Vial transfer and injection equipment and methods

Abstract

To provide a disposable single-use device for transferring contents of one or more vials to a disposable injection device and mixing them.SOLUTION: A device for filtering a liquid drug comprises a housing including an injectable fluid passage, and a liquid drug filter with a liquid drug pore diameter or a liquid drug effective pore diameter, which is arranged within the injectable fluid passage and which is constituted to remove particulate matter.SELECTED DRAWING: Figure 17

Description

Technical Field

[0001] This application claims the benefit and priority of both U.S. Provisional Patent Application No. 61 / 979,816, filed on April 15, 2014, and U.S. Provisional Patent Application No. 61 / 836,266, filed on June 18, 2013, which are hereby incorporated by reference in their entirety.

[0002] The subject matter of this application generally relates to devices and methods for administering the contents of vials, and more particularly to disposable, single-use instruments and methods for transferring and mixing the contents of one or more vials into a disposable injection device for administration to a human-like subject.

Background Art

[0003] Vials are one of the preferred container closure systems used by the pharmaceutical industry because of the wide variety of drugs and their extensive history of long-term stability records. Pharmaceuticals, including biologics, are often first introduced commercially in standard containers such as vials. Furthermore, the industry has made significant investments in major equipment for aseptic vial filling. However, vials require the transfer of the drug from the vial to an injection device for delivery to the patient. New sealed systems such as pre-filled syringes and cartridges have been introduced, which allow for the direct transfer of the drug from the syringe or cartridge to the patient. Injection devices such as auto-injectors and pens have been developed to utilize these newer forms of sealed containers. Due to the uncertainty of long-term drug stability and the already appropriate extensive manufacturing resources, devices that incorporate standard container closure systems such as vials, pre-filled syringes or cartridges are much preferred in the pharmaceutical industry over devices that require a unique form of drug encapsulation.

[0004] However, vials, pre-filled syringes, and cartridges are not necessarily the best containers for drug delivery devices, especially when dealing with relatively high volumes of drugs (2-20 cc) or high viscosity drugs (15 cP or more). Vials, pre-filled syringes, and cartridges are almost entirely made of glass, which imposes design constraints in terms of force and shape. Typical syringes and autoinjectors are limited not only by the force applied to the glass sealed container system but also by the viscosity of the drug that can be delivered. New injectors, including pumps that use proprietary sealed containers for insulin delivery, are being developed, but these systems are very expensive, cannot generate high force or pressure, and are generally reusable and / or refillable.

[0005] Due to factors including stability and time to market, pharmaceuticals, including biologics, are often first brought to market in lyophilized, powder, or concentrated liquid form. Such drugs packaged in vials in liquid or powder form may require considerable preparation before administration. To facilitate the administration of liquid formulations in vials, vial drugs are often packaged with an empty syringe and multiple needles for drawing from the vial and injecting into the patient. In the case of powder formulations, an additional diluent or solution vial may be provided to reconstitute the powder formulation into a solution available for injection.

[0006] The risks associated with the preparation and administration of these dosage forms are significant. These risks include not only needle stick injuries during the reconstitution and administration process, but also the possibility of improper mixing, inaccurate dosages, and inaccurate concentrations. This requires considerable effort from both trained caregivers and patients receiving drug therapy. Similar risk issues can also apply to the transport of pre-prepared medications that must be transferred from vials to injection devices. This transfer requires removing the drug from the vial, measuring the appropriate dosage, and administering it to the patient using a syringe. Incomplete transfer of the vial's maximum volume requires overfilling of the vial by 25-30% and the associated waste. Contamination of the injectable drug may occur due to non-sterile outside air introduced into the vial or contamination of the drug due to improper aseptic techniques.

[0007] Therefore, there continues to be a need for new and / or improved instruments and methods for the transfer, mixing, and injection of drugs from a source vial or multiple vials into a target.

[0008] The following description is for illustrative purposes only and is not intended to be restrictive. This subject matter may apply to various devices, systems, and methods not described below. [Overview of the project]

[0009] This subject matter is directed, in part, to disposable, single-use devices and methods that, preferably initiated by a user, automatically mix and / or transfer the injectable contents of one or more vials into a single injection device, and preferably simultaneously and subsequently automatically pressurize the injection device for injection into a patient. The contents of the vials may also be injectable drugs in any appropriate use for the purposes of this description and claims. "Injectable drugs" includes, without limitation, therapeutic, diagnostic, antibiotics, biologics, sedatives, sterile water and other injectable materials, alone or in combination with other injectable drugs, with or without the need for pre-injection reconstitution or adjustment of concentration or other processes. While various features of this subject matter may be described in the context of reconstitution for injection of powder formulations, the devices and methods disclosed herein are not limited to specific applications and may also be used for liquid injectable drugs that only require preparation for injection and transfer from vials to an injection device. Furthermore, the disclosed apparatus and methods may be used for injectable drugs and / or injection applications that do not require reconstitution or concentration adjustment and are mixed before injection (so that the two liquid preparations are mixed for drug therapy).

[0010] The apparatus and methods described herein may be any suitable detailed structure, but are preferably structures for transferring the contents of a vial to an injection device. The apparatus may also be configured to mix or process the contents of the vial that require reconstitution or concentration adjustment during the transfer process. The apparatus may also be configured to allow the user to select the dosage for injection and may further include a lockout function that requires such selection before communication with or transfer of the contents of the vial by the apparatus is permitted or before mixing or other processing is initiated. The apparatus may further be configured to filter the drug before transferring it to the injection device to remove particulate matter or drug particles, and may include a sterile filter to filter out displacement air discharged into the vial or multiple vials. The apparatus may also include a lockout to prevent the user from removing or operating the injection device before drug transfer until the injection device is removed from the transfer apparatus.

[0011] This subject may include a vial holder configured to hold one or more vials in a predetermined relationship for cooperation with a transport device. For example, a vial holder may be configured to include one receiving area or cavity for one vial (e.g., a vial containing a liquid). Alternatively, a vial holder may be configured to include a first vial receiving area or cavity for a first vial (such as one containing a lyophilized drug) and a second vial receiving area or cavity for a second vial (such as one containing a diluent). The vial holder contains the vials in a predetermined relationship to cooperate with a transport device to load or, if necessary, access and process the contents of the vials (e.g., mix and reconstitute the drug). The vials may be configured to accept only a diluent-containing vial in one receiving area and only a powder vial in the other receiving area to prevent vials from being mixed up in the wrong position. The vial holder may include a removable cover configured to attach to the vial cap so as to cover the vial access member. Removing the cover simultaneously removes the vial cap, exposing the vial to the access component for pre-disinfectant coating or connection to a transfer device, if necessary. If the vial cap is sufficiently sterile within the cover, coating may not be necessary, although it is preferable for careful handling. Alternatively, the vial holder with the vial inserted may be mounted on a transfer device with the vial cap removed. Sterility of the vial stopper and vial access component may be maintained throughout the product's lifespan, eliminating the need for the user to remove the vial cap and wipe the top of the vial.

[0012] This subject matter includes any suitable detailed structure of injection devices, but injection devices that are particularly useful in combination with this device are described in U.S. Patent Application No. 61 / 326,492 filed April 21, 2010, U.S. Patent Application No. 13 / 637,756 filed September 27, 2012, and U.S. Patent Application No. 61 / 704,922 filed September 24, 2012, all of which are incorporated herein by reference. As seen in these applications, the illustrated injection devices use an expandable member, such as a balloon, to automatically release or inject a drug when activated by the user. Long-term storage of drugs in a pressurized member presents design and manufacturing challenges, and a particularly advantageous aspect of one embodiment of this subject matter is that the injection device can remain in an unpressurized state (e.g., an unfilled, uninflated, low-energy balloon), and the injectable drug remains in a standard original vial or multiple vials for an enhanced shelf life until injection is required. In this application, the injectable drug is preferably automatically transferred from a vial or multiple vials to the injection device (along with any associated mixing, dilution, or other necessary processing) by a transfer device, which simultaneously charges the injection device (e.g., by inflating an expandable component or balloon by introducing the injectable drug under pressure), preparing the injection device for automated injection to the patient upon user disclosure. In this application, the injectable drug is in the injection device for only a very limited time, such as a few seconds or minutes, reducing the shelf life, design, and manufacturing of materials for long-term drug storage.

[0013] According to another aspect of this subject, although this could be used in any suitable injection device, the expandable member (like a balloon) may be configured to be stretched and gradually collapse from one end to the other during injection. The arrangement of the stretched expandable member, which is generally a flat spiral or helical structure, may vary in specific construction but is relatively small so that an expandable member of considerable length and volume can be applied to and left on the patient's skin. The injection device may have a viewing window for the user to see the expandable member and to check the approximate state of the injection by the amount of the collapsible and / or expandable portion, and / or the expandable member or viewing window may be graduated with appropriate markings so that the user can determine the amount of injection.

[0014] Vial holders, transfer devices and injection devices and methods of using them are separate aspects of this subject matter, each having its own utility and claimed separately; however, various combinations or partial combinations, such as combinations of transfer devices and injection devices, or combinations of vial holders, transfer devices and injection devices, and / or methods of using such, are also claimed. [Brief explanation of the drawing]

[0015] Specific examples of the subject matter of this application are shown in the attached figures for illustrative purposes only, and not for limitation. [Figure 1] This is a perspective view of a single vial system, including a vial holder, transfer device, and injection device, which specifically represents the subject of this article. [Figure 2] This is a perspective view of a double vial system, including a vial holder, transfer device, and injection device system, which specifically represents the subject of this article. [Figure 3] This image shows a perspective view of a single vial holder with a removable top, a cross-sectional view of a single vial holder with a removable top, and a perspective view of a single vial holder with the removable top and vial cap removed. [Figure 4]This is a perspective view including the removable top, and a cross-sectional view of the double vial holder with the removable top and vial cap removed. [Figure 5] Figure 2 is a cross-sectional view of the vial holder region showing the position of the vial access member relative to the vial partition. [Figure 6] Figure 1 is a cross-sectional view of the vial holder region, showing that the access member has penetrated the vial's partition wall. [Figure 7] Figure 1 is a perspective view of the transfer device, showing the vial holder and injection device receiving area. [Figure 8] This is an enlarged view of Figure 5, showing a vial access member that penetrates the partition wall of a vial, which has a foldable vial access member shielding material. [Figure 9] Figure 2 is a schematic diagram of a vial transfer system having a first vial, a second vial, a transfer device having first and second variable pressure chambers, and an injection device including a fluid flow path. [Figure 10] This is a cross-sectional view of the position before injection, as shown in Figure 2. [Figure 11] Figure 1 is a schematic diagram of a single vial transfer system, which includes a drug vial, a transfer device having a first variable pressure chamber, and an injection device including a fluid flow path. [Figure 12] This is a cross-sectional view of Figure 1. [Figure 13] Figure 2 is a schematic diagram of another embodiment of a double vial transfer system, which includes a transfer device having a first vial, a second vial, and a first pressurized chamber, and an injection device including a fluid flow path. [Figure 14] Figure 2 is a schematic diagram of another embodiment of a double vial transfer system, which includes a first vial, a second vial, a transfer device having first and second variable pressure chambers, and an injection device including a fluid flow path. [Figure 15] Figure 2 is a schematic diagram of another embodiment of a double vial transfer system, which includes a first vial, a second vial, a transfer device having a first pressure chamber, a double lumen connector, and an injection device including a fluid flow path. [Figure 16]It is a cross-sectional view of FIG. 1. [Figure 17] It is a schematic diagram of another embodiment of a single vial transfer system in FIG. 1, including a drug vial, a transfer device having a first variable pressure chamber, an injection device including a fluid flow path having a check valve, and a flow restrictor. [Figure 18] It is a cross-sectional view of FIG. 2. [Figure 19] It is a cross-sectional view of FIG. 2. [Figure 20] It is a perspective view of the injection device. [Figure 21] It is a top view of the filled injection device, showing the filled delivery indicator. [Figure 22] It is a top view of the filled injection device, showing the empty delivery indicator. [Figure 23] It is a perspective view showing the underside of the injection device having the attached tape and the filling port. [Figure 24] It is a perspective view showing the underside of the injection device having the peeled tape, the exposed filling port, and the administration port. [Figure 25] It is a cross-sectional view of the injection device on the transfer device. [Figure 26] It is a perspective view of the injection device with the safety device installed, attached to the skin. [Figure 27] It is a perspective view of the injection device with the safety device removed and the button raised to the pre-injection state, attached to the skin. [Figure 28] It is a perspective view of the injection device with the safety device removed and the button lowered to the injection state, attached to the skin. [Figure 29] It is a cross-sectional view of the injection device with the button raised to the pre-injection state, attached to the skin. [Figure 30] It is a cross-sectional view of the injection device with the button lowered to the first injection state, attached to the skin. [Figure 31] It is a cross-sectional view of the injection device with the button lowered to the administration state, attached to the skin. [Figure 32] It is a cross-sectional view of the injection device with the end of the delivery indicator not triggered, attached to the skin. [Figure 33] This is a cross-sectional view of an injection device with the end of the delivery indicator raised, attached to the skin. [Figure 34] This is a cross-sectional view of an injection device attached to the skin, with the button locked out in the post-injection position. [Figure 35] This is a perspective view of an injection device removed from the skin, with a bandage still attached. [Figure 36] This is a perspective view of a filled syringe with the top housing removed. [Figure 37] Figure 36 is a top view of the injection device. [Figure 38] This is a perspective view of an empty syringe with the top housing removed. [Figure 39] Figure 38 is a top view of the injection device. [Figure 40] A perspective view of a single vial system in packaging. [Figure 41] A perspective view of a single vial system with its packaging opened. [Figure 42] This is a perspective view of a single vial system inside a package with the lid removed, exposing the contents of the package. [Figure 43] This is a perspective view of a single vial system with the vial holder removed from its packaging and the vial cap removed. [Figure 44] This is a perspective view of a single vial system with a vial holder fully inserted into a transfer device. [Figure 45] This is a perspective view of a double vial system with a vial holder inserted. [Figure 46] Figure 45 is a top view showing the volume control unit in its state before configuration. [Figure 47] This is a top view of Figure 45, showing the volume control unit in its configured state. [Figure 48] This is a perspective view of a double vial system in which the volume control unit has been removed and the vial holder has been pushed down into the transfer device to initiate the mixing and transfer process. [Figure 49]This is a perspective view of the double vial system after the injection device has been filled, the injection device removal connector has been released, and the mixing and transfer process is complete. [Figure 50] This is a perspective view of a single vial system filled with an injection device and removed from its packaging. [Figure 51] This is a perspective view of an injection device placed on the skin and equipped with a safety device. [Figure 52] This is a perspective view of an injection device placed on the skin with the safety device removed. [Figure 53] This is a perspective view of an injection device placed on the skin with the button pressed to begin the injection. [Figure 54] This is a perspective view of an injection device with the button locked up, leaving a bandage on the skin, and removed from the skin after injection. [Figure 55] This is a perspective view of the injection device representing the subject of this article. [Figure 56] Figure 55 is a cross-sectional view showing an injection device having a button in a first position. [Figure 57] This diagram illustrates the four stages of needle penetration into tissue, including a) non-contact, b) boundary replacement, c) tip insertion, and d) shaft insertion (Van Gerwen, DJ Needle-Tissue Interaction by Experiment. Ph.D. Thesis, Delft University of Technology, 2013. ISBN 978-94-6186-238-9, pg. 11). [Figure 58] Figure 55 is a cross-sectional view showing an injection device with a button at a second position or administration position. [Figure 59] This is a perspective view of a single vial transfer system into which a drug vial and injection device are inserted for use with this subject. [Figure 60] Figure 59 is a cross-sectional view illustrating the region of the vial holder showing the drug vial, vial access member, and expandable member located below. [Figure 61]Figure 59 is a cross-sectional view illustrating the region of the vial holder showing the drug vial, vial access member, and expandable member located above it. [Figure 62] Figure 59 is a cross-sectional view with the box and tray removed, illustrating the pressure chamber and fluid flow path. [Figure 63] Figure 59 is a cross-sectional view illustrating one surface of the vial holder region, showing the drug vial and the vial access member. [Figure 64] This is a cross-sectional view of a single vial system including a single vial holder, transfer device, and injection device system. [Figure 65] Figure 64 is a schematic diagram of another embodiment of a single vial transfer system, comprising a drug vial, a transfer device having a first variable pressure chamber, and an injection device including a fluid flow path with a check valve and a flow throttling. [Figure 66] Figure 55 is a cross-sectional view showing the adhesive and the device, and the interface between the adhesive and the skin. [Figure 67] This is a perspective view of the bottom of the injection device, showing different areas of adhesive. [Figure 68] Figure 55 is a cross-sectional view showing swollen tissue on a device with a permanently attached adhesive. [Figure 69] Figure 55 is a cross-sectional view showing an expanded tissue on the apparatus with adhesive applied to multiple regions. [Figure 70] This is a top perspective view of another injection device. [Figure 71] Figure 70 is a cross-sectional view showing the disengaged removal sensor and the needle locked in the dosing position. [Figure 72] Figure 70 is a cross-sectional view showing the engaged removal center, the needle, and the button retracted to the post-injection position. [Figure 73] Figure 55 is a cross-sectional view showing an injection device with a button in a first position or resting position. [Figure 74] Figure 55 is a cross-sectional view showing an injection device with a button at a second position or administration position. [Figure 75] Figure 55 is a cross-sectional view showing an injection device with the needle retracted and the button raised to the post-injection position. [Figure 76] Figure 55 is a cross-sectional view showing an injection device with the button in the second or administration position. [Figure 77] This is a perspective view of a single-vial transfer device. [Figure 78] This is a perspective view of an injection device. [Figure 79] Figure 78 is a cross-sectional view showing an injection device with the button in the second or administration position. [Figure 80] Figure 64 is a schematic diagram of another embodiment of a single vial transfer system, which includes a drug vial, a transfer device having a first variable pressure chamber, an injection device including a fluid passage with a check valve, and a flow throttling. [Figure 81] Figure 77 is a cross-sectional view illustrating one aspect of the vial-receptor region. [Figure 82] This is a schematic diagram of a double vial transfer system having a first vial, a second vial, a transfer device having first and second variable pressure chambers, and an injection device including a fluid flow path. [Figure 83] A perspective view of an injection device with an attached safety sleeve. [Figure 84] Figure 55 is a cross-sectional view showing an injection device with the button in the second or administration position. [Figure 85] Figure 59 is a cross-sectional view illustrating one curved view of the vial holder region showing the drug vial, vial access member, and angle sensor in the open position. [Figure 86] Figure 59 is a cross-sectional view illustrating one curved view of the vial holder region showing the drug vial, vial access member, and angle sensor in the closed position. [Figure 87] This is a schematic diagram of another embodiment of a single vial transfer system having a drug vial, a transfer device having a first variable pressure chamber, an injection device including a fluid passage with a check valve, and a flow throttling. [Modes for carrying out the invention]

[0016] As shown in Figures 1 and 2, and more specifically as described below, the disposable, single-use single vial transfer and injection system 1 shown in Figure 1 may comprise a single vial holder 2, a transfer device 3, and an injection device 7. The disposable, single-use double vial mixing, transfer, and injection system 4 shown in Figure 2 may comprise a double vial holder 5, a transfer device 6, and an injection device 7. As previously mentioned, each aspect has distinct utility and can be claimed separately and / or in combination or in subordinate combinations.

[0017] As shown in Figures 3 and 4, a single vial holder 2 includes a housing 8 with side walls 9, end walls 10 and an opening or viewing window 11. Alternatively, the material of the vial holder 2 may be transparent to allow visualization of the contents of the vial 12. As shown in Figure 4, the housing 8 is formed to define at least one or more cavities 13 or areas for vial accommodation to ensure that each cavity 12 is held in its respective cavity 13. The cavities 13 of the vial holder 5 may be sized to accommodate standard injectable vials 12 of different sizes, for example, from 1 to 30 ml. The vials 12 may be the same size or different sizes and may contain any desired contents (fluids, liquids, injectable drugs, pharmaceuticals, or mixtures) 14. In the double vial holder 5 illustrated in Figure 4, the vials may include a vial 15 of powder, lyophilized, or liquid medicine and a vial 16 of liquid or diluent. The vial holder 5 may contain vials that have been pre-packaged and assembled by, for example, a pharmaceutical manufacturer, or it may contain vials that have been inserted into the vial holder 5 by an end user or a medical professional such as a pharmacist or nurse. The vial holder 5 may have appropriate patterns and / or features to allow only specific vials to be assembled into specific cavities 13. For example, a vial 15 containing a powder may be inserted into a specific cavity 13 of the vial holder 5, and a vial 16 containing a diluent may be inserted into a different cavity 13 of the vial holder 5. An opening or viewing window 11 of the vial holder 5 allows for direct visualization of the contents 14 of the vial.

[0018] As shown in Figures 3 and 4, a further option is that the vial holder 5 may be an assembly of individual vial holders 2, each having a single vial 12. For example, if necessary, a manufacturer of injectable drugs may pre-assemble the vials 12 in independent vial holders 2, which can be combined with another vial holder 2 of another vial 12 at the time of injection if necessary. For example, a pharmaceutical manufacturer may provide lyophilized drugs in vial holders 2 and diluents such as sterile water or saline in separate vial holders. The user or medical professional may, if necessary, combine the individual vial holders 2 to form a vial holder assembly (vial holder 5) for connection to the transport device 6 shown in Figure 2.

[0019] Returning to Figure 3, the vial holder 2 may typically include a removable cover 17 that covers and protects the end 18 of the vial during transport and storage. A typical, standard commercial vial 12 includes a punctureable partition 19 located at the neck of the vial to access the contents 14 of the vial, which is covered by a removable vial cap (or closure) 20. The removable cover 17 may be configured to engage with the vial cap 20 so that removal of the cover simultaneously removes the vial cap 20, exposing the partition 19 of the vial to access the contents 14 after disinfectant application of the partition 19, which may be deemed necessary by the user. After the vial cap 20 is removed with the cover 17, the vial holder 2 may recess the vial 12 inside, and to reduce the chance of contamination by the user before insertion of the vial holder 2 into the transport device 3, the punctureable partition 19 is fitted within the scope of the vial holder 2, as shown in Figure 1. This system can be applied to a single vial holder 2 and a double vial holder 5.

[0020] As shown in Figure 3, the vial holder 2 may include a coupling device 27 to prevent the vial 12 from being removed once it has been inserted into the vial holder 2. This helps prevent the vial 12 from coming loose or being accidentally removed during handling.

[0021] As shown in Figure 5, the vial holder 5 may be assembled to the transfer device 6 by the device manufacturer with the vial cap removed and the vial already inside the vial holder 5. The exposed vial partition 19 is held adjacent to the vial access members 21, 52 before activation. This configuration provides convenience by eliminating the need for the user to remove the vial cap, wipe the partition 19 at the top of the vial, and assemble the vial holder 5 to the transfer device 6 before using the system 4.

[0022] As shown in Figure 6, the vial holder 2 may be packaged separately from the transport device 3. In this case, the user removes the vial cap with a removable cover 17, wipes the septum 19 at the top of the vial (if necessary), and incorporates the vial holder 2 into the transport device 3. As shown in Figure 6, the vial holder 2 may include a lockout function 22 that interacts with the transport device 3 to prevent accidental removal of the vial holder 2 from the transport device 3 after it has been activated by the user.

[0023] As shown in Figure 5, the vial holder 5 is preferably assembled to the transfer device 6 so that the vials 15, 16 are positioned upside down in a vertical position. This allows any contents (or fluid, liquid, mixture) 23 in the vials to be in direct contact with the vial access members 21, 52 after insertion into the vial holder 5. This also allows air 24 to be transferred to the top of the vials in this arrangement. To keep the partition walls 19 uncontaminated after removal of the vial caps and before insertion into the vial holder 5, the partition walls 19 of the exposed vials may be fitted into the vial holder 5 to prevent accidental contact, as shown in Figure 4. This configuration can be applied to single vial holder and double vial holder configurations.

[0024] As shown in Figure 6, the vial holder 2 is preferably mechanically configured within the transport device 3, along with an insertion function 25, to operate like an on / off switch, i.e., to have only two states, open and closed, like a light switch. This prevents the user from partially pushing the vial holder 2 into the transport device 3, preventing the vial access member 21 from piercing the partition 19 and preventing communication between the contents 14 of the vial 12 and the transport device 3. Furthermore, the vial holder 2 may be coupled to a coupling device 26 to lock the vial holder 2 in the closed position after it is fully inserted within the transport device 3, in order to prevent the vial holder 2 from being removed from the transport device 3 after insertion.

[0025] As shown in Figure 7, the transport device 3 comprises an outer housing 28 defining a vial holder docking area (or first receiving station, vial holder docking station, docking station) 29 and (for a removable injector) an injector docking station (or second receiving station) 30. In the illustrated structure, the vial holder docking area 29 and the injector docking station 30 are located on opposite sides of the outer housing 28 of the transport device.

[0026] As shown in Figure 7, the transfer device 3 may have an outer housing 28 integrated with the system packaging 31. The outer packaging 31 can essentially form the bottom and side walls of the outer housing 28 of the transfer device. All operational steps in using the system, up to the removal of the injection device, take place within this packaging 31. This can reduce costs and improve ease of use for the user. Furthermore, by incorporating all transfer devices 3 into the packaging 31, user errors that may occur if the user is required to remove the transfer devices 3 from the packaging 31 can be eliminated. The packaging 31 may include a plastic tab or tray containing the system. Moreover, the packaging 31 may also include everything within a transport carton 32 that houses the entire system.

[0027] As shown in Figure 7, the transfer device 3 includes a vial holder docking area 29 which may include an extended vial access member (or puncture member) 21. This vial access member 21 may be configured as a pointed or blunt cannula or needle. As shown in Figure 8, the vial holder 5 with the vial 12 attached is inserted into the vial holder docking area 29, showing that the vial access member 21 punctures the vial partition 19, allowing access to the contents 14 of the vial 12. The vial access member 21 may include a foldable seal 33 to maintain sterility of the vial access member 21 and the fluid flow path before activation. The foldable seal 33 may be attached to the outside of the vial 12 and seal the vial access member 21 to maintain sterility before activation.

[0028] As shown in Figure 8, the vial access member 21 of the transfer device 3 may be equipped with a multi-lubricated tube 34 for communicating with the fluid passage 35 inside the transfer device 3. Preferably, the vial access member 21 includes one inlet tube 36 and one outlet tube 37 that allows air or fluid to exit the vial 12. These inlet tubes 36 and outlet tubes 37 may be separate and distinguishable and may lead to different fluid passages in the transfer device 3. Since the vial 12 is inverted vertically, the lumen opening 38 of the vial access member 21 may be oriented such that the opening of the inlet tube 36 is above the opening of the outlet tube 37. This orientation allows for the introduction of compressed air or liquid through the upper inlet tube 36 and the discharge of the vial contents 14 through the lower outlet tube 37. Furthermore, the opening of the outlet tube 37 may be located near the bottom of the vial 12 and adjacent to the partition wall 19 in order to allow all the contents 14 of the vial 12 to be drawn into the outlet tube 37 and removed from the vial 12.

[0029] As shown in Figures 9 and 10, the transfer device 6 is configured, preferably automatically, after the user initiates the procedure, to transfer the contents 14 contained in the vials 15 and 16, reconfigure them (if necessary), and perform all the steps necessary to transfer the mixture to the injection device 7. The transfer device 6 is preferably configured to include a propulsion system, such as an electrically driven (e.g., battery-driven) or mechanically driven (e.g., equipped with a spring) pump, or a plurality of propulsion systems, to direct the diluent from the diluent vial 16 into the vial 15 of the injectable powder and the contents 14 through the transfer device 6 to the injection device 7.

[0030] As shown in Figures 9 and 10, the transfer device 6 may also include a row of internal fluid channels 35 when required to perform transfer, reconstitution, mixing, dilution or other procedures of the contents 14 and transfer from vials 15, 16 in the vial holder 5 to the injection device 7. The fluid channels 35 may include flexible or rigid pipes or tubes. These fluid channels 35 may also include check valves (filters, flow throttling or other means) 40 for directing the drug from vials 15, 16 to the transfer device 6.

[0031] As shown in Figures 9 and 10, the transfer device 6 may include a variable-volume pressure chamber or cylinder having a movable spring-loaded piston inside that leads directly to an internal fluid passage 35. The volume of each chamber in the variable-volume chamber may be defined by the diameter of the chamber and the position of the piston. The first pressure chamber 41 in the transfer device 6 may have an initial volume set by the manufacturer, preferably in the range of 1 to 30 milliliters. The initial contents of the first pressure chamber 41 may preferably include air 45. In the first pressure chamber 41, whose volume is set by the manufacturer, the piston 43 may be moved by a spring (compression spring) 44. The spring-loaded piston 43 may be large and configured to generate a static pressure of 1 to 50 psi in the first pressure chamber 41. The volume of air 45 during operation depends on the diameter of the first pressure chamber 41 and the stroke position of the piston 43. This pressure depends on the relative volume of air 45 displaced by the piston 43 and the force exerted by the spring 44. In other words, the product of the force exerted by the spring 44 and the area of ​​the piston 43 in the first pressure chamber 41 determines the static pressure in the first pressure chamber 41. The force exerted by the spring 44 at the contact height or the start of the stroke may be much greater than the force exerted by the spring 44 at the end of the movement. The spring 44 may be of an appropriate size to control the rate at which air is discharged from the first pressure chamber 41 and the rate at which the fluid is transferred within the transfer device 6. The first pressure chamber 41 is preferably configured to discharge all of the air 45 from the first pressure chamber 41. Alternatively, a flow restriction 55 in the fluid passage (or output passage) 35 of the first pressure chamber 41 may be used to control the rate at which the air 45 is ejected from the first pressure chamber 41.

[0032] As shown in Figures 9 and 10, the volume of the second pressure chamber 42 may be set by the manufacturer. Alternatively, the volume to be filled for the second pressure chamber 42 may be in the range of 0.5 to 30 milliliters and may be set by the user when using the dosage selection unit (or volume control unit, dosage indicator) 48. The spring-loaded piston 46 of the second pressure chamber 42 may be large and configured to generate a pressure of 1 to 200 psi in the second pressure chamber 42. The dosage selection unit 48 allows the user to select a predetermined dosage to be injected by the injector 7 by setting the volume of the second pressure chamber 42 to be filled. The dosage selection unit 48 may be any suitable configuration. The dosage selection unit 48 may be directly coupled to a plunger (or pressure plunger assembly, pressure chamber plunger assembly) 93 that can move within the second pressure chamber 42. Once the piston reaches a position corresponding to the full volume setting, the trigger 49 within the pressure plunger assembly 93 releases the piston 46 in the second pressure chamber 42. The user selects the desired dosage in the second pressure chamber 42 by moving the dosage selection unit 48, which determines the position of the plunger 93, to set a full volume equal to the desired injectable dose. Alternatively, the position of the plunger 93 may already be determined for a product that matches the delivery dose, and the user may operate the device without adjusting the dosage.

[0033] As shown in Figures 9 and 10, the transfer device 6 for transfer for a double vial system 4 that provides mixing and transfer includes a vial holder 5 having a first vial 16 and a second vial 15, a first pressure chamber 41 with variable volume, a second pressure chamber 42 with variable volume, a fluid passage 35, and a check valve 40 for directing air from the first pressure chamber 41 towards the first vial 16 and the contents 23 of the first vial 16 towards the second pressure chamber 42 and then towards the injection device 7.

[0034] As shown in Figure 8, the user's complete insertion of the vial holder 5 into the transfer device 6, followed by the introduction of the vial 12 into the chamber through the partition 19 of the vial access member 21, allows the pressure chamber trigger 50 to open, as shown in Figure 10.

[0035] As shown in Figures 9 and 10, the release of the trigger 50 releases the spring 44 of the first pressure chamber, advancing the piston 43 of the first pressure chamber 41, forcing the air 45 in the first pressure chamber 41 through the fluid passage 35 inside the transfer device 6 and into the first vial 16 through the inlet pipe 36 of the first vial access member 21. With more air 45 forced out of the first pressure chamber 41 and into the first vial 16 by the inlet pipe 36, the air 45 rises to the top of the first vial 16 due to its vertical position within the vial holder 5. The increasing pressure in the first vial 16 causes the contents 23 inside the vial 16 to be ejected by the outlet pipe 37 of the first vial access member 21 and by the inlet pipe 51 of the second vial access member 52. The contents 23 entering the second vial 15 from the first vial 16 mix with the contents of the second vial 15, which may contain a liquid or powdered drug, and exit into the second pressure chamber 42 through the outlet tube 53 of the second vial access member 52. Similarly, in the reconfiguration structure, the piston (or plunger, feeding plunger) 43 of the first pressure chamber 41 continues to push the mixture of the first contents 23 and air 45 through the first vial 16 into the second vial 15. The increasing pressure at the top of the second vial 15 causes the reconfigured contents 14 at the bottom of the second vial 15 to be released out into the second pressure chamber 42. A “pop-off” or check valve 40 or other type of valve may be present in the outlet pipe 53 of the second vial access member 52 to allow all of the contents 23 of the first vial 16 into the second vial 15 before the contents 14 of the second vial 15 are released into the second pressure chamber 42. The valve will not open until the pressure matches that of the piston 43 pushing substantially all of the air 45 out of the first pressure chamber 41. This ensures that the contents 54 of the second vial 15 are thoroughly mixed with the contents 23 of the first vial 16 before the contents 14 exit the second vial 15, thereby pressurizing the second pressure chamber 42. Alternatively, a flow restriction 55 may be used in the fluid passage 35 to extend the transfer and increase the mixing time.

[0036] As shown in Figures 9 and 10, the injectable contents 14 flow from the second vial 15 into the second pressure chamber 42 after reconstitution, filling the second pressure chamber 42 to the limit permitted by the piston 46, corresponding to the desired dosage selected by the user or manufacturer using the dosage selection unit 48. When the desired volume of the second pressure chamber 42 is achieved, the trigger 49 of the second pressure chamber releases the spring 47, forcing the piston 46 to advance and releasing the selected amount of contents 14 under pressure into the injection device 7. The dosage calibration indicated by the dosage selection unit 48 and the actual dosage received by the user may require taking into account fluid loss in the fluid passages 35 inside the transfer device 6. The injection device 7 is now filled and ready to be removed from the transfer device 6.

[0037] As shown in Figures 11 and 12, a separate transfer device 3 within the single vial system 1 is provided, which simply transfers the contents 14 from one vial 15 to an injection device 7 without performing mixing. This separate transfer device 3 includes a vial holder 2 having a single vial 15, a volume-variable pressure chamber 56, a fluid passage 35 and a check valve 40 for directing the contents 14 from the vial 15 to the injection device 7. The inlet pipe 36 of the vial access member 21 is exposed to the environment 57 to allow air 58 to enter the vial 15. The outlet pipe 37 of the vial access member 21 is connected to the pressure chamber 56.

[0038] As shown in Figures 11 and 12, the full insertion of the vial holder 2 into the transfer device 3 by the user allows the introduction of the vial access member 21 through the partition 19 of the vial 15 to access the contents 14 of the vial 15. This also triggers the release of the pressure chamber trigger 49. The trigger (pressure release trigger) 49 releases the plunger 60 in the pressure chamber 56, which is connected to a retraction spring 61. The retraction spring 61 forces the plunger 60 to retract the contents 14 from the vial 15 and fill the pressure chamber 56. The specific amount of contents 14 retracted by the pressure chamber 56 can be set by the manufacturer by limiting the retraction of the plunger 60. Furthermore, the pressure chamber 56 can be configured to retract all of the contents 14 from the vial 15 by retracting the plunger 60 to its maximum travel distance. Once the plunger 60 reaches its set position in the pressure chamber 56, it interacts with a dosing trigger 62 which releases a dosing spring 63 to force the contents 14 out of the pressure chamber 56 into the injection device 7. A check valve 40 may be used to prevent the contents 14 from returning to the vial 15.

[0039] As shown in Figure 13, another transfer device 6 for the double vial system 4 that provides mixing and transfer includes a vial holder 5 containing a first vial 16 and a second vial 15, a variable-volume pressure chamber 56, a fluid passage 35, and a check valve 40 for directing the contents 23 of the first vial 16 into the second vial 15 and the resulting contents 14 into the pressure chamber 56. The contents 14 are then transferred back into the second vial 15 and subsequently transferred to the injection device 7. In this embodiment, the inlet pipe 36 of the first vial access member 21 is exposed to the environment 57 to allow air 58 into the vial 16. The outlet pipe 37 of the first vial access member 21 is connected to the inlet pipe 51 of the second vial access member 52. The outlet pipe 53 of the second vial access member 52 is connected to the variable-volume pressure chamber 56. The fluid passage 35 includes a check valve 40 located between the first vial access member 21, the second vial access member 52, and the injection device 7.

[0040] As shown in Figure 13, the user's complete insertion of the vial holder 5 into the transfer device 6 allows access to the contents 23, 54 of each vial 15, 16 through the partition 19 of the vials 15, 16 by introducing vial access members 21, 52. This also triggers the release of the pressure chamber trigger, which releases the plunger 60 within the pressure chamber 56 connected to the retraction spring. The retraction spring forces the plunger 60 to retract the contents 23 from the first vial 16 and fill the second vial 15. This filling causes mixing of the contents 23 from the first vial 16 and the contents 54 from the second vial 15. The resulting contents 14 from the second vial 15 fill the pressure chamber 56 until all of the contents 23 have been removed from the first vial 16. The rate at which the first vial 16 fills the second vial 15 can be controlled by a check valve 40 or a flow throttling 55. The amount of contents 23 drawn in from the first vial 16 can be set by the manufacturer in the pressure chamber 56. Once the plunger 60 in the pressure chamber 56 is in the set position, it interacts with a dosing trigger that releases a dosing spring, forcing the contents 14 out of the pressure chamber 56 and back into the second vial 15. This is advantageous for further mixing the contents 23 from the first vial 16 and the contents 14 from the second vial 15. Once all of the contents 14 from the pressure chamber 56 has been administered, the contents 14 are transferred to the injector 7. The volume of the pressure chamber 56 can be set larger than the total fluid volume so that additional air 58 is drawn into the pressure chamber 56. The additional air 58 may help ensure that all of the contents 14 are transferred to the injector 7 or otherwise remain in the fluid passage 35. The check valve 40 can be used anywhere in the fluid passage 35 to prevent the contents 14 from returning to the first vial during the transfer of the contents 14 from the second vial 15 to the injection device 7. A flow restriction 55 can be used anywhere in the fluid passage 35 to control the mixing time in the second vial 15 before the transfer of the contents 14 to the injection device 7.

[0041] As shown in Figure 14, another transfer device 6 for the double vial system 4 that provides mixing and transfer includes a vial holder 5 having a first vial 16 and a second vial 15, a first variable-volume pressure chamber 56, a second variable-volume pressure chamber 42, a fluid passage 35, and a check valve 40 that directs the contents of the first vial 16 toward the second vial 15 and the resulting contents 14 toward the pressure chamber 56. The contents 14 are then transferred from the first pressure chamber 56 to the second pressure chamber 42 and then transferred to the injection device 7. In this embodiment, the inlet pipe 36 of the first vial access member 21 is exposed to the environment 57 to allow air 58 to enter the vial 16. The outlet pipe 37 of the first vial access member 21 is connected to the inlet pipe 51 of the second vial access member 52. The outlet pipe 53 of the second vial access member 52 is connected to the first variable-volume pressure chamber 56. The fluid passage 35 includes a check valve 40 located between the first vial access member 21, the second vial access member 52, the second pressure chamber 42, and the injection device 7.

[0042] As shown in Figure 14, the user's complete insertion of the vial holder 5 into the transfer device 6 allows access to the contents 23, 54 of each vial 15, 16 through the partition 19 of the vials 15, 16 by introducing the vial access members 21, 52. This also triggers the release of the pressure chamber trigger. The pressure chamber trigger releases the plunger 60 within the pressure chamber 56, which is connected to a retraction spring. The retraction spring forces the plunger 60 to retract the contents 23 from the first vial 16 and fill the second vial 15. This filling also mixes the contents 23 from the first vial 16 with the contents 54 from the second vial 15. The resulting contents 14 from the second vial 15 fill the pressure chamber 56 until all of the contents 23 have been removed from the first vial 16. The rate at which the first vial 16 fills the second vial 15 can be controlled by a check valve 40 or a flow throttling valve 55. The amount of contents 23 drawn from the first vial 16 can be set by the manufacturer in the pressure chamber 56. Once the plunger 60 in the pressure chamber 56 reaches the set position within the pressure chamber 56, it interacts with a dosing trigger that releases a dosing spring to force the contents 14 out of the pressure chamber 56 and back into the second vial 15. Once all the contents 14 have been dispensed from the pressure chamber 56 into the second vial 15, the contents 14 are transferred to the second pressure chamber 42, filling the second pressure chamber 42 to a limit allowed by a piston 46 selected by the user or manufacturer, corresponding to the desired dosage. Once the desired volume of the second pressure chamber is reached, the trigger of the second pressure chamber releases the second pressure chamber spring, forcing the piston 46 to advance and discharging the selected volume of injectable contents 14 under pressure into the injector. A check valve 40 may be used anywhere in the fluid passage 35 to prevent the contents 14 from returning to the first vial during the transfer of the contents 14 from the second vial 15 to the second pressure chamber 42 and the injector 7. A flow restriction 55 may be used anywhere in the fluid passage 35 to control the mixing time in the second vial 15 before the transfer of the contents 14 to the second pressure chamber 42.

[0043] As shown in Figure 15, another transfer device 6 for the twin vial system 4 that provides mixing and transfer includes a vial holder 5 having a first vial 16 and a second vial 15, a variable volume pressure chamber 56, a twin lumen connector 94, an inlet passage 95, an outlet passage 96, and a check valve 40 for directing the contents 23 of the first vial 16 through the inlet passage 95 to the pressure chamber 56 during the retraction of the plunger 60 in the pressure chamber 56. The forward movement of the plunger 60 after maximum retraction in the pressure chamber 56 causes the fluid contents 23 to flow from the pressure chamber 56 into the second vial 15, where it mixes with the contents of the second vial 15, and the resulting contents 14 flow into the injection device 7. The check valve 40 in the outlet passage 96 will prevent the contents 56 of the second vial 15 from being drawn into the pressure chamber 56 during the retraction phase. During the forward movement of the plunger 60, the check valve 40 in the inlet passage 95 prevents the contents 23 of the fluid in the pressure chamber 56 from being transferred back to the first vial 16. Check valves in the fluid passage 35 from the second vial 15 and the injection device 7 prevent the mixture from being transferred back from the injection device 7 to the second vial. A flow restriction 55 may be used anywhere in the fluid passages 35, 95, and 96 to control the fluid transfer rate. Alternatively, the use of a double lumen connector 94 may also be used in the single vial transfer system 1 to take fluid out of and advance fluid from different fluid passages.

[0044] As shown in Figure 16, the pressure chamber in the above embodiment may be configured with an outlet port 64 that is deflected or off-center compared to a normal syringe in order to utilize gravity. When the pressure chamber 59 is filled with contents 14 during the transfer process, there may be some air 58 introduced into the pressure chamber 59 in addition to the contents 14. During the process of releasing the contents 14 from the pressure chamber 59, it may be advantageous to control the order in which the air 58 or contents 14 are released from the pressure chamber 59. For example, if the outlet port 64 of the pressure chamber 59 is pointed downwards during the release of the contents 14 from the pressure chamber 59, the bubbles are directed upwards in the pressure chamber 59, so all the contents 14 are released first, followed by the remaining air 58 last. Conversely, if the outlet port 64 of the pressure chamber 59 is pointed upwards during the release of the contents 14 from the pressure chamber 59, all the air 58 is released first, followed by the remaining contents 14 last. This is particularly advantageous when a hydrophilic or hydrophobic filter is used to remove unwanted air 58 from the line during the transfer of the contents 14 to the injection device 7.

[0045] Transfer devices may use various devices or procedures to enhance mixing. For example, a transfer device may inject a diluent into a drug-containing vial in a swirling motion, and / or may use or introduce mixing-enhancing components such as dynamic or static mixers, such as a mixing ball, boat drill or propeller, or oscillating syringe. These techniques may be used in one of the second vials or syringes. Furthermore, a transfer device may have an intermediate chamber between the second vial access member and the outlet tube and pressure chamber for the aforementioned mixing-enhancing techniques and procedures. A transfer device may also be configured to induce turbulence by, for example, rotating the injectable vial, to introduce the vial of injectable drug in order to enhance mixing. To increase the transfer time for greater mixing, flow throttling may be used in the air or drug flow path.

[0046] As shown in Figures 16 and 17, an optional other feature of the transfer device 3 is a filter 65 in the fluid channel 35 for the injectable drug to filter the injectable contents 14 to remove particles before it is introduced into the injection device 7. The filter 65 may be a membrane, depth filter or other suitable filtering medium having a pore size small enough or effective pore size to remove undesirable particles, which may include, but are not limited to, undissolved injectable drugs in situations where the injectable drug is reconstituted by the transfer device 3.

[0047] As shown in Figures 16 and 17, the recovery of the injectable drug from the vial 15 may require or enhance the introduction of air (replacement air) 58 into the vial 15. In another aspect of this subject, the transfer device 3 may include a replacement air channel or hole 66 communicating with the inside of the vial to allow the introduction of air (replacement air) 58 into the vial 15 when the injectable contents 14 are drawn in. As discussed earlier, the vial access member 21 that pierces the vial partition 19 may have an inlet tube 36 and an outlet tube 37, one for the injectable contents 14 to flow out of the vial 15 and the other for the air (replacement air) 58 to flow into the vial 15. The air (replacement air) 58 flows through a fluid channel 35 in the transfer device 3, which may include a filter 65 such as a membrane or filter (depth filter, sterile filter) 65 with an actual or effective pore size of about 0.22 μm or less for filtering the air (replacement air) 58. The size of such holes is small enough to prevent pathogens from being introduced into the vial 15 by air (displacement air) 58, thereby reducing the risk of contamination of the injectable contents 14.

[0048] As shown in Figures 16 and 17, the transfer device 3 may include an air remover 67 communicating with the fluid passage 35 of the injectable contents 14 extending from the vial 15 to the injection device 7. An air remover 67 may include other components of the fluid passage 35 of the injectable contents 14, such as a bubble trap or air gap, which removes air 58 from the fluid passage 35 of the injectable contents 14 before the injectable contents 14 are introduced into the injection device 7. The air remover 67 may consist of a hydrophobic filter 6 or a combination of a hydrophobic filter 68 and a hydrophilic filter 69. The hydrophobic filter 68 allows air to be expelled from the transfer device 3 rather than the passage of the contents 14. The hydrophilic filter 69 allows the contents 14 to pass through, rather than particles or air 58. The combination of positions of the hydrophilic filter 69 within the fluid passage 35 preferably removes all air 58 during the transfer process.

[0049] As shown in Figures 18 and 19, the transport device 6 may have additional features beyond those described above. One such feature is a coupling device 70 between the dosage selection unit 48 and the vial holder docking area 29. This could be, for example, a mechanical interference member 97 that prevents the user from loading vials into the vial holder docking area 29 until a dosage is selected. Mechanically, the dosage selection unit 48 may even be coupled to the interference member 97 in the vial holder docking area 29, which is normally in the loading prevention position, to prevent insertion of the vial holder 5 into the vial holder docking area 29 until the dosage selection unit 48 is moved to the dosage selection position and then to the loading permission position. Naturally, the transport device does not need to include dosage selection capabilities if all injectable drugs are to be administered from a vial containing a single dose to be injected or from a single vial.

[0050] As shown in Figures 18 and 19, the transfer device 6 may include a connecting member 71 between the transfer device 6 and the injection device 7 to prevent the injection device from being removed before filling and to indicate that the injection device 7 is ready to be removed from the transfer device 6. Mechanically, a locking pin 72 may be connected to the injection device 7 by the transfer device 6 to prevent removal of the injection device 7 before it is fully filled. The locking pin 72 may be part of the transfer device 6 and may communicate with a piston in a second pressure chamber 42. When the second pressure chamber 42 releases all of the injectable contents 14, this mechanically induces the locking pin 72 to move away from the injection device 7, allowing the user to remove the injection device 7 from the transfer device 6.

[0051] As shown in Figure 18, the transfer device 6 may include a coupling device between the transfer device 6 and the injection device 7 to control how the injection device 7 is removed from the transfer device 6. Mechanically, flanges or other projections 73 on the injection device 7 may be mechanically coupled to notches in the transfer device 6. This configuration allows for unidirectional rotation of the injection device 7 relative to the transfer device 6 during removal by the user.

[0052] As shown in Figures 18 and 19, the transfer device 6 may include features to lock the injection device 7 to prevent it from being activated. For example, a mechanical interference member such as a locking pin 72, an arch, or other means may extend outside the transfer device 6 and mechanically lock the injection device 7 in the upper position with an actuator or button. Alternatively, the mechanical interference member 72 may be a shielding member that covers the entire injection device 7 to prevent access to the injection device 7 on the transfer device 6. The arch or shielding member (mechanical interference member 72) may be part of the transfer device 6 and communicate with a second pressure chamber 42. When the second pressure chamber 42 has released all of the contents 14 into the injection device 7, it may mechanically trigger the release of the lock on the arch or shielding member (mechanical interference member 72), causing it to move away from the injection device 7. This allows the user to access the injection device 7 and remove it from the transfer device 6.

[0053] Another optional feature of the transfer device is the rapid release of the filling port or access member between the transfer device and the injection device to allow for the rapid release of the injection device from the transfer device and prevent the injection device from coming into contact with the transfer device again. After the injection device is filled and ready to be removed from the transfer device, the user can remove the injection device. The filling tube (or access member) 83 of the transfer device may be a spring that is loaded when the injection device is removed from the transfer device, and the filling tube 83 is lowered into the transfer device by the spring. This prevents accidental leakage of the injection device at the filling port 81 and allows for the rapid release of the filling tube 83 from the filling port 81 of the injection device. This also prevents the user from accessing the filling tube 83 and prevents the injection device from coming into contact with the transfer device again.

[0054] As shown in Figure 18, the injection device 7 and the transfer device 6 are preferably configured for a detachable attachment of the injection device 7. In the present embodiment, after the transfer of the injectable contents 14 from the second pressure chamber 42 to the injection device 7 within the transfer device 6 and the release of the connecting member 71 on the transfer device 6, the injection device 7 is prepared to be separated from the injection device docking station 30 of the transfer device 6 for application to the target skin. As described above, another embodiment described herein involves the direct transfer of the injectable fluid from a single pressure chamber to the injection device.

[0055] As shown in Figure 20, the injection device 7 can be any suitable configuration. As previously described, the injection device may advantageously utilize one or more of the features of injection devices described in U.S. Patent Application No. 61 / 326,492 filed April 21, 2010, U.S. Patent Application No. 13 / 637,756 filed September 27, 2012, and U.S. Patent Application No. 61 / 704,922 filed September 24, 2012, which are incorporated herein by reference in their entirety.

[0056] As shown in Figures 20-22, the injection device 7 comprises a generally flattened, dish-shaped housing 74 having an upper surface 75 and a lower surface 76, from which an injection needle or cannula protrudes when activated by a user. The upper surface 75 for initiating the injection has an actuator or button 77 and a transparent portion 80 of the housing 74 for the subject or medical professional to visually inspect an expandable member 78 to confirm the amount of injectable fluid (drug, injectable drug) 79 in the injection device 7. For example, the user can determine whether the injection has been started or completed. More preferably, the expandable member 78 and / or the transparent portion 80 of the housing 74 may be marked with line markings 127, etc., so that the patient or medical professional can visually determine with good accuracy the amount of remaining injectable fluid 79, for example, about 50% complete or about 75% complete. Furthermore, the expandable member 78 may include or interact with other features of the housing 74 to indicate the amount of remaining injectable fluid 79. For example, when the injection device 7 is filled with fluid 79, the transparent portion 80 will show one color, but is not limited to, green. When the fluid 79 in the injection device 7 is empty, the transparent portion 80 may show another color, but is not limited to, red. During administration, the transparent portion 80 may show a combination of colors.

[0057] As shown in Figures 23-25, the lower surface 76 of the injection device 7 includes a filling port 81 and a dosing port 82. The filling port 81 is an interface that allows a transfer device to fill the filling tube 83 in order to transfer fluid 79 to the injection device 7. The dosing port 82 also includes a fluid channel (internal flow path 86) between the injectable fluid 79 released from the expandable member 78 and the needle (dosing needle, injection needle) 85. The filling port 81 and the dosing port 82 may communicate directly through the fluid channel (internal flow path 86) or may be coupled to a single port.

[0058] As shown in Figures 23-25, when the injection device 7 is removed from the transfer device 6 and the filling port 81 is removed from the filling tube 83, the injection device may preferably include a filling port 81 that includes a check valve 87 to prevent pressurized injectable fluid 79 from leaking out of the injection device 7.

[0059] As shown in Figures 23-25, the injection device 7 may also have a filling port 81 configured to accept the insertion of a syringe. This syringe may consist of a Luer connector or a needle. The configuration of the filling port 81 allows the user to manually fill the injection device. A transfer device 6 may still be used, but would not be necessary in this configuration.

[0060] As shown in Figures 23-25, the injection device 7 may also have an administration port 82 configured to connect directly to a venous cannula via an attached tube or a standard needle port.

[0061] As shown in Figures 23-25, the underside 76 of the injection device 7 carries adhesive 88 to temporarily secure the injection device 7 to the target skin until the injection is complete. The adhesive tape backing 89 may be automatically removed, exposing the adhesive surface 88 on the underside 76 of the injection device 7, so that it can be used to adhere the injection device 7 to the patient's skin during removal. Alternatively, the adhesive tape backing 89 may have a tab 90 for the user to pull to remove it by hand before the injection device 7 adheres to the skin. Alternatively, this tab may be attached to the surface of the transport device 6 so that the tape backing is automatically removed when the injection device 7 is removed.

[0062] As shown in Figures 23-25, the injection device 7 may have an adhesive flange 91 of adhesive tape that extends beyond the lower surface (base) 76. The adhesive flange 91 of the adhesive (adhesive tape) 88 can act to relieve strain between the injection device 7 and the skin surface, reducing the risk of the injection device 7 being accidentally removed from the skin. In other words, similar to the adhesive strain relief on a wire entering the connection, the extended adhesive flange 91 works to distribute the load to both sides of the connection point between the adhesive 88 and the lower surface (base) 76 of the injection device 7 in order to reduce stress concentration at the interface between the adhesive 88 and the skin.

[0063] As shown in Figures 23-25, the injection device may be configured such that the adhesive flange 91 has a tapered lower surface 98 that presses the adhesive 88 firmly against the skin, allowing the user to securely fix the injection device 7 to the skin without further user interference. When the injection device 7 is pressed against the skin, the tapered lower surface 98 of the injection device 7 effectively presses the flange 91 of the adhesive 88 against the skin using the conformity of human skin, but the exposed upper surface of the flange 91 does not have exposed adhesion and is therefore not attached to that portion of the tapered lower surface 98. The user does not need to run their fingers around the flange 91 to securely attach the injection device 7 to the skin, which considerably simplifies the method of applying the adhesive 88.

[0064] As shown in Figures 23-25, the injection device 7 may have a flexible or conformable lower surface 76 instead of being rigid in order to allow for improved mounting of the injection device 7 during application.

[0065] As shown in Figures 26-28, after the injection device 7 is pressed or adhered to the skin 99, the safety mechanism or lockout mechanism may be automatically released, and the injection device 7 is ready for injection. In other words, the injection device 7 is prevented from being activated (locked out) until it is placed on the skin. Alternatively, the user may manually remove a safety mechanism (safety device) 100, such as a safety pin, safety sleeve, or collar, to prepare the injection device for injection. The safety mechanism 100 may be activated passively or actively, manually by the user or automatically by the injection device 7.

[0066] As shown in Figures 26-28, the injection device 7 may use an actuator or button 77 in combination with a visual indicator 101 to define the state of the injection device 7 after it has been removed from the transporter. For example, when the button 77 is in the upper position and the indicator 101 is unspecified but has a single color such as green, the injection device 7 may indicate that it is ready to begin injection. Furthermore, the button 77 may have a side wall 102 that is a different color from the button top 103. When the button 77 is pressed, the user cannot see the side wall 102 of the button 77. This may indicate that the injection device 7 is in use. When the injection of the drug is complete, the injection device 7 may alert the user. This alert may be in the form of a visual indicator, an audible sound, a mechanical movement, or a combination thereof. The button 77 is ideally designed to provide the user with audible, visible, and tactile feedback when it appears in the lockout position. The injection device 7 may indicate to the user that administration is complete and the full dose has been delivered to the patient by having the button 77 in the upper position and the indicator (indicator window) 101 indicate that the injection device is empty. For example, the injection device 7 may indicate that the injection is complete when the button 77 is in the upper position and the indicator 101 shows a different color, such as red, but not limited to red.

[0067] As shown in Figures 29-31, the injection device 7 may be equipped with an actuator or a button 77 that the user presses on the injection device 7 to begin the injection. The button 77 may be configured to be an on / off switch, i.e., to have only two states, open and closed, like a light switch. This can prevent the user from pressing the button 77 only partway and not activating the injection device 7. Once activated, this “light switch” type button 77 will quickly insert the needle 85 into the skin 99, independently of the user’s operation of the button 77. Alternatively, the button 77 may have a continuous motion to allow the user to slowly insert the needle 85 into the skin 99. The button 77 may be preferably directly bonded to the needle 85 using the adhesive 104 that makes up the button 77 and the needle 85.

[0068] As shown in Figures 29-31, when the button 77 is activated, the injection device 7 moves the needle 85 into the skin 99 to advance to the first position or depth as shown in Figure 30, and then automatically retracts slightly to the second depth position as shown in Figure 31. The first depth shown in Figure 30 is reached by the movement of the button 77 during operation. The first depth can be controlled by a component 105 within the button 77, which is in direct contact with the base 106 of the injection device 7. The final depth of the needle 85 is suitable for subcutaneous injection. Alternatively, the final depth of the needle 85 may be reduced for intradermal injection. Alternatively, the final depth of the needle 85 may be increased for intramuscular injection. Immediately upon reaching the first depth, the needle 85 is retracted to the second depth as shown in Figure 31. The distance the needle is retracted to the second depth is in the range of 0.1-2 mm. This retraction function is preferred to prevent the needle 85 from being blocked by tissue during the initial insertion process. Obstruction of this tissue may require very high pressure to overcome, which could prevent the injector 7 from delivering the drug. The retraction of the needle 85 from the first position to the second position creates an open pocket in front of the needle tip 107, allowing a reduction in the pressure required to initiate the flow of drug from the needle 85. This pressure reduction for initiating the flow of drug from the needle is preferable for the injector 7 in order to maintain a relatively constant pressure during injection.

[0069] As shown in Figures 29-31, the injection device 7 may include a needle 85 with a lateral hole 108. As shown in Figure 31, once the button 77 of the injection device 7 is fully pressed, the needle 85 is fully inserted into the skin 99 through the administration port 82, and the injection device 7 begins administering the injectable drug. Until the button 77 is fully pressed, the lateral hole 108 and therefore the lumen of the needle 85 are not in communication with the fluid channel 86 of the administration port 82. Both the lateral hole 108 and the needle tip 107 are held within the septum 109. With the lateral hole 108 and needle tip 107 held within the septum 109, the entire drug pathway is kept sterile until use. When the button 77 is fully pressed and the needle 85 is in the administration position, the lateral hole 108 of the needle 85 communicates with the fluid channel 86 of the administration port 82, and the injection of the liquid begins.

[0070] As shown in Figures 29-31, the septum 109 offers the advantage of sealing the needle tip 107 and lateral hole 108 from the injectable drug before and after administration. Sealing the needle tip 107 and lateral hole 108 of the needle 85 at the end of the injection is particularly advantageous in preventing the injectable drug from dripping from the injection device 7 after the end of administration and / or removal from the skin surface. It also prevents contaminants from entering the needle hole before entering the skin. The septum 109 may be made of any suitable material that allows it to seal once the needle 85 has punctured. The material of the septum 109 is preferably silicone. Alternatively, the specific composition of the septum may include, but is not limited to, mixtures of different materials including bromobutyl, chlorobutyl, isoprene, polyisoprene, SBR, polybutadiene, EPDM, natural rubber and silicone. Alternatively, the fluid channel 86, including the administration port 82, may be a rigid plastic that is injection-molded to produce the aforementioned septum having silicone.

[0071] As shown in Figures 29-31, the partition 109 of the administration port 82 may protrude slightly into the surface of the skin 99 from the underside of the injection device 7 in order to pressurize the surface of the skin 99 at the injection site. This pressure on the surface of the skin 99 by the administration port 82 after the needle is retracted can eliminate the injectable drug coming out of the injection site, commonly known as recoil.

[0072] As shown in Figures 29-31, the injection device 7 may include a set of spring tabs 110 that engage with a button 77 for performing a locking function. As shown in Figure 29, the spring tabs 110 are deflected to lock into a notch 111 within the button 77 in order to position the button 77 in a first upper or pre-injection position. The shape of the notch 111 and the spring tabs 110 help to produce the illumination switch operation described above. This illumination switch operation is achieved by replacing the button 77 with the spring tabs 110 and fitting the surface of the notch 111.

[0073] As shown in Figures 29-31, the injection device 7 may include a spring tab 112 that interacts with a button 77 within the injection device 7 to perform a locking function, and when the button 77 is actuated to a first depth and slightly retracted to return to a second depth or the dosing position, a notch function 113 within the button 77 allows the spring tab 112 to hold the button 77 in the dosing position until the injection device 7 completes the administration.

[0074] As shown in Figures 32-33, the injector 7 may include a delivery indicator or empty indicator 114 to sense when all of the fluid 79 has been released from the expandable member 78 and the injector 7 has completed administration. The empty indicator 114 may be configured to have a slot or other opening 115 at the outlet port through which the expandable member 78 slides when the expandable member 78 is deflated after all of the fluid has been released. The empty indicator can be in two states. As shown in Figure 32, when the expandable member 78 is filled with fluid 79 and not contained within the slot or opening 115, the empty indicator may be in a first position or deflected outward. The first state can be rephrased as non-empty when the diameter of the expandable member 78 is greater than its minimum due to the residual fluid 79 contained inside. As shown in Figure 33, when the expandable member 78 is partially or completely contained within the slot or opening 115, the empty indicator 114 may be in a second position or deflected inward. When the diameter is at its minimum, the second position can be described as the empty state of the expandable member 78.

[0075] As shown in Figures 32-33, the injection device 7 may include a mechanism that automatically retracts the needle at the end of administration. This mechanism, as described above, includes a direct coupling between the spring tab 112, the button's notch function 113, and the empty indicator 114. When the expandable member 78 is filled with fluid 79 and the button 77 is pushed from the first pre-injection position to the second administration position, as shown in Figure 33, the button's notch function 113 allows the spring tab 112 to hold the button 77 in the administration position until the injection device 7 completes the administration. The spring tab 112 may also be directly coupled to the empty indicator 114, which is naturally in the first position or a position deflected outward. The movement of pushing the button 77 to the second position or administration position allows the spring tab 112 to deflect or apply an initial load, prompting the post function 116 in the button 77 to deflect the empty indicator 114 to the second position or inward. However, since the expandable member 78 is initially filled with injectable fluid 79 and has a large diameter, the empty indicator 114 cannot move to the second position or the inwardly deflected state, as shown in Figure 32. After the button 77 is pressed, the fluid 79 begins to be released from the expandable member 78 through the needle, as described above. Once the expandable member 78 has released all of the fluid 79 and is at its minimum diameter, the empty indicator 114 (under the initial load from the spring tab 112) moves to the second position or the inwardly deflected state, as shown in Figure 33. The spring tab 112, which is also directly coupled to the empty indicator 114, moves with the empty indicator 114. This movement releases the spring tab 112 from the notch function 113 in the button 77 in order to raise the button 77 (and needle) to the final or post-injection position after administration is complete, as shown in Figure 34.

[0076] As shown in Figure 34, the lockout spring tab 117 may interact with the button 77 within the injector 7 to perform a locking function when injection is complete and the button 77 is released and prompted by the return spring 118 to return the button 77 to the final or post-injection position. The height of the button 77 relative to the top of the injector 7 in the final or post-injection position (Figure 34) may be higher than in the pre-injection position (Figure 29). The end of the lockout spring tab 117 moves within the housing 74 toward the outer diameter surface 119 of the button 77 to lock the button 77 in the upper or post-injection position and prevent the button 77 from starting to act again.

[0077] As shown in Figure 34, the injection device 7 may include a return spring 118 that interacts with the button 77 to deflect the button to a first upper position or post-injection position. When the button is lowered to a second depth or administration position, the return spring 118 is compressed, causing further deflection or preload. At the end of the administration period, after administration is complete as described above, the button 77 is unlocked from the second depth or administration position (Figure 31) and raised to the final position or post-injection position. It is the deflection of the return spring 118 that forces the button 77 to rise to the final position or post-injection position.

[0078] As shown in Figures 34-35, upon removal of the injection device 7 from the skin 99, the injection device 7 is preferably locked out, thereby preventing non-destructive access to the needle or reuse of the injection device 7. The injection device 7 may inform the user that the complete dose has been delivered. This indication may be in the form of a visual indicator, an audible sound, a mechanical movement, or a combination thereof.

[0079] As shown in Figure 35, simultaneously with the removal of the injection device 7 from the skin 99, the bandage 120 may be released from the injection device 7 and remain on the surface of the skin 99. This may be influenced by the use of adhesive in the bandage portion that adheres more strongly to the skin than the adhesive that attaches the bandage to the injection device 7. When the housing is thus lifted from the skin, the bandage 120 remains on the injection area as described in U.S. Patent No. 7,637,891 and U.S. Patent Application No. 12 / 630,996 filed December 4, 2009, which are incorporated hereby by reference.

[0080] As shown in Figures 36-39, the injection device 7 may preferably include a manifold 121 assembled to an expandable member 78, a filling port 81, and a dosing port 82, providing direct fluid communication between the expandable member 78, the filling port 81, and the dosing port 82 of the injection device 7. As described above, the manifold 121 may be assembled to the end of the expandable member 78 and configured such that the expandable member 78 has a large diameter to facilitate filling and discharge of all fluid 79 out of the expandable member 78. The manifold 121 may preferably include an internal flow path 122 to allow fluid to flow in and out of the expandable member 78. The manifold 121 may be configured with a filter 123 to filter the injectable fluid 79 in the flow path 122 of the injectable fluid to remove particles before and after it is introduced into the expandable member 78. The filter 123 may be a membrane, depth filter, or other suitable filtration medium having a pore size that is small enough or effective enough to remove undesirable particulate matter. Undesirable particulate matter, though not limited to particulate matter, may include undissolved particulate matter 79 in situations where the injectable fluid 79 is reconstituted by the transfer device. The manifold 121 may also consist of a filter 123 for removal or air. Such a filter (air removal filter) 123 may include a bubble trap, an air gap of other configurations, within the injectable fluid flow path 122 to remove air from the injectable fluid flow path 122 before it is introduced into the expandable member 78. This filter 123 may consist of a hydrophobic filter or a combination of a hydrophobic filter and a hydrophilic filter. The hydrophobic filter prevents liquid from passing through while allowing air to be discharged from the transfer device. The hydrophilic filter prevents particulate matter or air from passing through while allowing liquid to pass through. To discharge trapped air, the filter 123 may also have a check valve. Alternatively, the filter 123 may be located at any position in the fluid flow path from the filling port 81 to the needle 85. For example, the furthest downstream point in the fluid flow path is the end 128 of the expandable member 78. The internal core 124 may be connected to the end 128 of the expandable member 78. A filter 123 may be integrated at this downstream point to allow for the discharge of trapped air while the injection device 7 is being filled.Furthermore, the core 124 may include slots along its length that communicate with a downstream filter 123 that helps expel air during the filling process.

[0081] As shown in Figures 36-39, the injection device 7 may include a strong expandable member 78, such as an elastic balloon or air bladder. The specific composition of the expandable member 78 is preferably silicone. Alternatively, the specific composition of the expandable member 78 may include, but not limited to, a mixture of different materials including bromobutyl, chlorobutyl, isoprene, polyisoprene, SBR, polybutadiene, EPDM, natural rubber, and silicone. In addition, the expandable member 78 may be coated to improve its surface properties. The coating may include parylene, silicone, Teflon, and fluorine gas treatment. Alternatively, the expandable member 78 may be made from a thermoplastic elastomer.

[0082] As shown in Figures 36-39, the injection device 7 may include a strong expandable member 78 into which the fluid 79 is transferred under pressure. This enlarges the expandable member 78, and the repulsive force of the expandable member 78 creates a pressure that tends to release the fluid 79. As described above, the pressure chamber of the transfer device (or other pump or pressurizing means used in the transfer device) transfers the fluid 79 to the injection device 7 under pressure. Introducing the fluid 79 into the expandable member 78 under pressure causes it to stretch and expand in diameter and length. An example of this is inflating a long, thin balloon. The volume range of the injection device 7 may be 0.5 to 30 milliliters. When expanded, as described above, the fluid 79 contained in the expandable member 78 causes the strong expandable member 78 to exert a release pressure in the range of 1 to 200 psi, so that the injection device 7 can be automatically prepared to administer the fluid 79 by being triggered by the user by pressing a button. Thus, the transfer device does not, as described above, transfer a measured amount of fluid 79 (which may be mixed, diluted, and filtered as needed) to the injection device 7 solely for the purpose of transfer, but rather simultaneously imposes or provides a forceful pressure on the injection device 7 (by expanding the strong expandable member 78) so that when activated by the user, the injection device 7 is ready to automatically dispense the fluid 79 under pressure that shakes the injection device 7, which is then shaken by the strong expandable member 78.

[0083] This aspect of the transfer device (simultaneous transfer and loading) is particularly beneficial. While the above application shows the injector 7 in an unfilled or loaded state for the injection of fluid 79 when the injector 7 is activated, in this disclosure, the injector 7 may remain empty and the expandable member 78 may be in a more relaxed and unfilled state, i.e., unloaded or unfilled, until the administration of the injectable fluid 79 is required. Only then is the injectable fluid 79 mixed or processed as needed and introduced into the injector 7, causing the expandable member 78 to expand to a filled (loaded) state. In this disclosure, the drug is stored in the initial sealed container (vial) until use. Since the fluid 79 is typically injected within a few seconds to a few hours after being transferred from the vial to the injector 7, the shelf life of the drug and the compatibility of materials in the fluid flow path within the injector 7 are not major concerns. The challenge and expense of designing the injector 7 and selecting materials for the long shelf life of a pre-filled injector 7 are considerably reduced.

[0084] As shown in Figures 36-39, the subject matter may utilize the features of the injection device 7 described in the patent application incorporated herein by reference, as previously stated. However, as illustrated, the expandable member 78 used in the injection device 7 herein may also preferably take the form of an elongated balloon or air bladder, for example, a planar helical or arranged in a helical configuration. As previously stated, the injection device 7 includes a circular housing (outer housing or injection housing) 74 in which a helical slot or recess (or slot, helical channel) 125 is made. The expandable member (elongated balloon or air bladder) 78 is placed in the recess 125, with one end communicating directly or indirectly with the needle 85 through the fluid channel 122, and the other end communicating directly or indirectly with the administration indicator 101. The elongated helical configuration gives the expandable member 78 a considerable volume for the desired amount of fluid 79, while also contributing to the inconspicuous configuration of the injection device 7. In other words, by utilizing a relatively long expandable member 78 with a considerable length-to-diameter ratio, this is achieved with the minimum force required, resulting in very high pressure and volume. Furthermore, by changing the filling length, the volume of the expandable member 78 can be changed without significantly altering the pressure / volume curve of the expandable member 78.

[0085] As shown in Figures 36-39, one of the other aspects used in the subject matter described in U.S. Patent Application No. 61 / 704,922 filed September 24, 2012, is the use of an insert or plug or spindle 124 for prestressing the expandable member 78 to a slightly expanded position when unfilled, within the expandable member 78. Thus, as shown in Figures 38 and 39, when the expandable member 78 releases the fluid 79, it is still stretched or under pressure, and continues to contract or deflate while pressure is exerted on the internal fluid. This better ensures that all or substantially all of the fluid 79 is completely released from the injector 7. The shaft or spindle 124 may be an expandable member filled with fluid as needed. This takes into account a variable-size spindle 124. Alternatively, the expandable member 78 may have a sufficiently small internal volume (small diameter) when unpressurized so that substantially all of the fluid 79 is released without the need for an internal shaft or spindle 124. Furthermore, the expandable member 78 can be flattened / stretched by "wrapping" its surface like a cylindrical wall 134 within the injection device. The prestress generated within the expandable member 78 will work to remove any remaining fluid volume inside.

[0086] As described above, there are several different ways to expand and / or arc the expandable member 78. Returning to Figure 34, one method is to design the expandable member 78 to have a thicker walled region 126 in one region around the circumference of the expandable member 78 that expands to circulate around the expandable member 78. Alternatively, the region (separating element) 126 may be attached along the length of the expandable member 78 to effectively stiffen the expandable member 78 in the circumferential portion that expands the expandable member 78 in an arc shape. Returning to Figure 36, another method is to use internal features such as slots or recesses 125 in the housing 74 of the injector 7 that guide the expandable member 78 around, for example, a circular or spiral passage. These features can interact with the expandable member 78 in several ways, most simply the shape of the expandable member being constrained by the recesses 125 in the housing 74 of the injector 7. Friction between the expandable member 78 and the recess 125 on the inner surface of the housing 74 can be reduced by applying oil to the outer surface of the expandable member 78, or by inserting the expandable member 78 into a spring with a low spring rate that limits friction and the outer diameter of the expandable member 78 but does not restrict its length.

[0087] As shown in Figures 36-39, the elongated expandable member 78 may preferably be configured to expand along an arc to a predetermined tube diameter within the range of the injection device without the help of a wall or guide. Looking at a cross-sectional view of the elongated expandable member 78 and returning to Figure 34, a thicker wall region 126 may be added to a small portion of the circumference of the expandable member 78 to expand in an arc as described above. The arc-shaped expandable member 78 increases in length due to the increase in internal pressure and volume, and the thicker region 126 is less deflected than the thinner region.

[0088] As shown in Figure 36, the arc-shaped expandable member 78 expands in length in an arc shape, deflecting the region inward from the circle to direct the region 126 below its heavy wall thickness. Increasing the wall thickness region 126 of the expandable member 78 within a small region 126 around the circumference effectively continues to decrease the radius of the arc of the expandable member 78. The increase in the wall thickness region 126 can be achieved by forming or extruding the arc-shaped expandable member 78 by joining small pieces of material to one side of the region 126 of the expandable member, or by causing that portion of the wall region 126 to stretch at a slower rate. This then causes the expandable member 78 to expand in an arc shape, as previously described.

[0089] As shown in Figure 37, the end of the expandable member 78 may be fitted with an element such as an indicator 101, which is then forced to follow a guide path within a recess 125 on the inner surface of the housing 74. Alternatively, the expandable member 78 may be pre-stretched and flattened around a circular diameter within the injection device 7, such as a wall 134, so as to be consistent with the length of the expandable member. Alternatively, a straight or curved mandrel 124, longer than the unstretched expandable member, may be used to pull the expandable member into a circular shape within the injection device 7 before filling. Alternatively, the mandrel 124 may be used as a visual indicator to show the state of the injection device 7 and the progress of injection. The mandrel 124 may be colored to allow it to be easily seen by the housing.

[0090] As shown in Figures 36-39, the fluid 79 is injected into the expandable member 78 with a transfer device, and the expandable member 78 is expanded to a specific outer diameter controlled by the configuration of the recess 125 on the inner surface of the housing 74. In this way, the entire length of the expandable member 78 can be filled with a known amount of fluid, and the outer diameter is known at each longitudinal location along the expandable member 78. It is desirable to fill and empty the expandable member 78 from one end to the other in a controlled manner, so as to completely empty the expandable member 78 and so as to allow for easy and accurate measurement of the fluid 79 inside the expandable member. To help visually determine how much fluid 79 is inside the expandable member 78, scale markings may be printed on the expandable member 78, such as a syringe, to indicate the volume remaining inside the expandable member 78. As mentioned above, and as shown in Figures 21-22, the expandable member 78 and housing 74 may be transparent to allow the user to see the fluid 79 and the volume remaining in the injector 7. Alternatively, scale markings 127 may be printed on the housing 74 to indicate the volume remaining in the expandable member 78.

[0091] As shown in Figures 36 to 39, according to the aspects of this subject described above, the injectable fluid 79 is preferably discharged in stages from the end 128 of the extended expandable member 78 toward the proximal end (proximal outlet port end) 129. The proximal end 129 of the expandable member is closest to the needle 85 or cannula. This allows the user to visually confirm or estimate the injection state, with or without the help of the transparent portion (window, indicator window, transparent area or other indicator) 80 on the housing 74 or the scale markings 127 on the expandable member 78. The staged discharge can be achieved in various ways. For example, the injectable fluid 79 exits from the expandable member 78 in a manifold 121 located at the proximal end 129 of the extended expandable member (e.g., balloon or air bag) in the area 130 of the proximal outlet port. The wall thickness of the expandable member 78 varies, may be constant, or increase in a stepwise direction along its length from the end 128 to the proximal end 129. Due to the constraints imposed by the wall of the recess 125 in which the expandable member 78 is placed, the expandable member 78 expands to a substantially single diameter along its length with the injectable fluid 79. However, the thicker wall at the end 128 of the expandable member 78 imposes greater constraints on the injectable fluid 79, while the thinner wall at the proximal end 129 causes the diameter to fold or shrink during the release of the injectable fluid 79. The expandable member 78 gradually folds from the end 128 to the proximal end 129 as the wall of the expandable member 78 becomes thicker along its length from the end 128 to the proximal end 129. The thickness of the expandable member 78 preferably increases substantially uniformly from the proximal end 129 to the terminal (or closed end) 128, so that the tension force on the walls of the expandable member 78 increases when expanded, substantially uniformly along the length of the expandable member 78 from the proximal end 129 to the terminal 128. Thus, when the injectable fluid 79 is released into the target, the expandable member 78 gradually folds in diameter and shortens in length, and the diametrical folding and lengthening are preferably visible to the user as described above. The terminal 128 of the expandable member may be connected to an indicator (movable indicator element) 101 of the injection device 7 that follows the lengthening of the extended expandable member 78.The indicator 101 is preferably visible to the user through the housing 74 and shows the status of the injection device 7 and the progress of injection. Alternatively, the expandable member 78 is constructed of a constant wall thickness, filled from the proximal end 129 to the terminal end 128, and prestressed during manufacturing to deflect it to fold or empty in a stepwise manner from the terminal end 128 to the proximal end 129 as described above.

[0092] As shown in Figures 36-39, the extended expandable member 78 of the injection device 7 may be configured to have a region 130 of the expandable member 78 adjacent to the proximal end 129 that is filled first and last folded during the filling and discharging of the injectable fluid 79 from the injection device 7. In other words, it is advantageous to have a region 130 at the most proximal outlet port end of the expandable member 78 where the injectable drug is first filled during the filling of the injection device 7 by the transfer device. Furthermore, it is advantageous to have the volume of the injectable fluid 79 that remains until the end in the region 130 at the most proximal outlet port of the expandable member during the administration of the injectable fluid 79 from the injection device 7. The above configuration has several advantages. The proximal end region 130 of the expandable member 78 may have a thin wall that remains inflated even under lower pressures than the rest of the expandable member 78. The region 130 of the expandable member 78 will certainly remain inflated until all of the injectable fluid 79 has been discharged from the rest of the expandable member 78. As previously discussed, area 130 may be directly coupled to a blank indicator to indicate filling or emptying. Furthermore, as previously discussed, area 130 may be mechanically coupled to a blank indicator to cause automatic retraction of the button 77 and needle 85 when the discharge of the injectable fluid 79 is complete.

[0093] As shown in Figures 36 to 39, in another or further modification of the wall thickness region 126 of the expandable member 78, the extended internal shaft or mandrel 124 within the expandable member 78 gradually (constantly or stepwise) reduces the cross-sectional area and length of the expandable member 78 from the proximal end 129 to the terminal (closed end) 128 of the expandable member 78. Furthermore, the manifold 121 that causes the expandable member 78 to be attached to the injection device 7 may also be configured to have a large diameter region 130 at the proximal end 129 of the expandable member 78. The large diameter region 130 of the mandrel 124 or manifold 121 at the proximal end 129 of the expandable member 78 ensures that the expandable member 78 first fills this region 129 with the injectable fluid 79. In other words, the expandable member 78 is held at its proximal end 129 with a nearly filled diameter by the large-diameter region 130 of the spindle 124 or manifold 121. The fluid 79 first fills the expandable member 78, first reaching the diameter of the large-diameter region 130, and then, as described above, gradually filling along the length of the expandable member 78 from the proximal end 129 toward the terminal end 128.

[0094] As shown in Figures 36-39, as previously described, during the administration of the injectable fluid 79 from the expandable member 78, the diameter of the expandable member 78 continues to gradually fold at the end (like a long, thin balloon contracting) from the end 128 towards the proximal end 129 until all the fluid has been released from the expandable member 78. The large-diameter area 130 of the spindle 124 or manifold 121 at the proximal end 129 of the expandable member 78 provides the same benefit (as described above regarding filling) during the administration of the injectable fluid 79. This large-diameter area 130 ensures that the last remaining fluid 79 in the expandable member 78 is contained within this area 130 and administered from there. As previously discussed, area 130 is directly coupled to the empty indicator to provide a filled or empty indication for the automatic retraction of the button 77 and needle 85 when the release of the injectable fluid 79 is complete.

[0095] [Operation and Instructions] As shown in Figures 40-42, the sterile injection device 7 is attached to the transport device 3 in a covered tray 132, and the separately packaged vial holder 2 with filled vials is provided in a carton 131. The user places the carton 131 on a clean, flat surface. To expose the assembly of the transport device 3 and the vial holder 2, the user opens the lid 133 onto the carton 131. To expose the transport device 3 and the injection device 7, the user removes the cover from the tray 132 of the transport device 3. When instructed, the user is instructed to remove only the injection device 7 and leave the transport device 3 in the carton 131.

[0096] As shown in Figures 43-44, when in use, the user removes the vial holder 2 assembly from the carton 131. Then, using the attached cap remover, the user removes the vial cap from the vial being used. The user inserts the vial holder 2 into the transfer device 3. The user pushes the vial holder 2 with the vial 16 attached to the transfer device 3 to move the system 1. This does three things in the illustrated embodiment. First, it captures the vial holder 2 with the vial 16 attached in a lower position within the range of the transfer device 3. Then, by introducing an access member through the vial partition, it automatically initiates fluid communication between the vial 16 and the contents 23 of the transfer device 3. Third, it moves the transfer device 3 sequence, starting mixing (if necessary). This sequence occurs automatically and does not require any further input from the user to proceed.

[0097] As shown in Figures 45-47, in a dual-vial system 4 where mixing is required, the user may have the ability to adjust the delivery dose. The dose selection unit 48 is moved from the initial position shown in Figure 46 to the final delivery dose position in Figure 47. Here, the vial holder 5 is to be freely pushed in by the user to initiate mixing and transfer. First, the diluent fluid is transferred from the diluent vial to the powdered, lyophilized, injectable vial. The fluid is brought to the powder vial in such a manner that all powder is removed as the fluid is transferred from the vial. Mixing of the diluent and powder may occur entirely in the powder vial or may be completed in the transfer device. Static or dynamic mixing elements may be taken into the transfer device or brought into the powder vial and diluent in the transfer device to thoroughly prepare the powdered drug or other injectable drug. Mixing may take up to several minutes to complete. Mixing is performed in the gentlest direction possible to minimize foaming / bubbling and shear stress. Mixing is carried out in such a manner that the powder is completely combined and no lumps are present. In-line filters, valves, or other means may be used to remove lumps or air. An indicator may be located above the transfer device to show that mixing is progressing.

[0098] As shown in Figures 45-47, in the double vial holder 5 system, the reconstituted solution is added to a powder vial or transfer device 6, and the set volume of solution, determined by the manufacturer or set by the user, is automatically adjusted in the pressure drinking chamber. This set volume is then automatically transferred to the injection device 7. To ensure that the maximum percentage of the drug is transferred to the injection device 7, the fluid flow volume between the tube, pipe valve, and any other vial and transfer device 6 is minimized.

[0099] As shown in Figures 48-50, once the required dose is delivered to the injector 7, the transparent sections 80,101 of the injector 7 allow the user to see the mixed solution to ensure complete mixing. Ideally, the user should be able to visually inspect the entire volume of medication within the range of the injector 7. An indicator (like a relative fill gauge) 101 may also be present to indicate that the correct dose has been delivered to the injector 7. The completion of mixing and transfer to the injector 7 then "unlocks" the injector 7, allowing it to be removed from the transfer device 3, 6 or the injector docking station. The injector 7 may indicate to the user that it is ready by having the button 77 in the up or ready position and the transparent sections 80,101 indicating that the injector is filled.

[0100] As shown in Figure 50, the user may detach the injection device 7 from the transport device 3 by twisting or removing the injection device 7 from the transport device 3. During the removal of the injection device 7, the adhesive tape lining may be automatically removed, exposing the adhesive surface on the bottom of the injection device used to adhere the device to the patient's skin. Alternatively, the tape liner may have tabs that the user pulls to manually transfer the device to the skin before it adheres.

[0101] As shown in Figure 51, the user places the injection device 7 on the skin 99. Adhesive may be present on the bottom of the injection device 7 to allow adhesion to the skin surface 99 and hands-free operation. The adhesive may spread beyond the contour of the injection device to allow the user to firmly attach the tape to the skin. Alternatively, the user may hold the injection device 7 firmly against the skin 99 during the injection.

[0102] As shown in Figures 51-53, the user removes the safety mechanism (safety device) 100 and presses button 77 on the injection device 7 to begin the injection. Once button 77 on the injection device 7 is fully pressed, it locks securely, the needle is fully inserted into the patient, and the injection device 7 begins dispensing the injectable medication. The injection device 7 may issue an alarm to the user indicating that the injection of medication has begun. This alarm may be in the form of a visual indication, an audible sound, a mechanical movement, or a combination thereof. The injection time can range from a few seconds to several hours. The injection device 7 may indicate to the user that the medication is being administered by the locked button 77 in the lower position and the indicator (indicator window) 101 showing that the injection device 7 is less than full. The injection device 7 preferably has a transparent section 80 that allows the user to easily measure the amount of medication remaining in the injection device 7.

[0103] As shown in Figure 54, the user is warned when the drug injection is complete. This warning may be in the form of a visual indicator, an audible sound, a mechanical movement, or a combination thereof. The injection device 7 may indicate to the user that administration is complete tactilely, with an audible sound, by moving button 77 to the lock-up position, or by an indicator (indicator window) 101 indicating that the injection device is empty. At the end of administration, the needle is automatically retracted to the locked position within the injection device 7.

[0104] As shown in Figure 54, simultaneously with the removal of the injection device 7 from the skin 99, the bandage 120 is released from the injection device 7 and may remain on the skin surface 99. Simultaneously with removal from the skin 99, the injection device 7 is preferably locked out and prevents non-destructive access to the needle or reuse of the injection device 7. The injection device 7 may inform the user that a complete dose has been delivered. This indication may be in the form of a visual indication, an audible sound, a mechanical movement, or a combination thereof.

[0105] To elaborate further on this subject, when administering an injection with a syringe and needle intended for subcutaneous injection, it is desirable to know whether the needle is properly positioned within the skin's boundaries or improperly within the blood vessels. For users administering intradermal (ID), subcutaneous (SC), or intramuscular (IM) injections, it is common practice to pull the syringe back by retracting the plunger to cause a pressure drop within the syringe's boundaries in order to see if visible blood is coming onto the needle. If blood is visualized, this indicates that the needle tip is in a blood vessel. Injectable medications intended for subcutaneous injection are specifically instructed not to be injected intravenously. Blood aspiration using a syringe and needle is a general skill and can be performed by anyone with sufficient training. However, more and more medications are indicated in autoinjectors, and the ability to manually aspiration blood with this type of system does not exist. Once the injection device is placed on the skin and the needle is fired, there is no way for the user to know whether the needle is properly positioned within the skin's boundaries or improperly within the blood vessels. Therefore, there is a need for blood aspiration devices and methods within autoinjectors.

[0106] As shown in Figures 55-56, the injection device 7 may allow a needle 85, which has a lateral hole 108 that engages with a button 77, to slide within the range of a septum 109 that advances into the skin 99. The button 77 may have a viewing window 160 in the button top 103, which is in fluid communication with the proximal end 161 of the needle 85. The button top 103 may contain a cavity 162 so that blood 159 can accumulate and be seen by the user through the viewing window (button window) 160. The cavity 162 may contain a central hole 163 that allows fluid communication with the proximal end 161 of the needle 85 through the lumen (needle lumen) 165. The outer wall 164 of the cavity 162 is formed by the button top 103. Furthermore, part of the outer wall 164 may contain a hydrophobic filter 166. In this configuration, the proximal end 161 of the needle 85 is at atmospheric pressure. If the contents 14 or blood 159 move onto the lumen 165 inside the needle 85, it exits the proximal end 161 of the needle 85 and fills the cavity 162. The air 167 in the cavity 162 is easily replaced by the hydrophobic filter 166 until all of the air 167 is removed from the cavity 162, and then it is filled with the contents 14 or blood 159. Here, the contents 14 or blood 159 cannot pass through the hydrophobic filter 166, the flow of contents 14 or blood 159 is stopped and can be easily seen by the user through the viewing window 160 on the top of the button 103.

[0107] As shown in Figure 56, upon activation (or pressing) of button 77, the needle 85 and button 77 move to the initial position or depth as shown in Figure 56. At this initial position or depth, the lateral hole 108 is covered by the septum 109, and therefore the lumen 165 of the needle 85 does not communicate with the fluid channel of the administration port 82. If the needle tip 107 is in the vein 158 at the first position or depth, the pressure in the vein 158 causes the blood 159 to rise through the lumen 165 toward the proximal end 161 of the needle 85, filling the cavity 162 with blood 159, which is visible through the viewing window 160 of the button top 103 of button 77, thus providing a way to determine whether the needle 85 of the injection device 7 is in the vein 158.

[0108] As shown in Figure 57, needle insertion into tissue can generally be divided into four stages. These include non-contact, boundary displacement, tip insertion, and shaft insertion. During boundary displacement, the tissue boundary in the contact area bends due to the load applied by the needle tip, but the needle tip has not yet penetrated the tissue. The skin boundary follows the needle tip in the contact area until the maximum boundary displacement point where the needle tip begins to penetrate the skin. After the needle tip has penetrated the skin, the shaft is inserted into the tissue. Even after the insertion of the tip and shaft, the skin boundary surface in the contact area does not return to its original non-contact state but remains displaced by a distance x. The amount of boundary displacement x is not limited but is a function of several parameters, including the needle diameter, the shape of the needle tip, the friction of the needle shaft, the needle insertion speed, and physical skin properties. The skin boundary displacement x in the contact area is characteristic in needle-based injection devices because it affects how far the needle penetrates the skin, and therefore the actual needle penetration depth can be reduced by the magnitude of the boundary displacement x. If boundary displacement x is intentionally induced by stretching or preloading the needle so that it pushes against the skin outside the contact area prior to the needle tip, then during insertion there will be no further boundary displacement by the needle tip or shaft, and the needle tip depth will be determined as expected. This intentional displacement is advantageous in that the amount of needle penetration into the tissue is not affected by changes in boundary displacement. If boundary displacement is not intentionally induced at the skin surface before insertion of the needle tip, the actual needle penetration depth into the skin is not specifically known. This is because, as shown in Figure 57, some of the needle length is outside the skin due to the naturally occurring boundary displacement x (depending on the parameters described above). On the other hand, if the maximum boundary displacement is induced at the contact area, the actual needle penetration depth will not change with respect to changes in the parameters described above, including the needle diameter, needle shape, friction of the needle shaft, needle insertion speed, and the physical properties of the skin.

[0109] As shown in Figure 58, the injection device 7 may have a skin boundary replacement extension or structure such as a lower surface 76 including an extension 138 in, around, or as part of the administration port 82. When the injection device 7 is placed against the skin 99, the extension 138 protrudes from the surface of the skin 99, causing displacement of the membrane 99 in this contact area 139. During the operation of the button 77 from the pre-injection state to the first position, the needle 85 advances from the injection device 7 through the administration port 82 and / or extension 138 into the skin 99 to begin drug administration. For the reasons stated above, as the needle 85 advances from the injection device 7, the needle tip 107 does not cause further boundary displacement 141 (already deliberately induced by the extension 138) in the contact area 139 of the skin 99. Thus, the actual needle penetration depth 140 into the skin 99 is better characterized and controlled.

[0110] As shown in Figure 60, the vial access member 21 of the transfer device 3 may have multiple lumens, for example, a multi-lumen tube 34, to communicate with the fluid passage 35 inside the transfer device 3. Preferably, the vial access member 21 includes one inlet tube 36 through which air or fluid enters the vial 12, and one outlet tube 37 through which air or fluid exits the vial 12. As shown in Figure 59, for example, when the vial is inverted, the lumen opening 38 of the vial access member 21 may be oriented such that the opening of the inlet tube 36 is above the opening of the outlet tube 37. This orientation allows air or liquid to be introduced into the vial through the upper inlet tube 36 and exited through the lower outlet tube 37. Furthermore, the opening of the outlet tube 37 may be located near the lower end of the inverted vial 12, adjacent to the partition wall 19, so that all the contents 14 of the vial 12 enter the outlet tube 37 and are removed from the vial 12. When the vial 12 is placed in the vial holder docking area 29 of the transfer device 3, the vial access member 21 can access the contents 14 of the vial 12. As the transfer device 3 draws the contents 14 from the vial 12 to the outlet tube 37, a pressure drop 154 ​​occurs in the vial 12. This pressure drop 154 ​​causes air (replacement air) 58 to be drawn into the vial 12 through the opening of the inlet tube 36 of the vial access member 21, replacing the drawn-in contents 14. In some cases, depending on the amount of contents 14 in the vial 12, the liquid level 153 of the vial 12 may be above the vial access member 21, and specifically above the opening of the inlet tube 36. When air 58 is drawn into the vial 12 through the opening of the inlet tube 36, it creates bubbles 155 in the contents 14. Buoyancy causes the bubbles 155 to move to the top of the vial 12 along with the existing air 58. In some contents 14, it is undesirable to introduce bubbles (air bubbles) 155 into the solution. This causes more foaming and leads to bubbles, fizzing, and effervescence within the contents 14.

[0111] As shown in Figure 61, the expandable member 156 can be slidably moved within the opening of the inlet tube 36 of the vial access member 21. The outer diameter of the expandable member 156 may be in close contact with the inner diameter of the opening of the inlet tube 36. The expandable member 156 may have an inner diameter that allows air 58 to pass through. When air 58 is drawn into the vial 12 through the opening of the inlet tube 36 due to the pressure drop 154 ​​in the vial 12, the air 58 initially pushes the piston-like expandable member 156 within the opening of the inlet tube 36. The expandable member 156 is long enough not to extend beyond the opening of the inlet tube 36. The expandable member 156 continues to slide through the opening of the inlet tube 36 until its end rises above the liquid level 153 in the vial and stops at the top 157 of the vial 12. The inverted lid of the vial 12 serves to stop the expandable member 156. The tip of the expansion member 156 may be tapered so as not to obstruct the flow through its inner diameter when it contacts the top of the inverted vial 12. Air 58 continues to move within the inner diameter of the expandable member 156 until all of the contents 14 in the vial 12 have been removed from the vial 12 to the outlet tube 37. As described above, the outer diameter of the expandable member 156 is in close contact with the inner diameter of the opening of the inlet tube 36, preventing air leakage at this contact surface. The expandable member 156 ensures that air 58 does not enter the vial 12 and cause bubbles 155.

[0112] As shown in Figure 62, the pressure chamber 59 may be configured with an inlet port 168 that brings contents 14 and air 58 into the chamber. Furthermore, the pressure chamber 59 may be configured to have an outlet port 64 for ejecting contents 14 and air 58 from the pressure chamber 59. These ports 168, 64 may be offset from the center of the pressure chamber 59 to help control the flow of contents 14 and air 58 introduced into and / or discharged from the pressure chamber 59. As previously stated, the outlet port 64 of the pressure chamber 59 is located below the inlet port, and during the discharge of contents 14 from the pressure chamber 59, all contents 14 are discharged first, and then the remaining air 58 is discharged last. All air in the pressure chamber 59 is directed upward toward the top of the pressure chamber 59. Furthermore, as shown in Figure 62, the shape of the outlet port may be non-circular in order to allow all the liquid contents 14 in the pressure chamber 59 to exit through the outlet port 64 and be removed from the pressure chamber 59 before the air is removed from the pressure chamber 59. Furthermore, as shown in Figure 62, a portion 170 of the outlet port 64 may be placed below the surface 171 of the pressure chamber 59. This can act as a trap to allow all the liquid contents to enter the outlet port 64 from the pressure chamber 59 and be removed from the pressure chamber 59 prior to the removal of the air 58 from the pressure chamber 59.

[0113] As shown in Figure 63, when the contents 14 are removed from the vial 12 using the vial access member 21, only the contents 14 are removed through the opening of the outlet tube 37 until the liquid level 153 falls below the top of the opening of the outlet tube 37. At this time, the mixture of contents 14 and air 58 is removed. As shown in Figure 63, the vial access member 21 may have an opening in the outlet tube 37 that is further configured to be non-circular in shape, by reducing the height of the opening and increasing the width of the opening to allow more liquid contents 14 from the vial 12 into the outlet tube 37 and remove it before removing the air from the vial 12.

[0114] As shown in Figures 64 and 65, the combination of a hydrophobic filter 68 and a hydrophilic filter 69 in the fluid channel 35 between the vial 15 and the injection device 7 preferably allows for filtration of the contents 14 and removal of air 58 during the transfer process. These filters may be separate elements or combined into a single element. Each filter may be composed of different materials, but are not limited to, mixed cellulose ester (MCE), polymerized vinylidene difluoride (PVDF), polytetrafluoroethylene (PTFE), nylon, and polyethersulfone (PES). Each filter may have a pore size in the range of 0.22 to 3 μm. Each filter is coated to be hydrophobic or hydrophilic.

[0115] When administering injections intended to be delivered under the skin, a common reaction is swelling of the injection site. This reaction is particularly pronounced in subcutaneous locations where the injection volume is high and / or the injection rate is fast. If the injection is performed using a syringe, needle, and dosing set, swelling of the injection site does not affect the injection device. However, as more drugs are used in autoinjectors that are attached to the body during injection, swelling of the injection site presents difficulties in securely keeping the autoinjector on the body. In particular, if the adhesive of the injection device is not properly designed, lumps or bulges formed by the solution injected onto the skin surface may cause the autoinjector to detach from the injection site. Therefore, there is a need for autoinjectors with properly designed adhesives that allow swelling at the injection site without compromising the device's adhesion to the patient.

[0116] As shown in Figure 66, there are two interfaces for adhering the injection device 7 to the skin 99. The first is the adhesive / device interface 173, and the second is the adhesive / skin interface 174.

[0117] As shown in Figure 67, the adhesive 88 may be configured in an injection device 7 having at least two regions. The first region 175 may contain a permanent adhesive between the adhesive 88 and the injection device 7 using mechanical or chemical means, and may be located within the periphery of the injection device 7. The second region 176 may be configured adjacent to the outside of region 1 (for example, radially outward) so that it can be peeled off or removed from the injection device 7.

[0118] As shown in Figure 68, if the adhesive 88 is completely attached to the bottom surface (bottom) 76 of the injection device 7, this adhesive / skin interface 174 is weaker than the adhesive / device interface 173, so during the tissue bulge 177, the adhesive at the adhesive / skin interface 174 will begin to peel away from the skin 99. This is shown in the bulging surface shown in Figure 68. This will cause the injection device 7 to detach from the surface of the skin 99 and fall from the patient.

[0119] As shown in Figures 67 and 69, instead of completely and permanently attaching the adhesive 88 to the underside (bottom) 76 of the injection device 7 as shown in Figure 68, the adhesive 88 may be configured in the aforementioned regions 175, 176 of the injection device 7. In this configuration, while tissue swelling 177 occurs, the adhesive 88 in the second region 176 detaches from the injection device 7 and adheres firmly to the skin 99 at the adhesive / skin interface 174. This allows for the transfer of the skin edge 178 from the adhesive / skin interface 174 to the adhesive / device interface 173, effectively relieving distortion at the adhesive / skin interface. The adhesive / device interface 173 may be designed to be stronger, preventing the injection device 7 from separating from the surface of the skin 99.

[0120] When self-injecting using an automated injection device, protecting the user from needle-stick injuries is a valuable requirement for the device. Generally, the needle is retracted within the device's range before and after use, preventing the user from accessing it. However, during injection, the needle is extended outside the device. If a user falls carelessly during injection while wearing the automated injection device, the needle poses a potential risk of needle-stick injury. Therefore, automated injection devices require a skin removal sensor that automatically retracts the needle if the device becomes dislodged from the skin during injection.

[0121] As shown in Figures 70-72, the skin removal sensor 179 is operably engaged with a flexible latch 181 on the button 77 and is slidable within the lower housing 180 of the injection device 7. As shown in Figure 71, when the injection device 7 is attached to the surface of the skin 99, the skin removal sensor 179 is forced to be in a first or upper position 182 on the injection device 7. When the button 77 is activated to the ejection position or the second or dosing position (exposing the needle 85), the flexible latch 181 is forced by the skin removal sensor 179 to be in a locked position 187 under the latch plate 183. The latch plate 183 holds the button 77 on the latch plate surface 84, with the button 77 pressed in the ejection position or in the dosing position until dosing is complete. At the end of dosing, the latch plate 183 is released from the latch plate surface 184 on the button 77, the button 77 and needle 85 are retracted to the post-ejection position, and the needle is retracted into the injection device 7. As shown in Figure 72, if the injection device 7 is removed from the surface of the skin 99 during injection, the skin removal sensor 179 extends to a second or lower position 185 outside the injection device 7. This springs back the flexible latch 181 to the unlocked position, separating it from the latch plate 183. This also retracts the button 77 and the needle 85 to the post-launch position, with the needle 85 housed inside the injection device 7.

[0122] When self-injecting with a syringe and needle, the user may need to temporarily stop or interrupt the injection due to severe pain or irritation at the injection site. This interruption of the flow of injectable medication to the injection site is achieved by releasing the pressure on the plunger rod of the syringe, allowing for a larger dose of the injectable medication fluid, giving it more time to diffuse into the surrounding tissue, reducing local pressure, and thus reducing the associated pain and inflammation. However, more medications are indicated by autoinjectors, and it is not possible to manually interrupt this type of automated system. Once the autoinjector is placed on the skin and the cannula is withdrawn, there is no way for the user to pause the injection due to pain or irritation at the injection site. Therefore, there is a need for the user to be able to pause the autoinjector system.

[0123] As shown in Figures 73-74, upon activation of the button 77, the needle 85 and the button 77 move to a first position or depth, as shown in Figure 73. In this first position or depth, the lateral opening 108 is covered by the partition 109. Therefore, the lumen 165 of the needle 85 is not in communication with the fluid channel 86 of the administration port 82. The button 77 is intentionally held in the first position or depth to prevent the injectable contents 14 from flowing through the fluid channel 86 into the lateral opening 108 of the needle 85 and into the skin 99. As shown in Figure 74, when the button 77 is released, the needle 85 and the button 77 return to a second position or administration position, the lateral opening 108 is exposed to the fluid channel 86, and the injectable contents 14 are allowed to flow from the fluid channel 86 into the lateral opening 108 of the needle 85 and into the skin 99 until the end of the injection. This action of pressing the button 77 to the first position or depth can be performed as many times as necessary throughout the entire injection.

[0124] As shown in Figures 75-76, the force (actuating force, load) 186 of the button 77 is the transfer of load applied to the button 77 when the button 77 and needle 85 are required to begin displacement from the pre-injection position to the injection or administration position. Until this transfer load is met, the force 186 on the button 77 is transferred directly to the injection device 7. In particular, this force 186 may be transferred to the adhesive / skin interface 174 and / or adhesive / device interface 173, resulting in better certainty of the injection device 7 onto the surface of the skin 99 before the injection device 7 is activated.

[0125] As shown in Figure 77, an indicator window 172 of the transfer device 3 may be present to indicate that the transfer and / or mixing of the contents 14 is in progress. The indicator window 172 may be configured in the base of the transfer device 3 and may track the movement of the plunger 93 in the pressure chamber 56 within the transfer device 3. The indicator window 172 may be configured with a scale or other means to track the movement of the plunger 93. Alternatively, the plunger 93 may be configured with different colors to facilitate tracking its movement within the indicator window 172. The combination of the indicator window 172 and the plunger 93 may provide progress in the drawing of the contents 14 from the vial 12 and filling of the pressure chamber 56. The combination of the indicator window 172 and the plunger 93 may also provide progress in the transfer of the contents 14 from the pressure chamber 56 to the injection device 7.

[0126] As shown in Figures 78-79, the arched expandable member 78 is arranged in an arch shape in length and / or, preferably, is stretched. In the illustrated embodiment, the arching is induced by providing a region of less strength, such as a thicker or heavier wall region 126. In that region, the expandable member will bend less, forming an expanded arch. The thicker wall region 126 can be configured in any shape that causes the expandable member 78 to arch during expansion. A more preferred structure of the thicker wall region 126 is to minimize its thickness or the circumferential mounting 150 of the expandable member 78 on the wall, and to minimize its radial thickness or projections 151 away from the expandable member 78. This helps to encourage the expandable member 78 to expand into an arch shape, while minimizing the amount of surrounding material that is not affected by the thicker wall region 126 for expansion. A T-shaped configuration, though not limited to this, may be configured at the ends of radial projections 152 to help the expandable member 78 expand into an arch shape.

[0127] As shown in Figure 80, the volume of the pressure chamber 56 may be set to be greater than the volume of the total fluid in the vial 15 in order to draw additional air 58 from the vial 15 into the pressure chamber 56. This additional air may help to ensure that all contents 14 are removed from the vial 15 and that any remaining contents 14 are removed and cleaned from the fluid passage 35 between the vial 15 and the pressure chamber 56. Furthermore, during the transfer of contents 14 from the pressure chamber 56 to the injection device 7, additional air may help to remove or clean any remaining contents 14 in the fluid passage 35 between the pressure chamber 56 and the injection device 7.

[0128] As shown in Figure 81, the transfer device 3 includes a vial holder docking area 29 which may include an elongated vial access member 21. The vial holder docking area 29 may include a vial access protection section 136. The vial access protection section 136 is locked and held in the vial holder docking area 29 at a first position above the vial access member 21 by a locking finger 137 to cover the vial access member 21 prior to the insertion of a vial 12 or vial holder, preventing the vial access member from inadvertently pricking the user. When a vial 12 or vial holder is inserted into the vial holder docking area 29, the vial 12 or vial holder displaces the locking finger 137, releasing the lock on the vial access protection section 136. Once released, the vial access protection section 136 can slide and move together with the vial 12 or vial holder within the vial holder docking area 29.

[0129] As shown in Figure 82, a flow restriction 55 may be used to control and / or delay the transfer time and / or increase the mixing time within the fluid passage 35. Smaller lumen tubes may be used to restrict the flow at any point in the fluid passage 35 and increase the mixing / transfer time to more than one hour. One way to control and / or delay the transfer time and / or increase the mixing time between the second pressure chamber 42 and the injector 7 is to use a multi-lumen fluid passage 142 between the second pressure chamber 42 and the injector 7. Each lumen 143,144 of the fluid passage 142 is positioned at specific locations 145,146 in the second pressure chamber 42, preferably spaced by the distance the piston travels, with inner diameters 147,148 having a size that gives a specific flow velocity through the lumen 143,144 based on the pressure in the second pressure chamber 42. Initially, when the piston 46 of the second pressure chamber begins to move forward within the second pressure chamber 42, the fluid contents 14 are injected into the fluid flow path 142 through all the lumens 143 and 144 toward the injection device 7. When the piston passes the attachment point 145 between the lumen 143 and the second pressure chamber 42, the fluid flow through that lumen 143 stops, and the contents 14 are forced to flow through the remaining lumen 144. Multiple lumens and attachment points can be arranged along the pressure chamber. The final lumen 144 available from the flow of contents 14 will have a very small inner diameter. Thus, the flow velocity will be very slow, and the time to transfer the contents 14 from the second pressure chamber 42 to the injection device 7 will increase. This transfer delay increases the mixing time.

[0130] As shown in Figure 83, a safety mechanism (safety device) 100, such as a safety pin or safety sleeve, may be configured to be detached from the injection device 7 in any direction of release in order to release the injection device 7 for preparation for injection.

[0131] As shown in Figure 84, when the button 77 of the injection device 7 is fully pressed, the injection device 7 includes a needle 85 with a lateral hole 108 that allows fluid communication between the fluid channel 86 and the skin 99. This initiation administers the injectable contents 14. The lumen 165 of the needle 85 is important in controlling the rate at which fluid is administered from the injection device 7. Referring to the Hagen-Poiseuille equation for fluid flow in a tube, the flow velocity through the tube is proportional to the fourth power of the tube's radius. Therefore, even a small change in the inner diameter of the needle 85 significantly alters the flow through the needle 85, especially when the lumen 165 is small. The needle 85 in the injection device 7 can range from 21G to 34G (Stubs Iron Wire Gauge System) for various wall thicknesses. This range corresponds to a range of 0.021” to 0.003” of the inner diameter of the lumen 165 of the needle, with manufacturing variations and tolerances for any given needle size. This is based on needle size, with an inner diameter variation of approximately ±0.00075”. Regardless of the needle size, the needle 85 may be modified before being assembled into the injection device 7 to limit the range of inner diameter of the lumen 165 and consequently limit flow variation. This modification may include bending, flattening, or rolling the needle from round to non-round, for more than a portion of its length, to a new, defined effective inner diameter of the lumen 165. This has the advantage of allowing control of a specific delivery rate from the injection device 7.

[0132] As shown in Figures 85-86, the luminal opening 38 of the vial access member 21 can be directed to allow pressurized air or liquid to be introduced through the upper inlet tube 36 and to output the contents 14 of the vial through the lower outlet tube 37. Furthermore, the opening of the outlet tube 37 can be positioned near the bottom of the inverted vial 12, adjacent to the partition 19, so that all the contents 14 of the vial 12 enter the outlet tube 37 and are removed from the vial 12. The preferred order for removing the contents 14 from the vial 12 is first all the contents 14 in the vial 12, and then the air 58 from the vial 12. This is achieved in the current embodiment when the direction of the transfer device 3 is directed as shown in Figures 85-86. Based on the shape of the vial access member 21 inside the vial 12, this order of removal of all contents 23 and then air 58 can be achieved when the angle of the transfer device 3 is from horizontal to ±45°. Beyond this angle, air 58 is introduced during the removal of the contents 14 from the vial 12. A sensor (angle sensor) 149 is positioned inside or around the vial access member 21 to sense the angle of the transfer device 3. It may have direct communication with each or both of the lumen openings 38 and / or between each or both of the inlet and outlet pipes 36 and 37. In the current embodiment shown in Figure 85, when the transfer device 3 is at an angle less than 45°, the sensor 149 allows fluid communication between the outlet pipe 37 and the fluid passage 35. As shown in Figure 86, if the transfer device 3 is tilted greater than 45°, the sensor 149 rotates or moves to a new position to block the fluid communication between the outlet pipe 37 and the fluid passage 35.

[0133] As shown in Figure 87, a separate transfer device 3 is provided within the single vial system that does not perform mixing but transfers the contents 14 from a single vial 12 to an injection device 7. This separate transfer device 3 includes a vial 12, a variable-volume pressure chamber 56, and a fluid passage 35 to direct the contents 14 from the vial 12 to the injection device 7. The inlet pipe 36 of the vial access member 21 is connected to the variable-volume pressure chamber 56 having the fluid passage 35. The outlet pipe 37 of the vial access member 21 is connected to the injection device 7 through the pressure chamber 56 of the fluid passage.

[0134] As shown in Figure 87, the user's full insertion of the vial 12 into the transfer device 3 causes the introduction of the vial access member 21 through the partition 19 of the vial 12 to access the contents 14 of the vial 12. This also triggers the release of the pressure chamber trigger 49. With the plunger 60 in the retracted position, the pressure chamber 56 is filled with air 135. The trigger 49 releases the plunger 60 into the pressure chamber 56, which is connected to the dosing spring 63. The dosing spring 63 advances the plunger 60, causing the air 135 to be replaced from the pressure chamber 56 into the single vial 12 through the inlet tube 36. The air 135 entering the vial 12, through the outlet tube 37, replaces the contents 14 outside the vial 12 into the injection device 7. This continues until all the contents 14 have been replaced outside the vial 12 into the injection device 7. The check valve 40 may be used to prevent the contents 14 from returning to the vial 12, or to prevent the contents 14 from returning to the pressure chamber 56.

[0135] This subject is described solely for explanatory purposes, not as a limitation, and in relation to specific examples. The scope of the subject matter is not limited to the illustrated embodiments or their equivalents, and it should be understood that there are broader embodiments with applications in modified configurations and uses, some of which will become immediately apparent upon reading this description and others, and others that will become apparent after some study and / or development.

Claims

1. An apparatus for filtering liquid medicine, including a liquid medicine transfer device, a. A housing including an injectable fluid passage, comprising a vial receiving portion and a liquid outlet port, wherein the injectable fluid passage includes an injectable fluid passage inlet configured to receive a liquid drug from a vial placed in the vial receiving portion and an injectable fluid outlet that is in fluid communication with the liquid outlet port, b. A liquid drug filter having a liquid drug pore size or liquid drug effective pore size, which is disposed within the injectable fluid passage and configured to remove particulate matter, c. The housing of the transfer device further includes a displacement air passage having a displacement air passage inlet that is in fluid communication with a source of displacement air pressurized to a predetermined pressure, a displacement air passage outlet configured to guide the displacement air into a vial, and a displacement air filter having a sufficiently small pore size to prevent pathogens from being introduced into the vial. d. The liquid drug filter is a hydrophilic filter, Furthermore, it is equipped with a hydrophobic filter and a vent filter housing, The vent filter housing is positioned in the injectable fluid passage and houses the hydrophobic filter and the hydrophilic filter of the liquid drug, The hydrophobic filter is in fluid communication with a vent that exhausts air from the transfer device in order to remove air during the transfer process of the liquid drug. The apparatus wherein the hydrophilic filter of the liquid drug is in fluid communication with the liquid outlet port.

2. The transfer device is configured to reconstitute the freeze-dried drug as the liquid drug. The apparatus according to claim 1, wherein the liquid drug pore diameter or the liquid drug effective pore diameter is configured to remove undissolved freeze-dried drug.

3. The apparatus according to claim 1, wherein the displacement air filter has a pore size or effective pore size of approximately 0.22 μm or less.

4. The apparatus according to claim 1, wherein the displacement air filter is a membrane.

5. The apparatus according to claim 1, wherein the displacement air filter is a depth filter.

6. The apparatus according to claim 1, wherein the inlet for the displacement air passage is a vent, and the source of the displacement air is the atmosphere.

7. The apparatus according to claim 1, wherein the hydrophilic filter for the liquid drug has a pore size or effective pore size that is at least partially based on the predetermined pressure so that displacement air does not pass through the liquid outlet port.

8. Includes a liquid drug injection device, The housing includes a skin-facing surface that includes a needle opening from which the injection needle extends, The apparatus according to claim 1, wherein the injection needle has an injection needle lumen that is in fluid communication with the outlet of the injectable fluid passage.

9. The apparatus according to claim 8, further comprising, within the housing, an elastic bag that is expandable in an arc shape and configured to hold a certain volume of liquid medicine, wherein the expandable elastic bag is in fluid communication with the inlet of the injectable fluid passage.

Images