Patent Description:
Individuals with chronic medical conditions often use infusion sets to deliver medication from a pump to an insertion site on the body. For example, patients with insulin-dependent diabetes (also referred to simply as "diabetes") who use continuous insulin infusion therapy often use insulin infusion sets to deliver insulin through an insertion site on the abdomen, thigh, arm, lower back, or buttock. The infusion set carries insulin from the pump through a tube to a needle or cannula mounted on an insertion hub and inserted into a subcutaneous space on the patient's body.

Patients using an infusion set to deliver a medication to the insertion site may desire delivery of a second medication in addition to the primary medication. For example, patients with insulin-dependent diabetes may experience hypoglycemic events in which their glucose levels drop too low. This can happen, for instance, when the patient administers too much insulin, when the patient exercises, when the patient has not eaten for an extended time, or when the patient is asleep for an extended time. If the hypoglycemic event is mild, it may be treated by ingesting fast-acting carbohydrates. However, in cases of severe hypoglycemia and/or when the patient is unable to eat or drink, it may be treated by administering one or more therapeutic agents operative to raise a patient's glucose levels (e.g., blood glucose levels or interstitial glucose levels), such as glucagon, glucagon analogs, glucagon derivatives (simply referred to herein as "glucagon").

Glucagon may be administered using an emergency glucagon kit. Such emergency kits may comprise an injection device that stores a single, full dose of glucagon and, when pressed against a portion of the patient's body and activated, injects the entire dose via a subcutaneous needle injection. Alternatively, such emergency kits may comprise one or more vials of glucagon and a syringe that the patient may manually fill and inject. However, these emergency glucagon kits may suffer from several disadvantages.

For example, patients with diabetes are generally already burdened by the need to carry and manage various devices and supplies, such as a blood-glucose monitor (BGM), a continuous-glucose monitor (CGM), insulin pump lancing device, spare lancets, infusion sets, pump cartridges, alcohol swabs, adhesives, syringes, insulin, and/or fast-acting carbohydrates. The cognitive and emotional load of carrying a separate emergency glucagon kit in addition to all these devices and supplies may take a toll, and many patients may refuse or forget to carry an emergency glucagon kit with them.

Furthermore, emergency glucagon kits require a separate subcutaneous injection to administer glucagon (i.e., separate from a pre-inserted infusion hub delivering the primary drug), thereby requiring another injection site on the patient and increasing the risk of additional pain, infection, or other complications.

Therefore, a need exists for a delivery device assembly that is attachable to an infusion hub and is configured to deliver a secondary drug through a pre-inserted cannula.

<CIT> discloses a basal hub for attaching to an infusion base. The hub includes a fluid reservoir and pressure actuating device. A septum portion of the reservoir is configured to be opened by a flow cannula that is in fluid communication with an infusion cannula of the infusion base, when the basal hub is attached to the infusion base. The pressure actuating device applies pressure to the fluid reservoir, such that when the septum portion of the fluid reservoir is pierced by the by the flow cannula, liquid stored in the fluid reservoir is released from the fluid reservoir into the infusion cannula of the infusion base via the flow cannula. The basal hub is configured to deliver a basal dose of insulin during periods of inactivity, such as during sleep time.

<CIT> discloses a device to co-deliver at least two medicaments where a first reservoir containing a primary medicament is connected to a manifold and cannula and where one or more additional reservoirs are placed in fluid communication with the manifold in parallel or inline flow. The additional reservoir (s) can be located within the device or as part of an attachable medicated module that connects to an external port located on the device housing. Both medicaments are delivered through a cannula subcutaneously. The device is configured to be user wearable through attachment directly to the skin by an adhesive.

The present disclosure relates to drug-delivery systems including drug-delivery device assemblies that are attachable to an infusion hub with a pre-inserted cannula. In illustrated embodiments, such devices allow patients with diabetes to administer a secondary drug as needed via the cannula of the infusion hub. In some embodiments, the device is low-profile, discrete, and easy-to-assemble onto the infusion set hub. In some embodiments, such devices are relatively non-intrusive and easy-to-carry, increasing the likelihood that the patient will carry the device and thereby facilitating a discrete way to administer a secondary drug for convenience and for emergency situations.

In the illustrated embodiments, the devices are configured to administer the secondary drug through the same cannula of the infusion hub used to deliver the primary drug. Alternatively, the infusion hub may include a second pre-inserted cannula for delivery of the secondary drug in addition to the first pre-inserted cannula for delivery of the primary drug.

In addition to glucagon, the drug-delivery device assemblies of the present disclosure may be used to deliver any suitable type of secondary drugs. For example, such drug-delivery device assemblies may be used to deliver a different type of insulin than the insulin already delivered through the infusion hub. More specifically, the infusion hub may be connected to a pump and reservoir designed to deliver basal insulin (the primary drug), and the drug-delivery device assembly of the present disclosure may deliver meal-time bolus insulin (the secondary drug). As another example, drug-delivery device assemblies of the present disclosure may be used to deliver a nonsteroidal anti-inflammatory drug (NSAID). NSAIDs are a class of drugs that reduce pain, decrease fever, reduce the likelihood of blood clots, and decrease inflammation. Doses of NSAIDs to an infusion set injection site may aid in reducing or delaying inflammation in or around the site, which in turn may increase the effectiveness or prolong the life of the injection site. NSAIDs may also reduce pain in the injection site. As another example, when an infusion set is being used to deliver a chemotherapy agent for treatment of cancer, the drug delivery device assemblies of the present disclosure may contain an antiemetic (anti-nausea) drug for delivery as a secondary drug.

In a first aspect of the present disclosure there is disclosed to a drug-delivery device assembly comprising: a manifold configured to detachably couple with an infusion hub configured to subcutaneously deliver a primary drug into a patient's body, the manifold defining a fluid channel that connects a proximal surface of the manifold with a distal surface of the manifold; a screw cap having an internal surface that, when the screw cap is coupled to the manifold, opposes the distal surface of the manifold; and a flexible drug reservoir disposed between the distal surface of the manifold and the internal surface of the screw cap, the flexible drug reservoir configured to store a secondary drug, wherein the screw cap is configured to couple to the manifold using screw threads such that rotation of the screw cap relative to the manifold causes a distance between the internal surface of the screw cap and the distal surface of the manifold to decrease, thereby compressing the flexible drug reservoir such that the secondary drug is expelled from the reservoir, through the fluid channel in the manifold, and through the infusion hub.

In some embodiments of this first aspect the infusion hub is configured to deliver the primary drug via a lumen inserted subcutaneously into the patient's body; and compression of the flexible drug reservoir causes the secondary drug to be delivered subcutaneously into the patient's body via the same lumen.

In some embodiments of this first aspect the infusion hub comprises a hub septum; the proximal surface of the manifold comprises a hub-mate septum; and the drug-delivery device assembly further comprises a needle hub having a staked double-pointed needle with a proximal end and a distal end, wherein, when the drug-delivery device assembly is coupled with the infusion hub, the distal end of the double-pointed needle is configured to pierce the hub-mate septum and the proximal end of the double-pointed needle is configured to pierce the hub septum, thereby providing a passage for the secondary drug to flow from the drug-delivery device assembly into the infusion hub.

In some embodiments of this first aspect the drug-delivery device assembly further comprises a valve disposed between the flexible drug reservoir and the fluid channel in the manifold, the valve being configured to prevent the secondary drug from flowing into the fluid channel until the flexible drug reservoir is compressed by rotation of the screw cap relative to the manifold.

In some embodiments of this first aspect the flexible drug reservoir comprises at least one rigid plate affixed to a flexible film using a fluid-tight seal. In some embodiments, the rigid plate defines a first fluid passage configured to connect with the fluid channel in the manifold. In some embodiments, the rigid plate defines a second fluid passage for filling the flexible drug reservoir, the second fluid passage being sealed with a removable stopper when the drug reservoir is not being filled.

In some embodiments of this first aspect the manifold defines a second fluid passage for filling the flexible drug reservoir.

In some embodiments of this first aspect the flexible drug reservoir stores multiple doses of the secondary drug.

In some embodiments of this first aspect the drug-delivery device assembly further comprises a locking mechanism that prevents rotation of the screw cap relative to the manifold unless the mechanism is unlocked. The locking mechanism may comprise a spring-loaded pin.

In some embodiments of this first aspect the drug-delivery device assembly further comprises a wireless antenna and a circuit board communicably coupled to the wireless antenna, wherein the circuit board is configured to control rotation of the screw cap relative to the manifold in accordance with one or more wireless signals received via the wireless antenna. Some of these embodiments further comprises a screw-cap subassembly having a nut and a torsion spring coupled to the screw cap and the nut, the torsion spring being held in a pre-loaded state by a release mechanism controlled by the circuit board, wherein the circuit board is configured to release the release mechanism in accordance with the one or more wireless signals such that stored energy in the pre-loaded torsion spring causes the nut to rotate relative to the screw cap. The release mechanism may comprise at least one of an electrically-actuated mechanical switch, an electrically-actuated gear, and a fuse pin. In some of these embodiments, rotation of the nut relative to the screw cap causes the nut to translate proximally so as to compress the flexible drug reservoir. In some of these embodiments, rotation of the nut relative to the screw cap causes a piston in the screw-cap subassembly to translate proximally so as to compress the flexible drug reservoir.

In some embodiments of this first aspect the primary drug is at least one of an insulin and an insulin analog, and the secondary drug is at least one of glucagon and a nonsteroidal anti-inflammatory drug (NSAID).

In some of these embodiments of this first aspect the flexible drug reservoir has two or more compartments, each filled with a different drug constituent; and the two or more compartments are separated from one another by one or more frangible seals such that, when the screw cap is rotated relative to the manifold, positive pressure generated by compression of at least one of the compartments causes the one or more frangible seals to break, thereby allowing the drug constituents to mix.

In a second aspect of the present disclosure there is disclosed a method for using a drug-delivery device assembly to deliver a secondary drug to a patient's body via an infusion hub positioned on the patient's body for delivering a primary drug, the infusion hub having a hub septum, the method comprising: providing the drug-delivery device assembly, the assembly comprising a manifold defining a fluid channel for delivering the secondary drug, the fluid channel being connected to a hub-mate septum on a proximal surface of the manifold, and a needle hub separate from the manifold, the needle hub having a staked double-pointed needle with a proximal end and a distal end; pushing the needle hub against the proximal surface of the manifold such that the distal end of the double-pointed needle pierces the hub-mate septum of the manifold; pushing the manifold and the needle hub against the infusion hub such that the proximal end of the double-pointed needle pierces the hub septum of the infusion hub, thereby providing a passage for the secondary drug to flow from the fluid channel into the infusion hub. This method does not form part of the invention and is merely disclosed for illustrative purposes.

In some embodiments of this second aspect, the drug-delivery device assembly further comprises a screw cap with an interior surface coupled to the manifold using screw threads, and a flexible drug reservoir disposed between the interior surface of the screw cap and the manifold; wherein the method further comprises rotating the screw cap relative to the manifold to cause a distance between the internal surface of the screw cap and the manifold to decrease, thereby compressing the flexible drug reservoir such that the secondary drug is expelled from the reservoir, through the fluid channel in the manifold and the double-pointed needle in the needle hub, and through the infusion hub.

In a third aspect of the present disclosure there is disclosed a drug-delivery device assembly including an infusion hub that is configured to receive a primary drug from a primary drug-delivery device and deliver the primary drug into a patient's body. A manifold is configured to detachably couple with the infusion hub, and the manifold includes a drug channel. The drug-delivery device assembly further includes a drug reservoir that is configured to store a secondary drug, and the drug reservoir is disposed within the manifold and coupled to the drug channel. A drug plunger is movable relative to the drug reservoir. A biasing member is configured to move away from a loaded state and toward an unloaded state to move the drug plunger relative to the drug reservoir and force the secondary drug from the drug reservoir, through the drug channel, through the infusion hub, and into the patient's body.

The above mentioned and other features of this present disclosure, and the manner of attaining them, will become more apparent and will be better understood by reference to the following description of embodiments of the present disclosure taken in conjunction with the accompanying drawings, wherein only <FIG> show drug delivery devices according to the present invention.

Corresponding reference characters indicate corresponding parts throughout the several views. Although the exemplification set out herein illustrates embodiments of the present disclosure, in several forms, the embodiments disclosed below are not intended to be exhaustive or to be construed as limiting the scope of the invention to the precise forms disclosed.

The present disclosure relates to drug-delivery systems including drug-delivery device assemblies, or "hub mates," that attach to an infusion hub. The infusion hub may be connected to a source of a primary drug and may be configured to deliver the primary drug subcutaneously into the patient's body via a lumen of a needle or cannula inserted into an infusion site. The drug-delivery device assemblies may carry and deliver a secondary drug into the patient's body via the needle or cannula of the infusion hub together with any of the primary drug that is also present in the infusion hub or at a time when delivery of the primary drug through the needle or cannula is halted. The primary drug or secondary drug may include one or more therapeutic agents such as insulins, insulin analogs such as insulin lispro or insulin glargine, insulin derivatives, GLP-<NUM> receptor agonists such as dulaglutide or liraglutide, gastric inhibitory polypeptide (GIP), GIP analogs, GIP derivatives, oxyntomodulin analogs, oxyntomodulin derivatives, therapeutic antibodies such as IL-<NUM> antibody analogs or derivatives, such as mirikizumab, IL-<NUM> antibody analogs or derivatives, such as ixekizumab, therapeutic agents for pain related treatments, such as galcanezumab or lasmiditan, chemotherapy drugs, or any other therapeutic agent that is capable of delivery by an infusion hub. The primary drug or secondary drug may be formulated with one or more excipients.

In exemplary embodiments disclosed herein, the secondary drug includes one or more therapeutic agents such as those designed to raise a patient's glucose levels (such as glucagon), a type of insulin different than a primary insulin being delivered through the infusion hub, NSAIDs, antiemetic (anti-nausea) drugs, or any other suitable therapeutic agent that is capable of delivery through an infusion hub. Exemplary secondary drugs include, for example, meloxicam, bromfenac sodium, acetylsalicylic acid, salicylic acid, paracetamol, heparin, and dexamethasone, although other suitable drugs may be provided for delivery by the drug-delivery device assemblies of the present disclosure.

In some embodiments, the drug delivery device assembly delivers a secondary drug that is a different type of insulin than an insulin normally being delivered through the infusion set hub. For instance, the infusion set hub may be connected to a pump (<FIG>) and reservoir designed to deliver basal insulin (the primary drug), but the patient may use the drug delivery device assembly of the present disclosure to deliver doses of rapid-acting bolus or meal-time insulin (the secondary drug).

Referring initially to <FIG>, an exemplary embodiment of a drug-delivery system <NUM> is illustrated. Generally, the drug-delivery system <NUM> includes an infusion hub <NUM> that is configured to be attached, such as with an adhesive, to a patient's body at an infusion site. The infusion hub <NUM> includes a needle or cannula <NUM> that is configured to be inserted into a subcutaneous space at the infusion site. A lumen of the needle <NUM> is configured to deliver drugs to the patient at the infusion site. The infusion hub <NUM> receives a primary drug from a primary drug source <NUM> (for example, an insulin pump) via a primary drug conduit <NUM>. The infusion hub <NUM> also receives a secondary drug from a selectively-attachable drug-delivery device assembly <NUM> or "hub mate. " Exemplary embodiments of an infusion hub <NUM> and a drug-delivery device assembly <NUM> are illustrated and described herein.

Referring now to <FIG>, a perspective view of a first embodiment of a drug-delivery device assembly <NUM> of system <NUM> (<FIG>) is illustrated in a disassembled state. As used in all the figures and descriptions herein, and as illustrated by double arrow <NUM>, the terms "distal" and "proximal" refer to axial locations relative to an infusion site when a drug-delivery device assembly is oriented for use at such site, whereby, for example, proximal end of the assembly refers to the assembly end that is closest to such infusion site, and distal end of the assembly refers to the assembly end that is furthest from such infusion site. Assembly <NUM> includes a screw cap <NUM> having internal screw threads <NUM>, a main manifold <NUM> having external screw threads <NUM>, and a needle hub <NUM> having a double-staked needle <NUM>. The manifold <NUM> of assembly <NUM> includes features that enable it to mate to an infusion set hub <NUM> configured to deliver a primary drug into a patient's body. Such features include additional screw threads, tabs that snap-fit into recesses, and/or flanges that lock into tabs. Assembly <NUM> further includes a flexible drug reservoir <NUM> disposed on a distal surface of valve capture plate <NUM>, which is in turn disposed on a distal surface of manifold <NUM>. Drug reservoir <NUM> may store, or be configured to store, a secondary drug for delivery into a patient via the infusion set hub. As discussed above, this secondary drug may include glucagon, one or more NSAIDs, an insulin or insulin derivative, or any other drug that may be stored in a flexible drug reservoir.

<FIG> provides a profile cutaway view of assembly <NUM> in a disassembled state. As depicted in this cutaway view, manifold <NUM> of assembly <NUM> also includes a hub-mate septum <NUM> that resides between fluid channels <NUM> and <NUM>. Fluid channels <NUM> and <NUM> run through the axial length of manifold <NUM> to provide a pathway for fluids to pass from a distal surface of manifold <NUM> to a proximal surface of manifold <NUM>. A valve <NUM> is further disposed between fluid channel <NUM> and the flexible drug reservoir <NUM>, and valve <NUM> is held in place between valve capture plate <NUM> and manifold <NUM>. Valve capture plate <NUM> may be joined together with manifold <NUM> during device assembly (e.g., by laser welding, ultrasonic welding, or adhesive bonding).

Flexible drug reservoir <NUM> may be made from a thin, flexible, drug-compatible film, such as cyclic olefin copolymer (COC), cyclic olefin polymers (COP), high-density polyethylene (HDPE), and/or polychlorotrifluoroethylene (PCTFE). Other materials may also be used, depending upon the drug stored therein. In some embodiments, drug reservoir <NUM> may comprise a single compartment that stores a single type of drug. In other embodiments, drug reservoir <NUM> may comprise two or more compartments, each filled with a different drug constituent. For example, reservoir <NUM> may comprise a first compartment stacked on top of (e.g., located distal to) a second compartment, wherein the first compartment stores a liquid diluent and the second compartment stores a lyophilized drug powder, such as glucagon powder. This arrangement is illustrated by the horizontal dashed line drawn through the center of reservoir <NUM> in <FIG> and <FIG>. In other embodiments (not shown), the two or more compartments may be located next to each other in the same plane, such that neither compartment is distal or proximal relative to the other compartment. When drug reservoir <NUM> comprises two or more compartments, the compartments may be separated from one another by one or more frangible seals.

Drug reservoir <NUM> may be heat-sealed or otherwise affixed in a fluid-tight manner to valve capture plate <NUM>. In this way, valve capture plate <NUM> provides a rigid bottom surface on which flexible drug reservoir <NUM> rests. Valve capture plate <NUM> and manifold <NUM> may define a through-hole <NUM> which may be used to fill reservoir <NUM>. After filling, through-hole <NUM> may be stoppered by an elastic stopper <NUM>.

Infusion set hub <NUM> is connected to a source of a primary drug (e.g., device <NUM> of <FIG>) via tube <NUM>. The source of the primary drug may comprise an infusion pump, an infusion bag, a drug reservoir, or any other component capable of supplying the primary drug. While in use, the primary drug passes through tube <NUM> and into infusion set hub <NUM>, where it is delivered into the patient's body via lumen <NUM>, which may be a needle, catheter, or cannula. Infusion set hub <NUM> further includes a hub septum <NUM> disposed on a distal surface of hub <NUM>; hub septum <NUM> is also connected to lumen <NUM> via secondary drug channel <NUM>.

<FIG> provides a profile cutaway view of assembly <NUM> in an assembled state. When fully assembled, screw cap <NUM> mates with manifold <NUM> such that internal screw threads <NUM> on screw cap <NUM> engage with external screw threads <NUM> on manifold <NUM>. The fluid drug reservoir <NUM> is situated between an internal, proximal surface of screw cap <NUM> and a distal surface of valve capture plate <NUM>. When assembly <NUM> is mated with infusion hub <NUM>, needle hub <NUM> is held in place between a proximal surface of manifold <NUM> and a distal surface of hub <NUM>. A distal end of double-staked needle <NUM> pierces hub-mate septum <NUM> while a proximal end of double-staked needle <NUM> pierces hub septum <NUM>. In this way, double-pointed needle <NUM> provides a fluid conduit between the manifold <NUM> and the infusion hub <NUM>.

To dispense the secondary drug from the drug reservoir <NUM>, a user (e.g., the patient, a caregiver, and/or a healthcare professional) rotates screw cap <NUM> relative to manifold <NUM>. Due to the engagement between internal screw threads <NUM> and external threads <NUM>, rotation of the screw cap causes a distance between the internal surface of the screw cap <NUM> and the distal surface of manifold <NUM> to decrease. This decrease in distance compresses the flexible drug reservoir <NUM> such that the secondary drug is expelled from the reservoir <NUM>, through valve <NUM>, fluid channel <NUM>, hub-mate septum <NUM>, double-staked needle <NUM>, hub septum <NUM>, secondary drug channel <NUM>, and lumen <NUM>, and into the patient's body. The minimum dose that can be dispensed from assembly <NUM> will depend upon the thread size and pitch of the screw cap threads and the size of the area of the flexible drug reservoir <NUM> that is compressed when the screw cap <NUM> is rotated relative to manifold <NUM>. The accuracy of the dose will depend upon the thread pitch, tolerances on the parts, and the uniformity with which the flexible reservoir <NUM> is compressed by the screw cap <NUM>.

In embodiments where reservoir <NUM> includes a first compartment storing a liquid diluent that is stacked on top of (i.e., located distal to) a second compartment storing a lyophilized drug powder, compression of reservoir <NUM> generates sufficient positive pressure within the first compartment to break a frangible seal between the first and the second compartment. When the frangible seal is broken, the diluent flows from the first compartment into the second compartment to mix with the lyophilized drug powder stored in the second compartment. The mixture of the diluent with the lyophilized drug powder creates a reconstituted liquid drug mixture that is then expelled from the second compartment and into the patient's body along the fluid path described previously.

Screw cap <NUM> may include a lock (not shown) that may take the form of, for example, a spring-loaded pin. The lock, when engaged, prevents the cap <NUM> from rotating with respect to the manifold <NUM>. In some cases, reservoir <NUM> may hold only enough secondary drug for a single dose-in such cases, the user may rotate cap <NUM> until it rotates no further with every use. After every such use, the reservoir <NUM> will need to be replaced or re-filled. In some cases, reservoir <NUM> may hold enough secondary drug for multiple doses-in such cases, the user may rotate cap <NUM> partially with every dose, and optionally engage the lock between doses to prevent the cap <NUM> from rotating further. The user may also rotate the cap <NUM> by different amounts to administer different amounts of secondary drug. The cap <NUM> and/or external surface of manifold <NUM> may also include markings that indicate to a user how far he or she should turn the cap <NUM> in order to administer a certain amount of secondary drug. For instance, the markings may indicate that a half-rotation (<NUM>°) or full-rotation (<NUM>°) of cap <NUM> relative to manifold <NUM> will result in a dose of <NUM> unit of secondary drug.

Valve <NUM> may be configured to open only when compression of the drug reservoir <NUM> generates sufficient positive pressure of the secondary drug. The cracking pressure of valve <NUM> may be tailored to be high enough that it prevents the secondary drug from being dispensed due to environmental changes, such as heating and cooling of thermoplastic parts, and/or atmospheric pressure changes. The valve also prevents backflow of liquid into reservoir <NUM>. During storage, use, or filling, the secondary drug may come into fluid contact with various surfaces of device assembly <NUM>, such as valve <NUM>, stopper <NUM>, and the inside surfaces of fluid channel <NUM>, hub-mate septum <NUM>, double-staked needle <NUM>, hub septum <NUM>, secondary drug channel <NUM>, lumen <NUM>, and through-hole <NUM>. These surfaces may be made from or coated with drug-compatible materials, such as fluoroelastomer (FKM), chlorobutyl bromobutyl, silicone, or other such elastomers.

Table <NUM> below provides an exemplary set of parameters for assembly <NUM>.

Since assembly <NUM> utilizes the same lumen <NUM> for delivery of both the primary and the secondary drug, there is a volume of space within infusion set hub <NUM> in which the two drugs may mix. This volume of space includes the volume where secondary drug channel <NUM> intersects with the drug channel carrying primary drug supplied by tube <NUM>, as well as the volume within lumen <NUM>. In some embodiments, it may be advantageous to minimize the volume of this space by making the fluid channels small at this union. With appropriate design (e.g., with channels having less than <NUM> inches inner diameter), the total volume of space shared by the primary and the secondary drug may be kept to less than three microliters.

<FIG> provides a perspective view of a second embodiment of a drug-delivery device assembly <NUM> in a disassembled state. Assembly <NUM> is similar to assembly <NUM>, and like components of the two assemblies have same reference numerals. In assembly <NUM>, flexible drug reservoir <NUM> is not integrated with manifold <NUM> but instead rests on a reservoir bottom <NUM> that is separable from manifold <NUM>.

<FIG> provides a profile cutaway view of assembly <NUM> in a disassembled state, while <FIG> provides a profile cutaway view of assembly <NUM> in an assembled state. In these views, it can be seen that reservoir bottom <NUM> includes the valve capture plate <NUM>, valve <NUM>, fluid channel <NUM>, hub-mate septum <NUM>, through-hole <NUM>, and stopper <NUM> described above. The manifold <NUM> includes only fluid channel <NUM> described above. The configuration of components in assembly <NUM> makes filling and storage of reservoir <NUM> easier. Unlike assembly <NUM>, reservoir <NUM> in assembly <NUM> is not integrally attached to manifold <NUM>. Since reservoir <NUM> and reservoir bottom <NUM> can be detached from manifold <NUM>, the reservoir <NUM> and reservoir bottom <NUM> can be separately transported, stored, handled, filled, and/or re-filled. This increases the likelihood that transportation, storage, and handling of reservoir <NUM> is easy and convenient, particularly if the drug(s) stored in reservoir <NUM> must be kept at a cold temperature during manufacturing, assembly, and distribution.

For both assembly <NUM> and assembly <NUM>, to preserve the sterility of the secondary drug stored in reservoir <NUM>, it will typically be advantageous to maintain hub-mate septum <NUM> in an un-pierced state during storage. However, for ease of use and/or assembly, the drug-delivery device assembly may be packaged in a way that positions the distal end of double-pointed needle <NUM> directly below hub-mate septum <NUM>. An exemplary set of user steps for piercing hub-mate septum <NUM> and for attaching a drug-delivery device assembly to an infusion set hub is depicted in <FIG>. This set of user steps applies to both assemblies <NUM>, <NUM>, as well as other suitable embodiments of the drug-delivery device assembly.

As illustrated in <FIG>, a user may first attach an infusion set hub onto his or her body. As discussed above, attaching the infusion set hub may comprise inserting a needle, catheter or cannula into an infusion injection site on the user's body, such as on the user's abdomen, thigh, arm, lower back, or buttock. Although not shown in <FIG>, the infusion set hub may also be connected to a pump or a source of a primary drug by a tube.

As illustrated in <FIG>, the user may then retrieve a drug-delivery device assembly from packaging. The assembly may be packaged such that the needle hub <NUM> having the double-staked needle <NUM> is positioned directly below manifold <NUM>, such that the distal end of needle <NUM> is positioned immediately below (but does not pierce) hub-mate septum <NUM>.

As illustrated in <FIG>, the user may then push needle hub <NUM> "in", i.e., in the distal direction. This pushes the needle hub <NUM> against a proximal surface of manifold <NUM>, and also causes the distal end of double-staked needle <NUM> to pierce hub-mate septum <NUM>.

As illustrated in <FIG>, the user may then remove a needle shield (not shown in <FIG>) from the proximal end of needle <NUM>. The needle shield may be a protective cover made of plastic or some other material that covers the proximal end of double-staked needle while the drug-delivery device assembly is in storage. Once the needle shield is removed, the proximal end of needle <NUM> is exposed.

As illustrated in <FIG>, the user may then attach the assembly to the infusion set hub by pushing the assembly down (i.e., in the proximal direction) against the distal surface of the infusion set hub. Pushing the assembly down causes the proximal end of needle <NUM> to pierce the hub septum <NUM>, thereby establishing a conduit for the secondary drug to flow from the reservoir <NUM>, into the infusion set, and from there into the patient's body.

As illustrated in <FIG>, once the drug-delivery device assembly has been attached to the infusion set hub, the user may then twist the screw-cap <NUM> to administer a dose, as described previously.

In the embodiments described so far, the drug-delivery device assembly is operated manually; that is, the user is responsible for manually actuating the assembly to deliver a dose of the secondary drug. However, in other embodiments, the assembly may also be operated automatically to, for example, dispense the secondary drug in response to a wireless signal from an external device, such as a glucose monitor or a mobile device that is receiving blood glucose values from a glucose monitor.

An example of one such embodiment is illustrated in <FIG>, <FIG>, and <FIG>. <FIG> illustrates a perspective view of a modified screw cap sub-assembly <NUM> in a disassembled, exploded state. <FIG> illustrates a profile, cutaway view of screw cap sub-assembly <NUM> in an assembled state, as well as other previously-described components of a drug-delivery device assembly. <FIG> illustrates a profile cutaway view of a drug-delivery device assembly that uses screw cap sub-assembly <NUM>, wherein the drug-delivery device assembly is in a fully assembled state.

Referring to <FIG>, screw cap sub-assembly <NUM> includes a screw cap <NUM>, on top of which is arranged a printed circuit board (PCB) <NUM> having a battery <NUM>. Screw cap <NUM> also includes an internal pocket <NUM> sized to accommodate torsion spring <NUM>, nut <NUM>, and piston <NUM>. As best seen in <FIG>, nut <NUM> includes a proximal surface <NUM> that defines an opening <NUM>. As illustrated in both <FIG> and <FIG>, piston <NUM> includes a piston plate <NUM> and a piston rod <NUM> perpendicular to piston plate <NUM>. When screw cap sub-assembly <NUM> is assembled, piston rod <NUM> fits through opening <NUM> defined in proximal surface <NUM> of nut <NUM>. At least a portion of the surface of piston rod <NUM> includes external screw threads that engage with internal screw threads situated on the internal surface of opening <NUM>, such that rotation of piston rod <NUM> about longitudinal axis <NUM> relative to nut <NUM> causes piston rod <NUM> (and therefore piston <NUM>) to translate in the proximal or distal direction along longitudinal axis <NUM> relative to nut <NUM>.

When assembled, piston plate <NUM> may directly abut proximal surface <NUM> as shown in <FIG>, or there may be a gap between proximal surface <NUM> and piston plate <NUM>. Torsion spring <NUM> fits within nut <NUM> on top of proximal surface <NUM>, and the combined piston <NUM>, nut <NUM>, and torsion spring <NUM> fit within the internal pocket <NUM> of screw cap <NUM>. When assembled, the distal end of piston rod <NUM> fits within anti-rotation pocket <NUM> on the bottom (proximal) side of screw cap <NUM>.

As best seen in <FIG>, piston rod <NUM> illustratively is shaped like a rounded wedge and is sized and shaped to fit snugly within anti-rotation pocket <NUM>. When inserted into pocket <NUM>, the shape of the two components prevents piston <NUM> from rotating about longitudinal axis <NUM> relative to screw cap <NUM>. The aforementioned external screw threads on piston rod <NUM> (that engage with the internal screw threads in opening <NUM>) are situated on the rounded portion of the rounded wedge shape. Thus, when assembled, piston <NUM> may translate along longitudinal axis <NUM> relative to screw cap <NUM>, but may not rotate relative to screw cap <NUM>.

One end of torsion spring <NUM> (e.g., the central end) is attached to screw cap <NUM> (potentially via a tab or spindle that protrudes proximally from the proximal surface of screw cap <NUM>), while the other end of torsion spring <NUM> (e.g., the external end) is attached to an internal surface of nut <NUM>. When assembled, torsion spring is held in a pre-loaded, coiled state by a release mechanism controlled by PCB <NUM>. This release mechanism (not shown) may take the form of a fuse pin that prevents torsion spring <NUM> from uncoiling - the PCB <NUM> may release the release mechanism by using stored energy from battery <NUM> to heat and melt the fuse pin, thus releasing torsion spring <NUM> and allowing it to uncoil. Alternatively, the release mechanism may take the form of a mechanical micro-switch that acts as a latch to hold the torsion spring <NUM> in place - when the micro-switch is moved, the torsion spring <NUM> is unlatched and allowed to uncoil. In yet other embodiments, the release mechanism may take the form of an actuated gear that can control the extent to which torsion spring <NUM> is allowed to uncoil. Other release mechanisms known in the art may also be used to hold the torsion spring <NUM> in its pre-loaded, coiled state until released by PCB <NUM>. PCB <NUM> may trigger the release mechanism in response to an instruction to administer some or all of the secondary drug in reservoir <NUM>. This instruction may be based on a wireless signal received from an external device (e.g., a smartphone or glucose monitor), based on the push of a button situated on drug-delivery device assembly <NUM>, and/or based on internal logic programmed or embodied on PCB <NUM>.

When the PCB <NUM> triggers the release mechanism, the uncoiling of the pre-loaded torsion spring <NUM> causes nut <NUM> to rotate about longitudinal axis <NUM> relative to screw cap <NUM>. Since piston <NUM> is prevented from rotating relative to screw cap <NUM> by the interface between piston rod <NUM> and anti-rotation pocket <NUM>, nut <NUM> also rotates relative to piston <NUM>. Rotation of nut <NUM> relative to piston <NUM> causes piston <NUM> to translate in the proximal direction along longitudinal axis <NUM> due to the aforementioned engagement between the external screw threads on piston rod <NUM> and the internal screw threads in opening <NUM>. When the piston <NUM> translates in the proximal direction, it compresses drug reservoir <NUM>, thus dispensing the secondary drug along the previously-described fluid pathway into the patient. In this way, screw cap sub-assembly <NUM> allows the drug-delivery device assembly to automatically dispense the secondary drug (e.g., in response to a wireless instruction or signal from an external device) without requiring the user to manually actuate or twist the screw cap.

Although <FIG>, <FIG>, and <FIG> depict modified screw cap sub-assembly <NUM> as being used with the drug-delivery device assembly <NUM> disclosed herein with <FIG>, screw cap sub-assembly <NUM> may also be used with assembly <NUM> of <FIG>. For ease of illustration and explanation, some features within manifold <NUM> have been omitted from <FIG> and <FIG>, e.g., through-hole <NUM> and stopper <NUM>. It is understood that these features may also be present in some embodiments.

<FIG> illustrates yet another embodiment of a screw cap that allows for automatic dispensing of the secondary drug from a drug delivery device assembly. This modified screw cap may also be used with either of drug-delivery device assemblies <NUM>, <NUM>. <FIG> provides a cutaway view of another modified screw cap sub-assembly <NUM>. Assembly <NUM> includes a screw cap <NUM>, on top of which is arranged a printed circuit board (PCB) <NUM> having a battery <NUM>. Screw cap <NUM> also includes an internal pocket <NUM> sized to accommodate torsion spring <NUM> and nut <NUM>. Unlike screw cap sub-assembly <NUM> depicted in <FIG>, <FIG>, and <FIG>, modified screw top assembly <NUM> does not include a piston.

Torsion spring <NUM> includes a tab <NUM> that extends from a central end of spring <NUM>. Tab <NUM> is attached to a central spindle portion <NUM> of screw cap <NUM>. The other, external end of spring <NUM> is attached to an interior surface of nut <NUM>. The external surface <NUM> of nut <NUM> includes external screw threads that engage with internal screw threads disposed on interior surface <NUM> of pocket <NUM>. The engagement between these screw threads causes nut <NUM> to translate in the proximal or distal direction when nut <NUM> is rotated relative to screw cap <NUM> about longitudinal axis <NUM>.

Similar to the screw top assembly <NUM> described herein, the torsion spring <NUM> is held in a pre-loaded, coiled state by a release mechanism controlled by PCB <NUM>. This release mechanism may take the form of any of the release mechanisms described above in relation to screw top assembly <NUM>. When the PCB <NUM> triggers the release mechanism, the uncoiling of the pre-loaded torsion spring <NUM> causes nut <NUM> to rotate about longitudinal axis <NUM> relative to screw cap <NUM>. Rotation of nut <NUM> relative to screw cap <NUM> causes nut <NUM> to translate in the proximal direction along longitudinal axis <NUM> due to the aforementioned engagement between the external screw threads on surface <NUM> of nut <NUM>, and the internal screw threads on internal surface <NUM> of pocket <NUM>. When the nut <NUM> translates in the proximal direction, a proximal surface <NUM> of nut <NUM> compresses drug reservoir <NUM> (not shown), thus dispensing the secondary drug along the previously-described fluid pathway into the patient. In this way, screw cap sub-assembly <NUM> also allows the drug-delivery device assembly to automatically dispense the secondary drug (e.g., in response to a wireless instruction or signal from an external device) without requiring the user to manually actuate or twist the screw cap.

<FIG> are exploded views of the infusion hub <NUM> and the drug-delivery device assembly <NUM> of <FIG> according to another exemplary embodiment. As used in all the figures and descriptions herein, and as illustrated by double arrow <NUM>, the terms "distal" and "proximal" refer to axial locations relative to an infusion site when a drug-delivery device assembly <NUM> and an infusion hub <NUM> are oriented for use at such site, whereby, for example, proximal end of the assembly refers to features that are closer to the infusion site, and distal end of the assembly refers to features that are farther from the infusion site.

Referring to <FIG>, the infusion hub <NUM> includes an internal drug-delivery channel <NUM> coupled to the needle <NUM>. The drug-delivery channel <NUM> is also coupled to a primary drug channel <NUM>, and the primary drug channel <NUM> is coupled to the primary drug conduit <NUM>. The drug-delivery channel <NUM> is further coupled to a secondary drug channel <NUM>, and the secondary drug channel <NUM> carries a pierceable septum <NUM>.

Referring again to <FIG>, the drug-delivery device assembly <NUM> includes a manifold <NUM> that carries a secondary drug and is selectively attachable to the infusion hub <NUM>. The manifold <NUM> may be made of any of various appropriate materials, such as cyclic olefin copolymer (COC), cyclic olefin polymers (COP), high-density polyethylene (HDPE), and/or polychlorotrifluoroethylene (PCTFE). The manifold <NUM> includes a first, or lower, manifold portion <NUM> and a second, or upper, manifold portion <NUM>. The lower manifold portion <NUM> includes a lower chamber <NUM> that receives the infusion hub <NUM>, and a protrusion <NUM> is disposed with the lower chamber <NUM>. The protrusion <NUM> pierces the septum <NUM> of the infusion hub <NUM>, and the protrusion <NUM> includes a manifold drug channel <NUM> for delivering the secondary drug to the secondary drug channel <NUM> of the infusion hub <NUM>. The upper manifold portion <NUM> includes an inner wall <NUM> that defines a drug reservoir <NUM>. The drug reservoir <NUM> initially receives the secondary drug via a fill port <NUM>, which receives a stopper <NUM> after filling the drug reservoir <NUM>. The drug reservoir <NUM> is coupled to the manifold drug channel <NUM> of the lower manifold portion <NUM>.

In the illustrated embodiment, the manifold <NUM> also includes features that facilitate delivering the secondary drug continuously to a patient over a relatively long period. Generally, these features include one or more resistance channels <NUM> (illustratively, three resistance channels <NUM>) that carry a motion-inhibiting or resistance medium (shown elsewhere), such as a high-viscosity liquid/gel for example. The high-viscosity liquid may be Newtonian having a constant velocity, such as glycerol for example. The high-viscosity liquid may be thixotropic wherein the viscosity decreases in shear. An example of a thixotropic liquid is a medical-grade "grease", such as a grease manufactured by Nye Lubricants (Fairhaven, MA). These optional features are described in further detail below. In other embodiments, the manifold <NUM> does not include such resistance channels configured to slow drug delivery.

The drug-delivery device assembly <NUM> further includes a plunger assembly <NUM> that is movably coupled to the manifold <NUM>. Generally, the plunger assembly <NUM> may include any appropriate drug-compatible materials, such as FKM, chlorobutyl, bromobutyl, or silicone. The plunger assembly <NUM> includes a plunger base <NUM> and a drug plunger <NUM>, and one or more resistance plungers <NUM> (illustratively, three resistance plungers <NUM>) extend proximally from the plunger base <NUM>. The drug plunger <NUM> and the resistance plungers <NUM> are movable together with the plunger base <NUM>. The drug plunger <NUM> is movably and sealingly received in the drug reservoir <NUM> of the manifold <NUM>. As such and as described in further detail below, the drug plunger <NUM> is proximally movable in the drug reservoir <NUM> to force the secondary drug from the drug reservoir <NUM>, through the manifold drug channel <NUM>, through the infusion hub <NUM>, and into the patient's body together with any of the primary drug that is also present in the infusion hub <NUM>. The resistance plungers <NUM> are movably and sealingly received in the resistance channels <NUM>. As such and as described in further detail below, the resistance plungers <NUM> are proximally movable in the resistance channels <NUM> to move the resistance medium in the resistance channels <NUM>, and the resistance medium thereby provides resistance to movement of the plunger assembly <NUM> relative to the manifold <NUM>. In some embodiments, the resistance provided by the resistance medium facilitates delivering secondary drugs continuously to a patient over a relatively long time period.

With continued reference to <FIG>, the drug-delivery device assembly <NUM> also includes a biasing member <NUM> that is disposed between the plunger assembly <NUM> and a cover <NUM> coupled to the manifold <NUM>. The biasing member <NUM> releases stored energy, or, stated another way, moves away from a loaded state and toward an unloaded state (as used herein, a "loaded state" and an "unloaded state" are used as relative terms to describe states in which a biasing member stores relatively high and relatively low amounts of energy, respectively), to move the plunger assembly <NUM> proximally relative to the manifold <NUM> and, as described in further detail below, facilitate delivery of the secondary drug to the patient. The biasing member <NUM> may take various forms. For example and as shown in <FIG>, the biasing member <NUM> may be a compression spring, more specifically a wave washer. In such embodiments, the wave washer is relatively compressed in the loaded state and relatively uncompressed in the unloaded state. Other types of biasing members <NUM> are described in further detail below and shown elsewhere.

In some embodiments, the drug-delivery device assembly <NUM> also includes a detachable or releasable locking mechanism (not shown) for initially holding the biasing member <NUM> in a loaded state. Such mechanisms may take a variety of forms. In one example, a locking mechanism includes a detachable pin that extends through the cover <NUM> and into the plunger assembly <NUM> to hold the biasing member <NUM> in a loaded state between the cover <NUM> and the plunger assembly <NUM>. In another example, the cover <NUM> includes tabs that lock to corresponding tabs on the top portion of the plunger assembly <NUM> to hold the biasing member <NUM> in a loaded state. When the cover <NUM> is rotated with respect to the biasing member <NUM>, the interlocking tabs are freed thereby releasing the biasing member <NUM>.

<FIG> illustrate the drug-delivery device assembly <NUM> and the infusion hub <NUM> with the biasing member <NUM> in different states. More specifically, <FIG> illustrates the biasing member <NUM> in a loaded state, and <FIG> illustrates the biasing member <NUM> in an unloaded state. As described above, the biasing member <NUM> moves away from the loaded state and toward the unloaded state to move the plunger assembly <NUM> proximally relative to the manifold <NUM>. As such, the biasing member <NUM> (a) moves the drug plunger <NUM> in the drug reservoir <NUM> to force the secondary drug <NUM> from the drug reservoir <NUM>, through the manifold drug channel <NUM>, through the infusion hub <NUM>, and into the patient's body together with any primary drug that is also present in the infusion hub <NUM>; and (b) moves the resistance plungers <NUM> in the resistance channels <NUM> to move the resistance medium in the resistance channels <NUM> (all shown elsewhere), and the resistance medium thereby provides resistance to movement of the plunger assembly <NUM> relative to the manifold <NUM>.

<FIG> illustrates the plunger assembly <NUM> exploded from the manifold <NUM> of the drug-delivery device assembly <NUM>, and the resistance medium is shown as being absent from one of the resistance channels <NUM> for clarity. <FIG> illustrate the plunger assembly <NUM> and one of the resistance plungers <NUM> in different positions relative to the manifold <NUM>. More specifically, <FIG> illustrates the position of the plunger assembly <NUM> in a loaded state of the biasing member <NUM>, <FIG> illustrates the position of the plunger assembly <NUM> in an intermediate state of the biasing member <NUM> (shown elsewhere), and <FIG> illustrates the position of the plunger assembly <NUM> in an unloaded state of the biasing member <NUM>. <FIG> also illustrate how one of the resistance plungers <NUM> forces the resistance medium <NUM> to move in one of the resistance channels <NUM> as the plunger assembly <NUM> moves relative to the manifold <NUM>. <FIG> further illustrate an exemplary structure of one of the resistance channels <NUM>. More specifically, the resistance channel <NUM> includes an input channel portion <NUM> and an output channel portion <NUM> formed in the upper manifold portion <NUM>. An intermediate channel portion <NUM> formed in the lower manifold portion <NUM> couples the input channel portion <NUM> to the output channel portion <NUM>. As described further below, the resistance plunger <NUM> forces the resistance medium <NUM> to move through the input channel portion <NUM>, through the intermediate channel portion <NUM>, and into the output channel portion <NUM> of the resistance channels <NUM> as the plunger assembly <NUM> moves relative to the manifold <NUM>.

One or more characteristics of the biasing member <NUM>, the plunger assembly <NUM>, the manifold <NUM>, the resistance medium <NUM>, and the secondary drug <NUM> may be selected to provide a desired delivery duration and/or delivery rate of the secondary drug <NUM> to the patient. These characteristics include, for example, the elastic constant of the biasing member <NUM>, the cross-sectional area and length of the resistance channels <NUM>, the number of resistance plungers <NUM> and resistance channels <NUM>, the viscosity of the resistance medium <NUM>, the cross-sectional area of the drug reservoir <NUM>, the viscosity of the secondary drug <NUM>, and the cross-sectional area of the manifold drug channel <NUM>. In some embodiments, one or more characteristics may be configured such that the biasing member <NUM> moves away from the loaded state and toward the unloaded state at a substantially constant rate (for example, constant to within +/-<NUM> percent). For example, the cross-sectional area of the input channel portion <NUM> may be relatively small compared to the cross-sectional areas of the intermediate channel portion <NUM> and the output channel portion <NUM>. In these embodiments, the resistance provided by the resistance channels <NUM> and the resistance medium <NUM> is largely caused by the input channel portions <NUM>. As the biasing member <NUM> moves from the loaded state and towards the unloaded state, the resistance plunger <NUM> moves the resistance medium <NUM> through the input channel portion <NUM>, the amount of the resistance medium <NUM> in the input channel portion <NUM> decreases, and the resistance decreases in a substantially linear manner. Meanwhile, the force exerted by the biasing member <NUM> decreases in a substantially linear manner. As such, the biasing member <NUM> may move away from the loaded state and toward the unloaded state at a substantially constant rate, and the secondary drug <NUM> may be delivered at a substantially constant rate.

In one example, the resistance channels have a round cross-section and contain a viscous, incompressible, Newtonian resistance medium that moves in laminar flow. In this example, movement of the plunger assembly <NUM>, driven by the spring force, is governed by Poiseuille's equation. The flow of drug out of the drug reservoir is given by this equation:<MAT> where Q is the flow rate of the drug out of the drug reservoir, R is the radius of the resistive channel, k is the spring force, N is the number of resistive channels, and µ is the viscosity of the damping medium. When R, k, N and µ are constants, the flow rate Q of the drug will likewise be constant.

In another example, a constant delivery rate is facilitated by limiting the unloading of the biasing member <NUM>. For example, the biasing member <NUM> may have an unloading distance over which the biasing member <NUM> moves from a fully-loaded state to a fully-unloaded state, but the drug-delivery device assembly <NUM> may be designed to operate through fifty percent (or some other suitable percentage) of that range, so that the biasing member <NUM> moves only fifty percent of the unloading distance during use. As such, the force exerted by the biasing member <NUM> may remain more constant in use, the biasing member <NUM> may move away from the loaded state and toward the unloaded state at a substantially constant rate, and the secondary drug <NUM> may be delivered at a substantially constant rate.

<FIG> illustrate another embodiment of a drug-delivery device assembly <NUM>' and an infusion hub <NUM>'. The drug-delivery device assembly <NUM>' and the infusion hub <NUM>' are substantially similar to drug-delivery device assembly <NUM> and the infusion hub <NUM>, respectively, with like reference numerals indicating like parts, except as described below. Like the infusion hub <NUM>, the infusion hub <NUM>' may receive a primary drug from a primary drug source (shown elsewhere - for example, the primary drug source <NUM> of <FIG>). The infusion hub <NUM>' has a recessed upper surface portion <NUM>' to accommodate features of the drug-delivery device assembly <NUM>', as described in further detail below. The following components of the drug-delivery device assembly <NUM>' are shown in <FIG>: a lower manifold portion <NUM>', an upper manifold portion <NUM>', a plunger assembly <NUM>', a biasing member <NUM>', and a cover <NUM>'.

The drug-delivery device assembly <NUM>' also includes a flexible drug reservoir <NUM>' carried within the upper manifold portion <NUM>', and the flexible drug reservoir <NUM>' carries the secondary drug <NUM>'. The flexible drug reservoir <NUM>' may be made from a thin, flexible, drug-compatible film, such as COP, COC, HDPE, and/or PCTFE. Other materials may also be used, depending upon the secondary drug <NUM>' carried therein. The flexible drug reservoir <NUM>' includes an open proximal side <NUM>' to facilitate (<NUM>) initially receiving the secondary drug <NUM>' via a proximally-extending fill port <NUM>' (which is disposed distally relative to the recessed upper surface portion <NUM>' of the infusion hub <NUM> and receives a stopper <NUM>' after filling the flexible drug reservoir <NUM>'); and (<NUM>) delivering the secondary drug <NUM>' to the manifold drug channel <NUM>' of the lower manifold portion <NUM>' and ultimately the patient (when the biasing member <NUM>' moves from a loaded state and toward an unloaded state to move the plunger assembly <NUM>' proximally and compress the flexible drug reservoir <NUM>').

The manifold <NUM>' also includes features that facilitate delivering the secondary drug <NUM>' to a patient at a substantially constant rate. More specifically, each input channel portion <NUM>' of the upper manifold <NUM>' includes a cross-sectional area (for example, a circular area) that increases in the proximal direction. As a resistance plunger <NUM>' moves proximally in such a tapering input channel portion <NUM>', the distance between the resistance plunger <NUM>' and the wall of the input channel portion <NUM>' increases. Tendrils of the resistance medium <NUM>' around the resistance plunger <NUM>' increase in thickness, and the shear stress around the resistance plunger <NUM>' decreases. This decreases the resistance force applied to the plunger assembly <NUM>', which compensates for an increasing shear stress applied to the resistance plunger <NUM>' due to its increasing contact length against the resistance medium <NUM>'. The decreasing resistance force also compensates for a decreasing force exerted by the biasing member <NUM>' as it moves from a loaded state (for example, as shown in <FIG>) and toward an unloaded state (for example, as shown in <FIG>; that is, as the biasing member <NUM>' moves the plunger assembly <NUM>' proximally). Overall, these changing forces cause the plunger assembly <NUM>' to move proximally at a substantially constant rate, and the drug-delivery device assembly <NUM>' may thereby deliver the secondary drug <NUM>' to a patient at a substantially constant rate.

The embodiments of the drug-delivery device assemblies <NUM>, <NUM>' described above include drug reservoirs and resistance channels that are arranged in parallel to each other. In some cases, parallel arrangements of drug reservoirs and resistance channels may be advantageous for one or more of the following reasons: (<NUM>) such arrangements facilitate providing a low-profile drug-device delivery assembly; (<NUM>) such arrangements provide by decoupling the size and location of the resistance channels from those of the drug reservoir; and (<NUM>) such arrangements permit the resistance medium to be gradually discharged from the output channel portions. The resulting decrease in shear stress may compensate for the decrease of the force exerted by the biasing member, and a drug-delivery device assembly may thereby deliver the secondary drug to a patient at a substantially constant rate. Alternatively, in some embodiments reservoirs and resistance channels of drug-delivery device assemblies are arranged in series with each other. Exemplary embodiments of such drug-delivery device assemblies are described in further detail below.

<FIG> illustrate another embodiment of a drug-delivery device assembly <NUM>" and an infusion hub <NUM>". The drug-delivery device assembly <NUM>" and the infusion hub <NUM>" are substantially similar to drug-delivery device assembly <NUM> and the infusion hub <NUM>, respectively, with like reference numerals indicating like parts, except as described below. Like the infusion hub <NUM>, the infusion hub <NUM>" may receive a primary drug from a primary drug source (shown elsewhere - for example, the primary drug source <NUM> of <FIG>). The infusion hub <NUM>" has a recessed upper surface portion <NUM>" to accommodate features of the drug-delivery device assembly <NUM>". The infusion hub <NUM>" also includes a generally transversely extending secondary drug channel <NUM>", and the secondary drug channel <NUM>" and the septum <NUM>" may be unused or omitted.

The following components of the drug-delivery device assembly <NUM>" are shown in <FIG>: a manifold <NUM>", a plunger assembly <NUM>", a biasing member <NUM>", and a cover <NUM>". The manifold <NUM>" includes a manifold drug channel <NUM>" coupled to the secondary drug channel <NUM>" of the infusion hub <NUM>". The manifold drug channel <NUM>" is also coupled to a common reservoir <NUM>". The common reservoir <NUM>" defines both a drug reservoir and a resistance channel. That is, the common reservoir <NUM>" initially carries the secondary drug <NUM>" at a proximal end (that is, adjacent to the manifold drug channel <NUM>"). The drug plunger <NUM>", which is separate from the remainder of the plunger assembly <NUM>", is disposed distally from the secondary drug <NUM>" in the reservoir. The resistance medium <NUM>" is disposed distally from the drug plunger <NUM>" in the common reservoir <NUM>". The resistance plunger <NUM>" is disposed distally from the resistance medium <NUM>" and is also received in the common reservoir <NUM>".

The biasing member <NUM>" may move from a loaded state (for example, as shown in <FIG>) and toward an unloaded state (for example, as shown in <FIG>) to move the resistance plunger <NUM>" proximally. The resistance plunger <NUM>" thereby moves the resistance medium <NUM>" proximally while the resistance medium <NUM>" exerts a resistance force in the opposite direction. The resistance medium <NUM>" moves the drug plunger <NUM>" proximally, which forces the secondary drug <NUM>" from the reservoir <NUM>", through the manifold drug channel <NUM>", through the infusion hub <NUM>", and into the patient's body together with any of the primary drug that is also present in the infusion hub <NUM>".

In some embodiments, the infusion hub <NUM>" and the drug-delivery device assembly <NUM>" may advantageously provide a low-profile and simple structure for delivering a relatively low volume dose of the secondary drug <NUM>". In these embodiments, the biasing member <NUM>" may move over a relatively small portion of its unloading distance to deliver the dose of the secondary drug <NUM>". The force exerted by the biasing member <NUM>" may remain substantially constant over such a distance, and the secondary drug <NUM>" is thereby delivered at a substantially constant rate.

<FIG> illustrate another embodiment of a drug-delivery device assembly <NUM>‴ and an infusion hub <NUM>"'. The drug-delivery device assembly <NUM>‴ and the infusion hub <NUM>‴ are substantially similar to drug-delivery device assembly <NUM> and the infusion hub <NUM>, respectively, with like reference numerals indicating like parts, except as described below. Like the infusion hub <NUM>, the infusion hub <NUM>‴ may receive a primary drug from a primary drug source (shown elsewhere - for example, the primary drug source <NUM> of <FIG>). The infusion hub <NUM>‴ has a recessed upper surface portion <NUM>‴ to accommodate features of the drug-delivery device assembly <NUM>"'. The infusion hub <NUM>‴ also includes a generally transversely extending secondary drug channel <NUM>‴ and a septum <NUM>"', and the secondary drug channel <NUM>‴ and the septum <NUM>‴ may be unused or omitted.

The following components of the drug-delivery device assembly <NUM>‴ are shown in <FIG>: a manifold <NUM>"', a plunger assembly <NUM>‴, a biasing member <NUM>"', and a cover <NUM>‴. The manifold <NUM>‴ includes a protrusion <NUM>‴ that pierces the septum <NUM>‴ of the infusion hub <NUM>"'. The protrusion <NUM>‴ includes a manifold drug channel <NUM>‴ for delivering the secondary drug <NUM>‴ to the secondary drug channel <NUM>‴ of the infusion hub <NUM>"'. The manifold drug channel <NUM>‴ is also coupled to a drug reservoir <NUM>"'. The drug reservoir <NUM>‴ initially carries a secondary drug <NUM>‴ at a proximal end (that is, adjacent to the manifold drug channel <NUM>‴). A drug plunger <NUM>‴, which is separate from the remainder of the plunger assembly <NUM>‴, is disposed distally from the secondary drug <NUM>‴ in the drug reservoir <NUM>"'. The drug reservoir <NUM>‴ is coupled to a transversely extending resistance channel <NUM>"', and a resistance medium <NUM>‴ is carried in the resistance channel <NUM>"'. The resistance channel <NUM>‴ may have a relatively small cross-sectional area (for example, a circular area) to slow movement of the resistance medium <NUM>‴, which facilitates delivering the secondary drug <NUM>‴ over a relatively long time period. The resistance channel <NUM>‴ also carries a resistance plunger <NUM>‴ distally from the resistance medium <NUM>"'.

The biasing member <NUM>‴ may be, for example and as illustrated in <FIG>, a compression spring, more specifically a conical spring. In some embodiments, the coils of the conical spring may nest inside one another in the loaded state, which advantageously facilitates providing the drug-delivery device assembly <NUM>‴ with a low-profile structure. Further, the conical spring may move over a relatively small portion of its unloading distance to deliver the dose of the secondary drug <NUM>"'. The force exerted by the biasing member <NUM>‴ may remain substantially constant over such a distance, and the secondary drug <NUM>‴ is thereby delivered at a substantially constant rate.

The biasing member <NUM>‴ may move from a loaded state (for example, as shown in <FIG>) and toward an unloaded state (for example, as shown in <FIG>) to move the resistance plunger <NUM>‴ proximally. The resistance plunger <NUM>‴ thereby moves the resistance medium <NUM>‴ transversely in the resistance channel <NUM>‴ while the resistance medium <NUM>‴ exerts a resistance force in the opposite direction. The resistance medium <NUM>‴ moves the drug plunger <NUM>‴ proximally, which forces the secondary drug <NUM>‴ from the drug reservoir <NUM>"', through the manifold drug channel <NUM>‴, through the infusion hub <NUM>"', and into the patient's body together with any of the primary drug that is also present in the infusion hub <NUM>"'.

Claim 1:
A drug-delivery device assembly (<NUM>, <NUM>', <NUM>", <NUM>"') comprising:
a manifold (<NUM>, <NUM>', <NUM>", <NUM>‴) comprising a drug channel (<NUM>, <NUM>', <NUM>", <NUM>"'), the manifold (<NUM>, <NUM>', <NUM>", <NUM>‴) configured to detachably couple with an infusion hub (<NUM>, <NUM>', <NUM>", <NUM>‴) configured to subcutaneously deliver a primary drug into a patient's body;
a drug reservoir (<NUM>, <NUM>') configured to store a secondary drug (<NUM>, <NUM>', <NUM>", <NUM>‴), the drug reservoir (<NUM>, <NUM>') disposed within the manifold (<NUM>, <NUM>', <NUM>", <NUM>‴) and coupled to the drug channel (<NUM>, <NUM>', <NUM>", <NUM>‴);
a drug plunger (<NUM>, <NUM>", <NUM>"') being movable relative to the drug reservoir (<NUM>, <NUM>'); and
a biasing member (<NUM>, <NUM>', <NUM>", <NUM>‴) configured to move away from a loaded state and toward an unloaded state to move the drug plunger (<NUM>, <NUM>", <NUM>‴) relative to the drug reservoir (<NUM>, <NUM>') and force the secondary drug (<NUM>, <NUM>', <NUM>", <NUM>‴) from the drug reservoir (<NUM>, <NUM>'), through the drug channel (<NUM>, <NUM>', <NUM>", <NUM>‴), through the infusion hub (<NUM>, <NUM>', <NUM>", <NUM>‴), and into the patient's body;
characterized in that the manifold (<NUM>, <NUM>', <NUM>", <NUM>‴) further comprises a resistance channel (<NUM>, <NUM>", <NUM>"') configured to carry a resistance medium (<NUM>, <NUM>', <NUM>", <NUM>‴), wherein a movement of the resistance medium (<NUM>, <NUM>', <NUM>", <NUM>‴) in the resistance channel (<NUM>, <NUM>", <NUM>‴) provides resistance to a movement of the biasing member (<NUM>, <NUM>', <NUM>", <NUM>"') away from the loaded state and toward the unloaded state.