CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a 35 U.S.C. § 371 National Stage application of International Application PCT/EP2018/072400 (published as WO 2019/042802), filed Aug. 20, 2018, which claims priority to European Patent Application 17188590.8, filed Aug. 30, 2017, the contents of all above-named applications are incorporated herein by reference.

The present invention relates to medical delivery devices adapted for transcutaneous delivery of an amount of drug. In a specific aspect the invention relates to a preservative-containing flow communication unit to be used in combination with or forming part of a drug delivery assembly.

BACKGROUND OF THE INVENTION

In the disclosure of the present invention reference is mostly made to the treatment of diabetes by delivery of liquid insulin formulation, however, this is only an exemplary use of the present invention.

Drug delivery devices in the form of drug injection devices have greatly improved the lives of patients who must self-administer liquid drugs and biological agents. Drug injection devices may take many forms, including simple disposable devices that are little more than an ampoule with an injection means or they may be highly sophisticated electronically controlled instruments with numerous functions. Some devices are intended for single-use and may come with an integrated needle, e.g. comprising a so-called pre-filled syringe. However, in case the drug delivery device is intended to be used for multiple injections, it will typically be designed for use with a replaceable needle or cannula unit which ideally is to be replaced for each injection of a dose of drug. Regardless of their form, they have proven to be great aids in assisting patients to self-administer injectable drugs and biological agents. They also greatly assist care givers in administering injectable medicines to those incapable of performing self-injections.

In particular pen-style injection devices have proven to provide an accurate, convenient, and often discrete, way to administer drugs and biological agents, such as insulin. While pen-style injection devices are typically cylindrically shaped with a mounted needle protruding from the most distal portion of one end of the device, some devices have other shapes with the needle no longer protruding from the most distal part of an end of the device, e.g. Innovo® and InnoLet® from Novo Nordisk A/S, Bagsvrd, Denmark.

Typically, injection devices use a pre-filled cartridge containing the liquid medication of interest, e.g. 1.5 or 3.0 ml of insulin or growth hormone formulation. The cartridge is typically in the form of a generally cylindrical transparent glass cylinder having a distal bottle neck portion with a distal opening closed by a needle pierceable septum and an opposed proximal opening in which an elastomeric piston is received, the piston being arranged to be moved by the dosing mechanism of the injection device. The injection devices generally are of two types: “Durable” devices and “disposable” devices. A durable device is designed to allow a user to replace one cartridge with another cartridge, typically a new cartridge in place of an empty cartridge. In contrast, a disposable device is provided with an integrated cartridge which cannot be replaced by the user; when the cartridge is empty the entire device is discarded.

As described above, a drug delivery device intended to be used for multiple injections is typically designed to be used in combination with a replaceable needle unit comprising a proximal needle portion adapted to be inserted into the drug-filled cartridge through a needle-penetrable septum seal and a distal needle portion adapted to be introduced subcutaneously, this allowing a given dose amount of liquid drug formulation to be injected subcutaneously through the hollow needle. Since the proximal needle portion penetrates the seal of the cannula and provides a flow path from the inside of the cannula to the outside, a risk of contamination of the cartridge contents is introduced.

The risk of contamination is primarily related to removal of the needle unit after use. As long as the cannula is penetrating the cartridge seal, it provides access from surroundings to the drug formulation and should thus be removed immediately after injection. However, after injection but prior to removal of the needle, the small volume of drug formulation inside the needle itself may be contaminated either from body fluids or from bacteria in the surroundings when the cannula is extracted from the skin of the user. When the cannula is removed from the cartridge, some of the remaining fluid in the cannula may be sucked into the cartridge, thereby contaminating the drug formulation in the cartridge.

Therefore, drug formulations for use in multi dose injection devices must contain a sufficient level of preservatives to insure biostatic conditions during the expected in-use time of the cartridge to counter such contamination. This requirement is included in chapters on injectable drug formulations in current versions of international pharmacopeia.

The use of preservatives may in some cases reduce the efficacy of the drug and in some cases be incompatible with the drug, which means that such type of drug formulations cannot be used with a multi-dose injection device. For example, the necessary preservatives would destroy the drug substance in the cartridge by precipitating the drug substance or chemically react with it.

Having regard to the above, it is an object of the present invention to provide components, devices and methods which enables the use of drug formulations with little or no preservatives in cartridges to be used in multi-dose drug delivery devices adapted to be used in combination with replaceable subcutaneous needle units. It is a specific object of the invention to provide means allowing the above to be realized in a user-friendly and cost-effective way.

DISCLOSURE OF THE INVENTION

In the disclosure of the present invention, embodiments and aspects will be described which will address one or more of the above objects or which will address objects apparent from the below disclosure as well as from the description of exemplary embodiments.

Thus, in a general aspect of the invention an assembly is provided, comprising a reservoir with a drug-filled interior and an outlet, a flow conducting device, and a flow communication unit adapted to provide flow communication between the cartridge and the flow conducting device. The flow conducting device comprises a hollow tubular structure with a skin-piercing distal end, and a proximal flow inlet. The flow communication unit comprises a proximal inlet adapted to be arranged in flow communication with the reservoir, a first flow way in flow communication with the proximal inlet and comprising pressure-controlled valve means, a second flow way in flow communication with the first flow way, an amount of preservative arranged to react with a substance received by the second flow way, and distal flow communication means adapted to provide flow communication between the second flow way and the flow conducting device flow inlet. A combined flow way can be established between the reservoir interior and the expelling needle via the proximal inlet and the first and second flow ways when the reservoir, the flow communication unit and the flow conducting device are connected to each other. The valve means is controlled to open when the cartridge interior is pressurized. The preservative can react with a substance introduced to the second flow way via the expelling needle.

By such an arrangement the likelihood of contamination of the reservoir would be reduced, this allowing the use of drug formulations with little or no preservatives in reservoirs to be used in multi-dose drug delivery devices adapted to be used in combination with replaceable subcutaneous flow conducting devices.

In a further aspect the flow conducting device is a needle unit, wherein the hollow tubular structure is a hollow expelling needle with a skin-piercing distal end.

In a specific aspect of the invention an assembly is provided comprising a cartridge with a drug-filled interior, a needle unit, and a flow communication unit adapted to provide flow communication between the cartridge and the needle unit. The drug-filled cartridge comprises an outlet sealed by a needle-penetrable septum. The needle unit comprises a hollow expelling needle with a skin-piercing distal end, and a proximal flow inlet. The flow communication unit comprises a proximal hollow needle adapted to penetrate the needle-penetrable septum, a first flow way in flow communication with the proximal needle and comprising pressure-controlled valve means, a second flow way in flow communication with the first flow way, an amount of preservative arranged to react with a substance received by the second flow way, and distal flow communication means adapted to provide flow communication between the second flow way and the needle unit flow inlet. A combined flow way can thereby be established between the cartridge interior and the expelling needle via the proximal needle and the first and second flow ways when the cartridge, the flow communication unit and the needle unit are connected to each other. The valve means is controlled to open when the cartridge interior is pressurized, and the preservative can react with a substance introduced to the second flow way via the expelling needle. Depending on the specific design of second flow way, the preservative may react with a substance received by an inner and/or an outer surface of the second flow way.

In a first exemplary embodiment the flow communication unit comprises a tubular conduit comprising a distal portion with an open end, the tubular conduit forming the second flow way, and a preservative unit comprising an amount of preservative and having a first axial position in which the hollow conduit distal portion is embedded in preservative, and a second axial position in which the hollow conduit distal portion protrudes distally from the preservative unit. The preservative unit can be moved from the first to the second position when the needle unit is connected to the flow communication unit, the hollow conduit distal portion thereby providing the distal flow communication means.

The preservative unit may comprise a reservoir with an amount of fluid preservative. The reservoir may be provided with a needle-penetrable septum portion adapted to be penetrated by the hollow conduit distal portion when the preservative unit is moved from the first to the second position. The preservative unit may be provided with biasing means returning the preservative unit from the second to the first position when the needle unit is disconnected from the flow communication unit.

In a second exemplary embodiment the needle unit comprises a tubular conduit comprising a proximal portion with an open end forming the proximal flow inlet, and the second flow way of the flow communication unit is adapted to receive the tubular conduit proximal portion when the needle unit is connected to the flow communication unit. The second flow way may be in the form of a conduit comprising an amount of fluid preservative, the conduit being closed by a septum adapted to be penetrated by the tubular conduit proximal portion when the needle unit is connected to the flow communication unit.

The flow communication unit may comprise a reservoir with an amount of fluid preservative, a preservative flow communication being provided between the conduit and the reservoir, wherein the preservative flow communication is operated between an initial open state and an operational closed state when the needle unit is connected to the flow communication unit. The flow communication unit septum may be flexible allowing it to be moved axially from an initial distal position to a proximal operational position to thereby close the preservative flow communication when the needle unit is connected to the flow communication unit.

In a further aspect the flow conducting device is an infusion set, wherein the hollow tubular structure is a catheter with a hollow expelling needle with a skin-piercing distal end. In this way the flow communication unit can be used in connection with a pump system infusing a medicament through an infusion set.

In the above an assembly has been described, however, the described flow communication unit may also be provided as a separate unit per se. Correspondingly, in a further aspect of the invention a flow communication unit is provided, comprising a proximal hollow needle adapted to penetrate a needle-penetrable septum, a first flow way in flow communication with the proximal needle and comprising pressure-controlled valve means, a second flow way in flow communication with the first flow way, an amount of preservative arranged to react with a substance received by the second flow way, and distal flow communication means adapted to provide flow communication between the second flow way and a flow conducting device flow inlet, wherein the valve means is controlled to open when the proximal hollow needle is pressurized.

In an exemplary embodiment the flow conducting device flow inlet may be the inlet of a needle unit or an infusion set.

In an exemplary embodiment the flow communication unit further comprises a tubular conduit comprising a distal portion with an open end, the tubular conduit forming the second flow way, and a preservative unit comprising an amount of preservative and having a first axial position in which the hollow conduit distal portion is embedded in preservative, and a second axial position in which the hollow conduit distal portion protrudes distally from the preservative unit. The preservative unit may be provided with a reservoir with an amount of fluid preservative, the reservoir comprising a needle-penetrable septum portion adapted to be penetrated by the hollow conduit distal portion when the preservative unit is moved from the first to the second position.

In a further exemplary embodiment the second flow way of the flow communication unit is in the form of a conduit comprising an amount of fluid preservative, the conduit being closed by a needle-penetrable septum, either permanently or when the flow communication unit is operated between an initial and an operational state.

The flow communication unit may further comprise a reservoir with an amount of fluid preservative, wherein a preservative flow communication is provided between the conduit and the reservoir. This allows the preservative flow communication to be operated between an initial open state and an operational closed state. The septum may be flexible and can be moved axially from an initial distal position to a proximal operational position to thereby close the preservative flow communication.

As used herein, the term “insulin” is meant to encompass any drug-containing flowable medicine capable of being passed through a delivery means such as a cannula or hollow needle in a controlled manner, such as a liquid, solution, gel or fine suspension, and which has a blood glucose controlling effect, e.g. human insulin and analogues thereof as well as non-insulins such as GLP-1 and analogues thereof. In the description of exemplary embodiments reference will be made to the use of insulin.

