WO1992001485A1

WO1992001485A1 - Two compartment syringe

Info

Publication number: WO1992001485A1
Application number: PCT/DK1991/000177
Authority: WO
Inventors: Ib Hansen
Original assignee: Novo Nordisk A/S
Priority date: 1990-07-20
Filing date: 1991-06-28
Publication date: 1992-02-06
Also published as: AU8239291A; DK174390D0

Abstract

A two-compartment syringe comprising a barrel (10) comprising a distal and a proximal section, the distal section (13) comprising at least one by-pass (15) and the proximal section comprising in the ready to sell form of the syringe a separate cylindrical insert (50) comprising a distal (52) and a proximal piston (60), the interior of the insert (50) having such a shape and dimension that the pistons (52, 60) are displaceable from the insert (50) into the distal section (13) of the barrel (10).

Description

TWO COMPARTMENT SYRINGE

The present invention relates to a two-compartment syringe comprising an elongate barrel having a tip extending from the distal end of said barrel and having a passageway therethrough, a distal piston and a proximal piston both being slidably positioned within said barrel so as to define a distal compartment for holding a first component and located between said tip and said distal piston and a proximal compartment for holding a second component in the form of a liquid and located between said distal piston and said proximal piston, a plunger rod for axially displacing the proximal piston, and at least one by-pass of an axial length which exceeds the axial length of said distal piston so as to allow the liquid to pass from the second compartment to the first compartment when the distal piston is positioned in the zone defined by said by-pass.

Some drugs show a rapid loss of potency when they are in a ready to use injectable composition.

A solution to this problem is found in using a two compartment syringe having a distal compartment containing a component which may be a solid, e.g. a lyophilized powder, and a proximal compartment containing a liquid component, in the following designated the solvent, and means for allowing the solvent to flow from the proximal compartment to the distal compartment before an injection is to be performed. These means may comprise a distal piston and a proximal piston both being slidably positioned within the barrel and at least one by-pass providing liquid communication between the two compartments when the distal piston is positioned in the by-pass zone.

Two compartment syringes of this type are described in Danish patent application No. 3752/84, EP O 295 337 Al and EP 0 172 990 Al.

Due to the ease of moulding and/or processing plastic materials it would be preferable to manufacture the barrels of two compartment syringes from plastic materials. However, since plastic materials may give off trace amounts of components which are unacceptable in injectable preparations, barrels for two compartment syringes are ordinarily made from glass.

The use of glass barrels presents several disadvantages. Thus it is difficult and laborious to provide by-passes in the wall of a glass barrel and the rate of discarding is high. Consequently production costs become relatively high. Further¬ more, the dimensions of glass barrels inevitably vary consider¬ ably, which is inconvenient and may necessitate a separate control step in the production. The object of the invention is to eliminate or con¬ siderably reduce the above mentioned drawbacks of the prior art two compartment syringes.

This object and other objects which will appear from the following description are achieved with the syringe of the invention which syringe is characterized in that the barrel comprises a distal and a proximal section, the distal section having a smaller inner diameter than the proximal one, and the distal section comprising the by-pass and the proximal section comprising in the ready to sell form of the syringe a separate cylindrical insert comprising the distal and proximal pistons, the interior of the insert having such a shape and dimension that the pistons are displaceable from the insert into the distal section of the barrel.

The invention is based on the discovery that by using a separate insert comprising the distal and proximal piston and consequently forming the proximal compartment only the insert has to be made from a material which is compatible with the solvent whereas the remaining parts of the syringe can be made from any suitable material including a plastic material which is easy to mould and/or process.

Thus the inventin permits the insert to be made from e.g. glass and the barrel from a thermoplastic material.

If the barrel is prepared by e.g. injection moulding, it is a simple task to provide by-passes in the wall of the barrel and both the number of by-passes and the dimensions of such by¬ passes can be adjusted to the solvent used. A particularly preferred embodiment of the syringe of the invention comprises vents in the form of axially extending grooves provided on the inside of the proximal section of the barrel. By using a barrel comprising such vents it is possible to lyophilize the solid substance in situ i.e. after it has been introduced into the distal compartment in the form of a solution and after the insert has been partially introduced into the barrel. The insert together with the barrel functions as a valve which can be closed by pressing the insert fully home in the barrel. When this is done as soon as the lyophilization process is completed, the risk of a subsequent contamination is minimized. Another particularly preferred embodiment of the syringe of the invention comprises a barrel comprising a proximal part and a distal part having means for joining the two parts together to form a unit.

When using such a two part barrel the proximal part and the insert can be removed when the solvent has been transferred from the proximal compartment to the distal compartment and the remaining components can be used in connection with a separate injection assembly, e.g. a pen-like syringe or a delivery pump. The barrels used in the syringes of the invention are preferably made from a thermoplastic material which can be moulded e.g. injection moulded. Examples of suitable thermo¬ plastic materials are polyamides, polycarbonate, polyethylene, polypropylene and polyesters.

The insert is preferably made from glass or another material which does not give off substances which are incom¬ patible with medication solvents.

The invention will now be described in further detail with reference to the drawing in which

Fig. 1 shows a longitudinal sectional view of a barrel for use in a preferred embodiment of the syringe of the invention. Fig. 2 shows a cross sectional view of a syringe barrel as shown in Fig. 1 at the line A-A. Fig. 3 shows a cross sectional view of a syringe barrel as shown in Fig. 1 at the line B-B. Fig. 4 shows a proximal end view of a syringe barrel as shown in Fig. 1 having a flange fixed to its proximal end. Fig. 5 shows a longitudinal sectional view of the barrel illustrated in Fig. 1 and a cylindrical insert partly inserted in said barrel.

Fig. 6 shows a longitudinal sectional view of a fully assembled syringe. Fig. 7 shows a longitudinal sectional view of a barrel consisting of two parts. Figs. 8-9 show other preferred embodiments of the distal end of syringes of the invention.

Fig. 1 shows a barrel 10 comprising a tip 11 having a central passage 12, a distal section 13 and a proximal section

14. The internal diameter of the distal section 13 is smaller than the internal diameter of the proximal section 14, and a by-pass 15 in the form of grooves are provided on the inside of the distal section 13 of the barrel. The proximal section 14 of the barrel comprises a number of vents 16 in the form of grooves provided on the inside of the proximal section 14 of the barrel 10 and extending axially from the proximal end of the barrel 10. The tip 11 of the barrel 10 is sealed by a piercable membrane 17 secured by a metal cap 18.

In Fig. 2, 20 is the wall of the distal section 13 of the barrel 10 having a by-pass 15 in the form of a groove formed therein.

In Fig. 3, 30 is the wall of the proximal section 14 of the barrel 10 having a number of vents 16 in the form of grooves formed therein.

In Fig. 4, 40 is a flange fixed to the proximal end of the barrel 10.

Fig. 5 shows an insert 50 in the form of a tube partly inserted in a barrel as shown in Fig. 1. The insert 50 has a sealing ring 51 provided on the outside of its distal end and serving to establish a liquid-tight contact between the insert 50 and the inside of the barrel 10. The sealing ring 51 may be acσomodated in a circumferential groove. As will appear from Fig. 6 the insert 50 further comprises a distal piston 52 and a proximal piston 60 which together delimit a compartment 61 serving to hold a liquid component. The proximal piston 60 can be displaced by means of a plunger rod 62 having a pressure head 63. In the fully assembled form of the syringe shown in Fig. 6 the insert 50 is aligned with the bore of the distal section 13 of the barrel 10 and since it has the same internal diameter as said bore the pistons 52, 60 can be displaced into the distal section 13 of the barrel 10. Thus, after filling the interior of the insert 50 with a solvent and the interior of the distal section 13 of the barrel 10 with a substance to be mixed with or dissolved in the solvent, the plunger rod 62 can be depressed. Before the depression of the plunger rod 62 is initiated an open outlet through the tip 11 is established e.g. by mounting a hypodermic needle thereon. The depression causes the two pistons 52, 60 to move towards the distal section 13 of the barrel 10 and when the piston 52 has moved into the zone defined by the by-pass 15, liquid can flow from the insert 50 via the by-pass 15 into the interior of the distal section 13 of the barrel. This flow will continue until the piston 60 contacts the piston 52. When the solvent has been transferred to the distal section 13 of the barrel 10 it may be desirable to shake the syringe to make sure that the substance contained in the distal section is fully dissolved in the solvent.

During the transfer of the liquid component from the proximal compartment to the distal compartment the syringe is preferably held with its distal end pointing upwards in order to allow the air contained in the distal compartment to escape through the tip.

A further depression of the plunger rod 62 will cause the pistons 52, 60 to move into the distal section 13 of the barrel 10 and to press liquid out through the passage 12 of the tip 11 of the barrel 10.

When the insert 50 is positioned in the barrel 10 in the manner shown in Fig. 5 the interior of the distal section 13 of the barrel 10 communicates with the surrounding atmosphere through the vents 16. Thus a solution of a substance may be lyophilized in situ i.e. after it has been introduced into the interior of the distal section 13 of the barrel 10.

Immediately after the lyophilization process has been completed the insert 50 is pressed fully home in the barrel 10 as shown in Fig. 6 and thus the communication between the distal compartment and the surrounding atmosphere is inter¬ rupted. When the barrel 10 and the insert 50 are used for lyophilization in situ the solvent and the proximal piston 60 of the insert 50 can only be added after the lyphilization is completed.

The insert 50 can be secured in its final position e.g. by means of the flange 40 of Fig. 4 which can be snapped on or otherwise fixed on the proximal end of the barrel 10 after the insert 50 has been pressed fully home. The central hole in the flange 40 has a smaller diameter than the outside diameter of the insert 50. Alternatively the insert 50 can be retained by inwardly protruding projections at the distal end of the proximal section 14 of the barrel 10 or by means of an adhesive.

Fig. 7 shows a barrel comprising two parts viz. a distal part 70 which is similar to the distal section 13 of the barrel shown in Fig. 1 and a proximal upper part 71 corresponding to the proximal section 14 of the barrel shown in Fig. 1. However, the proximal end of the distal part 70 and the distal end of the proximal part 71 comprise threads 72 and 73 which allow the two parts to be screwed together to form a unit and which allows the unit to be separated into two parts.

By using a barrel as shown in Fig. 7 it is possible to remove the proximal part 71 together with the emptied insert when the solvent has been transferred to the interior of the distal part 70 of the barrel simply by unscrewing the proximal part 71 from the distal part 70.

When these parts have been removed the remaining components may be used in a separate injection assembly, e.g. a pen-like syringe or a delivery pump.

Fig. 8 and Fig. 9 show alternative embodiments of the tip 11 of the barrel 10. In Fig. 8, the tip is fitted with a fixed needle 80, and in Fig. 9, the tip assumes the form of an elongate standard tapered cone 90 which can be covered with a protection cap (not shown) .

Claims

1. A two-compartment syringe comprising an elongate barrel having a tip extending from the distal end of said barrel and having a passageway therethrough, a distal piston and a proximal piston both being slidably positioned within said barrel so as to define a distal compartment for holding a first component and located between said tip and said distal piston and a proximal compartment for holding a second com¬ ponent in the form of a liquid and located between said distal piston and said proximal piston, a plunger rod for axially displacing the proximal piston, and at least one by-pass of an axial length which exceeds the axial length of said distal piston so as to allow the liquid to pass from the second compartment to the first compartment when the distal piston is positioned in the zone defined by said by-pass, characterized in that the barrel comprises a distal and a proximal section, the distal section having a smaller inner diameter than the proximal one and the distal section comprising the by-pass and the proximal section comprising in the ready to sell form of the syringe a separate cylindrical insert comprising the distal and proximal pistons, the interior of the insert having such a shape and dimension that the pistons are displaceable from the insert into the distal section of the barrel.

2. A syringe according to claim l, characterized in that the barrel is made from a plastic material and the insert from glass.

3. A syringe according to claim 1 or claim 2, charac¬ terized in that it comprises vents in the form of axially extending grooves provided on the outside of the proximal section of the barrel.

4. A syringe according to any of the preceding claims, characterized in that the barrel comprises a proximal part and a distal part having means for joining the two parts together to form a unit.

5. Any novel feature or combination of features as herein described.