WO2018006105A1

WO2018006105A1 - Neonatal drug delivery device

Info

Publication number: WO2018006105A1
Application number: PCT/ZA2017/050036
Authority: WO
Inventors: Annie VAN JAARSVELD; Hazel Ann BIRNS
Original assignee: K2 Medical (Pty) Limited
Priority date: 2016-06-30
Filing date: 2017-06-28
Publication date: 2018-01-04

Abstract

This invention relates to a neonatal drug delivery device (80) comprising a primary tube (50), having a connector (90) at its first end (10) for connecting the tube to an IV bag (30); a filter element (40), for filtering endotoxins at least partially from solution, the filter element (40) being arranged in direct fluid flow communication with the primary tube (50), and further being arranged proximate the first tube's other end (160); and a secondary tube (60), having its first end (110) arranged in direct fluid flow communication with the filter (40), and its second end (20) terminating in a connector (25) for connecting the device (80) to a neonatal cannula (140), The invention also extends to a neonatal drug delivery device (80) assembly (190) comprising a series of at least two such devices (80), each device (80) being maintained in fluid flow communication with each other via a common manifold (200).

Description

Field Of The Invention

THIS INVENTION relates, broadly, to a neonatal drug delivery device. More particularly, the invention relates to an intravenous neonatal drug delivery device.

Background To The Invention

For purposes of this invention, the term "neonatal" is understood to extend to newborn babies and also to infants younger than 3 months old, and to relatively undersized infants.

Certainly, intravenous drug delivery devices are well-known - they are known commonly in the art as intravenous ("IV) administration lines. At the simplest level, IV lines typically comprise a bag containing a drug in solution, the bag being connected to a tube, through which the solution passes, and the tube terminating in a cannula at its other end - the cannula most often taking the form of a hollow needle that is inserted into a patient's vein.

Over the years, IV lines have been improved iteratively, and certain developments include the addition of filter elements to filter-out contaminants and pathogens. Another improvement is the addition of a secondary and ternary tubes into existing IV administration line devices, so as to permit the administration of multiple drug solutions simultaneously through a single intravenous line. In order to describe the invention in context, it is necessary, first, to understand a phenomenon that is known in the art as the 'dead volume* prob!em (sometimes also known as the "residual volume' or the "hold-up volume* problem). In essence, this refers to the quantity of a drug (in solution) that remains in the IV administration line after a bolus injection is administered. A bolus injection, in tum, refers to a particular dose of a specified drug (in solution) that is required to be administered to a patient rapidly. Typically, administration is performed via a needle-free access port to the !V line at a point as close to the patient as possible. In an attempt to alleviate the problem, and in order to ensure that the full volume of drug is administered to the patient, it is conventional practice that double the volume of fluid in the hold-up section of the administration line is flushed through it and. from there, into the patient's vein.

It will also be appreciated that, the longer the length of total tubing in an IV administration device, the greater will be the extent of the dead volume problem.

Despite the advances in technology, a number of disadvantages have been associated with known, conventional IV administration devices. For example, and significantly, a great many of these are unsuitable for use in neonatal patients, purely because of the size of the patients - that alone, makes it unfeasible to flush IV administration devices, purely because the tiny neonatal body cannot tolerate high or additional volumes of fluid. A consequence of this has been a regression in the state of technology, in that many medical practitioners have opted to have filter elements and/or secondary tubes removed from IV administration devices for neonatal patients, in an effort to minimise total tube length (and hence: the total fluid volume required in order to administer a drug in its entirety). This, of course, is highly undesirable as it necessarily surrenders the advantages that are associated with filter elements and secondary tubes.

An associated limitation of the prior art solutions is that, in many cases, filters demonstrate an inability to accommodate the administration of lipid-based suspensions or emulsions through an IV administration line (owing to the fact that lipid- based fluids cannot pass through filter elements). This, necessarily limits, their scope of application.

A further disadvantage associated with conventionai IV administration devices intended for neonatal patients is that none address the issue of endotoxin safety (Endotoxins are particles derived as a result of Gram-negative bacterial contamination in an IV line - it is undesirable that these particles should find their way into a patient's bloodstream via the IV line). This is particularly so in cases in which an ionic solution (typically: saline) is switched for a non-ionic solution (such as dextrose) where the same IV administration device is used for the patient. This often results in endotoxin contamination.

Yet another disadvantage of conventional Luer lock connections - despite their appeal in universal fit - is that the lock mechanism themselves are often exposed to unsterile environments during assembly of an intravenous administration line, which runs the risk of introducing at least some contamination into the intravenous administration line. This, of course, is undesirable. Object Of The Invention

It is an object of the present invention to provide a neonatal drug delivery device that will overcome, at least partially, the disadvantages described above.

Summary Of The Invention

According to a first aspect of the invention, there is provided a neonatal drug delivery device comprising:

• a primary tube, having a connector at its first end for connecting the lube to an IV bag;

• a filter element, for filtering endotoxins at least partially from solution, the filter element being arranged in direct fluid flow communication with the primary tube, and further being arranged proximate the first tube's other end; and

• a secondary tube, having its first end arranged in direct fluid flow communication with the filter, and its second end terminating in a connector for connecting the device to a neonatal cannula.

The neonatal drug delivery device may further include at least one ternary tube, each such ternary tube being coupled in fluid flow communication with the primary tube.

The primary tube and a ternary tube may be arranged in bifurcated, fluid- flow communication with each other. The filter element may Include a charged nylon membrane for filtering endotoxins at least partially from the fluid flow when the device is in use.

Preferably, the primary tube and the filter element may be enclosed integrally, in fixed relative arrangement, within a continuous sleeve.

Alternatively, the secondary tube and the filter element may be enclosed Integrally, in fixed relative arrangement, within a continuous sleeve.

Further alternatively, the primary tube, the secondary tube and the filter element may all three be enclosed integrally, in fixed relative arrangement, within a continuous sleeve.

The primary tube may include a needle-free access port at its first end. Preferably, the primary tube terminates in a split septum needle-free access port.

Preferably, the split septum needle-free access port is dimensioned and configured to engage a comptimentarily-shaped Luer lock connection on an IV bag.

The secondary tube may include a slip connection at its second end, the slip connection being dimensioned and configured to engage a cannula.

The secondary tube may further include an additional access port for facilitating emergency drug administration. Preferably, each ternary tube is substantially identical to the primary tube in shape, configuration and component-assembly.

Brief Description Of The Drawings

In order to describe the invention, embodiments thereof are described hereunder, purely as examples, without limiting the scope of the invention, wherein: depicts a typical prior art intravenous drug delivery device; depicts a neonatal drug delivery device in accordance with a first aspect of the invention;

Figure 3 is an exploded view of the invention as depicted in Figure 2;

Figure 4 depicts a variant embodiment of the neonatal drug delivery device depicted in Figure 2; and depicts a neonatal drug delivery device assembly in accordance with a second aspect of the invention

Detailed Description Of The Drawings

Before describing the invention, reference is made, first, to Figure 1 , which depicts a typical intravenous drug delivery device 5 that is known in the prior art. it will be noted, in particular, that the device 5 includes a Luer lock connection 25 at both of its terminal ends (10, 20) - end 10 being proximate the IV bag in use (end AA), and end 20 being proximate the patient's vein in use (end BB). This is significant: the Luer lock connections 25 are very large, relatively speaking, and can often cause trauma to the patient when used in neonatal patients, owing to their remarkably small size.

The prior art device 5 further comprises a primary tube 50 and a secondary tube 60, the two tubes meeting at a filter device 40. It will be appreciated that, in use, fluid moves from the IV bag 30 at AA, to the patient (not depicted) at BB. However, the mere presence of the filter 40 necessitates the total length of tubes 50, 60 to be iengthier than would be the case of filter 40 was absent. This is significant: neonatal bodies, by virtue of their remarkably small volume, are limited to the volumes of fluid that may be taken-up intravenously without harming the patient. This, in turn, necessarily limits the volume of drug that is capable of being delivered intravenously in any given period of time. As a general rule of thumb, the flush volume in such devices 5, typically, is twice the total length of tubes 50, 60.

Attention is now turned to the invention. Referring to Figures 2 and 3, which depict a preferred embodiment of the invention, a neonatal drug delivery device in accordance with the invention is provided, and is referred to generally by numeral 80. Comparable components in the prior art, as depicted in Figure 1, are given identical reference numerals in Figures 2 and 3. It is convenient to describe the invention from top (AA) to bottom (BB). as this traces the direction of fluid flow through the device 80 in use. The device 60 includes a primary tube 50 and a secondary tube 60. The primary tube 50 has a connection 90 at its first terminal end 10. That connection 90 is dimensioned and configured to engage a comp!imentarily shaped connection 100 at the base of an IV bag 30. In the preferred embodiment of the invention depicted here, that connection takes the form of a split septum needle-free access port, which slips into a Luer lock connection 100 on the IV bag 30. it will be appreciated by the person skilled in the art that the split septum is wholly contained within the port 90, and is this not exposed to the environment at any point during the connection of the primary tube 50 to the IV bag 30 - a distinct advantage over the prior art.

The primary tube 50 terminates at its other end 160 in filter 40. More specifically, the filter 40 depicted here is a Pall™ Neo 96 Nanodyne filter, incorporating a positively charged nylon 66 membrane, which serves to filter endotoxins from the intravenous solution. It wili be clear, of course, that the primary tube 50 and the filter 40 are arranged relative to each other to ensure direct fluid flow communication from the former to the latter.

Progressing further along the intravenous administration line: at the other end of the filter 40 is a secondary tube 60. The first end 110 of the secondary tube 60 is proximate the filter 40, the two also being arranged in direct fluid flow communication with each other. The other end 120 of the secondary tube 60 terminates in a connector 130 for connecting the secondary tube 60 with a cannula 140. In the preferred embodiment of the invention depicted here, the connector 130 takes the form of a slip connection, and the cannula 140 is a neonatal hollow needle. Naturally, the slip connection 130, in use, envelops an end of the needle 140 hermetically, in friction-fit fashion. It will be noted that the total length of the primary tube 50 plus secondary tube 60 in the prior art device 5 (Figure 1) is substantially lengthier than the corresponding total length in the device (Figure 2 & 3). It has been found in devices 80 tested that a hold-up volume of approximately 0.4 ml has been achieved - which in turn would necessitate a flush volume in the order of approximately 0.8 ml. This is a significant improvement over prior art devices 5 where, typically, a hold-up volume in the order of 0.7 ml (and hence a flush volume in the order of 1.4 ml) Accordingly, if in use it becomes necessary to flush any bolus from the intravenous administration iine, it follows that proportionally less fluid is necessary in order to achieve this. This necessarily alleviates the extent of the dead volume problem that plagues the prior art. It will also be appreciated by the person skilled in the art that the particular connector incorporated in the invention alleviates the problem of trauma caused to neonatal patients when using prior art devices 5.

Preferably, the invention 80 also includes at least one ternary tube 150. In the preferred embodiment depicted in Figures 2 and 3_: the device 80 has a single ternary tube 150, which is coupled to the primary tube 50 at a point proximate second end 160. ft will be well understood that ternary tube 150 would be used in cases in which a second (or additional) IV bag of medication would be required for intravenous administration to the neonatal patient. One such occasion would be cases in which two different drugs (each in solution) may not be mixed in a single solution, and require independent storage. Note, in particular, how the primary tube 50 and ternary tube 150 are connected in bifurcated arrangement, and meet proximate second end 160. This is by design, to ensure that al! fluids passing through both primary tube 50 and ternary tube 150 pass through filter 40.

The device 80 is depicted in Figure 3 in exploded form, purely for illustrative purposes. While it is certainly envisaged that the primary tube 50, secondary tube 60 and filter 40 may be assembled separately, as discreet components, in order to minimise contamination, it is also envisaged that in some embodiments of the invention, the primary tube 50 and the filter 40 will be enclosed integrally, within a single continuous sleeve (not depicted). In another embodiment, the filter 40 and the secondary tube 60 will be enclosed integrally, within a single continuous sleeve (not depicted). In yet another embodiment of the invention, all three of the primary tube 50, filter 40 and secondary tube 50 will be enclosed integrally, within a single continuous sleeve (not depicted). in the preferred embodiment that is illustrated in Figures 2 & 3, both the primary tube 50 and the ternary tube 150 terminate in a split septum needle-free access port 90, to facilitate connection to their respective IV bags 30.

The secondary tube 60 further includes an additional access port 170 for facilitating emergency drug administration. Typically, this port 170 will be a needle- access port, dimensioned and configured to receive a conventional syringe needle, through which the emergency dose will be administered. The embodiment of the device 80 depicted in Figure 4 is slightly different to that depicted in Figures 2 and 3, in that the terminal end (180) of ternary tube (150) connects to the device (80) at a point below filter element (40). The advantage achieved from this arrangement will be apparent to the expert in the field: it prevents the flow of any fluid directed through ternary tube (150) from passing through filter element (40). This makes the invention (80) particularly useful in cases in which a lipid-based suspension or emulsion is required to be administered to a neonatal patient, either on its own or in combination with another fluid. It is also advantageous in the emergency situations (described immediately above) in that an emergency dose of medication (be it lipid-based or not) administered through ternary tube (150) reaches the neonatal patient sooner than if administered through either primary tube (50) or secondary tube (60), by virtue of the fact that it necessarily bypasses filter element (40).

Yet a further advantage achieved by the invention is that offered by its second aspect: a neonatal drug delivery device assembly (190), which is illustrated in Figure 5, The assembly (190) comprises a series of at least two of the devices (80) described above (in Figure 5, precisely 2 devices are depicted, although it will be appreciated that, in principle, no upper limits exists on the number of devices (80) that may be employed in other embodiments (not depicted)). Each device (80) is maintained in fluid flow communication with each other via a common manifold (200). it is within the manifold that the full series of fluids for administration will combine (if administered simultaneously), and that manifold (200) terminates ultimately in a slip connection (25) that is dimensioned and configured to engage a cannula (140) - as has been described above, it will be appreciated that this assembly (190) provides a distinct advantage: in the event that a neonatal patient is in need of IV administration of multiple fluids, the assembly (190) provides an efficient, ready apparatus to achieve this, and - perhaps most importantly - through the use of a single cannula (140), which makes the invention relatively non-traumatic to the patient, minimising the risk of injury caused by cannulae to neonatal patients.

The inventors conducted a series of comparative experiments to assess the device against the closest comparative prior art devices. The following results were returned:

Table 1: Assessment Of Prior Art Device

A Pali™ NE096 filter and "j-loop" device was tested with a 0.9% saline solution at 1m head height, and on administration, the following readings were noted:

Table 2: Assessment Of Device According To The Invention

Comparatively, a Frezenius-Kabi Volumat Azilia infusion pump at 1m head height was tested at room temperature, on each of three embodiments of the invention. On administration, the following readings were noted:

The results of these experiments indicate that the device (80) demonstrates both a superior maximum flow rate and a superior total hold-up volume, relative to the prior art solutions. This is true for ail three of the embodiments tested.

it will be appreciated that numerous embodiments of the invention couid be performed without departing from the scope of the invention as defined in the consistory statements above. For example: in each instance in this description in which reference is made to a Luer lock, it will be appreciated by the expert in the field that slip- lock fittings, alternatively bayonet fittings, are ready mechanical substitutes to achieve the same result

Claims

1. A neonatal drug delivery device (80) comprising:

• a primary tube (50), having a connector (90) at its first end (10) for connecting the tube to an IV bag (30);

• a filter element (40), for filtering endotoxins at least partially from solution, the filter element (40) being arranged in direct fluid flow communication with the primary tube (50), and further being arranged proximate the first tube^'s other end (160); and

• a secondary tube (60). having its first end (1 10) arranged in direct fluid flow communication with the filter (40), and its second end (20) terminating in a connector (25) for connecting the device (80) to a neonatal cannula (140).

2. A drug delivery device (80) according to claim 1 which further includes at least one ternary tube (150), each such ternary tube (150) being coupled in fluid flow communication with the primary tube (50).

3. A drug delivery device (80) according to claim 2. wherein the primary tube (50) and a ternary tube (150) are arranged in bifurcated, fluid-flow communication with each other.

4. A drug delivery device (80) according to claim 1 wherein the filter element (40) includes a charged nylon membrane for filtering endotoxins at least partially from the fluid flow when the device is in use.

5. A drug delivery device (80) according to claim 1 wherein the primary tube (50) and the filter element (40) are enclosed integrally, in fixed relative arrangement, within a continuous sleeve.

6. A drug delivery device (80) according to claim 1 wherein the secondary tube (60) and the filter element (40) are enclosed integrally, in fixed relative arrangement, within a continuous sleeve.

7. A drug delivery device (80) according to claim 1 wherein the primary tube (50), the secondary tube (60) and the filter element (40) are all three enclosed integrally, in fixed relative arrangement, within a continuous sleeve.

8. A drug delivery device (80) according to claim 1 wherein the primary tube (50) includes a needle-free access port (90) at its first end (10).

9. A drug delivery device (80) according to claim 8 wherein the access port (90) is a split septum needle-free access port, that is dimensioned and configured to engage a comp!imentariiy-shaped Luer lock connection on an IV bag.

A drug delivery device (80) according to claim 1 wherein the secondary tube (60) include a slip connection (25) at its second end (20), the slip connection (25) being dimensioned and configured to engage a cannula (140).

11. A drug delivery device (80) according to claim 1 wherein the secondary tube (60) further includes an additional access port (170) for facilitating emergency drug administration.

12. A drug delivery device (80) according to claim 1 wherein the terminal end (180) of ternary tube (150) connects to the device at a point below filter element (40), in order to prevent the flow of any fluid directed through ternary tube (150) from passing through filter element (40).

13. A drug delivery device (80) according to claim 2 wherein each ternary tube (150) is substantially identical to the primary tube (50) in shape, configuration and component-assembly.

14. A neonatal drug delivery device (80) assembly (190) comprising a series of at least two devices (80) according to any one of claims 1 - 13, each device (80) being maintained in fluid flow communication with each other via a common manifold (200). characterised in that the manifold (200) terminates ultimately in a slip connection (25) that is dimensioned and configured to engage a cannula (140).