Surgery – Means for introducing or removing material from body for... – Treating material introduced into or removed from body...
Reexamination Certificate
1998-02-18
2002-05-14
Jastrzab, Jeffrey R. (Department: 3762)
Surgery
Means for introducing or removing material from body for...
Treating material introduced into or removed from body...
C604S181000, C604S082000, C206S221000
Reexamination Certificate
active
06387074
ABSTRACT:
BACKGROUND
The present invention relates to a membrane and a chamber of a drug delivery device which is for delivery of a drug comprising a mixture of first and second substances and which includes the chamber for housing the first substance, another chamber for housing the second substance and the membrane for partitioning the first chamber from the second chamber to prevent mixture of the first and second substances until the device is activated. The invention further relates to a drug delivery device of the aforementioned type, one example of which being an automatic injector.
There are certain instances when a person will need to inject a drug solution at a time which cannot be predicted, for example soldiers in the field who have been subject to a nerve gas attack. It is therefore important that such a person be provided with an injector which can be handled and activated in a simple and quick manner and which is reliable. Automatic injectors have therefore been developed in response to this need.
Automatic injectors will invariably be stored for many years prior to use and preferably such storage should be able to be at elevated temperatures up to 40° C., that is to say, there should be no need for cold storage under normal conditions (normal ambient temperatures, body temperatures). Automatic injectors will also often be subjected to hard conditions during the period when potential users carry them. The shelf-life of automatic injectors is therefore equally important With this in mind, the stability of drug solutions may deteriorate when stored for long periods. This is the case for certain nerve gas antidotes which are stable in powder form but which prove difficult to stabilise in solution for long storage periods.
There is thus a demand for an automatic injector for delivery of a drug solution which is simple, quick and reliable, in which it is possible to store the components which when mixed form the drug solution separately for a long period and in which means are provided which on activation of the injector causes the components to be mixed easily for injection of the drug solution.
An automatic injector which meets this requirement is made known in EP-A-288443.
EP-A-288443 makes known an automatic injector for delivery of a drug solution comprising a mixture of first and second substances, the device having a first chamber which contains the first substance, a second chamber which contains the second substance and a membrane which on activation of the injector moves from a first disposition in which it partitions the first and second chambers to prevent mixture of the first and second substances to a second disposition in which it enables the first and second substances to be mixed for injection thereof.
It will be apparent that the construction of the membrane needs to be such as to prevent premature mixing of the first and second substances. The membrane must therefore present a barrier against migration of the first and second substances therethrough. The membrane should also (i) be relatively easy to manufacture, (ii) not absorb substances from the substances in the chambers nor emit substances to those substances, and (iii) meet high standards in regard of gas permeability and radiation, e.g. should be able to withstand the normal radiations used for sterilisation, for example gamma and lambda radiation.
The automatic injector of EP-A-288443 is described with reference to its use for delivery of a drug solution formed on mixing of a powder with a liquid, as needed for the nerve gas antidotes of the type mentioned hereinabove which are stable in powder form but not stable for long periods when in solution. One of the chambers of the injector thus houses the powder (hereinafter the “powder chamber”) while the other chamber houses a liquid for the powder to be mixed with (hereinafter the “liquid chamber”). As mentioned above, it should be possible to store the injector for long periods and preferably at an elevated temperature. This means that the long-term and short-term requirements regarding the impermeability of the membrane to the liquid and liquid vapour has to be very strict.
In most cases the liquid for mixing with the powder will be water-based. With this in mind, it is previously known to use a membrane which contains aluminium as a barrier material to water and water vapour, as for example in the automatic injector of EP-A-288443.
In certain instances it may be that the pH of the substances in the chambers needs adjusting for stabilising purposes, this being particularly so for storage at elevated temperatures. This can have an adverse effect on the long-term integrity of the membrane. Furthermore, one of the substances may be chemically aggressive per se with respect to the material/materials of the membrane and thus also have an impact on the long-term integrity of the membrane, a condition being aggravated at elevated temperatures.
This is the case where the automatic injector of EP-A-288443 is to deliver a nerve gas antidote with the powder chamber of the injector containing HI-6 powder and the liquid chamber housing a mixture of Atropine and Avizaphone. In this instance, the pH of the Avizaphone/Atropine mixture is adjusted to a low pH value of pH 4 to increase the stability of the Atropine. This low pH value, however, has a deleterious effect over time on the aluminium contained in the membrane. Moreover, Avizaphone is chemically aggressive with respect to aluminium. The shelf-life of the automatic injector is thus handicapped by the poor resistance of the aluminium barrier material to the properties of the Atropine/Avizaphone liquid mixture.
There is thus a need for a membrane separating the liquid and powder chambers in this automatic injector which has improved resistance against the liquid mixture in addition to presenting a barrier against liquid or liquid vapour permeating into the powder chamber from the liquid chamber and adversely affecting the powder, for example by causing the powder to recrystallise and hence decrease the solubility of the powder or otherwise deteriorate the powder.
In the automatic injector of EP-A-288443 the membrane in its first disposition is welded across the powder chamber to close off the powder chamber and separate the contents of the powder chamber from the contents of the liquid chamber. A piston then acts on the powder in the powder chamber on activation of the injector to build up sufficient hydraulic pressure to bring the membrane to the second disposition by rupture thereof A recent development to the injector, though, has seen the piston being provided with a leading edge which on activation of the injector causes the membrane to be brought to the second disposition by peeling of the membrane off the powder chamber This has the advantage that the membrane can be made stronger. On the other hand, though, this places certain requirements on the weld formed between the membrane and the powder chamber.
With this in mind, it has been previously proposed to form the powder chamber from polypropylene with the membrane having a laminate construction comprising a layer of aluminium on one of the major surfaces of which a layer of welding material is adhered for welding the membrane to the powder chamber. The use of polypropylene to form the powder chamber, however, gives rise to difficulties in finding a material suitable for welding the membrane to the powder chamber. The welding materials either form a weld joint which is too weak thereby compromising the shelf-life of the injector or a weld joint that is too strong thereby compromising the ability of the membrane to be easily displaced to the second disposition on activation of the injector by peeling off.
There is thus also the need for a powder chamber which presents a surface to which it is easier to weld the membrane.
The present invention therefore proposes to satisfy these needs. It is to be pointed out, however, that the invention has application to the general field of devices which are for delivering a drug comprising a mixture of substances and
Friis Jörgen
Horppu Petri
Astra Aktiebolag
Bianco Patricia
Jastrzab Jeffrey R.
White & Case LLP
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