WO2000028941A2

WO2000028941A2 - Transfer device

Info

Publication number: WO2000028941A2
Application number: PCT/DK1999/000633
Authority: WO
Inventors: Thomas Buch-Rasmussen; Henrik Ljunggreen; Jens Ulrik Poulsen
Original assignee: Novo Nordisk AS
Current assignee: Novo Nordisk AS
Priority date: 1998-11-17
Filing date: 1999-11-17
Publication date: 2000-05-25
Anticipated expiration: 2001-05-17
Also published as: AU1263600A; WO2000028941A3

Abstract

The present invention relates to a precision transfer device for transferring medicament from a medicament container to a syringe with a needle. The transfer device is arranged for transferring insulin, growth hormone and the like medicaments, and comprises a medicament container having one end sealed with a piercable sealing, and a piston slidably arranged within the container. The medicament container is preferably containing a large volume of medicament, whereby the container has a larger cross-section area than usual medicament containers. The precision medicament container wall is produced so that the volume of medicament being displaced by the piston, when the piston is driven forwards one length unit, is substantially identical for each length unit of the container, preferably substantially identical to a predetermined volume standard.

Description

Transfer device

The present invention relates to a transfer device for transferring medicaments to a syringe with needle as well as a method for filling syringes.

Background

Some patients may parenterally administer medicaments on a regular basis. Medicaments, such as insulin or growth hormone, are very important to dose accu- rately. Often the dose is aspirated from a vial to a calibrated syringe, and due to the potency of the medicament it is important that the amount of the medicament aspirated into the syringe for each dose is precise. The accuracy depends on a variety of factors, such as the calibration of the syringe, the patient's vision as well as general motoric abilities to precisely dose the medicament. Very often the doses are very small amounts of medicament further leading to problems when trying to dose accurately.

To remedy this several dosage measuring devices have been presented wherein the calibration is carried out by an apparatus comprising a medicament-containing container and a piston whereby the medicament is expelled into the syringe from the container. In order to increase patient's compliance the systems must be designed as small and handy as possible, to be carried for example in a normal pocket. Usual systems are to be used with glass containers exhibiting an in inner diameter of 6 to 10 mm and a volume of 1 to 4 ml. Thereby frequent replacement of the emptied container with a filled container is envisaged, the frequency of course depending on the amount of medicament administered daily.

Increasing the volume of a container may be construed by increasing the length of the container and/or the cross-section area, for a cylinder the diameter. However, increasing the length would not lead to a small, handy system. On the other hand, increasing the diameter would lead to another problem, in that the reliability with respect to dose accuracy diminishes when the parameters of the container increase, such as increasing the cross-section of the container and piston. It is thus an object of the present invention to provide a transfer device having a large volume, yet still provide safe and accurate dosing means.

Summary of the invention

This is provided by a transfer device for transferring variable doses of medicament from a multi-dose medicament container to a syringe with a needle, comprising

a medicament container having one end sealed with a pierceable sealing, and a piston slidably arranged within the container, the container further comprising a container wall enclosing the medicament, and

means for mounting the syringe to the device with the needle piercing the seal- ing,

the device further comprising dosing means including a piston driver, said dosing means being adapted for forwards calibrated movement for transferring medicament from the container to the syringe via the needle,

the container wall being produced so that the volume of medicament being displaced by the piston, when the piston is driven forwards one length unit, is substantially identical for each length unit of the container.

Glass containers produced by the usual processes of drawing the glass into long tubes to be cut into the smaller containers as is known by the person skilled in the art normally exhibits a variation of about 2 % as compared to a predetermined value for the cross-section area at relevant dimensions. This variation arises in particular due to day to day variations in the production but is also caused by variations of the diameter of the glass tube from one end to the other. Accordingly, it is not possible to produce a batch of glass containers for the above mentioned purpose having substantially identical cross-sections.

The variation of the glass containers is non-acceptable when increasing the diame- ter and thereby the cross-section of the container, in that the variation is transferred to the dose transferred to the syringe, leaving the patient with a less accurate dosing system. Eventually, this may even lead to serious complications to the patient, in that even small variations in the doses administered for medicaments, such as insulin, are very important. Accordingly, it is important that the container is made of a material, whereby it is possible to obtain a very little variation, so that the volume of medicament being displaced by the piston, when the piston is driven forwards one length unit, is substantially identical for each length unit of the container.

By the term substantially identical volume, is meant the volume displaced by the piston travelling one length unit varies by at the most 1.2 %, such as varies less than

1 %, preferably less than 0.9 %. The term "length unit" is used in its normal meaning, i.e. a length unit as measured by the SI system, such as 1 mm.

It is of importance that the cross-section of each container is substantially identical throughout the whole length of the container. However, it is also important that each container produced does not vary from a predetermined standard. Thus, it is preferred that the volume being displaced by the piston, when the piston is driven forwards one length unit, is substantially identical to a predetermined volume standard. Thus, the cross-section area of the container may not vary more than 1.2 % as compared to a predetermined value for the cross-section area in order to fulfil the criteria set out for the container.

The container material is preferably made by a machine-processable material, such as a mouldable material. In a preferred embodiment the material is a plastic mate- rial, in that it has been shown that the processes for producing plastic containers can be adjusted to such a degree, that the moulded containers can be made with very small dimensional variations.

The moulded containers are preferably produced in a mould comprising a core of dimensions corresponding exactly to the predetermined inner dimensions of the container, such as the inner cross-section of the container. Thereby, any variations of the inner dimensions are substantially avoided, and a container having an inner cross-section throughout the whole length of the container substantially identical with a predetermined standard is producible. In order to obtain a container containing a larger volume of medicament without increasing the length of the device in total, the inner cross-section area of the container is at least 75 mm², preferably at least 90 mm² , more preferably at least 130 mm² . By the term "inner cross-section" is meant the cross-section area of the lumen for the medicament not including the walls. The container may obtain any shape, such as having a circular or non-circular cross-section, the non-circular cross-section being oval, tri-angular or square-formed, for example. When the container is circular the inner cross-section may be calculated from the inner diameter, excluding the walls.

The container forms an enclosed chamber filled with the medicament liquid and has an open end closed by a piston. The piston is slidable longitudinally relative to the container, and the piston is in fluid-tight connection with the container wall in any position of the piston sliding movement.

The dosing means is coupled to the container in any suitable manner allowing the dosing means to activate the piston driver moving the piston forwards. Preferably, the dosing means is coupled through a threaded coupling to the container so that rotating the dosing means in a rotary direction relative to the container drives the piston in the container towards the sealing end of the container.

The piston is driven forwards by a piston driver into the container by a movement corresponding to the dose to be transferred into the syringe. By increasing the cross-section of the container, the piston have to be driven a shorter distance into the container, to transfer the same amount of medicament. Therefore, variations in the transmission from the dosing means to the piston become of greater importance than for dosing from a container having a smaller cross-section.

The relation of cross-section and volume displaced is shown for two examples of containers in the table below:

Since the cross-section dimensions are determining the volume displaced, any variations of the cross-section is directly reflected on the volume transferred to the syringe for any given distance travelled by the piston. Furthermore, as discussed below in this text, the volumes normally transferred for example for insulin are about 0.01 to 0.7 ml, whereby even a small variation in the cross-section area will lead to an unacceptable variation in the amount of medicament transferred.

Accordingly, it is an object of the present invention to provide a transfer device, wherein the piston driver is unitarily moulded with the dosing means, in order to shorten the transmission chain reducing variations.

In the present context, the movement towards the sealing is denoted forwards movement. The movement is calibrated, which in a preferred embodiment is made by providing the device with means for precisely indicating the volume of medicament which as been transferred from the container to the syringe. The amount of medicament delivered into the syringe may be indicated in several ways. The amount can be easily and precisely controlled by controlling the number of full and partial revolutions of the dosing means relative to the container. The control is eased by providing an audible sound for each partial revolution, e.g. a click per unit of medicament.

The indication may be carried out in any suitable way as is apparent to the skilled person. In a preferred embodiment the indication is provided by including at least one detent lock protruding from the container and at least one ridge axially extending along the outer surface of the piston driver. The detent ridge sized and positioned to engage the detent lock each time the dosing means is rotated a set distance. In a further preferred embodiment at least two detent locks are provided op- posite each other whereby a rotation half-way the circumference of the container is indicated by a click sound, for example. However, the detent lock also may be positioned on the piston or the piston driver, or even elsewhere on the dosing means, the requirement only being that the ridge is positioned correspondingly on a part of the device passing the detent lock on activating the dosing means.

The number of detent locks and/or ridges may be adjusted to the purpose of the container, i.e. the medicament to be transferred. In a most preferred embodiment at least ten units of medicaments are indicated during a full rotation of the dosing means, even more preferred twenty doses. This may be carried out by arranging 10 (20) ridges on the piston driver combined with one or two (even three) detent locks.

Another example would be 10 to 20 detent locks and 1-3 ridges.

The container may be arranged in a housing, whereby the dosing means may be coupled to the housing instead of the container itself. However, in a preferred em- bodiment, in order to reduce the amount of parts to be assembled for the device, the container is produced, preferably moulded, in a manner providing the container with coupling means for coupling the dosing means directly to the container.

In order to further secure an accurate dosing mechanism for each dose transferred from the container, it is of importance to prevent backward movement of the piston driver. Accordingly, the dosing means may be provided with locking means.

The locking means may be any means preventing the backward movement of the piston driver. In a preferred embodiment the locking means are included in the de- tent lock described above. Using the detent lock for locking means as well, it is preferred to arrange at least two detents on the container to give a more secure engagement of the dosing means in relation to the piston while the device is not in use.

In another preferred embodiment the locking means are provided by arranging de- tent locks on the inner face of the dosing means corresponding to the threaded cou- pling on the container. Thereby, the coupling is functionally a unidirectionaly threaded coupling.

Alternatively, the detent locks may be provided as locking means only, whereby the indication means may be a scale on the outside of the container and/or dosing means with a indication for each unit of medicament. A combination of a scale and audible indication means are also envisaged by the present invention.

For further securing that the piston does not move within the container unless driven forwards by the piston driver during activation of the dosing means, the piston driver may be adapted to be non-releasably engaged with the piston during transfer of the medicament from the vial to the syringe via the needle.

In one embodiment the piston may be coupled to the piston driver by engagement means. The engagement means may be any suitable means, such as a snap lock, a threaded coupling, a bajonet lock, a luer lock or a suitable combination thereof or any other coupling that secure that the piston is engaged to the piston driver during transfer.

The snap lock may be a rotatable snap lock, whereby rotation of the piston driver is not transmitted as rotation of the piston during dosing. In another embodiment the snap lock may be a unidirectional, rotatable snap lock.

In a further embodiment the piston is integrated with the piston driver. The integra- tion process may be carried out by any suitable process known to the skilled person. The piston may be moulded onto the piston driver by a two-component moulding process, or the piston may be moulded of the same material as the piston driver in one process. In the latter case, the fluid-tight engagement of the piston to the container wall may be secured by an O-ring on the piston.

Integration can also be carried out be applying glue or adhesive on the part of the piston driver abutting the piston, whereby when inserting the piston driver into the container, the piston and the piston driver are connected and remain so for the lifetime of the container. The syringe may be any syringe, such as a hypodermic syringe. The syringe may be non-calibrated in that the calibration and the dosing is conducted by the transfer device. Thereby, the device provides a very economic system because non- calibrated syringes are sold at much lower prices than calibrated syringes.

The needle on the syringe may be fixedly attached to the syringe or may be releas- able. Any needle suitable for injections may be used. Preferably the same needle is used for transferring the medicament and for injecting the medicament to the patient. Accordingly, any needle normally used for injections may be applied to the syringe.

In a preferred embodiment the needle is integrated in the syringe. Thereby the excess space in the needle and coupling between the needle and the syringe is diminished. This will lead to a more precise dosing in that only a small amount of air inherently present in the syringe/needle will interfere with dosage during injection.

The syringe may be mounted to the device by means of a syringe holder, such as a housing having a central bore, wherein the syringe is mounted pointing the needle towards the sealing of the container. The syringe holder may be coupled to the container via any suitable coupling means, such as a snap lock optionally a rotatable or uni-directional rotatable snap, a threaded coupling, a bajonet lock, a luer lock or a suitable combination thereof. The syringe holder may be releasably coupled to the container, whereby the syringe holder can be reused after emptying the container. In another embodiment, the syringe holder may be unitarily moulded with the container to reduce the amount of parts to be assembled after the moulding process.

However, in a further embodiment the syringe is coupled directly to the container by means of a releasable coupling, such as a releasable snap lock optionally a ro- tatable or uni-directional rotatable snap, a threaded coupling, a bajonet lock, a luer lock or a suitable combination thereof. In this case means for directing the needle towards the sealing of the container is preferably provided.

The normal dosage for a patient in need of insulin is from 1 to 70 units, which for most insulin formulations correspond to about 0,01 to 0,7 ml per dosage, with an average of about 10 units. The multi-dose container preferably contains a volume of medicament suitable for dosages for several days, such as from 1 to 10 ml, preferably from 3 to 10 ml. Accordingly, the container comprises at least two dosages of medicament. Therefore, the sealing of the container must be adapted to being re- peatedly pierced by a needle without leaking any medicament in between the transfer of medicaments.

Another object of the present invention is a method for filling a syringe having a needle with medicament from a container, using a device as defined above, com- prising coupling a syringe to the device with the needle piercing the sealing of the container, activating the dosing means to drive the piston towards the sealing, transferring medicament from the container to the syringe via the needle, and removing the syringe containing medicament from the device after the transfer has been finalised. The syringe then contains the correct amount of medicament corre- sponding to the amount metered by the dosing means, and the syringe is ready for injecting the medicament to the patient in need thereof.

When the container is empty it may be replaced with a container filled with medicament, reusing the dosing means and the syringe holder, which may be mounted on the filled container. In another embodiment the container is discarded together with the dosing means and/or the syringe holder.

Yet another aspect of the invention is a method for producing a container wall for a multi-dose medicament container in a transfer device for transferring variable doses of medicament as defined above, comprising selecting a machine-processable material, selecting a mould having a size substantially corresponding to the container wall, arranging an amount of the machine-processable material corresponding to the container wall in the mould, moulding the container wall, and obtaining the container wall.

As described above the machine-processable material is preferably a mouldable material, such as a plastic material. The mouldable material may be moulded by any suitable moulding technique known to the person skilled in the art, such as blow moulding, injection moulding, extrusion moulding and compression moulding, whereby it is possible to mould the container exhibiting substantially no intra- or in- ter-container variations. It is preferred that the container wall is produced by injection moulding.

More preferred the container wall is moulded in a mould comprising a core the outer dimensions of which corresponds to the predetermined inner dimensions of the container. Thereby any day-to-day variations in the process is avoided with respect to the cross-section dimensions of the container.

Drawings

Fig. 1 is a schematic view of the device according to the invention in a transfer situation comprising a syringe with a needle piercing the sealing.

Fig. 2 is showing the device of Fig. 1 in greater detail.

Fig. 3 shows another embodiment of the device.

Fig. 4 shows the details of the dosing means of the device according to Fig. 3.

Fig. 5 shows the container and a piston with O-ring.

Description of the invention

In the following the invention is described in greater detail referring to the figures.

Fig. 1 shows the device 1 with the container 2 comprising one end with coupling means 3 for the syringe holder 11, said end being sealed with a sealing 12. The interior lumen 4 of the container is containing the medicament. Fig. 1 further shows the dosing means 7 mounted to the container 2 via a threaded coupling. Further- more, container 2 comprises piston 10 abutting piston driver 8, the coupling between the piston and the piston driver is denoted 17. The piston is in slidable fluid-tight engagement with the container wall 19. The piston may be produced from any suitable material, such a rubber or a flexible plastic material. In the syringe holder 11 the syringe 14 is mounted with the needle 15 piercing the sealing 12. In this position the device 1 is ready for dosing the correct amount of medicament from the container 2 to the syringe 14, by rotating the dosing means 7 with respect to the container.

Fig. 2 shows the various parts of the device 1 in greater detail. A ring 5 having two detent locks 6^' and 6^" is adapted to be mounted to the container 2 to provide the container with locking means. The ring 5 is located in a recess 16 moulded in the end of the container opposite the sealing 12. The piston 10 is inserted into the end of the container 2 opposite the sealing to close the container 2 after filling the medicament into the container 2.

After insertion of the piston 10 the dosing means 7 may be coupled to the container 2, and the device 1 is ready for use.

The syringe holder 11 comprises threads 13 for engagement with the coupling means 3.

Fig. 3 shows a device 1 as in Fig. 1, however in Fig. 3 the piston driver 8 is unitarily moulded with the dosing means 7. Furthermore, the piston driver 8 is snapped on the piston 10. The fluid-tight engagement is secured by the O-ring 18 surrounding the piston 10. The O-ring may be made of any flexible material, such as rubber or plastic. By the use of an O-ring the requirements to the piston material is reduced, the piston 10 may be produced of any suitable material, even a non-flexible material, such as the plastic material used for the piston driver 8.

Fig. 4 shows interior details of a dosing means 7 for the device 1 of Fig. 3 comprising the piston driver 8. The piston driver 8 is provided with 20 ridges 9 to engage the detent lock 6^', 6^" on the container 2, whereby an audible click is made for each unit transferred corresponding to each partly rotation.

Fig. 5 shows a piston 10 with a recess for receiving the O-ring 18.

Claims

Claims:

1. A transfer device for transferring variable doses of medicament from a multi- dose medicament container to a syringe with a needle, comprising

means for mounting the syringe to the device with the needle piercing the sealing,

the device further comprising dosing means including a piston driver, said dosing means being adapted for forwards calibrated movement for transferring me- dicament from the container to the syringe via the needle,

2. The device according to claim 1 , wherein the volume being displaced is substantially identical to a predetermined volume standard.

3. The device according to claim 1 or 2, wherein the container wall is made from a machine-processable material.

4. The device according to claim 1 , 2 or 3, wherein the container wall is made of plastic material.

5. The device according to claim 4, wherein the container is produced by moulding.

6. The device according to any of the preceding claims, wherein the inner cross- section area of the container is at least 75 mm², preferably at least 90 mm² , more preferably at least 130 mm² .

7. The device according to any of the preceding claims, wherein the piston driver is unitarily moulded with the dosing means.

8. The device according to any of the preceding claims, wherein the dosing means is coupled through a threaded coupling to the container, so that rotating the dosing means in a rotary direction relative to the container drives the piston in the container towards the sealing end of the container.

9. The device according to any of the preceding claims, wherein the device com- prises means for precisely indicating the volume of medicament which as been transferred from the container to the syringe.

10. The device according to claim 9, wherein the indicating means includes at least one detent lock at the container and at least one ridge on the piston driver.

11. The device according to any of the preceding claims, wherein the dosing means is provided with locking means for preventing backward movement of the piston driver.

12. The device according to claim 11 , wherein the locking means is included in the detent lock indicating the medicament transferred.

13. The device according to any of the preceding claims, wherein the piston driver is adapted to be non-releasably engaged with the piston during transfer of the me- dicament from the container to the syringe via the needle.

14. The device according to any of the preceding claims, wherein the piston driver is coupled to the piston by engagement means.

15. The device according to claim 14, wherein the engagement means is a snap lock, such as a rotatable snap lock.

16. The device according to any of claims 1 to 13, wherein the piston is integrated with the plunger.

17. The device according to claim 16, wherein the piston is moulded with the plunger.

18. The device according to any of claims 1 to 13, wherein the piston comprises an O-ring.

19. The device according to any of the preceding claims, wherein the multi-dose container comprises at least two doses of medicament.

20. The device according to any of the preceding claims, wherein the sealing is adapted to being repeatedly pierced by a needle.

21. A method for producing a container wall for a multi-dose medicament container in a transfer device for transferring variable doses of medicament as defined in any of claims 1-20, comprising

selecting a machine-processable material,

selecting a mould having a size substantially corresponding to the container wall,

arranging an amount of the machine-processable material corresponding to the container wall in the mould,

moulding the container wall, and

obtaining the container wall.

22. The method according to claim 21 , wherein the machine-processable material is a plastic material.

23. The method according to claim 20 or 21 , wherein the container wall is produced by injection moulding.

24. The method according to any of the claims 21-23, wherein the mould comprises a core the outer dimensions of which corresponds to the predetermined inner dimensions of the container.

25. A method for filling a syringe having a needle with medicament from a container, using a device as defined in any of the preceding claims, comprising

coupling a syringe to the device with the needle piercing the sealing of the container,

activating the dosing means to drive the piston towards the sealing,

transferring medicament from the container to the syringe via the needle, and

removing the syringe containing medicament from the device.