have a small enough pull-out force so that it can be used by any user, including users who are debilitated by, for example, illness. But it also needs to have a large enough pull-out force to avoid unintentional removal of the needle cover or tip cap, for example during transport or storage. Summary of the Invention [Problem to be solved by the invention]

[0007] It is an object of the present invention to provide a tip cover that exhibits reduced pull-out forces when separated from a syringe compared to conventional tip covers, the reduced pull-out forces being achieved without altering the biocompatibility or other properties of the tip cover.

[0008] Additionally, the tip cover sealingly engages the syringe on which it is disposed. Such engagement can prevent contamination of the medicinal fluid disposed in the syringe from the external environment, thereby ensuring the hermeticity of the container. The tip cover can further prevent leakage of the medicinal fluid from the syringe. To that end, a tip cover with reduced pull-out force is required to prevent unintentional removal and to maintain the hermeticity of the container over extended periods of time, such as after extended storage periods. [Means for solving the problem]

[0009] To this end, the present invention proposes a method of treating a tip cover of an injection device to reduce the pull-out force of the tip cover. The method includes applying a quantity of a first silicone oil having a first viscosity and a quantity of a second silicone oil having a second viscosity different from the first viscosity to an inner surface of the tip cover. The inner surface of the tip cover is configured to engage with an outer surface of the tip of the injection device. The method further includes treating the first and second silicone oils to form a crosslinked silicone coating on the inner surface of the tip cover.

[0010] Specific preferred but non-limiting features of the method of treating a tip cover described above, individually or in combination, are as follows: The silicone oil includes polydimethylsiloxane. The tip cover includes an elastomeric material and a cross-linked silicone coating is disposed on the elastomeric material; the elastomeric material of the tip cover includes rubber; treating the first and second silicone oils to form a crosslinked silicone coating includes one of plasma treating, heat treating, or radiation treating the first and second silicone oils; Before the silicone oil is treated, at least one of the first and second silicone oils has a viscosity in the range of 300 to 35,000 centistokes (cSt) or 25,000 to 35,000 cSt; The second viscosity is lower than the first viscosity; The step of applying a certain amount of the first and second silicone oils to the inner surface of the tip cover is 10 to 300 μg / cm 2 The first and second silicone oils are applied to the inner surface of the tip cover, preferably at a concentration of 20 to 200 μg / cm 2 applying the first and second silicone oils to an inner surface of the tip cover; the amount of the first silicone oil applied to the inner surface of the tip cover is less than the amount of the second silicone oil applied to the inner surface of the tip cover; and / or The pull-out force to remove the tip cover from the tip of the injection device is 5% to 35% less than the pull-out force to remove a tip cover of the same configuration having the same amount of non-crosslinked silicone oil thereon.

[0011] The present invention also provides a tip cover comprising a crosslinked silicone coating formed by the above-described method.

[0012] Specific preferred but non-limiting features of the tip cover described above, individually or in combination, are as follows: the tip cover includes a needle shield having an inner needle shield formed of an elastomeric material and a rigid outer needle shield surrounding the inner needle shield; the inner needle shield having an inner surface configured to sealingly engage the needle of the injection device therein; A cross-linked silicone coating is disposed on the inner surface of the inner needle shield; the tip cover has an integral tip cap; and / or The one-piece tip cap includes an inner surface configured for sealing engagement with the luer tip of the injection device, and a cross-linked silicone coating is disposed on the inner surface of the one-piece tip cap.

[0013] The present invention also proposes an injection device comprising a barrel having a chamber configured to hold a medicinal solution therein, the barrel having a proximal end and a distal end, the distal end comprising a fluid passageway for the passage of the medicinal solution therethrough, and a tip cover disposed at the distal end of the barrel. [Brief description of the drawings]

[0014] The figures shown herein are not meant to be actual diagrams of particular components, devices, or systems, but are merely idealized representations used to describe embodiments of the invention. Other features, objectives, and advantages of the invention will become more clearly apparent upon reading the following detailed description and by reference to the drawings, which are provided as non-limiting examples. [Figure 1]FIG. [Diagram 2] 2 is a cross-sectional view of the tip cap of FIG. 1 attached to an injection device. [Diagram 3] FIG. 2 is a side view of an injection device having a tip cap. [Figure 4] FIG. 2 is an exploded cross-sectional view of the needle shield. [Diagram 5] FIG. 2 is a perspective view of the injection device. [Figure 6] FIG. 6 is a side view of the injection device of FIG. 5 with a needle shield. [Figure 7] 1 is a graph showing the correlation of pull-out force with time. [Figure 8] 1 is a graph showing the change in length of an injection device as a function of time. [Figure 9] 1 is a graph showing the force applied to a tip cap when attaching the tip cap to a syringe. [Figure 10] 1 is a graph showing the force applied to a tip cap when attaching the tip cap to a syringe. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0015] As used herein, the term "proximal" refers to a location, e.g., the proximal end is the end closer to a reference point, such as the contact point of a user applying a force to a plunger rod of an injection device described herein. As used herein, the term "distal" refers to a location, e.g., the distal end is the end further away from a reference point, such as the contact point of a user applying a force to a plunger of an injection device described herein. Thus, the terms "proximal" and "distal" refer, for example, to directions closer and further away, respectively, from a user administering a medical fluid to a patient.

[0016] As used herein, the terms "axial," "axially," "longitudinal," and "longitudinally" generally mean and refer to a direction along or parallel to the longitudinal axis of an element of the injection device being described.

[0017] As used herein, the terms "radial", "radially" and "lateral" and "laterally" generally mean and refer to a direction perpendicular to the central longitudinal axis of the element of the injection device being described.

[0018] As used herein, the term "and / or" includes any and all combinations of one or more of the associated listed items.

[0019] The term "configured" as used herein refers to the size, shape, material composition, material distribution, orientation, and arrangement of at least one structure and at least one device that facilitates the operation of the at least one structure in a predetermined manner.

[0020] The term "tip cover" as used herein refers to a disposable device at the distal end of an injection device, such as a syringe, to cover the tip. For example, the tip cover may be a tip cap, a plastic rigid tip cap, a needle cover, etc. In this disclosure, the term "tip cover" is used to refer individually or collectively to a tip cap, as described in detail herein, and a needle cover, as described in detail herein.

[0021] 1-2 show a tip cap 1 according to one embodiment of the present disclosure. In some embodiments, the tip cap 1 is configured to be placed on the luer tip of an injection device. Because the tip cap 1 is monolithically formed, it is known in the art as a one-piece tip cap.

[0022] Tip cap 1 includes a cavity 14 defined by its inner surface 10. Inner surface 10 is configured to engage an outer surface 31 of tip 27 of injection device 20 (FIG. 2). Cavity 14 extends from proximal end 9 of tip cap 1 along longitudinal axis 2 toward distal end 4.

[0023] The tip cap 1 comprises a closed distal portion 3 proximate the distal end 4 and an open proximal portion 7 proximate the proximal end 9. In some embodiments, the closed distal portion 3 comprises a plurality of notches 6 circumferentially spaced along an outer surface 8. The notches 6 form a ribbed outer surface configured to be gripped by a user when removing the tip cap 1 from the injection device 20. In other embodiments, the outer surface 8 of the closed distal portion 3 may be smooth (i.e., notched). The open proximal portion 7 is configured as a cylindrical peripheral skirt such that the injection device 20 is receivable into the tip cap 1. The open proximal portion 7 includes a cavity 14.

[0024] The inner surface 10 of the tip cap 1 is configured to seal the distal end 29 of the injection device 20. The inner surface 10 of the tip cap 1 includes a protrusion 11 extending from the proximal end 5 of the closed distal end portion 3. The inner surface 10 of the tip cap 1 further includes an inner surface 16 of the closed distal portion 3. The inner surface 16 extends annularly around the protrusion 11.

[0025] The tip cap 1 is formed of an elastomeric material, which is a material having elastomeric properties. The tip cap 1 is made of a thermoplastic elastomer (TPE) or rubber. Materials with elastomeric properties that are sterilizable are preferred.

[0026] Materials with elastomeric properties are preferred for sealing the syringe tip, as such materials conform to the shape of the tip 27 of the injection device 20 .

[0027] As shown in Fig. 2, the tip cap 1 is placed on the injection device 20 and sealingly engages with the injection device 20. In operation, the injection device 20 is filled with a medicinal liquid. Prior to use, the tip cap 1 is provided such that the medicinal liquid in the barrel 22 of the injection device 20 cannot flow out of the injection device 20. Thus, the tip cap 1 fluid-tightly engages with the injection device 20. Furthermore, the tip cap 1 can prevent external contaminants from entering the injection device 20 to maintain the hermeticity of its container.

[0028] Injection device 20 includes a barrel 22 extending axially along a longitudinal axis 21 between a distal end 24 and a proximal end 23. Barrel 22 is configured to hold a medical fluid within a cavity 26. Cavity 26 is defined by a cylindrical sidewall 25.

[0029] Distal end 24 includes a fluid passageway for the passage of a medical fluid therethrough. More specifically, injection device 20 includes a tip 27 having a fluid passageway 28 defined by an inner surface 30 of tip 27.

[0030] A tip 27 of the injection device 20 extends from the cylindrical sidewall 25 of the barrel 22. The tip 27 includes an annular outer surface 31 and a distal-most surface 17. A fluid passage 28 is in fluid communication with the chamber 26.

[0031] In operation, once the tip cap 1 is removed from the tip 27 of the injection device 20, a cannula (e.g., a disposable needle) can be coupled to the tip 27 for injecting a medical fluid into a patient. The cannula is coupled to the distal end 24, such as by threading, via an adapter that is snap-fitted or glued to the distal end 24 (see FIG. 3). Alternatively, the cannula is loaded directly onto the distal end 24 of the injection device 20 (see FIG. 5).

[0032] When the tip cap 1 is placed on the tip 27 of the injection device 20, the inner surface 10 of the tip cap 1 engages the outer surface 31 of the tip 27. Also, the distal-most surface 17 of the tip 27 abuts the inner surface 16 of the closed distal portion 3, and a portion of the projection 11 is disposed within the fluid passageway 28.

[0033] As shown in FIG. 3, the injection device 20 includes a stopper 32 disposed within the barrel 22 and coupled to a plunger rod 34. In operation, the plunger rod 34 and stopper 32 are axially displaced along the axis 21 within the barrel 22 to expel the medical fluid from the chamber 26 through the fluid passageway 28 into the needle and into the patient. In FIG. 3, the injection device 20 does not include a fixed needle. Instead, an adapter is attached to the distal end of the barrel 22 to allow attachment of a needle to the injection device 20 prior to injection. In that case, when the injection device 20 includes the adapter, a rigid plastic tip cap is attached to the adapter to prevent external contaminants from entering the injection device 20 and to maintain the hermeticity of the container.

[0034] The plastic rigid tip cap is made of an elastomeric material, which is a material that has elastomeric properties. The tip cap 1 is made of a thermoplastic elastomer (TPE) or rubber. A material with elastomeric properties that is sterilizable is preferred.

[0035] The material of barrel 22 will vary depending on the medicinal fluid to be placed therein. Barrel 22 may be formed of a polymeric material (e.g., plastic) or glass.

[0036] 4 illustrates a needle cover 100 according to one embodiment of the present disclosure. In some embodiments, the needle cover 100 comprises an inner needle shield 104 and an outer needle shield 106 that surrounds the inner needle shield 104.

[0037] The inner needle shield 104 is formed of a flexible material. The outer needle shield 106 is formed of a rigid material (eg, a material that is less flexible than the inner needle shield 104).

[0038] The inner needle shield 104 is made of an elastomeric material, which is a material that has elastomeric properties. The inner needle shield 104 is made of a thermoplastic elastomer (TPE) or rubber. A material with elastomeric properties that is sterilizable is preferred. The elastomeric material of the inner needle shield 104 is penetrable by the needle 103 of the injection device 120.

[0039] The inner needle shield 104 has an inner surface configured to sealingly engage the needle of an injection device therein and to sealingly engage the tip of an injection device 120 .

[0040] The outer needle shield 106 is formed from a hard plastic and is configured to surround the inner needle shield 104 .

[0041] The needle cover 100 includes a cavity 114 defined by its inner surface 110. Similar to the tip cap 1, the inner surface 110 is configured to engage an outer surface of the tip 127 of an injection device 120 (FIG. 5).

[0042] 5, the needle 103 is coupled to the tip 127 of the barrel 122 before the needle cover 100 is attached to the injection device 120. Thus, the inner surface 110 of the needle cover 100 is configured to engage the outer surface of the tip 127 of the injection device 120 with the needle 103 coupled to the tip 127 of the injection device 120.

[0043] The cavity 114 extends from the proximal end 109 of the needle cover 100 along the longitudinal axis 102 toward the distal end 104 .

[0044] The open proximal portion 107 is configured as a cylindrical peripheral skirt such that a portion of the injection device 120 (typically the tip 127) is received within the needle cover 100. The open proximal portion 107 includes a cavity 114.

[0045] More specifically, the inner surface 110 of the needle cover 100 is configured to fluidly seal the distal end of the injection device 120. The inner surface 110 of the needle cover 100 may have a variety of shapes. As a non-limiting example, the inner surface 110 has a portion configured to engage the tip 127 of the barrel 122 and another portion configured to engage the needle 103.

[0046] 4, the inner surface 110 comprises a first portion 110a, a second portion 110b, and a third portion 110c. The first portion 110a is located proximal to the proximal end 109, the third portion 110c is located proximal to the distal end 104, and the second portion 110b is located between the first portion 110a and the third portion 110c.

[0047] The first portion 110a and the second portion 110b are configured to sealingly engage with differently sized portions 127a, 127b of the tip 127 of the barrel 122, and the third portion 110c is configured to sealingly engage with the needle 103.

[0048] Alternatively, the needle cover 100 includes an inner needle shield configured to engage a needle-free syringe and an outer needle shield formed from a hard plastic and configured to surround the inner needle shield.

[0049] 6, the needle cover 100 is placed over and sealingly engaged with the injection device 120. In operation, the injection device 120 can be filled with a medicinal fluid. Prior to use, the needle cover 100 is provided such that the medicinal fluid within the barrel 122 of the injection device 120 cannot flow out of the injection device 120.

[0050] Injection device 120 includes a barrel 122 extending axially along a longitudinal axis 121 between a distal end 124 and a proximal end 123. Barrel 122 is configured to hold a medical fluid within a chamber. Similar to chamber 26, the chamber of barrel 122 may be defined by a cylindrical sidewall and an annular wall.

[0051] Injection device 10 includes a stopper 132 disposed within barrel 122 and coupled to plunger rod 134. In operation, plunger rod 134 and stopper 132 are displaced axially along axis 121 within barrel 122 to expel medical fluid from the chamber, through the fluid passageway, into needle 103 and to the patient.

[0052] In accordance with the present disclosure, the tip cover includes a cross-linked silicone coating disposed on its inner surface 10, 110. The cross-linked silicone coating is disposed on at least a portion of the inner surface 10, 110. For example, the portion of the inner surface 10, 110 that engages the outer surface of the tip 27, 127 of the injection device 20 includes the cross-linked silicone coating. Optionally, the entire inner surface 10, 110 may include the cross-linked silicone coating.

[0053] A silicone oil is applied to at least a portion of the interior surface 10, 110 to form a crosslinked silicone coating. In some embodiments, more than one silicone oil is applied to the interior surface 10, 110. For example, a first silicone oil having a first viscosity is applied to the interior surface 10, 110, and a second silicone oil having a second viscosity, optionally different from the first viscosity, is applied to the interior surface. The silicone oil or oils can be applied in any suitable manner, including, but not limited to, spraying, dipping, and washing in a water-silicone emulsion.

[0054] The silicone oil comprises polydimethylsiloxane, or PDMS, In some embodiments, the silicone oil is comprised of PDMS.

[0055] The silicone oil has a viscosity in the range of 100 to 50,000 centistokes (cSt), preferably in the range of 300 to 35,000 cSt, more specifically in the range of 1,000 to 30,000 cSt. More specifically, the silicone oil has a viscosity of 1,000 cSt or a viscosity of 30,000 cSt before being treated. As mentioned above, in some embodiments, a first silicone oil having a viscosity of 30,000 cSt and a second silicone oil having a viscosity of 1,000 cSt are applied to the inner surface 10, 110. The aforementioned viscosities are measured at 25°C using a standard viscometer.

[0056] The concentration of silicone oil applied to the inner surface of the tip cover is 10 μg / cm 2 ~300μg / cm 2More specifically, in the range of 20 μg / cm 2 ~200μg / cm 2 In some embodiments, the concentration of the silicone oil is about 25 μg / cm 2 In another embodiment, the concentration of the silicone oil is about 200 μg / cm 2 The concentration of silicone oil is determined by extraction in a solvent followed by atomic emission spectroscopy.

[0057] After the silicone oil is applied to the interior surface 10, 110, the silicone oil is treated to crosslink the silicone oil into a silicone coating. Methods for treating the silicone oil to form a crosslinked silicone coating include one of plasma treating, heat treating, or radiation treating the silicone oil.

[0058] In some embodiments, a plasma treatment is applied to the silicone oil to crosslink the silicone oil. The plasma treatment may be an oxidizing plasma treatment.

[0059] The plasma treatment is carried out in an atmosphere containing oxygen and argon. The plasma treatment is applied to crosslink the silicone oil to form the lubricating coating. The plasma treatment is preferably carried out in an oxidizing atmosphere.

[0060] According to a preferred embodiment, the atmosphere is a mixture of 15-30% oxygen and 85-70% argon partial pressures, more preferably the atmosphere contains 25% oxygen and 75% argon.

[0061] Generally speaking, plasma may be generated by a variety of techniques, such as corona discharge, microwave, radio frequency, or any other convenient method.

[0062] Preferably, the high frequency plasma treatment is used at a frequency in the range of 10 to 20 MHz, more preferably at a frequency in the range of 11 to 14 MHz. The power applied to generate the plasma may be 50 to 300 W, preferably 100 to 250 W, and the plasma treatment may be carried out at room temperature (i.e., 25° C.) and under a vacuum in the range of 1.33 to 13.3 Pa (10 to 100 mTorr) absolute.

[0063] The exposure time of the silicone oil layer to the plasma is typically between 10 and 40 seconds.

[0064] The above parameters depend on the geometry of the plasma reactor, the surface area and volume of the tip cover containing the silicone coating, the placement of the device within the plasma reactor, the thickness of the silicone layer, the surface density of the silicone, and the like.

[0065] As a result, slight changes in the parameters can result in different coatings, and one skilled in the art will select the parameters of the plasma treatment to optimize the process depending on the equipment used and the device being treated.

[0066] As a result of the plasma treatment, the silicone oil is crosslinked to form a crosslinked coating on the inner surface 10, 110. A tip cover having a coating formed by crosslinking a quantity of silicone oil obtains a pull-off force when removing the tip cover from the tip of the injection device that is less than the pull-off force when removing a tip cover having the same composition and the same amount of silicone oil thereon that is not crosslinked. More specifically, a tip cover having a crosslinked silicone coating thereon obtains a pull-off force that is at least 5% less and up to 35% less than the pull-off force for removing a tip cover having the same composition and the same amount of silicone oil thereon that is not crosslinked. Said reduced pull-off force is measured in the range of 5 days to 9 weeks after placing the tip cover on the injection device. Such pull-off force is measured before or after a sterilization process. More preferably, a tip cover having a crosslinked silicone coating thereon obtains a pull-off force that is at least 10%, at least 15%, or at least 20% less than the pull-off force for removing a tip cover having the same composition and the same amount of silicone oil thereon that is not crosslinked. The pull-out force is measured for each tip cover using a traction bench according to the procedure described below.

[0067] The pull-out force required to remove the tip cover varies based on the configuration of the tip cover. For example, less pull-out force is required to remove the tip cap described with reference to Figures 1-3 from a syringe than to remove the needle cover 100 described with reference to Figures 4-6 from a syringe. With respect to tip cap 10, a tip cap having a cross-linked silicone coating thereon will achieve a pull-out force in the range of 2N to 10N.

[0068] Experimental Data The following experimental data, by way of comparison, shows the effect of a cross-linked silicone coating according to the present disclosure on the pull-out force of a tip cap from a syringe, which is affected as a function of the amount of silicone oil applied to the inner surface of the tip cap and / or the cross-linking of the silicone oil applied to the inner surface of the tip cap.

[0069] Experimental data is provided for the following samples: The tip cap does not contain silicone oil (indicates "No Silicone"); As described herein, about 25 μg / cm 3 having a viscosity of 30,000 cSt measured at 25° C. 2 a tip cap (depicted as "Reference") having silicone oil (also known in the art as "transport silicone") of It has a viscosity of 30,000 cSt measured at 25°C and is approximately 25 μg / cm 2 a tip cap (depicting "Ref+Cross-linked") disposed on its inner surface having silicone oil cross-linked according to the plasma treatment described herein; It has a viscosity of 30,000 cSt measured at 25°C and is approximately 25 μg / cm 2 silicone oil and has a viscosity of 1,000 cSt measured at 25°C and a viscosity of about 175 μg / cm 2 a tip cap (shown as "Sil2") having silicone oil disposed on its inner surface; It has a viscosity of 30,000 cSt measured at 25°C and is approximately 25 μg / cm 2 and a silicone oil having a viscosity of 1,000 cSt measured at 25° C. and a viscosity of about 175 μg / cm 2 1. A tip cap (designated "Sil2+Cross-linked") having silicone oil disposed on its inner surface that is cross-linked according to the plasma treatment described herein.

[0070] The end caps of each of the foregoing samples are the same and include the following features: a material that is styrene butadiene rubber; and A configuration as described herein with reference to the tip cap of Figures 1-3.

[0071] Approximately 25 μg / cm with a viscosity of 30,000 cSt to form the "Reference" and "Ref+Cross-linked" cross-linked silicone coatings. 2 of silicone oil is applied to the inside surface of the tip cap.

[0072] The silicone oil of “Reference” remains in a non-crosslinked state, and the silicone oil of “Ref+Cross-linked” undergoes a plasma treatment process with the following preferred conditions: Plasma type: Capacitively coupled plasma driven by a 13.56MHz high frequency power source. Processing time: 30 seconds, Power: 200W, Pressure: 8 Pa (0.06 Torr), Atmosphere: 15 / 75 partial pressures of oxygen and argon respectively.

[0073] Approximately 25 μg / cm with a viscosity of 30,000 cSt to form the cross-linked silicone coatings "Sil2" and "Sil2+Cross-linked". 2 of silicone oil having a viscosity of 1,000 cSt is applied to the inside surface of the tip cap, followed by about 175 μg / cm 2 Silicone oil of "Sil2" is left in a non-crosslinked state, while "Sil2+Cross-linked" silicone oil is subjected to a plasma treatment process under the aforementioned conditions.

[0074] Pull-out force Measurements of the force required to remove the tip cap from the glass syringe are made. Table 1 identifies the tip cap for each sample type, the number of tip capped samples for which the above measurements were made, and the time delay between attachment of the tip cap to the syringe and the measurement of each sample. For the steam sterilized samples, the sterilization process was performed one week after the tip cap was attached to the syringe, and the POF measurements were taken one week after the sterilization process.

[0075] [Table 1]

[0076] The pull-out test was carried out using a towing bench. The method consisted of the following steps: Place the syringe in the holder Pneumatic jaws hold the tip cap, and The syringe is then pulled at a constant displacement rate to remove the tip cap.

[0077] The force required to remove the tip cap is recorded as a function of syringe displacement. Measurements of the force required to remove the tip cap from the syringe are performed according to ISO standard 11040-4:2015 Annex G.6 with two exceptions: (1) the tip is oriented downwards instead of upwards as specified in the aforementioned ISO standard, and (2) the grip length is greater than 2 mm, whereas the ISO standard uses a grip length of 2 mm. The displacement rate is 500 mm / min.

[0078] The pull-out force is the maximum force recorded during the pull-out force test described.

[0079] Figure 7 shows the pull-out force of the tip cap measured at fixed times after the tip cap was attached to the syringe and after steam sterilization. The pull-out force (POF) value (in Newtons (N)) required to remove the tip cap is recorded four times: (1) 5 days after the tip cap was attached to the syringe, (2) 3 weeks after the tip cap was attached to the syringe, (3) 9 weeks after the tip cap was attached to the syringe, and (4) after the steam sterilization process. The steam sterilization process is carried out at a temperature of 120°C to 125°C for 30 to 40 minutes.

[0080] Table 2 below provides the pull-out force values ​​measured for the aforementioned samples shown in FIG.

[0081] [Table 2]

[0082] These results show that the application of a cross-linked silicone coating to the inner surface of the tip cap reduces the pull-out force. When comparing samples with the same amount of silicone oil applied, the cross-linking of the silicone oil reduces the pull-out force. (e.g., compare "Reference" to "Ref+Cross-linked" and "Sil2" to "Sil2+Cross-linked"). On average, tip caps with cross-linked silicone coatings have a pull-out force that is about 25% lower compared to tip caps with non-cross-linked silicone oil. Tip covers with cross-linked silicone coatings have a pull-out force that is at least about 14% lower and up to about 20% lower than the pull-out force to remove tip covers of the same composition and with the same amount of non-cross-linked silicone oil thereon. As shown in Figure 7 and Table 2, the presence of the cross-linked silicone coating reduces the pull-out force by about 50% or more compared to tip caps without silicone oil.

[0083] A tip cap according to the present disclosure provides a pull-out force in the range of 2N to 10N to remove the tip cover from the tip of an injection device.

[0084] As shown in Figure 7 and Table 2, steam sterilization increases the pull-out force. Nevertheless, for a similar amount of silicone, the tip caps with cross-linked silicone coatings have lower pull-out forces compared to the tip caps with non-cross-linked silicone oil, even after steam sterilization.

[0085] In the normal course of preparing an injection device for use, the pharmaceutical industry standard is to sterilize the injection device, for example, by steam or ethylene oxide sterilization. Typically, a tip cap is attached to the end of the syringe prior to such steam or ethylene oxide sterilization. It is desirable to reduce the pull-out force because the tip cap is easily removed when a pull-out force is applied, but the extent to which the pull-out force can be reduced is limited by undesirable removal of the tip cap when no pull-out force is applied. For example, a tip cap configured to reduce the pull-out force will move relative to the syringe in which it is placed during the steam sterilization process or thereafter during storage of the syringe. Such displacement of the cap is undesirable because it disrupts the seal of the container.

[0086] Figure 8 is a graph of the change in length of the injection device over the same time period as shown with reference to Figure 1. The measured change in length of the injection device is due to movement of the tip cap relative to the syringe during storage. Table 3 shows the average values ​​of the change in length shown in Figure 8.

[0087] [Table 3]

[0088] As shown in FIG. 8 and Table 3, the tip caps of each sample have limited tip cap displacement after steam sterilization for 5 days and 3 weeks, and the "Reference" and "Ref+Cross-linked" samples are within the acceptable range. However, after steam sterilization, samples containing additional non-crosslinked and crosslinked silicone (e.g., "Sil2" and "Sil2+Cross-linked") obtain large tip cap displacement. The steam sterilization process contributes to the movement of the tip cap relative to the syringe, and the samples containing additional non-crosslinked and crosslinked silicone (e.g., "Sil2" and "Sil2+Cross-linked") obtain lower pull-out forces, making the tip cap more likely to slip off. The results show larger tip cap movement, enough to potentially jeopardize the seal of the container. Therefore, to reduce the tip cap movement relative to the syringe while also reducing the pull-out force, it is preferable to add additional silicone with a minimal amount of silicone crosslinked.

[0089] Stick-slip during assembly As mentioned above, the tip cap must be placed on the syringe. When attaching the tip cap to the syringe, a stick-slip phenomenon can be observed. The stick-slip phenomenon can be observed when two objects slide relative to one another, such as the movement of the tip cap relative to the syringe during assembly.

[0090] The stick-slip phenomenon affects the automation and processability of the tip cap assembly with the syringe. Figures 9 and 10 are diagrams of the force applied to the "Reference" and "Ref+Cross-linked" tip caps, respectively, as a function of the distance traveled by the tip cap during assembly of the syringe. Figures 9 and 10 show that the cross-linked silicone coating limits or even eliminates the stick-slip phenomenon of the tip cap with the syringe, compared to non-cross-linked silicone oil. The most relevant part of the curve is the part displaying the force applied between about 2 mm and 5 mm. At a distance of less than 2 mm, the tip cap is not yet attached to the tip of the syringe. At a distance of more than 5 mm, the tip cap abuts (e.g., is pressed against) the tip of the syringe and is compressed. The stick-slip phenomenon is seen in the diagrams for samples that do not contain cross-linked silicone (e.g., "Reference"). In the diagrams, the force required to keep the tip cap moving increases and decreases (e.g., fluctuates) rapidly between 2 mm and 5 mm for the "reference" lacking cross-linked silicone. This behavior is not exhibited over the same distances in samples having cross-linked silicone on the surface. Therefore, providing a cross-linked silicone coating on the inside surface of the tip cap improves the processability of the tip cap with a syringe.

[0091] While the present disclosure has been described herein with respect to certain exemplary embodiments, those skilled in the art will recognize and understand that the disclosure is not limited thereto. Rather, many additions, deletions, and modifications to the illustrated embodiments may be made without departing from the scope of the present disclosure, including its legal equivalents. Furthermore, features of one embodiment may be combined with features of another embodiment while remaining within the scope of the invention as contemplated by the inventors.

Claims

1. 1. A method for treating a tip cover (1, 100) of an injection device (20, 120) to reduce a pull-out force of the tip cover (1, 100), comprising: applying a quantity of a first silicone oil having a first viscosity to an inner surface (10, 110) of the tip cover (1, 100), the inner surface (10, 110) being configured to engage an outer surface of the tip of the tip cover; applying a quantity of a second silicone oil having a second viscosity to the inner surface (10, 110) of the tip cover (1, 100), the second viscosity being different from the first viscosity; treating the first and second silicone oils to form a cross-linked silicone coating on the inner surface (10, 110) of the tip cover (1, 100); A method for providing the above.

2. The method of claim 1 , wherein the first or second silicone oil comprises polydimethylsiloxane.

3. The method of claim 1 , wherein the tip cover (1, 100) comprises an elastomeric material and the cross-linked silicone coating is disposed on the elastomeric material.

4. The method of claim 3 , wherein the elastomeric material comprises rubber.

5. 2. The method of claim 1, wherein treating the first and second silicone oils to form the crosslinked silicone coating comprises one of plasma treating, heat treating, or radiation treating the first and second silicone oils.

6. 2. The method of claim 1, wherein the step of applying a quantity of the first and second silicone oils to the inner surface (10, 110) of the tip cover (1, 100) includes applying first and second silicone oils having viscosities in the range of 300 to 35,000 centistokes (cSt).

7. The method of claim 1 , wherein the second viscosity is lower than the first viscosity.

8. Applying a certain amount of the first and second silicone oils to the inner surface (10, 110) of the tip cover (1, 100) is 10 to 300 μg / cm 2 of the first and second silicone oils are applied to the inner surface (10, 110), preferably in a concentration of 20 to 200 μg / cm 2 2. The method of claim 1, further comprising applying said first and second silicone oils to said inner surface (10, 110).

9. 2. The method of claim 1, wherein the amount of the first silicone oil applied to the inner surface (10, 110) of the tip cover (1, 100) is less than the amount of the second silicone oil applied to the inner surface (10, 110) of the tip cover (1, 100).

10. 2. The method of claim 1, wherein the pull force to remove the tip cover (1, 100) from the tip of the injection device is 5% to 35% less than the pull force to remove a tip cover of the same configuration having the same amount of non-crosslinked silicone oil thereon.

11. 2. The method of claim 1, wherein the amount of the first silicone oil applied to the inner surface of the tip cover is less than the amount of the second silicone oil applied to the inner surface of the tip cover.

12. A tip cover comprising a crosslinked silicone coating formed by the method of claim 1.

13. A needle shield (110), The needle shield (110) comprises: an inner needle shield (104) formed from an elastomeric material and having an inner surface configured to sealingly engage a needle of the injection device (20); a rigid outer needle shield (106) surrounding said inner needle shield (104); having The tip cover (10, 110) of claim 12, wherein the cross-linked silicone coating is disposed on an interior surface of the inner needle shield (104).

14. Includes an integral tip cap; 13. The tip cover (10, 110) of claim 12, wherein the one-piece tip cap comprises an inner surface configured for sealing engagement with a luer tip of an injection device, and the cross-linked silicone coating is disposed on the inner surface of the one-piece tip cap.

15. a barrel (22) having a cavity (26) configured to hold a medical fluid therein, said barrel (22) having a proximal end (23) and a distal end (24), said distal end (24) defining a fluid passageway for the passage of said medical fluid; A tip cover (1, 100) according to any one of claims 12 to 14, disposed at the distal end (24) of the barrel (22); An injection device (20).

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