AU742148B2

AU742148B2 - Device for filling reservoirs with a pharmaceutical liquid

Info

Publication number: AU742148B2
Application number: AU25254/99A
Authority: AU
Inventors: Michel Guy; Michel Lamoise; Eric Teillaud
Original assignee: Iomed LLC
Current assignee: Iomed LLC
Priority date: 1998-02-23
Filing date: 1999-02-19
Publication date: 2001-12-20
Anticipated expiration: 2019-02-19
Also published as: FR2775190B1; WO1999042174A1; EP1058568A1; AU2525499A; CA2321887A1; JP2002503532A; FR2775190A1

Description

WO 99/42174 1 PCT/FR99100382 DEVICE FOR FILLING RESERVOIRS WITH A PHARMACEUTICAL LIQUID The present invention relates to a device for the filling of reservoirs with a liquid containing a pharmacologically-active principle, with these reservoirs being able to be used, in particular, within the framework of a transdermal administration of drugs by means of ionophoresis or even by means of a passive diffusion (use of "patches").

Pharmacologically-active principles, as well as the liquids that they contain, frequently have the characteristic of being unstable, in such a manner that it is absolutely necessary to preserve them under very specific conditions before using them. Before the administration of such a principle by transdermal channel, a "reservoir", which is commonly composed of a layer of hydrogel or of a compress, is 0: loaded with a precisely dosed solution of the principle.

For these reasons, the filling of the reservoirs that are used in the framework of a transdermal administration of drugs by means of ionophoresis or by a passive diffusion must be carried out a very short time before use, and the volume of liquid that is sent into these reservoirs must be able to be controlled in a rigorous manner.

ee i A device that makes it possible to fill the reservoir adjacent to the electrode of a device for the transdermal administration of a drug by means of ionophoresis with a liquid containing the active principle at the moment of its use, with this liquid being Initially contained in an immovable reserve of the flexible syringe type, is already known from the American patent by Jacobsen, number 4 166 457.

In accordance with this document, the filling is carried out through a lateral injection channel parallel to the level of diffusion. Its injection channel is blocked by a self- WO 99/42174 2 PCTIFR99/00382 closing membrane, and the placing of the fluid of the syringe into communication with the reservoir is carried out in two phases: first, the placing of the syringe into a waiting position, and then the piercing of the foil sealing.

This device has the following disadvantages, however: First of all, it does not permit the simultaneous filling of several reservoirs. Next, it requires relatively complex manual operations, comprising several stages: the presentation of the syringe, the piercing of the foil sealing, the filling of the reservoir, and then the withdrawal of the syringe. These steps are not mechanized, so that they require a certain level of skill and a certain attention on the part of the operator. Finally, this apparatus does not include any safety devices: it does not have proof of inviolability that makes It certain that the liquid that is to be injected into the reservoir is genuine; it does not have means that make it possible to easily monitor the precision of the dose of liquid being injected; and, finally, it does not have means for preventing the movement of the piston back into the syringe..

The present invention has the objective of providing a device which allows the filling of reservoirs with a liquid, containing a pharmacologically-active principle that does not have the disadvantages stated above and which, in particular, allows the simultaneous filling of two reservoirs used in the framework of a transdermal administration of drugs by ionophoresis or by means of passive diffusion.

These two reservoirs rhay form part of an electrodes assembly such as described in the French patent application No. 2 747 313 In the name of the present applicant.

These objectives of the Invention, as well as others which will emerge from a reading of the description that follows, are achieved by means of a device for the filling of at least the first and the second reservoirs with at least one liquid containing a pharmacologically-active principle, with these reservoirs being intended for the transdermal administration of the said principle, which is noteworthy in that WO 99/42174 3 PCTIFR99/00382 it comprises means for simultaneously putting the said fluid into communication with at least the first and second reservoirs, with at least the first and second reserves, respectively, containing the said liquid, and for concomitantly emptying the said liquid from the said reserves towards the said reservoirs.

According to other characteristics of the device in accordance with the present invention: o The said means comprise a component for rotational movement linked mechanically with at least the first and second pistons, in such a manner that a rotation of the said component for rotational movement brings about a rectilinear displacement of the said pistons and a concomitant emptying of the said liquid from the said reserves and towards the said reservoirs; ee o The said component for rotational movement and the said pistons are linked by means of a mechanism of the rack and pinion type; o The said racks are disengaged from the said pinion when the said component for rotational movement is at the end of its stroke; o The said device comprises at least the first and second chambers, which are suitable for receiving the said at least first and second reserves, respectively, with the said at least first and second pistons being movable within the said at least first and second chambers, respectively, in order to flatten the said reserves against the base of the said chambers and to bring about the .puncturing and the concomitant emptying of the said reserves towards the said reservoirs; o The bases of the said chambers each comprise a hollow needle which permit fluid. from the said reserves to be placed into communication with the said reservoirs, and the said hollow needles protrude into the base of the said chambers in such a WO 99142174 4 PCTIFR99/00382 manner as to ensure the puncturing of the said reserves during their flattening by the said pistons.

As will be seen further below, this device makes it possible to fill, in a simple manner, at least two reservoirs with the liquid contained in at least two independent reserves, and makes it possible to rigorously monitor the dosage of the liquid transferred.

Other characteristics and advantages of the present invention will emerge upon the reading of the description that follows and upon an examination of the attached diagram, in which: o Figure 1 Is a view of the device for the filling of reservoirs along .the cross-sectional line 1-1 indicated in Figure o Figure 2 Is a view of the device for the filling of reservoirs along the cross-sectional line 11-11 indicated in Figure o Figure 3 is a view of the device for the filling of reservoirs along .the cross-sectional line ll-il indicated in Figure 1; go S* o Figure is a side view of the device for the filling of reservoirs along along the cross-sectional line VI-VI indicated in Figure 4; along, the. cross-sectional line VI-V1 indicated in Figure 4; WO 99142174 5 PCTIFR99100382 o Figure 7 is a view of the device for the filling of reservoirs along the cross-sectional line VII VII indicated in Figure Reference is made to Figures 1 and 2 of the attached diagram, in which one preferred manner of implementation of the device for the filling of reservoirs in accordance with the invention has been represented. In these figures and those that follow, identical numerical references represent identical or analogous components or elements.

A casing (71, 72), comprising two parts and 72) articulated with each other by means of two hinges (8 i and 82), is depicted in Figures 1 and 2.

The upper part of the casing (71, 72) comprises two reserves (21 and 22), accommodated within two cylindrical chambers (1.03 and 104) of parallel axes, respectively. At least one of these reserves contains a solution of a pharmacologically-active principle, with this solution obligatorily being ionic in the case of a transdermal administration by means of ionophoresis. The axes of the two chambers are themselves parallel to the middle level of the said upper part. The two chambers are open at one of their ends, in such a manner that it is possible to introduce pistons of a cylindrical section (10, and 102) into them, which pistons are able to flatten the two reserves against the bases of the two chambers.

WO 99142174 6 PCTIFR99/00382 The two reserves (21 and 22) have folding envelopes of the "accordion" type; that is to say, these envelopes have previously-set regular folds which allow the easy compression of the reserves under the action of a longitudinal stress.

In accordance with one variant, which is not represented, these two reserves may likewise include syringes which comprise, in the known manner, a chamber within the interior of which a piston slides.

The two pistons (10, and 102) comprise racks (4 and 4j, which are positioned along the generators of the pistons. These racks engage with the same pinion which is integrally formed with a component for rotational movement with the axes of this pinion and of the component-for rotational movement being joined and perpendicular to the middle level of the upper part (71) of the casing 72).

The component for rotational movement has a gripping component on top of it, which makes it possible for an operator to easily apply a rotational stress to this component for rotational movement.

A number of hollow needles (11 12,, and 112, 122) project, at the same time, into the base of the chambers (103, 104) and in relation to the upper part of the casing 7 2 WO 99/42174 7 PCTIFR99/00382 The lower part (72) of the casing (71, 72) is a support base of roughly rectangular form. This support base is designed in such a manner that, when the casing is closed, It is possible to place the electrodes assembly described in the patent application stated above between the two parts of the casing. The upper portion of the upper part (71) of the casing has a geometry which makes it possible to block the part of the electrodes assembly when the casing is closed. The part is the receptacle for the casing of the electronic control of the electrodes assembly. This receptacle is integrally formed with a bearing plate which is itself integrally formed with the two reservoirs and 12) adjacent to the electrodes.

In order to likewise be able to fill the two reservoirs (11 and 12) of the electrodes assembly described in the patent application stated above, the two hollow needles (111, 12, and 112, 122) are arranged in such a manner that the closing of the casing 72) has the effect of bringing the lower ends of these hollow needles into the respective centers of the two reservoirs. The two reservoirs include sealings of rubber (13, and 132), which permit the placing of fluid between the two hollow needles and the two reservoirs into communication.

A clasp which makes it possible to keep the casing (71, 72) closed is depicted in Figures 4 and 6. This clasp, which has an roughly rectangular form, is articulated with the lower part (72) of the casing. On the upper part of the clasp, a notch makes it possible to interlock the clasp with the upper part (71) of the casing.

WO 99142174 8 PCTIFR99/00382 An opening cam which is integrally formed with the rotational movement component is depicted in Figure 6. This opening cam consists of an expansion which is located on the radius of the component for rotational movement, in such a manner that, when this cam is present to the right of the clasp during the rotation of the component for rotational movement in a clockwise direction, this cam has the effect of removing the clasp from the upper part of the cpsing 72), An opening (19) of roughly rectangular shape is depicted in Figures and 6. This opening is integrally formed with the component for rotational movement and is located on the component for rotational movement in such a manner that, during the rotation of the component'for the rotational movement in a clockwise direction, this opening comes to be presented to the right of the clasp immediately behind the cam The dimensions of this opening are such that this opening can accommodate the clasp when this clasp is closed again.

A breakable safety lug (18) is depicted in Figures 5 and 6. This tab is integrally formed with the upper part of the casing 72). A receptacle (17), which is integrally formed with the component for rotational movement accommodates this tab when the device in accordance with the invention is not being used, that is to say, when the effort of rotation has not been applied to the component for rotational movement. The relative positions of the tab and of the receptacle may, of course, be reversed without thereby leaving the framework of the present invention.

9 A circular toothed profile with an axis joined with that of the component for rotational movement is depicted in Figure 7. This profile is integrally formed with the component for rotational movement, and is placed above the component for rotational movement. The radius of the toothed profile is greater than that of the pinion (43) and less than that of the component for rotational movement. The angle to the centre of the toothed profile is about 270', for example. The toothed profile is o tangential to an anti-return tab (15) which is integrally formed with the o i oo upper part (71) of the casing with this tab being of a roughly 10 rectangular shape.

l l* The operation of the device in accordance with the invention is as follows. First of all, the electrodes assembly descried in the patent application stated above is placed between the two parts (71 and 72) of the casing. This casing is reclosed, which has the effect of placing the fluid of 15 the two reservoirs (11 and 12) of the electrodes assembly into l° communication with the two hollow needles (111, 121 and 112, 122).

The operator exerts an effort of rotation in a clockwise direction relative to the component for rotational movement This effort has the effect of breaking the safety lug which serves the purpose of providing a visual proof of opening. In carrying out the rotation of the component for rotational movement, the operator transmits translational movements, by way of the pinion rack mechanism (41, 42, 43), in the direction opposite to the two pistons (10, and 102). The two pistons then flatten the two reserves (21 and 22) against the bases of the chambers (103 25 and 104).

WO 99/42174 10 PCTIFR99100382 Under the effect of the flattening, the two protruding hollow needles (111, 12,, and 112, 122) come to puncture the two reserves, thus carrying out the placing of fluid of the two reserves into communication with the two reservoirs and 12).

In carrying out the rotation of the component for rotational movement the operator empties the contents of the two reserves (21 and 22) into the two reservoirs and 12). The toothed profile (14) and the anti-return tab (15) prevent the component for rotational movement from turning in a counterclockwise direction, thus avoiding any error in handling which could lead to reaspirating a certain quantity of the liquid sent into the two reservoirs.

When the filling of the two reservoirs (11 and 12) has been completed, the cam (16) arrives at the right of the clasp This cam then removes the clasp from the upper part (71) of the casing 72), which has the effect of opening the casing and of releasing the electrodes assembly described in the patent application stated above. The electrodes assembly is then ready for use on the patient.

Once the assembly of the electrodes described in the patent application noted above has been used on the patient, it is useful to be able to put it back into the casing (71, 72) and to be able to reclose the casing, in order to send the assembly for recycling. The opening makes it possible to reclose the clasp when the component for rotational movement is turned to the end of its stroke. It is necessary to note, in addition, that the lengths of the racks (41 and 42) of the pistons and 102) are such that these racks disengage from the pinion starting from WO 99142174 11 PCT/FR99/00382 the time that the cam (16) opens the clasp. This characteristic makes It possible to bring the component for rotational movement to the end of its stroke without continuing to exert an effort on the two reserves and 22), which have already been completely flattened at the base of the chambers (103 and 104).

In accordance with one particular mode of implementation of the device in accordance with the invention, which is described by way of illustration and not of limitation, the casing (71, 72), as well as the hinges and 82), the clasp the safety lug and the tab are all made from the same piece of injected polypropylene. The component for rotational movement is a clipped button made from "Hostaform" (registered trademark). The pistons (10, and 102) are likewise made from "Hostaform". The envelopes of the reserves and 22) are made of polyethylene of low thickness.

Also in accordance with one particular mode of implementation of the invention, different parameters appearing in the dimensioning of the components that constitute the present invention may be calculated, in such a manner that: o The two reserves (21 and 22) are completely punctured after the displacement of the two pistons (10, and 102) by 2.5 mm, corresponding to one rotation of the component for a rotational movement by 24"; o The transfer of the liquid of the two reserves towards the two reservoirs and 1i) is carried out by continuing the rotation WO 99142174 12 PCT/FR99/00382 from 240 to 215", corresponding to a displacement of the two pistons (10, and 102) by 20 mm; o The casing (71, 72) is opened automatically by the opening cam (16) after a supplementary rotation of o The component for rotational movement is immobilized at the end of a stroke at the position of 270*.

(C 'The invention is not, of course, limited to the modes of implementation that have been described and represented., which have only been presented by way of examples. Thus, the pinion rack mechanism 42, 43) could be replaced by a connecting rod I crank mechanism. It Will be noted, however, that such a mechanism would probably be more expensive to carry out within the framework of an industrial production.

The invention is not limited to the device described, the form of which depends strictly upon that of the electrodes assembly that is described in the patent application.noted above. The technician in this area could easily adapt this device to the filling of reservoirs of electrodes or of electrode assemblies which are formed differently and which are intended for the administration of drugs by passive transdermal means, or assisted by means of ionophoresis.

WO 99/42174 PCTIFR99/00382 Moreover, in accordance with one possible variant, the present invention could serve for the filling of more than two reservoirs; in accordance with another possible variant, the present invention could make it possible to fill the two reservoirs with a solution containing a pharmacologically-active principle, and the other reservoir with a solution ionic without a pharmacologically-active principle, with this ionic solution simply ensuring the conductivity of the electrodes assembly when it is applied to the skin of the patient.

Claims

1. A device for filling at least a first (11) and a second (12) reservoir with at least one liquid containing a pharmacologically-active principle, with these reservoirs being intended for the transdermal administration of the said principle, said device comprising means 41, 42, 43, 102) for simultaneously putting the said fluid into communication with at least the first (11) and second (12) reservoirs, with at least the first (21) and the second (22) reserves, respectively, containing the said liquid, and for concomitantly emptying the said liquid from the 10 reserves (21, 22) towards the said reservoirs (11, 12), characterised in that, the said means comprise a component for rotational movement a which is mechanically linked to at least the first and the a second (102) pistons, in such a manner that a rotation of the said component for rotational movement brings about a rectilinear i 15 displacement of the said pistons (101, 102) and a concomitant emptying of the said liquid of the said reserves (21, 22) towards the said reservoirs (11, 12).

2. A device in accordance with claim 1, characterised in that, the said component for rotational movement and the said pistons 102) are linked by means of a mechanism of the pinion/rack type 42, 43).

3. A device in accordance with the claim 2, characterised in that, the said racks (41, 42) are disengaged from the said pinion (43) when is the said component of rotational movement is at the end of the stroke.

4. A device in accordance with any one of the claims 1 to 3, characterised in that, said device comprises at least the first (103) and second (104) chambers suitable for accommodating the said at least first (21) and second (22) reserves, respectively, with the at least first (101) and second (102) pistons, respectively, being movable within the said at least first chambers in order to flatten (103) and second (104) the said reserves (21, 22) against a base of each of the said chambers and to bring about the puncturing and concomitant emptying of the said reserves (21,22) towards the said reservoirs (11, 12)' A device in accordance with the claim 4, characterised in that, the bases of the said chambers (103, 104) each includes a hollow needle (111, 121; 112, 122) which makes it possible to place the fluid of the said reserves (21, 22) into communication with the said reservoirs (11, 12), and in that, the said hollow needles project into the base of the said chambers (103, 104) in such a manner as to ensure the puncturing of the said reserves during their flattening by means of the said pistons (101, 102)'

6. A device in accordance with any one of the claims 1 to characterised in that, the said reserves (21, 22) are placed in a part (71) of a casing (71, 72) which comprises two parts articulated with one .4 t 1 16 another (71 and 72), between which the said reservoirs (11, 12) are inserted.

7. A device in accordance with the claims 5 and 6, characterised in that, the said hollow needles (111, 121; 112, 122) likewise project, in relation to the part of the said casing (71, 72), in such a manner as to ensure the puncturing of the said reservoirs (11, 12) during the closing of the said casing (71, 72). A device in accordance with one of the claims 6 or 7, characterised in that, the said reservoirs (11, 12) are integrally formed 10 with a bearing plate which is inserted, practically without clearance, between the parts (71 and 72) of the casing (71, 72).

9. A device in accordance with any one of the claims 6 to 8, characterised in that, said device includes a clasp that can be moved between a locked position, where the clasp holds the 15 casing (71, 72) closed, and an unlocked position, where it permits the casing (71, 72) to be opened. A device in accordance with the claim 9, characterised in that, the said component for rotational movement comprises an opening cam (16) which makes it possible to open the said clasp at the end of the loading of the said reservoirs (11, 12).

11. A device in accordance with the claim 10, characterised in that, the said component for rotational movement comprises an opening (19) which makes it possible to reclose the parts (71 and 72) of the 17 said casing (71,72) with the help of the said clasp when the said movement component is at the end of its stroke.

12. A device in accordance with any one of the claims 6 to 11, characterised in that, said device comprises an anti-return mechanism, which is composed of a toothed profile (14) on the said rotational movement component and of an anti-return tab (15) which is integrally formed with the casing (71, 72). a

13. A device in accordance with any one of the claims 6 to 12, ai characterised in that, the said component for rotational movement (3) 10 comprises a receptacle (17) accommodating a breakable safety lug (18) which is integrally formed with the said casing (71, 72), in such a a manner that the said rotational movement component has the oeeo o* a. "effect of breaking the said safety lug (18). :14. A device in accordance with any one of the previous claims, aO.. S" 15 characterised in that, the said reserves (21, 22) each comprise an envelope with an "accordion" type folding. A device in accordance with any one of the previous claims, characterised in that, the said reservoirs (11, 12) are positioned adjacent to the electrodes of a device for the transdermal administration of drugs by means of ionophoresis.

16. A device in accordance with any one of the previous claims, characterised in that, the said reservoirs (11, 12) form a part of a "patch" for the transdermal administration of drugs by passive z diffusion.