Patent Application
20090036867
The present invention relates to a medication delivery device for delivering a liquid medicament from a collapsible reservoir to the human body. The medication delivery device employs a displacement pump where the displacement stroke volume can be adjusted. The present invention further relates to a collapsible reservoir for containing a medicament.
A prior art medication delivery device is disclosed in US 2002/007154. In the medication delivery device according to US 2002/007154 a liquid medicament is stored in a glass cartridge closed in the one end with a piston. Typically 3 ml. of a liquid medicament is stored in such glass cartridge. Furthermore, the medication delivery device of US 2002/007154 comprises a piston rod, acting on the piston, having a length sufficient to press the entire content of the glass cartridge out through a conduit mounted on the distal end of the medication delivery device. As disclosed in US 2002/007154 the piston rod is bendable in order to shorten the over all length of the medication delivery device, this bending however adds to the width of the delivery device.
Although one of the most refined medication delivery devices known in the art is the delivery device disclosed in US 2002/007154 it has nevertheless a number of important drawbacks.
A major drawback of a conventional medication delivery device of a type similar to the one disclosed in US 2002/007154 is that the only viable way for precise dosing of medicament is by controlled mechanical displacement of the piston. The displacement has to be extremely well controlled due to the large area of the dosing piston as even minute deviations from ideal piston position may result in either overdosing or under dosing of medicament. Another drawback of conventional medication delivery devices is that the length of the piston rod for expelling medicament from a cartridge needs to at least match the length of the cartridge containing the medicament. Thus, the length of the piston rod essentially dictates the overall length of the medication delivery device.
Another complicating problem with the above-mentioned type of medication delivery device is that comparably high forces are needed to displace the piston. Thus, high mechanical demands are put on the mechanical actuation system.
As a result of the need of a long piston rod and the high mechanical demands put on the mechanical actuation system delivery devices similar to the one described in US 2002/007154 tend to be rather bulky.
Smaller and more handy dosing systems are disclosed in the literature. A good example on a compact and portable system is given in WO 03/099358. Although small, the device disclosed in WO 03/099358 is a pre-filled single use auto injector. One important limitation of the system disclosed in WO 03/099358 is that it lacks the dose setting flexibility often required in modern therapy. If e.g. the medicament is needed for treatment of diabetes mellitus a wide range of doses is needed. The exact dose to be delivered to a patient depends among other things on the recent carbohydrate intake and on the amount of recent exercise. Thus, efficient treating of a disease like diabetes mellitus requires that the device can deliver a range of doses.
A great number of different dosing systems are described in the literature. Among these many of the described systems are small and convenient to use while others are precise and offers the flexibility required for treatment of complex diseases like diabetes mellitus. At the time of writing there is, however, a need for small, precise dosing systems that are at the same time simple and convenient to use.
It is an object of the present invention to provide a novel strategy for dosing systems having the virtues of advanced devices as described in 2002/007154 but the size and convenience of the simple devices as exemplified by WO 03/099358.
It is a further object of the present invention to provide a delivery device from which set doses can be administered said device being smaller and lighter compared to the present state of the art.
It is a still further object of the present invention to provide delivery means for medicament with a higher dose precision compared to any commercial available device.
It is a still further object of the present invention to provide a method for making delivery devices which are potentially more precise than conventional devices based on dosing from a glass cartridge.
The above-mentioned objects and other objects are complied with by substituting the glass cartridge normally employed in flexible dosing systems with a collapsible reservoir special in that the pressure difference between the inside of the reservoir and the ambient is very small. This reservoir may be combined with a displacement pump where the displacement stroke volume can be adjusted according to the needs of the user.
A very precise and light dosing system can be obtained based on a collapsible reservoir and a displacement pump having an adjustable displacement volume. The most important virtue of a collapsible reservoir is in this context its pressure neutrality, i.e. the pressure inside the reservoir is approximately the same as the pressure outside the reservoir. Other important virtues over normal non-collapsible glass cartridge based reservoirs are low weight, compactness and low manufacturing costs. By taking advantage of the pressure neutrality it is possible to employ a displacement pump having an adjustable displacement volume to deliver very precise doses of medicament.
If a displacement pump is to be applied on a standard glass cartridge in a reliable manner, a force must be applied to the piston in order to overcome the erratic friction between the piston and the glass vessel. This would imply a permanently pressurised cartridge as the friction between the piston and the glass vessel is highly variable. However, a pressurised cartridge is not acceptable as failure of the pump may result in overdosing of medicament.
By avoiding the traditional piston rod and drive mechanism great simplification can be gained in the design of the medication delivery device.
If the medication delivery device is to be operated by electromechanical means the number of strokes required to deliver a given dose can be chosen randomly at no cost in the complexity of the system.
If the medication delivery device is to be operated manually or by a simple spring actuated mechanisms, the operation of the device is highly simplified if the complete dose of medicament is measured and delivered in a single stroke cycle. If the mechanical design of the device is such that only a single stroke of medicament can be delivered this furthermore improves the safety of the device significantly since multiple doses can not be delivered due to mechanical or electrical malfunctions.
By making a part of the collapsible reservoir from for example a sheet-like material it is possible to make a reservoir that is easily collapsible if the pressure outside the reservoir exceeds the inner pressure of the reservoir. As explained in details later, the term “collapsible” is not limited to reservoirs where the outer surface can collapse. This definition does also apply to a reservoir comprising a rigid outer shell but having an inner collapsible membrane made from a sheet-like material.
If a very simple, cheap and robust medication delivery device is wanted direct actuation of the pumping means may be the best choice. Direct actuation would typically be the preferred option for a third world device or a device containing a critical lifesaving drug. Direct actuation of the pumping unit may furthermore be an option if the mechanical actuation of the pumping unit fails.
Thus, in a first aspect the present invention relates to a medication delivery device for delivering a medicament, the medication delivery device comprising
In the present content the term “collapsible” should be interpreted broadly. Thus, collapsible is to cover a reservoir comprising a flexible sheet-like material which changes its form with changes of the volume of the reservoir. In addition, the term collapsible is also to cover any arrangement which allows changes in a volume of a reservoir. Such changes in volume could be provided by moveable wall portions of the reservoir as long as the pressure inside the reservoir maintains at approximately the same level as the pressure outside the reservoir.
In the context of the present invention, “hypodermic needle” should be interpreted broadly, i.e. comprising injection needles, infusion sets, micro-needle arrays or other suitable means for mechanically penetrating the dermis, hereby allowing for infusion of a substance.
A pressure difference of around 0.1 bar between the interior of the collapsible reservoir and the surroundings may be acceptable. However, it is an advantage of the present invention that the interior pressure in the collapsible reservoir is kept at essentially the same level—independent of the amount of medicament in the collapsible reservoir.
The medication contained in the collapsible reservoir may in principle be any kind of medication, such as one or more peptides, one or more proteins or a combination hereof. Thus, the peptides or proteins may comprise insulin, insulin analogues, GLP or GLP analogues or a mixture comprising one or more of these.
The pump means and the collapsible reservoir may be rigidly arranged relative to each other. Such a rigidly arrangement between reservoir and pump means may be established by attaching at least part of the reservoir directly to a part of the pump means. The pump means and the collapsible reservoir may be arranged within an at least partly closed shell or housing. Openings allowing setting of a dose to be expelled may be provided.
The collapsible reservoir may comprise a substantially rigid portion and a collapsible portion, the collapsible portion being adapted to collapse into at least part of the substantially rigid portion upon changing the volume of the collapsible reservoir. Part of an inner surface of the collapsible portion of the collapsible reservoir may comprise a sheet material. A more detailed description of the required properties of such sheet material is given below.
The medicament contained in the collapsible reservoir may be sucked out of the reservoir applying displacement pump means. A displacement stroke and/or a restoring stroke of a pump cycle may at least partly be actuated by the user of the medication delivery device. Thus, the appliance of a force by the user of the medication delivery device may at least partly be utilized to expel the medicament from the stroke volume. Alternatively, or in addition, the displacement stroke and/or a restoring stroke of a pump cycle may at least partly be actuated by a spring mechanism. This spring mechanism may comprise a torsion spring, a linear spring or a combination thereof. Finally, the displacement stroke and/or a restoring stroke of a pump cycle may at least partly be actuated by an electromechanical actuator being controlled by an electronic control circuit comprising a microprocessor.
The medication delivery device according to the present invention may further comprise dose counting means which allows the user of the medication delivery device to set the dose of medicament to be expelled. The medication delivery device may further comprise end of content indicating means which informs the user of the medication delivery device that the collapsible reservoir is empty, or close to being empty, and, thus, needs to be replaced.
The medication delivery device may further comprise means for assisting the user of the medication delivery device deciding on the proper dose of medication. This assisting means may at least partly form part of a module, said module being adapted to be secured to the medication delivery device. A control unit may further be provided. The control unit may be adapted to communicate with the medication delivery device and/or with the module secured thereto.
The medication delivery device may further comprise at least one display member, said display member being arranged on the medication delivery device, on the module being adapted to be secured to the medication delivery device or as part of the control unit adapted to communicate with for example the medication delivery device.
The medication delivery device, the module adapted to be secured to the medication delivery device or the control unit may further comprise at least one microcontroller arranged in the medication delivery device, the attached module or in the control unit. The microcontroller may facilitate that dose information is fed to electromechanical means for controlling the delivered dose.
In order to power the medication delivery device according to the present invention the device may comprise power supplying means, such as a battery. Finally, the medication delivery device may be equipped with a hypodermic needle.
In a second aspect, the present invention relates to a method for delivering a set dose of medicament from a medication delivery device, the method comprising the steps of
Thus, according to the present invention the stroke volume is set in accordance to the dose of medicament to be expelled. This implies that the stroke volume may be set to expel the set dose in a single pump stroke, or in a series of pump strokes with potentially different stroke volumes. Thus, a maximum of ten, eight, six, four or two pump strokes may be applied to expel the set dose of medicament. As already mentioned a single pump stroke may also be applied to expel the complete dose.
Similarly, a set dose of medicament may be expelled using a first pump stroke having a first stroke volume, said first pump stroke being followed by a second pump stroke having a second stroke volume, wherein the first stroke volume is different from the second stroke volume. The first and second stroke volumes may also be equal, as well as the number of applied pump strokes may differ from two.
In a third aspect, the present invention relates to a reservoir for medication delivery devices and for containing a medicament, the reservoir comprising a substantially rigid portion and a collapsible portion wherein at least a part of the rigid portion and at least a part of the collapsible portion are adapted to contact the medicament to be contained in the reservoir and wherein the collapsible portion is adapted to collapse into at least part of the substantially rigid portion upon expelling medicament from the reservoir.
As already mentioned the term “collapsible” should be interpreted broadly. Thus, collapsible is to cover a reservoir comprising a flexible sheet-like material which changes its form with changes of the volume of the reservoir. In addition, the term collapsible is also to cover any arrangement which allows changes in a volume of a reservoir. Such changes in volume could be provided by moveable wall portions of the reservoir as long as the pressure inside the reservoir maintains at approximately the same level as the pressure outside the reservoir.
The sheet-like material may comprise a sheet comprising a thermoplastic material which may form part of a multilayer sheet structure. The sheet material may further comprise one or more barrier layers. The sheet material may have a thickness smaller than 1 mm, such as smaller than 0.8 mm, such as smaller than 0.5 mm, such as smaller than 0.3 mm.
The present invention will now be explained in further details with reference to the accompanying figures, wherein
While the invention is susceptible to various modifications and alternative forms, specific embodiments have been shown by way of example in the drawings and will be described in detail herein. It should be understood, however, that the invention is not intended to be limited to the particular forms disclosed. Rather, the invention is to cover all modifications, equivalents, and alternatives falling within the spirit and scope of the invention as defined by the appended claims.
In its most general aspect the present invention relates to a medication delivery device comprising some sort of displacement pump having an adjustable pumping stroke volume. This arrangement facilitates that the medication delivery device is capable of expelling an arbitrary preset dose of medication by applying one or more adjusted pump strokes. As the delivered dose depends not only on the number of pumping strokes but also on the chosen stroke volume very high dose precision can be obtained using one or few pumping strokes.
Thus, it is an advantage of the medication delivery device according to the present invention that the delivered dose is not proportional to the number of pumping strokes as the stroke volume of the pump arrangement can be adjusted to match a set dose of medication to be expelled.
The function of an exemplary medication delivery device made according to the present invention will now be explained with reference to
In
The overall function of the medication delivery device is that medication is drawn from the collapsible reservoir 7 (only shown in
Position A: The neutral position of the device. The volume enclosed by the cylinder 1 and the piston is minimised.
Position A-B: The device is prepared for drawing medication from the collapsible reservoir 7 to the cylinder 1 by moving the slider 3. By movement of the slider 3 the suction spring 4 and the dosing spring 5 are energized.
Position B-C: When the slider 3 is in its position to the right of
Position C-A: After having measured medication into the volume defined by the cylinder 1 and the piston 2 the medication device is ready to deliver the measured dose. The measured dose is delivered by releasing the dosing spring 5+6 such that the piston is repositioned to the neutral position, hereby forcing the medication out of the cylinder.
In its simplest form the reservoir is made from sheet material which is folded and welded, thus forming a closed bag (
Due to the many conflicting demands on the sheet material, the sheet material may be a multilayer structure made from two or more layers having different properties. The sheet material will often be made predominantly from a laminate of multiple thermoplastic layers having the required mechanical properties. One or more barrier layers will be sandwiched between thermoplastic layers. Among inorganic barrier layers inorganic materials like Al AlOx, AlxOyNz, SiOx, SiOxNy, SiNx are preferred. The numbers x, y, z does not refer to any specific stochiometric composition but rather indicate a range of numbers as barrier layers often are non-stochiometric substances. Among organic barrier layers polyvinylchloride (PVC), polyparylene, cyclo olefin copolymer (COC) polypropylene (PP) and polychlorotrifluoroethylene (PCTFE) are preferred materials. Among these PP, PVC, COC and PCTFE have a high mechanical strength. They may hence be used either in a laminate or as single layer sheets.
The sheet thickness strongly depends on the stiffness and barrier properties of the sheet material. In a preferred embodiment of the present invention the average thickness of the sheet material is less than 1 mm. In a more preferred embodiment of the invention the average thickness of the sheet material is less than 0.3 mm.
Depending on the properties of the sheet material a number of different strategies for joining may be employed, including adhesive bonding, welding and mechanical joining. Among these welding, preferably laser welding, RF welding or heat welding are preferred.
If a coupling unit (
The use of fully collapsible reservoirs as illustrated in
In
In
In this embodiment of the invention there is a closed channel or conduit 402 connecting the collapsible reservoir 401 and the pumping unit 405, 406. From the pumping unit there is an additional conduit 403 connecting the pumping unit 405, 406 to an outlet 404.
Upon use the device is prepared for injection by retraction of the piston 405 in the cylinder 406 hereby pulling the medication from the collapsible reservoir 401 into the cylinder 406. The device is now ready to deliver an amount of medication identical to the volume evacuated into the cylinder 406 by the withdrawal of the piston 405. Now a hypodermic needle is attached to the outlet 404 and the needle is inserted. Hereafter the piston is pushed back to its original position hereby forcing the medication stored in the cylinder to the outlet 404 where it runs to the needle.
In some embodiments, the outlet 404 is provided with a piercable septum for closing off conduit 403 during transfer of medication from reservoir 401 to cylinder 406. Said piercable septum is adapted to establish fluid communication when patient access means are attached to the outlet. Alternatively, or in addition, a valve arrangement can be arranged to provide fluid communication during discharge of medication from cylinder 406 and to provide termination of fluid flow through conduit 403 during transfer of medication from reservoir 401 to cylinder 406. Also, valve means may be adapted to control one-way fluid flow from reservoir 401 to cylinder 406.
One important advantage of a device having the dosing cylinder integrated with the reservoir containing medication is that the concentration of the medication and the piston area can be changed simultaneously. Thus, if the potency of a drug is changed and the area of the piston is changed accordingly, the stroke length of the piston will remain unaltered although the drug has been changed. If the device comprises a manually operated piston this is a very important comfort factor for the user as any change in use pattern is normally associated with uncertainty and discomfort.
If a simple device or a very rugged device is wanted the pumping unit can be reduced to a fully manual operated mechanism reminiscent to a simple syringe. In
By minor modifications the simple rugged device shown in
A device made according to this embodiment may or may not include direct visual indications of a set dose, or direct visual indication of an expelled dose as found in the simple device. However, the same information may be presented in a graphic display.
One feature which might be beneficial to certain groups is the possibility to pre-program the device to give certain fixed amounts of medication. Although such a feature can be implemented in a purely mechanical device it is especially simple to implement a fixed-dose feature in a motor driven device.
Different strategies are to be employed to fill collapsible reservoirs. If a pre-assembled semi-rigid reservoir of the type presented in
After the filling has been completed the plunger 707 is pressed to an end stop corresponding to the position shown in
By proper design of the plunger 707, it is possible to have it acting as a barrier during storage. Later when medication has to be drawn from the reservoir, the plunger has been designed such that the cylindrical lip portions 708 at the rightmost end of plunger 707 may collapse upon a negative pressure gradient from the cylinder towards the collapsible reservoir. Thus, upon drawing medication from the reservoir to the cylinder, the plunger acts like a single pass valve. Plunger 707 may be provided with a concave portion to receive a slideable piston (not shown) inserted into the right-hand side of cylinder 706.
In the embodiment shown in
Common to all parts in drug contact is that they should be compatible with the medication. The materials in contact with medication could be chosen from polyvinylchloride (PVC), cyclo olefin copolymer (COC), polyethylenethraphtalate (PET), polyethylene (PE), polyurethane (PU), polypropylene (PP), polychlorotrifluoroethylene (PCTFE), polyphenylsulphone (PPSU) and polyetherimide (PEI). Further materials for sealing's are needed. Among these thermoplastic elastomers based on PP, EPDM, SEBS or mixtures as well as liquid silicone rubber (LSR) are preferred. However the choice of materials is not limited to these.
Although a fully integrated reservoir has been used to exemplify the virtues of the collapsible reservoir it is also possible to implement a system where the collapsible reservoir is only an integral part of the dosing unit during use but not during manufacture and transportation. This embodiment of the invention is especially beneficial if the medication has a short shelf life, if different types of medication are to be delivered using the same mechanical device or if the pumping unit is reusable.
Evidently, the medication delivery device according to the present invention facilitates injection of in principle any fluid, solution or suspension containing any combination of therapeutic proteins and/or peptides. In a preferred embodiment the injected medication comprises insulin, insulin analogues, GLP or GLP analogues especially suitable for treatment of diabetes. In an equally preferred embodiment the injected medication comprises human growth hormones or human growth hormone analogues.
| Number | Date | Country | Kind |
|---|---|---|---|
| 06388002.5 | Jan 2006 | EP | regional |
| Filing Document | Filing Date | Country | Kind | 371c Date |
|---|---|---|---|---|
| PCT/EP2007/050119 | 1/5/2007 | WO | 00 | 9/17/2008 |
| Number | Date | Country | |
|---|---|---|---|
| 60760569 | Jan 2006 | US |
