WO1999026581A1

WO1999026581A1 - Fluid transfer device connecting two medicinal vessels in closed system

Info

Publication number: WO1999026581A1
Application number: PCT/IT1998/000327
Authority: WO
Inventors: Antonello Russo
Original assignee: Eurospital SpA
Current assignee: Eurospital SpA
Priority date: 1997-11-24
Filing date: 1998-11-19
Publication date: 1999-06-03
Anticipated expiration: 2000-05-24
Also published as: IT236231Y1; ITRM970252V0; AU1259499A; ITRM970252U1

Abstract

A fluid transfer device connecting two medicinal vessels for enabling the mixing in closed system of the two products contained therein by means of a syringe, comprising a three-way plug valve assembly (3) with a first port ending in a connector (5) for a syringe, and a second and a third port (8, 7), each one provided into a respective spike (1, 2) having a housing (20, 21) for a container of medicinal product. Within the two spikes (1, 2) two further independent channels (12, 15) are provided for the inlet and the outlet of air, which channels do not pass through the said valve assembly (3) but communicate, each one separately, with the external environment through two hydrophobic filters (13, 14) included in the device.

Description

FLUID TRANSFER DEVICE CONNECTING TWO MEDICINAL VESSELS IN

CLOSED SYSTEM

SPECIFICATION

The present invention concerns a fluid transfer device connecting two medicinal vessels in closed system. More specifically, the invention relates to a device provided with a three-way valve, allowing to transfer two pharmaceutical products from the respective bottles or vials by means of a syringe. The device is used to obtain the mixture of the two products by transfer from one vessel to the other, without removing any one of the three elements (i.e., vessels and syringe) from the assembly until the end of the operation.

As it is known, many medicinal products for intravenous administration are diluted before use in suitably proportioned amounts of injectable or perfu- sionai solutions, in order to be injected or infused to the patient by the intravenous route, i.e. in the phleboclysis form. In some cases these medicaments are placed on the market in the liquid form, e.g. as solutions or as stable suspensions, while in other cases they are in the dry powder form. Active ingredients in the dry powder form must be reconstituted before use by the addition of a measured amount of liquid. The transfer and the dilution or the reconstitu- tion of the said medicinal products before use are conventionally carried out by means of a syringe provided with needle.

When a medicament to be reconstituted is used, a predetermined amount of injectable diluent solution or of perfusional solution is taken by means of a syringe from the relevant container, and is introduced in the bottle or vial of medicament. The latter is normally provided with a pierceable rubber stopper. Once it has been diluted, the drug is taken up from its bottle with the syringe and is administered to the patient intravenously, or it is transferred, wholly or in part, in the container of the perfusional solution, so as to obtain the desired dosage of active ingredient to be infused.

It is evident that the operations referred to above unavoidably involve the production of splashes and aerosols that diffuse through the air from the syringe, for instance when air is expelled from the syringe during the dosing operation, or when the needle is extracted from the bottle of medicament. In the particularly important case where the medicament is an anticancer drug, the medical personnel coming into contact with the drug, or breathing it, during the preparation of the intravenous infusion set is exposed to a non negligible risk. The prolonged and repeated exposure to doses even extremely reduced of such substances may result in long term effects of the same kind as those borne by the patients. For some antineoplastic drugs, such as, e.g., cyclo- phosphamide, a carcinogenic activity has already been ascertained, while other drugs are still under evaluation in this respect.

Another case where the formation of drug-containing aerosols is particularly harmful is the case of antibiotics. In this case the active ingredient released in the environment may cause the development of resistance by the bacterial strains present therein. The foregoing may easily result in the devel- opment of infections difficult to overcome, specially in the hospital environment.

A further problem involved by the conventional operations of transfer and reconstitution of drugs by means of a syringe is the impossibility of maintaining a complete sterility in the manipulation. The micro-organisms present in the environment or on the operator's hands may come into contact with the needle, and from here they may be carried into the solution to be infused or injected to the patient. Since the said solution is injected directly in the patient's bloodstream, the foregoing involves a remarkable risk of infections, specially in view of the weakened conditions of the patient receiving such therapies.

In order to reduce to some extent the occurrence of the first one of the problems cited above, that is the formation of splashes and aerosols, some devices known as "vented spike" are already available on the market. Such devices are spikes provided with a hydrophobic filter that are placed between the syringe (without needle) and the container of medicinal product, serving as a port for the inlet and the outlet of air during the movements of the syringe plunger and, if desired, as a filter for the liquid transferred. The vented spike devices consist of a hollow spike suitable to perforate the stopper of a pharmaceutical container in the same way as a syringe, of an aperture for the passage of air, provided with a hydrophobic filter of a porosity suitable to prevent both the passage of aerosol toward the exterior and the passage of mi- cro-organisms towards the interior, optionally of a filter placed on the liquid path and of a connector for a syringe.

Although they actually reduce the production of aerosols, the vented spike devices do not constitute systems completely isolated from the exterior, as they do not connect both vessels at the same time, and require that the device be removed from the first vessel in order to transfer the liquid to the second vessel. Therefore, the risk of contamination of the medicament still exists, and the risk that the operator comes into contact with the drug is still not totally avoided.

The PCT application publ. No. 96/29113, in the name of Medimop Medical Projects Ltd. et al., discloses a transfer device for medicinal fluids having at least three ports, one of which is connected with a syringe (also in this case, without needle). The device is provided with a plug cock, that may be rotated to establish fluid communication between two of the three ports, in turn. At least one of the three ports is provided with an adaptor for connection with the upper part of a bottle, said adaptor having a hollow spike.

In some of its embodiments, the said transfer device is designed to connect a syringe, previously filled in with diluting solution, a vial of medicament to be reconstituted and, on the third port, directly the patient to be treated. Other embodiments concern the connection of two medicinal contain- ers (through the syringe), in order to obtain a closed system that allows the blending of two different liquid products through the syringe, without removing any one of the three elements up to the completion of the operation. Such device, according to the disclosure of the document, is designed so as to allow an antiseptic administration of the drug, as it prevents any contact of the latter and of the injectable or perfusional solution with the external environment for the whole mixing and dosing operation, up to the administration to the patient. In the embodiments providing the connection of two vessels, the device at issue is endowed with two opposedly placed housings for the head of two vials or bottles, each housing being provided with a hollow spike. Between the said two housings there is provided a valve assembly consisting of a three-way plug cock with the third port connected to a housing for the syringe tip. After connecting the two vessels and the syringe to the device, the cock is positioned so as to put the syringe in communication with the bottle containing the perfusional solution or with the vial containing the injectable solution, and the solution is sucked into the syringe. Then, the cock is rotated so as to con- nect the syringe with the bottle of medicament to be reconstituted, and the liquid is injected from the syringe in the bottle. Once diluted, the medicament is sucked from its bottle and, in the case of preparation of products to be administered by infusion, the cock is rotated so as to connect again the syringe with the bottle of perfusional solution and the diluted medicament is trans- ferred from the syringe to the bottle of solution, to give the product ready for infusion.

The last one of the 29 figures accompanying the above PCT application shows an embodiment which takes into account (at least in part) that this series of operations, carried out in a closed system, requires the presence of some apertures for the passage of air. According to the disclosure, one of the two spikes is provided with two internal channels, one for the liquid and the other for the air passage, the latter terminating in an external hydrophobic filter.

In the development of a transfer device for connecting two containers of pharmaceutical products in closed system according to the last embodiment taught by the PCT application publ. No. WO 96/29113 it has been noticed that the problem of the passage of air from and toward the exterior is not adequately solved by the solution proposed. As a mater of fact, venting must be possible in all the phases of the transfer and mixing operation described above. Each time that some liquid is withdrawn, by means of the syringe, from one of the two vessels a depression is created inside the vessel. Such depression makes the sucking more and more difficult as the operation pro- ceeds, and that should be compensated by the entry of air from the exterior. Each time that some liquid is injected from the syringe into a vessel the inner pressure thereof is raised, and this may result in some liquid escaping from the vessel in the form of an aerosol. In each one of the said phases not only the entry of potentially contaminated air from the exterior must be avoided, but also the escape of any aerosol containing drugs, as this not only represents a loss of active ingredient, but is also harmful for the operators.

It should also be noted that the transfer devices of the kind concerned herein are generally intended for use as disposable devices, and should be easy to use and inexpensive to produce. Accordingly, the structure of the transfer device should be as simple as possible, its size should be small and the number and complexity of its components should be limited.

Therefore, the object of the present invention is to provide an improved device of the kind previously disclosed, suitable for mixing, reconsti- tuting and transferring drugs in closed system, wherein the pressures within the two vessels connected is maintained to values substantially not different from the external pressure. This is obtained by allowing the passage of air from and into both vessels, and preventing at the same time the entry of micro-organisms and the escape of droplets of liquid. To such purpose, the solution proposed consists substantially in endowing the two containers with two autonomous channels for the passage of air, each provided as an additional channel in the corresponding spike, and connected to an autonomous external hydrophobic filter. It is to be remarked that between the two channels for the passage of air there must not be any communication, as this would create a short-cut for the liquid between the two containers. Therefore, two external hydrophobic filters are to be provided, and even in the event that the two filters are joined together into one only element, both the said filters and the connected air channels must be kept separate internally. Therefore, the present invention specifically provides a fluid transfer device connecting two medicinal vessels for enabling the mixing in closed system of the two products contained therein, comprising a three-way plug valve assembly with a first port, provided along the rotation axis of said valve, ending in a connector for a syringe, and a second and a third port, opposite to each other and both orthogonal to said first port, each one provided into a respective spike having a housing for a container of medicinal product, the said valve being so shaped as to alternatively connect said first port with said second port or with said third port, characterised in that within the said two spikes two further independent channels are provided for the inlet and the outlet of air, which channels do not pass through the said valve assembly but communicate, each one separately, with the external environment through two hydrophobic filters included in the device.

Further structural and functional features of the device according to the invention are specified in the dependent claims. The said features, as well as the advantages of the invention, will be clearer with reference to a specific embodiment thereof, which is shown by way of example in the accompanying drawings, wherein:

Figure 1 is a perspective view of a fluid transfer device according to the invention;

Figure 2 is a vertical cross-sectional view of the device of Figure 1 , with some elements not sectioned; Figure 3 is a vertical cross-sectional view of the only structural frame element of the device of Figure 1 ;

Figure 4 is a side elevation view of the same structural element of Figure 3, with a portion thereof represented in vertical section;

Figure 5 is a front elevation view of the adaptor element for the filters of the device of Figure 1 , rotated by 90° about the horizontal axis with respect to Figure 1 ;

Figure 6 is a vertical cross-sectional view of the element of Figure 5; and

Figures 7 and 8 are respectively two side elevation views from the left hand-side and from the right hand-side of the element of Figure 5.

As it is shown in Figures 1 and 2, the device according to the invention comprises a spike (1 ) capable of piercing the rubber stopper of a bottle or vial of medicament, e.g. a powder medicament to be reconstituted or a medicament in a concentrated liquid form, a second spike (2) capable of piercing the rubber stopper of a bottle containing a perfusional solution and a three- way valve assembly (3). The plug (4) of the valve assembly (3) is provided with a coaxial port with a luer lock female connector (5) for a needle-less syringe.

In Figures 1 and 2 the valve (3) is represented in the position that puts in communication, through the hole (6), the syringe connected in (5) with a vessel of injectable solution of any size or a vessel of perfusional or intrave- nous solution, connected to the spike (2). To that end, the spike (2) is provided with a channel (7) for the liquid flow. By rotating the valve (3) by 180°, the hole (6) becomes aligned with the channel (8) for the liquid flow provided in the spike (1 ) connected to the medicament vial, thus putting the latter in communication with the syringe. In Figure 2 only, the spikes (1 ) and (2) are represented covered by the corresponding protection caps (9) and (10) (not sectioned), with which they are marketed. Also, the connector (5) for the syringe is (schematically) shown closed by a screw cap (11 ). Preferably, the device is entirely made of plastic material; by way of example, the main structural body of the device can be made of polycarbonate and the valve plug (4) can be made of polypropylene.

Within the spike (1 ) there is provided a second channel (12) for the passage of air, so as to allow venting of the vial connected thereto during the transfer and mixing operations. The channel (12) is completely separate from the three-way valve assembly (3), and communicates with a hydrophobic filter (13). In the embodiment shown in the figure, the filter (13) has a diameter of 13 mm. The internal membrane of the hydrophobic filter (13) has a porosity of 0.22 μm, suitable to prevent both the escape of aerosol toward the exterior and the entrance of any micro-organisms, which might penetrate in the system with the air sucked in from the atmosphere, thus polluting the product. A hydrophobic filter (14) of similar structure and porosity, but of greater diameter (in the embodiment depicted, 25 mm), is provided at the end of the channel (15) for the passage of air provided in the spike (2). Figure 2 represents the filter (14) partially sectioned, showing the porous membrane (16). Both filters (13, 14) can be made, for instance, of PVC, with a commercially available porous membrane made of a modified acrylic copolymer cast on a non-woven nylon support, post-treated for hydrophobicity through UV B beam polymerisation.

The choice of different diameters for the two air filters (13, 14) is mainly made in order to optimise the air flow rate allowed through each filter as a function of the size of the bottle connected to the corresponding spike.

It is important to notice that the two systems for the inlet and the outlet of air in and from the two containers, each comprising a channel (12, 15), the corresponding spike (1 , 2) and a hydrophobic filter (13, 14), are completely separate from each other. This is aimed at preventing the liquid contained in one of the two vessels from being transferred directly in the other vessel without passing through the valve assembly (3) and the syringe, thus overcoming the dosage control by the operator.

The connection of each of the two air channels (12, 15) with the corresponding hydrophobic filter (13, 14) is obtained, in the embodiment shown in the figures, by means of a suitably designed adaptor element (17). The adaptor element (17) is illustrated alone in Figures 5-8, rotated by 90° with respect to the position shown in Figure 2. The passage of air between each one of the two chambers (18) and (19) (see Figure 2) - each connected to one of the two spikes (1 ) and (2) - and the corresponding filter (13) and (14) is obtained by means of the system of cylindrical eccentric bodies shown in Figures 5-8, with no contact between the two air paths. It is also possible to join the two hydrophobic filters into one only compact structure, as long as the two filters are maintained functionally separate and independent from each other.

As it is shown in Figures 1 and 2, and in greater detail in Figures 3 and 4, the spike (1 ) for the bottle or vial of medicament is provided with a housing (20) for the latter, that consists of a circular plate on which the neck of the bottle abuts when the latter is inserted on the spike (1 ). The spike (2) for the bottle of physiological solution is in turn provided with a housing (21 ) ca- pable of partially enclosing and fastening the neck of the said bottle. The housing (21 ) has a substantially cylindrical shape, lacking the lower base and two or more vertical bands of the side walls, the upper base thereof being centered at the base of the spike (2). At its lower edge, the housing (21 ) in- eludes an edge (22) projecting toward the interior of the cylindrical side wall and bevelled, of such size as to snap fasten the neck of a container of medicinal product (dimensioned, e.g., for standard bottles with 29 mm neck diameter, or with 33 mm neck diameter, or for bottles of other sizes in accordance with the specifications of the manufacturers). The shape of the housing (21 ) and of the edge (22) thereof is designed so as to firmly connect the bottle to the transfer device of the invention, and to guide the spike (2) to perforate the bottle stopper exactly in the centre thereof. The requirement of a perfectly central perforation of the rubber stopper is due to the fact that, after the mixing operation carried out by means of the claimed device, the bottle containing the dosed medicament is normally connected to the drip chamber of an infusion set for intravenous administration to the patient, and thus the stopper will have to be pierced a second time. It is evident that, in order to avoid any leakage of the liquid during the infusion, both perforations must be made exactly in the centre of the stopper. In alternative designs, the housing (20) for the bottle or vial of medicament may have a shape similar to that of the housing (21) for the bottle of physiological solution, with two or more vertical bands of a cylindrical shell encompassing the neck of the vial. It is also possible to provide a housing (20) with one only vertical band, i.e. with a single arm extending vertically, at right angles with the base of the spike (1 ), provided that a suitable fastening system for the peripheral edge of the vial neck is present on the said band or arm.

Alternative configurations of the housing (21 ) provided on the spike (2) for the bottle of physiological solution include those specifically designed for use with plastic bottles. Many commercially available plastic bottles have a cap with an eccentrically placed pierceable region, and thus the spike (2) is not inserted at a central position with respect to the bottle neck, as it happens with the ordinary glass bottles with rubber stopper. In this case, a suitable design for the housing (21 ) includes, instead of the cylindrical shell, a single vertical arm, extending at right angles with the base of the spike (2) at a distance from the axis of the spike (2) suitable to fit the neck of the plastic bottle on the side of the latter which is far from the point of insertion of the spike (2). The terminal section of the arm is bent towards the vertical axis of the device, so as to form a hook that fastens the bottle by engaging the peripheral edge of the bottle neck. The spike (2) is inserted with the fastening arm facing the side of the cap closer to the insertion point, and once the spike (2) is inserted the device is rotated with respect to the bottle, so as to have the arm engage the neck of the bottle at a point where the vertical wall of the cap is farther from the point of insertion of the spike (2) .

The procedure of use of the device according to the invention is as follows. First, both containers are inserted on the corresponding spikes (1 ) and (2) and the syringe is introduced in the luer lock connector (5), with the valve (3) opening (and, correspondingly, the valve knob) turned towards the container of injectable or perfusional solution and the latter in the upward position. Then, the desired amount of liquid is sucked by means of the syringe from the bottie of solution; further, the valve (3) is rotated towards the vial of medicament (which is placed in the lower position) and the solution is injected in the vial. Subsequently, the whole assembly is turned upside-down and the diluted drug is drawn in the syringe. At this stage the syringe can be disconnected to provide it with a needle and inject the diluted/reconstituted drug to the patient. In the alternative, after rotating the valve (3) knob again towards the bottle of solution, the diluted/reconstituted drug is introduced in the bottle of solution for the administration by infusion. The above overturning operations have the object of making the liquid always flow downwards in every transfer step.

Since the diluted medicament is sucked in the syringe with the vial placed upside-down, the corresponding spike (1 ) is provided, on the inlet hole of the channel (8) for the liquid passage, with a particularly sharp cut, as it is more clearly shown in Figure 2. This arrangement makes it possible to suck completely the liquid contained in the vial without any risk of disconnecting the spike (1 ) from the device, as it may happen when the vial is lifted too much from its seat in order to drive the remaining liquid into the channel (8).

The present invention has been disclosed with particular reference to some specific embodiments thereof, but it should be understood that modifications and changes may be made by the persons skilled in the art without departing from the scope of the invention as defined in the appended claims.

Claims

1. A fluid transfer device connecting two medicinal vessels for enabling the mixing in closed system of the two products contained therein, com- prising a three-way plug valve assembly (3) with a first port, provided along the rotation axis of said valve (3), ending in a connector (5) for a syringe, and a second and a third port (8, 7), opposite to each other and both orthogonal to said first port, each one provided into a respective spike (1 , 2) having a housing (20, 21 ) for a container of medicinal product, the said valve (3) being so shaped as to alternatively connect said first port with said second port (8) or with said third port (7), characterised in that within the said two spikes (1 , 2) two further independent channels (12, 15) are provided for the inlet and the outlet of air, which channels do not pass through the said valve assembly (3) but communicate, each one separately, with the external environment through two hydrophobic filters (13, 14) included in the device.

2. Device according to claim 1 , wherein said housing (20) for the container of medicinal product to be connected through the said second port (8) is a circular plate centered at the base of the corresponding spike (1 ) and orthogonal thereto.

3. Device according to claims 1 or 2, wherein said housing (21 ) for the container of medicinal product to be connected through the said third port (7) has the shape of a cylinder lacking the lower base and two or more axial bands of the lateral wall, the upper base of which is centered at the base of the corresponding spike (2) and is orthogonal thereto, the said cylinder being of a size suitable to fit the neck of a medicinal container.

4. Device according to claim 3, wherein the remaining axial bands of the said lateral wall terminate at the bottom in a thickened edge (22), projecting towards the interior of said lateral wall and suitable to snap fasten the neck of said medicinal container.

5. Device according to claims 1 or 2 for use with plastic bottles of medicinal products with eccentric pierceable zone on the cap, wherein said housing (21 ) for the container of medicinal product to be connected through the said third port (7) includes a vertical arm extending at right angles with the base of the spike (2) at a distance from the axis of the spike (2) suitable to fit the neck of said plastic bottle on the side of the latter which is farther from the point of insertion of the spike (2), the terminal section of said arm being bent towards the vertical axis of the device, so as to engage the peripheral edge of the bottle neck.

6. Device according to any one of claims 1-5, wherein each one of the said two channels (12, 15) for the passage of air communicates with the external environment through a structurally distinct hydrophobic filter (13, 14).

7. Device according to any one of claims 1-5, wherein said two channels (12, 15) for the passage of air communicate with the external environment through two hydrophobic filters (13, 14) which are functionally separate and independent from each other, but are joined in a single compact structure.