US20030135159A1 - Drug delivery device - Google Patents
Drug delivery device Download PDFInfo
- Publication number
- US20030135159A1 US20030135159A1 US10/336,459 US33645903A US2003135159A1 US 20030135159 A1 US20030135159 A1 US 20030135159A1 US 33645903 A US33645903 A US 33645903A US 2003135159 A1 US2003135159 A1 US 2003135159A1
- Authority
- US
- United States
- Prior art keywords
- drug delivery
- chamber
- drug
- delivery device
- internal
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
- A61M5/14—Infusion devices, e.g. infusing by gravity; Blood infusion; Accessories therefor
- A61M5/142—Pressure infusion, e.g. using pumps
- A61M5/14244—Pressure infusion, e.g. using pumps adapted to be carried by the patient, e.g. portable on the body
- A61M5/14248—Pressure infusion, e.g. using pumps adapted to be carried by the patient, e.g. portable on the body of the skin patch type
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
- A61M5/14—Infusion devices, e.g. infusing by gravity; Blood infusion; Accessories therefor
- A61M5/142—Pressure infusion, e.g. using pumps
- A61M5/145—Pressure infusion, e.g. using pumps using pressurised reservoirs, e.g. pressurised by means of pistons
- A61M5/155—Pressure infusion, e.g. using pumps using pressurised reservoirs, e.g. pressurised by means of pistons pressurised by gas introduced into the reservoir
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
- A61M5/14—Infusion devices, e.g. infusing by gravity; Blood infusion; Accessories therefor
- A61M5/142—Pressure infusion, e.g. using pumps
- A61M2005/14204—Pressure infusion, e.g. using pumps with gas-producing electrochemical cell
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
- A61M5/14—Infusion devices, e.g. infusing by gravity; Blood infusion; Accessories therefor
- A61M5/142—Pressure infusion, e.g. using pumps
- A61M5/14244—Pressure infusion, e.g. using pumps adapted to be carried by the patient, e.g. portable on the body
- A61M5/14248—Pressure infusion, e.g. using pumps adapted to be carried by the patient, e.g. portable on the body of the skin patch type
- A61M2005/14252—Pressure infusion, e.g. using pumps adapted to be carried by the patient, e.g. portable on the body of the skin patch type with needle insertion means
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
- A61M5/14—Infusion devices, e.g. infusing by gravity; Blood infusion; Accessories therefor
- A61M5/142—Pressure infusion, e.g. using pumps
- A61M5/14244—Pressure infusion, e.g. using pumps adapted to be carried by the patient, e.g. portable on the body
- A61M5/14248—Pressure infusion, e.g. using pumps adapted to be carried by the patient, e.g. portable on the body of the skin patch type
- A61M2005/1426—Pressure infusion, e.g. using pumps adapted to be carried by the patient, e.g. portable on the body of the skin patch type with means for preventing access to the needle after use
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
- A61M5/14—Infusion devices, e.g. infusing by gravity; Blood infusion; Accessories therefor
- A61M5/142—Pressure infusion, e.g. using pumps
- A61M5/14244—Pressure infusion, e.g. using pumps adapted to be carried by the patient, e.g. portable on the body
- A61M2005/14264—Pressure infusion, e.g. using pumps adapted to be carried by the patient, e.g. portable on the body with means for compensating influence from the environment
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M2206/00—Characteristics of a physical parameter; associated device therefor
- A61M2206/10—Flow characteristics
- A61M2206/22—Flow characteristics eliminating pulsatile flows, e.g. by the provision of a dampening chamber
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
- A61M5/14—Infusion devices, e.g. infusing by gravity; Blood infusion; Accessories therefor
- A61M5/142—Pressure infusion, e.g. using pumps
- A61M5/145—Pressure infusion, e.g. using pumps using pressurised reservoirs, e.g. pressurised by means of pistons
- A61M5/14586—Pressure infusion, e.g. using pumps using pressurised reservoirs, e.g. pressurised by means of pistons pressurised by means of a flexible diaphragm
- A61M5/14593—Pressure infusion, e.g. using pumps using pressurised reservoirs, e.g. pressurised by means of pistons pressurised by means of a flexible diaphragm the diaphragm being actuated by fluid pressure
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
- A61M5/14—Infusion devices, e.g. infusing by gravity; Blood infusion; Accessories therefor
- A61M5/168—Means for controlling media flow to the body or for metering media to the body, e.g. drip meters, counters ; Monitoring media flow to the body
- A61M5/16877—Adjusting flow; Devices for setting a flow rate
Definitions
- subcutaneous drug delivery devices A wide range of subcutaneous drug delivery devices are known in which a drug is stored in an expandable-contractible reservoir. In such devices, the drug is delivered from the reservoir by forcing the reservoir to contract.
- subcutaneous includes subcutaneous, intradermal and intravenous.
- Such devices can be filled in the factory or can be filled by the pharmacist, physician or patient immediately prior to use.
- it is difficult to ensure that the drug has completely filled the reservoir i.e. that the reservoir and fluid path do not contain any air bubbles.
- this requires priming the device by filling it in a certain orientation which ensures that the air bubbles are pushed ahead of the drug, such as with the filling inlet at the bottom and the delivery outlet at the top (to allow the bubbles of air to rise during filling).
- a further problem associated with subcutaneous drug delivery devices is that in many cases gas generation is used to compress the reservoir. While it may be possible to ensure a constant or a controllably varying rate of gas generation (for example by passing a constant current through an electrolytic cell), this does not ensure a constant rate of drug delivery.
- the amount of compression of the reservoir depends on the amount by which the volume of the gas generation chamber expands.
- WO 95/13838 discloses an intradermal device of this type having a displaceable cover which is moved between a first position in which the needle is retracted before use and a second position in which the needle is exposed during use. Removal of the device from the skin causes the cover to return to the first position in which the needle is again retracted before disposal.
- this device does not include a locking mechanism in the assembly for locking the device prior to use to minimize accidental contact with the needle and/or accidental actuation of the device that may occur during shipping and/or storage.
- the conventional method is to use a syringe, which carries the risk of accidental injury.
- the present invention has as a further aim the improvement of safety when syringes are used.
- the present invention also aims to decrease the possibilities that the needle could become exposed by accident before or after use, for example, by a child playing with the device if not properly disposed of.
- any possibility of accidental infection must be minimized to the utmost and preferably eliminated entirely.
- the present invention overcomes these and other disadvantages associated with prior art drug delivery devices and filling systems.
- the present invention provides for a drug delivery device having a housing that has an internal reservoir and an expandable chamber disposed relative to the reservoir.
- the device also has a drug delivery needle extending from the housing for penetration of the skin of a subject.
- the needle has an outlet for drug delivery.
- the drug delivery device of the present invention further includes a fluid path defined between the delivery needle outlet and the reservoir and means for providing a gas at a controllable rate into the expandable chamber.
- the device also includes a flow regulating chamber, in communication with the fluid path, which is capable of volumetric changes in response to temperature and/or pressure changes.
- the expandable chamber causes contraction of the reservoir in use.
- the flow regulating chamber alters the drug delivery rate by varying the flow resistance between the reservoir and the outlet.
- the flow regulating chamber is associated with a blocking member which upon expansion of the flow regulating chamber moves within the fluid path so as to restrict the flow of drug.
- the blocking member comprises a formation provided on a displaceable member which at least partially bounds the flow regulating chamber, the formation being disposed adjacent to an inlet of a conduit forming part of the fluid path, such that restriction of the fluid path occurs when the blocking member is moved into the inlet of the conduit.
- the shape of the blocking member is adapted to cut off the fluid path completely with a predetermined degree of expansion of the flow regulating chamber.
- the formation can be shaped such that the fluid path is never entirely cut off.
- a displaceable cover is connected to the housing such that displacement of the housing relative to the cover when the cover has been applied to the skin of a subject causes the delivery needle to penetrate the skin of the subject.
- a displaceable cover is suitable for concealing the needle before and after application to the skin of a subject, which prevents injury and reduces the possibility of contamination of the needle.
- the expandable chamber is provided with a release valve operatively connected to the displaceable cover such that the movement of the housing relative to the cover controls the closing of the valve and thereby the sealing of the expandable chamber. This feature is not dependent on the existence of the flow regulating chamber.
- the valve enables the device to be supplied with the displaceable member positioned such that the volume of the (empty) reservoir is minimized and that of the expandable chamber maximized.
- the reservoir can be of substantially zero volume initially, with no entrapped air volume.
- the device can then be primed or loaded by filling the reservoir, for example using a syringe- or cartridge-based filling mechanism.
- the displaceable member moves to expand the reservoir and thereby contract the expandable chamber.
- the valve allows the air or other gas in the expandable chamber to be exhausted into the atmosphere.
- the device can then be applied to the skin of the user.
- the housing moves relative to the cover which is applied to the skin, not only does the needle penetrate the skin, but also (because the valve is operatively connected to the cover) the valve is closed to seal the expandable chamber. If the valve remained open then gas supplied into the expandable chamber would be free to escape and delivery would not be effected. While it would be possible for the user to close the valve manually, this would clearly leave open the possibility of error. Instead, by connecting the valve operatively to the cover, it is possible to ensure that the valve is always closed when the device is applied to the skin.
- the valve comprises two components one of which is connected to the cover and the other of which is connected to the expandable chamber, such that relative movement of the housing towards the cover causes the valve to close.
- the invention includes a displaceable cover that is displaceable relative to the housing between a first position in which the needle is concealed from the exterior of the device, and a second position in which the delivery needle protrudes from the device for penetration of the skin.
- a further aspect of the present invention comprises means for locking the device in the first position after a single reciprocation of the device from the first position to the second position and back to the first position.
- the displaceable cover is an advantageous feature since it solves a problem unaddressed by prior art devices.
- Our prior art device has a locking mechanism to lock the housing in place after use and keep the needle concealed.
- the locking means engages automatically when the cover and housing are reciprocated relative to one another, i.e. the housing and cover are moved relative to one another to cause the needle to protrude when the device is applied to the skin. This relative movement is reversed when the device is removed thereby concealing the needle but also engaging the locking means to prevent the needle from being exposed again by accident.
- the locking means comprises a mechanical latch which is brought into operation by the reciprocation.
- the latch comprises a pair of elements mounted on the cover and the housing respectively. It is preferred that the elements be shaped such that they can have two relative configurations when the cover is in the first position relative to the housing. It is preferred the elements have a first movable configuration in which the elements are mutually movable, and a second locked configuration in which the elements are prevented from mutual movement. It is also preferred that the reciprocation of the cover and the housing causes the elements to pass from the first movable configuration, through an intermediate configuration when the cover is in the second position relative to the housing, and then to the second locked configuration, thereby preventing any further movement of the cover relative to the housing.
- one of the elements is provided with a recess which is adapted to receive a projection on the other of the elements, the recess and the projection being spaced apart from one another in the movable configuration, and being in engagement with one another in the locked configuration.
- the removable locking member comprises a laminar member inserted between the cover and the housing.
- the surface of the housing from which the needle extends or the surface of the displaceable cover, if present is of a concave cross-section.
- the needle extends from the lower surface of the housing is replaced by a tube extending from the housing.
- the tube is adapted for carrying a drug delivery needle.
- Such a device is preferred for intravenous delivery of a drug as the needle carried on the end of the tube can be accurately located in a suitable vein.
- the needle may be integral with the tube or supplied separately.
- the drug reservoir is separated from the expandable chamber by a diaphragm.
- the diaphragm exhibits bistable behavior such that in one stable state the reservoir is full and in the other stable state the reservoir is empty.
- the diaphragm is shaped to minimize the energy required in the transition between the stable states.
- the diaphragm is in the form of a body having a peripheral lip connected to a substantially flat central section by a flexible annular section.
- the flexible annular section assumes a substantially frusta-conical cross-section in one of the states and assuming an arcuate curved cross-section in the other state.
- the means for providing a gas comprises an electrical circuit in which any transistors are bipolar transistors having a gain of not less than 500, such that the circuit can be irradiated by ionizing radiation without destroying the circuit.
- This type of transistor has been found to be advantageous as it enables the device to be sterilized using gamma radiation with the electronic components intact. While a certain loss of performance results from the irradiation, the high gain transistor still has an adequate gain after irradiation to operate reliably. It is preferred that the current gain of the or each transistor is not less than 750. For example, a transistor having a rated current gain of 800 has been found to give an excellent performance after irradiation, despite the fact that irradiation lowers the current gain characteristics of the transistor by a factor of ten or more. The initial high gain compensates for the subsequent reduction arising from irradiation. The fact that the effects of irradiation can be predicted means that the performance after irradiation is reliable.
- the circuit further include a reference component across which a fixed potential drop is measurable.
- the reference component is essentially unchanged by the ionizing radiation. If a reference voltage is used which is not affected by the irradiation process, then the operation of the other components in the circuit may be determined by this reference voltage. For example, while the current gain of a group of transistors may vary individually when a batch is irradiated, each such transistor can be used to make an identically functioning amplifier if the output current of the amplifier is matched against a given reference component.
- the reference component of the preferred embodiment comprises a light-emitting diode.
- Gallium arsenide (GaAs) LEDs are virtually unaffected by gamma rays.
- the light emitting diode employs gallium arsenide as a semiconductor.
- the present invention provides for a subcutaneous drug delivery kit including a drug delivery device as described above.
- the device is provided with a filling mechanism associated with the reservoir.
- the filling mechanism includes means for receiving a filling adapter.
- the filling adapter includes a body which is adapted to accommodate a drug cartridge. The body has means for engaging the adapter-receiving means of the drug delivery device at one end thereof, means for receiving a cartridge at the other end thereof, and transfer means for transferring a liquid from a cartridge to the filling mechanism of the device as the cartridge is emptied.
- the adapter-receiving means and the corresponding engaging means provided on the adapter together constitute a releasable locking mechanism which holds the adapter in place on the device once engaged.
- the locking mechanism is disengaged by the cartridge when the cartridge is emptied within the adapter.
- the kit according to the invention is advantageous because it eliminates the need for a bulky filling mechanism which accommodates the cartridge within the device, and instead employs an adapter which is releasable from the device so as to enable the filled device to be less bulky than prior art cartridge-based devices.
- the locking mechanism employed is only disengaged when the cartridge has been completely emptied, i.e., the rubber stopper within the cartridge is pushed to the bottom. If the cartridge used is of a type which will empty when the stopper is pushed to the bottom, this feature ensures accurate loading of the reservoir, i.e. it is not possible to easily remove the device before the reservoir is filled with the correct dose of medicament.
- the transfer means comprises a hollow double-ended needle, one end of which is associated with the engaging means such that it communicates with the filling mechanism when the adapter is engaged with the device, and the other end of which is associated with the cartridge receiving means such that it communicates with the interior of a cartridge having a penetrable stopper when such a cartridge is received by the adapter.
- Such a hollow double ended needle can be replaced by a pair of needles which are connected by a conduit, such as a moulded conduit running through the body of the adapter and having a needle mounted at either end such that it is functionally equivalent to a double ended needle.
- a conduit such as a moulded conduit running through the body of the adapter and having a needle mounted at either end such that it is functionally equivalent to a double ended needle.
- both ends of the needle are disposed within the body of the adapter such that they are recessed from the exterior of the body when the adapter is disengaged from the device. This arrangement is preferable for safety reasons, as it allows the adapter to be disposed of without fear of accidental injury occurring from casual handling of the adapter.
- the releasable locking mechanism comprises a pair of locking members provided on the adapter receiving means and the corresponding engaging means, respectively.
- One of the locking members is movable between a locking position and a disengaging position.
- the movable locking member is disposed relative to the body such that, in use, when a cartridge is emptied within the body, the movable locking member is moved from the locking position to the disengaging position under the action of the cartridge.
- the body can receive the cartridge within a passage having a diameter sufficient to completely accommodate the cartridge.
- the end of the passage is of slightly narrower diameter on account of a projection provided on the movable locking member.
- the movable locking member is resiliently biased towards the locking position.
- the movable locking member is a latch which automatically locks the adapter and device to one another when engaged together. It is preferred that the cartridge is emptied by moving the penetrable stopper against the adapter
- the present invention further provides a subcutaneous drug delivery kit including a device according to any preceding claim further comprising a filling mechanism associated with the reservoir, the filling mechanism comprising means for receiving a filling adapter as defined herein and a filling adapter.
- the filling adapter has a body adapted to receive a syringe.
- the body has means for engagement with the adapter-receiving means of the device at one end thereof, syringe-receiving means at the other end thereof and transfer means for transferring a liquid from the syringe to the filling mechanism of the device as the syringe is emptied.
- the transfer means includes a conduit associated with the syringe receiving means, the conduit leads to a needle which is associated with the engagement means and is disposed within the body of the filling adapter.
- the needle disposed within the body of the filling adapter is recessed from the exterior of the body when the adapter is disengaged from the device. It is also preferred that the adapter receive the syringe without a needle. Since the needle on the adapter is recessed from the exterior of the adapter body and the syringe has no needle when filling, a conventional syringe (minus needle) can be used to fill the device without any risk of accidental injury.
- a further aspect of the present invention provides a method of filling a drug delivery device.
- the method includes providing a drug delivery device having a drug reservoir.
- the reservoir is associated with a filling mechanism having filling adapter receiving means.
- the method further includes providing a filling adapter having a first end for engagement with the adapter receiving means, and a second end for receiving a syringe and causing the filling adapter receiving means to receive the filling adapter.
- the method further includes causing the second end of the filling adapter to receive a syringe having liquid stored therein and a needle, and providing a conduit for communication between the liquid stored within the syringe and the first end of the filling adapter.
- the method of filling further includes emptying the syringe and concurrently transferring the liquid from the syringe to the device via the conduit.
- the invention provides a filling adapter as defined above and a diaphragm as defined above.
- the electrical circuit used to provide gas to the expandable chamber includes a high voltage supply, such as, for example, between one and three batteries and current stabilizing elements, such as, for example, two resistors connected in series.
- the electrical circuit of this preferred embodiment simplifies the electrical circuit and stabilizes the current supplied to the electrolytic cell without using components such as transistors which are sensitive to gamma radiation used for sterilization.
- Another aspect of a preferred embodiment of the drug delivery system of the present invention includes an occlusion prevention mechanism. Further, it is not desirable that the delivery rate of the drug delivery device be altitude dependent.
- An element such as, for example, a valve in the drug delivery device, creates a constant high, back pressure within the gas chamber, minimizing or preferably preventing the formation of boli of drugs.
- an optical window such as, for example, a ring like structure, provides a more accurate assessment of the quantity of drug delivered or alternatively, the quantity of drug remaining in the drug reservoir.
- the embodiment makes use of the principle of light reflected from the elastomeric membrane or diaphragm containing the drug.
- the optical window appears black as the elastomeric membrane is extended away from the housing as the drug fills it.
- the optical window appears blue in color, for example, as the elastomeric membrane is proximate to the housing as drug delivery is close to completion.
- the subcutaneous drug delivery device includes a pressure sensitive mechanism for preventing a rapid injection of a drug to a user.
- the pressure sensitive mechanism can include a switch that forms a part of the electrical circuit which controls the power supply to a gas generating portion of the drug delivery device.
- the switch can include different preferred components to complete the circuit, such as one including a conductive membrane and a conductive lever, or alternatively, electrodes and a droplet of mercury.
- the electrical circuit is completed as long as the pressure in the gas generating portion is less than the pressure within a chamber.
- the drug delivery system in accordance with the present invention includes a visual indicator to indicate proper application and operation to a user.
- the indicator can be, for example, a color marking system.
- the color marking system can be used to indicate to a user components of the system which should be removed from the system prior to use.
- Another preferred embodiment of the drug delivery system of the present invention includes an insert, for example, a foam insert that receives the internal components of the device and accommodates design tolerances.
- the insert maintains an accurate internal volume so that upon assembly, the volume of the internal housing, and thus the drug reservoir, is within an accurate range.
- the drug delivery system of the present invention includes an activation mechanism, such as, for example, an activation lever to initiate gas generation in the expandable chamber which in turn controls the delivery of the drug from the device.
- the activation mechanism also includes a puncturing device and an electrical contact. In operation, upon depression, the puncturing device punctures the foil cover of the electrolytic cell, thereby allowing the chemical ingredients to release gas for expanding the expandable chamber. As a result, the proximate drug reservoir is compressed and drug delivery is initiated.
- Another preferred embodiment of the drug delivery system relates to controlling the rate of delivery which is controlled by several parameters.
- the parameters include, but are not limited to, circuit current, residual air volume, material permeability, material properties of plastic material in device, and membrane seal.
- the permeability of the drug delivery system components such as the permeability of the materials used in the base affects the delivery rate of the drugs delivered.
- materials such as, for example, PET that minimizes or preferably prevents the permeation of the gases generated in the device, for example, hydrogen is used.
- a constant delivery rate can be maintained.
- material changes can control the delivery rate of drugs.
- Another aspect of the present invention includes packaging of the drug delivery system to insulate the system from storage and use in different altitudes.
- the electrolyte in the electrolytic cell used to generate gas in the expandable chamber is affected by environmental conditions.
- the performance of the barometric pressure valve can be affected by the environmental conditions as it relies on a reference pressure of a fixed amount of the air. At high altitudes, air from the reference cell can diffuse out of the device due to expansion. of the air.
- the barometric pressure valve has only one position, that is, it is a stationary valve as the pressure inside the device is constant.
- FIG. 1 is a sectional side view of a first embodiment of drug delivery device according to the present invention.
- FIG. 2 is an exploded perspective view of the flow regulating chamber and needle assembly of the first embodiment of the device of FIG. 1;
- FIG. 3 is an enlarged sectional side view of the flow regulating chamber and needle assembly of the first embodiment of the device of FIG. 1;
- FIGS. 4 - 6 are sectional side views of a second embodiment of drug delivery device according to the invention, shown before, during and after use, respectively;
- FIGS. 7 - 9 are enlarged perspective views of the locking mechanism of the device of FIGS. 4 - 6 , shown before, during and after use, respectively;
- FIGS. 10A, 10B and 10 C are schematic elevations of a first alternative embodiment of a locking mechanism, shown before, during and after use, respectively;
- FIG. 10D is a perspective view of the locking mechanism as shown in FIG. 10A;
- FIGS. 11A, 11B and 11 C are schematic elevations of a second alternative embodiment of a locking mechanism, shown before, during and after use, respectively;
- FIG. 11D is a perspective view of the locking mechanism as shown in FIG. 11A;
- FIGS. 12A, 12B and 12 C are schematic elevations of a third alternative embodiment of a locking mechanism, shown before, during and after use, respectively;
- FIG. 12D is a perspective view of the locking mechanism as shown in FIG. 12A;
- FIGS. 13A, 13B and 13 C are schematic elevations of a fourth alternative embodiment of a locking mechanism, shown before, during and after use, respectively;
- FIG. 13D is a side elevation of the locking mechanism as shown in FIG. 13A;
- FIG. 13E is a perspective view of the locking mechanism as shown in FIG. 13A;
- FIGS. 14 and 15 are sectional elevations of a third embodiment of drug delivery device according to the invention, shown before and during use, respectively;
- FIG. 16 is a partially cut away perspective view of the lower part of the housing on the device of FIGS. 14 and 15, including various components housed therein;
- FIG. 17 is an exploded perspective view of the electrolytic cell used in the embodiment of FIGS. 14 and 15;
- FIG. 18 is a sectional side view of the electrolytic cell used in the embodiment of FIGS. 14 and 15;
- FIGS. 19 and 20 are sectional side views of a fourth embodiment of drug delivery device according to the invention, shown before and during use, respectively;
- FIG. 21 is a sectional plan view of a drug delivery kit comprising the first embodiment of FIG. 1, a filling adapter and a medicament cartridge;
- FIG. 22 is a perspective view of a subassembly used in the adapter shown in FIG. 21;
- FIGS. 23 and 24 are sectional side views of the drug delivery kit of FIG. 21, shown during and after filling of the device, respectively;
- FIGS. 25 and 26 are sectional side views of fifth and sixth embodiments, respectively, of drug delivery device according to the invention.
- FIGS. 27 and 28 are sectional side views of a diaphragm suitable for use in a device according to the invention.
- FIG. 29 is a diagram of an electronic controller circuit suitable for use in a device according to the invention.
- FIGS. 30 and 31 are perspective views of the top side and underside, respectively, of a displaceable cover from a device according to the invention.
- FIG. 32A schematically illustrates a preferred embodiment of an electrical circuit for an electrolytic cell in a drug delivery device in accordance with the present invention
- FIG. 32B graphically illustrates the current profile of the electrolytic cell shown in FIG. 32A in accordance with the present invention
- FIGS. 33 A- 33 F illustrate both schematically and graphically, an embodiment of a drug delivery device which can be compromised by an occlusion
- FIGS. 34A and 34B schematically and graphically illustrate a preferred embodiment of a drug delivery device having an occlusion prevention mechanism in accordance with the present invention
- FIG. 35 schematically illustrates a preferred embodiment of the drug delivery device in accordance with the present invention.
- FIGS. 36 A- 36 C schematically illustrate the changes in the drug reservoir of a drug delivery device in accordance with the present invention
- FIG. 37A is a perspective view of a printed circuit board with a pressure sensitive mechanism
- FIGS. 37B and 37C schematically illustrate a preferred embodiment of a pressure sensitive mechanism of FIG. 37A included in a drug delivery device in accordance with the present invention
- FIG. 37D is a schematic illustration of an electrical circuit for the drug delivery system incorporating elements of FIG. 32A and FIG. 37A.
- FIGS. 38A and 38B schematically illustrate another preferred embodiment of a pressure sensitive mechanism included in a drug delivery device in accordance with the present invention
- FIG. 39A is a perspective view of a pressure sensitive mechanism, with portions broken away on a printed circuit board;
- FIGS. 39B and 39C schematically illustrate the preferred embodiment of a pressure sensitive mechanism of FIG. 39A included in a drug delivery device in accordance with the present invention
- FIG. 40 schematically illustrates a preferred embodiment of a drug delivery device including an insert in accordance with the present invention
- FIGS. 41A and 41B illustrates a preferred embodiment of a drug delivery device including an activation lever in accordance with the present invention
- FIG. 42 graphically illustrates the delivery of drugs using a preferred embodiment of the drug delivery device which controls residual air volume in accordance with the present invention
- FIG. 43 graphically illustrates the delivery of drugs using a preferred embodiment of the drug delivery device which controls the system permeability in accordance with the present invention
- FIG. 44A illustrates a full assembly of the drug delivery device including a stationary barometric pressure valve in accordance with the present invention
- FIG. 44B is an enlarged sectional view of the stationary valve of FIG. 44A;
- FIG. 45 illustrates a preferred embodiment of the packaging used for the drug delivery device in accordance with the present invention.
- FIG. 46 illustrates an alternate embodiment of packaging used for the drug delivery device in accordance with the present invention
- FIGS. 47 A- 47 C illustrate another embodiment of packaging used for the drug delivery device in accordance with the present invention.
- FIG. 48 is a sectional side view of an alternative embodiment of a drug delivery device
- FIG. 49 is a sectional side view of an alternative embodiment of a drug delivery device
- FIG. 50A is a sectional side view of the alternative embodiment of the drug delivery device of FIG. 48 with the luer connection on to be an epidural needle;
- FIG. 50B is a sectional side view of the alternative embodiment of the drug delivery device of FIG. 48 with the luer connection to an epidural needle with a hydrophobic membrane and a hydrofoil membrane.
- FIG. 1 indicates a subcutaneous drug delivery device 10 according to the invention.
- a housing 11 defines a reservoir 12 which is partially bounded by an elastomeric diaphragm 13 which allows the reservoir to expand and contract.
- the diaphragm 13 also bounds an expandable chamber 14 such that expansion of the expandable chamber causes the reservoir 12 to contract and vice versa.
- the reservoir 12 is at full volume and contains a drug, while the expandable chamber 14 is at minimum volume.
- a circuit board 15 having an electrolytic cell 48 mounted thereon (explained in greater detail below) is mounted in the lower part 16 of the housing 11 .
- the electrolytic cell 48 feeds a gas into the expandable chamber 14 via an aperture 17 in a supporting member 18 .
- the reservoir 12 is provided with an inlet 19 which is in communication with a filling mechanism 20 (explained in greater detail below).
- a delivery needle 21 provided with an outlet 22 is in communication with the reservoir 12 via a fluid path 23 which is indicated by arrows.
- the fluid path 23 passes around an air-filled flow-regulating chamber 35 which comprises a top member 24 , annular member 25 and flow diaphragm 26 .
- the fluid path 23 also passes via a needle holder 27 to the needle 21 .
- the inlet 19 to the needle 21 is partially restricted by a projection 28 on the flow diaphragm 26 , such that any upward movement of the projection 28 reduces resistance to flow and any downward movement of the projection increases flow resistance.
- the flow regulating chamber 35 can be seen in exploded view.
- Annular member 25 receives the flow diaphragm 26 , and top member 24 and the three components fit together to form an airtight chamber 36 which is positioned above the needle holder 27 .
- the inlet 19 in the needle holder 27 leading to the needle 21 can be clearly seen on the top surface of the needle holder.
- Projection 28 extends into the inlet 19 .
- FIG. 1 Further features of device 10 which can be seen in FIG. 1 are a displaceable cover 29 attached to the housing 11 by a hinge 30 .
- the displaceable cover 29 is affixed to the skin using an adhesive coating 29 ′ provided on the surface thereof distal from the housing (“the underside”).
- the displaceable cover 29 has a concave shape when viewed from the underside. This shape is advantageous because if a flat or convex surface is provided, the edges of the cover 29 will be more easily peeled away from the skin by accident, i.e. the use of a convex surface is less likely to have protruding edges, and the force required to peel the device away is a shear force rather than a simple peeling force.
- the housing 11 is covered by a protective top cover 32 which can provide a more aesthetically pleasing appearance to the device, as well as one which is ergonomically more advantageous for the user.
- An aperture in protective top cover 32 indicated at 33 , allows a transparent portion 34 of the housing 11 to be seen, thereby allowing the user to visually check the reservoir to see whether drug is present.
- the protective top cover 32 also protects the housing 11 and its component parts if the device 10 is mishandled or dropped.
- the flow regulating chamber 35 is shown in greater detail in FIG. 3 and comprises the top member 24 , the annular member 25 , and the flow diaphragm 26 , as explained above.
- the construction ensures that the airtight space 36 exists in the interior of the chamber 35 .
- a fluid path between the reservoir and the needle (FIG. 1) is shown with heavy arrows.
- projection 28 on the flow diaphragm 26 extends into the inlet 37 in the needle holder 27 leading to the needle 21 .
- the fluid has to push up on the flow diaphragm 26 in order to reach the needle 21 . Little force is required to do this, as the air in the chamber 36 is compressible.
- a further feature of the device of FIGS. 1 - 3 is an o-ring 38 located on displaceable cover 29 (see FIG. 1).
- the o-ring 38 forms a seal with needle holder 27 and thereby assists in protecting the puncture point of the needle 21 into the skin of the user from contact with soap, water, perspiration or other contaminates. If water or other liquid contacts the needle 21 , the needle 21 may act as a switch and allow water to be drawn into the puncture.
- adhesive 29 ′ on the displaceable cover 29 prevents water from reaching the needle 21 via the underside of the cover, and the o-ring 38 prevents water from reaching the needle via the upper side of displaceable cover.
- Top member 24 , annular member 25 , flow diaphragm 26 and needle holder 27 and all other parts in the fluid pathway are preferably made of a polycarbon material.
- Polycarbon materials are essentially inert and will not react with the liquid drug. Moreover, the polycarbon material withstands gamma radiation without degradation of any properties.
- FIGS. 4, 5, and 6 show a device similar to that of FIG. 1 before, during and after use, respectively.
- the device, indicated generally at 50 differs slightly from the FIG. 1 device and accordingly different reference numerals are used in relative to FIG. 1.
- the device 50 is shown in FIG. 4 with the needle 51 concealed by the displaceable cover 52 because the displaceable cover 52 is displaced relative to the housing 53 about the hinge 54 .
- a removable tab 55 prevents the displaceable cover 52 from being moved towards housing 53 , as will be described further below.
- the underside 56 of the displaceable cover 52 is coated with a contact adhesive 56 , and during storage, the adhesive is protected by a release liner.
- the adhesive-coated underside 56 is pressed against the skin to ensure good adhesion (the concave surface assists in obtaining good adhesion) and the tab 55 is removed.
- the housing 53 is then pushed towards the skin and the needle 51 penetrates the skin as the displaceable cover 52 and housing 53 move together about hinge 54 , leading to the configuration shown in FIG. 5.
- a start button is pressed to activate a gas generating electrolytic cell 57 .
- a diaphragm 58 is pushed upwards to drive a liquid drug from the reservoir 59 (which was filled before use via inlet 60 ) and thereby force the drug through a fluid path 61 around the flow regulating chamber 62 (as explained above in relation to FIGS. 1 - 3 ) and to the patient via the delivery needle 51 .
- the diaphragm 58 When delivery has been completed, the diaphragm 58 will have moved up such that the space occupied by the reservoir 59 at the beginning of delivery (see FIGS. 4 and 5) is now occupied by the expandable chamber 14 (see FIG. 6), since the expansion of the expandable chamber causes contraction of the reservoir.
- the device 50 is removed from the skin by pulling upwards on the upper protective cover 63 (FIG. 6). This causes the needle 51 to be retracted behind the displaceable cover 52 once again because the adhesive force holding the displaceable cover 52 against the skin is greater than the force exerted by the locking mechanism 64 (explained in greater detail below).
- the locking mechanism 64 holds the displaceable cover 52 permanently in the position shown in FIG. 6, i.e. away from the housing 53 with the needle 51 concealed.
- FIG. 7 shows locking mechanism 64 in greater detail, with the protective top cover 63 removed for illustrative purposes. The locking mechanism 64 is illustrated before use, i.e. when the displaceable cover is positioned as shown in FIG. 4.
- a projection 65 mounted on the front of housing 53 is positioned at the upper end of a slot 66 .
- the slot 66 has an enlarged portion 67 at the lower end and is provided with wedge projections 68 , 69 at the exterior surface of the upper portion thereof.
- the slot 66 is formed in a member 70 which is attached to displaceable cover 52 by connecting arms 72 which allow a slight degree of flexibility.
- a widened rib is provided on the projection 65 , and the width of this rib is greater than that of the upper portion of the slot 66 .
- the member 70 is biased slightly against this rib.
- the removable tab 55 (see FIG. 4) is positioned so as to engage wings 71 and prevent them from moving towards the cover 52 . This effectively prevents the entire housing 53 from being moved towards the cover 52 and prevents the device from being activated prematurely.
- the tab 55 is removed, as shown in FIG. 7, the displaceable cover 52 can be snapped towards the housing 53 by pressing down on the housing.
- the locking mechanism adopting the configuration shown in FIG. 8, wherein the projection 65 has moved to the lower end of the slot 66 , allowing a lipped member 73 to pass through the enlarged portion 67 at the lower end of slot 66 . This allows a member 70 , which was biased in the direction of projection 65 , to relax. The sides of the lipped member 73 rest against the member 70 .
- FIGS. 4 - 8 An additional feature of the device of FIGS. 4 - 8 relative to that of FIG. 1 can be seen with reference to FIGS. 4 - 6 .
- a pair of projections 74 grip the flow regulating chamber 62 before use to block the path between the reservoir 59 and the needle 51 before use (FIG. 4).
- the projections 74 are resilient and move together when the flow regulating chamber 62 moves downwards. In this position the projections 74 hold flow regulating chamber 62 in a fixed position both during delivery (FIG. 5), and when the device is removed from the skin (FIG. 6).
- a further feature of the embodiment of FIGS. 4 - 6 is an annular elastomeric inwardly extending lip 75 which seals the skin at the point of entry of the needle 51 in the same manner as the o-ring 38 in the FIG. 1 embodiment. This feature reduces the danger of infection due to wicking by the needle of unwanted substances into the skin.
- FIGS. 10 A- 10 D, 11 A- 11 D, 12 A- 12 D, and 13 A- 13 E Four alternative embodiments of different locking mechanisms according to the invention are shown in FIGS. 10 A- 10 D, 11 A- 11 D, 12 A- 12 D, and 13 A- 13 E.
- the mechanism is shown schematically in “pre-use” (A), “in-use” (B) and “post-use” (C) configurations as well as in one or two perspective views (D/E).
- the mechanism can in each case be moved from position A to position B and from position B to position C with little difficulty (although generally some resistance is present to prevent spontaneous or accidental movement), but once in position C, the mechanism is effectively locked permanently and is no longer capable of operation.
- the first alternative embodiment of a locking mechanism comprises a resilient arm and related assembly and is shown in FIGS. 10 A- 10 D.
- the locking mechanism is indicated generally at 80 and comprises a biasing member 81 and a resilient strut 82 mounted on a housing 83 , and the resilient arm 84 and a post 85 mounted on a displaceable cover 86 .
- the resilient arm 84 is flexibly hinged at the base thereof 87 .
- the biasing member 81 pushes the resilient arm 84 against the post 85 .
- the resilient arm 84 and post 85 are mutually shaped to allow the arm 84 to pass over the top of the post 85 , where it latches (see FIG. 10B) and is prevented from returning to the position shown in FIG. 10A.
- FIG. 10D shows the mechanism in the position illustrated in FIG. 10A.
- An additional feature visible in FIG. 10D is a snap mechanism comprising an arm 90 depending from either side of the housing 83 .
- a raised protuberance 91 on the inner surface of each arm 90 acts against a sloped surface 92 on the displaceable cover 86 to provide resistance to movement.
- the effect of the snap mechanism is to add further resistance to any unintended relative movement between the housing 83 and the displaceable cover 86 .
- a further effect is that the movement of the housing 83 relative to the cover 86 between the configurations of FIGS. 10A and 10B, and the configurations of FIGS. 10B and 10C, is extremely rapid, causing the penetration of the needle into the skin and the removal of the needle from the skin to be quick and painless.
- the second alternative embodiment of a locking mechanism of the present invention comprises an inverted V-shaped assembly and is shown in FIGS. 11 A- 11 D.
- the locking mechanism is indicated generally at 100 and comprises a member 101 resiliently mounted on a housing 102 , and a pin 103 supported in a frame 104 mounted on a displaceable cover 105 .
- the member 101 has an inverted V-shape slot 106 therein.
- the slot 106 has an outer slot portion 107 connected at the upper end thereof to an inner slot portion 108 , and a dividing member 109 between the outer and inner slot portions 107 , 108 below the upper ends.
- the (fixed) pin 103 moves up the outer slot 107 , acting against the dividing member 109 until it springs past the dividing member 109 at the top of the outer slot. In the position shown in FIG. 11B, the pin 103 is located above the top of the inner slot 108 .
- the pin moves down inner slot 108 , acting against the dividing member 109 to push the member 101 sideways.
- the pin 103 locates a recess 110 (see FIG. 11B) in the lower end of inner slot 108 , which allows the member 101 to relax slightly but still keeping a certain degree of stress on the member 101 by holding it away from the equilibrium position relative to the housing 102 .
- the pin 103 latches into the recess 110 and locks the mechanism 100 permanently in the “post-use” configuration.
- FIG. 11D the mechanism 100 can be seen in the “pre-use” configuration, with the member 101 , housing 102 , pin 103 , frame 104 , and displaceable cover 105 visible.
- the third alternative embodiment of a locking mechanism of the present invention comprises generally a rotatable pawl assembly and is shown in FIGS. 12 A- 12 D.
- the mechanism indicated generally at 120 , comprises a rotatable pawl 121 mounted on the displaceable cover 122 and which is rotated by an arm 123 in moving from the “pre-use” to “in-use” positions (FIGS. 12A and 12B, respectively).
- a recess 124 FIG. 12A
- receives a projection 125 located on a resilient portion 126 of the displaceable cover 122 providing a degree of resistance to further movement.
- the rotatable pawl 121 acts against a flexible strut 127 depending from the housing 128 .
- the rotatable pawl 121 is in the FIG. 12B position, further clockwise rotation of the pawl is prevented by the arm 123 .
- the arm 123 prevents any counter-clockwise rotation of the rotatable pawl 121 , while the strut 127 prevents any clockwise rotation thereby locking the rotatable pawl 121 in position and preventing any further downward movement of the housing 128 towards displaceable cover 122 .
- the fourth alternative embodiment of a locking mechanism of the present invention comprises generally a flexible post assembly as shown in FIGS. 13 A- 13 E.
- the locking mechanism is indicated generally at 130 and comprises a vertical flexible post 131 (see FIGS. 13D and 13E) mounted on the displaceable cover 132 and having a projection 133 extending therefrom towards a sloped surface 134 on the housing 135 .
- a slot 136 in surface 134 connects two apertures, namely a lower aperture 137 (see FIG. 13B) which is of smaller diameter than the widest part of projection 133 , and an upper aperture 138 which is of larger diameter than the widest part of projection 133 .
- projection 133 is positioned at the lower aperture.
- the flexible arm 131 is bent back until the projection 133 reaches the upper aperture 138 whereupon it springs back into position as the projection 133 moves through the upper aperture 138 .
- the projection 133 is constrained by the slot 136 and the arm 131 is bent forward until the projection 133 reaches the lower aperture 137 which provides a recess for the projection 133 to spring back into (but not through). Because the arm 131 remains bent forward slightly, this effectively traps the projection 133 in the lower aperture 137 and thereby holds the mechanism permanently in the “post-use” configuration, as shown in FIG. 13C.
- FIG. 14 there is another drug delivery device 140 according to the invention similar in many respects to the embodiments previously described.
- the device 140 has a protective upper cover 141 , a housing 142 , a displaceable cover 143 , a delivery needle 144 , a flow regulating chamber 145 and a three position locking mechanism 146 .
- the internal space of the drug delivery device 140 of FIG. 14 defines an expandable chamber 147 when the diaphragm 148 is in the position shown or a reservoir when the diaphragm is in the position shown in dotted outline at 149 .
- the expandable chamber 147 is initially air filled (FIG. 14 shows the device in the pre-use configuration before medicament has been loaded). Thus, the reservoir is substantially of zero volume.
- the expandable chamber 147 communicates with the atmosphere via an open valve 150 .
- the reservoir is initially of substantially zero volume, it does not require filling in any particular orientation. While prior art devices have required careful loading in order to ensure that all air bubbles are vented from the drug supply before delivery begins, the only air in the drug path of the device of FIG. 14 is in the short, narrow portion of the device between the reservoir and the needle 144 . Thus, when drug enters the reservoir it immediately pushes the small amount of air ahead of it through the narrow space towards the needle 144 , irrespective of the orientation of the device 140 . By filling with the drug until a drop of the drug appears on the end of the needle 144 one can be sure that no air remains in the fluid path.
- the diaphragm 148 When the device 140 has been filled with drug, the diaphragm 148 is at the position shown at 149 , and the valve 150 is open. However, when the displaceable cover 143 is applied to the skin, and the housing is pushed downwards, the valve 150 is closed and the closing of the valve actuates a switch 151 to begin generation of gas by an electrolytic cell 152 (described in more detail below).
- the device 140 is then in the “in-use” position shown in FIG. 15, with reservoir 147 filled with drug, the diaphragm 148 in position 149 , valve 150 and switch 151 closed, and electrolytic cell 152 actuated to generate a gas and hence begin delivery of drug from reservoir to the patient through delivery needle 144 .
- Valve 150 is closed by a connecting member 153 which is connected to displaceable cover 143 .
- connecting member 153 fits into a valve 150 and pushes it home to seal the expandable chamber 147 (the area below diaphragm 149 ) from the atmosphere.
- a gas is generated by the electrolytic cell 152 , it pressurizes the reservoir 147 .
- a coloured plastic member 154 forming part of locking mechanism 146 protrudes through an aperture 155 in the protective upper cover 141 when the device 140 is in the position as shown in FIG. 15.
- the coloured member 154 visually indicates that the device 140 has been actuated.
- FIG. 16 is a detail view of the lower section 156 of the housing 142 (see FIG. 15).
- the lower section 156 houses a battery 157 and an electrolytic cell 158 , both mounted on a printed circuit board (PCB) 159 .
- the PCB 159 can be provided with controlling circuitry as required in order, for example, to vary the rate of delivery, stop delivery if the rate of gas generation is too high, or control the operation of the device 140 in any other way required.
- the device 140 is a disposable single-rate device which does not require advanced controlling circuitry, but more sophisticated devices are of course within the scope of the invention.
- a cylindrical outlet 160 is formed in section 156 , and this provides a valve seat for the valve 150 .
- the valve 150 When the valve 150 is pushed upwards into an outlet 160 it makes an airtight seal, as shown in FIG. 15.
- a recess 161 in the valve 150 tightly accommodates the connecting member 153 (FIG. 15), and the force used to push the housing 142 down onto displaceable cover 143 as described above is sufficient to jam the connecting member 153 into the valve 150 .
- This design enables the device 140 to be removed from the skin by pulling housing 142 away from displaceable cover 143 to the “post-use” position, causing the connecting member 153 (which is permanently mounted on displaceable cover 143 and at this stage jammed into valve 150 also) to pull the valve 150 down and out of outlet 160 so as to open the valve.
- the connecting member 153 which is permanently mounted on displaceable cover 143 and at this stage jammed into valve 150 also
- the valve 150 down and out of outlet 160 so as to open the valve.
- valve 150 when the valve 150 is closed, it actuates a switch 151 (see FIG. 15) which comprises a fixed contact 162 and a rocking contact 163 . This completes a circuit to connect a battery 157 to an electrolytic cell 158 .
- the switch 151 should automatically disconnect because of the resilience of rocking contact 163 which pivots about a fulcrum 164 .
- the opening of the valve 150 is generally a redundant feature and is important as a safety feature if the switch 151 does not automatically disconnect (leading to an unwanted continuation of delivery or, if the reservoir 147 is already empty, to a build up of gas pressure inside the device 140 ).
- the electrolytic cell 158 comprises (see also FIGS. 17 and 18) a body 165 defining an internal space 166 for an electrolyte and through which a pair of electrodes 167 pass, each electrode being connected to a terminal of battery 157 (FIG. 16).
- the internal space 166 is enclosed above and below by a pair of hydrophobic filters 168 and 169 . These filters 168 and 69 retain the electrolyte but allow gas generated in the cell 158 to be released to the expandable chamber 147 .
- the hydrophobic filters 168 and 169 are positioned on the body 165 such that gas will transfer out of the gas generator irrespective of the orientation.
- the top and bottom of the body 165 is provided with a seating 170 .
- the filters 168 and 169 are placed in the seating 170 above and below the body 165 and are sealed in place.
- the body 165 is an injected molded high density poly ethylene (HDPE) to minimize permabilty.
- HDPE high density poly ethylene
- the cell 158 is then sealed above and below by aluminum foil layers 171 and 172 .
- a connecting cell 174 sealed at both ends by foil layers 171 and 172 enables gas passing through the hydrophobic filters 168 and 169 to be released, once the top foil layer 171 has been pierced.
- a gap adjacent to the seating 170 enables gas escaping through hydrophobic filters 168 and 169 to reach the connecting cell 174 .
- the foil layer 171 is pierced by a spike 175 carried on rocking contact 163 (see FIG. 16).
- a hydrophobic filter 176 (see FIG. 17) is also carried in the body 165 to enable the cell 158 to be filled with electrolyte by injection.
- FIGS. 19 and 20 a further embodiment 180 of the invention is shown.
- This embodiment differs from the embodiment of FIGS. 14 - 18 only in that the valve member 181 is not held by the displaceable cover 182 when the device 180 is removed from the skin after use.
- the valve 181 nevertheless achieves the primary purpose of allowing the internal space 183 to be occupied entirely by the expandable chamber when received by the user, with the diaphragm 184 moving to the position shown at 185 when the device 180 is loaded with medicament. This means that no air bubbles can be entrapped in the reservoir during filling, and the reservoir can thus be filled quickly and easily.
- the valve 181 closes automatically when the housing 186 is pressed towards the displaceable cover 182 (see FIG. 20).
- FIG. 21 shows a device 190 according to the invention which is identical to the device of FIG. 1, together with a filling adapter 191 and a drug-containing cartridge 192 .
- Cartridge 192 is cylindrical in shape, closed at one end 193 thereof and sealed at the other end 194 by an elastomeric stopper 195 which is fittably mounted in the cartridge 192 . Because the cartridge's liquid-filled internal space 196 is sealed, the stopper 195 is prevented by the incompressible nature of the liquid from moving in either direction.
- the adapter 191 has a housing 197 in which a cannula subassembly 198 is mounted.
- the subassembly 198 (see FIG. 22) includes a plastic body 199 moulded in two halves 200 , 201 , which when assembled together clamp a double-ended hollow needle or cannula 202 in place.
- a device 190 is provided with a socket 203 for receiving the adapter 191 .
- a cylindrical projection 204 on the end of the adapter 191 is designed to fit into the socket 203 , and also to conceal the cannula 202 to prevent injury before and after the adapter 191 is mounted on the device 190 .
- a self-sealing penetrable plug 205 mounted in the socket 203 leads to a conduit 206 and an inlet for the reservoir (see inlet 19 in FIG. 1).
- a subassembly 198 is mounted in a channel 207 of the adapter 191 such that it can be pushed inward until a shoulder 208 meets the end of the structure 209 defining the channel 207 .
- the cannula 202 will penetrate the plug 205 enabling communication between the cannula 202 and the reservoir of device 190 .
- a cartridge 192 is pushed into the adapter 191 , whereby a stopper 195 causes the subassembly 198 to be pushed inwards and the cannula 202 to penetrate the plug 205 . Since the subassembly 198 can move no further inward, further pushing of the cartridge 192 into the adapter 191 causes cannula 202 to penetrate stopper 195 , thus putting drugfilled space 196 in indirect communication with the reservoir of device 190 .
- the stopper 195 is then held by subassembly 198 , further pushing of the cartridge 192 inwards causes the stopper 195 (which remains stationary) to move relative to the cartridge 192 (which is progressively accommodated in the interior of adapter 191 ), with a consequent emptying of the contents of the cartridge 192 through the cannula 202 into the reservoir of device 190 .
- FIG. 23 shows a sectional view of the components shown in sectional plan view in FIG. 21, after the cartridge 192 has been pushed most of the way home into adapter 191 . It can be seen that at this point, the stopper 195 (penetrated by cannula 202 which also penetrates plug 205 ) has almost reached the end 203 of cartridge 192 .
- the adapter 191 is not only held by the fit of the projection 204 into the socket 203 , but also by a releasable locking mechanism 210 .
- the releasable locking mechanism comprises 210 an aperture 211 on the device 190 and a resilient catch 212 on the adapter 191 which is biased into the position shown in FIG. 23 so as to hold the adapter firmly in place on device.
- the adapter 191 and the device 190 are sold together in kit form, optionally with the adapter already mounted on the device.
- FIG. 24 shows the kit after the cartridge 192 has disengaged the catch 212 allowing it to be withdrawn from the aperture 211 . This permits the adapter 191 to be removed from the device 190 by pulling the projection 204 from the socket 203 whereupon the plug 205 seals itself and thereby isolates the reservoir of the device.
- the adapter 191 can be safely disposed of without risk of injury.
- the adapter 191 allows the drug to be transferred to the reservoir with sterility ensured, since the user does not at any time handle any of the components in the fluid path.
- FIG. 25 shows another alternative embodiment of the device according to the invention, indicated generally at 220 .
- This embodiment differs from previous ones in that instead of a needle extending directly from the housing 221 , a tube 222 extends from the housing 221 and carries a connector 223 thereon to which a needle may be affixed before use.
- This device 220 is particularly suitable for intravenous drug delivery because the tube 222 allows the needle to be accurately positioned in a vein.
- FIG. 26 shows an alternative intravenous embodiment, indicated generally at 230 .
- the displaceable lower cover has been omitted and the device is actuated by a contact switch 231 positioned on the underside of the housing 232 .
- the switch 231 is pressed inwards (to the position shown in FIG. 26), thereby closing an electrical circuit and actuating a gas generating electrolytic cell 233 in the manner previously described.
- the cover can be omitted without interfering with other functions of the device.
- FIG. 27 shows the elastomeric diaphragm 240 utilized in the above-described devices according to the invention.
- the diaphragm 240 can also be used in other drug delivery devices according to the invention.
- the diaphragm 240 is shown in FIG. 27 in its relaxed position, as it would be when the reservoir is empty (see FIG. 6, for example).
- the diaphragm 240 substantially has the form of a truncated cone having a sloped portion 241 surrounding a flat portion 242 , with a lip 243 surrounding sloped portion 241 (lip 243 is used to attach diaphragm 240 to the housing of a drug delivery device).
- FIG. 28 shows the diaphragm 240 in the configuration in which the reservoir is full (see FIG. 1, for example).
- the central portion 242 is still flat, and the surrounding portion 241 has an arcuate curved cross-section, in the form of a substantially inverted U shape.
- the diaphragm 240 is bistable, such that it is stable in either the FIG. 27 or the FIG. 28 configuration.
- a particular advantage has been found to result from the fact that in moving from the reservoir full (FIG. 28) configuration to the reservoir empty (FIG. 27) configuration, very little energy is needed.
- bistable arrangements Unlike many bistable arrangements, only minimal force is required to move between the stable configurations. In many bistable arrangements a substantial amount of energy is required to move from one configuration to a midpoint, at which the amount of stored energy is relatively high, following which the stored energy is released to complete the transition.
- the diaphragm 240 rather than flipping between configurations, makes a smooth transition. However, in contrast to a completely pliable body, which cannot be depended on to exert force uniformly, the diaphragm 240 will behave dependably since it is constrained in its movement between configurations. This means that a predictable manner of movement is combined with a minimal expenditure of energy in actually effecting the transition between bistable configurations.
- the elastomeric diaphragm 240 (and others shown in alternative embodiments) and the flow diaphragm 26 of the flow regulating chamber 35 are elastomers. There are two preferred sources for this material. One is a bromobutyl compound made by Vernay Laboratories, Inc. of Yellow Springs, Ohio (material number: VL 911N7). The second is an ethyl propylene diene monomer (“EPDM”) material number Bryant 85055, made by Bryant Rubber.
- EPDM ethyl propylene diene monomer
- the material has a low durometer, which enables the material to remain soft. Moreover, it enables the diaphragm to keep air out and deflect from one stable position to the other with little energy. In addition, these elastomers provide a long shelf life. Another advantage is the ability to withstand gamma radiation without degradation of properties. As stated above, gamma radiation is used in some sterilization procedures. The ability of these materials to withstand gamma radiation is very important as these materials will be assembled in the device and sterilized. An additional advantage of using these materials is their lack of toxicity.
- FIG. 29 shows a circuit diagram of a controlling circuit particularly useful or a drug delivery device according to the invention.
- the components shown are a battery B 1 , a switch S 1 (activated by applying the device to the body), fixed resistors R 1 -R 6 and R 9 -R 10 , variable resistors R 7 and R 8 , a capacitor C 1 , transistors Q 2 -Q 6 , measurement terminals TP 1 and TP 2 , a light emitting diode LED, and a load U 1 which represents the electrolytic cell or other gas generating means.
- Reference numeral 251 denotes a section of the circuit 250 which functions as a current driver
- reference numeral 252 denotes a section of the circuit 250 which functions as an error circuit.
- the current through the electrolytic cell Ul determines the potential drop across variable the resistance comprising resistors R 7 and R 8 (which may be adjusted to calibrate the device or set the delivery rate). This potential drop is compared by the error circuit with the potential drop across a reference resistor R 1 , which itself depends on the voltage drop across the LED.
- the value of resistor R 1 is chosen to provide a potential drop equal to the drop measured across the resistors R 7 and R 8 when the correct current is flowing through the cell U 1 .
- the error circuit 252 forces the driver 251 to increase the current flow to the correct value. In practice, the error circuit 252 continually ensures that the current does not deviate from the correct value by constant feedback operation.
- Each of the transistors in the circuit 250 is a silicon-based bipolar transistor.
- the advantage of using bipolar transistors in particular is that they have been discovered to surprisingly withstand gamma radiation to a far greater extent than other types of transistors.
- the use of silicon as semiconductor is not essential but this material is currently less expensive than many other semiconductors. It has been found that by employing a circuit in which the or each transistor is a bipolar transistor, the circuit and hence the entire device can be subjected to intense gamma irradiation as a means of sterilizing the device after manufacture. Conventional integrated circuits are destroyed by the intense radiation required to sterilize a device quickly.
- a dose of 2.5 Mrad (25 kJ/kg) of gamma radiation may be required to sterilize a device.
- 2.5 Mrad (25 kJ/kg) of gamma radiation may be required to sterilize a device.
- the electronic components used in space missions such as the U.S. Space Shuttle missions. It was found that the same degree of radiation resistance was not required because the absorbed dose measured on the Space Shuttle averages approximately 0.4-0.5 Mrad.
- the drop in current gain exhibited after irradiation can be compensated for in advance.
- This drop in gain can be of the order of a tenfold drop or more, but can be predicted well in advance.
- current values which are sufficiently low the drop in voltage at the silicon junction of the transistor occurring as a result of the irradiation only slightly affects performance.
- a further advantage is gained using a circuit which employs a light emitting diode as a basis for the reference voltage used in the error correction circuit, since the LED reference source is not affected by the gamma radiation.
- the LED used is a gallium arsenide (GaAs) based LED which has been found to provide particularly good resistance to gamma radiation.
- FIG. 30 is a perspective view of the top side of a displaceable cover 160 forming part of a device according to the invention.
- FIG. 31 is a perspective view of the underside of cover 160 .
- Such a cover is described generally above in relation to the embodiment of FIGS. 4 - 8 , for example.
- the cover 160 is provided with formations 161 forming part of a locking mechanism as described above, with an aperture 162 through which a delivery needle protrudes in use.
- the cover 160 also has hinge formations 163 which enable the cover to be displaced relative to the housing between first and second positions as previously described.
- the cover 160 is shaped to improve retention of the device against the skin: thus. the top side 164 (FIG. 30) is convex, and the underside 165 (FIG. 31) from which the needle protrudes in use is concave. Accordingly, when the device has been applied to the skin of a subject removal of the device is resisted because the cover 160 conforms more closely to the skin. It is less likely that the device will peel from the skin without a conscious effort by the user since there is a lower likelihood of the periphery of the cover being detached from the skin.
- FIG. 32A schematically illustrates an alternative preferred embodiment of an electrical circuit 250 within a subcutaneous drug delivery device.
- the circuit 250 replaces the entire circuitry of FIG. 29.
- the delivery system 254 requires a constant current.
- This electrical circuit stabilizes the current supplied to the electrolytic cell without using components such as transistors which are sensitive to gamma radiation during sterilization. Gamma radiation is a standard method of sterilization of medical devices.
- a constant current supplied to the electrolytic cell results in a volume of gas which provides a desired constant delivery rate.
- the circuit uses a higher voltage than the previous embodiments along with current stabilizing resistive elements, such as, for example, resistors in series.
- FIG. 32A shows an electrical circuit 250 having a pair of batteries 253 coupled to a drug delivery system 254 by a current stabilizer 256 .
- the batteries 253 in the electrical circuit 250 can include, for example, but is not limited to, between one and three batteries, having voltages of, for example, 1.5 or 3V.
- FIG. 32A illustrates an embodiment having two batteries 253 .
- the current stabilizer 256 can calibrate the electrical circuit 250 to provide an appropriate current for the subcutaneous drug delivery device.
- the electrical circuit 250 can also include a switch 255 .
- the current stabilizer 256 can use a single resistor or alternatively as shown in FIG. 32A, the current stabilizer 256 includes two resistors 260 connected in series. In a preferred embodiment, the two resistors 260 have identical resistance values. The use of multiple resistors 260 can reduce the current charge as a result of accidental short circuiting of a resistor. The maximal delivery rate of the delivery system 254 with a short circuit condition at one resistor can only be twice the nominal rate. A change of battery voltage and a change of resistance of the electrical circuit 250 can change the current profile at the circuit 250 . In one embodiment, it is possible to control the current profile by selecting the voltage and number of batteries used in the circuit 250 . In a preferred embodiment, the current profile 257 is constant over time, as illustrated in FIG. 32B.
- FIGS. 33 A- 33 F schematically illustrate a drug delivery system in which an undesired delivery of a bolus of a medicament can occur.
- FIG. 33A schematically shows a delivery device 262 having a gas chamber 264 , a drug chamber 266 , a flexible diaphragm 265 , and a needle 270 .
- the gas is produced at a constant rate by the gas generator. As the gas is produced, the drug within the drug chamber can flow constantly to keep equal pressure within the device 262 .
- FIG. 33B shows the linear relationship of drug delivery over time.
- FIG. 33C shows an occlusion 268 occurring in needle 270 of the delivery device 262 .
- the pressure in the gas chamber 264 will rise as the gas generator continues to produce gas and the drug within the drug chamber 266 does not flow.
- FIG. 33D illustrates that an occlusion can result in the reduction or termination of delivery of the drug over time.
- the pressure in the gas chamber 264 can reach a high enough level to overcome and remove the occlusion.
- the drug within the drug chamber 264 can flow rapidly until back pressure in the gas chamber 264 and the pressure in the drug chamber 266 equalize, therein creating a bolus delivery of the drug.
- FIGS. 33E and 33F illustrate the relationship between drug delivery and time, as the occlusion is removed and the pressures equilibrate.
- the occlusion time duration depends upon the gas generation rate and the volume of the gas within the gas chamber 264 . The longer the time the subcutaneous drug delivery device worked before the occlusion, the bigger the volume of the gas in the chamber 264 , the longer the time needed to rise to the pressure to remove the occlusion 268 , the larger the bolus.
- FIG. 33F shows a graphical representation of the rapid flow of a drug delivery system as an occlusion is removed from a needle and the pressure equalizes.
- FIG. 34A shows a bolus prevention mechanism 272 within a drug delivery device 262 created by forming a constant, relatively high pressure level in the drug reservoir.
- the mechanism 272 is a valve 274 .
- the use of a valve 274 can create a constant high pressure 276 within the gas chamber 264 , while maintaining a low pressure 278 within the needle 270 of the delivery device 262 .
- the high back pressure 276 and the low pressure 278 within the needle 270 can prevent occlusions from clogging the delivery device 262 for lengthy periods of time, therefore minimizing or preferably preventing the formation and delivery of boli.
- FIG. 34B shows a graphical representation of the steady delivery of drugs over time created by the use of a bolus prevention mechanism within the drug delivery device of the present invention.
- a preferred embodiment of the subcutaneous drug delivery device 282 can also include an optical window 280 , shown in FIG. 35, which indicates to a user when delivery of a drug contained within the device 282 is complete.
- the drug is typically contained between the plastic housing and the elastomeric membrane or diaphragm that moves away from the housing as the drug fills the reservoir.
- the elastomeric membrane is proximate to the housing.
- the optical window 280 is located on the housing. When the membrane is proximate to the housing, the optical effect of the direct reflection of light from the elastomeric membrane results in clearly visible membrane color, for example, blue.
- the optical window 280 is a circular structure which allows light to enter and includes a pair of opaque sections 284 matching the membrane color and a transparent annular ring section 286 which allows the light to enter.
- the ring-like structure provides a more accurate assessment of the quantity of drug delivered.
- FIGS. 36 A- 36 C show changes to the optical path through the window during drug delivery which indicate to a user the amount of fluid in the reservoir of the drug delivery device.
- FIG. 36A illustrates a drug reservoir 290 bounded by a diaphragm 288 and a reservoir housing element 292 .
- the reservoir housing element 292 has the drug window 280 which includes both the opaque section 284 and the transparent section 286 .
- the color of the colored section 284 and the diaphragm 288 are the same, for example, both the colored section 284 and the diaphragm 288 are light blue in color.
- the drug reservoir 290 can be full of a medication to be delivered to a patient.
- the transparent section 286 of the optical window 280 appears as a different color to that of the colored section 284 and the diaphragm 288 .
- the transparent section 286 will appear as black.
- FIG. 36B illustrates a drug reservoir 290 after drug delivery has been partially completed.
- the diaphragm 288 can partially contact the optical window 280 and can block a portion of the transparent section 286 .
- Such a blockage optically changes the appearance of a portion of the transparent section 286 , that is, instead of appearing black, it appears as the same color as the colored section 284 .
- Such a change in color indicates to a user that drug delivery is partially completed.
- FIG. 36C illustrates a drug reservoir 290 after drug delivery has been completed.
- the diaphragm 288 can completely contact the optical window 280 and can block the entire transparent section 286 .
- the contact of the diaphragm 288 against the transparent section 286 can optically change the appearance of the color of the transparent section 286 , that is, instead of appearing black, the diaphragm becomes visible.
- a complete change in color of the transparent section 286 can indicate to a user the end of drug delivery.
- the drug delivery system can include an optical indicator to indicate proper application and operation to a user.
- the indicator can be, for example, a color marking system.
- the color marking system can be used to indicate to a user components of the drug delivery system which should be removed from the system prior to use.
- the color marking system can also indicate to the user whether or not the drug delivery system has been applied correctly or is operational.
- the color marking is, for example, yellow in color.
- the color marking can be applied directly to components of the drug delivery system or can be applied in the form of a colored label.
- the filling adaptor or syringe adaptor of the subcutaneous drug delivery device can have yellow labeling attached thereon to indicate to a user that the adaptor should be removed before activating the delivery device.
- the base of the delivery device can be produced (for example, dye in the plastic) with a color which contrasts with the color of the cover.
- the cover of the delivery device can be hingedly moved towards the base and covers all but a small portion at the base. The disappearance of the contrastingly colored base can indicate to a user that the drug delivery device has been correctly applied and activated.
- none of the parts of the device which include color marking or color labeling, can be visible to the user.
- the subcutaneous drug delivery device can include a pressure sensitive mechanism, such as in FIG. 37A, for preventing bolus delivery or rapid injection of a drug into the user.
- a switch 300 can prevent a rapid injection of drug to a user as a result of an increase in pressure in the drug delivery device.
- the switch 300 can help to avoid an increase in pressure within the drug delivery device caused by blockage of the needle.
- the switch 300 can form part of a circuit 250 , as shown in FIG. 32A, which controls the power supply to a gas generating portion of the drug delivery device.
- FIGS. 37 A- 37 C One embodiment of the switch 300 is shown in FIGS. 37 A- 37 C.
- the switch 300 which is part of a circuit 308 , is made from a conductive membrane 302 and a conductive lever 306 is located on the printed circuit board 159 , as seen in FIG. 37A.
- the switch 300 has a chamber 304 which is sealed by the conductive membrane 302 as seen in FIGS. 37B and 37C.
- the chamber 304 contains an accurate amount of gas, such as, for example, air, and can be made of a solid material whose volume is not affected by pressure and is non conductive electrically, referred to as a solid isolator.
- the membrane 302 has a raised annular portion to allow the membrane to flex depending on the pressure differential between the chamber 304 and the expandable chamber 14 .
- the lever 306 is designed to rest upon the membrane 302 during operation. When the conductive lever 306 contacts the conductive membrane 302 , the circuit 308 can be closed, thereby allowing the gas generating portion of the device to operate 310 . As long as the pressure within the gas generating portion of the delivery system is lower than the pressure within the chamber 304 , the lever 306 can contact the membrane 302 .
- the pressure within the gas generating portion can increase to a higher level than the pressure within the chamber 304 .
- the pressure within the chamber 304 is lower relative to the expandable chamber 14 and the membrane 302 is pushed away from contact with the lever 306 , as shown in FIG. 37B.
- the lever 306 is no longer in electrical contact with the membrane 304 and the circuit opens, thus shutting off power to the gas generating portion of the device. This, in turn, stops any pressure build-up and potential for a boli delivery.
- the conductive membrane or lever can be made from aluminum or copper, for example.
- FIG. 37D illustrates circuit 308 as part of circuit 256 which was shown in FIG. 32A.
- the switch 300 is in series with switch 255 . Both switches 255 and 300 must be closed to generate gas. Switch 300 is normally closed and switch 255 is closed to start the gas generation. As indicated above, switch 300 only opens if the pressure increases to a current level, such as due to a blockage.
- FIGS. 38A and 38B illustrate an alternative embodiment of a pressure sensitive mechanism 300 .
- the switch 300 includes an isolator membrane 314 , mounted above a chamber 304 , and a conductive thread 316 combined with the membrane 314 .
- the thread will remain intact, thereby completing the circuit for the gas generator, which remains in an on position 310 .
- the gas generating portion can increase to a higher level than the pressure within the chamber 304 .
- the pressure differential can cause the membrane 314 to sink into the chamber 304 , thereby severing the thread 316 .
- Such a break can open the circuit 308 , thereby preventing the gas generator from producing gas 312 and preventing an increase in pressure in the drug reservoir.
- the circuit once the circuit is open the circuit cannot be closed again, i.e. once the membrane is depressed the thread is severed.
- FIGS. 39 A- 39 C illustrate another preferred embodiment of a pressure sensitive switch 300 .
- FIG. 39A is an enlarged perspective view of the switch 300 with portions broken away.
- FIGS. 39B and 39C are schematics of the switch 300 .
- the switch 300 is formed from a pair of electrodes 318 , extending into a capsule 319 .
- Each electrode 318 connected to the circuit 308 contacts a droplet of mercury 320 located in a channel which opens onto a large chamber 304 .
- the droplet 320 of mercury maintains the current between contacts as long as the pressure in the gas generating portion is less than the pressure within the chamber 304 . Such a contact can close the circuit 308 , thereby allowing the gas generator to operate 310 .
- the pressure in the chamber 304 can be lower than the pressure within the gas generating portion of the delivery device, thereby causing the mercury droplet 320 to move towards the chamber 304 and away from the electrodes 318 .
- the mercury droplet responds to the relative pressure between the gas generating portion and the chamber 304 . Such a movement opens the circuit 308 , thereby preventing the gas generator from producing gas and increasing the pressure in the drug reservoir.
- FIGS. 37 A- 37 D While both the first embodiment, FIGS. 37 A- 37 D, and the third embodiment, FIGS. 39 A- 39 C, have the capability to have the switch 300 closed again if the pressure equalizes, it is contemplated that the pressure will not decrease and therefore once the switch is open, it will remain open and the power to the gas generator will not be restored.
- Another preferred embodiment of the subcutaneous drug delivery system includes a mechanism which reduces tolerances and thus errors during manufacture of the device.
- certain components need to have a particular tolerance.
- the volume of the internal housing may be outside of a specified desired range.
- an insert for example, a foam insert that receives the internal components of the device, maintains an accurate internal volume so that upon assembly, the volume of the internal housing, and thus, the drug reservoir is within an accurate range.
- a subcutaneous drug delivery device 322 is shown in FIG. 40.
- the device 322 can have a cover 324 and a base 326 and can house an inner component 328 .
- the device 322 can also have an internal volume 330 between the cover 324 and the inner component 328 .
- the base 326 , cover 324 , and inner components 328 need to be manufactured within certain tolerances. Due to the tolerances of the components, the internal volume 330 can be outside of a specific range.
- an insert 332 can be used to maintain the precise drug reservoir 12 necessary within the device 322 . The insert 332 forces the inner component 328 toward the cover 324 of the delivery device 322 .
- the internal air volume 330 includes the internal chamber which defines the reservoir 12 and the expandable chamber 14 , and air volume between components and below the expandable chamber 14 , which is referred to as a dead air volume. Dead air can also be defined as residual air below the diaphragm after the primming.
- the insert 332 is a flexible material. In a preferred embodiment, the insert 332 is closed foam; the air pockets or bubbles are sealed so not forming a part of the dead air.
- the internal volume 330 of the device 322 can be used as a drug reservoir.
- the drug delivery device 336 can include an activation lever 334 , as shown in FIGS. 41A and 41B to initiate gas generation in the expandable chamber which in turn controls the delivery of the drug from the device.
- the activation lever 334 includes a puncturing device 340 and an electrical contact 342 .
- the drug delivery device 336 includes an electrolytic cell 338 mounted next to the activation lever 334 .
- the electrolytic cell 338 has a foil cover, for example, aluminum foil, to preserve chemical ingredients within the cell 338 . Without the foil, the electrolyte water content could evaporate during storage affecting the performance of the device 336 .
- the activation lever 334 can be mounted to the drug delivery device by a pivot 344 .
- the puncturing device 340 of the activation lever 334 can puncture the foil cover of the electrolytic cell 338 , thereby allowing the gases generated by the cell operation to escape and to expand the expandable gas chamber and thereby compressing the drug reservoir of the delivery device 336 .
- the electrical contact 342 on the lever 334 engages a contact 346 on the printed circuit board of the device 336 which starts the delivery of the drug.
- the contact 342 on the lever 334 engages the two contact 346 on the delivery device 336 moving one of the contacts 346 into engagement with the other contact 346 for an indefinite time period.
- the lever 334 can be made from a plastic material.
- a plastic lever 334 can be economically produced using an injection molding technique, for example.
- the plastic lever 334 can be secured to the pivot 344 by a snap fit and thereby not require soldering.
- the plastic lever 334 can be manufactured such that the lever does not bend when forming an electrical contact with the drug delivery device 336 or when puncturing the foil on the electrolytic cell 338 .
- Another embodiment of the drug delivery system relates to controlling the rate of delivery by parameters such as, for example, residual air volume, base permeability, membrane seal and membrane permeability.
- an air space can be created within a drug delivery system by providing a cavity for air, for example.
- Such an air space can be considered as a residual or dead air volume and can have an effect on the drug delivery rate.
- the larger a residual air volume the greater the effect on delivery rate.
- Residual air volume can be controlled by design characteristics of the geometry of the inner parts of the device.
- a high residual air volume within the device can add a delivery period between the activation of the drug delivery system and the actual start of drug delivery.
- FIG. 42 illustrates a graph of a delivery 350 of drugs through a drug delivery system under normal or low residual air volume conditions and delivery 352 under high residual air volume conditions.
- the drugs delivered under high residual air volume conditions are delayed 354 between the activation of the system and the start of drug delivery.
- the delay can be reduced or eliminated within the system.
- Another embodiment of the drug delivery system relates to controlling the material characteristics of the device components, such as, for example, the permeability of the system which in turn affects the delivery rate of the drug.
- Permeability can be controlled, for example, by both changing the geometery of the inner components of the delivery system and by changing the materials used to manufacture the system.
- By lowering the permeability of the delivery system less gas can diffuse out from the system. With less gas leaving the system, the variance in delivery rate can be lowered or eliminated.
- a constant delivery rate of the drug can be maintained.
- FIG. 43 illustrates a graph of delivery 356 of drugs for a low permeability system and delivery 358 for high permeability system. As shown, a high permeability yields a higher delivery rate at the onset of delivery 359 and a lower rate of delivery 360 as time goes on, compared to a delivery system having a normal permeability 356 .
- Packaging of a drug delivery device can be an important factor relating to the practical storage and use of the device at different altitudes and humidities. For example, proper packaging of the device can extend the storage period of the device, without an appreciable affect on the device performed. Proper packaging can also prevent environmental affects, such as, the diffusion of water from the electrolyte that provides for the gas generation from the drug delivery device without additional protection, internal to the device.
- a hermetic packaging for a drug delivery system achieves extended shelf conditions and simplifies the barometric pressure valve and the electrolytic cell of the system.
- the drug delivery system was packaged using a blister and a Tyvek lid to maintain sterility and protect the device during a two year shelf life.
- the Tyvek lid is gas permeable when exposed to atmospheric conditions, such as, for example, non-controlled pressure and humidity conditions.
- the valve has two positions. In one position, the storage position, the valve membrane can move. In another position, the working position, the valve builds pressure against the drug delivery system needle.
- the electrolytic cell can be fully protected by aluminum foil. Further, the foil seal requires the use of an activation lever. Pinching of this foil around the cell is required for system operation.
- the blister and Tyvek lid packaging can be replaced by a hermetically sealed packaging.
- the issues of valve position and adverse environmental impact, such as, for example, diffusion can be solved without any internal feature protection.
- an alternative drug delivery system 362 is shown with a stationary valve 368 .
- the drug delivery system 362 is shown without the displaceable cover 143 , such as shown in FIGS. 14 and 15.
- the internal space of the drug delivery device 362 of FIG. 44A defines an expandable chamber 147 when the diaphragm 148 is in the position shown or a reservoir when the diaphragm is in the position shown in dotted outline at 149 .
- the device 362 has a switch 151 which is engaged by a valve 150 , such as seen in FIGS. 14 - 16 , to close the switch to activate the process.
- the stationary valve 368 does not move.
- the stationary valve 368 has an airtight chamber 370 sealed by a flow diaphragm 372 , similar to the airtight chamber 36 and diaphragm 26 of FIG. 3.
- the flow diaphragm 372 of this embodiment does not have a projection which is received in the inlet associated with the needle such as in some of the previous embodiments.
- the flow diaphragm 372 has a flat circular portion 374 for sealing the top of the needle 376 .
- the drug flows through a port 378 from the reservoir to an annular chamber 380 underlying the flow diaphragm 372 .
- the pressure in the reservoir and the annular chamber 380 is equal to the pressure inside the controlled volume, the airtight chamber 370 , therein stressing/flexing the flow diaphragm 372 and opening the entrance to the needle 376 .
- the valve can become a stationary valve, more accurate and with longer shelf life in extreme conditions.
- the aluminum protective liner and the pincher mechanism are no longer needed for the cell functioning.
- the packaging is illustrated in FIG. 45.
- the drug delivery system 362 can be enclosed between a foil layer 364 and a non-permeable blister 366 to maintain internal pressure despite environmental parameter changes, such as pressure and temperature.
- the blister is a semi-rigid package with an aluminum cover or low permeability plastic welded at its bottom.
- the drug delivery device is inserted into the cavity.
- the blister is made of PET.
- the cover is made of aluminum foil 38 micron with 2 micron of H.S.C. for the welding.
- the surface area of the package is about 0.034 m 2 with an average thickness of 0.3 mm, with a permeability factor of about 0.4. Given these dimensions, the pressure in the device is calculated to decrease up to about 3% in two years.
- the foil layer 364 can be, for example, an aluminum foil.
- a secondary packaging device can be used with a primary gas permeable packaging, such as a blister and Tyvek lid, to extend the storage life of the device.
- a primary gas permeable packaging such as a blister and Tyvek lid
- the use of secondary packaging can increase the shelf life of a delivery device without altering the drug delivery rate.
- the secondary packaging device 380 can be a cylindrical container 382 , as shown in FIG. 46.
- the cylindrical container 382 can be an aluminum or tin can, for example.
- the container 382 can hold either four delivery device packages 384 , as shown in FIG. 46, or can hold more delivery device packages 384 .
- the drug delivery device Prior to storing the drug delivery packages 384 within the container 382 , in one embodiment, the drug delivery device can be packaged between a blister and a Tyvek lid and then sterilized.
- FIGS. 47 A- 47 C illustrate an alternative embodiment for a secondary packaging device 380 .
- the secondary packaging device is a rectangular container 386 .
- the rectangular container 386 can have a cover portion 390 and a base portion 388 where the base portion 388 can be used for storage of drug delivery packages 384 .
- FIG. 47A shows an embodiment of the cover portion 390 in a closed position while FIG. 47B shows an embodiment of the cover portion 390 in an open position where the cover 390 can completely disconnect from the base portion 388 .
- the cover portion 390 can be hingedly attached to the base portion 388 .
- the rectangular container 386 in one embodiment, can be designed to hold up to four drug delivery devices 384 , as shown in FIG. 47B. In another embodiment, the container 386 can be sized to hold a single delivery device 384 , as shown in FIG. 47C. A limitation to the use of the container 386 holding four delivery devices 384 can include using the fourth, or last, device within opening the container 386 . For a container 386 holding up to four delivery devices, the dimensions of the container can be about 240 mm ⁇ 148 mm ⁇ 70 mm. For a container 386 holding a single delivery device, the dimensions of the container can be about 120 mm ⁇ 110 mm ⁇ 35 mm.
- the container 386 can be made from a plastic material.
- the container 386 can include aluminum foil covered with, for example, polyethylene lamination to close the packaging using heat.
- FIG. 48 shows an alternative embodiment of the drug delivery device indicated generally at 400 .
- the delivery system is adapted for epidural, intraterial and intrathecial administration.
- a tube 404 extends from a barometric pressure valve 406 to a location on the housing 402 .
- a catheter 410 is secured by a collet gripper 408 to connect to the tube 404 .
- An alternative embodiment drug delivery device 412 of FIG. 49 has a piece of tubing 414 from an epidural needle 416 connected directly to a tube 418 located within the housing 402 .
- the tube 418 extends from the barometric valve 406 .
- FIG. 50A shows a drug delivery device 420 with a luer 422 for attaching a tubing 424 from an epidural needle 416 .
- a tube 404 extends from the barometric valve 406 to the luer 422 .
- FIG. 50B shows the drug delivery device 420 with the luer 422 .
- the tubing 424 from the epidural needle 416 attaches to the luer 422 .
- the epidural needle set has a hydrophilic membrane 428 for filtration.
- drug used herein includes but is not limited to peptides or proteins, hormones, analgesics, anti-migraine agents, anti-coagulant agents, narcotic antagonists, cleating agents, anti-anginal agents, chemotherapy agents, sedatives, antineoplastics, prostaglandins and antidiuretic agents.
- Typical drugs include peptides, proteins or hormones such as insulin, calcitonin, calcitonin gene regulating protein, atrial natriuretic protein, colony stimulating factor, betaseron, erythrogpoietin (EPO), interferons such as a,b or g interferon, somatropin, somatotropin, somastostatin, insulin-like growth factor (somatomedins), luteinizing hormone releasing hormone (LHRH), tissue plasminogen activator (TPA), growth hormone releasing hormone (GHRH), oxytocin, estradiol, growth hormones, leuprolide acetate, factor VM, interleukins such as interleukin-2, and analogues thereof; analgesics such as fentanyl, sufentanil, butorphanol, buprenorpbine, levorphanol, morphine, hydromorphone, hydrocodone, oxymorphone, methad
Abstract
A drug delivery device having a housing having an internal reservoir in communication with a drug delivery outlet via a fluid path. An expandable chamber disposed adjacent to the reservoir forces drug from the reservoir to the outlet when supplied with a gas. A flow regulating chamber, in communication with the fluid path, is capable of volumetric changes in response to temperature and/or pressure changes. An increase in the volume of the flow regulating chamber increases flow resistance to the outlet and thereby counteracts the corresponding increase in delivery rate resulting from the expansion of the expandable chamber due to the same volumetric changes in response to temperature and/or pressure. In a preferred embodiment, an electrical circuit has a current stabilizing element in electrical communication with an electrolytic cell which supplies the gas. A throttling device maintains a higher pressure in the device to reduce possible clogging of the fluid path. In a preferred embodiment, the drug delivery device is packaged to insulate the device from atmospheric pressure and humidity.
Description
- This application is a divisional of U.S. Ser. No. 09/577,033 filed on May 23, 2000, which is a continuation-in-part of U.S. Ser. No. 09/072,875 filed on May 5, 1998 which claims priority to U.S. Provisional Application No. 60/045,745 filed May 6, 1997, and all of whose entire disclosures are incorporated herein by reference.
- A wide range of subcutaneous drug delivery devices are known in which a drug is stored in an expandable-contractible reservoir. In such devices, the drug is delivered from the reservoir by forcing the reservoir to contract. (The term “subcutaneous” as used herein includes subcutaneous, intradermal and intravenous.)
- Such devices can be filled in the factory or can be filled by the pharmacist, physician or patient immediately prior to use. In the former case it may be difficult to provide the required drug stability in the device since the drug will be stored in the reservoir for a shelf life of from several months to a number of years. In the latter case, it is difficult to ensure that the drug has completely filled the reservoir, i.e. that the reservoir and fluid path do not contain any air bubbles. In general, this requires priming the device by filling it in a certain orientation which ensures that the air bubbles are pushed ahead of the drug, such as with the filling inlet at the bottom and the delivery outlet at the top (to allow the bubbles of air to rise during filling).
- A further problem associated with subcutaneous drug delivery devices is that in many cases gas generation is used to compress the reservoir. While it may be possible to ensure a constant or a controllably varying rate of gas generation (for example by passing a constant current through an electrolytic cell), this does not ensure a constant rate of drug delivery.
- The amount of compression of the reservoir (and thus the rate of delivery of drug) depends on the amount by which the volume of the gas generation chamber expands. The behavior of an ideal gas is governed by the equation PV=nRT, in which the volume of gas, V, is proportional to the number of moles of gas, n, and the temperature, T, and inversely proportional to the pressure, P.
- An electrolytic cell working at constant current will generate a constant number of moles of gas per unit time. However, changes in the temperature of the gas and in the atmospheric pressure exerted on the gas will cause the volume to vary. Even if the temperature of the device remains constant, the fact that atmospheric pressure drops by approximately 3% for every increase in altitude of 300 m means that the delivery rate will vary substantially between a location at sea level and a higher altitude location (for example, Denver, Colo. is approximately 1 mile or 1.6 kilometers above sea level, so atmospheric pressure will be approximately 17% lower on average than at sea level). Similarly, normal changes in atmospheric pressure due to the weather cause the delivery rate of this type of device to vary.
- For devices which employ a needle to penetrate the skin there is a danger that after use the device may accidentally infect the patient or others if not properly disposed of. WO 95/13838 discloses an intradermal device of this type having a displaceable cover which is moved between a first position in which the needle is retracted before use and a second position in which the needle is exposed during use. Removal of the device from the skin causes the cover to return to the first position in which the needle is again retracted before disposal. However, this device does not include a locking mechanism in the assembly for locking the device prior to use to minimize accidental contact with the needle and/or accidental actuation of the device that may occur during shipping and/or storage.
- When filling a drug delivery device, the conventional method is to use a syringe, which carries the risk of accidental injury. The present invention has as a further aim the improvement of safety when syringes are used. The present invention also aims to decrease the possibilities that the needle could become exposed by accident before or after use, for example, by a child playing with the device if not properly disposed of. Clearly given the risks associated with infectious diseases, particularly those carried by blood, any possibility of accidental infection must be minimized to the utmost and preferably eliminated entirely.
- Our International Application No. PCT/IE 96/00059 discloses a medicament delivery device having a filling mechanism integral within the housing which receives a cylindrical cartridge (or “vial”) sealed by a sliding stopper. When the cartridge is pushed into the filling mechanism, a hollow needle in the filling mechanism penetrates the stopper and establishes communication between the interior of the cartridge and the device's internal reservoir. Continued movement of the cartridge into the filling mechanism causes the stopper to slide into the cartridge and act as a piston to pump the medicament from the cartridge into the reservoir. While this mechanism overcomes some of the disadvantages of using a syringe, it also makes the device bulkier.
- Thus, there is a need to provide a subcutaneous drug delivery device having an improved filling mechanism which facilitates filling the device in an orientation-independent manner.
- There is a further need to provide a filling system that is less bulky.
- There is still a further need to provide a filling system that maintains the needles within the system in a recessed fashion so as to minimize the risk of injury associated with needles.
- There is yet a further need to provide a device which operates at a substantially constant delivery rate independently of the ambient atmospheric pressure.
- There is a further need to provide a drug delivery device in which the needle is retracted from the housing surface before and after use so as to minimize injury due to accidental contact with the needle.
- There is yet a further need to provide a device having improved adhesion to the skin, i.e. for which there is less likelihood that the device will become detached during use.
- The present invention overcomes these and other disadvantages associated with prior art drug delivery devices and filling systems. Stated generally, the present invention provides for a drug delivery device having a housing that has an internal reservoir and an expandable chamber disposed relative to the reservoir. The device also has a drug delivery needle extending from the housing for penetration of the skin of a subject. The needle has an outlet for drug delivery. The drug delivery device of the present invention further includes a fluid path defined between the delivery needle outlet and the reservoir and means for providing a gas at a controllable rate into the expandable chamber. The device also includes a flow regulating chamber, in communication with the fluid path, which is capable of volumetric changes in response to temperature and/or pressure changes.
- By calibrating the degree of increase or decrease in flow resistance, it is possible to compensate for differences occurring in the rate of delivery which arise because of pressure- or temperature-induced differences in the volume of a given mass of gas in the expandable chamber. Thus, if the ambient atmospheric pressure drops, the gas in the expandable chamber will tend to expand and thereby force more drug from the reservoir. This will however be counteracted by the flow regulating chamber which will increase flow resistance along the fluid path and thereby counteract the increased flow rate arising from the effect of the tendency for the expandable chamber to expand.
- Preferably, the expandable chamber causes contraction of the reservoir in use. Further, preferably, the flow regulating chamber alters the drug delivery rate by varying the flow resistance between the reservoir and the outlet. Preferably, the flow regulating chamber is associated with a blocking member which upon expansion of the flow regulating chamber moves within the fluid path so as to restrict the flow of drug.
- Further, preferably, the blocking member comprises a formation provided on a displaceable member which at least partially bounds the flow regulating chamber, the formation being disposed adjacent to an inlet of a conduit forming part of the fluid path, such that restriction of the fluid path occurs when the blocking member is moved into the inlet of the conduit. By having a suitably shaped and sized formation relative to the inlet, it is possible to precisely vary the flow resistance of the conduit, and thereby precisely control the delivery rate notwithstanding changes in ambient temperature and/or pressure.
- Suitably, the shape of the blocking member is adapted to cut off the fluid path completely with a predetermined degree of expansion of the flow regulating chamber. Alternatively, the formation can be shaped such that the fluid path is never entirely cut off.
- In preferred embodiments of the invention, a displaceable cover is connected to the housing such that displacement of the housing relative to the cover when the cover has been applied to the skin of a subject causes the delivery needle to penetrate the skin of the subject. Such a displaceable cover is suitable for concealing the needle before and after application to the skin of a subject, which prevents injury and reduces the possibility of contamination of the needle.
- In another aspect of the invention the expandable chamber is provided with a release valve operatively connected to the displaceable cover such that the movement of the housing relative to the cover controls the closing of the valve and thereby the sealing of the expandable chamber. This feature is not dependent on the existence of the flow regulating chamber.
- The valve enables the device to be supplied with the displaceable member positioned such that the volume of the (empty) reservoir is minimized and that of the expandable chamber maximized. Thus, the reservoir can be of substantially zero volume initially, with no entrapped air volume. The device can then be primed or loaded by filling the reservoir, for example using a syringe- or cartridge-based filling mechanism. As the reservoir is filled, the displaceable member moves to expand the reservoir and thereby contract the expandable chamber. The valve allows the air or other gas in the expandable chamber to be exhausted into the atmosphere.
- The device can then be applied to the skin of the user. When the device is applied the housing moves relative to the cover which is applied to the skin, not only does the needle penetrate the skin, but also (because the valve is operatively connected to the cover) the valve is closed to seal the expandable chamber. If the valve remained open then gas supplied into the expandable chamber would be free to escape and delivery would not be effected. While it would be possible for the user to close the valve manually, this would clearly leave open the possibility of error. Instead, by connecting the valve operatively to the cover, it is possible to ensure that the valve is always closed when the device is applied to the skin.
- Preferably the valve comprises two components one of which is connected to the cover and the other of which is connected to the expandable chamber, such that relative movement of the housing towards the cover causes the valve to close.
- The invention includes a displaceable cover that is displaceable relative to the housing between a first position in which the needle is concealed from the exterior of the device, and a second position in which the delivery needle protrudes from the device for penetration of the skin. A further aspect of the present invention comprises means for locking the device in the first position after a single reciprocation of the device from the first position to the second position and back to the first position.
- The displaceable cover is an advantageous feature since it solves a problem unaddressed by prior art devices. Our prior art device has a locking mechanism to lock the housing in place after use and keep the needle concealed. However, there is no mechanism to prevent premature activation prior to intended use that may cause the needle to protrude accidentally thereby giving rise to injury. According to the present invention, however, the locking means engages automatically when the cover and housing are reciprocated relative to one another, i.e. the housing and cover are moved relative to one another to cause the needle to protrude when the device is applied to the skin. This relative movement is reversed when the device is removed thereby concealing the needle but also engaging the locking means to prevent the needle from being exposed again by accident.
- In a preferred embodiment, the locking means comprises a mechanical latch which is brought into operation by the reciprocation. Further, it is preferred that the latch comprises a pair of elements mounted on the cover and the housing respectively. It is preferred that the elements be shaped such that they can have two relative configurations when the cover is in the first position relative to the housing. It is preferred the elements have a first movable configuration in which the elements are mutually movable, and a second locked configuration in which the elements are prevented from mutual movement. It is also preferred that the reciprocation of the cover and the housing causes the elements to pass from the first movable configuration, through an intermediate configuration when the cover is in the second position relative to the housing, and then to the second locked configuration, thereby preventing any further movement of the cover relative to the housing.
- In preferred embodiments illustrated further below, one of the elements is provided with a recess which is adapted to receive a projection on the other of the elements, the recess and the projection being spaced apart from one another in the movable configuration, and being in engagement with one another in the locked configuration.
- These embodiments are preferred because while they are mechanically simple and easy to make, their very simplicity provides fewer opportunities for malfunction.
- In a preferred embodiment of the present invention, movement of the cover relative to the housing is initially prevented by a removable locking member. This feature helps to prevent accidental injury occurring because the needle is only exposed when the housing is moved relative to the cover, i.e. only after the user has specifically removed the removable locking member. The presence of the removable locking member also prevents the means for providing a gas from being actuated. This prevents the device from being exhausted by accidental switching on at an incorrect time. In a preferred embodiment of the present invention, the removable locking member comprises a laminar member inserted between the cover and the housing.
- In a further aspect of the invention, the surface of the housing from which the needle extends or the surface of the displaceable cover, if present, is of a concave cross-section. When the device has been applied to the skin of a subject, removal of the device is resisted because the cover conforms more closely to the skin. In prior art devices, it has been found that retention on the skin of the user is problematic because of adhesive failure, for example. Using a concave surface causes the device to be retained more effectively by adhesive means.
- With prior art devices the lower surface tends to be peeled away from the skin more easily as the edges of the device can be detached relatively easily. Where a concave lower surface is used the edges tend to remain in contact with the skin and removing the device is thus more difficult. In effect a shear force is required rather than a simple peeling, and this assists in preventing accidental removal. This feature is not dependent on the existence of the other aspects of the invention.
- In a modified device according to the invention, the needle extends from the lower surface of the housing is replaced by a tube extending from the housing. The tube is adapted for carrying a drug delivery needle. Such a device is preferred for intravenous delivery of a drug as the needle carried on the end of the tube can be accurately located in a suitable vein. The needle may be integral with the tube or supplied separately.
- In a further preferred feature of the present invention, the drug reservoir is separated from the expandable chamber by a diaphragm. The diaphragm exhibits bistable behavior such that in one stable state the reservoir is full and in the other stable state the reservoir is empty. The diaphragm is shaped to minimize the energy required in the transition between the stable states. In a preferred embodiment of the present invention, the diaphragm is in the form of a body having a peripheral lip connected to a substantially flat central section by a flexible annular section. The flexible annular section assumes a substantially frusta-conical cross-section in one of the states and assuming an arcuate curved cross-section in the other state.
- Preferably, the means for providing a gas comprises an electrical circuit in which any transistors are bipolar transistors having a gain of not less than 500, such that the circuit can be irradiated by ionizing radiation without destroying the circuit.
- This type of transistor has been found to be advantageous as it enables the device to be sterilized using gamma radiation with the electronic components intact. While a certain loss of performance results from the irradiation, the high gain transistor still has an adequate gain after irradiation to operate reliably. It is preferred that the current gain of the or each transistor is not less than 750. For example, a transistor having a rated current gain of 800 has been found to give an excellent performance after irradiation, despite the fact that irradiation lowers the current gain characteristics of the transistor by a factor of ten or more. The initial high gain compensates for the subsequent reduction arising from irradiation. The fact that the effects of irradiation can be predicted means that the performance after irradiation is reliable.
- It is also preferred that the circuit further include a reference component across which a fixed potential drop is measurable. The reference component is essentially unchanged by the ionizing radiation. If a reference voltage is used which is not affected by the irradiation process, then the operation of the other components in the circuit may be determined by this reference voltage. For example, while the current gain of a group of transistors may vary individually when a batch is irradiated, each such transistor can be used to make an identically functioning amplifier if the output current of the amplifier is matched against a given reference component.
- Light emitting diodes (LEDs) have been found to be affected less than other standard components when irradiated by gamma radiation. Thus, the reference component of the preferred embodiment comprises a light-emitting diode. Gallium arsenide (GaAs) LEDs are virtually unaffected by gamma rays. Thus, it is preferred that the light emitting diode employs gallium arsenide as a semiconductor.
- In a further aspect, the present invention provides for a subcutaneous drug delivery kit including a drug delivery device as described above. The device is provided with a filling mechanism associated with the reservoir. The filling mechanism includes means for receiving a filling adapter. The filling adapter includes a body which is adapted to accommodate a drug cartridge. The body has means for engaging the adapter-receiving means of the drug delivery device at one end thereof, means for receiving a cartridge at the other end thereof, and transfer means for transferring a liquid from a cartridge to the filling mechanism of the device as the cartridge is emptied. The adapter-receiving means and the corresponding engaging means provided on the adapter together constitute a releasable locking mechanism which holds the adapter in place on the device once engaged. The locking mechanism is disengaged by the cartridge when the cartridge is emptied within the adapter.
- The kit according to the invention is advantageous because it eliminates the need for a bulky filling mechanism which accommodates the cartridge within the device, and instead employs an adapter which is releasable from the device so as to enable the filled device to be less bulky than prior art cartridge-based devices.
- Furthermore, the locking mechanism employed is only disengaged when the cartridge has been completely emptied, i.e., the rubber stopper within the cartridge is pushed to the bottom. If the cartridge used is of a type which will empty when the stopper is pushed to the bottom, this feature ensures accurate loading of the reservoir, i.e. it is not possible to easily remove the device before the reservoir is filled with the correct dose of medicament.
- Suitably, the transfer means comprises a hollow double-ended needle, one end of which is associated with the engaging means such that it communicates with the filling mechanism when the adapter is engaged with the device, and the other end of which is associated with the cartridge receiving means such that it communicates with the interior of a cartridge having a penetrable stopper when such a cartridge is received by the adapter.
- Such a hollow double ended needle can be replaced by a pair of needles which are connected by a conduit, such as a moulded conduit running through the body of the adapter and having a needle mounted at either end such that it is functionally equivalent to a double ended needle. Preferably, both ends of the needle are disposed within the body of the adapter such that they are recessed from the exterior of the body when the adapter is disengaged from the device. This arrangement is preferable for safety reasons, as it allows the adapter to be disposed of without fear of accidental injury occurring from casual handling of the adapter.
- In a preferred embodiment, the releasable locking mechanism comprises a pair of locking members provided on the adapter receiving means and the corresponding engaging means, respectively. One of the locking members is movable between a locking position and a disengaging position. The movable locking member is disposed relative to the body such that, in use, when a cartridge is emptied within the body, the movable locking member is moved from the locking position to the disengaging position under the action of the cartridge.
- Where a substantially cylindrical cartridge is employed, the body can receive the cartridge within a passage having a diameter sufficient to completely accommodate the cartridge. However, the end of the passage is of slightly narrower diameter on account of a projection provided on the movable locking member. Thus, when the cartridge completely emptied by pushing the stopper to the bottom, it contacts the movable locking member and pushes it out of the way, thereby disengaging the locking mechanism.
- Suitably, the movable locking member is resiliently biased towards the locking position. Preferably, the movable locking member is a latch which automatically locks the adapter and device to one another when engaged together. It is preferred that the cartridge is emptied by moving the penetrable stopper against the adapter
- The present invention further provides a subcutaneous drug delivery kit including a device according to any preceding claim further comprising a filling mechanism associated with the reservoir, the filling mechanism comprising means for receiving a filling adapter as defined herein and a filling adapter. The filling adapter has a body adapted to receive a syringe. The body has means for engagement with the adapter-receiving means of the device at one end thereof, syringe-receiving means at the other end thereof and transfer means for transferring a liquid from the syringe to the filling mechanism of the device as the syringe is emptied. The transfer means includes a conduit associated with the syringe receiving means, the conduit leads to a needle which is associated with the engagement means and is disposed within the body of the filling adapter.
- It is preferred that the needle disposed within the body of the filling adapter is recessed from the exterior of the body when the adapter is disengaged from the device. It is also preferred that the adapter receive the syringe without a needle. Since the needle on the adapter is recessed from the exterior of the adapter body and the syringe has no needle when filling, a conventional syringe (minus needle) can be used to fill the device without any risk of accidental injury.
- A further aspect of the present invention provides a method of filling a drug delivery device. The method includes providing a drug delivery device having a drug reservoir. The reservoir is associated with a filling mechanism having filling adapter receiving means. The method further includes providing a filling adapter having a first end for engagement with the adapter receiving means, and a second end for receiving a syringe and causing the filling adapter receiving means to receive the filling adapter. The method further includes causing the second end of the filling adapter to receive a syringe having liquid stored therein and a needle, and providing a conduit for communication between the liquid stored within the syringe and the first end of the filling adapter. The method of filling further includes emptying the syringe and concurrently transferring the liquid from the syringe to the device via the conduit. In yet further aspects, the invention provides a filling adapter as defined above and a diaphragm as defined above.
- In a preferred embodiment of the present invention, the electrical circuit used to provide gas to the expandable chamber includes a high voltage supply, such as, for example, between one and three batteries and current stabilizing elements, such as, for example, two resistors connected in series. The electrical circuit of this preferred embodiment simplifies the electrical circuit and stabilizes the current supplied to the electrolytic cell without using components such as transistors which are sensitive to gamma radiation used for sterilization.
- Another aspect of a preferred embodiment of the drug delivery system of the present invention includes an occlusion prevention mechanism. Further, it is not desirable that the delivery rate of the drug delivery device be altitude dependent. An element, such as, for example, a valve in the drug delivery device, creates a constant high, back pressure within the gas chamber, minimizing or preferably preventing the formation of boli of drugs.
- In a preferred embodiment of the present invention, an optical window, such as, for example, a ring like structure, provides a more accurate assessment of the quantity of drug delivered or alternatively, the quantity of drug remaining in the drug reservoir. The embodiment makes use of the principle of light reflected from the elastomeric membrane or diaphragm containing the drug. When the drug reservoir is approximately full, the optical window appears black as the elastomeric membrane is extended away from the housing as the drug fills it. However, when the drug reservoir is approximately empty, the optical window appears blue in color, for example, as the elastomeric membrane is proximate to the housing as drug delivery is close to completion.
- Further, in a preferred embodiment, the subcutaneous drug delivery device includes a pressure sensitive mechanism for preventing a rapid injection of a drug to a user. For example, the pressure sensitive mechanism can include a switch that forms a part of the electrical circuit which controls the power supply to a gas generating portion of the drug delivery device. The switch can include different preferred components to complete the circuit, such as one including a conductive membrane and a conductive lever, or alternatively, electrodes and a droplet of mercury. The electrical circuit is completed as long as the pressure in the gas generating portion is less than the pressure within a chamber.
- In another preferred embodiment, the drug delivery system in accordance with the present invention includes a visual indicator to indicate proper application and operation to a user. The indicator can be, for example, a color marking system. The color marking system can be used to indicate to a user components of the system which should be removed from the system prior to use.
- Another preferred embodiment of the drug delivery system of the present invention includes an insert, for example, a foam insert that receives the internal components of the device and accommodates design tolerances. The insert maintains an accurate internal volume so that upon assembly, the volume of the internal housing, and thus the drug reservoir, is within an accurate range.
- In a preferred embodiment, the drug delivery system of the present invention includes an activation mechanism, such as, for example, an activation lever to initiate gas generation in the expandable chamber which in turn controls the delivery of the drug from the device. The activation mechanism also includes a puncturing device and an electrical contact. In operation, upon depression, the puncturing device punctures the foil cover of the electrolytic cell, thereby allowing the chemical ingredients to release gas for expanding the expandable chamber. As a result, the proximate drug reservoir is compressed and drug delivery is initiated.
- Another preferred embodiment of the drug delivery system relates to controlling the rate of delivery which is controlled by several parameters. The parameters include, but are not limited to, circuit current, residual air volume, material permeability, material properties of plastic material in device, and membrane seal. For example, the permeability of the drug delivery system components, such as the permeability of the materials used in the base affects the delivery rate of the drugs delivered. thus, materials such as, for example, PET that minimizes or preferably prevents the permeation of the gases generated in the device, for example, hydrogen is used. By minimizing the permeability of the gases of the expandable chamber, a constant delivery rate can be maintained. As the diffusion rate of the gases controls the delivery rate of the drug, material changes can control the delivery rate of drugs.
- Another aspect of the present invention includes packaging of the drug delivery system to insulate the system from storage and use in different altitudes. In particular, the electrolyte in the electrolytic cell used to generate gas in the expandable chamber is affected by environmental conditions. Further, the performance of the barometric pressure valve can be affected by the environmental conditions as it relies on a reference pressure of a fixed amount of the air. At high altitudes, air from the reference cell can diffuse out of the device due to expansion. of the air. In a preferred embodiment, by hermetically packaging the device, the barometric pressure valve has only one position, that is, it is a stationary valve as the pressure inside the device is constant.
- Thus, it is an object of the present invention to provide a subcutaneous drug delivery device having an improved filling mechanism which facilitates filling the device in an orientation-independent manner.
- It is a further object of the present invention to provide a filling system that is less bulky.
- It is still a further object of the present invention to provide a filling system that maintains the needles within the system in a recessed fashion so as to minimize the risk of injury associated with needles.
- It is yet a further object of the present invention to provide a device which operates at a substantially constant delivery rate independently of the ambient atmospheric pressure.
- It is even yet a further object of the present invention to provide a drug delivery device in which the needle is retracted from the housing surface before and after use so as to minimize injury due to accidental contact with the needle.
- It is yet a further object of the present invention to provide a device having improved adhesion to the skin, i.e. for which there is less likelihood that the device will become detached during use.
- Other objects, features and advantages of the present invention will be apparent upon reading the following specification taken in conjunction with the drawings and appended claims.
- The foregoing and other objects, features and advantages of the invention will be apparent from the following more particular description of preferred embodiments of the invention, as illustrated in the accompanying drawings in which like reference characters refer to the same parts throughout the different views. The drawings are not necessarily to scale, emphasis instead being placed upon illustrating the principles of the invention.
- FIG. 1 is a sectional side view of a first embodiment of drug delivery device according to the present invention;
- FIG. 2 is an exploded perspective view of the flow regulating chamber and needle assembly of the first embodiment of the device of FIG. 1;
- FIG. 3 is an enlarged sectional side view of the flow regulating chamber and needle assembly of the first embodiment of the device of FIG. 1;
- FIGS.4-6 are sectional side views of a second embodiment of drug delivery device according to the invention, shown before, during and after use, respectively;
- FIGS.7-9 are enlarged perspective views of the locking mechanism of the device of FIGS. 4-6, shown before, during and after use, respectively;
- FIGS. 10A, 10B and10C are schematic elevations of a first alternative embodiment of a locking mechanism, shown before, during and after use, respectively;
- FIGS. 10D is a perspective view of the locking mechanism as shown in FIG. 10A;
- FIGS. 11A, 11B and11C are schematic elevations of a second alternative embodiment of a locking mechanism, shown before, during and after use, respectively;
- FIG. 11D is a perspective view of the locking mechanism as shown in FIG. 11A;
- FIGS. 12A, 12B and12C are schematic elevations of a third alternative embodiment of a locking mechanism, shown before, during and after use, respectively;
- FIG. 12D is a perspective view of the locking mechanism as shown in FIG. 12A;
- FIGS. 13A, 13B and13C are schematic elevations of a fourth alternative embodiment of a locking mechanism, shown before, during and after use, respectively;
- FIG. 13D is a side elevation of the locking mechanism as shown in FIG. 13A;
- FIG. 13E is a perspective view of the locking mechanism as shown in FIG. 13A;
- FIGS. 14 and 15 are sectional elevations of a third embodiment of drug delivery device according to the invention, shown before and during use, respectively;
- FIG. 16 is a partially cut away perspective view of the lower part of the housing on the device of FIGS. 14 and 15, including various components housed therein;
- FIG. 17 is an exploded perspective view of the electrolytic cell used in the embodiment of FIGS. 14 and 15;
- FIG. 18 is a sectional side view of the electrolytic cell used in the embodiment of FIGS. 14 and 15;
- FIGS. 19 and 20 are sectional side views of a fourth embodiment of drug delivery device according to the invention, shown before and during use, respectively;
- FIG. 21 is a sectional plan view of a drug delivery kit comprising the first embodiment of FIG. 1, a filling adapter and a medicament cartridge;
- FIG. 22 is a perspective view of a subassembly used in the adapter shown in FIG. 21;
- FIGS. 23 and 24 are sectional side views of the drug delivery kit of FIG. 21, shown during and after filling of the device, respectively;
- FIGS. 25 and 26 are sectional side views of fifth and sixth embodiments, respectively, of drug delivery device according to the invention;
- FIGS. 27 and 28 are sectional side views of a diaphragm suitable for use in a device according to the invention;
- FIG. 29 is a diagram of an electronic controller circuit suitable for use in a device according to the invention;
- FIGS. 30 and 31 are perspective views of the top side and underside, respectively, of a displaceable cover from a device according to the invention;
- FIG. 32A schematically illustrates a preferred embodiment of an electrical circuit for an electrolytic cell in a drug delivery device in accordance with the present invention;
- FIG. 32B graphically illustrates the current profile of the electrolytic cell shown in FIG. 32A in accordance with the present invention;
- FIGS.33A-33F illustrate both schematically and graphically, an embodiment of a drug delivery device which can be compromised by an occlusion;
- FIGS. 34A and 34B schematically and graphically illustrate a preferred embodiment of a drug delivery device having an occlusion prevention mechanism in accordance with the present invention;
- FIG. 35 schematically illustrates a preferred embodiment of the drug delivery device in accordance with the present invention;
- FIGS.36A-36C schematically illustrate the changes in the drug reservoir of a drug delivery device in accordance with the present invention;
- FIG. 37A is a perspective view of a printed circuit board with a pressure sensitive mechanism;
- FIGS. 37B and 37C schematically illustrate a preferred embodiment of a pressure sensitive mechanism of FIG. 37A included in a drug delivery device in accordance with the present invention;
- FIG. 37D is a schematic illustration of an electrical circuit for the drug delivery system incorporating elements of FIG. 32A and FIG. 37A.
- FIGS. 38A and 38B schematically illustrate another preferred embodiment of a pressure sensitive mechanism included in a drug delivery device in accordance with the present invention;
- FIG. 39A is a perspective view of a pressure sensitive mechanism, with portions broken away on a printed circuit board;
- FIGS. 39B and 39C schematically illustrate the preferred embodiment of a pressure sensitive mechanism of FIG. 39A included in a drug delivery device in accordance with the present invention;
- FIG. 40 schematically illustrates a preferred embodiment of a drug delivery device including an insert in accordance with the present invention;
- FIGS. 41A and 41B illustrates a preferred embodiment of a drug delivery device including an activation lever in accordance with the present invention;
- FIG. 42 graphically illustrates the delivery of drugs using a preferred embodiment of the drug delivery device which controls residual air volume in accordance with the present invention;
- FIG. 43 graphically illustrates the delivery of drugs using a preferred embodiment of the drug delivery device which controls the system permeability in accordance with the present invention;
- FIG. 44A illustrates a full assembly of the drug delivery device including a stationary barometric pressure valve in accordance with the present invention;
- FIG. 44B is an enlarged sectional view of the stationary valve of FIG. 44A;
- FIG. 45 illustrates a preferred embodiment of the packaging used for the drug delivery device in accordance with the present invention;
- FIG. 46 illustrates an alternate embodiment of packaging used for the drug delivery device in accordance with the present invention;
- FIGS.47A-47C illustrate another embodiment of packaging used for the drug delivery device in accordance with the present invention;
- FIG. 48 is a sectional side view of an alternative embodiment of a drug delivery device;
- FIG. 49 is a sectional side view of an alternative embodiment of a drug delivery device;
- FIG. 50A is a sectional side view of the alternative embodiment of the drug delivery device of FIG. 48 with the luer connection on to be an epidural needle; and
- FIG. 50B is a sectional side view of the alternative embodiment of the drug delivery device of FIG. 48 with the luer connection to an epidural needle with a hydrophobic membrane and a hydrofoil membrane.
- Referring now in more detail to the drawings, in which like numerals refer to like parts throughout the several view, FIG. 1 indicates a subcutaneous
drug delivery device 10 according to the invention. - A
housing 11 defines areservoir 12 which is partially bounded by anelastomeric diaphragm 13 which allows the reservoir to expand and contract. Thediaphragm 13 also bounds anexpandable chamber 14 such that expansion of the expandable chamber causes thereservoir 12 to contract and vice versa. In FIG. 1, thereservoir 12 is at full volume and contains a drug, while theexpandable chamber 14 is at minimum volume. - A
circuit board 15 having anelectrolytic cell 48 mounted thereon (explained in greater detail below) is mounted in thelower part 16 of thehousing 11. In use, theelectrolytic cell 48 feeds a gas into theexpandable chamber 14 via anaperture 17 in a supportingmember 18. - The
reservoir 12 is provided with aninlet 19 which is in communication with a filling mechanism 20 (explained in greater detail below). Adelivery needle 21 provided with anoutlet 22 is in communication with thereservoir 12 via afluid path 23 which is indicated by arrows. Thefluid path 23 passes around an air-filled flow-regulatingchamber 35 which comprises atop member 24,annular member 25 and flowdiaphragm 26. Thefluid path 23 also passes via aneedle holder 27 to theneedle 21. Theinlet 19 to theneedle 21 is partially restricted by aprojection 28 on theflow diaphragm 26, such that any upward movement of theprojection 28 reduces resistance to flow and any downward movement of the projection increases flow resistance. - Referring additionally to FIG. 2, the
flow regulating chamber 35 can be seen in exploded view.Annular member 25 receives theflow diaphragm 26, andtop member 24 and the three components fit together to form anairtight chamber 36 which is positioned above theneedle holder 27. Theinlet 19 in theneedle holder 27 leading to theneedle 21 can be clearly seen on the top surface of the needle holder.Projection 28 extends into theinlet 19. - Further features of
device 10 which can be seen in FIG. 1 are adisplaceable cover 29 attached to thehousing 11 by ahinge 30. The movement of thedisplaceable cover 29 between the position shown in FIG. 1 (wherein theneedle 21 protrudes through the displaceable cover) and a position in which theneedle 21 is substantially concealed by the displaceable cover 29 (as shown in FIG. 4), is controlled by a locking mechanism indicated generally at 31 and explained in greater detail below. - In use, the
displaceable cover 29 is affixed to the skin using anadhesive coating 29′ provided on the surface thereof distal from the housing (“the underside”). Thedisplaceable cover 29 has a concave shape when viewed from the underside. This shape is advantageous because if a flat or convex surface is provided, the edges of thecover 29 will be more easily peeled away from the skin by accident, i.e. the use of a convex surface is less likely to have protruding edges, and the force required to peel the device away is a shear force rather than a simple peeling force. - The
housing 11 is covered by a protectivetop cover 32 which can provide a more aesthetically pleasing appearance to the device, as well as one which is ergonomically more advantageous for the user. An aperture in protectivetop cover 32, indicated at 33, allows atransparent portion 34 of thehousing 11 to be seen, thereby allowing the user to visually check the reservoir to see whether drug is present. The protectivetop cover 32 also protects thehousing 11 and its component parts if thedevice 10 is mishandled or dropped. - The
flow regulating chamber 35 is shown in greater detail in FIG. 3 and comprises thetop member 24, theannular member 25, and theflow diaphragm 26, as explained above. The construction ensures that theairtight space 36 exists in the interior of thechamber 35. A fluid path between the reservoir and the needle (FIG. 1) is shown with heavy arrows. As can be seen,projection 28 on theflow diaphragm 26 extends into theinlet 37 in theneedle holder 27 leading to theneedle 21. The fluid has to push up on theflow diaphragm 26 in order to reach theneedle 21. Little force is required to do this, as the air in thechamber 36 is compressible. - However, if the ambient atmospheric pressure drops, for example due to an increase in altitude, the fixed mass of air in the
chamber 36 tends to expand (since for ideal gases at fixed temperature the product of pressure and volume is a constant). This makes it more difficult for fluid to flow past theflow diaphragm 26 intoneedle holder 27 and would thus tend to cause a decrease in the rate of delivery of drug. - The fact that the drug is being driven by a gas-filled
expandable chamber 14, however, means that the expandable chamber tends also to increase in volume due to this increase in altitude, and the effect of an increase in expandable chamber volume is to speed up the rate of delivery. - Therefore, by calibrating the
flow regulating chamber 35 correctly, barometric changes which would otherwise tend to increase or decrease the rate of delivery of drug are counteracted by the corresponding increase or decrease in the amount of flow resistance exerted by the flow regulating chamber, thereby allowing a constant delivery rate to be maintained. It will be appreciated that changes in temperature which would cause the gas in the expandable chamber to expand or contract are also counteracted in the same way. - A further feature of the device of FIGS.1-3 is an o-
ring 38 located on displaceable cover 29 (see FIG. 1). The o-ring 38 forms a seal withneedle holder 27 and thereby assists in protecting the puncture point of theneedle 21 into the skin of the user from contact with soap, water, perspiration or other contaminates. If water or other liquid contacts theneedle 21, theneedle 21 may act as a switch and allow water to be drawn into the puncture. However, adhesive 29′ on thedisplaceable cover 29 prevents water from reaching theneedle 21 via the underside of the cover, and the o-ring 38 prevents water from reaching the needle via the upper side of displaceable cover.Top member 24,annular member 25,flow diaphragm 26 andneedle holder 27 and all other parts in the fluid pathway are preferably made of a polycarbon material. Polycarbon materials are essentially inert and will not react with the liquid drug. Moreover, the polycarbon material withstands gamma radiation without degradation of any properties. - FIGS. 4, 5, and6 show a device similar to that of FIG. 1 before, during and after use, respectively. The device, indicated generally at 50, differs slightly from the FIG. 1 device and accordingly different reference numerals are used in relative to FIG. 1. The
device 50 is shown in FIG. 4 with theneedle 51 concealed by thedisplaceable cover 52 because thedisplaceable cover 52 is displaced relative to thehousing 53 about thehinge 54. Aremovable tab 55 prevents thedisplaceable cover 52 from being moved towardshousing 53, as will be described further below. Theunderside 56 of thedisplaceable cover 52 is coated with acontact adhesive 56, and during storage, the adhesive is protected by a release liner. - When the release liner is removed, the adhesive-coated
underside 56 is pressed against the skin to ensure good adhesion (the concave surface assists in obtaining good adhesion) and thetab 55 is removed. Thehousing 53 is then pushed towards the skin and theneedle 51 penetrates the skin as thedisplaceable cover 52 andhousing 53 move together abouthinge 54, leading to the configuration shown in FIG. 5. - A start button is pressed to activate a gas generating
electrolytic cell 57. As gas is generated, adiaphragm 58 is pushed upwards to drive a liquid drug from the reservoir 59 (which was filled before use via inlet 60) and thereby force the drug through afluid path 61 around the flow regulating chamber 62 (as explained above in relation to FIGS. 1-3) and to the patient via thedelivery needle 51. - When delivery has been completed, the
diaphragm 58 will have moved up such that the space occupied by thereservoir 59 at the beginning of delivery (see FIGS. 4 and 5) is now occupied by the expandable chamber 14 (see FIG. 6), since the expansion of the expandable chamber causes contraction of the reservoir. - The
device 50 is removed from the skin by pulling upwards on the upper protective cover 63 (FIG. 6). This causes theneedle 51 to be retracted behind thedisplaceable cover 52 once again because the adhesive force holding thedisplaceable cover 52 against the skin is greater than the force exerted by the locking mechanism 64 (explained in greater detail below). Once theneedle 51 is retracted in this way, thelocking mechanism 64 holds thedisplaceable cover 52 permanently in the position shown in FIG. 6, i.e. away from thehousing 53 with theneedle 51 concealed. FIG. 7shows locking mechanism 64 in greater detail, with the protectivetop cover 63 removed for illustrative purposes. Thelocking mechanism 64 is illustrated before use, i.e. when the displaceable cover is positioned as shown in FIG. 4. In other words, there is a gap between thehousing 53 and thedisplaceable cover 52, and the needle 51 (FIG. 4) is recessed in this gap and thereby concealed by thedisplaceable cover 52. Aprojection 65 mounted on the front ofhousing 53 is positioned at the upper end of aslot 66. Theslot 66 has anenlarged portion 67 at the lower end and is provided withwedge projections slot 66 is formed in amember 70 which is attached todisplaceable cover 52 by connectingarms 72 which allow a slight degree of flexibility. A widened rib is provided on theprojection 65, and the width of this rib is greater than that of the upper portion of theslot 66. Themember 70 is biased slightly against this rib. - The removable tab55 (see FIG. 4) is positioned so as to engage
wings 71 and prevent them from moving towards thecover 52. This effectively prevents theentire housing 53 from being moved towards thecover 52 and prevents the device from being activated prematurely. When thetab 55 is removed, as shown in FIG. 7, thedisplaceable cover 52 can be snapped towards thehousing 53 by pressing down on the housing. This results in the locking mechanism adopting the configuration shown in FIG. 8, wherein theprojection 65 has moved to the lower end of theslot 66, allowing alipped member 73 to pass through theenlarged portion 67 at the lower end ofslot 66. This allows amember 70, which was biased in the direction ofprojection 65, to relax. The sides of thelipped member 73 rest against themember 70. - When delivery is complete and the
housing 53 is lifted away from thedisplaceable cover 52, this disengages the lips of thelipped member 73 from resting againstmember 70 and again moves theprojection 65 to the upper end of theslot 66. However, thelipped member 73 passes over thewedge projections wedge projections lipped member 73 and prevent it from moving back down. This effectively locks thelocking mechanism 64 permanently in the configuration shown in FIG. 9, thereby concealing theneedle 51 permanently from view and making thedevice 50 safe for disposal. - An additional feature of the device of FIGS.4-8 relative to that of FIG. 1 can be seen with reference to FIGS. 4-6. A pair of
projections 74 grip theflow regulating chamber 62 before use to block the path between thereservoir 59 and theneedle 51 before use (FIG. 4). When gas generation begins, the pressure of liquid in thereservoir 59 forces theflow regulating chamber 62 downwards relative to theprojections 74. Theprojections 74 are resilient and move together when theflow regulating chamber 62 moves downwards. In this position theprojections 74 holdflow regulating chamber 62 in a fixed position both during delivery (FIG. 5), and when the device is removed from the skin (FIG. 6). Thus, after delivery, accidental leakage of medicament from the needle 51 (e.g. due to gravity) is prevented by the fixed position of theflow regulating chamber 62 and no gas being generated to create a higher pressure than within theflow regulating chamber 62 to lift the projection which seals the inlet to the needle. - A further feature of the embodiment of FIGS.4-6 is an annular elastomeric inwardly extending
lip 75 which seals the skin at the point of entry of theneedle 51 in the same manner as the o-ring 38 in the FIG. 1 embodiment. This feature reduces the danger of infection due to wicking by the needle of unwanted substances into the skin. - Four alternative embodiments of different locking mechanisms according to the invention are shown in FIGS.10A-10D, 11A-11D, 12A-12D, and 13A-13E. In each case the mechanism is shown schematically in “pre-use” (A), “in-use” (B) and “post-use” (C) configurations as well as in one or two perspective views (D/E). The mechanism can in each case be moved from position A to position B and from position B to position C with little difficulty (although generally some resistance is present to prevent spontaneous or accidental movement), but once in position C, the mechanism is effectively locked permanently and is no longer capable of operation.
- The first alternative embodiment of a locking mechanism comprises a resilient arm and related assembly and is shown in FIGS.10A-10D. In FIG. 10A the locking mechanism is indicated generally at 80 and comprises a biasing
member 81 and aresilient strut 82 mounted on ahousing 83, and theresilient arm 84 and apost 85 mounted on adisplaceable cover 86. - The
resilient arm 84 is flexibly hinged at thebase thereof 87. When thehousing 83 is pushed towards thedisplaceable cover 86, the biasingmember 81 pushes theresilient arm 84 against thepost 85. Theresilient arm 84 and post 85 are mutually shaped to allow thearm 84 to pass over the top of thepost 85, where it latches (see FIG. 10B) and is prevented from returning to the position shown in FIG. 10A. - In passing over the top of the
post 85, thearm 84 acts against theresilient strut 82, momentarily bending thestrut 82 away from the biasingmember 81. Although when thearm 84 has passed fully over the top of thepost 85 thestrut 82 has returned to its relaxed (straight) position (FIG. 10B). - When (after use) the
housing 83 is pulled away from thedisplaceable cover 86, this causes thestrut 82 to again be bent away from biasing member 81 (becausearm 84 which is now locked in place bypost 85 impedes the path of strut 82). However, when the end 88 ofstrut 82 has cleared thearm 84, it springs back into position, past aprojection 89 on arm 84 (see FIG. 10C). In fact, strut 82 latches behindprojection 89, preventing the strut from moving back to the position shown in FIG. 10B, and thereby permanently locking themechanism 80 in the FIG. 10C configuration. - The perspective view in FIG. 10D shows the mechanism in the position illustrated in FIG. 10A. An additional feature visible in FIG. 10D is a snap mechanism comprising an
arm 90 depending from either side of thehousing 83. A raisedprotuberance 91 on the inner surface of eacharm 90 acts against a slopedsurface 92 on thedisplaceable cover 86 to provide resistance to movement. The effect of the snap mechanism is to add further resistance to any unintended relative movement between thehousing 83 and thedisplaceable cover 86. A further effect is that the movement of thehousing 83 relative to thecover 86 between the configurations of FIGS. 10A and 10B, and the configurations of FIGS. 10B and 10C, is extremely rapid, causing the penetration of the needle into the skin and the removal of the needle from the skin to be quick and painless. - The second alternative embodiment of a locking mechanism of the present invention comprises an inverted V-shaped assembly and is shown in FIGS.11A-11D. In FIG. 11A the locking mechanism is indicated generally at 100 and comprises a
member 101 resiliently mounted on ahousing 102, and apin 103 supported in aframe 104 mounted on adisplaceable cover 105. Themember 101 has an inverted V-shape slot 106 therein. Theslot 106 has anouter slot portion 107 connected at the upper end thereof to aninner slot portion 108, and a dividingmember 109 between the outer andinner slot portions - In moving from the “pre-use” position to the “in-use” position, the (fixed)
pin 103 moves up theouter slot 107, acting against the dividingmember 109 until it springs past the dividingmember 109 at the top of the outer slot. In the position shown in FIG. 11B, thepin 103 is located above the top of theinner slot 108. - When the
housing 102 is subsequently pulled away from the displaceable cover 105 (moving from FIG. 11B to FIG. 11C, the pin moves downinner slot 108, acting against the dividingmember 109 to push themember 101 sideways. When the position shown in FIG. 11C is reached, thepin 103 locates a recess 110 (see FIG. 11B) in the lower end ofinner slot 108, which allows themember 101 to relax slightly but still keeping a certain degree of stress on themember 101 by holding it away from the equilibrium position relative to thehousing 102. In this way, thepin 103 latches into therecess 110 and locks themechanism 100 permanently in the “post-use” configuration. In FIG. 11D, themechanism 100 can be seen in the “pre-use” configuration, with themember 101,housing 102,pin 103,frame 104, anddisplaceable cover 105 visible. - The third alternative embodiment of a locking mechanism of the present invention comprises generally a rotatable pawl assembly and is shown in FIGS.12A-12D. The mechanism, indicated generally at 120, comprises a
rotatable pawl 121 mounted on thedisplaceable cover 122 and which is rotated by anarm 123 in moving from the “pre-use” to “in-use” positions (FIGS. 12A and 12B, respectively). When therotatable pawl 121 reaches the “in-use” position, a recess 124 (FIG. 12A) receives aprojection 125 located on aresilient portion 126 of thedisplaceable cover 122, providing a degree of resistance to further movement. - In moving from the FIGS. 12A to12B positions, the
rotatable pawl 121 acts against aflexible strut 127 depending from thehousing 128. When therotatable pawl 121 is in the FIG. 12B position, further clockwise rotation of the pawl is prevented by thearm 123. - When the
housing 128 is lifted (moving from FIGS. 12B to 12C), thestrut 127 acts against aprojection 129 urging therotatable member 121 in a clockwise direction, but thearm 123 prevents such rotation. As the housing reaches the FIG. 12C position, thestrut 127 springs past theprojection 129 to sit in a recess above theprojection 129, and thearm 123 clears the upper corner of therotatable pawl 121. When in this configuration, thearm 123 prevents any counter-clockwise rotation of therotatable pawl 121, while thestrut 127 prevents any clockwise rotation thereby locking therotatable pawl 121 in position and preventing any further downward movement of thehousing 128 towardsdisplaceable cover 122. - The fourth alternative embodiment of a locking mechanism of the present invention comprises generally a flexible post assembly as shown in FIGS.13A-13E. In FIG. 13A the locking mechanism is indicated generally at 130 and comprises a vertical flexible post 131 (see FIGS. 13D and 13E) mounted on the
displaceable cover 132 and having aprojection 133 extending therefrom towards asloped surface 134 on thehousing 135. - A
slot 136 insurface 134 connects two apertures, namely a lower aperture 137 (see FIG. 13B) which is of smaller diameter than the widest part ofprojection 133, and anupper aperture 138 which is of larger diameter than the widest part ofprojection 133. - In the “pre-use” position,
projection 133 is positioned at the lower aperture. As the housing moves towards the “in-use” position (FIG. 13B) theflexible arm 131 is bent back until theprojection 133 reaches theupper aperture 138 whereupon it springs back into position as theprojection 133 moves through theupper aperture 138. In moving to the “post-use” position, theprojection 133 is constrained by theslot 136 and thearm 131 is bent forward until theprojection 133 reaches thelower aperture 137 which provides a recess for theprojection 133 to spring back into (but not through). Because thearm 131 remains bent forward slightly, this effectively traps theprojection 133 in thelower aperture 137 and thereby holds the mechanism permanently in the “post-use” configuration, as shown in FIG. 13C. - In FIG. 14 there is another
drug delivery device 140 according to the invention similar in many respects to the embodiments previously described. Thedevice 140 has a protectiveupper cover 141, ahousing 142, adisplaceable cover 143, adelivery needle 144, aflow regulating chamber 145 and a threeposition locking mechanism 146. - The internal space of the
drug delivery device 140 of FIG. 14 defines anexpandable chamber 147 when thediaphragm 148 is in the position shown or a reservoir when the diaphragm is in the position shown in dotted outline at 149. Theexpandable chamber 147 is initially air filled (FIG. 14 shows the device in the pre-use configuration before medicament has been loaded). Thus, the reservoir is substantially of zero volume. Theexpandable chamber 147 communicates with the atmosphere via anopen valve 150. - When liquid drug is loaded into the reservoir via a fill, the
diaphragm 148 moves downwards toposition 149, with the reservoir filling with air and theexpandable chamber 147 being emptied as the volume thereof decreases. Because theexpandable chamber 147 is in communication with the atmosphere, the air initially filling thechamber 147 is exhausted into the atmosphere via thevalve 150 without any necessity for action on the part of the user. - Furthermore, because the reservoir is initially of substantially zero volume, it does not require filling in any particular orientation. While prior art devices have required careful loading in order to ensure that all air bubbles are vented from the drug supply before delivery begins, the only air in the drug path of the device of FIG. 14 is in the short, narrow portion of the device between the reservoir and the
needle 144. Thus, when drug enters the reservoir it immediately pushes the small amount of air ahead of it through the narrow space towards theneedle 144, irrespective of the orientation of thedevice 140. By filling with the drug until a drop of the drug appears on the end of theneedle 144 one can be sure that no air remains in the fluid path. - When the
device 140 has been filled with drug, thediaphragm 148 is at the position shown at 149, and thevalve 150 is open. However, when thedisplaceable cover 143 is applied to the skin, and the housing is pushed downwards, thevalve 150 is closed and the closing of the valve actuates aswitch 151 to begin generation of gas by an electrolytic cell 152 (described in more detail below). - The
device 140 is then in the “in-use” position shown in FIG. 15, withreservoir 147 filled with drug, thediaphragm 148 inposition 149,valve 150 and switch 151 closed, andelectrolytic cell 152 actuated to generate a gas and hence begin delivery of drug from reservoir to the patient throughdelivery needle 144. -
Valve 150 is closed by a connectingmember 153 which is connected todisplaceable cover 143. Whendisplaceable cover 143 moves towardshousing 142, connectingmember 153 fits into avalve 150 and pushes it home to seal the expandable chamber 147 (the area below diaphragm 149) from the atmosphere. When a gas is generated by theelectrolytic cell 152, it pressurizes thereservoir 147. - A
coloured plastic member 154 forming part oflocking mechanism 146 protrudes through anaperture 155 in the protectiveupper cover 141 when thedevice 140 is in the position as shown in FIG. 15. Thecoloured member 154 visually indicates that thedevice 140 has been actuated. - FIG. 16 is a detail view of the
lower section 156 of the housing 142 (see FIG. 15). Thelower section 156 houses abattery 157 and anelectrolytic cell 158, both mounted on a printed circuit board (PCB) 159. ThePCB 159 can be provided with controlling circuitry as required in order, for example, to vary the rate of delivery, stop delivery if the rate of gas generation is too high, or control the operation of thedevice 140 in any other way required. In the embodiment shown, thedevice 140 is a disposable single-rate device which does not require advanced controlling circuitry, but more sophisticated devices are of course within the scope of the invention. - A
cylindrical outlet 160 is formed insection 156, and this provides a valve seat for thevalve 150. When thevalve 150 is pushed upwards into anoutlet 160 it makes an airtight seal, as shown in FIG. 15. Arecess 161 in thevalve 150 tightly accommodates the connecting member 153 (FIG. 15), and the force used to push thehousing 142 down ontodisplaceable cover 143 as described above is sufficient to jam the connectingmember 153 into thevalve 150. This design enables thedevice 140 to be removed from the skin by pullinghousing 142 away fromdisplaceable cover 143 to the “post-use” position, causing the connecting member 153 (which is permanently mounted ondisplaceable cover 143 and at this stage jammed intovalve 150 also) to pull thevalve 150 down and out ofoutlet 160 so as to open the valve. Using this design, if thereservoir 147 is not empty when thedevice 140 is removed, and if gas generation continues, then the gas will escape throughoutlet 160 rather than driving further drug through theneedle 144. - As described above, when the
valve 150 is closed, it actuates a switch 151 (see FIG. 15) which comprises a fixedcontact 162 and arocking contact 163. This completes a circuit to connect abattery 157 to anelectrolytic cell 158. When thevalve 150 is pulled downwards as thedevice 140 is removed from the skin, theswitch 151 should automatically disconnect because of the resilience of rockingcontact 163 which pivots about afulcrum 164. Thus, the opening of thevalve 150 is generally a redundant feature and is important as a safety feature if theswitch 151 does not automatically disconnect (leading to an unwanted continuation of delivery or, if thereservoir 147 is already empty, to a build up of gas pressure inside the device 140). - The
electrolytic cell 158 comprises (see also FIGS. 17 and 18) abody 165 defining aninternal space 166 for an electrolyte and through which a pair ofelectrodes 167 pass, each electrode being connected to a terminal of battery 157 (FIG. 16). Theinternal space 166 is enclosed above and below by a pair ofhydrophobic filters filters cell 158 to be released to theexpandable chamber 147. Thehydrophobic filters body 165 such that gas will transfer out of the gas generator irrespective of the orientation. The top and bottom of thebody 165 is provided with aseating 170. Thefilters seating 170 above and below thebody 165 and are sealed in place. In a preferred embodiment, thebody 165 is an injected molded high density poly ethylene (HDPE) to minimize permabilty. - The
cell 158 is then sealed above and below by aluminum foil layers 171 and 172. A connectingcell 174 sealed at both ends byfoil layers hydrophobic filters top foil layer 171 has been pierced. A gap adjacent to theseating 170, enables gas escaping throughhydrophobic filters cell 174. Thefoil layer 171 is pierced by aspike 175 carried on rocking contact 163 (see FIG. 16). Thus, when thedevice 140 is actuated, thefoil layer 171 is pierced to unseal thecell 158. A hydrophobic filter 176 (see FIG. 17) is also carried in thebody 165 to enable thecell 158 to be filled with electrolyte by injection. - In FIGS. 19 and 20, a
further embodiment 180 of the invention is shown. This embodiment differs from the embodiment of FIGS. 14-18 only in that thevalve member 181 is not held by thedisplaceable cover 182 when thedevice 180 is removed from the skin after use. However, thevalve 181 nevertheless achieves the primary purpose of allowing theinternal space 183 to be occupied entirely by the expandable chamber when received by the user, with thediaphragm 184 moving to the position shown at 185 when thedevice 180 is loaded with medicament. This means that no air bubbles can be entrapped in the reservoir during filling, and the reservoir can thus be filled quickly and easily. Thevalve 181 closes automatically when thehousing 186 is pressed towards the displaceable cover 182 (see FIG. 20). - FIG. 21 shows a
device 190 according to the invention which is identical to the device of FIG. 1, together with a fillingadapter 191 and a drug-containingcartridge 192.Cartridge 192 is cylindrical in shape, closed at oneend 193 thereof and sealed at theother end 194 by anelastomeric stopper 195 which is fittably mounted in thecartridge 192. Because the cartridge's liquid-filledinternal space 196 is sealed, thestopper 195 is prevented by the incompressible nature of the liquid from moving in either direction. - The
adapter 191 has ahousing 197 in which acannula subassembly 198 is mounted. The subassembly 198 (see FIG. 22) includes aplastic body 199 moulded in twohalves cannula 202 in place. - A
device 190 is provided with asocket 203 for receiving theadapter 191. Acylindrical projection 204 on the end of theadapter 191 is designed to fit into thesocket 203, and also to conceal thecannula 202 to prevent injury before and after theadapter 191 is mounted on thedevice 190. A self-sealingpenetrable plug 205 mounted in thesocket 203 leads to aconduit 206 and an inlet for the reservoir (seeinlet 19 in FIG. 1). Asubassembly 198 is mounted in achannel 207 of theadapter 191 such that it can be pushed inward until ashoulder 208 meets the end of thestructure 209 defining thechannel 207. At this point, thecannula 202 will penetrate theplug 205 enabling communication between thecannula 202 and the reservoir ofdevice 190. In use, acartridge 192 is pushed into theadapter 191, whereby astopper 195 causes thesubassembly 198 to be pushed inwards and thecannula 202 to penetrate theplug 205. Since thesubassembly 198 can move no further inward, further pushing of thecartridge 192 into theadapter 191 causes cannula 202 to penetratestopper 195, thus puttingdrugfilled space 196 in indirect communication with the reservoir ofdevice 190. - The
stopper 195 is then held bysubassembly 198, further pushing of thecartridge 192 inwards causes the stopper 195 (which remains stationary) to move relative to the cartridge 192 (which is progressively accommodated in the interior of adapter 191), with a consequent emptying of the contents of thecartridge 192 through thecannula 202 into the reservoir ofdevice 190. - This is illustrated best in FIG. 23, which shows a sectional view of the components shown in sectional plan view in FIG. 21, after the
cartridge 192 has been pushed most of the way home intoadapter 191. It can be seen that at this point, the stopper 195 (penetrated bycannula 202 which also penetrates plug 205) has almost reached theend 203 ofcartridge 192. - The
adapter 191 is not only held by the fit of theprojection 204 into thesocket 203, but also by areleasable locking mechanism 210. The releasable locking mechanism comprises 210 anaperture 211 on thedevice 190 and aresilient catch 212 on theadapter 191 which is biased into the position shown in FIG. 23 so as to hold the adapter firmly in place on device. Preferably theadapter 191 and thedevice 190 are sold together in kit form, optionally with the adapter already mounted on the device. - When the
cartridge 192 is pushed fully home it acts on a sloped section 213 ofwall 214 ofadapter 191 so as to pushresilient catch 212, which is an extension ofwall 214, downwards. This disengages thelocking mechanism 210, allowing theadapter 191 to be removed from thedevice 190. - FIG. 24 shows the kit after the
cartridge 192 has disengaged thecatch 212 allowing it to be withdrawn from theaperture 211. This permits theadapter 191 to be removed from thedevice 190 by pulling theprojection 204 from thesocket 203 whereupon theplug 205 seals itself and thereby isolates the reservoir of the device. - Because the
catch 212 is only disengaged when thecartridge 192 is fully emptied (i.e. when the stopper is pushed to theclosed end 193 of the cartridge 192), one can ensure that the reservoir is loaded with exactly the correct amount of drug every time, thereby eliminating human error and making the kit more suitable for home administration. - Furthermore, because both ends of the
cannula 202 at all times are concealed, theadapter 191 can be safely disposed of without risk of injury. Theadapter 191 allows the drug to be transferred to the reservoir with sterility ensured, since the user does not at any time handle any of the components in the fluid path. - FIG. 25 shows another alternative embodiment of the device according to the invention, indicated generally at220. This embodiment differs from previous ones in that instead of a needle extending directly from the
housing 221, atube 222 extends from thehousing 221 and carries aconnector 223 thereon to which a needle may be affixed before use. Thisdevice 220 is particularly suitable for intravenous drug delivery because thetube 222 allows the needle to be accurately positioned in a vein. - FIG. 26 shows an alternative intravenous embodiment, indicated generally at230. In this embodiment the displaceable lower cover has been omitted and the device is actuated by a
contact switch 231 positioned on the underside of thehousing 232. When the device is applied to the skin, theswitch 231 is pressed inwards (to the position shown in FIG. 26), thereby closing an electrical circuit and actuating a gas generatingelectrolytic cell 233 in the manner previously described. As the snap action provided by previously described devices is not required to cause a needle to penetrate the skin, the cover can be omitted without interfering with other functions of the device. - FIG. 27 shows the
elastomeric diaphragm 240 utilized in the above-described devices according to the invention. Thediaphragm 240 can also be used in other drug delivery devices according to the invention. Thediaphragm 240 is shown in FIG. 27 in its relaxed position, as it would be when the reservoir is empty (see FIG. 6, for example). In this configuration thediaphragm 240 substantially has the form of a truncated cone having a slopedportion 241 surrounding aflat portion 242, with alip 243 surrounding sloped portion 241 (lip 243 is used to attachdiaphragm 240 to the housing of a drug delivery device). - FIG. 28 shows the
diaphragm 240 in the configuration in which the reservoir is full (see FIG. 1, for example). In this configuration, thecentral portion 242 is still flat, and the surroundingportion 241 has an arcuate curved cross-section, in the form of a substantially inverted U shape. - The
diaphragm 240 is bistable, such that it is stable in either the FIG. 27 or the FIG. 28 configuration. However, a particular advantage has been found to result from the fact that in moving from the reservoir full (FIG. 28) configuration to the reservoir empty (FIG. 27) configuration, very little energy is needed. - Unlike many bistable arrangements, only minimal force is required to move between the stable configurations. In many bistable arrangements a substantial amount of energy is required to move from one configuration to a midpoint, at which the amount of stored energy is relatively high, following which the stored energy is released to complete the transition. The
diaphragm 240, rather than flipping between configurations, makes a smooth transition. However, in contrast to a completely pliable body, which cannot be depended on to exert force uniformly, thediaphragm 240 will behave dependably since it is constrained in its movement between configurations. This means that a predictable manner of movement is combined with a minimal expenditure of energy in actually effecting the transition between bistable configurations. - The elastomeric diaphragm240 (and others shown in alternative embodiments) and the
flow diaphragm 26 of theflow regulating chamber 35 are elastomers. There are two preferred sources for this material. One is a bromobutyl compound made by Vernay Laboratories, Inc. of Yellow Springs, Ohio (material number: VL 911N7). The second is an ethyl propylene diene monomer (“EPDM”) material number Bryant 85055, made by Bryant Rubber. - There are several advantages in using these two materials. First, the material has a low durometer, which enables the material to remain soft. Moreover, it enables the diaphragm to keep air out and deflect from one stable position to the other with little energy. In addition, these elastomers provide a long shelf life. Another advantage is the ability to withstand gamma radiation without degradation of properties. As stated above, gamma radiation is used in some sterilization procedures. The ability of these materials to withstand gamma radiation is very important as these materials will be assembled in the device and sterilized. An additional advantage of using these materials is their lack of toxicity.
- FIG. 29 shows a circuit diagram of a controlling circuit particularly useful or a drug delivery device according to the invention. In the
circuit 250, all symbols have their normal meanings within the art. The components shown are a battery B1, a switch S1 (activated by applying the device to the body), fixed resistors R1-R6 and R9-R10, variable resistors R7 and R8, a capacitor C1, transistors Q2-Q6, measurement terminals TP1 and TP2, a light emitting diode LED, and a load U1 which represents the electrolytic cell or other gas generating means.Reference numeral 251 denotes a section of thecircuit 250 which functions as a current driver, andreference numeral 252 denotes a section of thecircuit 250 which functions as an error circuit. - The current through the electrolytic cell Ul determines the potential drop across variable the resistance comprising resistors R7 and R8 (which may be adjusted to calibrate the device or set the delivery rate). This potential drop is compared by the error circuit with the potential drop across a reference resistor R1, which itself depends on the voltage drop across the LED. The value of resistor R1 is chosen to provide a potential drop equal to the drop measured across the resistors R7 and R8 when the correct current is flowing through the cell U1.
- If the potential drop across the resistors R7 and R8 is lower than the constant potential measured across the resistor R1, indicating that the current through the cell U1 is too low (e.g. because of fading battery power, changes in the internal resistance of electrolytic cell U1 as the reactants are consumed, etc.), the
error circuit 252 forces thedriver 251 to increase the current flow to the correct value. In practice, theerror circuit 252 continually ensures that the current does not deviate from the correct value by constant feedback operation. - Each of the transistors in the
circuit 250 is a silicon-based bipolar transistor. The advantage of using bipolar transistors in particular is that they have been discovered to surprisingly withstand gamma radiation to a far greater extent than other types of transistors. The use of silicon as semiconductor is not essential but this material is currently less expensive than many other semiconductors. It has been found that by employing a circuit in which the or each transistor is a bipolar transistor, the circuit and hence the entire device can be subjected to intense gamma irradiation as a means of sterilizing the device after manufacture. Conventional integrated circuits are destroyed by the intense radiation required to sterilize a device quickly. - For example, a dose of 2.5 Mrad (25 kJ/kg) of gamma radiation may be required to sterilize a device. In trying to design a circuit which would withstand such harsh conditions we consulted data regarding the electronic components used in space missions, such as the U.S. Space Shuttle missions. It was found that the same degree of radiation resistance was not required because the absorbed dose measured on the Space Shuttle averages approximately 0.4-0.5 Mrad.
- As a rule, all electronic components will undergo a degree of degradation when subjected to irradiation. However, by selecting components which are resistant to irradiation as far as possible and whose performance can be predicted after receiving a given dose of radiation, it is possible to design a circuit which will withstand intense gamma radiation and still function in a predictable manner.
- In particular, by using a bipolar transistor with a high current gain (e.g. a current gain of at least 600 but preferably 800 or more) the drop in current gain exhibited after irradiation can be compensated for in advance. This drop in gain can be of the order of a tenfold drop or more, but can be predicted well in advance. Furthermore, by using current values which are sufficiently low, the drop in voltage at the silicon junction of the transistor occurring as a result of the irradiation only slightly affects performance.
- A further advantage is gained using a circuit which employs a light emitting diode as a basis for the reference voltage used in the error correction circuit, since the LED reference source is not affected by the gamma radiation. The LED used is a gallium arsenide (GaAs) based LED which has been found to provide particularly good resistance to gamma radiation.
- In summary, the components and circuit employed have been found to be suitable for gamma irradiation, following which they give a well predictable performance in use. This enables the manufacture to be completed more efficiently, with the assembled device sterilizable by gamma radiation.
- FIG. 30 is a perspective view of the top side of a
displaceable cover 160 forming part of a device according to the invention. FIG. 31 is a perspective view of the underside ofcover 160. Such a cover is described generally above in relation to the embodiment of FIGS. 4-8, for example. - The
cover 160 is provided withformations 161 forming part of a locking mechanism as described above, with anaperture 162 through which a delivery needle protrudes in use. Thecover 160 also hashinge formations 163 which enable the cover to be displaced relative to the housing between first and second positions as previously described. - The
cover 160 is shaped to improve retention of the device against the skin: thus. the top side 164 (FIG. 30) is convex, and the underside 165 (FIG. 31) from which the needle protrudes in use is concave. Accordingly, when the device has been applied to the skin of a subject removal of the device is resisted because thecover 160 conforms more closely to the skin. It is less likely that the device will peel from the skin without a conscious effort by the user since there is a lower likelihood of the periphery of the cover being detached from the skin. - FIG. 32A schematically illustrates an alternative preferred embodiment of an
electrical circuit 250 within a subcutaneous drug delivery device. Thecircuit 250 replaces the entire circuitry of FIG. 29. In order to provide a constant rate of drug delivery, thedelivery system 254 requires a constant current. This electrical circuit stabilizes the current supplied to the electrolytic cell without using components such as transistors which are sensitive to gamma radiation during sterilization. Gamma radiation is a standard method of sterilization of medical devices. A constant current supplied to the electrolytic cell results in a volume of gas which provides a desired constant delivery rate. The circuit uses a higher voltage than the previous embodiments along with current stabilizing resistive elements, such as, for example, resistors in series. FIG. 32A shows anelectrical circuit 250 having a pair ofbatteries 253 coupled to adrug delivery system 254 by acurrent stabilizer 256. Thebatteries 253 in theelectrical circuit 250 can include, for example, but is not limited to, between one and three batteries, having voltages of, for example, 1.5 or 3V. FIG. 32A illustrates an embodiment having twobatteries 253. Thecurrent stabilizer 256 can calibrate theelectrical circuit 250 to provide an appropriate current for the subcutaneous drug delivery device. Theelectrical circuit 250 can also include aswitch 255. - In the alternative embodiment described in the preceding paragraph, the
current stabilizer 256 can use a single resistor or alternatively as shown in FIG. 32A, thecurrent stabilizer 256 includes tworesistors 260 connected in series. In a preferred embodiment, the tworesistors 260 have identical resistance values. The use ofmultiple resistors 260 can reduce the current charge as a result of accidental short circuiting of a resistor. The maximal delivery rate of thedelivery system 254 with a short circuit condition at one resistor can only be twice the nominal rate. A change of battery voltage and a change of resistance of theelectrical circuit 250 can change the current profile at thecircuit 250. In one embodiment, it is possible to control the current profile by selecting the voltage and number of batteries used in thecircuit 250. In a preferred embodiment, thecurrent profile 257 is constant over time, as illustrated in FIG. 32B. - The subcutaneous drug delivery device can also include an occlusion prevention mechanism. FIGS.33A-33F schematically illustrate a drug delivery system in which an undesired delivery of a bolus of a medicament can occur. FIG. 33A schematically shows a
delivery device 262 having agas chamber 264, adrug chamber 266, aflexible diaphragm 265, and aneedle 270. There is a lower risk of bolus delivery if the back pressure in thegas chamber 264 is constant. The gas is produced at a constant rate by the gas generator. As the gas is produced, the drug within the drug chamber can flow constantly to keep equal pressure within thedevice 262. FIG. 33B shows the linear relationship of drug delivery over time. - FIG. 33C shows an
occlusion 268 occurring inneedle 270 of thedelivery device 262. Once occluded, the pressure in thegas chamber 264 will rise as the gas generator continues to produce gas and the drug within thedrug chamber 266 does not flow. FIG. 33D illustrates that an occlusion can result in the reduction or termination of delivery of the drug over time. The pressure in thegas chamber 264 can reach a high enough level to overcome and remove the occlusion. Once the occlusion is removed, the drug within thedrug chamber 264 can flow rapidly until back pressure in thegas chamber 264 and the pressure in thedrug chamber 266 equalize, therein creating a bolus delivery of the drug. - FIGS. 33E and 33F illustrate the relationship between drug delivery and time, as the occlusion is removed and the pressures equilibrate. The size of the bolus can depend on the time duration of the occlusion and the nominal flow rate without the occlusion (Volume bolus=Time occlusion*Flow rate). The occlusion time duration depends upon the gas generation rate and the volume of the gas within the
gas chamber 264. The longer the time the subcutaneous drug delivery device worked before the occlusion, the bigger the volume of the gas in thechamber 264, the longer the time needed to rise to the pressure to remove theocclusion 268, the larger the bolus. FIG. 33F shows a graphical representation of the rapid flow of a drug delivery system as an occlusion is removed from a needle and the pressure equalizes. - FIG. 34A shows a
bolus prevention mechanism 272 within adrug delivery device 262 created by forming a constant, relatively high pressure level in the drug reservoir. In a preferred embodiment, themechanism 272 is avalve 274. The use of avalve 274 can create a constanthigh pressure 276 within thegas chamber 264, while maintaining alow pressure 278 within theneedle 270 of thedelivery device 262. Thehigh back pressure 276 and thelow pressure 278 within theneedle 270 can prevent occlusions from clogging thedelivery device 262 for lengthy periods of time, therefore minimizing or preferably preventing the formation and delivery of boli. As long as thehigh back pressure 276 is higher than the pressure needed to deliver the drugs subcutaneously, the flow of the drug will not be adversely affected. FIG. 34B shows a graphical representation of the steady delivery of drugs over time created by the use of a bolus prevention mechanism within the drug delivery device of the present invention. - A preferred embodiment of the subcutaneous
drug delivery device 282 can also include anoptical window 280, shown in FIG. 35, which indicates to a user when delivery of a drug contained within thedevice 282 is complete. The drug is typically contained between the plastic housing and the elastomeric membrane or diaphragm that moves away from the housing as the drug fills the reservoir. When the drug delivery device does not contain the drug, the elastomeric membrane is proximate to the housing. Theoptical window 280 is located on the housing. When the membrane is proximate to the housing, the optical effect of the direct reflection of light from the elastomeric membrane results in clearly visible membrane color, for example, blue. However, when the reservoir is full, the light is diffused in the drug chamber results in the appearance of the black color. In a preferred embodiment, theoptical window 280 is a circular structure which allows light to enter and includes a pair ofopaque sections 284 matching the membrane color and a transparentannular ring section 286 which allows the light to enter. The ring-like structure provides a more accurate assessment of the quantity of drug delivered. FIGS. 36A-36C show changes to the optical path through the window during drug delivery which indicate to a user the amount of fluid in the reservoir of the drug delivery device. - FIG. 36A illustrates a
drug reservoir 290 bounded by adiaphragm 288 and areservoir housing element 292. Thereservoir housing element 292 has thedrug window 280 which includes both theopaque section 284 and thetransparent section 286. In a preferred embodiment, the color of thecolored section 284 and thediaphragm 288 are the same, for example, both thecolored section 284 and thediaphragm 288 are light blue in color. At the onset of drug delivery, thedrug reservoir 290 can be full of a medication to be delivered to a patient. When thereservoir 290 is full, thetransparent section 286 of theoptical window 280 appears as a different color to that of thecolored section 284 and thediaphragm 288. In one embodiment, thetransparent section 286 will appear as black. - FIG. 36B illustrates a
drug reservoir 290 after drug delivery has been partially completed. At this stage of drug delivery, thediaphragm 288 can partially contact theoptical window 280 and can block a portion of thetransparent section 286. Such a blockage optically changes the appearance of a portion of thetransparent section 286, that is, instead of appearing black, it appears as the same color as thecolored section 284. Such a change in color indicates to a user that drug delivery is partially completed. - FIG. 36C illustrates a
drug reservoir 290 after drug delivery has been completed. At this stage of drug delivery, thediaphragm 288 can completely contact theoptical window 280 and can block the entiretransparent section 286. The contact of thediaphragm 288 against thetransparent section 286 can optically change the appearance of the color of thetransparent section 286, that is, instead of appearing black, the diaphragm becomes visible. A complete change in color of thetransparent section 286 can indicate to a user the end of drug delivery. - In another preferred embodiment, the drug delivery system can include an optical indicator to indicate proper application and operation to a user. The indicator can be, for example, a color marking system. The color marking system can be used to indicate to a user components of the drug delivery system which should be removed from the system prior to use. The color marking system can also indicate to the user whether or not the drug delivery system has been applied correctly or is operational. In a preferred embodiment, the color marking is, for example, yellow in color. The color marking can be applied directly to components of the drug delivery system or can be applied in the form of a colored label.
- In one embodiment, the filling adaptor or syringe adaptor of the subcutaneous drug delivery device can have yellow labeling attached thereon to indicate to a user that the adaptor should be removed before activating the delivery device. In another embodiment, the base of the delivery device can be produced (for example, dye in the plastic) with a color which contrasts with the color of the cover. During use, the cover of the delivery device can be hingedly moved towards the base and covers all but a small portion at the base. The disappearance of the contrastingly colored base can indicate to a user that the drug delivery device has been correctly applied and activated. Generally, when the drug delivery device is correctly applied and started, none of the parts of the device, which include color marking or color labeling, can be visible to the user.
- In another preferred embodiment, the subcutaneous drug delivery device can include a pressure sensitive mechanism, such as in FIG. 37A, for preventing bolus delivery or rapid injection of a drug into the user. A
switch 300 can prevent a rapid injection of drug to a user as a result of an increase in pressure in the drug delivery device. Theswitch 300 can help to avoid an increase in pressure within the drug delivery device caused by blockage of the needle. Theswitch 300 can form part of acircuit 250, as shown in FIG. 32A, which controls the power supply to a gas generating portion of the drug delivery device. - One embodiment of the
switch 300 is shown in FIGS. 37A-37C. In this embodiment, theswitch 300, which is part of acircuit 308, is made from aconductive membrane 302 and aconductive lever 306 is located on the printedcircuit board 159, as seen in FIG. 37A. Theswitch 300 has achamber 304 which is sealed by theconductive membrane 302 as seen in FIGS. 37B and 37C. Thechamber 304 contains an accurate amount of gas, such as, for example, air, and can be made of a solid material whose volume is not affected by pressure and is non conductive electrically, referred to as a solid isolator. Themembrane 302 has a raised annular portion to allow the membrane to flex depending on the pressure differential between thechamber 304 and theexpandable chamber 14. Thelever 306 is designed to rest upon themembrane 302 during operation. When theconductive lever 306 contacts theconductive membrane 302, thecircuit 308 can be closed, thereby allowing the gas generating portion of the device to operate 310. As long as the pressure within the gas generating portion of the delivery system is lower than the pressure within thechamber 304, thelever 306 can contact themembrane 302. - In the event that the pressure within the drug reservoir increases, such as caused by a blockage in the needle, the pressure within the gas generating portion can increase to a higher level than the pressure within the
chamber 304. In the event pressure within the drug reservoir and theexpandable chamber 14 increases, the pressure within thechamber 304 is lower relative to theexpandable chamber 14 and themembrane 302 is pushed away from contact with thelever 306, as shown in FIG. 37B. As a result, thelever 306 is no longer in electrical contact with themembrane 304 and the circuit opens, thus shutting off power to the gas generating portion of the device. This, in turn, stops any pressure build-up and potential for a boli delivery. The conductive membrane or lever can be made from aluminum or copper, for example. - FIG. 37D illustrates
circuit 308 as part ofcircuit 256 which was shown in FIG. 32A. Theswitch 300 is in series withswitch 255. Bothswitches Switch 300 is normally closed and switch 255 is closed to start the gas generation. As indicated above, switch 300 only opens if the pressure increases to a current level, such as due to a blockage. - FIGS. 38A and 38B illustrate an alternative embodiment of a pressure
sensitive mechanism 300. In this embodiment, theswitch 300 includes anisolator membrane 314, mounted above achamber 304, and aconductive thread 316 combined with themembrane 314. As long as the pressure within the gas generating portion is lower than the pressure within thechamber 304, the thread will remain intact, thereby completing the circuit for the gas generator, which remains in an onposition 310. In the event of an increase in pressure in the drug reservoir, as shown in FIG. 38B, the gas generating portion can increase to a higher level than the pressure within thechamber 304. The pressure differential can cause themembrane 314 to sink into thechamber 304, thereby severing thethread 316. Such a break can open thecircuit 308, thereby preventing the gas generator from producinggas 312 and preventing an increase in pressure in the drug reservoir. In contrast to the previous embodiment, once the circuit is open the circuit cannot be closed again, i.e. once the membrane is depressed the thread is severed. - FIGS.39A-39C illustrate another preferred embodiment of a pressure
sensitive switch 300. FIG. 39A is an enlarged perspective view of theswitch 300 with portions broken away. FIGS. 39B and 39C are schematics of theswitch 300. In this embodiment, theswitch 300 is formed from a pair ofelectrodes 318, extending into acapsule 319. Eachelectrode 318 connected to thecircuit 308 contacts a droplet ofmercury 320 located in a channel which opens onto alarge chamber 304. Thedroplet 320 of mercury maintains the current between contacts as long as the pressure in the gas generating portion is less than the pressure within thechamber 304. Such a contact can close thecircuit 308, thereby allowing the gas generator to operate 310. Under a high enough pressure in the drug reservoir, as shown in FIG. 39B, the pressure in thechamber 304 can be lower than the pressure within the gas generating portion of the delivery device, thereby causing themercury droplet 320 to move towards thechamber 304 and away from theelectrodes 318. The mercury droplet responds to the relative pressure between the gas generating portion and thechamber 304. Such a movement opens thecircuit 308, thereby preventing the gas generator from producing gas and increasing the pressure in the drug reservoir. - While both the first embodiment, FIGS.37A-37D, and the third embodiment, FIGS. 39A-39C, have the capability to have the
switch 300 closed again if the pressure equalizes, it is contemplated that the pressure will not decrease and therefore once the switch is open, it will remain open and the power to the gas generator will not be restored. - Another preferred embodiment of the subcutaneous drug delivery system includes a mechanism which reduces tolerances and thus errors during manufacture of the device. During manufacture, certain components need to have a particular tolerance. When the device is assembled, if the tolerances of each component are significant, the volume of the internal housing may be outside of a specified desired range. Thus, an insert, for example, a foam insert that receives the internal components of the device, maintains an accurate internal volume so that upon assembly, the volume of the internal housing, and thus, the drug reservoir is within an accurate range.
- A subcutaneous drug delivery device322 is shown in FIG. 40. The device 322 can have a
cover 324 and abase 326 and can house aninner component 328. The device 322 can also have aninternal volume 330 between thecover 324 and theinner component 328. During manufacture of the device, thebase 326,cover 324, andinner components 328 need to be manufactured within certain tolerances. Due to the tolerances of the components, theinternal volume 330 can be outside of a specific range. To eliminate any variability due to tolerances, aninsert 332 can be used to maintain theprecise drug reservoir 12 necessary within the device 322. Theinsert 332 forces theinner component 328 toward thecover 324 of the delivery device 322. This eliminates assembly tolerance errors during manufacturing and can get theinternal volume 330 of the device 322 within an accurate and acceptable range. Theinternal air volume 330 includes the internal chamber which defines thereservoir 12 and theexpandable chamber 14, and air volume between components and below theexpandable chamber 14, which is referred to as a dead air volume. Dead air can also be defined as residual air below the diaphragm after the primming. In one embodiment, theinsert 332 is a flexible material. In a preferred embodiment, theinsert 332 is closed foam; the air pockets or bubbles are sealed so not forming a part of the dead air. Theinternal volume 330 of the device 322 can be used as a drug reservoir. - In another embodiment, the
drug delivery device 336 can include anactivation lever 334, as shown in FIGS. 41A and 41B to initiate gas generation in the expandable chamber which in turn controls the delivery of the drug from the device. Theactivation lever 334 includes apuncturing device 340 and anelectrical contact 342. Thedrug delivery device 336 includes anelectrolytic cell 338 mounted next to theactivation lever 334. On the printed circuit board, theelectrolytic cell 338 has a foil cover, for example, aluminum foil, to preserve chemical ingredients within thecell 338. Without the foil, the electrolyte water content could evaporate during storage affecting the performance of thedevice 336. Theactivation lever 334 can be mounted to the drug delivery device by apivot 344. Upon depression, thepuncturing device 340 of theactivation lever 334 can puncture the foil cover of theelectrolytic cell 338, thereby allowing the gases generated by the cell operation to escape and to expand the expandable gas chamber and thereby compressing the drug reservoir of thedelivery device 336. Also upon depression of theactivation lever 334, theelectrical contact 342 on thelever 334 engages a contact 346 on the printed circuit board of thedevice 336 which starts the delivery of the drug. Thecontact 342 on thelever 334 engages the two contact 346 on thedelivery device 336 moving one of the contacts 346 into engagement with the other contact 346 for an indefinite time period. - In a preferred embodiment, the
lever 334 can be made from a plastic material. Aplastic lever 334 can be economically produced using an injection molding technique, for example. Theplastic lever 334 can be secured to thepivot 344 by a snap fit and thereby not require soldering. Theplastic lever 334 can be manufactured such that the lever does not bend when forming an electrical contact with thedrug delivery device 336 or when puncturing the foil on theelectrolytic cell 338. - Another embodiment of the drug delivery system relates to controlling the rate of delivery by parameters such as, for example, residual air volume, base permeability, membrane seal and membrane permeability. In particular, with regards to the residual air volume, an air space can be created within a drug delivery system by providing a cavity for air, for example. Such an air space can be considered as a residual or dead air volume and can have an effect on the drug delivery rate. The larger a residual air volume, the greater the effect on delivery rate. For example, the expansion of the air volume because of a temperature increase can create a bolus effect in the device delivery. Residual air volume can be controlled by design characteristics of the geometry of the inner parts of the device. A high residual air volume within the device can add a delivery period between the activation of the drug delivery system and the actual start of drug delivery.
- FIG. 42 illustrates a graph of a
delivery 350 of drugs through a drug delivery system under normal or low residual air volume conditions anddelivery 352 under high residual air volume conditions. The drugs delivered under high residual air volume conditions are delayed 354 between the activation of the system and the start of drug delivery. By altering the residual air volume within the delivery system by changing the design characteristics, the delay can be reduced or eliminated within the system. - Another embodiment of the drug delivery system relates to controlling the material characteristics of the device components, such as, for example, the permeability of the system which in turn affects the delivery rate of the drug. Permeability can be controlled, for example, by both changing the geometery of the inner components of the delivery system and by changing the materials used to manufacture the system. By lowering the permeability of the delivery system, less gas can diffuse out from the system. With less gas leaving the system, the variance in delivery rate can be lowered or eliminated. By minimizing the permeability to gases of the expandable chamber, a constant delivery rate of the drug can be maintained.
- For example, by using PET plastic, the gas leak rate or permeability is minimized. Alternatively, a highly permeable material can allow a large amount of gas to diffuse out of the drug delivery system which can reduce the drug delivery rate. FIG. 43 illustrates a graph of
delivery 356 of drugs for a low permeability system anddelivery 358 for high permeability system. As shown, a high permeability yields a higher delivery rate at the onset ofdelivery 359 and a lower rate ofdelivery 360 as time goes on, compared to a delivery system having anormal permeability 356. - Packaging of a drug delivery device can be an important factor relating to the practical storage and use of the device at different altitudes and humidities. For example, proper packaging of the device can extend the storage period of the device, without an appreciable affect on the device performed. Proper packaging can also prevent environmental affects, such as, the diffusion of water from the electrolyte that provides for the gas generation from the drug delivery device without additional protection, internal to the device.
- In a preferred embodiment, a hermetic packaging for a drug delivery system achieves extended shelf conditions and simplifies the barometric pressure valve and the electrolytic cell of the system.
- In a previous embodiment, the drug delivery system was packaged using a blister and a Tyvek lid to maintain sterility and protect the device during a two year shelf life. In this embodiment, the Tyvek lid is gas permeable when exposed to atmospheric conditions, such as, for example, non-controlled pressure and humidity conditions. With this type of packaging, issues can arise as to the maintenance of barometric pressure valve performance and the prevention of drug evaporation from the delivery system. To maintain the desired performance of the barometric pressure valve of the delivery device, the valve has two positions. In one position, the storage position, the valve membrane can move. In another position, the working position, the valve builds pressure against the drug delivery system needle. In order to prevent evaporation of the electrolyte, the electrolytic cell can be fully protected by aluminum foil. Further, the foil seal requires the use of an activation lever. Pinching of this foil around the cell is required for system operation.
- In the preferred embodiment, the blister and Tyvek lid packaging can be replaced by a hermetically sealed packaging. By changing the packaging, the issues of valve position and adverse environmental impact, such as, for example, diffusion can be solved without any internal feature protection.
- Referring to FIG. 44A, an alternative
drug delivery system 362 is shown with astationary valve 368. Thedrug delivery system 362 is shown without thedisplaceable cover 143, such as shown in FIGS. 14 and 15. The internal space of thedrug delivery device 362 of FIG. 44A defines anexpandable chamber 147 when thediaphragm 148 is in the position shown or a reservoir when the diaphragm is in the position shown in dotted outline at 149. Thedevice 362 has aswitch 151 which is engaged by avalve 150, such as seen in FIGS. 14-16, to close the switch to activate the process. - In contrast to the air-filled flow-regulating
chamber chamber 35 moved with the flow of fluid (the drug) both above and below the chamber, thestationary valve 368 does not move. Thestationary valve 368 has anairtight chamber 370 sealed by aflow diaphragm 372, similar to theairtight chamber 36 anddiaphragm 26 of FIG. 3. However, another distinction is that theflow diaphragm 372 of this embodiment does not have a projection which is received in the inlet associated with the needle such as in some of the previous embodiments. - In contrast, referring to FIG. 44B, the
flow diaphragm 372 has a flat circular portion 374 for sealing the top of theneedle 376. The drug flows through aport 378 from the reservoir to anannular chamber 380 underlying theflow diaphragm 372. The pressure in the reservoir and theannular chamber 380 is equal to the pressure inside the controlled volume, theairtight chamber 370, therein stressing/flexing theflow diaphragm 372 and opening the entrance to theneedle 376. In this embodiment, the valve can become a stationary valve, more accurate and with longer shelf life in extreme conditions. The aluminum protective liner and the pincher mechanism are no longer needed for the cell functioning. - The packaging is illustrated in FIG. 45. The
drug delivery system 362 can be enclosed between afoil layer 364 and anon-permeable blister 366 to maintain internal pressure despite environmental parameter changes, such as pressure and temperature. The blister is a semi-rigid package with an aluminum cover or low permeability plastic welded at its bottom. The drug delivery device is inserted into the cavity. The blister is made of PET. The cover is made ofaluminum foil 38 micron with 2 micron of H.S.C. for the welding. The leak through the materials due to relative pressure at the storage time, designed to effect less than permitted by the drug delivery system specification. The surface area of the package is about 0.034 m2 with an average thickness of 0.3 mm, with a permeability factor of about 0.4. Given these dimensions, the pressure in the device is calculated to decrease up to about 3% in two years. Thefoil layer 364 can be, for example, an aluminum foil. - Over-pressurization of the package during manufacturing can provide a longer shelf life as there is more time for the air to leak before getting to the minimum required pressure, and thus adding shelf life.
- In an alternative embodiment for packaging a drug delivery device, a secondary packaging device can be used with a primary gas permeable packaging, such as a blister and Tyvek lid, to extend the storage life of the device. The use of secondary packaging can increase the shelf life of a delivery device without altering the drug delivery rate.
- In a preferred embodiment, the
secondary packaging device 380 can be acylindrical container 382, as shown in FIG. 46. Thecylindrical container 382 can be an aluminum or tin can, for example. In an embodiment, thecontainer 382 can hold either four delivery device packages 384, as shown in FIG. 46, or can hold more delivery device packages 384. Prior to storing thedrug delivery packages 384 within thecontainer 382, in one embodiment, the drug delivery device can be packaged between a blister and a Tyvek lid and then sterilized. - FIGS.47A-47C illustrate an alternative embodiment for a
secondary packaging device 380. In this embodiment, as shown, the secondary packaging device is arectangular container 386. Therectangular container 386 can have acover portion 390 and abase portion 388 where thebase portion 388 can be used for storage of drug delivery packages 384. FIG. 47A shows an embodiment of thecover portion 390 in a closed position while FIG. 47B shows an embodiment of thecover portion 390 in an open position where thecover 390 can completely disconnect from thebase portion 388. In an alternate embodiment, thecover portion 390 can be hingedly attached to thebase portion 388. - The
rectangular container 386, in one embodiment, can be designed to hold up to fourdrug delivery devices 384, as shown in FIG. 47B. In another embodiment, thecontainer 386 can be sized to hold asingle delivery device 384, as shown in FIG. 47C. A limitation to the use of thecontainer 386 holding fourdelivery devices 384 can include using the fourth, or last, device within opening thecontainer 386. For acontainer 386 holding up to four delivery devices, the dimensions of the container can be about 240 mm×148 mm×70 mm. For acontainer 386 holding a single delivery device, the dimensions of the container can be about 120 mm×110 mm×35 mm. Thecontainer 386 can be made from a plastic material. Thecontainer 386 can include aluminum foil covered with, for example, polyethylene lamination to close the packaging using heat. - FIG. 48 shows an alternative embodiment of the drug delivery device indicated generally at400. The delivery system is adapted for epidural, intraterial and intrathecial administration. Instead of a hypodermic needle extending directly from a
housing 402, atube 404 extends from abarometric pressure valve 406 to a location on thehousing 402. Acatheter 410 is secured by acollet gripper 408 to connect to thetube 404. - An alternative embodiment
drug delivery device 412 of FIG. 49 has a piece oftubing 414 from anepidural needle 416 connected directly to atube 418 located within thehousing 402. Thetube 418 extends from thebarometric valve 406. - FIG. 50A shows a
drug delivery device 420 with aluer 422 for attaching atubing 424 from anepidural needle 416. Atube 404 extends from thebarometric valve 406 to theluer 422. - FIG. 50B shows the
drug delivery device 420 with theluer 422. Thetubing 424 from theepidural needle 416 attaches to theluer 422. The epidural needle set has a hydrophilic membrane 428 for filtration. - It is further appreciated that the present invention may be used to deliver a number of drugs. The term “drug” used herein includes but is not limited to peptides or proteins, hormones, analgesics, anti-migraine agents, anti-coagulant agents, narcotic antagonists, cleating agents, anti-anginal agents, chemotherapy agents, sedatives, antineoplastics, prostaglandins and antidiuretic agents.
- Typical drugs include peptides, proteins or hormones such as insulin, calcitonin, calcitonin gene regulating protein, atrial natriuretic protein, colony stimulating factor, betaseron, erythrogpoietin (EPO), interferons such as a,b or g interferon, somatropin, somatotropin, somastostatin, insulin-like growth factor (somatomedins), luteinizing hormone releasing hormone (LHRH), tissue plasminogen activator (TPA), growth hormone releasing hormone (GHRH), oxytocin, estradiol, growth hormones, leuprolide acetate, factor VM, interleukins such as interleukin-2, and analogues thereof; analgesics such as fentanyl, sufentanil, butorphanol, buprenorpbine, levorphanol, morphine, hydromorphone, hydrocodone, oxymorphone, methadone, lidocaine, bupivacaine, diclofenac, naproxen, paverin, and analogues thereof; anti-migraine agents such as sumatriptan, ergot alkaloids, and analogues thereof; anti-coagulant agents such as heparin, hirudin, and analogues thereof; anti-emetic agents such as scopolamine, ondansetron, domperidone, metocloprarnide, and analogues thereof; cardiovascular agents, anti-hypertensive agents and vasodilators such as diltiazem, clonidine, nifedipine, varapmil, isosorbide-5-mononitrate, organic nitrates, agents used in treatment of heart disorders, and analogues thereof; sedatives such as benzodiazepines, phenothiozines, and analogues thereof; chelating agents such as deferoxamine, and analogues thereof; anti-diuretic agents such as desmopressin, vasopressin, and analogues thereof; anti-anginal agents such as nitroglycerine, and analogues thereof; anti-neoplastics such as fluorouracil, bleomycin, and analogues thereof; prostaglandins and analogues thereof; and chemotherapy agents such as vincristine, and analogues thereof.
- While this invention has been particularly shown and described with references to preferred embodiments thereof, it will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the scope of the invention encompassed by the appended claims.
Claims (50)
1. A drug delivery device comprising:
a housing having an internal chamber;
an elastomeric diaphragm within said internal chamber for defining an internal drug reservoir chamber and an expandable gas chamber which forms a pair of variable area chambers;
a gas generator for expanding the area of said expandable gas chamber and decreasing the area of said internal drug reservoir;
a lumen having an inlet and an outlet;
a fluid path defined between said internal drug reservoir and said lumen input;
a flow regulator, in communication with said fluid path, for effecting volumetric changes in response to ambient condition changes, said flow regulator comprising a chamber filled with fixed volume of air and a flexible chamber surface that opens or closes said lumen inlet based on a pressure differential between said fluid path and said internal drug reservoir chamber; and
means for maintaining a specific flow rate of drug delivery, said means for maintaining a specific flow rate comprising an electrical circuit that controls said gas generator.
2. The drug delivery device of claim 1 wherein said lumen is a needle and said flexible chamber surface is a diaphragm.
3. The drug delivery device of claim 2 wherein said gas generator generates a sufficient gas pressure to drive the drug through said fluid path and to deform said diaphragm to allow said drug to flow through said needle and prevent a bolus delivery of drug that may be caused by an occlusion in said needle.
4. A drug delivery device comprising:
a housing having an internal chamber;
an elastomeric diaphragm within said internal chamber for defining an internal drug reservoir chamber and an expandable gas chamber which form. a pair of variable area chambers;
a gas generator for expanding the area of said expandable gas chamber and decreasing the area of said internal reservoir;
a drug delivery outlet;
a fluid path defined between said internal reservoir and said drug delivery outlet;
a flow regulator, in communication with said fluid path, for effecting volumetric changes in response to ambient condition changes; and
means for maintaining a specific flow rate of drug delivery, said means for maintaining a specific flow rate comprising:
an electrical circuit that controls said gas generator; and
an electrical switch, coupled to said electrical circuit, that which controls power to said electrical circuit, said electrical switch being is controlled by the pressure differential between said expandable gas chamber and a third chamber filled with a predetermined volume of gas.
5. The drug delivery device of claim 4 wherein said electrical switch comprises a conductive lever that interfaces with a conductive membrane which forms a surface of said third chamber filled with said predetermined volume of gas, said lever either contacting, or not contacting, said membrane which can flex depending on the pressure differential between said expandable gas chamber and said third chamber, to open or close said switch.
6. The drug delivery device of claim 4 wherein said electrical switch cannot be closed, once opened, said switch comprising:
an isolator membrane that forms a flexible surface of said third chamber;
a conductive thread that runs along said flexible surface; and
said conductive thread conveying power to said electrical circuit whenever the pressure in said expandable gas chamber is less than the pressure in said third chamber, said conductive thread severing whenever the pressure in said expandable gas chamber exceeds the pressure in said third chamber, thereby terminating power to said electrical circuit.
7. The drug delivery device of claim 4 wherein said electrical switch comprises:
a channel having a first end exposed to said expandable gas chamber and a second end exposed to said third chamber;
a pair of electrodes across the width of said channel;
a conductive metal droplet that can move inside said chamber; and
wherein whenever the pressure in said expandable gas chamber is less than the pressure in said third chamber, said conductive metal droplet electrically couples said pair of electrodes together and whenever the pressure in said expandable gas chamber exceeds the pressure in said third chamber, said conductive meal droplet is driven out of contact with said pair of electrodes.
8. The drug delivery device of claim 7 wherein said conductive metal droplet comprises mercury.
9. A method of controlling the rate of drug delivery, said method comprising the steps of:
providing a drug delivery device having a housing including an internal chamber and an elastomeric diaphragm within said internal chamber for defining an internal drug reservoir chamber and an expandable gas chamber that form a pair of variable area chambers;
expanding the area of the expandable gas chamber and decreasing the area of the internal area by generating a gas in an electrolytic cell controlled by an electrical circuit to drive the drug out of said reservoir at a specific flow rate; and
altering the flow which is in communication with the fluid path between the internal reservoir and a needle outlet in response to ambient condition changes by valving a needle input and requiring that the driven drug pressure required to open the valve be equal to, or greater than, ambient pressure.
10. A method of preventing a bolus delivery of drug from a drug delivery device, said method comprising the steps of:
providing a drug delivery device having a housing including an internal chamber and an elastomeric diaphragm within said internal chamber for defining an internal drug reservoir chamber and an expandable gas chamber that form a pair of variable area chambers;
expanding the area of the expandable gas chamber and decreasing the area of the internal area by generating a gas in an electrolytic cell controlled by an electrical circuit to drive the drug out of said reservoir at a specific flow rate; and
altering the flow which is in communication with the fluid path between the internal reservoir and a needle outlet by valving a needle input and requiring that the driven drug pressure required to open the valve be greater than back pressure created by an occlusion of said needle.
11. A method of preventing a bolus delivery of drug from a drug delivery device, said method comprising the steps of:
providing a drug delivery device having a housing including an internal chamber and an elastomeric diaphragm within said internal chamber for defining an internal drug reservoir chamber and an expandable gas chamber that form a pair of variable area chambers;
expanding the area of the expandable gas chamber and decreasing the area of the internal area by generating a gas in an electrolytic cell controlled by an electrical circuit to drive the drug out of said reservoir at a specific flow rate; and
de-activating said generation of gas by sensing a pressure differential between said expandable gas chamber and a reference gas chamber wherein the pressure in said expandable gas chamber exceeds the pressure in said reference gas chamber.
12. The method of claim 11 further comprising the step of re-activating said generation of gas whenever the pressure in said expandable gas chamber is less than the pressure in said reference gas chamber.
13. A drug delivery device comprising:
a housing having an internal chamber;
an elastomeric diaphragm within said internal chamber for defining an internal drug reservoir chamber and an expandable gas chamber which form a pair of variable area chambers;
an electrolytic cell controlled by an electrical circuit which generates a gas for expanding the area of the expandable gas chamber and decreasing the area of said internal reservoir;
a drug delivery outlet;
a fluid path defined between said internal reservoir and said drug delivery outlet;
a flow regulator, in communication with said fluid path, for effecting volumetric changes in response to ambient condition changes; and
a visual drug quantity indicator carried by said housing.
14. The drug delivery device of claim 13 wherein said elastomeric diaphragm comprises a color and wherein said visual drug quantity indicator comprises a window having a transparent portion and a portion having the color of said elastomeric diaphragm and wherein the color appearing in said window informs a user of the quantity of drug in said device.
15. The drug delivery device of claim 13 further comprising a visual usage indicator indicating proper usage of said device.
16. The drug delivery device of claim 15 wherein said visual usage indicator comprises a component which is to be hidden when properly installed on the user's body, said component including a color that can only be seen by the user if said device is installed improperly.
17. The drug delivery device of claim 15 wherein said visual usage indicator comprises a component which is to be removed prior to activating said device, said component including a color that alerts the user to remove said component before said device can be activated.
18. The drug delivery device of claim 13 wherein said electrolytic cell is covered by a foil cover.
19. The drug delivery device of claim 18 further comprising an activation mechanism having an electrical contact and a puncturing device for puncturing said foil cover of said electrolytic cell.
20. A method of controlling the rate of drug delivery comprising the steps of:
providing a drug delivery device having a housing including an internal chamber and an elastomeric diaphragm within said internal chamber for defining an internal drug reservoir chamber and an expandable gas chamber that form a pair of variable area chambers;
expanding the area of the expandable gas chamber and decreasing the area of the internal area by generating a gas in an electrolytic cell controlled by an electrical circuit;
altering the flow which is in communication with the fluid path between the internal reservoir and a drug delivery outlet in response to ambient condition changes; and
controlling residual air volume, material permeability, material properties of plastic material in said device and said membrane seal.
21. A method of controlling the rate of drug delivery comprising the steps of:
providing a drug delivery device having a housing including an internal chamber and an elastomeric diaphragm within said internal chamber for defining an internal drug reservoir chamber and an expandable gas chamber that form a pair of variable area chambers;
expanding the area of the expandable gas chamber and decreasing the area of the internal area by generating a gas in an electrolytic cell controlled by an electrical circuit;
altering the flow which is in communication with the fluid path between the internal reservoir and a drug delivery outlet in response to ambient condition changes; and
packaging said drug delivery system to insulate said device from environmental conditions.
22. The method of claim 21 wherein one of said environmental conditions is atmospheric pressure.
23. The method of claim 21 wherein one of said environmental conditions is humidity.
24. A method of controlling the rate of drug delivery comprising the steps of:
providing a drug delivery device having a housing including an internal chamber and an elastomeric diaphragm within said internal chamber for defining an internal drug reservoir chamber and an expandable gas chamber that form a pair of variable area chambers;
expanding the area of the expandable gas chamber and decreasing the area of the internal area by generating a gas in an electrolytic cell controlled by an electrical circuit;
altering the flow which is in communication with the fluid path between the internal reservoir and a drug delivery outlet in response to ambient condition changes; and
including an insertion device for accommodating design tolerances.
25. The method of claim 24 wherein said insertion device comprises foam.
26. A drug delivery device comprising:
a housing having an internal chamber;
providing a drug delivery device having a housing including an internal chamber and an elastomeric diaphragm within said internal chamber for defining an internal drug reservoir chamber and an expandable gas chamber that form a pair of variable area chambers;
a gas generator having an electrolytic cell and an electrical circuit, said gas generator providing gas at a controllable rate into said expandable gas chamber;
said electrical circuit having a current stabilizing element in electrical communication with said electrolytic cell;
a drug delivery outlet; and
a fluid path defined between said internal reservoir and said drug delivery outlet and said reservoir.
27. The drug delivery device of claim 26 further comprising a flow regulator, in communication with said fluid path, for effecting volumetric changes in response to ambient condition changes.
28. The drug delivery device of claim 26 wherein said drug delivery outlet comprises a tube extending from said housing.
29. The drug delivery device of claim 28 wherein said tubing is coupled to said housing at an outlet port having a luer connection.
30. The drug delivery device of claim 29 further comprising an epidural needle.
31. The drug delivery device of claim 24 wherein said drug delivery outlet comprises a needle extending from said housing for penetration of the skin of a subject.
32. The drug delivery device of claim 31 further comprising a displaceable cover that is coupled to said housing such that displacement of said housing relative to said cover when said cover has been applied to the skin of a subject causes said delivery needle to penetrate the skin of the subject.
33. The drug delivery device of claim 32 wherein said displaceable cover is displaceable relative to said housing between a first position in which said needle is concealed from the exterior of said device, a second position in which said delivery needle protrudes from said device for penetration of the skin, and wherein said device further comprises means for locking said device in said first position after a single reciprocation of said device from said first position to said second position and back to said first position.
34. The drug delivery device of claim 33 further comprising a visual usage indicator indicating proper usage of said device.
35. The drug delivery device of claim 34 wherein said visual usage indicator comprises a component which is to be hidden when properly installed on the user's body, said component including a color that can only be seen by the user if said device is installed improperly.
36. The drug delivery device of claim 34 wherein said visual usage indicator comprises a component which is to be removed prior to activating said device, said component including a color that alerts the user to remove said component before said device can be activated.
37. The drug delivery device of claim 33 wherein movement of said cover relative to said housing is initially prevented by a removable locking member.
38. The drug delivery device of claim 37 wherein the presence of said removable locking member also prevents said means for providing a gas from being actuated.
39. The drug delivery device of claim 27 wherein said flow regulator includes a member having a cavity and a flow diaphragm defining a closed space, said member being movable in said flow path.
40. The drug delivery device of claim 27 wherein said flow regulating chamber includes a member having a cavity and a flow diaphragm defining a closed space, said member being rigid relative to said flow path.
41. The drug delivery device of claim 38 further comprising packaging of said drug delivery device to insulate said device from environmental conditions.
42. The drug delivery device of claim 41 wherein one of said environmental conditions is atmospheric pressure.
43. The drug delivery device of claim 41 wherein one of said environmental conditions is humidity.
44. The drug delivery device of claim 26 further comprising a visual drug quantity indicator and wherein said elastomeric diaphragm comprises a color, said visual drug quantity indicator comprising a window having a transparent portion and a portion having the color of said elastomeric diaphragm and wherein the color appearing in said window informs a user of the quantity of drug in said device.
45. The drug delivery device of claim 44 wherein said drug delivery outlet comprises the outlet of a needle having an inlet, said drug delivery device further comprising a flow regulator, in communication with said fluid path, for effecting volumetric changes in response to ambient condition changes, said flow regulator comprising a chamber filled with a fixed volume of air and a flexible chamber surface that opens or closes said needle inlet based on a pressure differential between said fluid path and said internal drug reservoir chamber.
46. The drug delivery device of claim 45 wherein said current stabilizing element has at least a pair of resistors in series.
47. The drug delivery device of claim 46 further comprising a pressure sensitive mechanism that detects increased pressure in said internal chamber and prevents a pressure build-up.
48. The drug delivery device of claim 47 wherein said electrolytic cell is covered by a foil cover.
49. The drug delivery device of claim 49 further comprising an activation mechanism including an electrical contact and a puncturing device for puncturing said foil cover of said electrolytic cell.
50. The drug delivery device of claim 49 further comprising a visual usage indicator for indicating proper usage of said device.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US10/336,459 US20030135159A1 (en) | 1997-05-06 | 2003-01-03 | Drug delivery device |
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US4574597P | 1997-05-06 | 1997-05-06 | |
US09/072,875 US6186982B1 (en) | 1998-05-05 | 1998-05-05 | Subcutaneous drug delivery device with improved filling system |
US09/577,033 US6530900B1 (en) | 1997-05-06 | 2000-05-23 | Drug delivery device |
US10/336,459 US20030135159A1 (en) | 1997-05-06 | 2003-01-03 | Drug delivery device |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US09/577,033 Division US6530900B1 (en) | 1997-05-06 | 2000-05-23 | Drug delivery device |
Publications (1)
Publication Number | Publication Date |
---|---|
US20030135159A1 true US20030135159A1 (en) | 2003-07-17 |
Family
ID=24307007
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US09/577,033 Expired - Lifetime US6530900B1 (en) | 1997-05-06 | 2000-05-23 | Drug delivery device |
US10/336,459 Abandoned US20030135159A1 (en) | 1997-05-06 | 2003-01-03 | Drug delivery device |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US09/577,033 Expired - Lifetime US6530900B1 (en) | 1997-05-06 | 2000-05-23 | Drug delivery device |
Country Status (6)
Country | Link |
---|---|
US (2) | US6530900B1 (en) |
EP (1) | EP1284758A2 (en) |
JP (2) | JP5102927B2 (en) |
AU (1) | AU2001264887A1 (en) |
CA (1) | CA2411202A1 (en) |
WO (1) | WO2001089607A2 (en) |
Cited By (124)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20040116847A1 (en) * | 2002-09-12 | 2004-06-17 | Children's Hospital Medical Center | Method and device for painless injection of medication |
US20040138612A1 (en) * | 2002-07-22 | 2004-07-15 | Shermer Charles D. | Patch-like infusion device |
WO2005018703A2 (en) | 2003-08-12 | 2005-03-03 | Becton, Dickinson And Company | Patch-like infusion device |
US20060095014A1 (en) * | 2003-05-08 | 2006-05-04 | Novo Nordisk A/S | External inserter for transcutaneous device |
WO2006061354A1 (en) * | 2004-12-06 | 2006-06-15 | Novo Nordisk A/S | Ventilated skin mountable device |
US20060142698A1 (en) * | 2003-05-08 | 2006-06-29 | Novo Nordisk A/S | Internal needle inserter |
EP1708767A1 (en) * | 2003-12-16 | 2006-10-11 | Ultimate Medical Pty. Ltd. | Fluid delivery device |
US20070021733A1 (en) * | 2003-10-21 | 2007-01-25 | Novo Nordisk A/S | Internal fluid connector |
US20070049865A1 (en) * | 2003-08-01 | 2007-03-01 | Novo Nordisk A/S | Retraction means for transcutaneous device |
US20070104596A1 (en) * | 2004-03-30 | 2007-05-10 | Novo Nordisk A/S | Actuator system comprising lever mechanism |
US20070276320A1 (en) * | 2004-02-17 | 2007-11-29 | Wall Eric J | Injection Device for Administering a Vaccine |
US20080119790A1 (en) * | 2006-11-22 | 2008-05-22 | Seattle Medical Technologies | Disposable infusion device filling apparatus and method |
US20080157713A1 (en) * | 2004-06-14 | 2008-07-03 | Massachusetts Institute Of Technology | Electrochemical methods, devices, and structures |
US20080167641A1 (en) * | 2005-05-13 | 2008-07-10 | Novo Nordisk A/S | Medical Device Adapted To Detect Disengagement Of A Transcutaneous Device |
US20080215006A1 (en) * | 2004-09-22 | 2008-09-04 | Novo Nordisk A/S | Medical Device with Transcutaneous Cannula Device |
US20080287870A1 (en) * | 2005-10-17 | 2008-11-20 | Nov Nordisk A/S | Vented Drug Reservoir Unit |
US20080287871A1 (en) * | 2002-04-02 | 2008-11-20 | Wilkinson Bradley M | Method and Device for Intradermally Delivering a Substance |
US20090012472A1 (en) * | 2004-09-22 | 2009-01-08 | Novo Nordisk A/S | Medical Device with Cannula Inserter |
US20090014320A1 (en) * | 2004-06-14 | 2009-01-15 | Massachusetts Institute Of Technology | Electrochemical actuator |
US20090028824A1 (en) * | 2007-07-26 | 2009-01-29 | Entra Pharmaceuticals, Inc. | Systems and methods for delivering drugs |
US20090062778A1 (en) * | 2006-03-13 | 2009-03-05 | Novo Nordisk A/S | Medical System Comprising Dual-Purpose Communication Means |
US20090069868A1 (en) * | 2006-03-11 | 2009-03-12 | Henrik Bengtsson | Secure Pairing of Electronic Devices using Dual Means of Communication |
US20090076451A1 (en) * | 2005-01-24 | 2009-03-19 | Nova Nordisk A/S | Medical Device with Protected Transcutaneous Device |
US20090093792A1 (en) * | 2007-10-02 | 2009-04-09 | Yossi Gross | External drug pump |
US20090118682A1 (en) * | 2005-09-13 | 2009-05-07 | Novo Nordisk A/S | Reservoir Device With Inspection Aid For Detection Of Drug Condition |
US20090131860A1 (en) * | 2005-04-13 | 2009-05-21 | Novo Nordisk A/S | Medical Skin Mountable Device And System |
US20090163874A1 (en) * | 2006-04-26 | 2009-06-25 | Novo Nordisk A/S | Skin-Mountable Device in Packaging Comprising Coated Seal Member |
US20100063448A1 (en) * | 2007-03-06 | 2010-03-11 | Novo Nordisk A/S | Pump assembly comprising actuator system |
EP2168616A1 (en) * | 2008-09-30 | 2010-03-31 | Animas Corporation | Medical device mechanical pump |
US20100100048A1 (en) * | 2003-10-27 | 2010-04-22 | Novo Nordisk A/S | Medical Skin Mountable Device |
US20100145305A1 (en) * | 2008-11-10 | 2010-06-10 | Ruth Alon | Low volume accurate injector |
US20100168683A1 (en) * | 2008-12-30 | 2010-07-01 | Oz Cabiri | Needle assembly for drug pump |
US20110008206A1 (en) * | 2007-10-31 | 2011-01-13 | Novo Nordisk A/S | Non-Porous Material as Sterilization Barrier |
US7872396B2 (en) | 2004-06-14 | 2011-01-18 | Massachusetts Institute Of Technology | Electrochemical actuator |
US20110060289A1 (en) * | 2003-05-08 | 2011-03-10 | Novo Nordisk A/S | Integrated package |
US20110066131A1 (en) * | 2009-09-15 | 2011-03-17 | Oz Cabiri | Cartridge insertion assembly for drug delivery system |
US7923895B2 (en) | 2004-06-14 | 2011-04-12 | Massachusetts Institute Of Technology | Electrochemical methods, devices, and structures |
US20110137255A1 (en) * | 2003-10-27 | 2011-06-09 | Novo Nordisk A/S | Medical Skin Mountable Device |
US7967795B1 (en) | 2010-01-19 | 2011-06-28 | Lamodel Ltd. | Cartridge interface assembly with driving plunger |
US20110172638A1 (en) * | 2010-01-08 | 2011-07-14 | Ratio, Inc. | Drug delivery device including multi-functional cover |
WO2011090955A1 (en) | 2010-01-19 | 2011-07-28 | Lamodel Ltd. | Needle assembly for drug pump |
WO2012040528A1 (en) * | 2010-09-24 | 2012-03-29 | Perqflo, Llc | Infusion pumps |
US20120109066A1 (en) * | 2010-11-03 | 2012-05-03 | Flugen, Inc. | Wearable drug delivery device having spring drive and sliding actuation mechanism |
US20120118428A1 (en) * | 2010-11-16 | 2012-05-17 | Palyon Medical (Bvi) Limited | Propellant pillow manufacturing technique |
EP2460548A1 (en) | 2010-12-06 | 2012-06-06 | Roche Diagnostics GmbH | Medical assembly comprising monitoring device |
US20120209209A1 (en) * | 2006-02-09 | 2012-08-16 | Deka Products Limited Partnership | Adhesive and Peripheral Systems and Methods for Medical Devices |
US8247946B2 (en) | 2004-06-14 | 2012-08-21 | Massachusetts Institute Of Technology | Electrochemical actuator |
US8337457B2 (en) | 2010-05-05 | 2012-12-25 | Springleaf Therapeutics, Inc. | Systems and methods for delivering a therapeutic agent |
WO2012178164A1 (en) * | 2011-06-23 | 2012-12-27 | Ratio, Inc. | Drug delivery device including a dynamic drug reservoir and ergonomic user interface |
US8368285B2 (en) | 2010-12-17 | 2013-02-05 | Massachusette Institute Of Technology | Electrochemical actuators |
WO2013148435A1 (en) | 2012-03-26 | 2013-10-03 | Medimop Medical Projects Ltd. | Fail safe point protector for needle safety flap |
USD702834S1 (en) | 2011-03-22 | 2014-04-15 | Medimop Medical Projects Ltd. | Cartridge for use in injection device |
US8905972B2 (en) | 2010-11-20 | 2014-12-09 | Perqflo, Llc | Infusion pumps |
US8915879B2 (en) | 2010-09-24 | 2014-12-23 | Perqflo, Llc | Infusion pumps |
US8945071B2 (en) | 2010-09-02 | 2015-02-03 | Becton, Dickinson And Company | Self-injection device having needle cover with activation preventer |
US8961469B2 (en) | 2009-12-16 | 2015-02-24 | Becton, Dickinson And Company | Self-injection device |
US9011164B2 (en) | 2013-04-30 | 2015-04-21 | Medimop Medical Projects Ltd. | Clip contact for easy installation of printed circuit board PCB |
US9211378B2 (en) | 2010-10-22 | 2015-12-15 | Cequr Sa | Methods and systems for dosing a medicament |
US9216249B2 (en) | 2010-09-24 | 2015-12-22 | Perqflo, Llc | Infusion pumps |
US20160121043A1 (en) * | 2013-05-30 | 2016-05-05 | Weibel Cds Ag | Device for dispensing a fluid to a patient |
US9345836B2 (en) | 2007-10-02 | 2016-05-24 | Medimop Medical Projects Ltd. | Disengagement resistant telescoping assembly and unidirectional method of assembly for such |
US9399094B2 (en) | 2006-06-06 | 2016-07-26 | Novo Nordisk A/S | Assembly comprising skin-mountable device and packaging therefore |
US9421323B2 (en) | 2013-01-03 | 2016-08-23 | Medimop Medical Projects Ltd. | Door and doorstop for portable one use drug delivery apparatus |
US9439743B2 (en) | 2013-02-26 | 2016-09-13 | Primetech Corporation | Fluid delivery device |
US9452261B2 (en) | 2010-05-10 | 2016-09-27 | Medimop Medical Projects Ltd. | Low volume accurate injector |
US9463280B2 (en) | 2012-03-26 | 2016-10-11 | Medimop Medical Projects Ltd. | Motion activated septum puncturing drug delivery device |
US9498573B2 (en) | 2010-09-24 | 2016-11-22 | Perqflo, Llc | Infusion pumps |
US9555187B2 (en) | 2009-12-16 | 2017-01-31 | Becton, Dickinson And Company | Self-injection device |
US9579461B2 (en) | 2009-12-16 | 2017-02-28 | Becton, Dickinson And Company | Self-injection device |
US9656019B2 (en) | 2007-10-02 | 2017-05-23 | Medimop Medical Projects Ltd. | Apparatuses for securing components of a drug delivery system during transport and methods of using same |
US9717850B2 (en) | 2009-12-16 | 2017-08-01 | Becton, Dickinson And Company | Self-injection device |
US9744297B2 (en) | 2015-04-10 | 2017-08-29 | Medimop Medical Projects Ltd. | Needle cannula position as an input to operational control of an injection device |
US9795534B2 (en) | 2015-03-04 | 2017-10-24 | Medimop Medical Projects Ltd. | Compliant coupling assembly for cartridge coupling of a drug delivery device |
US9833562B2 (en) | 2009-12-16 | 2017-12-05 | Becton, Dickinson And Company | Self-injection device |
US9889256B2 (en) | 2013-05-03 | 2018-02-13 | Medimop Medical Projects Ltd. | Sensing a status of an infuser based on sensing motor control and power input |
USD810278S1 (en) | 2009-09-15 | 2018-02-13 | Medimop Medical Projects Ltd. | Injector device |
USD811583S1 (en) | 2009-09-15 | 2018-02-27 | Medimop Medical Projects Ltd. | Injector device |
US9987432B2 (en) | 2015-09-22 | 2018-06-05 | West Pharma. Services IL, Ltd. | Rotation resistant friction adapter for plunger driver of drug delivery device |
US10071196B2 (en) | 2012-05-15 | 2018-09-11 | West Pharma. Services IL, Ltd. | Method for selectively powering a battery-operated drug-delivery device and device therefor |
CN108704191A (en) * | 2013-05-31 | 2018-10-26 | 瓦莱里塔斯公司 | Fluid delivery system with the pre-filled cylinder of insertable |
US10149943B2 (en) | 2015-05-29 | 2018-12-11 | West Pharma. Services IL, Ltd. | Linear rotation stabilizer for a telescoping syringe stopper driverdriving assembly |
US10159786B2 (en) | 2014-09-30 | 2018-12-25 | Perqflo, Llc | Hybrid ambulatory infusion pumps |
US10195340B2 (en) | 2009-12-16 | 2019-02-05 | Becton, Dickinson And Company | Self-injection device |
US10251813B2 (en) | 2015-03-04 | 2019-04-09 | West Pharma. Services IL, Ltd. | Flexibly mounted cartridge alignment collar for drug delivery device |
US10278897B2 (en) | 2015-11-25 | 2019-05-07 | West Pharma. Services IL, Ltd. | Dual vial adapter assemblage including drug vial adapter with self-sealing access valve |
US10285907B2 (en) | 2015-01-05 | 2019-05-14 | West Pharma. Services IL, Ltd. | Dual vial adapter assemblages with quick release drug vial adapter for ensuring correct usage |
US10293120B2 (en) | 2015-04-10 | 2019-05-21 | West Pharma. Services IL, Ltd. | Redundant injection device status indication |
US10299990B2 (en) | 2012-08-26 | 2019-05-28 | West Pharma. Services IL, Ltd. | Liquid drug transfer devices |
US10335545B2 (en) | 2012-01-31 | 2019-07-02 | West Pharma. Services IL, Ltd. | Time dependent drug delivery apparatus |
US10357429B2 (en) | 2015-07-16 | 2019-07-23 | West Pharma. Services IL, Ltd. | Liquid drug transfer devices for secure telescopic snap fit on injection vials |
US10420880B2 (en) | 2007-10-02 | 2019-09-24 | West Pharma. Services IL, Ltd. | Key for securing components of a drug delivery system during assembly and/or transport and methods of using same |
US10646404B2 (en) | 2016-05-24 | 2020-05-12 | West Pharma. Services IL, Ltd. | Dual vial adapter assemblages including identical twin vial adapters |
US10668213B2 (en) | 2012-03-26 | 2020-06-02 | West Pharma. Services IL, Ltd. | Motion activated mechanisms for a drug delivery device |
US10688295B2 (en) | 2013-08-07 | 2020-06-23 | West Pharma. Services IL, Ltd. | Liquid transfer devices for use with infusion liquid containers |
US10765604B2 (en) | 2016-05-24 | 2020-09-08 | West Pharma. Services IL, Ltd. | Drug vial adapter assemblages including vented drug vial adapter and vented liquid vial adapter |
US10772797B2 (en) | 2016-12-06 | 2020-09-15 | West Pharma. Services IL, Ltd. | Liquid drug transfer devices for use with intact discrete injection vial release tool |
US10806667B2 (en) | 2016-06-06 | 2020-10-20 | West Pharma. Services IL, Ltd. | Fluid transfer devices for filling drug pump cartridges with liquid drug contents |
US10806671B2 (en) | 2016-08-21 | 2020-10-20 | West Pharma. Services IL, Ltd. | Syringe assembly |
US10814062B2 (en) | 2017-08-31 | 2020-10-27 | Becton, Dickinson And Company | Reservoir with low volume sensor |
US10945921B2 (en) | 2017-03-29 | 2021-03-16 | West Pharma. Services IL, Ltd. | User actuated liquid drug transfer devices for use in ready-to-use (RTU) liquid drug transfer assemblages |
USD917693S1 (en) | 2018-07-06 | 2021-04-27 | West Pharma. Services IL, Ltd. | Medication mixing apparatus |
USD923782S1 (en) | 2019-01-17 | 2021-06-29 | West Pharma. Services IL, Ltd. | Medication mixing apparatus |
USD923812S1 (en) | 2019-01-16 | 2021-06-29 | West Pharma. Services IL, Ltd. | Medication mixing apparatus |
US11103652B2 (en) | 2016-06-02 | 2021-08-31 | West Pharma. Services IL, Ltd. | Three position needle retraction |
US11167086B2 (en) | 2008-09-15 | 2021-11-09 | West Pharma. Services IL, Ltd. | Stabilized pen injector |
US11185629B2 (en) | 2016-06-08 | 2021-11-30 | Shl Medical Ag | Dosing apparatus and injection device |
US11253652B2 (en) | 2016-11-28 | 2022-02-22 | Shl Medical Ag | Device for dispensing a substance |
US11311674B2 (en) | 2016-01-21 | 2022-04-26 | West Pharma. Services IL, Ltd. | Medicament delivery device comprising a visual indicator |
US11318254B2 (en) | 2015-10-09 | 2022-05-03 | West Pharma. Services IL, Ltd. | Injector needle cap remover |
US11338090B2 (en) | 2016-08-01 | 2022-05-24 | West Pharma. Services IL, Ltd. | Anti-rotation cartridge pin |
USD954253S1 (en) | 2019-04-30 | 2022-06-07 | West Pharma. Services IL, Ltd. | Liquid transfer device |
US11364337B2 (en) | 2016-01-21 | 2022-06-21 | West Pharma. Services IL, Ltd. | Force containment in an automatic injector |
USD956958S1 (en) | 2020-07-13 | 2022-07-05 | West Pharma. Services IL, Ltd. | Liquid transfer device |
US11389597B2 (en) | 2016-03-16 | 2022-07-19 | West Pharma. Services IL, Ltd. | Staged telescopic screw assembly having different visual indicators |
US11547802B2 (en) | 2015-10-09 | 2023-01-10 | West Pharma. Services IL, Ltd. | Angled syringe patch injector |
US11642285B2 (en) | 2017-09-29 | 2023-05-09 | West Pharma. Services IL, Ltd. | Dual vial adapter assemblages including twin vented female vial adapters |
US11672909B2 (en) | 2016-02-12 | 2023-06-13 | Medtronic Minimed, Inc. | Ambulatory infusion pumps and assemblies for use with same |
US11672904B2 (en) | 2016-01-21 | 2023-06-13 | West Pharma. Services IL, Ltd. | Needle insertion and retraction mechanism |
US11684712B2 (en) | 2015-02-18 | 2023-06-27 | Medtronic Minimed, Inc. | Ambulatory infusion pumps and reservoir assemblies for use with same |
US11730892B2 (en) | 2016-08-01 | 2023-08-22 | West Pharma. Services IL, Ltd. | Partial door closure prevention spring |
US11819666B2 (en) | 2017-05-30 | 2023-11-21 | West Pharma. Services IL, Ltd. | Modular drive train for wearable injector |
US11857767B2 (en) | 2017-12-22 | 2024-01-02 | West Pharma. Services IL, Ltd. | Injector usable with different dimension cartridges |
US11918542B2 (en) | 2019-01-31 | 2024-03-05 | West Pharma. Services IL, Ltd. | Liquid transfer device |
US11931552B2 (en) | 2015-06-04 | 2024-03-19 | West Pharma Services Il, Ltd. | Cartridge insertion for drug delivery device |
Families Citing this family (95)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB0109001D0 (en) * | 2001-04-10 | 2001-05-30 | Glaxo Group Ltd | Dispenser |
US6981977B2 (en) * | 2001-10-26 | 2006-01-03 | Atrium Medical Corporation | Body fluid cartridge exchange platform device |
US6979316B1 (en) * | 2002-05-23 | 2005-12-27 | Seedlings Life Science Ventures Llc | Apparatus and method for rapid auto-injection of medication |
JP4565193B2 (en) | 2003-04-23 | 2010-10-20 | バレリタス, インコーポレイテッド | Hydraulically operated pump for long duration pharmaceutical administration |
EP1641616B1 (en) | 2003-06-27 | 2011-04-13 | Novo Nordisk A/S | High moisture barrier container for medical liquid compositions |
CN1898087A (en) | 2003-12-22 | 2007-01-17 | 诺沃挪第克公司 | Transparent, flexible, impermeable plastic container for storage of pharmaceutical liquids |
PL1732627T3 (en) | 2004-03-31 | 2010-09-30 | Lilly Co Eli | Injection apparatus having a needle cassette for delivering a pharmaceutical liquid |
WO2006014425A1 (en) | 2004-07-02 | 2006-02-09 | Biovalve Technologies, Inc. | Methods and devices for delivering glp-1 and uses thereof |
US20060058737A1 (en) * | 2004-09-16 | 2006-03-16 | Herweck Steve A | Catheter treatment stylet |
US11590286B2 (en) | 2004-11-22 | 2023-02-28 | Kaleo, Inc. | Devices, systems and methods for medicament delivery |
US10737028B2 (en) | 2004-11-22 | 2020-08-11 | Kaleo, Inc. | Devices, systems and methods for medicament delivery |
GB2453069B (en) * | 2004-11-22 | 2009-12-09 | Intelliject Llc | Devices,systems and methods for medicament delivery |
US7648482B2 (en) * | 2004-11-22 | 2010-01-19 | Intelliject, Inc. | Devices, systems, and methods for medicament delivery |
US7947017B2 (en) * | 2004-11-22 | 2011-05-24 | Intelliject, Inc. | Devices, systems and methods for medicament delivery |
US7648483B2 (en) | 2004-11-22 | 2010-01-19 | Intelliject, Inc. | Devices, systems and methods for medicament delivery |
ES2396745T3 (en) | 2005-02-01 | 2013-02-25 | Intelliject, Inc. | Devices for medication administration |
US8231573B2 (en) * | 2005-02-01 | 2012-07-31 | Intelliject, Inc. | Medicament delivery device having an electronic circuit system |
US9022980B2 (en) | 2005-02-01 | 2015-05-05 | Kaleo, Inc. | Medical injector simulation device |
US7731686B2 (en) | 2005-02-01 | 2010-06-08 | Intelliject, Inc. | Devices, systems and methods for medicament delivery |
US8206360B2 (en) | 2005-02-01 | 2012-06-26 | Intelliject, Inc. | Devices, systems and methods for medicament delivery |
US8361026B2 (en) | 2005-02-01 | 2013-01-29 | Intelliject, Inc. | Apparatus and methods for self-administration of vaccines and other medicaments |
AU2006214800B2 (en) * | 2005-02-16 | 2012-06-07 | Cy O'connor Erade Village Foundation | Methods of genetic analysis involving the amplification of complementary duplicons |
EP2005309B1 (en) | 2006-03-30 | 2016-02-17 | Valeritas, Inc. | Multi-cartridge fluid delivery device |
EP2037999B1 (en) | 2006-07-07 | 2016-12-28 | Proteus Digital Health, Inc. | Smart parenteral administration system |
US8187227B2 (en) | 2006-11-01 | 2012-05-29 | Medela Holding Ag | Self returning contamination barrier |
EP2104525A4 (en) * | 2006-12-29 | 2010-12-29 | Amir Genosar | Hypodermic drug delivery reservoir and apparatus |
EP2125075A2 (en) | 2007-01-22 | 2009-12-02 | Intelliject, Inc. | Medical injector with compliance tracking and monitoring |
WO2008129549A1 (en) * | 2007-04-23 | 2008-10-30 | Steadymed Ltd. | Controllable drug delivery device driven by expandable battery |
EP2211974A4 (en) | 2007-10-25 | 2013-02-27 | Proteus Digital Health Inc | Fluid transfer port information system |
EP2240232A4 (en) * | 2007-12-28 | 2011-03-16 | Aktivpak Inc | Dispenser and therapeutic package suitable for administering a therapeutic substance to a subject |
US8986253B2 (en) | 2008-01-25 | 2015-03-24 | Tandem Diabetes Care, Inc. | Two chamber pumps and related methods |
EP2244746B2 (en) | 2008-02-27 | 2019-01-02 | Aplion Medical Corporation | Wound dressing with uniform distribution |
US20090247982A1 (en) * | 2008-03-27 | 2009-10-01 | Lifescan Inc. | Medical Device Mechanical Pump |
USD994111S1 (en) | 2008-05-12 | 2023-08-01 | Kaleo, Inc. | Medicament delivery device cover |
US8021344B2 (en) | 2008-07-28 | 2011-09-20 | Intelliject, Inc. | Medicament delivery device configured to produce an audible output |
EP3372272A1 (en) * | 2008-05-14 | 2018-09-12 | Becton, Dickinson and Company | Separatable infusion set with cleanable interface and straight line attachment |
EP3821923A1 (en) * | 2008-06-26 | 2021-05-19 | Calibra Medical LLC | Disposable infusion device with cannula port cover |
US8361030B2 (en) | 2008-06-26 | 2013-01-29 | Calibra Medical, Inc. | Disposable infusion device with occlusion detector |
CN102149416B (en) * | 2008-09-10 | 2014-02-12 | 弗·哈夫曼-拉罗切有限公司 | Delivery device for use with therapeutic drug |
US8408421B2 (en) | 2008-09-16 | 2013-04-02 | Tandem Diabetes Care, Inc. | Flow regulating stopcocks and related methods |
US8650937B2 (en) | 2008-09-19 | 2014-02-18 | Tandem Diabetes Care, Inc. | Solute concentration measurement device and related methods |
US8696629B2 (en) * | 2008-10-07 | 2014-04-15 | Roche Diagnostics Operations Inc. | Skin securable drug delivery device with a shock absorbing protective shield |
EP2724739B1 (en) | 2009-07-30 | 2015-07-01 | Tandem Diabetes Care, Inc. | Portable infusion pump system |
WO2011022484A1 (en) * | 2009-08-18 | 2011-02-24 | Replenish Pumps. Llc | Electrolytic drug-delivery pump with adaptive control |
EP2512580A4 (en) * | 2009-12-16 | 2013-06-12 | Becton Dickinson Co | Self-injection device |
SG10201503428RA (en) | 2010-02-01 | 2015-06-29 | Proteus Digital Health Inc | Data Gathering System |
BR112012019212A2 (en) | 2010-02-01 | 2017-06-13 | Proteus Digital Health Inc | data collection system |
HRP20150963T4 (en) | 2010-06-07 | 2023-12-08 | Amgen Inc. | Drug delivery device |
EP2438938A1 (en) * | 2010-10-11 | 2012-04-11 | PharmaSens AG | Syringe type pump |
US8627816B2 (en) | 2011-02-28 | 2014-01-14 | Intelliject, Inc. | Medicament delivery device for administration of opioid antagonists including formulations for naloxone |
US9173999B2 (en) | 2011-01-26 | 2015-11-03 | Kaleo, Inc. | Devices and methods for delivering medicaments from a multi-chamber container |
US8939943B2 (en) | 2011-01-26 | 2015-01-27 | Kaleo, Inc. | Medicament delivery device for administration of opioid antagonists including formulations for naloxone |
US8696630B2 (en) * | 2011-01-28 | 2014-04-15 | Calibra Medical, Inc. | Detachable drug delivery device |
US20120253314A1 (en) * | 2011-03-30 | 2012-10-04 | Ziv Harish | Palm-controlled injectors |
WO2013134519A2 (en) * | 2012-03-07 | 2013-09-12 | Deka Products Limited Partnership | Apparatus, system and method for fluid delivery |
US9180242B2 (en) | 2012-05-17 | 2015-11-10 | Tandem Diabetes Care, Inc. | Methods and devices for multiple fluid transfer |
US9522235B2 (en) | 2012-05-22 | 2016-12-20 | Kaleo, Inc. | Devices and methods for delivering medicaments from a multi-chamber container |
US20140114248A1 (en) * | 2012-10-24 | 2014-04-24 | Nuance Designs, LLC | Power pack for an autoinjector |
GB2526948A (en) | 2012-12-27 | 2015-12-09 | Kaleo Inc | Systems for locating and interacting with medicament delivery devices |
US9173998B2 (en) | 2013-03-14 | 2015-11-03 | Tandem Diabetes Care, Inc. | System and method for detecting occlusions in an infusion pump |
EP3041548B1 (en) * | 2013-09-05 | 2018-12-19 | Sanofi-Aventis Deutschland GmbH | Drive mechanism for a needle insertion arrangement |
US9517307B2 (en) | 2014-07-18 | 2016-12-13 | Kaleo, Inc. | Devices and methods for delivering opioid antagonists including formulations for naloxone |
EP3274021B1 (en) | 2015-03-24 | 2024-02-14 | Kaleo, Inc. | Devices and methods for delivering a lyophilized medicament |
JP6830067B2 (en) | 2015-06-30 | 2021-02-17 | カレオ,インコーポレイテッド | Automatic syringe that administers medication in a prefilled syringe |
BR112018070965B1 (en) | 2016-04-15 | 2023-04-11 | E-Wha Meditech Inc | ADJUSTABLE INTERNAL PRESSURE LIQUID DRUG INJECTION DEVICE |
US10737023B2 (en) * | 2016-08-24 | 2020-08-11 | Avent, Inc. | Flow indicator for an infusion pump |
USD805189S1 (en) | 2016-09-26 | 2017-12-12 | West Pharmaceutical Services, Inc. | Injector device |
USD804019S1 (en) | 2016-09-26 | 2017-11-28 | West Pharmaceutical Services, Inc. | Injector device |
USD805188S1 (en) | 2016-09-26 | 2017-12-12 | West Pharmaceutical Services, Inc. | Injector device |
USD805190S1 (en) | 2016-09-26 | 2017-12-12 | West Pharmaceutical Services, Inc. | Injector device |
USD805187S1 (en) | 2016-09-26 | 2017-12-12 | West Pharmaceutical Services, Inc. | Injector device |
USD804650S1 (en) | 2016-09-26 | 2017-12-05 | West Pharmaceutical Services, Inc. | Injector device |
USD805186S1 (en) | 2016-09-26 | 2017-12-12 | West Pharmaceutical Services, Inc. | Injector device |
USD878555S1 (en) | 2016-10-26 | 2020-03-17 | West Pharmaceutical Services, Inc. | Injector device |
USD808011S1 (en) | 2016-10-26 | 2018-01-16 | West Pharmaceutical Services, Inc. | Injector device |
USD806863S1 (en) | 2016-10-26 | 2018-01-02 | West Pharmaceutical Services, Inc. | Injector device |
USD806234S1 (en) | 2016-10-26 | 2017-12-26 | West Pharmaceutical Services, Inc. | Injector device |
USD805633S1 (en) | 2016-10-26 | 2017-12-19 | West Pharmaceutical Services, Inc. | Injector device |
USD878556S1 (en) | 2016-10-26 | 2020-03-17 | West Pharmaceutical Services, Inc. | Injector device |
USD882765S1 (en) | 2016-10-26 | 2020-04-28 | West Pharmaceutical Services, Inc. | Injector device |
USD806235S1 (en) | 2016-10-26 | 2017-12-26 | West Pharmaceutical Services, Inc. | Injector device |
USD807499S1 (en) | 2016-10-26 | 2018-01-09 | West Pharmaceutical Services, Inc. | Injector device |
USD878557S1 (en) | 2016-10-26 | 2020-03-17 | West Pharmaceutical Services, Inc. | Injector device |
USD805632S1 (en) | 2016-10-26 | 2017-12-19 | West Pharmaceutical Services, Inc. | Injector device |
WO2018096534A1 (en) | 2016-11-22 | 2018-05-31 | Sorrel Medical Ltd. | Apparatus for delivering a therapeutic substance |
CA3046228A1 (en) | 2016-12-23 | 2018-06-28 | Kaleo, Inc. | Medicament delivery device and methods for delivering drugs to infants and children |
EP3570906A4 (en) | 2017-01-17 | 2020-10-21 | Kaleo, Inc. | Medicament delivery devices with wireless connectivity and event detection |
GB201712184D0 (en) * | 2017-07-28 | 2017-09-13 | Owen Mumford Ltd | Medicament delivery device |
WO2019071129A1 (en) * | 2017-10-05 | 2019-04-11 | Pirouette Medical LLC | Protective case for an auto-injector |
US11583633B2 (en) | 2018-04-03 | 2023-02-21 | Amgen Inc. | Systems and methods for delayed drug delivery |
US11929160B2 (en) | 2018-07-16 | 2024-03-12 | Kaleo, Inc. | Medicament delivery devices with wireless connectivity and compliance detection |
US11357909B2 (en) | 2018-10-05 | 2022-06-14 | Eitan Medical Ltd. | Triggering sequence |
EP3863699A1 (en) * | 2018-10-12 | 2021-08-18 | Debiotech S.A. | Cradle unit for delivery device |
EP4009936A4 (en) | 2019-08-09 | 2023-08-09 | Kaleo, Inc. | Devices and methods for delivery of substances within a prefilled syringe |
CN116829211A (en) * | 2020-12-17 | 2023-09-29 | 赛诺菲 | Automatic injector with gas |
Family Cites Families (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4708716A (en) * | 1983-08-18 | 1987-11-24 | Drug Delivery Systems Inc. | Transdermal drug applicator |
US4684367A (en) | 1985-04-12 | 1987-08-04 | Meditec Research Associates | Ambulatory intravenous delivery system |
US5527288A (en) | 1990-12-13 | 1996-06-18 | Elan Medical Technologies Limited | Intradermal drug delivery device and method for intradermal delivery of drugs |
JPH05122024A (en) * | 1991-10-24 | 1993-05-18 | Hitachi Ltd | Dynamic latch circuit |
US5398850A (en) | 1993-08-06 | 1995-03-21 | River Medical, Inc. | Gas delivery apparatus for infusion |
IE77523B1 (en) | 1995-09-11 | 1997-12-17 | Elan Med Tech | Medicament delivery device |
AU716445B2 (en) | 1995-09-11 | 2000-02-24 | Elan Corporation, Plc | Medicament delivery device |
US5779676A (en) | 1995-10-11 | 1998-07-14 | Science Incorporated | Fluid delivery device with bolus injection site |
AU7785998A (en) | 1998-06-04 | 1999-12-20 | Elan Corporation, Plc | Gas driven drug delivery device |
JP2000088646A (en) * | 1998-09-16 | 2000-03-31 | Hamamatsu Photonics Kk | Integral photodetector |
-
2000
- 2000-05-23 US US09/577,033 patent/US6530900B1/en not_active Expired - Lifetime
-
2001
- 2001-05-23 JP JP2001585847A patent/JP5102927B2/en not_active Expired - Lifetime
- 2001-05-23 CA CA002411202A patent/CA2411202A1/en not_active Abandoned
- 2001-05-23 EP EP01939359A patent/EP1284758A2/en not_active Withdrawn
- 2001-05-23 AU AU2001264887A patent/AU2001264887A1/en not_active Abandoned
- 2001-05-23 WO PCT/US2001/016763 patent/WO2001089607A2/en not_active Application Discontinuation
-
2003
- 2003-01-03 US US10/336,459 patent/US20030135159A1/en not_active Abandoned
-
2012
- 2012-04-20 JP JP2012097091A patent/JP2012152597A/en active Pending
Cited By (242)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20080287871A1 (en) * | 2002-04-02 | 2008-11-20 | Wilkinson Bradley M | Method and Device for Intradermally Delivering a Substance |
US7896837B2 (en) * | 2002-04-02 | 2011-03-01 | Becton, Dickinson And Company | Method and device for intradermally delivering a substance |
US20040138612A1 (en) * | 2002-07-22 | 2004-07-15 | Shermer Charles D. | Patch-like infusion device |
US20070203454A1 (en) * | 2002-07-22 | 2007-08-30 | Shermer Charles D | Patch-Like Infusion Device |
US7678079B2 (en) | 2002-07-22 | 2010-03-16 | Becton, Dickinson And Company | Patch-like infusion device |
US7250037B2 (en) | 2002-07-22 | 2007-07-31 | Becton, Dickinson And Company | Patch-like infusion device |
US20040116847A1 (en) * | 2002-09-12 | 2004-06-17 | Children's Hospital Medical Center | Method and device for painless injection of medication |
US20060095014A1 (en) * | 2003-05-08 | 2006-05-04 | Novo Nordisk A/S | External inserter for transcutaneous device |
US20060142698A1 (en) * | 2003-05-08 | 2006-06-29 | Novo Nordisk A/S | Internal needle inserter |
US7981085B2 (en) | 2003-05-08 | 2011-07-19 | Novo Nordisk A/S | Internal needle inserter |
US20110060289A1 (en) * | 2003-05-08 | 2011-03-10 | Novo Nordisk A/S | Integrated package |
US8740851B2 (en) | 2003-05-08 | 2014-06-03 | Novo Nordisk A/S | Integrated package |
US8029469B2 (en) | 2003-05-08 | 2011-10-04 | Novo Nordisk A/S | External inserter for transcutaneous device |
US10589023B2 (en) | 2003-07-22 | 2020-03-17 | Becton, Dickinson And Company | Patch-like infusion device |
US9999724B2 (en) | 2003-07-22 | 2018-06-19 | Becton, Dickinson And Company | Patch-like infusion device |
US8512287B2 (en) | 2003-07-22 | 2013-08-20 | Becton, Dickinson And Company | Patch-like infusion device |
US9364606B2 (en) | 2003-07-22 | 2016-06-14 | Becton, Dickinson And Company | Patch-like infusion device |
US9597450B2 (en) | 2003-07-22 | 2017-03-21 | Becton, Dickinson And Company | Patch-like infusion device |
US20050065472A1 (en) * | 2003-07-22 | 2005-03-24 | Cindrich Chris N. | Patch-like infusion device |
US7955297B2 (en) | 2003-08-01 | 2011-06-07 | Novo Nordisk A/S | Retraction means for transcutaneous device |
US20070049865A1 (en) * | 2003-08-01 | 2007-03-01 | Novo Nordisk A/S | Retraction means for transcutaneous device |
US20080215015A1 (en) * | 2003-08-12 | 2008-09-04 | Chris Cindrich | Patch-Like Infusion Device |
US20050065466A1 (en) * | 2003-08-12 | 2005-03-24 | Becton, Dickinson And Company | Patch-like infusion device |
WO2005018703A2 (en) | 2003-08-12 | 2005-03-03 | Becton, Dickinson And Company | Patch-like infusion device |
US8444604B2 (en) | 2003-08-12 | 2013-05-21 | Becton, Dickinson And Company | Patch-like infusion device |
WO2005018703A3 (en) * | 2003-08-12 | 2005-12-29 | Becton Dickinson Co | Patch-like infusion device |
US7857131B2 (en) | 2003-08-12 | 2010-12-28 | Becton, Dickinson And Company | Patch-like infusion device |
US8062253B2 (en) | 2003-10-21 | 2011-11-22 | Novo Nordisk A/S | Medical skin mountable device |
US20070021733A1 (en) * | 2003-10-21 | 2007-01-25 | Novo Nordisk A/S | Internal fluid connector |
US9592336B2 (en) | 2003-10-27 | 2017-03-14 | Novo Nordisk A/S | Medical skin mountable device |
US20100100048A1 (en) * | 2003-10-27 | 2010-04-22 | Novo Nordisk A/S | Medical Skin Mountable Device |
US20110137255A1 (en) * | 2003-10-27 | 2011-06-09 | Novo Nordisk A/S | Medical Skin Mountable Device |
EP1708767A4 (en) * | 2003-12-16 | 2008-10-22 | Ultimate Medical Pty Ltd | Fluid delivery device |
EP1708767A1 (en) * | 2003-12-16 | 2006-10-11 | Ultimate Medical Pty. Ltd. | Fluid delivery device |
US7896841B2 (en) | 2004-02-17 | 2011-03-01 | Children's Hospital Medical Center | Injection device for administering a vaccine |
US20070293826A1 (en) * | 2004-02-17 | 2007-12-20 | Wall Eric J | Injection Device for Administering a Vaccine |
US20070276320A1 (en) * | 2004-02-17 | 2007-11-29 | Wall Eric J | Injection Device for Administering a Vaccine |
US7670314B2 (en) | 2004-02-17 | 2010-03-02 | Children's Hospital Medical Center | Injection device for administering a vaccine |
US7922462B2 (en) | 2004-03-30 | 2011-04-12 | Novo Nordisk A/S | Actuator system comprising lever mechanism |
US20110166524A1 (en) * | 2004-03-30 | 2011-07-07 | Novo Nordisk A/S | Actuator System Comprising Lever Mechanism |
US20070104596A1 (en) * | 2004-03-30 | 2007-05-10 | Novo Nordisk A/S | Actuator system comprising lever mechanism |
US7872396B2 (en) | 2004-06-14 | 2011-01-18 | Massachusetts Institute Of Technology | Electrochemical actuator |
US8604664B2 (en) | 2004-06-14 | 2013-12-10 | Massachusetts Institute Of Technology | Electrochemical actuator |
US8378552B2 (en) | 2004-06-14 | 2013-02-19 | Massachusetts Institute Of Technology | Electrochemical actuator |
US20110098643A1 (en) * | 2004-06-14 | 2011-04-28 | Massachusetts Institute Of Technology | Electrochemical actuator |
US7994686B2 (en) | 2004-06-14 | 2011-08-09 | Massachusetts Institute Of Technology | Electrochemical methods, devices, and structures |
US20080157713A1 (en) * | 2004-06-14 | 2008-07-03 | Massachusetts Institute Of Technology | Electrochemical methods, devices, and structures |
US8310130B2 (en) | 2004-06-14 | 2012-11-13 | Massachusetts Institute Of Technology | Electrochemical methods, devices, and structures |
US8247946B2 (en) | 2004-06-14 | 2012-08-21 | Massachusetts Institute Of Technology | Electrochemical actuator |
US20090014320A1 (en) * | 2004-06-14 | 2009-01-15 | Massachusetts Institute Of Technology | Electrochemical actuator |
US7999435B2 (en) | 2004-06-14 | 2011-08-16 | Massachusetts Institute Of Technology | Electrochemical actuator |
US7923895B2 (en) | 2004-06-14 | 2011-04-12 | Massachusetts Institute Of Technology | Electrochemical methods, devices, and structures |
US8093781B2 (en) | 2004-06-14 | 2012-01-10 | Massachusetts Institute Of Technology | Electrochemical actuator |
US20080215006A1 (en) * | 2004-09-22 | 2008-09-04 | Novo Nordisk A/S | Medical Device with Transcutaneous Cannula Device |
US20090012472A1 (en) * | 2004-09-22 | 2009-01-08 | Novo Nordisk A/S | Medical Device with Cannula Inserter |
US20090048563A1 (en) * | 2004-12-06 | 2009-02-19 | Novo Nordisk A/S | Ventilated Skin Mountable Device |
WO2006061354A1 (en) * | 2004-12-06 | 2006-06-15 | Novo Nordisk A/S | Ventilated skin mountable device |
US8167841B2 (en) | 2005-01-24 | 2012-05-01 | Novo Nordisk A/S | Transcutaneous device assembly |
US20090076451A1 (en) * | 2005-01-24 | 2009-03-19 | Nova Nordisk A/S | Medical Device with Protected Transcutaneous Device |
US20090131860A1 (en) * | 2005-04-13 | 2009-05-21 | Novo Nordisk A/S | Medical Skin Mountable Device And System |
US8298172B2 (en) * | 2005-04-13 | 2012-10-30 | Novo Nordisk A/S | Medical skin mountable device and system |
US8747363B2 (en) | 2005-04-13 | 2014-06-10 | Novo Nordisk A/S | Medical skin mountable device and system |
US20080167641A1 (en) * | 2005-05-13 | 2008-07-10 | Novo Nordisk A/S | Medical Device Adapted To Detect Disengagement Of A Transcutaneous Device |
US20090118682A1 (en) * | 2005-09-13 | 2009-05-07 | Novo Nordisk A/S | Reservoir Device With Inspection Aid For Detection Of Drug Condition |
US20080287870A1 (en) * | 2005-10-17 | 2008-11-20 | Nov Nordisk A/S | Vented Drug Reservoir Unit |
US8486018B2 (en) * | 2006-02-09 | 2013-07-16 | Deka Products Limited Partnership | Adhesive and peripheral systems and methods for medical devices |
US20170056585A1 (en) * | 2006-02-09 | 2017-03-02 | Deka Products Limited Partnership | Adhesive and Peripheral Systems and Methods for Medical Devices |
US9861769B2 (en) * | 2006-02-09 | 2018-01-09 | Deka Products Limited Partnership | Adhesive and peripheral systems and methods for medical devices |
US20120209209A1 (en) * | 2006-02-09 | 2012-08-16 | Deka Products Limited Partnership | Adhesive and Peripheral Systems and Methods for Medical Devices |
US20090069868A1 (en) * | 2006-03-11 | 2009-03-12 | Henrik Bengtsson | Secure Pairing of Electronic Devices using Dual Means of Communication |
US9173992B2 (en) | 2006-03-13 | 2015-11-03 | Novo Nordisk A/S | Secure pairing of electronic devices using dual means of communication |
US20090062778A1 (en) * | 2006-03-13 | 2009-03-05 | Novo Nordisk A/S | Medical System Comprising Dual-Purpose Communication Means |
US20090163874A1 (en) * | 2006-04-26 | 2009-06-25 | Novo Nordisk A/S | Skin-Mountable Device in Packaging Comprising Coated Seal Member |
US9399094B2 (en) | 2006-06-06 | 2016-07-26 | Novo Nordisk A/S | Assembly comprising skin-mountable device and packaging therefore |
US8409151B2 (en) | 2006-11-22 | 2013-04-02 | Calibra Medical, Inc. | Disposable infusion device filling apparatus and method |
US8894612B2 (en) | 2006-11-22 | 2014-11-25 | Calibra Medical, Inc. | Disposable infusion device filling apparatus and method |
US20080119790A1 (en) * | 2006-11-22 | 2008-05-22 | Seattle Medical Technologies | Disposable infusion device filling apparatus and method |
US20110130742A1 (en) * | 2006-11-22 | 2011-06-02 | Calibra Medical, Inc. | Disposable infusion device filling apparatus and method |
US7938801B2 (en) * | 2006-11-22 | 2011-05-10 | Calibra Medical, Inc. | Disposable infusion device filling apparatus and method |
US20100063448A1 (en) * | 2007-03-06 | 2010-03-11 | Novo Nordisk A/S | Pump assembly comprising actuator system |
US20090028824A1 (en) * | 2007-07-26 | 2009-01-29 | Entra Pharmaceuticals, Inc. | Systems and methods for delivering drugs |
US7828771B2 (en) * | 2007-07-26 | 2010-11-09 | Entra Pharmaceuticals, Inc. | Systems and methods for delivering drugs |
US20110098676A1 (en) * | 2007-07-26 | 2011-04-28 | Yet-Ming Chiang | Systems and methods for delivering drugs |
US9656019B2 (en) | 2007-10-02 | 2017-05-23 | Medimop Medical Projects Ltd. | Apparatuses for securing components of a drug delivery system during transport and methods of using same |
US9782545B2 (en) | 2007-10-02 | 2017-10-10 | Medimop Medical Projects Ltd. | External drug pump |
US9345836B2 (en) | 2007-10-02 | 2016-05-24 | Medimop Medical Projects Ltd. | Disengagement resistant telescoping assembly and unidirectional method of assembly for such |
US20090093792A1 (en) * | 2007-10-02 | 2009-04-09 | Yossi Gross | External drug pump |
US11590291B2 (en) | 2007-10-02 | 2023-02-28 | West Pharma. Services IL, Ltd. | External drug pump |
US10413679B2 (en) | 2007-10-02 | 2019-09-17 | West Pharma. Services IL, Ltd. | External drug pump |
US9173997B2 (en) | 2007-10-02 | 2015-11-03 | Medimop Medical Projects Ltd. | External drug pump |
US10384017B2 (en) | 2007-10-02 | 2019-08-20 | West Pharma. Services IL, Ltd. | Anti-rotation feature for infusion pump cartridge |
US9861759B2 (en) | 2007-10-02 | 2018-01-09 | Medimop Medical Projects Ltd. | External drug pump |
US11504481B2 (en) | 2007-10-02 | 2022-11-22 | West Pharma. Services IL, Ltd. | Anti-rotation feature for infusion pump cartridge |
US10420880B2 (en) | 2007-10-02 | 2019-09-24 | West Pharma. Services IL, Ltd. | Key for securing components of a drug delivery system during assembly and/or transport and methods of using same |
US20110008206A1 (en) * | 2007-10-31 | 2011-01-13 | Novo Nordisk A/S | Non-Porous Material as Sterilization Barrier |
US8557179B2 (en) | 2007-10-31 | 2013-10-15 | Novo Nordisk A/S | Non-porous material as sterilization barrier |
US11167086B2 (en) | 2008-09-15 | 2021-11-09 | West Pharma. Services IL, Ltd. | Stabilized pen injector |
EP2168616A1 (en) * | 2008-09-30 | 2010-03-31 | Animas Corporation | Medical device mechanical pump |
US20100145305A1 (en) * | 2008-11-10 | 2010-06-10 | Ruth Alon | Low volume accurate injector |
US8152779B2 (en) | 2008-12-30 | 2012-04-10 | Medimop Medical Projects Ltd. | Needle assembly for drug pump |
US20100168683A1 (en) * | 2008-12-30 | 2010-07-01 | Oz Cabiri | Needle assembly for drug pump |
USD811584S1 (en) | 2009-09-15 | 2018-02-27 | Medimop Medical Projects Ltd. | Injector device |
USD817481S1 (en) | 2009-09-15 | 2018-05-08 | West Pharma. Services IL, Ltd. | Injector device |
USD811583S1 (en) | 2009-09-15 | 2018-02-27 | Medimop Medical Projects Ltd. | Injector device |
USD810279S1 (en) | 2009-09-15 | 2018-02-13 | Medimop Medical Projects Ltd. | Injector device |
US8157769B2 (en) | 2009-09-15 | 2012-04-17 | Medimop Medical Projects Ltd. | Cartridge insertion assembly for drug delivery system |
USD810278S1 (en) | 2009-09-15 | 2018-02-13 | Medimop Medical Projects Ltd. | Injector device |
US8465455B2 (en) | 2009-09-15 | 2013-06-18 | Medimop Medical Projects Ltd. | Cartridge insertion assembly |
US9572926B2 (en) | 2009-09-15 | 2017-02-21 | Medimop Medical Projects Ltd. | Cartridge insertion assembly |
US20110066131A1 (en) * | 2009-09-15 | 2011-03-17 | Oz Cabiri | Cartridge insertion assembly for drug delivery system |
USD838840S1 (en) | 2009-09-15 | 2019-01-22 | West Pharma. Services IL, Ltd. | Injector device |
US9717850B2 (en) | 2009-12-16 | 2017-08-01 | Becton, Dickinson And Company | Self-injection device |
US10080846B2 (en) | 2009-12-16 | 2018-09-25 | Becton, Dickinson And Company | Self-injection device |
US8961469B2 (en) | 2009-12-16 | 2015-02-24 | Becton, Dickinson And Company | Self-injection device |
US10195340B2 (en) | 2009-12-16 | 2019-02-05 | Becton, Dickinson And Company | Self-injection device |
US10357610B2 (en) | 2009-12-16 | 2019-07-23 | Becton, Dickinson And Company | Self-injection device |
US10420881B2 (en) | 2009-12-16 | 2019-09-24 | Becton, Dickinson And Company | Self-injection device |
US9579461B2 (en) | 2009-12-16 | 2017-02-28 | Becton, Dickinson And Company | Self-injection device |
US9833562B2 (en) | 2009-12-16 | 2017-12-05 | Becton, Dickinson And Company | Self-injection device |
US9555187B2 (en) | 2009-12-16 | 2017-01-31 | Becton, Dickinson And Company | Self-injection device |
US10967123B2 (en) | 2009-12-16 | 2021-04-06 | Becton, Dickinson And Company | Self-injection device |
US11007316B2 (en) | 2009-12-16 | 2021-05-18 | Becton, Dickinson And Company | Self-injection device |
US9919097B2 (en) | 2009-12-16 | 2018-03-20 | Becton, Dickinson And Company | Self-injection device |
US20110172638A1 (en) * | 2010-01-08 | 2011-07-14 | Ratio, Inc. | Drug delivery device including multi-functional cover |
US9259532B2 (en) | 2010-01-19 | 2016-02-16 | Medimop Medical Projects Ltd. | Cartridge interface assembly |
WO2011090955A1 (en) | 2010-01-19 | 2011-07-28 | Lamodel Ltd. | Needle assembly for drug pump |
CN102883759A (en) * | 2010-01-19 | 2013-01-16 | 麦迪莫普医疗工程有限公司 | Needle assembly for drug pump |
EP2732836A1 (en) * | 2010-01-19 | 2014-05-21 | Medimop Medical Projects Ltd. | Apparatus for administering a substance to a subject |
US7967795B1 (en) | 2010-01-19 | 2011-06-28 | Lamodel Ltd. | Cartridge interface assembly with driving plunger |
US8348898B2 (en) | 2010-01-19 | 2013-01-08 | Medimop Medical Projects Ltd. | Automatic needle for drug pump |
US8915882B2 (en) | 2010-01-19 | 2014-12-23 | Medimop Medical Projects Ltd. | Needle assembly for drug pump |
US20110178463A1 (en) * | 2010-01-19 | 2011-07-21 | Oz Cabiri | Cartridge interface assembly with driving plunger |
US9764092B2 (en) | 2010-01-19 | 2017-09-19 | Medimop Medical Projects Ltd. | Needle assembly for drug pump |
US9149575B2 (en) | 2010-01-19 | 2015-10-06 | Medimop Medical Projects Ltd. | Needle assembly for drug pump |
US9492610B2 (en) | 2010-01-19 | 2016-11-15 | MEDIMOP Projects Ltd. | Needle assembly for drug pump |
CN105251077A (en) * | 2010-01-19 | 2016-01-20 | 麦迪莫普医疗工程有限公司 | Needle assembly for drug pump |
US9522234B2 (en) | 2010-01-19 | 2016-12-20 | Medimop Medical Projects Ltd. | Needle assembly for drug pump |
US8337457B2 (en) | 2010-05-05 | 2012-12-25 | Springleaf Therapeutics, Inc. | Systems and methods for delivering a therapeutic agent |
US9452261B2 (en) | 2010-05-10 | 2016-09-27 | Medimop Medical Projects Ltd. | Low volume accurate injector |
US8945071B2 (en) | 2010-09-02 | 2015-02-03 | Becton, Dickinson And Company | Self-injection device having needle cover with activation preventer |
US9675752B2 (en) | 2010-09-02 | 2017-06-13 | Becton, Dickinson And Company | Self-injection device having needle cover with activation preventer |
US9498573B2 (en) | 2010-09-24 | 2016-11-22 | Perqflo, Llc | Infusion pumps |
US8915879B2 (en) | 2010-09-24 | 2014-12-23 | Perqflo, Llc | Infusion pumps |
US9320849B2 (en) | 2010-09-24 | 2016-04-26 | Perqflo, Llc | Infusion pumps |
US10272196B2 (en) | 2010-09-24 | 2019-04-30 | Perqflo, Llc | Infusion pumps |
US9216249B2 (en) | 2010-09-24 | 2015-12-22 | Perqflo, Llc | Infusion pumps |
US9381300B2 (en) | 2010-09-24 | 2016-07-05 | Perqflo, Llc | Infusion pumps |
US8777901B2 (en) | 2010-09-24 | 2014-07-15 | Perqflo, Llc | Infusion pumps |
US9750875B2 (en) | 2010-09-24 | 2017-09-05 | Perqflo, Llc | Infusion pumps |
US9308320B2 (en) | 2010-09-24 | 2016-04-12 | Perqflo, Llc | Infusion pumps |
WO2012040528A1 (en) * | 2010-09-24 | 2012-03-29 | Perqflo, Llc | Infusion pumps |
US11547792B2 (en) | 2010-09-24 | 2023-01-10 | Medtronic Minimed, Inc. | Infusion pumps |
US8430849B2 (en) | 2010-09-24 | 2013-04-30 | Perqflo, Llc | Infusion pumps and plunger pusher position-responsive cartridge lock for infusion pumps |
US9211378B2 (en) | 2010-10-22 | 2015-12-15 | Cequr Sa | Methods and systems for dosing a medicament |
US8668675B2 (en) * | 2010-11-03 | 2014-03-11 | Flugen, Inc. | Wearable drug delivery device having spring drive and sliding actuation mechanism |
US20120109066A1 (en) * | 2010-11-03 | 2012-05-03 | Flugen, Inc. | Wearable drug delivery device having spring drive and sliding actuation mechanism |
US8876771B2 (en) * | 2010-11-16 | 2014-11-04 | Palyon Medical (Bvi) Limited | Propellant pillow manufacturing technique |
US20120118428A1 (en) * | 2010-11-16 | 2012-05-17 | Palyon Medical (Bvi) Limited | Propellant pillow manufacturing technique |
US10029045B2 (en) | 2010-11-20 | 2018-07-24 | Perqflo, Llc | Infusion pumps |
US8905972B2 (en) | 2010-11-20 | 2014-12-09 | Perqflo, Llc | Infusion pumps |
US10967124B2 (en) | 2010-11-20 | 2021-04-06 | Medtronic Minimed, Inc. | Infusion pumps |
EP2460548A1 (en) | 2010-12-06 | 2012-06-06 | Roche Diagnostics GmbH | Medical assembly comprising monitoring device |
WO2012076343A2 (en) | 2010-12-06 | 2012-06-14 | F. Hoffmann-La Roche Ag | Medical assembly comprising monitoring device |
US8368285B2 (en) | 2010-12-17 | 2013-02-05 | Massachusette Institute Of Technology | Electrochemical actuators |
USD702834S1 (en) | 2011-03-22 | 2014-04-15 | Medimop Medical Projects Ltd. | Cartridge for use in injection device |
USD747799S1 (en) | 2011-03-22 | 2016-01-19 | Medimop Medical Projects Ltd. | Cartridge |
WO2012178164A1 (en) * | 2011-06-23 | 2012-12-27 | Ratio, Inc. | Drug delivery device including a dynamic drug reservoir and ergonomic user interface |
US10335545B2 (en) | 2012-01-31 | 2019-07-02 | West Pharma. Services IL, Ltd. | Time dependent drug delivery apparatus |
US9511190B2 (en) | 2012-03-26 | 2016-12-06 | Medimop Medical Projects Ltd. | Fail safe point protector for needle safety flap |
WO2013148435A1 (en) | 2012-03-26 | 2013-10-03 | Medimop Medical Projects Ltd. | Fail safe point protector for needle safety flap |
CN104245018A (en) * | 2012-03-26 | 2014-12-24 | 麦迪莫普医疗工程有限公司 | Fail safe point protector for needle safety flap |
US10159785B2 (en) | 2012-03-26 | 2018-12-25 | West Pharma. Services IL, Ltd. | Motion activated septum puncturing drug delivery device |
US10668213B2 (en) | 2012-03-26 | 2020-06-02 | West Pharma. Services IL, Ltd. | Motion activated mechanisms for a drug delivery device |
US10179204B2 (en) | 2012-03-26 | 2019-01-15 | West Pharma. Services IL, Ltd. | Motion-activated septum puncturing drug delivery device |
US9393365B2 (en) | 2012-03-26 | 2016-07-19 | Medimop Medical Projects Ltd. | Fail safe point protector for needle safety flap |
US9463280B2 (en) | 2012-03-26 | 2016-10-11 | Medimop Medical Projects Ltd. | Motion activated septum puncturing drug delivery device |
US9072827B2 (en) | 2012-03-26 | 2015-07-07 | Medimop Medical Projects Ltd. | Fail safe point protector for needle safety flap |
US9878091B2 (en) | 2012-03-26 | 2018-01-30 | Medimop Medical Projects Ltd. | Motion activated septum puncturing drug delivery device |
US10071196B2 (en) | 2012-05-15 | 2018-09-11 | West Pharma. Services IL, Ltd. | Method for selectively powering a battery-operated drug-delivery device and device therefor |
US10299990B2 (en) | 2012-08-26 | 2019-05-28 | West Pharma. Services IL, Ltd. | Liquid drug transfer devices |
US10071198B2 (en) | 2012-11-02 | 2018-09-11 | West Pharma. Servicees IL, Ltd. | Adhesive structure for medical device |
US9421323B2 (en) | 2013-01-03 | 2016-08-23 | Medimop Medical Projects Ltd. | Door and doorstop for portable one use drug delivery apparatus |
US9439743B2 (en) | 2013-02-26 | 2016-09-13 | Primetech Corporation | Fluid delivery device |
US9166313B2 (en) | 2013-04-30 | 2015-10-20 | Medimop Medical Projects | Power supply contact for installation of printed circuit board |
US9011164B2 (en) | 2013-04-30 | 2015-04-21 | Medimop Medical Projects Ltd. | Clip contact for easy installation of printed circuit board PCB |
US9889256B2 (en) | 2013-05-03 | 2018-02-13 | Medimop Medical Projects Ltd. | Sensing a status of an infuser based on sensing motor control and power input |
US10398837B2 (en) | 2013-05-03 | 2019-09-03 | West Pharma. Services IL, Ltd. | Sensing a status of an infuser based on sensing motor control and power input |
US20160121043A1 (en) * | 2013-05-30 | 2016-05-05 | Weibel Cds Ag | Device for dispensing a fluid to a patient |
US10603428B2 (en) * | 2013-05-30 | 2020-03-31 | Actelion Pharmaceuticals Ltd. | Device for dispensing a fluid to a patient |
CN108704191A (en) * | 2013-05-31 | 2018-10-26 | 瓦莱里塔斯公司 | Fluid delivery system with the pre-filled cylinder of insertable |
US11660387B2 (en) | 2013-05-31 | 2023-05-30 | Mannkind Corporation | Fluid delivery device having an insertable prefilled cartridge |
US10688295B2 (en) | 2013-08-07 | 2020-06-23 | West Pharma. Services IL, Ltd. | Liquid transfer devices for use with infusion liquid containers |
US10946137B2 (en) | 2014-09-30 | 2021-03-16 | Medtronic Minimed, Inc. | Hybrid ambulatory infusion pumps |
US10159786B2 (en) | 2014-09-30 | 2018-12-25 | Perqflo, Llc | Hybrid ambulatory infusion pumps |
US10285907B2 (en) | 2015-01-05 | 2019-05-14 | West Pharma. Services IL, Ltd. | Dual vial adapter assemblages with quick release drug vial adapter for ensuring correct usage |
US11684712B2 (en) | 2015-02-18 | 2023-06-27 | Medtronic Minimed, Inc. | Ambulatory infusion pumps and reservoir assemblies for use with same |
US10251813B2 (en) | 2015-03-04 | 2019-04-09 | West Pharma. Services IL, Ltd. | Flexibly mounted cartridge alignment collar for drug delivery device |
US11253429B2 (en) | 2015-03-04 | 2022-02-22 | West Pharma. Services IL, Ltd. | Flexibly mounted cartridge alignment collar for drug delivery device |
US9795534B2 (en) | 2015-03-04 | 2017-10-24 | Medimop Medical Projects Ltd. | Compliant coupling assembly for cartridge coupling of a drug delivery device |
US10617819B2 (en) | 2015-04-10 | 2020-04-14 | West Pharma. Services IL, Ltd. | Needle cannula position as an input to operational control of an injection device |
US10293120B2 (en) | 2015-04-10 | 2019-05-21 | West Pharma. Services IL, Ltd. | Redundant injection device status indication |
US9744297B2 (en) | 2015-04-10 | 2017-08-29 | Medimop Medical Projects Ltd. | Needle cannula position as an input to operational control of an injection device |
US10149943B2 (en) | 2015-05-29 | 2018-12-11 | West Pharma. Services IL, Ltd. | Linear rotation stabilizer for a telescoping syringe stopper driverdriving assembly |
US11931552B2 (en) | 2015-06-04 | 2024-03-19 | West Pharma Services Il, Ltd. | Cartridge insertion for drug delivery device |
US10357429B2 (en) | 2015-07-16 | 2019-07-23 | West Pharma. Services IL, Ltd. | Liquid drug transfer devices for secure telescopic snap fit on injection vials |
US9987432B2 (en) | 2015-09-22 | 2018-06-05 | West Pharma. Services IL, Ltd. | Rotation resistant friction adapter for plunger driver of drug delivery device |
US11724034B2 (en) | 2015-10-09 | 2023-08-15 | West Pharma. Services, IL, Ltd. | Injector system |
US11547802B2 (en) | 2015-10-09 | 2023-01-10 | West Pharma. Services IL, Ltd. | Angled syringe patch injector |
US11759573B2 (en) | 2015-10-09 | 2023-09-19 | West Pharma. Services, IL, Ltd. | Bent fluid path add on to a prefilled reservoir |
US11318254B2 (en) | 2015-10-09 | 2022-05-03 | West Pharma. Services IL, Ltd. | Injector needle cap remover |
US10278897B2 (en) | 2015-11-25 | 2019-05-07 | West Pharma. Services IL, Ltd. | Dual vial adapter assemblage including drug vial adapter with self-sealing access valve |
US11311674B2 (en) | 2016-01-21 | 2022-04-26 | West Pharma. Services IL, Ltd. | Medicament delivery device comprising a visual indicator |
US11672904B2 (en) | 2016-01-21 | 2023-06-13 | West Pharma. Services IL, Ltd. | Needle insertion and retraction mechanism |
US11364337B2 (en) | 2016-01-21 | 2022-06-21 | West Pharma. Services IL, Ltd. | Force containment in an automatic injector |
US11672909B2 (en) | 2016-02-12 | 2023-06-13 | Medtronic Minimed, Inc. | Ambulatory infusion pumps and assemblies for use with same |
US11389597B2 (en) | 2016-03-16 | 2022-07-19 | West Pharma. Services IL, Ltd. | Staged telescopic screw assembly having different visual indicators |
US10646404B2 (en) | 2016-05-24 | 2020-05-12 | West Pharma. Services IL, Ltd. | Dual vial adapter assemblages including identical twin vial adapters |
US10765604B2 (en) | 2016-05-24 | 2020-09-08 | West Pharma. Services IL, Ltd. | Drug vial adapter assemblages including vented drug vial adapter and vented liquid vial adapter |
US11819673B2 (en) | 2016-06-02 | 2023-11-21 | West Pharma. Services, IL, Ltd. | Three position needle retraction |
US11103652B2 (en) | 2016-06-02 | 2021-08-31 | West Pharma. Services IL, Ltd. | Three position needle retraction |
US10806667B2 (en) | 2016-06-06 | 2020-10-20 | West Pharma. Services IL, Ltd. | Fluid transfer devices for filling drug pump cartridges with liquid drug contents |
US11185629B2 (en) | 2016-06-08 | 2021-11-30 | Shl Medical Ag | Dosing apparatus and injection device |
US11338090B2 (en) | 2016-08-01 | 2022-05-24 | West Pharma. Services IL, Ltd. | Anti-rotation cartridge pin |
US11730892B2 (en) | 2016-08-01 | 2023-08-22 | West Pharma. Services IL, Ltd. | Partial door closure prevention spring |
US10806671B2 (en) | 2016-08-21 | 2020-10-20 | West Pharma. Services IL, Ltd. | Syringe assembly |
US11253652B2 (en) | 2016-11-28 | 2022-02-22 | Shl Medical Ag | Device for dispensing a substance |
US10772797B2 (en) | 2016-12-06 | 2020-09-15 | West Pharma. Services IL, Ltd. | Liquid drug transfer devices for use with intact discrete injection vial release tool |
US10772798B2 (en) | 2016-12-06 | 2020-09-15 | West Pharma Services Il, Ltd. | Liquid transfer device with integral telescopic vial adapter for use with infusion liquid container and discrete injection vial |
US11786443B2 (en) | 2016-12-06 | 2023-10-17 | West Pharma. Services IL, Ltd. | Liquid transfer device with integral telescopic vial adapter for use with infusion liquid container and discrete injection vial |
US10945921B2 (en) | 2017-03-29 | 2021-03-16 | West Pharma. Services IL, Ltd. | User actuated liquid drug transfer devices for use in ready-to-use (RTU) liquid drug transfer assemblages |
US11819666B2 (en) | 2017-05-30 | 2023-11-21 | West Pharma. Services IL, Ltd. | Modular drive train for wearable injector |
US10814062B2 (en) | 2017-08-31 | 2020-10-27 | Becton, Dickinson And Company | Reservoir with low volume sensor |
US11642285B2 (en) | 2017-09-29 | 2023-05-09 | West Pharma. Services IL, Ltd. | Dual vial adapter assemblages including twin vented female vial adapters |
US11857767B2 (en) | 2017-12-22 | 2024-01-02 | West Pharma. Services IL, Ltd. | Injector usable with different dimension cartridges |
USD917693S1 (en) | 2018-07-06 | 2021-04-27 | West Pharma. Services IL, Ltd. | Medication mixing apparatus |
USD923812S1 (en) | 2019-01-16 | 2021-06-29 | West Pharma. Services IL, Ltd. | Medication mixing apparatus |
USD923782S1 (en) | 2019-01-17 | 2021-06-29 | West Pharma. Services IL, Ltd. | Medication mixing apparatus |
US11918542B2 (en) | 2019-01-31 | 2024-03-05 | West Pharma. Services IL, Ltd. | Liquid transfer device |
US11484470B2 (en) | 2019-04-30 | 2022-11-01 | West Pharma. Services IL, Ltd. | Liquid transfer device with dual lumen IV spike |
US11786442B2 (en) | 2019-04-30 | 2023-10-17 | West Pharma. Services IL, Ltd. | Liquid transfer device with dual lumen IV spike |
USD954253S1 (en) | 2019-04-30 | 2022-06-07 | West Pharma. Services IL, Ltd. | Liquid transfer device |
USD956958S1 (en) | 2020-07-13 | 2022-07-05 | West Pharma. Services IL, Ltd. | Liquid transfer device |
Also Published As
Publication number | Publication date |
---|---|
WO2001089607A2 (en) | 2001-11-29 |
WO2001089607A3 (en) | 2002-02-28 |
EP1284758A2 (en) | 2003-02-26 |
CA2411202A1 (en) | 2001-11-29 |
JP2003534058A (en) | 2003-11-18 |
JP5102927B2 (en) | 2012-12-19 |
AU2001264887A1 (en) | 2001-12-03 |
US6530900B1 (en) | 2003-03-11 |
JP2012152597A (en) | 2012-08-16 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US6530900B1 (en) | Drug delivery device | |
US6186982B1 (en) | Subcutaneous drug delivery device with improved filling system | |
EP1082151A1 (en) | Gas driven drug delivery device | |
AU2019200616B2 (en) | Integrated pierceable seal fluid pathway connection and drug containers for drug delivery pumps | |
AU2017203997B2 (en) | Insertion mechanisms having vented fluid pathways for drug delivery pumps | |
US10994114B2 (en) | Integrated sliding seal fluid pathway connection and drug containers for drug delivery pumps | |
EP3415187B1 (en) | Insertion mechanism for a drug delivery pump | |
US5993421A (en) | Medicament dispenser | |
WO1999030769A1 (en) | Fluid delivery device with fill adapter | |
KR20200044070A (en) | Optionally mechanically operable pre-charged infusion pump unit | |
WO2001052918A2 (en) | Fluid delivery device with temperature controlled energy source | |
CN117545518A (en) | User removable filled containment flaps with integrated films | |
TW418101B (en) | Subcutaneous drug delivery device with improved filling system |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
STCB | Information on status: application discontinuation |
Free format text: ABANDONED -- FAILURE TO RESPOND TO AN OFFICE ACTION |