WO2004064901A2

WO2004064901A2 - Syringe to be pre-filled and for long-term storage of medicament

Info

Publication number: WO2004064901A2
Application number: PCT/DK2004/000030
Authority: WO
Inventors: Uffe Lunding Berg
Original assignee: Jarto Holding Aps
Priority date: 2003-01-20
Filing date: 2004-01-19
Publication date: 2004-08-05
Also published as: WO2004064901A3

Abstract

The invention relates to a syringe to be-filled and especially suitable for long-term storage of a medicament. The syringe is to be pre-filled with a medicament. The syringe has an interior wall (1) being made of a plastic material. The interior wall thereby defines a chamber (4). The syringe furthermore has a plunger sealing member comprising a polymeric silicone being non-loosely bounded to the material of the plunger sealing member, possibly the syringe has a plunger sealing member consisting of a polymeric silicone. The syringe is intended for having a medicament stored in the chamber.

Description

SYRINGE TO BE PRE-FILLED AND FOR LONG-TERM STORAGE OF MEDICAMENT

FIELD OF THE INVENTION

The invention relates to a syringe to be pre-filled and especially suitable for long-term storage of a medicament. The invention also relates to a use of such a syringe.

BACKGROUND OF THE INVENTION

The sealing member can take many forms, the two conventional forms being a stopper and an O-ring. The sealing members are often made of rubber or elastomeric materials. The interior chamber of some drug delivery systems is made of plastic. A fluid-tight relationship between the sealing member and the wall forming the interior chamber provides a large resistance to movement of the sealing member within the interior chamber.

This resistance may be reduced by pre-treating the interior chamber walls and the sealing member with a lubricating solution such as silicone. In the typical coating method, the sealing member is agitated with a solution of the silicone and then the sealing member is removed from the silicone solution and placed in the interior chamber of a drug delivery system. Typically, the surface of the walls of the interior chamber has also been pre- treated with a silicone solution.

There are several disadvantages with the typical lubricating method. The major disadvantage is that the lubricant typically is only loosely adhered to the sealing member or the interior chamber. This loose adherence permits the lubricating solution to become deposited into a medicament loaded in the drug delivery system. In some instances, spheres of silicone have been found suspended within the medicament solution.

US 2001/0002434 describes a syringe having two basic components. A chamber with a body made from a plastic material includes a lubricating substance within the plastic. A sealing member is slidably received within the chamber and has an exterior surface that sealing engages the inner surface of the chamber. The sealing member outer surface includes a lubricating silicone substance on the outer surface. The lubricating silicone substance is adhered to the outer surface of the sealing member by cross-linking bonds between molecules of the lubricating silicone.

US 6,200,627 describes a method for coating a sealing member of a drug delivery system with polymeric silicone to provide a lubrication layer on the sealing member. The polymeric silicone in the lubricating layer is cross-linked by radiation and adheres to the sealing member. Irradiating the coated sealing member forms cross-links between the molecules of the polymeric silicone and causes the cross-linked molecules to adhere to the sealing member, thus forming a lubricating layer. The method prevents the polymeric silicone from being deposited into the medicament.

US 4,500,310 describes a variable sealing pressure plunger rod assembly for use with a syringe barrel comprising a plunger rod and a flexible stopper. A flexible cup-shaped stopper includes an annular side wall and a front wall connected to the side wall. An exterior surface of the side wall is larger in diameter than the syringe barrel inside diameter. The stopper interior includes an inside surface of the front wall and a tapered annular inside wall connected to the side wall and to the inside surface. This tapered annular inside wall and the inside surface define a cavity which has the tapered tip portion received therein. The tapered annular inside wall and the tapered tip portion are inclined at approximately the same angle and adjacent to each other.

Thus, the prior art tries to solve the problem of silicone in the medicament, either by cross-linking the silicone to the plunger sealing member, or cross-linking to the interior surface of the syringe barrel or by designing special plunger sealing members.

However, although the problem of silicone depositions in the medicament loaded into the syringe may be overcome by one of the above mentioned techniques, still problems arise when having to store for a long-term medicaments perhaps not suitable for long-time storage in plastic syringes. This problem is solved by storing the medicament in glass syringes.

SUMMARY OF THE INVENTION

It is an object of the present invention to provide a syringe to be pre-filled, and which is capable of storing a medicament for a long-term period, without any risk of contaminating, degrading or in any way harming the medicament in the syringe.

This object is obtained by a syringe having an interior wall being made of a plastic material, said interior wall defining a chamber, said syringe furthermore having a plunger sealing member comprising a polymeric silicone being non-loosely bounded to the material of the plunger sealing member, possibly said syringe having a plunger sealing member consisting in a polymeric silicone, and said syringe intended for having a medicament stored in the chamber. The object may also be obtained by syringe having an interior wall being made of a plastic material, said interior wall defining a chamber, said interior wall of the syringe furthermore having a polymeric silicone non-loosely adhered to the material of the interior wall, and said syringe intended for having a medicament stored in the chamber.

The invention is a syringe having three basic components. A chamber is formed by a syringe body made from one of the group of plastic materials, preferably consisting of polypropylene (PP); polyethylene (PE); polyvinylchloride (PVC). In one embodiment a plunger with a sealing member is provided with a polymeric silicone non-loosely adhered to the material of the plunger sealing member. In another embodiment an interior wall of the syringe chamber is provided with a polymeric silicone non-loosely adhered to the material of the interior wall. In a third embodiment both the plunger sealing member and the chamber interior wall is provided with a polymeric silicone non-loosely adhered to the material both of the plunger sealing member and of the chamber interior wall.

Preferably, the polymeric silicone is adhered to said plunger sealing member, alternatively or additionally to said chamber interior wall by cross-linking bonds formed between molecules of said polymeric silicone. The polymeric silicone is preferably one of the group of phenyl substituted silicones consisting of polydimethyl siloxane, namely dimethyldiphenylpolysiloxane copolymers; dimethyl, methylphenylpolysiloxane copolymers; polymethylphenylsiloxane; and methylphenyl, dimethylsiloxane copolymers.

The chamber is intended for receiving a medicament. The plunger sealing member is slidably received within the chamber and has an exterior surface sealingly engaging the inner wall of the chamber. Either the plunger sealing member or the chamber interior wall, alternatively both the plunger sealing member and the chamber interior wall, includes the lubricating silicone substance on an outer surface of these parts of the syringe.

The lubricating silicone substance is adhered to the outer surface of these parts by cross- linking bonds between molecules of the lubricating silicone. Preferably, the cross-linking bonds preferably are formed by irradiating the plunger sealing member or the chamber interior wall, alternatively by irradiating both the plunger sealing member and the chamber interior wall, after the lubricating silicone has been applied to the outer surface.

The syringe according to the invention is preferably made by the method having the following basic steps. The syringe body is manufactured by injection moulding of the plastic, which the body is made from. The plunger is also manufactured by injection moulding of the material, which the plunger is made from. However, especially the moulding pressure used when injection moulding the plunger is relatively low, perhaps as low as 50 MPa. This considerably reduces possible internal stresses normally induced when injection moulding. Alternatively, at least the plunger, perhaps also the syringe body, may be manufactured by vacuum moulding. The lubricating substance is mixed into a plastic material during a process of compounding the plastic material. The chamber may be 5 moulded from a compounded plastic material containing the lubricating substance within it. At least an outer surface of the plunger sealing member is coated with the lubricating substance.

The lubricating substance used within the plastic material for the chamber can be, but is 10 not necessarily, the same lubricating substance used on the outer surface of the sealing member. Once the plunger sealing member is coated, the plunger sealing member and the lubricating substance are irradiated to induce cross-linked bonds between the molecules of the lubricating substance so that the substance adheres non-loosely to the outer surface of the plunger sealing member. Then the plunger with the plunger sealing member attached 15 is inserted into the chamber of the syringe body so that the outer surface of the sealing member is sealingly engaging the chamber interior wall.

Subsequently, the syringe according to the invention is filled with the medicament intended for long-term storage within the chamber of the syringe.

20 The syringe may then be packed in any type of exterior wrapping or casing preferably having information printed thereon suitable or necessary for using the syringe with the medicament. Non-depending on whether the syringe is packed in an outer wrapping or casing, the syringe with the medicament filled into the chamber of the syringe is heat- treated to a temperature above 100°C in order to sterilise the syringe. Heat-treating of the

25 , syringe is preferably done by autoclaving the syringe to a temperature above 110°C. By autoclaving or by any other heat-treatment the temperature may rise to as much as 120.5°C, and the period of time where such high temperature is maintained may be up to or above 20 minutes. Alternatively, the temperature may rise to as much as 121.0°C, and the period of time where such high temperature is maintained may be up to or more than

30 15 minutes.

BRIEF DESCRIPTION OF THE DRAWINGS

The invention will be described in more detail with reference to the drawings, where 35 fig. 1 and fig. 2 are cross-sections of an embodiment of a syringe body for a syringe according to the invention, fig. 3 and fig. 4 are perspective views of the embodiment of a syringe body for a syringe according to the invention, fig. 5 is a cross-sections of an embodiment of a syringe plunger for a syringe according to the invention, fig. 6 and fig. 7 are cross-sections of the embodiment of a syringe plunger for a syringe according to the invention, fig. 8 and fig. 9 are perspective views of an embodiment of plunger top cap for a syringe according to the invention, fig. 10 is a cross-sections of the embodiment of a plunger top button for a syringe according to the invention, fig. 11 is a perspective view an embodiment of a sealing member for a syringe according to the invention, fig. 12 is a plane view of the embodiment of a sealing member for a syringe according to the invention, fig. 13 is a cross-section of the embodiment of a sealing member for a syringe according to the invention. fig. 14 and fig. 15 are cross-sections of another embodiment of a syringe according to the invention, fig. 16 and fig. 17 are cross-sections of an alternative embodiment of a syringe plunger for a syringe according to the invention, fig. 18 and fig. 19 are perspective views of an alternative embodiment of plunger top cap for a syringe according to the invention, and fig. 20 is a cross-sections of the alternative embodiment of the alternative plunger top cap for a syringe according to the invention,

DETAILED DESCRIPTION OF THE INVENTION

Fig. 1-4 are drawings of a possible and preferred embodiment of a syringe body for a larger syringe according to the invention. The scale is 1: 1 compared to the actual size of the syringe body. In the embodiment shown the syringe body is for a syringe to store up to 20 ml of a medicament. However, the same features as described below could be present for any other size of syringe body. The syringe is preferably made of the material sold under the trade-name NOVOLEN 1170L Natural. The syringe body has side walls extending from a bottom 3 of the syringe body to a top 2 of the syringe body. The side walls exhibit an outer diameter Dl of the syringe body. In the embodiment shown, the outer diameter is about 22 mm. The side walls 1 together with the top 2 of the syringe body forms a chamber 4 being open at the bottom 3 of the syringe body. The chamber has an inner diameter dl, which in the embodiment shown is about 20 mm.

The top 2 of the syringe body is provided with a spout 5 constituting fluid orifice of a medicament and intended for holding a needle cannula (not shown), when medicament stored in the syringe is to be injected. The spout 5 has a conical shape. In the embodiment shown, the spout 5 is placed off-centre in relation to a central line A of the syringe body. In alternative embodiments, the spout 5 may be placed centrally along the central line A of the syringe body. The top 2 of the syringe body is slightly concave seen from the interior of the chamber 4 formed. The curvature of the concavity as seen from the interior of the chamber 4 has a semi-circular extension with a radius of between 25 mm and 50 mm, preferably about 35 mm.

The side walls 1 of the syringe body not only extend from the bottom 3 to the top 2, but extend a bit further beyond the top 2 so that a collar 6 is provided. The further extension b is about 3 mm. At an intersection 7 between the side walls 1 and the top 2 of the syringe body, an outer diameter of the side walls are decreased a bit, perhaps about 0.15 mm. The part 6 of the side walls 1 extending beyond the top 2 of the syringe body is furthermore slightly conical. In the embodiment shown, the conicity is of about 1.5°. Generally, the material thickness of all parts, i.e. the side walls 1, the top 2 and the spout 5 is about 1 mm, however with some deviations due to constructional and manufacturing requirements and restrictions. This result in the advantage that the risk is limited of shrinkage holes after injection moulding of the syringe body.

A flange 7 is provided at the bottom of the syringe body. The flange 7 is intended to act as finger-grips, when pushing the plunger (see fig. 5-7) towards the top 2 of the syringe. The flange 7 is provided with recesses 8 at a back of the flanges 7 in order to reduce the thickness of the flanges, thereby obtaining a more uniform thickness of all the parts of the syringe body. At an intersection 9 between the side walls 1 and the flange 7 at the bottom 3 of the syringe body, a reinforcing material thickness enlargement is provided. At the bottom 3, an interior of the side walls 1 are conical in order to establish walls 10 of an inlet for easing the insertion of the syringe plunger (see fig 5-7) into the chamber 4. In the embodiment shown, the conicity of the inlet 10 is about 20°.

Fig. 5-7 are drawings of a possible and, for relatively larger syringes, a preferred embodiment of a syringe plunger rod to be used together with the syringe body shown in fig. 1-4. The scale is 1: 1 compared to the actual size of the syringe plunger rod. In the embodiment shown the syringe plunger rod is for a syringe to store up to 20 ml of a medicament. However, the same features as described below could be present for any other size of syringe plunger rod. The syringe plunger rod comprises plunger rod walls 11 and a plunger top 12.

The plunger rod walls 11 are substantially cylindrically configured. The plunger rod walls exhibit an outer diameter Dll and an inner diameter dll. In the embodiment shown, the outer diameter Dll is about 20 mm, or at least less then the inner diameter of the chamber 4 (see fig. 1-4), and the inner diameter dll is about 18 mm. At the top 12 of the plunger rod, a recess 13 is provided, and in the bottom centre of the recess 13 a hole 14 is formed. The recess 13 extends from a top surface 15 of the plunger rod downwards into the interior of the cylindrical plunger rod. The recess has a bottom surface 19. The recess 13 is intended for taking up of part of a distance piece of a cap (see fig. 8-10) for holding a sealing member (see fig 11-13) to the plunger rod. In the embodiment shown, an inner diameter dl3 of the recess is about 10.5 mm. An inner depth 113 of the recess is about 3.5 mm, and an outer depth L13 of the recess is about 5.6 mm. As mentioned, in the bottom of the recess 13, a hole 14 is provided. The hole 14 is intended for taking up of an intermediate section of the cap (see fig. 8-10). In the embodiment shown, the diameter dl4 of the hole is about 8.0 mm. The overall length L of the plunger rod is about 103 mm.

The plunger rod walls 11 and the recess 13 are preferably manufactured by injection moulding with relatively low moulding pressures compared to the moulding pressures, which the person skilled in the art would commonly apply. This has the effect, that less tensions and strains are induced into the plastic material, which the plunger rod is made from than if the plunger rod was made by injection moulding at commonly applied moulding pressures or by extruding. However, control and regulation of any commonly applied injection moulding process or extruding process may be administered so that the plunger rod may be manufactures utilising any of these alternative processes in stead of injection moulding at lower moulding pressures, and still obtain a plunger rod not being prone to deformations due to tensions and strain, especially deformations occurring, when heat treating the plunger rod for sterilisation purposes, such as autoclaving or any other suitable heat treatment process.

The plunger rod walls 11 have at their bottom 16 a small collar 17 provided along an inside surface of the plunger rod walls 11. The very bottom 16 of the plunger rod is provided with a flange 18. The flange 18 is intended for providing a surface for the thumb of the user pushing the plunger rod towards the top 2 of the syringe body (see fig. 1-4), when injecting medicament by use of the syringe. The collar 17 is intended for possible engagement with a separate flange (not shown), having a part, which may be inserted into the bottom of the plunger rod. This part will have means corresponding to the collar for establishing the mutual engagement between the collar and this part of the separate flange. Such separate flange may serve as an enlarged surface for the thumb of the user pushing the plunger rod towards the top 2 of the syringe body (see fig. 1-4), when injecting medicament by use of the syringe. Generally, the material thickness of all parts, i.e. the plunger rod walls 11, the top 12 and the flange 18 is about 1 mm, however with some deviations due to constructional and manufacturing requirements and restrictions. This result in the advantage that the risk is limited of different mechanical behaviour of different parts of the plunger rod after moulding of the plunger rod and when heat treating the syringe and the plunger rod.

Fig. 8-10 are drawings of a plunger cap intended for engaging with the recess (see fig. 5- 7) at the top of the plunger rod. The scale of the plunger cap is 2: 1 compared to the actual size of the cap. In the embodiment shown the plunger cap is for a syringe to store up to 20 ml of a medicament. However, the same features as described below could be present for any other size of plunger cap. The cap has a disc-shaped top 20 and has a tenon-shaped bottom 21.

The tenon-shaped bottom 21 is intended for being introduced into the recess 13 (see fig. 5-7) and the hole 14 (see fig. 5-7) in the recess of the plunger top. The tenon comprises four legs 22 each divided by a slot 23. Each of the legs 22 is capable of resiliently bending inwards towards a central line B of the cap. Each of the legs 22 is divided into three sections. A first section 24 constitutes a locking means for locking the cap to the top of the plunger rod. A second section 25 is just an intermediate section between the first section and a third section 26. The third section 26 constitutes a distance piece establishing a certain distance between an underside 27 of the disc-shaped top 20 of the cap and the upper surface 15 (see fig. 5-6) of the plunger rod, when the cap is secured to the top of the plunger rod.

The disc-shaped top 20 has a diameter D20 being smaller than an outer diameter of a sealing member (see fig 11-13). The disc-shaped top 20 is intended for holding the sealing member to the plunger rod. When securing the cap to the plunger rod, the sealing member will be maintained to the plunger by being sandwiched between the top surface 15 (see fig. 5-6) of the plunger rod and the underside 27 of the cap. The cap is secured to the plunger rod by means of introducing the locking section 24 of the legs 22 into the hole 14 in the top of the plunger rod. The legs 22 are pushed as far as possible, whereby collars 28 of the locking section 24 will engage a bottom side 19 of the recess 15 in the top of the plunger rod. The intermediate section will extend through the hole 14 (see fig 5-6) from the upper side of the recess to the bottom side of the recess.

Because of the provision of the distance section 25 and because of the dimensions of the distance section 25 in relation to the dimensions of the recess 15 and the hold 14, the sealing member being sandwiched between the top surface 15 of the plunger rod and the underside 27 of the disc-shaped part 20 of the cap, will not be squeezed along an outer circumference of the sealing member, thus preventing any dimensional changes of the sealing member, when being sandwiched between the parts mentioned and before the plunger is introduced into the chamber of the syringe body. However, the underside 27 of the disc-shaped part 20 is slightly inclined so that an inner section of the sealing member may be squeezed outwards when being sandwiched between the top surface 15 of the plunger rod and the underside 27 of the disc-shaped part 20 of the cap. In the embodiment shown, the inclination α is about 91.5 degrees.

The disc-shaped part has a small indention in a top surface 29 of the disc-shape. This indention is provided so that any inlet remains from the injection moulding of the cap will be embedded in the indention. Thereby, the inlet remains will not obstruct a complete pushing forward of the plunger when injecting medicament by use of the syringe. If any inlet remains did protrude from the top surface of the disc-shaped part, this would prevent a complete pushing forwards and thus a complete emptying of the medicament form the syringe.

Fig. 11-13 are drawings of a sealing member for a syringe according to the invention. The scale is 5: 1 compared to the actual size of the sealing member. The sealing member has a torus-like shape. In the embodiment shown, the sealing member is for a syringe to store up to 20 ml of a medicament. However, the same features as described below could be present for any other size of sealing member. The sealing member is preferably made completely of silicone, most preferably made of the material sold under the trade-name SILOPREN LSR 4070. Alternatively, the sealing member may be made of rubber or another elastomeric material having silicone applied during manufacturing.

The sealing member has a central hole 30 having a diameter d31 and the sealing member has an outer diameter D32. A circumference 31 of the sealing member along the hole and along 30 and an outer circumference 32 is tapered and rounded so that the boundaries of the sealing member, in a non-stressed situation as shown, is constituted by a line, rather than a surface, said lines running along the circumference 31 of the hole and along the outer circumference 32.

However, when the sealing member is secured to the plunger rod, and when the plunger rod is inserted into the chamber of the syringe body, the circumferences 31,32 may be stressed. Thus, the abutment between the interior wall of the chamber 4 of the syringe body and the outer circumference 32, and the abutment between the distance section 26 (see fig. 8-10) of the cap and the circumference 31 of the hole 30 may be established along a surface rather than along a line. The sealing member is preferably made of silicone, but the silicone is cross-linked so that no silicone will be suspended within the medicament.

In the embodiment shown, the sealing member has a thickness T of about 1.3 mm. The sealing member is preferably manufactured by injection moulding. In the drawing it is shown, where a parting plane P of two halves of the manufacturing mould is established in relation to the sealing member. As shown, the parting plane P is established off centre in relation to a symmetry plane S of the sealing member. In the embodiment shown, the parting plane is established about 0.3 mm off centre OC the symmetry plan S. This ensures that any moulding remains in the parting plane P will not be present along the lines constituting the inner circumference 31 and the outer circumference 32. These lines lie in the symmetry plane S.

Thereby, the circumferences 31,32 constituting the abutment surfaces along the distance section 26 (see fig. 8-10) of the cap and along the interior walls of the chamber 4 (see fig. 1-4), respectively, will be even and smooth, ensuring a proper and safe abutment. When the sealing member is mounted to the plunger rod by sandwiching the sealing member between the top surface 15 (see fig. 5-6) of the plunger rod and the underside (see fig. 9- 10) of the disc-shaped part of the cap, and when the plunger subsequently is inserted into the chamber 4 (see fig. 1-4) of the syringe body, the outer circumference 32 of the sealing member will be in a fluid-tight relationship with the interior walls of the chamber.

Fig. 14-15 are drawings of a possible and preferred embodiment of a syringe body for a smaller syringe according to the invention. The scale of fig. 14 is about 1.4: 1 and the scale of fig. 15 is about 3.5: 1 compared to the actual size of the syringe body. In the embodiment shown the syringe body is for a syringe to store up to 2 ml of a medicament. However, the same features as described below could be present for any other size of syringe body. The syringe is preferably made of the material sold under the trade-name NOVOLEN 1170L Natural. The syringe body has side walls 1 extending from a bottom 3 of the syringe body to a top 2 of the syringe body. The side walls 1 exhibit an outer diameter Dl of the syringe body. In the embodiment shown, the outer diameter is about 10.4 mm. The side walls 1 together with the top 2 of the syringe body forms a chamber 4 being open at the bottom 3 of the syringe body. The chamber has an inner diameter dl, which in the embodiment shown is about 8.9 mm.

The top 2 of the syringe body is provided with a spout 5 constituting fluid orifice of a medicament and intended for holding a needle cannula (not shown), when medicament stored in the syringe is to be injected. The spout 5 has a conical shape. In the embodiment shown, the spout 5 is placed centrally in relation to a central line A of the syringe body. In alternative embodiments, the spout 5 may be placed off-centre in relation to the central line A of the syringe body. The top 2 of the syringe body is slightly concave seen from the interior of the chamber 4 formed. The curvature of the concavity as seen from the interior of the chamber 4 has a semi-circular extension with a radius of between 3 mm and 20 mm, preferably about 6 mm.

A flange 7 is provided at the bottom of the syringe body. The flange 7 is intended to act as finger-grips, when pushing the plunger (see fig. 16-17) towards the top 2 of the syringe. At an intersection 9 between the side walls 1 and the flange 7 at the bottom 3 of the syringe body, a reinforcing material thickness enlargement is provided. At the bottom 3, an interior of the side walls 1 are conical in order to establish walls 10 of an inlet for easing the insertion of the syringe plunger (see fig 16-17) into the chamber 4. In the embodiment shown, the conicity of the inlet 10 is about 60°.

Fig. 16-17 are drawings of a possible and, for relatively smaller syringes, a preferred embodiment of a syringe plunger rod to be used together with the syringe body shown in fig. 1-4. The scale of fig. 14 is about 1.4: 1 and the scale of fig. 15 is about 3.5: 1 compared to the actual size of the syringe plunger rod. In the embodiment shown the syringe plunger rod is for a syringe to store up to 2 ml of a medicament. However, the same features as described below could be present for any other size of syringe plunger rod. The syringe plunger rod comprises plunger rod walls 11 and a plunger top 12.

The plunger rod walls 11 are substantially cylindrically configured. The plunger rod walls exhibit an outer diameter Dll and an inner diameter dll. In the embodiment shown, the outer diameter Dll is about 8.4 mm, or at least less than the inner diameter of the chamber 4 (see fig. 15-16), and the inner diameter dll is about 6.8 mm. At the top 12 of the plunger rod, a recess 13 is provided, and in the bottom centre of the recess 13 a hole 14 is formed. The recess 13 extends from a top surface 15 of the plunger rod downwards into the interior of the cylindrical plunger rod. The recess leads directly to the hole 14. The recess 13 is intended for taking up of part of a distance piece of a cap (see fig. 18-20) for holding a sealing member (see fig 11-13) to the plunger rod. In the embodiment shown, an inner diameter dl3 of the recess is about 3.25 mm. An inner depth 113 of the recess is about 2.0 mm.

As mentioned, the recess 13 leads directly to a hole 14. The hole 14 is intended for. taking up of an intermediate section of the cap (see fig. 18-20). In the embodiment shown, the hole has a conical shape with a conicity of about 10°. The hole 14 leads to tongues 33 directed downwards into the plunger. The tongues 33 also have a conical shape with a conicity of about 13° and is intended for engagement with a stop (see fig. 18-20) of a plunger cap. The tongues 33 consist of four tongues each divided by a slot 34. Each of the tongues 33 is capable of resiliently bending away from a central line of the plunger rod. The overall length L of the plunger rod is about 63 mm.

The plunger rod walls 11 and the recess 13 are preferably manufactured by vacuum moulding. This has the effect, that less tensions and strains are induced into the plastic material, which the plunger rod is made from than if the plunger rod was made by injection moulding or by extruding. However, control and regulation of any injection moulding process or extruding process may be administered so that the plunger rod may be manufactures utilising any of these alternative processes in stead of vacuum moulding, and still obtain a plunger rod not being prone to deformations due to tensions and strain, especially deformations occurring, when heat treating the plunger rod for sterilisation purposes, such as autoclaving or any other suitable heat treatment process.

The very bottom 16 of the plunger rod is provided with a flange 18. The flange 18 is intended for providing a surface for the thumb of the user pushing the plunger rod towards the top 2 of the syringe body (see fig. 1-4), when injecting medicament by use of the syringe.

Generally, the material thickness of all parts, i.e. the plunger rod walls 11, the top 12 and the flange 18 is about 0.7 mm, however with some deviations due to constructional and ^• manufacturing requirements and restrictions. This result in the advantage that the risk is limited of different mechanical behaviour of different parts of the plunger rod after moulding of the plunger rod and when heat treating the syringe and the plunger rod.

Fig. 18-20 are drawings of a plunger cap intended for engaging with the recess, the hole and the tongues (see fig. 5-7) at the top of the plunger rod. The scale of the plunger cap is 5: 1 compared to the actual size of the cap. In the embodiment shown the plunger cap is for a syringe to store up to 2 ml of a medicament. However, the same features as described below could be present for any other size of plunger cap. The cap has a discshaped top 20 and has a tenon-shaped bottom 21.

The tenon-shaped bottom 21 is intended for being introduced into the recess 13 (see fig. 16-17) and the hole 14 (see fig. 16-17) in the plunger top. The tenon-shaped bottom is divided into three sections. A first section 24 constitutes a stop 35 for locking the cap to the top of the plunger rod. A second section 25 is just an intermediate section between the first section and a third section 26. The third section 26 constitutes a distance piece establishing a certain distance between an underside 27 of the disc-shaped top 20 of the cap and the upper surface 15 (see fig. 16-17) of the plunger rod, when the cap is secured to the top of the plunger rod.

The disc-shaped top 20 has a diameter D20 being smaller than an outer diameter of a sealing member (see fig 11-13). The disc-shaped top 20 is intended for holding the sealing member to the plunger rod. When securing the cap to the plunger rod, the sealing member will be maintained to the plunger by being sandwiched between the top surface 15 (see fig. 14-15) of the plunger rod and the underside 27 of the cap. The cap is secured to the plunger rod by means of introducing the stop 35 constituting the locking section 24 into the recess 13, further into the hole 14 and past the tongues 33 in the top of the plunger rod. The tenon-shaped bottom are pushed as far as possible, whereby the stop 35 of the locking section 24 will engage with the tongues 33 in the top of the plunger rod. The intermediate section will extend through the recess and through the hole 14 (see fig 16- 17) from the upper side of the plunger rod to where the hole leads to the tongues.

Because of the provision of the distance section 25 and because of the dimensions of the distance section 25 in relation to the dimensions of the recess 15 and the hold 14, the sealing member being sandwiched between the top surface 15 of the plunger rod and the underside 27 of the disc-shaped part 20 of the cap, will not be squeezed along an outer circumference of the sealing member, thus preventing any dimensional changes of the sealing member, when being sandwiched between the parts mentioned and before the plunger is introduced into the chamber of the syringe body. However, the underside 27 of the disc-shaped part 20 is slightly inclined so that an inner section of the sealing member may be squeezed outwards when being sandwiched between the top surface 15 of the plunger rod and the underside 27 of the disc-shaped part 20 of the cap. In the embodiment shown, the inclination α is about 92.25 degrees. The disc-shaped part has an indention in a top surface 29 of the disc-shape.

Polymeric silicones that may be used when manufacturing the sealing member include: phenyl substitute silicones, vinyl substitute silicones, hydrogen substituted silicones, and other suitable polymeric silicones. The silicones that may be used for manufacturing the sealing member have viscosities between 1,000 and 100,000 centistokes. Possible phenyl substituted silicones include: dimethyldiphenylpolysiloxane copolymers; dimethyl, methylphenylpolysiloxane copolymers; polymethylphenylsiloxane; and methylphenyl, dimethylsiloxane copolymers. The higher the phenyl content of the substituted silicone the lower the amount of cross-linking may occur. The phenyl substituted silicones may be used in a variety of viscosities especially between 12,500 centistokes and 100,000 centistokes.

The syringe according to the invention is especially well-suited for long-time storage of medicaments. Furthermore, the syringe is especially well-suited for long-time storage of the following medicaments, which otherwise must be stored in glass syringes.

The polymeric silicone used to lubricate the sealing member is preferably selected in order to be compatible with the particular medicament to be filled into the syringe and in order to hold the silicone in a non-loosely manner also during long-time storage of the medicament in the syringe. The polymeric silicone is also selected in consideration of the material composition of the sealing member. In addition, it is necessary to comply with governmental regulations regarding acceptable materials for use in a syringe for long-time storage of medicaments in a plastic syringe.

Apart form the sealing member having silicone cross-linked inside or onto the material of the sealing member, additionally or alternatively, and not necessarily, the syringe body may be manufactured having silicone cross-linked to the plastic material of the syringe body.

Vinyl substituted silicones that are advantageous in manufacturing syringe bodies having silicone cross-limed to the material of the syringe body include: vinyldimethyl terminated polydimethylsiloxanes; vinylmethyl, dimethylpolysiloxane copolymers; vinyldimethyl terminated vinylmethyl, dimethylpolysiloxane copolymers; divinylmethyl terminated polydimethylsiloxanes; polydimethylsiloxane, mono vinyl, mono n-butyldimethyl terminated; and vinylphenylmethyl terminated polydimethylsiloxanes. The vinyl substituted silicones also can be made in a variety of viscosities. Also to be noted is that higher vinyl content may provide more efficient cross-linking depending on the cross- linking process.

Hydrogen substituted silicones that are advantageous in manufacturing selaing members for syringe bodies having silicone cross-linked to the material of the syringe body include: dimethylhydro terminated polydimethylsiloxanes; methylhydro, dimethylpolysiloxanecopoly- mers; methylhydro terminated methyloctyl siloxane copolymers; and methylhydro, phenylmethyl siloxane copolymers. The hydrogen substituted siloxanes can be used in a variety of viscosities. Other substituted silicones that may be used include: polyfluoroalkylmethyl siloxanes; fluoralkyl, dimethyl siloxanecopolymers; and polymethylalkylsiloxanes.

The above description is only exemplary, and does not constitute a limitation of possible other embodiments according to the invention. Variations and modifications to the disclosed embodiments may be possible within the scope of the present invention to the person skilled in the art.

Claims

1. A syringe to be pre-filled with a medicament, said syringe having an interior wall being made of a plastic material, said interior wall defining a chamber, said syringe furthermore having a plunger sealing member comprising a polymeric silicone being non-loosely bounded to the material of the plunger sealing member, possibly said syringe having a plunger sealing member consisting in a polymeric silicone, and said syringe intended for having a medicament stored in the chamber.

2. A syringe according to claim 1, wherein the polymeric silicone is adhered to said plunger sealing member by cross-linking bonds formed between molecules of said polymeric silicone.

3. A syringe to be pre-filled with a medicament, said syringe having an interior wall being made of a plastic material, said interior wall defining a chamber, said interior wall of the syringe furthermore having a polymeric silicone non-loosely adhered to the material of the interior wall, and said syringe intended for having a medicament stored in the chamber.

4. A syringe according to claim 1, wherein the polymeric silicone is adhered to said interior wall of the syringe by cross-linking bonds formed between molecules of said polymeric silicone.

5. A syringe according to any of the preceding claims, wherein said polymeric silicone is one of the group of phenyl substituted silicones consisting of polydimethyl siloxane, namely dimethyldiphenylpolysiloxane copolymers; dimethyl, methylphenylpolysiloxane copolymers; polymethylphenylsiloxane; and methylphenyl, dimethylsiloxane copolymers.

6. A syringe according to any of the preceding claims, wherein said syringe, after having been filled with the medicament, has been heat-treated to a temperature above 100°C.

7. A syringe according to any of the preceding claims, wherein said syringe, after having been filled with the medicament, has been heat-treated to a temperature of at least 110°C for at least 20 minutes.

8. A syringe according to any of the preceding claims, wherein said syringe, after having been filled with the medicament, has been heat-treated to a temperature of at least 120°C for at least 15 minutes.

.

9. A syringe according to any of the preceding claims, wherein said syringe, after having been filled with the medicament, has been heat-treated by autoclaving.

10. A plastic material of a syringe according to any of the claims 1-9, wherein the plastic

5 material is at least one of the subgroup of polyolefins such as Polyethylene, Polypropylene, Polystyrene, Polyvinyl chloride, Polyvinylidene chloride or Polyvinyl acetate.

11. A plastic material of a syringe according to any of the claims 1-9, wherein the plastic material is at least one of the subgroup of acrylic polymers such as Polyacrylonitrile,

10 Polymethyl methacrylate, Polymethyl acrylate, polyethyl acrylate or Polyacrylate elastomers.

12. A plastic material of a syringe according to any of the claims 1-9, wherein the plastic material is at least one of the subgroup of fluorinated polymers such as

15 Polytetrafluoroethylene, Fluoroelastomers, Polyvinyl fluoride or Polyvinylidene fluoride.

13. A plastic material of a syringe according to any of the claims 1-9, wherein the plastic material is at least one of the subgroup of diene polymers such as Polybutadiene, Polychloroprene, or Polyisoprene.

20

14. A plastic material of a syringe according to any of the claims 1-9, wherein the plastic material is at least one of the subgroup of Vinyl copolymers such as Acrylonitrile- butadiene-styrene, Styrene-butadiene rubber, Styrene-acrylonitrile, Nitrile rubber, Butyl rubber, Styrene-butadiene and styrene-isoprene block copolymers, Ethylene-propylene

25 copolymers or Styrene-maleic anhydride copolymer.

15. A plastic material of a syringe according to any of the claims 1-9, wherein the plastic material is at least one of the subgroup of Aldehyde condensation polymers such as Phenol formaldehyde, Urea-formaldehyde polymers or Melamine-formaldehyde polymers.

30

16. A plastic material of a syringe according to any of the claims 1-9, wherein the plastic material is at least one of the subgroup of Cellulosics such as Rayon, Cellulose nitrate or Cellulose acetate.

35 17. A plastic material of a syringe according to any of the claims 1-9, wherein the plastic material is at least one of the subgroup of Polyamides such as Nylon or Aramids.

18. A plastic material of a syringe according to any of the claims 1-9, wherein the plastic material is at least. one of the subgroup of Polyesters such as Polyethylene terephthalate, Polybutylene terephthalate, Polycarbonate, Degradable polyesters, Alkyds or Unsaturated polyesters.

19. A plastic material of a syringe according to any the claims 1-9, wherein the plastic 5 material is at least one of the subgroup of Polyethers such as Polyacetal, Polyphenylene oxide, Polyetherketone, polyetheretherketone, or Aliphatic polyethers.

20. A plastic material of a syringe according to any of the claims 1-9, wherein the plastic material is at least one of the subgroup of Polyimides such as Polyamideimide or

10 Polyetherimide.

21. A plastic material of a syringe according to any of the claims 1-9, wherein the plastic material is at least one of the subgroup of Polysulfides such as Polyphenylene sulfide.

15 22. Use of a syringe according to any of the claims 1-9 for long-term storage of a medicament filled within the syringe.

23. Use of a plastic material according to any of the claims 10-21 for manufacturing a syringe according to any of the claims 1-9.