WO1999044658A1

WO1999044658A1 - Device for hypodermic injection without needle of a medicine in liquid form

Info

Publication number: WO1999044658A1
Application number: PCT/FR1999/000476
Authority: WO
Inventors: Tino Dalto
Original assignee: Tino Dalto
Priority date: 1998-03-03
Filing date: 1999-03-03
Publication date: 1999-09-10
Also published as: FR2775603A1; FR2775603B1; CA2321906A1; AU3257599A; EP1064036A1

Abstract

The invention concerns a device comprising an injecting head (9) defining a chamber (11) capable of containing a volume of said medicine, the tubular body (10) being closed, at one end, by a transverse wall (12) traversed by microchannels (131, 132) emerging on an external surface of the head (9). At the other end, the body is closed by a mobile plunger (15). Means are provided for filling the chamber (11) and forcing the medicine outside the injecting head (9), through the microchannels (131, 132). The invention is characterised in that the filling means comprise a) means (25) for temporarily closing the microchannels (131, 132) and b) a passage (26) for injecting a medicine into the head (9), said passage being equipped with a non-return valve (32) preventing the medicine from leaking outside the passage at all.

Description

1

DEVICE FOR SUB-SKIN INJECTION WITHOUT THE NEEDLE OF A MEDICAMENT IN LIQUID FORM

The present invention relates to a device for the needleless subcutaneous injection of a drug in liquid form and, more particularly, to such a device of the type which comprises a) an injection head consisting of a tubular body delimiting a chamber capable of containing a volume of said medicament, said tubular body being closed, at one end, by a transverse wall traversed by at least one microchannel opening onto an external face of the head designed to be applied to the skin of a patient and, at the other end, by a piston movable axially ^** in said chamber, b) means for filling the chamber and c) means for acting on said piston to force said medicament out of the injection head, through said microchannels.

A device of this type is known from international patent application WO 95/24176, this request being more particularly centered on the means designed to fill the chamber of the injection head with a volume of the drug to be administered. As shown in Figure 1 of the accompanying drawing, these means essentially comprise an apparatus 1 formed of a tubular cylindrical body 2, furnished with a cartridge 3 filled with medicament, said cartridge being equipped at one end with a piston 4 which can slide in the cartridge 3 under the thrust of an operating rod 5 projecting from one end of the body. At its other end, the cartridge 2 is closed by a cover 6.

The body 2 is closed, at its end opposite the end 5, by a sleeve 7 axially crossed by a hollow needle 8 projecting inside the tubular body 1. In a first position (not shown in FIG. 1), the cartridge 3 is moved away from the tip of this needle 8, which then does not pass through the cover 6. To discharge its content into an injection head 9 mounted on the sleeve 7, the cartridge is pushed towards the needle 8 which pierces this seal to penetrate the cartridge while pressing against the sleeve 7, as shown in FIG. 1. Then applying an axial thrust on the rod 5 - for controlling the piston 4, the contents of the cartridge 3 are emptied into the injection head, through the needle 8.

The filling means described in WO 95/24176 are adapted to an injection head comprising, for discharging its content after filling, a nozzle pierced with a single channel, the medicament being forced through this channel so as to form a jet clean medicine to penetrate under the skin of a patient by its only living force. It is through this single channel that the injection head is filled, the diameter of this channel being ordinarily very small, of the order of a few hundred microns for example. It is understood that this small diameter limits the flow of the drug in the injection head during filling thereof, which can then be long. There is also known a needleless injection head comprising, like the head 9 shown in FIG. 1 of the attached drawing, a tubular body 10 delimiting a chamber 11 suitable for containing a volume of the medicament, this body 10 being closed at one end. by a transverse wall 12 traversed by a plurality of microchannels such as 13ι, 13 ₂ , .... oriented parallel to the axis X of the injection head, these channels opening onto an external face 14 of the head 9 designed for be applied to the skin of a patient to administer the medicament contained in chamber 11. By dispensing thus the drug by means of several microchannels of small diameter, less than 200 μm for example, the pain felt by the patient during administration is reduced. At its other end, the injection head 9 is closed by a piston 15 movable along the axis X in the chamber 11. A propellant mechanism, generally identified 16, can receive the injection head 9 for suddenly driving the piston 15 towards the wall 12 of this head, thereby forcing the liquid contained in the head through the microchannels 13 and the skin of a patient, attached to the external face of this wall, the filling device 1 then being obviously separated from the injection head. The means for filling a single microchannel injection head of the type described in WO 95/24716 cited above are not suitable for ensuring rapid filling of a multiple microchannel head of the type shown in FIG. attached drawing. The object of the present invention is precisely to provide a device for the needleless subcutaneous injection of a medicament in liquid form comprising means for filling an injection head of said medicament which does not have the drawbacks of the the prior art and which, in particular, ensures rapid filling of said head.

This object of the invention is achieved, as well as others which will appear on reading the description which follows, with a device for the subcutaneous injection without needle of a medicament in liquid form of the type described in the preamble of the present description, remarkable in that the means for filling the head of this device comprise means for temporarily closing at least one microchannel for injecting the drug and at least one passage passing through the wall of the injection head and designed to cooperate with a medicament cartridge to allow the filling of the head with a volume of medicament coming from the cartridge, this passage being equipped with a non-return valve means opposing any leakage of said drug out of said head, through said passage.

As will be seen in more detail below, this passage can be dimensioned so as to allow rapid filling of the injection head, contrary to what is observed when one fills this head through the microchannel (s). injection of the drug under the skin of a patient.

Other characteristics and advantages of the present invention will appear on reading the description which follows and on examining the appended drawing in which:

FIGS. 1 and 1A represent an embodiment of the device according to the invention, already partially described in the preamble to this description, and

- Figures 2,2A, and 3 show variants of the injection head fitted to the device according to the invention.

Reference is again made to FIG. 1 of the appended drawing which represents, assembled in line on the X axis, the device 1 for filling an injection head 9 mounted on this device, and the propulsion mechanism 16 with reset. manual designed to actuate the injection head 9 of the device according to the invention during the administration of a medicament contained in this head. It is clear that during this actuation, the filling device 1 must be removed from the head to allow the application thereof, by its external face 14, on the skin of a patient, who is then in the outlet of the microchannels 13i, these can also take the form of microfentes. Similarly, during filling of the head 9 the propellant mechanism 16 is not mounted on this head.

This propellant mechanism 16 provides the injection under the skin of a patient of the drug, previously loaded in the chamber 11 of the head 9 by the filling means according to the present invention which will be described later in detail. The propellant mechanism essentially comprises a cylindrical tubular body 17 in which slides a ram 18 loaded by a spring 19. Balls 20ι, 20 ₂ , ... loaded by springs 21χ, 2l ₂ , ... in a groove dug on the outer surface of the body 10 of the injection head 9, make it possible to removably fix the latter on the propellant mechanism 16. The ram 18 can be locked in a high position, from the point of view of FIG. 1, spaced from the head 9 , by means not shown. Pressing a trigger button 23 releases the ram 18 which, under the pressure of the compressed spring 19, is thrown suddenly towards the piston 15 of the head 10 without compressing the (non-tight) volume of intermediate air 24, to expel constant speed the piston 15 of the head 9 towards the bottom of the latter. The medicament contained in the chamber 11 then exits at constant pressure from the chamber in a sprayed form, and penetrates under the skin of a patient applied against the surface 14 of the head, in place of the device for filling this head shown in Figure 1.

The present invention relates specifically to new means put in place to allow rapid filling of the head 9 with the drug to be administered in spray form.

According to a first embodiment of these means, represented in FIG. 1, these comprise means 25 for temporarily closing the microchannels 13i, a passage 26 passing axially, and in the central position, the wall 12 of the injection head and, between the ends of this passage 26, a housing 27 shaped to receive a tongue 28 (see FIG. 1A) of complementary shape.

Furthermore, the socket 7 mounted on the filling device 1 comprises an axial nozzle 29 which projects from the bottom of this socket to pass through the passage 26 and open into the chamber 11 of the head 9 when the latter is mounted on this socket. to be filled with medicine. The nozzle 29 is, for this purpose, crossed axially by the needle 8.

The microchannels of the head 9 are advantageously distributed symmetrically around the axis of symmetry of this head. By way of illustrative and nonlimiting example only, they may be two or more and have a diameter of 100 to 300 μm, in a ratio of 1/20 to 1/100 with the diameter of the chamber 11. Next a characteristic of the injection head according to the invention, a certain relationship is chosen between the diameter of the microchannels and the diameter of the cylindrical internal chamber 11 containing the liquid solution of the medicament, to guarantee the spraying and not the formation of a painful concentrated spray. This ratio is between 1/20 and 1/100 while remaining imperatively in the linear zone of the propellant mechanism and to maintain a small footprint at the injection head in order to guarantee the possibility of traditional manufacture. It is necessary to keep a kinematic viscosity of less than 3 Centistokes for the liquid to be injected, taking into account the increase in pressure when the liquid is pushed by the piston 15. Good results have been obtained with a chamber 11 8 mm in diameter, and microchannels 200 microns in diameter, ie 0.2 mm, the ratio being 8 / 0.2 = 40. Patent EP 0 367 677 of same applicant describes an injection head in which the liquid to be expelled under pressure passes through obliquely oriented channels forming an angle between them and opening into a rounded concave surface, thus creating turbulence and undergoing additional pressure drops. Contrary to this practice, and according to the invention, it is necessary to pass directly from the internal diameter of the cylindrical chamber to the microchannels without intermediaries to avoid any pressure drop.

According to the invention, the microchannels are no longer oriented to form an angle between them, and must necessarily remain perpendicular on the one hand to the internal face of the chamber 11 and on the other hand to the planar external face 14 of the head d injection which is in contact with the patient's skin, and be strictly parallel to each other.

This characteristic is fundamental because it conditions the perfect regularity of the resulting spraying. Likewise, any defect in perpendicularity would result in poor diffusion against the patient's skin and the sprayed solution would largely escape on the sides of the injection head applied against the skin. The injection of the entire prescribed dose would no longer be guaranteed, as would the effectiveness of the drug for the patient. The microchannels have a length equivalent to 5 to 10 times their diameter to avoid bursting at the time of injection and any risk of injury.

In addition, these same microchannels must be perfectly cylindrical in order to guarantee at their output a perfect quality of spraying, well aligned. That 8

prohibits manufacturing techniques such as certain laser beams (which act like small torches on the material), because the resulting hole will be irregular. Micro-drilling remains the most reliable process to date.

The operations of filling this head with a volume of medicament then operate as follows. The apparatus 1 being separated from the head, an axial pressure is exerted on the operating rod 5 of the piston 4 of the cartridge 3 of medicament placed in the apparatus 1 to bring the seal 6 of this cartridge into contact with the needle 8 which then pierces the cover, as we saw above. The axial movement of the cartridge 3 stops when the cartridge abuts against the sleeve 7. The medicament fills the needle 8 by expelling the air which is there.

The head 9 is then put in place on the sleeve 7 of the filling device 1. The sleeve 7 comprises for this purpose elastic claws 30ι, 30 ₂ , ... which engage with an annular shoulder formed on the head injection 9. The sealing means 25 are installed on the bottom of this socket to close the microchannels 13ι, 13 ₂ while the nozzle 29 passes through the passage 26. Following the displacement of the piston 4 in the empty cartridge the latter in the chamber 11 of the injection head 9. The piston 15 of the latter then passes from an initial position in which it bears on the bottom of the chamber, in contact with the nozzle 29, to a final position defined by the amount of medication received. By proceeding in this way, it is ensured that the chamber 11 contains only the medicament and not furthermore parasitic air. Furthermore, thanks to the sealing means 25, the medicament injected into the chamber 11 cannot come out of it by the microchannels 13ι, 13 ₂ . It is understood that the quantity of medicament injected into the chamber 11 can be adjusted precisely by various known means such as, for example, a micrometric adjustment of the stroke of the piston 4 in the cartridge 3. The head 9 can also be transparent and graduated to this effect.

The head being filled with a metered amount of medicament and the nozzle 29 released from the passage 26, the tongue 28 is inserted, according to the present invention, into the housing 27 so as to prevent the medicament contained in the chamber from coming out by passage 26, now closed by this tab, which thus constitutes a non-return member. In the embodiment shown in FIG. 1 by way of example only, the wall 12 of the head 9 is hollowed out with a transverse passage of cross section conforming, in the plane of the drawing, to that of the tongue 28, this passage constituting the accommodation 27.

It is then possible to disengage the head 9 from the filling device 1 and install it on the propulsor mechanism 16.

If drug losses by capillary action in the microchannels 13ι, 13 ₂ are to be feared, the closure means 25 are maintained on the outer ends of these microchannels. These means can then take the form of a cover made of a peelable adhesive film, pressed on the face 14 of the injection head. In this case, this cover can be put in place before the head filling operations. It is then removed just before the drug is administered. The presence of this seal also responds to hygiene requirements.

According to the present invention, it is the diameter D of the injection needle 8 which now limits the flow of the medicament into the chamber 11 during its 10

loading, and not that of the very fine microchannels 13ι, 13 ₂ , since these are no longer used during this loading, contrary to what described above WO 95/24176. This diameter D can then be chosen so that this loading is made as fast as desired. For example, the diameter D can be of the order of a millimeter, while the diameter of the microchannels 13ι, 13 ₂ is of the order of 100 to 300 μm.

It now appears that the embodiment of the invention shown in FIGS. 1,1A makes it possible to achieve the desired goal. It will be noted, however, that the use of a removable tongue 28, which must be installed in the head after filling thereof, makes this embodiment of use fairly delicate. The use of such a tab can also pose sealing problems during the injection of the medicament, due to the high pressure then prevailing in the chamber 11.

There are shown in Figures 2.2A and 3 variants of this embodiment, adapted to overcome these difficulties. In these figures, reference numerals identical to reference marks used in FIG. 1 correspond to identical or similar elements or members. In the variant of FIG. 2, the tongue 28 of the embodiment of FIG. 1 is replaced by a non-return valve 32 shown in more detail in FIG. 2A where it appears that this valve comprises a central leg 33 and a flexible transverse skirt 34. The central foot is designed to be forced into the passage 26, its skirt 34 being pressed against an internal face of the end wall 12 of the injection head 9, under the pressure of the drug contained in chamber 11. However, this skirt 34 is flexible and capable of being lifted from this internal face under the pressure of the 11

liquid medicament injected by the nozzle 29 projecting axially from the bottom of the sleeve 7, to allow this medicament to enter the chamber 11 during the filling operations of the head 9. For this purpose, the foot 33 carries grooves such as 35ι, 35 ₂ , ... providing between them passage spaces for the medicament around the foot 33, according to a well-known arrangement for this type of valve.

Thus, the medicament, pushed into the needle 8 in the direction of the arrow F by an apparatus of the type of the apparatus represented in FIG. 1, can it pass into the chamber 11 after having passed through the valve 32. Once the chamber 11 filled with a metered amount of the drug to be administered the valve 32 opposes any reflux of the drug through the central passage 26. The microchannels 13 _! , 13 ₂ are moreover closed by means 25 similar to those described in connection with FIG. 2.

This variant makes it possible to speed up the filling operations and possibly facilitate their automation, because they suppress the operation of inserting the tongue 28 of the embodiment of FIGS. 1,1A, after the filling of the chamber 11. We know moreover make flap valves having the required tightness at high pressures prevailing in the chamber 11 of the head 9 during the injection of the medicament.

In the variant of Figure 3, the valve 32, identical to that which equips the variant of Figure 2, is introduced into a passage 26 'pierced, not in the bottom 12 of the head 7, but along the axis of the piston 15.

The nozzle 29 is then modified in order to be able to hang on to the piston 15 during the filling operations. It is, for this purpose, provided with a ring of elastic claws 36ι, 36 ₂ , ... adapted to hang, removably, to a groove dug in a housing 12

annular 37 of the piston 15. In this position, the nozzle 29 can deliver a volume of medicament which enters the chamber 11 by a mechanism similar to that described in connection with FIGS. 2,2A. A plug 38 fitted with shutter means 25 is then applied against the face 14 of the head 9.

The variant of FIG. 3 makes it possible to simplify the structure of the wall of the head 9, the arrangements necessary for the reception of the non-return valve being transferred to the piston 15.

It is clear that the embodiment of Figure 1, like the variants of Figures 2 and 3, allow both manual loading of the drug into the injection head, just before administration of the drug to a patient, as automatic loading at the factory, the heads being delivered ready for use. It also appears that the variants of FIGS. 2 and 3 are better suited to rapid loading of the injection heads than the embodiment of FIG. 1, for the reasons indicated above.

Of course, the invention is not limited to the embodiments described and shown which have been given only by way of example. Thus, the invention, although described in its application to an injection head comprising a plurality of microchannels, is obviously applicable to an injection head comprising only one microchannel for injecting the drug. Also, non-return valves other than those described above, ball valves for example, could be used. It is thus also that one could substitute for the tongue 28 of FIG. 1 a tongue made of a self-healing material. This tab is permanently installed on the head, before the implementation of the filling operations of this head. When mounting the head on the 13

filling, a needle of the type of needle 8 pierces the self-healing tongue to allow a flow of drug in the head. When the head of this device is removed, the needle is withdrawn from the tongue which "heals" automatically, preventing any backflow of the liquid. By suitably shaping this tongue, it is possible to ensure that the strong pressure exerted by the drug on the scar of the tongue, during the administration of the drug, does not reopen the scar, but, on the contrary, reinforces its closure.

Also, the cartridge can be replaced by a bottle containing the liquid medicine or by any other packaging, the sleeve 7 then being adapted accordingly. For automatic filling in the factory, an appropriate automation makes this repetitive operation at a high rate in order to obtain injection heads preloaded at predetermined dose and delivered in sterile packaging. It is also possible to control by transparency the volume of medicament entering the internal chamber 11 if the injection head 9 is transparent and graduated like a syringe. This simplifies its filling. In a disposable version for single use, a molded injectable material is used to make this head. In a non-disposable version, the head can be made of steel and sterilized before use. The valve remains disposable and interchangeable. According to another characteristic of the invention, in certain applications encountered in particular in the particular and specific field of vaccination, the total passage through the skin is no longer sought.

In this case, it is necessary to carry out a very superficial injection on the surface of the 14

skin, like "scarification". To do this, it suffices to replace the microchannels 13 with microfentes, the characteristics of which are within the following tolerances, depending on the product used and its kinematic viscosity, also less than 3 Centistokes, as well as the desired effect, the pressure is always constant. As an indication, a microfente can have a width of between 10 μ and 500 μ, a length of between 100 μ and 5000 μ and a depth of between 100 μ and 5000 μ.

Claims

15 CLAIMS

1. Device for the needleless subcutaneous injection of a drug in liquid form of the type which comprises a) an injection head (9) consisting of a tubular body (10) delimiting a chamber (11) suitable for containing a volume of said medicament, said tubular body being closed at one end by a transverse wall (12) traversed by at least one microchannel (13 !, 132) opening onto — an external face of the head (9) designed to be applied to the skin of a patient and, at the other end, by a piston (15) movable axially in said chamber, b) means for filling the chamber and c) means (16) for acting on said piston (15) to force said medicament out of the injection head (9), through said microchannel (13χ, 13 ₂ ), this device being characterized in that said filling means comprise bi) means (25) for temporary sealing of said microchannel and, b ₂ ) at least one passage (26) passing through said injection head ction (9) and designed to cooperate with a cartridge (3) of medicament to authorize the filling of said head (9) with a volume of medicament coming from the cartridge (3), this passage being equipped with a check valve means -back (28; 32) opposing any leakage of said medicament from said head (9), through said passage (26).

2. Device according to claim 1, characterized in that said non-return valve means consists of a tongue (28) arranged so as to close off said passage (26), said tongue being installed in the passage (26) after filling said chamber (11) of the injection head (9).

3. Device according to claim 1, characterized in that said non-return valve means (32) comprises a central foot (33) inserted by force into the passage (26) by providing passage spaces between 16

said foot and the wall of said passage (26), and a skirt (34) extending transversely to the axis of said foot (33), said skirt (34) being flexible so as to be movable between a position where it closes said passage (26) under the pressure of the medicament contained in the chamber (11) and another position in which it opens said passage (26) under the pressure of the medicament entering this chamber, during filling of the latter.

4. Device according to any one of claims 2 and 3, characterized in that said passage (26) is drilled in said end wall (12) (12) of the injection head.

5. Device according to any one of claims 2 and 3, characterized in that said passage (26 ') is pierced in said piston (15) movable in said chamber (11) of said injection head (9).

6. Device according to any one of claims 1 to 5, characterized in that said sealing means (25) consist of a peelable adhesive cover applied against the external face (14) of the head (9) where opens one end of said microchannel (13ι, 13 ₂ ).

7. Device according to claim 1, characterized in that said non-return valve means is constituted by a ball valve.

8. Device according to claim 1, characterized in that said non-return valve means consists of a tongue made of a material pierceable by a needle forming part of the filling means for injecting said medicament into the chamber (11), said material being self-healing upon removal of said needle.

9. Device according to any one of claims 1 to 8, characterized in that it comprises a plurality of microchannels (13ι, 13 ₂ ). 17

10 Device according to any one of claims 1 to 9, characterized in that it comprises a propellant mechanism (16) for pushing the medicament out of the injection head (9) by acting on the piston (15), said mechanism working in a linear range of use to guarantee constant pressure and spraying of the drug by the microchannels (13ι, 13 ₂ ).

11. removable injection head forming part of the device according to any one of claims

1 to 10.

12. Head according to claim 11, characterized in that said microchannels (13ι, 13 ₂ ) have a diameter of 100 to 300 μm, in a ratio of 1/20 to 1/100 with the diameter of the chamber (11) .

13. Head according to claim 12, characterized in that it is filled with a medicament in liquid form with kinematic viscosity of less than approximately 3 Centistokes, to guarantee good spraying.

14. Head according to any one of claims 11 to 13, characterized in that the internal and external faces (14) of the wall (12) through which the microchannels (13χ, 13 ₂ ) are parallel.

15. Head according to claim 14, characterized in that the diameter of the microchannels (13ι, 13 ₂ ) is constant, throughout the crossing of the wall (12).

16. Head according to any one of claims 14 and 15, characterized in that the axes of the microchannels (13ι, 13 ₂ ) are perpendicular to the internal and external faces of the wall (12).

17. Head according to any one of claims 14 to 16, characterized in that the external face (14) of the wall (12) is perfectly flat. 18

18. Head according to any one of claims 11 to 17, characterized in that the microchannels (13ι, 13 ₂ ) are perfectly cylindrical.

19. Head according to any one of claims 11 to 18, characterized in that the microchannels (13χ, 13 ₂ ) have a length of 5 to 10 times, approximately, greater than their diameter.

20. Head according to any one of claims 11-to 19, characterized in that the axes of the microchannels (13ι, 13 ₂ ) are parallel to that of the chamber (11).

21. Head according to any one of claims 11 to 20, characterized in that the parts which constitute it are produced by injection molding.

22. Head according to any one of claims 11 to 21, characterized in that the microchannels (13χ, 13 ₂ ) take the form of microfentes of width, length and depth chosen, respectively, in the areas from 10 to 500 μm , 100 to 5000 μm and 100 to 5000 μm.