AU761828B2 - Hypodermic injection system - Google Patents

Description

Y

AUSTRALIA

PATENTS ACT 1990 DIVISIONAL APPLICATION NAME OF APPLICANT(S): Roche Diagnostics GmbH ADDRESS FOR SERVICE: DAVIES COLLISON CAVE Patent Attorneys 1 Little Collins Street Melbourne, 3000.

INVENTION TITLE: "Hypodermic injection system" The following statement is a full description of this invention, including the best method of performing it known to us: Q\OPER\ArI\2404214 094 Div.doc 9/4/01 P:OPER\RSH\24(M214div.doc-04A 4MI1 -1- Hypodermic Injection System This invention is in the field of the injection of liquid into tissue by generating a high pressure jet capable of passing through the skin.

In the field of medicine there are numerous methods for the targeted dispensing of medicines. Forms of medicine administration such as tablets, dragees, creams, and similar are all known. For a plurality of active ingredients such forms of administration are unsuitable because the physiologically active ingredient degrades before they can become active. In tablets which must be taken orally, the medicament, for example has to be constructed such that it is resistant to aggressive stomach acids and on the other hand can 2 be resorbed by the stomach or the intestinal wall into the blood circulation. For a large number of medicines it is not possible to develop a patient-friendiy form of adminstration such as a tablet or a dragee. In such cases it is therefore necessary to introduce the medicine directly into body tissue or into the vascular blood system. Today it is usual practice that the injection occurs using a synnge. In the prior art however injection devices have been known for a long time which can be operated without using a hollow needle which is uncomfortable for the patient. Injection systems without a hollow needle employ a jet of liquid which is ejected at high velocity from an orifice and is capable of penetrating through skin and tissue. Such an injection is significantly less painful and can be performed by personnel who have not been trained in the use of syringes.

Injection systems employing a pressurized liquid jet of medication which penetrates the skin o are called hypodermic injection systems within this application Hypodermic injection is meant to include intra-dermal, subcutaneous and intra-muscular injections.

With an injection system in accordance with a preferred embodiment of the invention, all medicines available in liquid form can be injected. The field of application covers for example painkillers (analgesics), insulin and also protein solutions. For protein solutions, especially solutions of human protein, remarkably it has been discovered that they can be administered substantially without any degradation by way of a high pressure jet.

Needle-free injection systems were described in the 50s and 60s. In US patents 2.322,244 and 3,335,722 devices have been described, which use explosive substances for the generation of the necessary high pressure jet. Present-day systems, such as for example Vitajet® of the company Vitajet Corporation, employ a steel spring for the generation of the high pressure jet. A device which operates in an analogous manner is also marketed by Mediject Corporation. Such systems have the disadvantage that the user has to perform several awkward operational steps. First of all, the liquid to be injected is introduced into the injection device. Thereafter a steel spring is loaded by the rotation of device parts against each other. Especially for persons, who are ill or like many diabetics who are physically disabled, the necessary operational steps requires the application of enormous effort. An alternative to this system is offered by the aforementioned injection systems using explosives, because the energy from the explosive substance is used and a complicated loading of the spring is not necessary. The turning away from such systems which has taken 3 place in the course of time is directly related to severe disadvantages with respect to hygiene and technical-safety aspects. US-3,335,722 reveals, that cross-contamination of explosives and medicines are a particular problem of such constructions. In the US patent an arrangement is suggested, in which capsules containing the medicine and the explosive substance are separated from each other and a special arrangement for the transfer of energy is employed. In the arrangement described an explosive is ignited by a contacting rod, as is the case, for example, with a rifle bullet. The gas resulting from the explosion accelerates a piston which is mechanically linked to a second piston which accelerates a rubber stopper which in turn forces a medicinal liquid out of the orifice on the opposite side. To prevent cross-contamination of combustion gases and medicine, complicated technical constructions are necessary which disadvantageously complicate the injection device and make it more expensive. Furthermore an ampule is required into which a rubber stopper is pushed.

Because of the pressure in the ampule created by the movement of the stopper, it is necessary to make arrangements to ensure prevention of leaks between the ampule and the stopper. In this respect the choice of material for the ampule is critical. because a deformation when pressure is applied must not lead to leaks in the region of the stopper.

The devices described in the prior art all exhibit generally the disadvantage that for the generation of pressure parts which can be compressed together, stoppers are employed and therefore sealing areas have to be controlled.

It is also proposed to provide devices for a needle-free injection of liquids which avoid stoppers or the like. European patent application 0 370 571 describes a system where an ampule which contains a liquid medication is being mechanically compressed by a rod.

This compression drives the liquid medication through one or more orifices to generate a liquid jet. While this apparatus mostly avoids the problems associated with frictional surfaces and stoppers moving in a cylinder this apparatus has a drawback that the flexible part of the ampule may be destroyed when pressed by the rod. A further drawback of this device is that the pressures which can be applied to the ampule are limited due to the risk of "destruction and also by the relatively low energy stored in a spring. Another disadvantage of this apparatus is that a mechanical compression of the ampule by a rod cannot guarantee that the liquid within the ampule is being ejected totally. Such a device is therefore insufficient when it is desired to inject a specific amount of medication.

P:\OPER\Arl35126OI sp.doc-27/02/03 -4- In FR-1.121.237 there is described a device for the hypodermic injection of liquids using a high pressurized liquid jet. The device comprises a compressible container for liquid medication which is attached to a unit having a fluid channel. The unit with the fluid channel is connected to a unit with a nozzle so that a continuous channel is being formed through which the liquid medication can be expelled. For a hypodermic injection the unit with the channel is placed on a mounting element so that the medication container is surrounded by a chamber and pressure is applied to said chamber by ignition of an explosive. The apparatus described in FR-1.121.237 teaches that the medication container and the unit with the channel are combined by the user. The user fills the liquid to be injected into the medication container and tightly closes the medication container by screwing on the unit with the fluid channel.

Such a process is not only cumbersome but it also bears the risk that the medication and/or the fluid channel is contaminated The injection of a contaminated medical fluid is totally unacceptable in the therapeutic field. This problem of contamination is mostly unresolved in the prior an of hypodermic liquid injection. Furthermore the FR-1.121.237 does not give any information regarding the pressure of the liquid jet and how this pressure can be controlled to be in a specific range or how the pressure can be changed by the user to comply with his specific needs. A further drawback of the system described in FR-1 121.237 is that no means for purging air from the liquid chamber are described.

'However, air within the liquid chamber leads to disadvantageous effects as described further below Reference GB-697,643 describes a device for hypodermic injections using a flexible or collapsible element which is being compressed. The device described in this document is very complicated and uses a recheargable pressure chamber into which a pressurized gas is introduced and in addition thereto a chamber with a hydraulic fluid is employed. With this device it is possible to control the pressure by which the liquid is being expelled from the container. However, a flexible container is needed into which the collapsible medication container is being introduced. From the function of this device it must be assumed that it is impossible to expel all of the fluid which is within the medication container. The document GB-697,643 further discloses a medication container which is sealed and can be used to store a medication under sterile conditions. However, this document does not disclose a medication container including a sterile nozzle. Therefore this document does not give an overall solution to the object of sterile injection.

US-3,308,818 proposes a device for hypodermic injections. A flexible medication container is being placed in a chamber and pressure is.

being applied to this chamber by an explosive to compress the medication container. While being compressed the medication container ruptures at the entrance of a fluid channel which ends in an orifice. The fluid is-then expelled from said flexible containers through the fluid channel and is being injected into a human or an animal. This very simple device has a number of drawbacks compared to the present invention. US- 3,308,818 does not describe how to control the pressure generated by the explosive.

Furthermore the device uses an area into which the wall of the flexible container ruptures when it is pressurized. The drawback of such an uncontrolled rupture is that small particles may be torn away from the flexible container which are introduced together with the liquid medication into the body. The injection of such particles may cause inflammations or allergic reactions. Another drawback of the system described in US-3.308,818 is that the fluid channel and the nozzle through which the medication is expelled are not kept under sterile conditions. Injections with such a device therefore may lead,to infections or inflammations.

*o In general it has been proposed to pressurize a flexible medication container to expel a liquid jet which is able to penetrate the skin. However, even if this concept has been known for a long time no system is available on the market which uses this concept. This shows that there are still technical roadblocks which have to be overcome e *g oo' *o P:\OPER\Arl\35126-0 1sp.doc-27/02/03 According the present invention, there is provided a handling unit for use in a hypodermic injection system, said handling unit comprising: a first shell having an explosion chamber and an explosive therein; a second shell having a piercing needle disposed therein, the piercing needle having a piercing end; and a medication unit having a concave portion, the medication unit being sandwiched between the first shell and the second shell, the concave portion being arranged adjacent to the piercing end of the needle so that when pressure is applied to the medication unit by an explosion in the first shell, the medication unit generates a flexing deformation of its concave portion that leads to the piercing needle piercing the medication unit.

The object of a preferred embodiment of the present invention is to provide an economically feasible but nevertheless reliable device for the needle-free injection of liquids. In particular, it is the object of the preferred embodiment of the invention to exclude with certainty the cross-contamination of explosion gas and medicine by use of simple means. Furthermore, it is the object of the preferred embodiment of the present invention to provide an injection device which can be operated by the user with a minimum of inconvenience and which is also of simple construction as well as 20 economically feasible. This preferred embodiment of the invention proposes handling unit which avoids contamination of a liquid medication prior to penetration of the skin.

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*oo$ *oo o*o* *o *o *ooo •go *ooo P:'OPER\UrI\35126-01 spe.doc-27/02/03 -6- In the handling unit of a preferred embodiment of the present invention, frictional surfaces and sealing surfaces between moving parts of a medication container are avoided. Instead of these a medication unit is used which possesses a concave region which is flexible and can therefore be deformed. The handling unit has also a second shell with an orifice through which liquid medication can escape from the medication unit when the concave region of the medication unit is deformed. The use of such a medication unit has the advantage that parts are avoided which have to be slid against each other, and sealing surfaces between these parts are avoided. To facilitate the squeezing or pressing together of the medication unit, the medication unit is sandwiched between the first and second shell such that a pressure change in the first shell leads to a deformation of the flexible concave region. This results in the medication unit being pierced by the needle so that liquid is forced out of the orifice.

The medication unit is preferably made of materials which can easily be deformed, such as plastics or metal foils.

ooo 0 o• o0o 20000 0000e 0000 P:OPER\Arl\35126-01 spe.doc-27/02/03 -7- In the embodiments described above, shearing and severe stretching of the wall material in the first shell of the handling unit are virtually completely avoided. Therefore usually the wall material may have modest mechanical properties, since it must only withstand low stresses. Plastics such as polyethylene, polypropylene or PVC are for example suitable, whereby the wall thickness of less than a millimeter can be realized. Particularly suitable wall thicknesses are in the region of 100 to 600 Am. Metal foils having a thickness in the range named-above can also be employed.

The handling unit has a second shell in which an orifice for the expulsion bf liquid is located. For this purpose, the piercing needle is situated in the side of the second shell which leads to the exiting orifice. The second shell is furthermore mechanically stable to such an extent that no significant deformation occurs as a result of the pressure which develops in the first container. Alternatively,-if the deformation is predictable, it can be allowed for in the design. A suitable geometrical arrangement should prevent the deformation of the exiting orifice However, even such a deformation can be allowed for if considered in the design. A suitable diameter of the orifice is known to those skilled in the an from the prior an. When explosive substances are used, extremely high pressures can be generated such that smaller openings in the region of 80 to 130 pm are feasible. These openings of the exiting orifice are smaller than those of the prior an and the injection is less 20 painful. There are no special requirements with respect to the geometrical form of the exit channel and the exit orifice. Advantaaeous is however a form in which the liquid jet is focussed. Particularly useful types of medication units including advantageous orifices are described further below.

@o P:OPERri\35126-01 spe.doc-27/0203 -8- For reasons of hygiene it is necessary to close the exit orifice to prevent liquid escaping and a contamination of the liquid in the first container. Preferably such a closure is realized by a knob/peg or the like which is connected to the second region by a predetermined breaking point. Furthermore, screw caps, lids and so on can serve this purpose.

The first and second shells of the handling unit are advantageously formed as a single unit which, however, can comprise two or more pieces. The handling unit can in particular be fabricated as one unit, similar to the designs known for eye-drop ampules. First of all, the second shell containing the exit channel is formed in an injection moulding process to which an open plastic jacket connects which later takes the form of the second shell.

Liquid is filled into the plastic jacket and the opening is sealed by welding the jacket material.

A preferred embodiment of the invention is advantageously constructed such that deformation only occurs in the first shell and no deformation of the second shell occurs.

Similarly the transition region from the first to the second shell should also, as far as is possible, undergo little deformation.

S: The handling unit of the present invention usually employs medication units suitable for hypodermic injection. Such medication units have to comply with some specific needs: 0oo* o*o• oo.o.

o*o• P:'OPER\Arl\35126-01 pe.doc-27/02/03 -9- They have to assure that the medication injected into the body does not come into contact with insterile parts of the medication unit or the injection system prior to entering the skin.

Another requirement is to avoid substantial amounts of air or gas in the medication unit. It is expected that most of the air will escape between nozzle and skin during injection but air might be carried beneath the skin if the nozzle is tightly pressed against the skin surface.

Additionally gas or air within the medication unit may cause interruptions in the jet stream and fluid motions perpendicular to the stream direction which can lead to incomplete injections or disadvantageous jet profiles. Furthermore the medication unit has to assure that the medication can be injected as completely as possible to control the amount of medication delivered to the user. It is a further requirement for the medication containers that they are made from a material that does not affect the medication even if the medication is stored for a time of months or years.

It has shown to be of particular advantage to produce the medication units with the so called blow-fill-seal process. This process leads to medication units enclosing only very little gas. The blow-fill-seal process comprises generally the following steps: a tube of softened plastic is closed at its lower end by compression.

pressure is generated within the tube to press the softened plasic against the walls of a mold to form an open ended container, liquid medication is filled into the open ended container, the opening of the container is closed by compression and welding with ultrasound o or heated pinchers).

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oo o The before described process is well known in the art and for example described in more detail in,,Plastic Mold Engineering Handbook" 4th ed., pp 540-545, Van Nostrand Reinhold, New York (1987) and DE 4439231.

Complete, bubble-free filling of containers produced by the standard blow-fill-seal process is not possible because the seal of the upper end of the container has to be made in a dry area to form a reliable weld. Therefore a headspace volume must be left empty. This results in an air bubble within the container. Within most applications such an air bubble is of no consequence as e.g. in case of eyedrop containers. However, air bubbles are unwanted within medication containers for hypodermic injections as explained before. The present invention therefore discloses new processes for the production of medication units for hypodermic injectors which avoid air bubbles in the medication unit.

A blow-fill-seal process which avoids gas within the medication units is described with reference to figure 3. This figure shows a vacuum approach to remove a headspace filled with gas. An open ended medication container (101) produced by conventional blow-fillseal process was filled with medication (102). The container still has an opening (104) and a headspace (103) beneath. This medication container is placed in a chamber which can be evacuated. The chamber (105) shown in figure 11 has two halves and a seal (106) to form a gas tight sealing between these halves. When the chamber is closed a vacuum pump can be connected to the chamber by a channel (109) communicating with the interior of the chamber (see figure 3A). Fortunately a hard vacuum is not needed to avoid a headspace It has been shown that pressures of less than 0.025 atmospheres are sufficient to avoid bubbles.

After evacuation the medication container is closed by pinching the container opening as shown in figure 3B. Advantageously the closing process can be performed by heated sealing tools (110) to form an air tight sealing (111). When the container is sealed and the vacuum in the chamber is released the chamber can be opened (figure 3C). Atmospheric Spressure acts on the container walls so that the headspace is filled with liquid.

Within this concept it has shown that some liquids tend to foam when a vacuum is applied due to gas physically absorbed in the liquid. Such a foaming is disadvantageous since liquid is pushed up and wets the closing area of the container. It is therefore advantageous to de- P:PERArl\35126-01 spe.doc-27/02/03 11 aerate the liquid by evacuation, warming up or other processes prior to filling them into the medication unit.

Within the scope of a preferred embodiment of the present invention there is also contemplated to avoid the headspace by the following processes: Prior to sealing the headspace of the medication unit is filled with carbon dioxide gas.

After sealing the carbon dioxide is readily absorbed by the liquid.

The headspace is filled with gas of substances boiling between 35 and 85 degree celsius.

After the sealing process these gases condense and the free headspace vanishes.

Particularly useful substances are ethanol and ethyl-ether.

The headspace is filled with water steam which condenses after the sealing process The sealing process is made within an inert gas atmosphere as e.g. helium, methane or nitrogen. Preferred are small molecules which readily diffuse through the material ot the medication container. After closing the container in the inert gas atmosphere the container is introduced into a vacuum to eliminate the gas from the headspace by diffusion.

o* Preferred embodiments of the present invention are directed to handling units which are particularly suitable for hypodermic injections.

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P:)PER\Arl\35126-01 pe.do-27/02/03 -12- A preferred embodiment of the invention may include an activatable gas generator. Possible gas generators are for example explosive substances such as black powder, nitrocellulose, pentaerythrittetranitrate and the like. Of particular advantage are explosive substances which do not contain heavy metals such as lead or mercury, thereby avoiding environmental pollution because such substances nearly completely degrade to carbon dioxide nitrogen and water upon explosion. Nitrocellulose, a propellant which is preferred for the embodiment produces substantial amounts of non-condensable gases, but no solid salt residues. Other propellants produce water vapour, which is condensable, and salt residues.

The explosion or kinetics of combustion can be controlled by selection of the explosive substance and its geometrical form. In the context of this preferred embodiment of the present invention it is advantageous when the explosive substance does not combust in an explosive manner, i.e.

the pressure wave generated by the combustion has a velocity less than the speed of sound.

It is particularly favorable when the total combustion of the explosive substance lies in the time period of 10to 20 msec. To achieve this, the explosive substance is usually highly compressed to slow down the progression of the zone of incandescence. A further factor which influences the kinetics of the increase in pressure is the size of the hollow in the second container, which prior to the activation of the gas generator is filled with gas or air.

The larger the space for gas, the slower the build up of pressure.

POPERWR3\3S 26-01 sp.do-27/0203 -13- Other devices can serve as gas generators which are suitable for the build up of pressure in the second container. Such a device can for example be a further container with extremely compressed gas or gas which was liquefied under pressure (such as for example CO 2 in a pressure vessel). Compressed gas which can be filled on-site, such as for example is known in the case of CO 2 cartridges for siphons or the gas can be compressed by the user himself as in the case in commercially available hypodermic injection systems.

In systems which operate using compressed gas filled on-site, the release can occur for example by the piercing of a seal in the pressurized container. Such a process is for example also used in CO 2 -siphons in which a CO 2 canister is screwed onto a sharp hollow needle whereby in so doing a metal foil in the CO 2 canister is ruptured allowing the CO 2 gas to flow out through the hollow needle. However, CO 2 -driven systems without pressure transformation are generally not suitable within preferred embodiments of the present invention. But there are known concepts to multiply the pressure e.g. with a large piston driven by CO 2 pressure which is connected to a small piston generating a higher pressure.

Furthermore the gas generation can result from the rapid evaporation of a liquid for example by use of an electrical heating spiral or by the electrical degradation (electrolysis) of a substance (usually a liquid) to a gas. An example of the latter process is the electrolysis of an aqueous solution yielding gaseous products, usually hydrogen and oxygen.

Furthermore, chemical processes for the generation of gas can be employed, for example the reaction of fine aluminum with sodium hydroxide solution, thereby liberating hydrogen.

A hypodermic injection system possesses an exiting orifice, through which liquid from the medication unit can escape. Preferably, the exiting orifice which is-part of the medication unit serves as a nozzle through which a liquid stream/jet can be injected directly through the skin. Embodiments are also possible in which the exiting orifice leads into a nozzle, through which liquid is ejected. This is for example possible when the medication unit and its second region in which the exiting orifice is located forces against a unit in which the nozzle is located such that exiting orifice and nozzle create a continuous channel. It is, however, 14 preferred to employ medication containers which are directly in fluid communication with a nozzle. The injection of the liquid can occur via an exiting orifice or via a nozzle. The term nozzle implies simply that the channel through which the liquid exits the first container has a form which, by virtue of its geometry, can control the flow of liquid. Liquid penetration to deeper tissue layers may be achieved by focussing the jet, and the generation of a diffuse jet results in an injection reaching upper tissue layers.

However, penetration depth can be controlled by the jet pressure and the orifice diameter.

Larger jets penetrate deeper at a given pressure, since they remain coherent longer before bereaking up. It has been discovered to be of importance that the nozzle or the exiting orifice is positioned close to the surface of the skin. If the distance is too large, the momentum of the liquid decreases and the jet cannot pentrate the skin. Providing the liquid jet is focusssed by the nozzle or the exiting orifice, a distance of several millimeters between the skin surface and the exiting orifice can be tolerated.

In cases in which the liquid leads to undesirable irritation of the surrounding tissue at higher concentrations, two or more exiting orifices instead of only one orifice can be provided through which the liquid to be injected may pass. Such means achieve the distribution of liquid over a larger area of tissue and local concentrations can be kept at a lower level.

Devices known in the prior art which operate using a steel spring or a compressed gas have the disadvantage that the pressure which can be generated by such means is relatively low and as such nozzles have to be employed which have a diameter between 130 and 200 m.

In the preferred embodiment of the invention which makes use of explosive substances. in contrast much higher pressures can be generated such that nozzles with a diameter of less than 130 pmn may be employed for these purposes at hand. Nozzles or exiting orifices having a diameter of between 80 rpm and 130 pm are favorable because very efficient injections using nozzles in this size range can be performed. Particular preferred are nozzle sizes in the range of 80 to 100 pm.

A particular advantage of a preferred embodiment of the invention is that the system of injection can be fashioned in a very compact and user-friendly manner. This is on the one hand because of the fact that when using explosive substances as a gas generator the space required for the gas generator is very small and also the means for the activation of the gas generator can be of very simple design. Furthermore, it is possible using the system to make disposable P:AOPERArW35126-01 spe.doc-27/02/03 modules commercially available, which consist of a medication unit, a surrounding container (which provides an explosion chamber) as well as a gas generator located within the surrounding container. Such a disposable module has only to be inserted in a handling facility, which contains an activator for the gas generator. It is even possible to provide a disposable injection system which in addition comprises a device for the activation of a gas generator. Such a system can for example be realized using an explosive substance as a generator, whereby the explosive substance is made to explode by the action of a friction igniter. Advantageously, the activation of the gas generator can occur using a piezo igniter such as for example is known for fire lighters.

The advantage stated previously, namely the possibility of making disposable modules commercially available is particularly justified due to the fact that the gas generator can be integrated into the module whereas in systems described in the pnor art the gas generator has to be integrated into the handling unit. Particularly suitable as gas generators for such a disposable module are those in which the energy is stored in a potential form and does not have to be generated by the user himself for example by virtue of his loading of a spring.

Particularly preferred are explosive substances as gas generators.

S* oo* P:'OPER\ArI3512-01 spe.doc-27/0203 -16- Preferred embodiments of the invention are described in more detail, by way of example only, with reference to the following figures: Figure 1 Injection system with a medication unit having a membrane and a surrounding container (prior to injection procedure) Figure 2 As in Figure 1 after the injection process Figure 3 Blow fill seal process under vacuum Figure 4 Handling unit Figure 5 Medication unit A preferred embodiment of the invention is illustrated in Figures 1 and 2. These figures show a disposable module which comprises a medication unit, a surrounding vessel and a gas generator.

e ee* (I I P:OPER\Ar35126-01 spe.doc-27/02/03 17 Between the reservoir (20) and the explosion chamber a primary membrane (23) is located, which by activation of the gas generator is locomoted from the position illustrated in Figure 1 to the position illustrated in Figure 2. The membrane (23) cari.be fabricated from a plastic such as polyethylene or also from a metal foil such as aluminum. In this embodiment of the-invention, components which can be slid against each other and the associated sealing problems are avoided. In Figures 1 and 2 moreover, a secondary membrane is illustrated which can be employed to advantage. After activation of the gas generator, the first membrane (23) is moved in the direction of the nozzle (25) and compresses the liquid contained in the first container whereby the secondary membrane (24) is forced in the direction of the-nozzle.(25) and whereby it is pierced by a hollow needle (33) which points in the direction of the first container. After piercing of the secondary membrane the liquid located in the first container is forced through the nozzle. Figures 1 and 2 furthermore show an air ent (31) which allows air to escape from the space (32) when the secondary membrane (24) is forced against the hollow needle The air vent (31) comprises an annular space around the hollow needle which is connected to bores in a second molded part (27) and clasp The air vent (31) avoids that a pressure is build up in the space (32) when the secondary membrane is moved. The air vent (31) is advantageous to improve the-seal between secondary membrane (24) and hollow needle (33) after piercing. The embodiment illustrated in Figures 1 and 2 has a first and a second shell (26,27) which are held together by a.clasp The primary and secondary membranes are clamped between the shells. The first preformed part (26) has a recess in which a shell (29) made from an electrically insulating material (29) is located which is penetrated by an electrical contact The first shell is fabricated preferably from an electrically conducting material such that the application of an electrical potential between first shell (26) and the electrical contact (30) gives rise to the ignition of an Sexplosive substance contained in the explosion chamber If the explosive substance is suitably selected, the hot wire or the like can be disposed of. Such explosive substances usually contain a finely divided metal such as for example aluminum by virtue of which a certain electrical conductivity of the explosive substance is achieved.

*ooo *.ooo- P:V'PERArl\35126-01 spdoc.27/02/03 18- Figure 4 shows a handling unit (150) loaded with a corresponding medication unit (151).

Figure 4A is a cross sectional planar view and figure 4B a perspective drawing of a cutted handling unit.

In this embodiment the medication container (151) is sandwiched between a first shell (152) and a second shell (153) which are fixed together. Within the shown embodiment the second shell (153) has an extending portion closely surrounding the lower shell.

However *oo s* So oo -19other fixations of the shells together are within the skill of an artisan in this field. The second shell further has a recess adapted to receive a medication unit. The first shell (152) contains an explosive (154) which can be ignited and then creates pressure within the explosion chamber (155). The embodiment shown in figure 13 does not have a wall to close the explosion chamber against the surrounding because this handling unit is designed to be placed in an injection system which provides a closing wall. However, handling units where a closing wall belonging to the handling unit shell is present are also in the scope of this invention. The second shell has a needle (156) inserted therein which serves as nozzle. The needle has a pointed tip at its first end facing into the handling unit to pierce the medication container. The second end of the needle points out of the upper shell so that it can be directed to a body surface where injection is desired. The handling unit further has a tab (157) connected to the second shell (153) via a predetermined.breaking area (158). Within the tab (157) there is located a plate (159) overlaying the needle. This plate facilitates the production process of the handling unit.

An important aspect of the embodiment is the medication unit (151) which is shown in more detail in figure 5. Figure 5A shows a cross sectional view whereas figure 5B is a perspective view. The medication unit (151) is made from a first segment (170) and a second segment (171) which are connected to one another so that a closed cavity for holding liquid medication therein is being formed. The two segments are preferably made fromi plastics. Particularly advantageous are polyethylene and polypropylene because ot their inert behaviour against most types of medication. The segments can be produced by e.g. injection molding. The two segments can be glued, welded or melted together. Welding and melting are preferred because no glues are necessary which could adversly affect the medication. Figure 5 shows a thickened portion (174) which annularly surrounds the medication cavity like a saturn ring. It has proven advantageous to use an additional amount of material in this region to ensure that the two segments can be readily welded together.

The second segment (171) has a concave portion (173) in the region where piercing of the :medication unit occurs. The first segment (170) has a convex portion (172) which prevent s piercing of this segment by the needle. For reasons of clarity figure 5 also shows the needle 1i'" (156) located beneath the second segment (171) which is pierced. When pressure is generated in the explosion chamber (155) this pressure acts on the first segment (170) deforming this portion so that pressure is generated within the medication container. Due to P:"OPERAr135126-0 spe.dc-27/02/03 this pressure the concave portion (173) of the second segment (171) flexes outwardly, contacts the needle (156) and is pierced. The pressure which is still acting on the first segment (170) deforms this segment until it closely lies on the inner wall of the second segment. However, the convex portion prevents piercing of the first segment. The convex portion can be covered by a membrane at its outer side which shelters the convex portion against combustion gases and pressure. A further aspect of the handling unit is that the upper shell (153) has a recess which supports the first segment (170) so that this segment only deforms in the concave region.

Throughout this specification and the claims which follow, unless the context requires otherwise, the word "comprise", and variations such as "comprises" and "comprising", will be understood to imply the inclusion of a stated integer or step or group of integers or steps but not the exclusion of any other integer or step or group of integers or steps.

The reference to any prior art in this specification is not, and should not be taken as, an acknowledgment or any form of suggestion that that prior art forms part of the common general knowledge in Australia.

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eeoo e 0 1 1I P:'OPER\Arl\35126-01 spc.doc-27/02/03 -21- List of reference numerals 0 0 0 reservoir (21) explosion chamber (23) primary membrane (24) secondary membrane nozzle (26) first shell (27) second shell (28) clasp (29) electrically insulating material electrical contact (31) vent (32) space (33) hollow needle (101) medication container (102) liquid medication (103) headspace (104) opening (105) chamber (106) seal (107) vacuum stream (108) vacuum (109) channel (110) heated pinching tools (111) air tight closure (150) handling unit (151) medication unit (152) first shell (153) second shell (154) explosive P:\OPERWAI\35I26-OI p,.d.c-27102103 22 (155) (156) (157) (158) (159) (170) (171) (172) (173) (174) explosion chamber needle tab predetermine breaking region plate first segment second segment convex portion concave portion annular wall

Claims (4)

1. A handling unit for use in a hypodermic injection system, said handling unit comprising: a first shell having an explosion chamber and an explosive therein; a second shell having a piercing needle disposed therein, the piercing needle having a piercing end; and a medication unit having a concave portion, the medication unit being sandwiched between the first shell and the second shell, the concave portion being arranged adjacent to the piercing end of the needle so that when pressure is applied to the medication unit by an explosion in the first shell, the medication unit generates a flexing deformation of its concave portion that leads to the piercing needle piercing the medication unit.

2. The handling unit of claim I, wherein the medication unit comprises a convex portion opposite to the concave portion which prevents piercing of the convex portion when the medication unit is deformed under pressure.

3. The handling unit of claim 1 or 2, wherein the second shell has a recess to receive 20 the medication unit therein and to support the portion of the medication unit that is adjacent to the second shell while allowing deformation of the concave portion.

4. The handling unit of any one of claims 1-3, wherein a space is formed between the concave portion of the medication unit and the second shell, and the handling unit 25 has a vent that allows gas to escape from the space when this concave portion is moved towards the second shell. P:\PER\Arl\35126-01 spe.doc-04/03/03 -24- A handling unit for use in a hypodermic injection system, substantially as described with reference to the drawings and/or examples. DATED THIS 2 7 t h day of February, 2003 Roche Diagnostics GmbH by DAVIES COLLISON CAVE Patent Attorneys for the Applicants