HK1028872A - Improvements related to medical containers - Google Patents

Description

Improvements in medical containers

The present invention relates to a port system suitable for use as an opening for a flexible medical container that allows multiple accesses to the container to establish fluid communication using a piercing device. The novel port system improves safety against contamination, is easy to use and can be prepared in a simple manner.

Attempts to develop a polymer container for parenteral administration instead of a glass bottle are described in international patent application WO95/08317 and in the not yet published swedish patent application SE 9601348-7. In order for regulatory agencies approved for medical systems to accept, such polymeric containers, after filling and final sealing, must be able to withstand autoclaving (i.e., autoclaving) sterilization with a durable barrier capability to the atmosphere and with the ability to safely remove potentially hazardous agents. Moreover, the container must maintain a suitable aesthetic value and be easily recyclable after use from an environmental point of view.

A particular problem in developing such containers is to provide a suitable opening or port therein for collecting or dispensing the liquid in which it is stored and for replenishing such supplemental agents which may degrade during storage. The opening must allow repeated access by means for establishing fluid communication with containers such as syringes, cannulas and spikes for instillation. Moreover, the opening must be able to withstand several types of sterilization and to provide a contamination-free inlet of said means for establishing liquid communication, so that the liquid in the container is not contaminated by microbial growth. Conventional bottle-like or polymer-like containers include a pierceable rubber stopper sealingly fitted over the upper portion of a neck-shaped opening having a flange to which a removable protective metal or polymer foil is sealed. In a polymeric bag for instillation, the rubber decap protects a film that can be inserted into the injection device through a spike. A drawback of these arrangements is that the pierceable upper (outer) surface or membrane of the stopper may be contaminated before it is sealed with a foil or cap, although the final sealed and filled container is autoclaved, but the sterilizing steam never properly reaches this portion. To overcome this problem and to provide a safer port for flexible polymer containers, a device for temporarily introducing a sterilizing steam into said portion is described in swedish patent application 9601540-9. The conventional form of opening or port in the polymeric container also suffers from the disadvantage that the rubber portion cannot be recycled with the rest of the plastic container, but must be collected separately.

In order to improve upon existing closure devices for containers, a new two-color molding process is disclosed in swedish patent application 9700597-9, which produces stoppers of elastomeric material with enhanced resealing characteristics.

The container openings or ports disclosed in said documents undergo complex processing steps in which an elastomeric stopper is moulded or inserted into a carrier which must then be placed into the port's interface sealed by a cap or foil, whereupon the port can be secured to a container or elastomeric material to form a container. The reduction in processing steps can both reduce processing costs and provide more aseptic processing conditions.

EP0097054(Hantakki Oy) discloses a flexible bag for medical liquids fitted with an injection port, having a closure comprising a shielded flexible pierceable gasket which reseals after piercing and protects the stored liquid. A drawback of this type of closure is that it requires complex processing and it is difficult to maintain sterility in all parts of the closure.

US4303067 (US hospital supply) describes an additional port for a medical bag through which a medicament can be supplied with an injection device. The port has a pierceable and resealable stopper formed of an elastomer. But not to the resealing or sterilizing capability of the closure.

US4975308 and US5247015 disclose moulded stoppers for blood vessels, consisting of a halobutyl rubber dispersed in a mixture of a polyolefin and a thermoplastic elastomer. Nor do they disclose their resealability or ability to withstand heat sterilization after needle insertion.

There are many other references in the literature to opening of various medicament containers, all made of glass or polymeric materials, which are suitable for hermetically storing medical fluids. For parenteral liquids (i.e. intravenous injection), medical professionals need to keep the opening isolated from the outside during steam sterilization and subsequent long-term storage. It is also desirable that such a closure should be capable of spontaneous and immediate resealing after withdrawal of the inserted needle. They must also be capable of resealing after multiple entries of an inserted needle, catheter or similar insertion device to collect liquid from a container or add components to be mixed with the contents of the container. Improper resealing of the closure cap will compromise the integrity of the stored liquid, possibly after insertion, by providing a pathway for microbial growth into the container. It is also desirable that the container closure be pierced to prevent leakage of the container during fluid communication, such as infusion of a fluid to a patient via a catheter. Moreover, the opening must be compatible with the stored liquid and not allow transfer of potentially hazardous reagents from any part thereof. The opening must also withstand conventional sterilization processes, including autoclaving at 121 ℃ or sterilization by radiation, without any loss of its sealing properties. It is also desirable for more and more medical professionals that each authorized container must be recyclable, and thus it is desirable that empty containers can be discarded without the need for extensive disassembly and sorting for single cycle processing.

It is an object of the present invention to provide a container port system that is manufactured by techniques that are sufficiently sterile so that a separate sterilization process is not required prior to attachment to the container or the elastomeric material from which the container is to be formed.

It is also an object of the present invention to limit the number of processing steps required to process the ports.

It is another object of the present invention to provide a port having resealability after piercing with a device for establishing fluid communication with a container.

It is another object of the present invention to eliminate the final sealing step of sealing the front end of the port with a foil or cap.

It is a further object of the present invention to provide a less hazardous port for moving potentially hazardous reagents from the port to the stored reservoir by avoiding or minimizing the use of polymeric materials that are hazardous for moving such reagents, and the stored reservoir.

It is another object of the present invention to provide a port that can discard the remaining containers for reuse without the need for separate separation and collection.

These objects are achieved by the invention disclosed in the following description and the appended claims.

A port system according to the present invention should establish fluid communication between a container storing a medical fluid and a device for adding or withdrawing fluid from said container. Such devices are typically syringes, catheters, spikes that are connected to infusion sets or devices with similar functionality. The port system includes at least one port having a sealed front end and a rear end opening into the interior of the container and a floor connectable to the container. Furthermore, the port has a pierceable membrane acting as a barrier for the stored liquid, which can be pierced by means for establishing fluid communication with the container. At its front end, the port comprises a cap extending axially into a substantially upper sleeve-shaped part, which is fitted with said pierceable membrane acting as a septum for the reservoir. The membrane is preferably placed at a given axial distance from the front end of the sleeve-shaped part, which is shorter than the axial distance from the rear open end of said sleeve-shaped part. The cap seal can pierce the upper surface of the membrane and prevent contamination during handling and storage of the port system and during loading thereof on the container or the flexible membrane of the container to be formed. Moreover, the cap seals the protected space above the membrane, which is inaccessible to microbial contamination. In order to open the port and provide the pierceable membrane to the means for establishing fluid communication, the port is provided with exposure means through which the user can easily expose the membrane when access to the container is required. Preferably the exposing means is adapted to partially or fully remove the cap and may be constituted by an area extending fully or partially around the port and having a predetermined weakness, so that a user can easily remove part of the port along said area by a defined twisting movement. As described in more detail below, such regions may preferably consist of a groove extending along the outer periphery and having a reduced material thickness, which groove may be formed when molding the port system. The skilled person can naturally consider the exposure means in the form of various other frangible structures in order to remove the appropriate portion of the port.

An important aspect of the present invention is that the port system is molded in a portion of the polyolefin material. The cap of the front end seal will extend directly into the sleeve-shaped part which extends directly into the bottom plate. By making the port system in a sealed mold at a temperature well above the sterilization temperature, it has been ascertained that the upper surface of the membrane and the headspace sealed by the front end cap are not likely to be contaminated by microorganisms. This is a great advantage when this part of the port system is finally fixed to the container being filled, since it is not reached by the sterilizing steam during the autoclaving to which it is subjected.

According to a particular embodiment of the invention, the pierceable sealing membrane is connected to a plug of elastic material, which can be considered as an extension of said membrane that is particularly adapted to the type of port accessed by a conventional syringe needle. The elastomeric plug fully occupies a predetermined space between the membrane and the forward end of the sleeve-shaped portion of the port. As disclosed below, the stopper is preferably introduced into the space by injection moulding with hot liquefied elastomer through a suitably sized hole in the sleeve-shaped part associated with a conventional injection nozzle, thus forming a pierceable elastomeric stopper through which the needle can be inserted repeatedly without any liquid leakage. It is important that the plug completely fills the predetermined space and properly closes the hole so that a passage into which microorganisms occasionally enter is not formed after fabrication.

According to another embodiment of the invention, the port is provided with a membrane adapted to be inserted with the spike of the injection device. In this case, the membrane is designed to be easily inserted, for example by being equipped with orientation means to correctly insert the pins, for example grooves that meet at the center of the central point of insertion. Moreover, the membrane has a certain suitable thickness, even to act as a membrane seal during the entire infusion process of the spike insertion, which means that the port will be held mouth down during gravity automatic infusion. Preferably, the front end of the sleeve-shaped part is provided with a socket designed to hold a common nail. In order to easily distinguish the port designated for the spike from the port designated for the syringe when they are all part of the same port system, the spike port may preferably have a substantially longer sleeve-shaped portion and may be provided with an annular flange around it.

In both embodiments described, the cap serves as an effective protective means by sealing the membrane of the stopper that can penetrate the front surface or prevent contamination during storage and use of the port system.

Different combinations of said ports are conceivable and within the scope of protection of a port system designed according to the invention. Although the port systems mentioned below each have only one port, any combination of said ports suitable for syringes or spikes will be conceivable.

The invention also relates to a method of manufacturing a port system for a flexible medical container of polymeric material comprising at least one sealed port and a bottom plate, wherein the port system is made in one piece by an injection moulding process in a closed mould at a temperature above about 180 ℃ to form the port with an at least partially detachable front end cap extending axially from said cap to the front surface of the sealing membrane in a sleeve-shaped part of the bottom plate. In order to enable the cap to be removed by a simple twisting movement by the user, the region or line of predetermined weakness in the material extending around the port is preferably already formed during the moulding step.

As also described in swedish patent application 9700597-9, the mould is of substantially conventional closed design to process hollow articles of polymeric material by injection moulding and allows the introduction of different materials (for example two-shot moulding). Further, the mold is equipped with a means for removing the core from the molding gate and a heat sealing bar for sealing the front end of the molding gate and forming a cap like the front end. Other features of the mould enable it to operate in a closed system and are not described in detail herein as it will be appreciated that the mould apparatus can be designed by a person skilled in the art within the capabilities thereof. Basically, the method of manufacture of the port system of the present invention, as described above, after it has been initially formed in a mold, comprises the steps of:

a) bringing the port system to its curing temperature in the mold;

b) removing the core pin from the mold gate with a core pin ejection system;

c) while still in the closed mold, the port front end is sealed with a heat seal bar to form a seal

The front end cap of (a); and finally;

d) the port system is removed from the mold.

The molded port system is not allowed to reach temperatures below about 60-80 c, preferably not below about 70 c, from its curing temperature, which is an important aspect of the process of the present invention.

In order to produce a port with an elastomer plug connected to the upper surface of the protective membrane by the method of the invention, the liquefied elastomer can be introduced into the closed mould and into said predetermined space above said membrane, preferably by high-pressure injection. The port system is then brought to its curing temperature, as described above, but not cooled below about 60-80 c, preferably not below about 70 c, prior to introducing the liquefied elastomer into the opening in the closed mold, preferably by high pressure injection, to form a resealable stopper of elastomer, and the port system is then removed from the mold. When forming the stopper, it is achieved by injecting the liquefied elastomer through a hole above the front surface of the membrane in the sleeve-shaped portion of the port to completely fill the predetermined area of said sleeve-shaped portion. The elastomer injection port may be performed before or after the front end thereof is sealed with a heated bar (i.e. before or after step c) above). However, even though both are conceivable to the person skilled in the art, it is preferred to inject the elastomer before sealing the cap in the mould.

Preferably, the elastomer is manufactured by high-pressure injection molding according to the method disclosed in swedish patent application 9700597-9, so that the film is formed with the necessary resealability at least according to standard specification DIN 58363. It is preferred to maintain the port system at an elevated sterilization temperature during removal of the port system from the mold until said elastomer introduced by heating completely fills the predetermined space above the membrane in the sleeve-shaped portion of the port. It is desirable to maintain sterilization temperatures (e.g., above 121 ℃) during processing of the port system to reduce the risk of microbial contamination of any portion thereof that would otherwise be contacted by the device establishing fluid communication with the container during normal operation. This can be achieved by keeping the temperature of the liquefied elastomer introduced in the high pressure moulding above 180 ℃ and moulding the remaining ports by the material which has just reached its curing temperature, but which has liquefied above 180 ℃.

The port system thus formed can now be connected to a container or flexible material to form a container by welding. The container is then filled by the technique described in swedish patent application 9601348-7, finally sealed and sterilized, preferably with high pressure steam (autoclaving). The final sterilisation will effectively sterilise the remaining surface of the sleeve-shaped part of the port between the membrane and the rear opening in contact with the liquid in the container.

The process of the invention enables to effectively seal the surface of the port system which normally presents a risk of contamination, thus providing a port system for flexible containers with a higher safety, while reducing the number of process steps, in particular compared to processes where the sealing foil finally has to be fixed before a separate sterilization, usually by gamma-irradiation.

The port system is preferably comprised of a medical grade polyolefin, which may be compounded with a portion of a thermoplastic elastomer. The material of the present port system must be capable of being fixed to the container, for example by a simple welding process, which means that it must be compatible with the material of the container. Preferably, the polyolefin is based on, i.e. mainly consists of, polypropylene or polyethylene, optionally copolymerized with ethylene or propylene. Pure polypropylene or polyethylene of different medical grades are also conceivable.

The elastomeric material of the processing stopper preferably comprises a polyolefin compatible with the carrier and the thermoplastic elastomer. Suitable commercially available materials are Dynaflex , available from GLS corporation, Santoprene , which contains polypropylene and SEBS (styrene-ethylene-butadiene-styrene), polypropylene and EPDM-rubber, Evoprene , and Craiwton , which are available from Evode, as well as different materials containing Polyisobutylene (PIB). It is also important that the stopper described in the present invention has a resealing ability which at least meets the requirements of DIN58363 part 15 of the standard specification, which should be resealable after piercing with a 0.6mm needle without any spillage of liquid.

The embodiments of the present invention will be described in detail below, but this is not to be construed as limiting the invention disclosed in the claims.

Fig. 1A is a side view of a port system according to the present invention having a specific port as an additive and a specific port for connection to a spike of an injection device.

FIG. 1B is a side view of a port system according to the present invention.

Fig. 1C is a top view of a port system according to the present invention.

FIG. 2 is a cross-sectional side view of one embodiment of a port according to the present invention.

FIG. 3A is a cross-sectional side view of another embodiment of a port according to the present invention.

Fig. 3B is a top view of the pierceable membrane of the port shown in fig. 3A.

FIG. 1A shows one embodiment of a port system 10 according to the present invention that includes two different ports 20, 30 and a base plate 40 that is connected to a flexible container. Port 20 is an additional port through which additional reagents are added to the liquid stored in the container. The port 30 is for connection to a spike of an injection device. The port typically comprises a cap 21, 31 on its front end extending into a sleeve-shaped part 22, 32, which is provided with a pierceable membrane 23, 33 near the front end of said sleeve-shaped part. Furthermore, the ports form a weakness in the material in the form of a groove 24, 34 along which a user can remove the cap 21, 31 by a simple twisting motion to expose a surface that can be pierced with a means of establishing fluid communication with the container. In the embodiment shown in fig. 1A, the two ports 20, 30 are readily distinguishable by characteristic different sizes, and the spike port 30 is also provided with a distinct flange 35 to allow the user of the container to simply identify the ports.

As best shown in fig. 2, the sleeve-shaped portion 22 of the port 20 for adding the supplemental agent to the stored liquid is provided with a pierceable membrane 23 which acts as a barrier between the stored liquid and a pierceable stopper 25 made of an elastomer to avoid migration of potentially hazardous agent from the elastomer into the liquid. The plug 25 extends from the membrane to the front end of the sleeve-shaped part and has a front surface protected from contamination by a cap. To avoid contamination of this area of the port, a plug is introduced into the space between the membrane and the front end of the sleeve-shaped part by injection moulding through a hole 26 in said sleeve-shaped part, while keeping the port system at a high sterilisation temperature before or during moulding of the elastomer. For the same reason it is also important that the space is completely and carefully filled with elastomer, so that the hole is completely sealed and no channels are formed in the plug. The front surface of the resilient stopper is protected from contamination by the cap during storage of the container.

Fig. 3A shows a side view of the front part of the sleeve-shaped part 32 of the port 30 for connection with a spike device of a common injection device. The membrane 33 is much thicker than in the additional port and therefore has sealing capability despite the relatively rough piercing mechanism of the stapling device piercing the membrane. The front part of the sleeve-shaped part is provided with a radially outwardly directed socket 36 for facilitating engagement with the stapling device. As shown in fig. 3B, the membrane 33 may be provided with grooves to facilitate orientation of the staples to a central position suitable for insertion, which also enables partial resealing after removal of the staples.

Claims (20)

1. A port system for bringing into fluid communication a container for storing a medical fluid and an insertion device for adding or withdrawing fluid to or from said container, comprising at least one port connected to a base plate which is fixable to a wall of the container, said port being provided with a sealing membrane having:

(i) a sealing front surface protected from contamination during processing thereof until exposed to the insertion device;

(ii) a rear surface for use as a barrier to liquid stored in the container;

and in that the port is further provided with a removable front end cap sealing the front face of the membrane.

2. A port system according to claim 1, characterized in that in the moulded part made of polyolefin material, the port comprises a front sealing cap extending directly into a generally sleeve-shaped part, which sleeve-shaped part extends further into the bottom plate.

3. Port system according to claim 2, wherein the sleeve-shaped portion extends axially between an open front end and an open rear end and is provided with a sealing membrane extending radially at a predetermined distance from said front end.

4. A port system according to claim 1 wherein the port is provided with a weakness in the material thereof such that the cap is at least partially removed to expose the pierceable front surface of the membrane.

5. Port system according to any of claims 1 to 4, wherein the membrane is connected to a plug of an elastic material.

6. Port system according to claim 4, wherein the port is provided with a hole for introducing an elastic material.

7. The port system of claim 6, wherein the aperture is located between the forward end of the sleeve portion and the sealing membrane.

8. The port system of claim 6, wherein the plug is formed by high pressure injection molding.

9. The port system of claim 5 wherein the stopper is resealable after multiple accesses to the container with the piercing device.

10. Port system according to claim 9, characterized in that the plug has an elastic capacity at least in compliance with the requirements of standard specification DIN58363 (part 15).

11. A port system according to any of claims 1-10, which consists of a polyolefin polymer, to the extent that it can be recycled in a single process.

12. A port system according to claim 11, characterized in that the polyolefin polymer comprises polypropylene or copolymers thereof.

13. A port system having two ports connected to a base plate, wherein a first port is adapted for syringe insertion and is provided with an elastomeric stopper according to claims 5-12, and a second port according to claims 1-4 having a sleeve-shaped portion longer than said first port and provided with an annular flange extending around the periphery of the sleeve-shaped portion thereof.

14. A port system according to claim 13, characterized in that the front surface of the membrane of its second port is provided with centrally intersecting grooves.

15. A port system according to claim 13, characterized in that the front end of the sleeve-shaped part of the second part is provided with a radially outward socket.

16. A method of manufacturing a port system for a medical flexible container of polymeric material, the system comprising at least one sealed port and a bottom plate, wherein the port system is made in one piece by injection moulding at a temperature exceeding about 180 ℃ in a closed mould so as to form the port with an at least partially detachable front end cap sealing the front surface of the membrane in a sleeve-shaped part extending axially from said cap towards the bottom plate.

17. The method of claim 16, wherein:

(i) bringing the port system to its curing temperature in the mold;

(ii) sealing the front end of the port while it is still in the closed mold to form a front end cap;

(iii) the port system is removed from the mold.

18. A method according to claim 17, characterised in that the injection of the liquefied elastomer while still in the closed mould is performed through a hole above the front surface of the membrane in the sleeve-shaped part, thus completely filling the predetermined area of said sleeve-shaped part when forming the stopper.

19. The method of claim 16, wherein the molded port system is maintained at a temperature greater than at least 121 ℃.

20. A method according to claim 16, wherein the cap is made removable by moulding a region of predetermined weakness in the material extending around the port.