GB2339545A

GB2339545A - Fluid mixing device for blending multi component pharmaceuticals

Info

Publication number: GB2339545A
Application number: GB9815385A
Authority: GB
Inventors: George Ayrton Fisher; Martin William Stow; Jacek Lech Basista; Nicholas John Smart; Paul Gocher
Original assignee: Johnson and Johnson Medical Ltd
Current assignee: Johnson and Johnson Medical Ltd
Priority date: 1998-07-15
Filing date: 1998-07-15
Publication date: 2000-02-02
Anticipated expiration: 2018-07-15
Also published as: WO2000003796A1; AU4921199A; GB2339545B; GB9815385D0

Description

2339545 NUXING DEVICE The present invention relates to a device suitable

for the mixing of fluids. In particular, the device is suitable to mix viscous and non- viscous fluids together instantaneously so 5 as to form a homogeneous blend.

Fluids of different viscosities or densities do not generally mix together spontaneously due to their differing physical characteristics. In the absence of any mixing force, such fluids either remain separated from each other or only gradually mix together over a significant period of time. In order to effect their mixing, some form of force must be generated within one or both fluids that causes a disturbance to one or both of the fluids and thus causes movement or interchange between the two.

Most pharmaceuticals are either in the form of fluids containing compounds dissolved within the fluid or are dry capsules.

If in a fluid form, pharmaceutical carriers usually comprise aqueous based solutions such as saline solution or comprise organic liquids such as ethanol or oils. Many such carriers, both aqueous and organic are of a viscous nature and are thus difficult to mix with non- viscous aqueous or organic solutions when the need arises.

Furthermore, most pharmaceutical components are expensive. Accordingly, when mixing the components, it is important that a technique is used that minimises wastage of any fluid material.

Devices suitable for mixing fluid components of a multiple component pharmaceutical have been previously described. The necessity for such devices arises in this field because although the individual components usually possess an adequately long shelf-life, once mixed in their effective form, many pharmaceuticals are unstable and are

3 0 thus relatively short-lived. Thus, most multi-component pharmaceuticals must be n-dxed immediately prior to delivery.

Mixing devices currently available for the purpose of mixing components of 2 pharmaceuticals comprise a number of different designs. For example, United States Patent 5,281,198 discloses an assembly, containing two cartridges whose contents are mixed using movable pistons. US Patent 5, 445,614 describes a unitary syringe assembly that contains a valve between two cartridges, so intentionally providing viscous resistance to aid mixing of the fluids. US Patent 5,569,193 describes a two component system wherein mixing of two sealed pre-filled compartments is effected using a plunger to break the seals. US Patent 5,033,650 describes a multiple barrel dispensing device, wherein mixing occurs in the channel of a nozzle that contains a static mixing element. A similar helical static mixing element is provided within an exit conduit of US Patent 4,538,920. US Patent 4,316,673 illustrates various structures with tortuous paths for mixing liquids. US Patent 4,305,672 describes a "diffuser" mechanism for mixing viscous liquids under pressure through a channel in the mechanism.

Emulsifying mechanisms are also known, that force separate liquids through a restricting zone into a turbulent zone (see, for example US Patent 4,217,145).

However, all of these devices suffer from the problem that they possess a significant void volume, meaning that some fluid is wasted. By void volume is meant the volume of liquid that must be introduced into the device to expel the air contained in the hollow regions of the device. In some cases, excessive pressure is required to force viscous liquids through the mixing devices at an acceptable rate. Furthermore, many of these devices are complicated and expensive to construct.

It is an object of the present invention to provide a simple, effective and inexpensive mixing device that has a low void volume. It is a further object of the invention to provide such a mixing device that enables an operator to monitor the mixing process visually. It is a further object of the present invention to provide such a mixing device that is compact, but does not require high pressures to force viscous fluids therethrough. It is yet a ffirther object to provide such a mixing device that can easily be assembled and 3 0 disassembled for cleaning between uses.

It has now been found that the above objects can be achieved by means of a mixing device in which the mixing channel has an elongate mean crosssection.

3 According to a first aspect of the present invention, there is provided a device for mixing a fluid comprising inlet means for introducing a fluid, a mixing conduit and outlet means for said fluid, characterised in that said mixing conduit has an elongate mean cross5 section.

According to a second aspect of the present invention there is provided an apparatus comprising a device according to the present invention, and additionally comprising two syringes coupled to the inlet thereof.

Me inlet means for introducing fluid may comprise any aperture or number of apertures through which fluid can be introduced. Preferably, the aperture is of a narrow bore so as to minimise the void volume in the device. Each aperture opens into a channel that leads to the mixing conduit.

In one embodiment of the invention, one entry port is provided, through which unn-dxed fluid can be directly added from a single container, such as a syringe. In an alternative embodiment, two or more entry ports are provided from which individual entry conduits lead to the mixing conduit. All conduits should be of as narrow bore as is possible, whilst striking a balance between on the one hand being able to introduce fluids without encountering so great a resistance as to make the device unusable and on the other hand as to minimise the void volume in the device.

By "elongate" is meant either that the mean width of the cross-section of the mixing conduit measured perpendicularly to the direction of fluid flow is significantly greater than its mean depth. It will be appreciated that the terms "width" and "depth" are relative terms that merely refer, respectively, to the major and minor cross-sectional dimensions of the conduit. By "significantly greater than its depth" is meant that preferably the mean width of the conduit is at least 2 times its mean depth, preferably at least 5 times its mean depth, still more preferably at least 10 times its mean depth, most preferably at least 20 times its mean depth and up to at least 50 times its mean depth or more. Preferably, the cross-section of the mixing channel is substantially constant along most of the length of the mixing channel.

4 In the mixing devices of the invention, a transparent material may be used to construct the whole device or a portion of the device so that an operator can monitor the mixing process by looking into the conduit.

It has been found that the use of a mixing channel having an elongate cross-section results in improved mixing of the fluids for a given void volume and/or pressure drop across the device, as compared to a conduit with a square or circular cross-section. The exact width or depth of the mixing conduit will depend on the viscosity, value and lo amount of fluid that is to be mixed. The greater the size of the conduit, the greater the amount of fluid that will remain in the device after mixing and dispensing of the fluid i.e. the void volume of the device will be greater.

Preferably, the mean width of the mixing conduit is from 2 mm to 25 mm, more preferably from 5 mrn to 15 mm.

As discussed above, the depth of the mixing conduit is dependent on its width, being measured in relation to this parameter. However, the conduit should be as shallow as possible. The reasons for this are two-fold. Firstly, the resistance to the flow of fluid through the conduit is increased. Accordingly, turbulence in the fluid correspondingly increases giving a greater mixing drive. Second, a shallow channel reduces the void volume.

The depth of the mixing conduit will also depend on the viscosity of the fluid. For example, for very viscous fluids, the conduit cannot be too shallow or else the resistance to flow of fluid through the device will be too great. Equally, for non-viscous fluids, the conduit should be extremely shallow so as to increase pressure and thus mixing drive. For most applications, the depth of the conduit will preferably be between 0.05 mm and 1.0 mm, more preferably 0.1 to 0.5mm.

It will be clear to the person of skill in the art that the dimensions of depth and width may be reversed without departing from the scope of the invention.

The length of the mixing conduit will depend on the nature of the fluids to be mixed. Obviously, the longer the conduit, the greater the degree of mixing of fluid. Accordingly, in order to mix fluids that differ markedly in viscosity, a long conduit should be used. However, a long conduit has increased dead volume and increase pressure drop, both of which are undesirable. Preferably, the length of the conduit is between 2cm and 60cm, more preferably it is between 5cm. and 40cm. Most preferably, the length of the conduit is about 25cm.

The internal surface of the mixing conduit will also depend on the nature of the fluids to 10 be mixed, since if smooth, the surface will hinder the flow of the fluid to a lesser degree. At least internal rough surface will therefore be preferable in order to mix fairly nonviscous fluids.

The mixing conduit can follow a straight path. However, in order to make the device 15 more compact and ergonomic the conduit can be formed into a spiral or helix. Preferably, the conduit follows a substantially twodimensional path, such as a twisting or tortuous path, especially a serpentine path. Both the two-dimensional path and the helical path are especially well suited to the two-piece construction and operation of the device as described fiuther below. As the fluid flows through the conduit, the tortuous nature of the conduit encourages the generation of turbulence within the fluid and thus its mixing.

The material from which the device is constructed may comprise any material that is impermeable to the fluid, to which fluid does not adsorb and which the fluid does not dissolve. T'hus, of particular suitability are plastic materials, such as polypropylene, polycarbonate or high density polyethylene (HDPE). However, for certain organic fluids that degrade or dissolve plastics (such as acetone), other material such as glass, fibrereinforced composite material or metal may be used.

Preferably, the material is plastic material. This material is inexpensive, easily moulded to shape, light and strong in structure. The device is thus durable and may be used on repeated occasions. Plastic is also inexpensive, meaning that the device and apparatus according to the present invention may be designed for a single use, being disposed of 6 subsequently. Plastic material is also easy to clean, so allowing an operator to use the device to mix different fluids without risk of contamination and preventing the mixing channel from becoming blocked.

Furthermore, plastics may be made transparent, so facilitating operator assessment of the degree to which mixing is occurring. An operator may thus follow the progression of fluid mixing and modify the mixing protocol accordingly. For example, it may be apparent that more pressure should be applied as the fluid is injected into the device, or that a different type of mixing apparatus is required, for example, one with a longer conduit. If it is desired for the material to be transparent, the device will preferably be constructed substantially from polycarbonate or polymethyl. methacrylate.

The material of the device may also be coloured. This may be desired for aesthetic reasons or to allow the typing of different mixing devices. For example, an operator may is possess a number of devices of different colours that are regularly used to mix certain fluids. For use with light-sensitive fluids, colouring the device may provide protection against unwanted degradation or reaction of the fluids. Colouring the devices may also ensure that the devices are not ever muddled.

The material from which the device is constructed may also differ in various parts of the device, or differ in colour.

For ease of manufacture, the device may comprise two complementary parts (a bottom portion and a top portion) that fit together in fluid-tight fashion to form the conduit. In a first embodiment of the invention, one portion of the device may form the bottom and sides of the mixing conduit and another portion may provide the top. For example, the conduit may be etched out of a surface of a first portion of the device, whilst the second portion of the device provides a flat surface which fits over said surface in fluid-tight fashion and forms the top of the mixing conduit.

In other preferred embodiments, each portion may have a part of the channel recessed into a surface thereof. This configuration will suit certain designs such as, for example, a device wherein the mixing conduit comprises a helical path. In this instance, it has been 7 found that the conduit is most easily formed by providing a cylindrical or frustoconical outer portion having one side of the conduit recessed into an internal surface thereof, in combination with a cylindrical or fi- ustoconical inner portion having the other half of the conduit recessed into the outer surface thereof, whereby the two portions fit together in a 5 mating engagement to define the 'conduit therebetween.

Devices according to the present invention may be permanently joined together, for example by ultrasonic welding or by gluing. Other methods of joining will be well known to those of skill in the art. Alternatively, the portions of the device may be clamped or clipped or snap-fitted together in demountable fashion so as to enable the device to be disassembled for easy cleaning. Preferably, the separate portions of the device are permanently joined.

The inlet means for introduction of fluid may comprise an entry port or ports, each designed so as to accommodate the attachment of a syringe. One entry port will be required in cases where it is desired to -mix a single preparation of unmixed fluid. In most cases, where it is desired to mix two or more separate fluids, the device will possess as many entry ports as there are separate fluids so that each syringe may deliver its content into the device.

In order to assist the delivery of equal amounts of separate fluids into the mixing device, it may be desired to use a yoke connected to the piston of each syringe. In order to deliver different quantities of two or more fluids, different size syringes may be yoked together.

The device may additionally incorporate mechanisms for securing syringes or fluid containers to the device. Such mechanisms may comprise, for example, arms or loops that are integrated into the structure of the device and which are designed to securely hold the syringes or containers in place.

The conduit for fluid present in the device ends in an outlet means for the mixed fluid. Suitable outlet means will be readily apparent to those of skill in the art. The outlet means preferably comprises a nozzle to facilitate the transfer of mixed fluid into a 8 container. The nozzle may be designed so as to accommodate the attachment of a needle or cannula, in cases where immediate delivery to a patient is required. The nozzle may also be designed so as to accommodate the attachment of a syringe or other suitable container, as required.

Figure I is a diagram showing the internal structure of a device according to the present invention, wherein the upper portion of the device has been removed for clarity.

Figure 2 shows the assembled device with two yoked syringes in position.

Figure 3 shows an alternative embodiment of the invention in which the mixing path is designed so as to form a helical path.

Figure 4 is a magnified cross-section of the assembled device, showing a preferred 15 aspect of this embodiment of the invention in which the mixing path is formed from notches on both the upper and lower portions of the device.

Figure 5 shows the assembled device of this embodiment of the invention with two yoked syringes in position.

Example 1

With reference to Figures I and 2 of the drawings, a device (1) of the present invention comprises two entry ports (2) for introducing fluids and a mixing conduit (3). The width 2 5 of the mixing conduit is 5mm and its depth is 0.2mm. The length of the conduit is about 25cm. The void volume of the device is approximately 25041.

The conduit includes 8 comers, each altering the direction of the path by 900.

3 0 The device comprises an upper (4) and a lower (5) portion that complement each other to form a tight fit when pressed or moulded together. Both portions are manufactured from acrylic material. The upper portion of the device is transparent.

9 The lower portion of the device defines two apertures (6) leading to entry conduits, the apertures each being capable of accommodating the nozzle portion of a syringe. The bore of the apertures is narrow in order to minimise the void volume of the device. The conduit (3) ends in a nozzle (7) that is capable of accommodating a needle, syringe, 5 cannula or other device or container.

In use, each fluid is injected into the device through the entry conduits by yoked syringe. The yoke mechanism ensures that equal quantities of the two fluids are introduced into the mechanism. As the fluid enters the mixing conduit, it is viewed through the transparent upper portion of the device to ensure that enough pressure is being applied to ensure complete mixing of the two fluids. A needle, attached to the exit nozzle of the devices, directs the transfer of mixed fluid into a collection container.

This embodiment of the invention possesses several advantages over curTently available mixing devices. First, the device is simple and inexpensive to manufacture, comprising two simple plastic components that many together to give a tight fit. Into either the bottom portion or into both portions of the device there is etched, moulded or embossed a shallow twisting channel that forms the mixing conduit. The surface of this channel may be produced so as to give a rough finish.

Second, the device can either be joined together permanently or be clipped together. The latter option allows easy disassembly so that the device can be cleaned. This is particularly important when very viscous fluids are mixed, which tend to become blocked.

Third, if required, the transparent nature of the upper portion of the device allows an operator to view the mixing process and to modify his technique accordingly. This is particularly important when mixed fluids are being prepared for direct injection, when the presence of air bubbles in the mixing conduit may prove disastrous.

Example 2

With reference to Figures 3 and 4 of the drawings, a device (1) of the present invention comprises two entry ports (2) for introducing fluids and a mixing conduit (3). The width of the mixing conduit is 5mrn and its depth is 0.2mm. The length of the conduit is about 25cm. The void volume of the device is approximately 2500.

The conduit is helical in nature, the conduit being formed from the marrying of two etched components that form a rectangular channel when fitted together (see figures 3 and 4). Both portions are manufactured from acrylic material.

The lower portion of the device defines two apertures (6) leading to entry conduits, the 10 apertures each being capable of accommodating the nozzle portion of a syringe. The bore of the apertures is narrow in order to minimise the void volume of the device. The conduit (3) ends in a nozzle (7) that is capable of accommodating a needle, syringe, cannula or other device or container.

In use, each fluid is injected into the device through the entry conduits by yoked syringe. The yoke mechanism ensures that equal quantities of the two fluids are introduced into the mechanism. A needle, attached to the exit nozzle of the devices, directs the transfer of mixed fluid into a collection container.

One advantage of this embodiment of the invention is that the mixing conduit is contained within a small area. Accordingly, the device is compact and may be operated using one hand only. This greatly facilitates the operation of the device.

It will of course be understood that the present invention has been described above 2 5 purely by way of example, and that modifications of detail can be made without departing from the scope of the invention.

Claims

1. A device for mixing a fluid comprising inlet means for introducing a fluid, a mixing conduit and outlet means for said fluid, characterised in that said 5 mixing conduit has an elongate mean cross-section.

2. The device of claim I wherein the mean width of said mixing conduit is at least 3 times its mean depth.

3. The device of claim 2 wherein the mean width of said mixing conduit is at least times its mean depth.

4. The device of any one of the preceding claims wherein the width of said mixing conduit is from 2 mm to 25 nun.

5. The device of any one of the preceding claims wherein the depth of said mixing conduit is between 0. 1 mm and 1.0 mm.

6. The device of any one of the preceding claims wherein the length of said mixing conduit is between 5cm and 40cm.

7. The device of any one of the preceding claims wherein an internal surface of said mixing conduit is rough.

8. The device of any one of the preceding claims wherein the mixing conduit follows a substantially two-dimensional path.

9. The device of claim 8, wherein the mixing conduit follows a substantially serpentine path.

10. The device of any one of claims 1 to 7, wherein the path of said mixing conduit is in the form of a spiral or helix.

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11. The device of any one of the preceding claims constructed substantially from plastic material.

12. The device of any preceding claim wherein the device is constructed at least in part from transparent material.

13. The device of any one of the preceding claims wherein the device is pre-printed with graphic material.

lo

14. The device of any one of the preceding claims wherein the device is coloured.

15. The device of any one of the preceding claims wherein said means for introducing fluid comprises one or more ports each designed so as to accommodate the attachment of a syringe.

16. The device of any one of the preceding claims wherein the outlet means comprises a nozzle.

17. The device of claim 16 wherein the nozzle of said device may accommodate the attachment of a needle, cannula, empty syringe or container.

18. A device according to any one of claims 1-17, comprising a base portion and a cover portion, wherein a surfaces of at least one of said base and cover portions is recessed to define a part of said conduit, and the portions fit together in a liquid tight fashion to form the mixing conduit.

19. The device of claim 18, wherein the base and cover portions are demountable.

20. The device of claim 18, wherein the base and cover portions are permanently joined together.

21. An apparatus comprising a device according to any one of claims I to 20, and additionally comprising two syringes coupled thereto.

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22. The apparatus of claim 21 wherein said syringes are yoked together.

23. A device substantially as hereinbefore described with reference to and as shown 5 in the accompanying drawings.