Reconstitution on-body drug delivery system

Abstract

A therapeutic substance delivery device (20) includes a housing (26), a therapeutic substance container (28), a delivery fluid path (30) including a container outlet needle (32) configured to penetrate the container, a container inlet needle (40) configured to penetrate the container, and a one-way filling port (46) coupled to the container inlet needle and configured to engage with a syringe (22) containing liquid (24). The liquid from the syringe can be injected into the container via the one-way filling port and the container inlet needle. As liquid is injected into the container, air within the container exits the container via the container outlet needle and enters an internal cavity (52) of the delivery device. Control circuity (50) drives a pump (48) to draw therapeutic substance from the container following injection of the liquid into the container, and deliver the therapeutic substance to the subject. Other applications are also described.

Description

[0001] RECONSTITUTION ON-BODY DRUG DELIVERY SYSTEM

[0002] CROSS REFERENCE TO RELATED APPLICATIONS

[0003] The present application claims the priority of US 63 / 623,486 to Ben-David et al., filed Jan. 22, 2024, entitled, “Reconstitution on-body drug delivery system,” which is assigned to the assignee of the present application and incorporated herein by reference.

[0004] The present application is related to an international patent application filed on even date herewith, entitled, "User-interactive drug delivery device packaging," which is assigned to the assignee of the present application, is incorporated herein by reference, and claims the priority of US 63 / 623,499 to Ben-David et al., filed Jan. 22, 2024, entitled, “User-interactive drug delivery device packaging,” which is assigned to the assignee of the present application and incorporated herein by reference.

[0005] FIELD OF THE INVENTION

[0006] The present invention relates generally to delivery of a therapeutic substance to a subject, and more specifically to wearable drug delivery devices.

[0007] BACKGROUND

[0008] Pumps are often used in the medical industry for delivering therapeutic substances, e.g., drugs, to subjects. Therapeutic substances such as saline solution, insulin, antibiotics, and chemotherapy drugs may all be delivered to a subject with medical pumps. While hospitalization is required for delivery of some therapeutic substances, other therapeutic substances, such as for example insulin, do not require that the subject be in the hospital. Wearable therapeutic substance delivery devices enable patients to go about their daily lives while receiving a therapeutic substance.

[0009] It is often the case that therapeutic substances are sold by pharmaceutical companies in lyophilized form. A lyophilized therapeutic substance needs to be reconstituted by mixing the lyophilized therapeutic substance with a liquid prior to being delivered to the subject. Additionally, some therapeutic substances are sold by pharmaceutical companies as separate liquids each containing part(s) of the therapeutic substance. The liquids containing the different parts of the therapeutic substance are intended to be mixed right before being delivered to the subject in order to avoid different parts of the therapeutic substance mixing with each other during shelf life of the therapeutic substance.

[0010] In many cases, needle syringes are used in order to fill a therapeutic substance container, e.g., to reconstitute a lyophilized drug within the container, or to mix different parts of a therapeutic substance together inside the container, or to fill an empty container, prior to delivery of the therapeutic substance to a subject.

[0011] SUMMARY OF THE INVENTION

[0012] In accordance with some applications of the present invention, a therapeutic substance delivery device is provided which enables a user, e.g., a patient or other non -healthcare- professional to perform a filling process of a therapeutic substance container disposed at least partially within a housing of the therapeutic substance delivery device by injecting liquid from a syringe, e.g., a prefilled syringe, into the therapeutic substance container via a filling port on the therapeutic substance delivery device. For some applications, the purpose of the filling process may be, for example, to reconstitute a lyophilized drug disposed within the therapeutic substance container of the therapeutic substance delivery device, to mix a therapeutic substance by adding a first liquid into the container of the therapeutic substance that already contains a second liquid, or to fill an empty container of the therapeutic substance delivery device. An advantage of being able to fill the therapeutic substance container via a needleless-filling port, while the container is already disposed within the therapeutic substance delivery device, is that the user is able to perform the therapeutic substance reconstitution, therapeutic substance mixing, or simple therapeutic substance filling without having to handle a needle syringe, or accessories such as a vial adapter.

[0013] Thus, in accordance with some applications of the present invention, a therapeutic substance delivery device is provided for delivering a therapeutic substance to a subject, i.e., a patient, and for use with a syringe containing a liquid, e.g., a pre-filled syringe. The therapeutic substance delivery device has a housing with a therapeutic substance container disposed at least partially within the housing. Typically, the therapeutic substance delivery device has two needles that interact with the therapeutic substance container: a container outlet needle and a container inlet needle. The container outlet needle is disposed at an upstream end of a delivery fluid path. Thus, during delivery of the therapeutic substance to the subject, therapeutic substance from the therapeutic substance container exits the container toward the subject via the container outlet needle. The container inlet needle is the needle through which the liquid from the syringe enters the container. Typically, both the container outlet needle and the container inlet needle are initially disposed outside of the container and subsequently penetrate the container, e.g., separately or together.

[0014] A one-way filling port is coupled to the container inlet needle and is configured to engage with the syringe, e.g., by a Luer Lock connection. During the filling process the liquid from the syringe is injected into the container via the one-way filling port and the container inlet needle. Typically, the therapeutic substance container is filled with air prior to the filling process. Thus, the container and the container outlet needle are arranged such that as the liquid is injected into the container, air within the container exits the container via the container outlet needle and enters an internal cavity of the therapeutic substance delivery device. In order to deliver the therapeutic substance to the subject, the therapeutic substance delivery device includes a pump that draws therapeutic substance from the container via the container outlet needle following the injection of the liquid into the container and delivers the therapeutic substance to the subject.

[0015] There is therefore provided, in accordance with some applications of the present invention, a therapeutic substance delivery device for delivering a therapeutic substance to a subject, for use with a syringe containing a liquid, the therapeutic substance delivery device including:

[0016] (a) a housing,

[0017] (b) a therapeutic substance container disposed at least partially within the housing,

[0018] (c) a delivery fluid path including a container outlet needle disposed at an upstream end of the delivery fluid path, the container outlet needle configured to penetrate the container,

[0019] (d) a container inlet needle configured to penetrate the container, and

[0020] (e) a one-way filling port coupled to the container inlet needle and configured to engage with the syringe,

[0021] (i) the one-way filling port, the container inlet needle, and the container arranged such that the liquid from the syringe can be injected into the container via the one-way filling port and the container inlet needle, and (ii) the container and the container outlet needle arranged such that as the liquid is injected into the container, air within the container exits the container via the container outlet needle and enters an internal cavity of the therapeutic substance delivery device,

[0022] (f) a pump configured to (i) draw therapeutic substance from the container via the container outlet needle following the injection of the liquid into the container and (ii) deliver the therapeutic substance to the subject, and

[0023] (g) control circuitry configured to drive the pump.

[0024] For some applications, the container is pre-filled with a lyophilized drug such that when the liquid is injected into the container the lyophilized drug is reconstituted.

[0025] For some applications, the therapeutic substance delivery device is for use with a syringe containing a liquid therapeutic substance, and the container is empty when the therapeutic substance delivery device is packaged for commercial sale.

[0026] For some applications, the therapeutic substance delivery device is for use with a syringe containing a first liquid, and the container is partially filled with a second liquid when the therapeutic substance delivery device is packaged for commercial sale, such that when the first liquid is injected into the container the first liquid and the second liquid mix to form a therapeutic substance.

[0027] For some applications: the delivery fluid path further includes an injection assembly at a downstream end of the delivery fluid path, the injection assembly comprising an injection needle, the injection needle disposed, in a pre-subject-injection state of the therapeutic substance delivery device, within the internal cavity of the therapeutic substance delivery device, and the delivery fluid path is arranged such that the entering of the air into the internal cavity of the therapeutic substance delivery device is via the injection needle.

[0028] For some applications, the therapeutic substance delivery device is arranged to accommodate a range of volumes of the therapeutic substance container, the range including a volume of 0.8 ml and a volume of 50 ml, and the therapeutic substance container has a volume that is within the range. For some applications: the container inlet needle includes a downstream end that is configured to penetrate the container, and the therapeutic substance delivery device further includes a container inlet needle block, and the container inlet needle and the container inlet needle block are arranged such that in a pre- activation state of the therapeutic substance delivery device, the downstream end of the container inlet needle is sealed by the container inlet needle block.

[0029] For some applications, the container inlet needle block includes a sealing septum of the therapeutic substance container.

[0030] For some applications, the sealing septum is 2-10 mm thick.

[0031] For some applications, the therapeutic substance delivery device is configured to transition from (i) a first state in which the downstream end of the container inlet needle is disposed within the container inlet needle block and outside of the container to (ii) a second state in which the downstream end of the container inlet needle is disposed outside of the container inlet needle block and within the container.

[0032] For some applications, the container includes a septum and the control circuitry is further configured to disinfect the septum of the container and to subsequently actuate the transition of the therapeutic substance delivery device from the first state to the second state upon activation of the therapeutic substance delivery device.

[0033] For some applications, the downstream end of the container inlet needle is configured to penetrate the container by the container inlet needle sliding from (i) a first position in which the downstream end of the container inlet needle is disposed within the container inlet needle block and outside of the container to (ii) a second position in which the downstream end of the container inlet needle is disposed outside of the container inlet needle block and within the container.

[0034] For some applications, the container includes a septum and the control circuitry is further configured to disinfect the septum of the container and to subsequently actuate the sliding of the container inlet needle from the first position to the second position upon activation of the therapeutic substance delivery device. For some applications, the container is a therapeutic substance container having an interior volume that decreases as the therapeutic substance is drawn from the container.

[0035] For some applications: the container is a therapeutic substance cartridge including a slidable plunger which in a pre-liquid-injection state of the therapeutic substance cartridge is disposed at a distal end of the therapeutic substance cartridge, the cartridge includes a septum at a proximal end of the cartridge opposite the distal end, the container inlet needle and the container outlet needle are configured to penetrate the septum, and the plunger is configured to slide from the distal end of the cartridge toward the proximal end of the cartridge in response to the pump drawing the therapeutic substance from the cartridge.

[0036] For some applications: the therapeutic substance container is a non-collapsible therapeutic substance container having an internal volume that does not decrease as the therapeutic substance is drawn from the non-collapsible container, and the therapeutic substance delivery device further includes a one-way air valve disposed within the internal cavity of the therapeutic substance delivery device, wherein: the non-collapsible container includes a septum, and the container inlet needle includes a downstream end and an upstream end, the downstream end of the container inlet needle configured to penetrate the septum, and the upstream end of the container inlet needle disposed in fluid communication with both (i) the one-way filling port and (ii) the one-way air valve, the one-way filling port (a) is disengageable from the syringe subsequently to the liquid from the syringe being injected into the non-collapsible container, and (b) is configured to self-seal subsequently to disengagement of the one-way filling port from the syringe, and the container inlet needle and the one-way air valve form an air-path to allow the air from within the internal cavity of the therapeutic substance delivery device to enter the non-collapsible container as the pump draws the therapeutic substance from the non- collapsible container via the container outlet needle. For some applications, the non-collapsible container is a therapeutic substance vial.

[0037] For some applications, the therapeutic substance delivery device further includes an airdetector disposed within the therapeutic substance delivery device and configured to detect air in the delivery fluid path downstream of the container outlet needle, and the control circuitry is configured to assess a status of the injection of the liquid into the container in response to an indication from the air-detector indicative of air within the delivery fluid path.

[0038] For some applications, the therapeutic substance delivery device further includes a vibration motor configured to vibrate the container, and the control circuitry is configured to activate the vibration motor to:

[0039] (a) in a first mode, mix the therapeutic substance within the container, and

[0040] (b) in a second mode, issue an alert to the subject regarding a status of the therapeutic substance delivery device.

[0041] For some applications, the therapeutic substance delivery device further includes an accelerometer configured to detect motion of the therapeutic substance delivery device, and the control circuitry is further configured to initiate driving the pump to draw the therapeutic substance from the container in response to an indication from the accelerometer that the therapeutic substance delivery device has been moved in a manner that mixes the therapeutic substance within the container.

[0042] For some applications, the therapeutic substance delivery device is configured to be placed on skin of the subject following the therapeutic substance delivery device being moved in a manner that mixes the therapeutic substance within the container, wherein: the therapeutic substance delivery device further includes a delivery-initiating user interface configured to be activated by the subject following placement of the therapeutic substance delivery device on the skin of the subject, and the control circuitry is configured to issue an alert if the delivery-initiating user interface is activated prior to the control circuitry having received the indication from the accelerometer that the therapeutic substance delivery device has been moved in a manner that mixes the therapeutic substance within the container.

[0043] For some applications, the therapeutic substance delivery device further includes an on- body sensor configured to sense that therapeutic substance delivery device is placed on the skin of the subject, the control circuitry is configured to issue an alert if the delivery -initiating user interface is activated prior to the control circuitry having received an indication from the on-body sensor that the therapeutic substance delivery device has been placed on the skin of the subject.

[0044] For some applications, the therapeutic substance delivery device further includes a temperature sensor disposed within the therapeutic substance delivery device and arranged to sense the temperature of the therapeutic substance within the container, and the control circuitry is further configured to initiate driving the pump to draw the therapeutic substance from the container in response to an indication from the temperature sensor that the temperature of the therapeutic substance within the container is above a threshold temperature.

[0045] The present invention will be more fully understood from the following detailed description of applications thereof, taken together with the drawings, in which:

[0046] BRIEF DESCRIPTION OF THE DRAWINGS

[0047] Fig. 1 is a schematic illustration of a therapeutic substance delivery device, in accordance with some applications of the present invention;

[0048] Fig. 2A shows an exploded view of various components of the therapeutic substance delivery device, in accordance with some applications of the present invention;

[0049] Fig. 2B is a schematic illustration of various components of the therapeutic substance delivery device, in accordance with some applications of the present invention; and

[0050] Figs. 3A-B, and 4 are schematic illustrations of the therapeutic substance delivery device, in accordance with some applications of the present invention.

[0051] DETAILED DESCRIPTION

[0052] Reference is now made to Fig. 1, which is a schematic illustration of a therapeutic substance delivery device 20 for delivering therapeutic substance to a subject, in accordance with some applications of the present invention. Typically, therapeutic substance delivery device 20 is for use with a syringe 22 containing a liquid 24. For some applications, syringe 22 is sold for commercial sale along with therapeutic substance delivery device 20, e.g., included in the same commercial packaging, or included as an accessory in its own commercial packaging. Therapeutic substance delivery device 20 has a housing 26 and a therapeutic substance container 28 disposed at least partially within housing 26.

[0053] As described hereinabove, for some applications therapeutic substance container 28 is prefilled with a lyophilized therapeutic substance. The lyophilized therapeutic substance needs to be reconstituted prior to delivery of the therapeutic substance to the patient. Thus, for some applications, liquid 24 within syringe 22 is a liquid, e.g., saline, that when mixed with the powder of the lyophilized therapeutic substance, i.e., when injected into therapeutic substance container 28, reconstitutes the therapeutic substance. Some examples of therapeutic substances that may be sold in lyophilized form include (a) antibiotics, such as some types of semi-synthetic penicillins and cephalosporins, (b) some of the salts of erythromycin, doxycycline, and chloramphenicol, and (c) various biological drugs. Some additional examples of therapeutic substances that may be sold in lyophilized form include Ethyol® (Medimmune), Zithromax® (Pfizer), Azactam® (Bristol Myers Squibb), and Cytovene® (Roche).

[0054] Alternatively, for some applications, liquid 24 within syringe 22 may be a first liquid containing a first part of the therapeutic substance, and container 28 may contain a second liquid containing a second part of the therapeutic substance. The first liquid and the second liquid need to be mixed in order to form the therapeutic substance prior to delivery of the therapeutic substance to the patient. For example, some therapeutic substances are maintained in separate liquid parts during shelf life in order to avoid certain ingredients within the therapeutic substance mixing together during the shelf life of the therapeutic substance. For some applications, maintaining the liquid parts of the therapeutic substance separate can increase the shelf-life of the therapeutic substance. For example, some chemotherapy drugs may be maintained in separate liquids that need to be mixed prior to delivery.

[0055] Alternatively, for some applications, container 28 of therapeutic substance delivery device 20 may be empty when therapeutic substance delivery device 20 is sold for commercial sale, and liquid 24 disposed within syringe 22 is the therapeutic substance, such that the filling processes fills empty container 28 with the therapeutic substance from syringe 22.

[0056] Reference is now made to Figs. 2A-B, which show, respectively, an exploded view of various components of therapeutic substance delivery device 20 and a schematic illustration of various components of therapeutic substance delivery device 20, in accordance with some applications of the present invention. Typically, a delivery fluid path 30, i.e., the fluid path through which the therapeutic substance travels from therapeutic substance container 28 to the subject, includes a container outlet needle 32 at an upstream end 34 of delivery fluid path 30. Container outlet needle 32 penetrates therapeutic substance container 28, i.e., a downstream end 36 of container outlet needle 32 penetrates therapeutic substance container 28. An upstream end 38 of container outlet needle 32 is in fluid communication with upstream end 34 of delivery fluid path 30, such that when container outlet needle 32 is in a state in which it is penetrating therapeutic substance container 28, container outlet needle 32 provides fluid communication between the interior of therapeutic substance container 28 and delivery fluid path 30.

[0057] Therapeutic substance delivery device 20 further includes a container inlet needle 40 which also penetrates therapeutic substance container 28, i.e., a downstream end 42 of container inlet needle 40 penetrates therapeutic substance container 28. A one-way filling port 46 is coupled to container inlet needle 40, i.e., to an upstream end 44 of container inlet needle 40, by a flexible tube 47. One-way filling port 46 can engage with syringe 22, e.g., by a Luer Lock connection, such that liquid 24 from syringe 22 can be injected into therapeutic substance container 28 via one-way filling port 46 and container inlet needle 40. Typically, a pump 48 (i) draws therapeutic substance from therapeutic substance container 28 via container outlet needle 32 following the injection of liquid 24 into therapeutic substance container 28 and (ii) delivers the therapeutic substance to the subject. Control circuitry 50 drives pump 48.

[0058] For some applications, therapeutic substance delivery device 20 can accommodate a range of volumes of therapeutic substance container 28. For some applications, the range of volumes includes 0.8 ml and 50 ml. For example, a collar 58 may be disposed within housing 26 such that therapeutic substance container 28 is held in place within housing 26 by collar 58. Collar 58 may accommodate a range of therapeutic substance containers of different sizes, e.g., small containers such as 0.8 ml containers up to large containers such as 50 ml containers.

[0059] Fig. 2B shows a schematic illustration of various components of therapeutic substance delivery device 20 which illustrates delivery fluid path 30. It is noted that, for example using techniques described in US Patent No. 11,357,909 to Ben-David et al., which is incorporated herein by reference, container outlet needle 32 and container inlet needle 40 may each (a) have an initial position in which downstream end 36 of container outlet needle 32 and downstream end 42 of container inlet needle 40 are disposed outside of therapeutic substance container 28, and (b) transition from the initial position to a subsequent position in which downstream end 36 and downstream end 42 have penetrated therapeutic substance container 28. Additionally, it is noted that delivery fluid path 30 may be arranged utilizing techniques described with respect to fluid path 26 and / or fluid intake path 128 described in US Patent No. 11,357,909.

[0060] Typically, prior to the filling process of therapeutic substance container 28, the container contains air. Thus, therapeutic substance container 28 and container outlet needle 32 are arranged such that as liquid 24 from syringe 22 is injected into therapeutic substance container 28, air within therapeutic substance container 28 exits the container via container outlet needle 32 and enters an internal cavity 52 of therapeutic substance delivery device 20, i.e., through delivery fluid path 30. For some applications, delivery fluid path 30 includes an injection assembly 54 at a downstream end 57 of delivery fluid path 30. Injection assembly 54 includes an injection needle 56 (shown in Fig. 2A). In a pre-subject- injection state of therapeutic substance delivery device 20, i.e., prior to injection needle 56 entering the skin of the subject, injection needle 56 is disposed within internal cavity 52 of therapeutic substance delivery device 20. Thus, for some applications, delivery path 30 is arranged such that the air from within therapeutic substance container 28 that enters internal cavity 52 during the filling process, enters the internal cavity via injection needle 56. It is noted that, for some applications, injection assembly 54 may utilize techniques such as those described with respect to body needle injection mechanism 28 of US Patent No. 11,357,909.

[0061] Reference is now made to Figs. 3A-B and Fig. 4, which are schematic illustrations of therapeutic substance delivery device 20, in accordance with some applications of the present invention. For some applications, upon activation of therapeutic substance delivery device 20, therapeutic substance delivery device 20 performs one or more startup steps. These startup steps may include, for example, (a) disinfecting a disinfection chamber 60 including a septum 62 of therapeutic substance container 28, e.g., by control circuitry 50 activating a disinfection assembly 63 (shown in Figs. 3A-B and 4) disposed within therapeutic substance delivery device 20, and (b) establishing fluid communication (i) between container inlet needle 40 and therapeutic substance container 28, and (ii) between container outlet needle 32 and therapeutic substance container 28, further described hereinbelow. It is noted that the disinfection of disinfection chamber 60 may utilize techniques described in US Patent No. 10,869,961 to Ben-David et al., which is incorporated herein by reference. Since, for some applications, in a pre-activation state of therapeutic substance delivery device 20, container inlet needle 40 is not in fluid communication with therapeutic substance container 28, it is advantageous for therapeutic substance delivery device 20 to prevent a user, e.g., the subject, from being able to inject liquid 24 from syringe 22 via filling port 46. Thus, for some applications, therapeutic substance delivery device 20 includes a container inlet needle block 64. Container inlet needle 40 and container inlet needle block 64 are arranged such that in a preactivation state of therapeutic substance delivery device 20, downstream end 42 of container inlet needle 40 is sealed by container inlet needle block 64. As described hereinabove, downstream end 42 of container inlet needle 40 penetrates therapeutic substance container 28 in order to establish the fluid communication between filling port 46 and therapeutic substance container 28. As illustrated in part (i) of Fig. 3 A, in the pre-activation state of therapeutic substance delivery device 20, downstream end 42 of container inlet needle 40 is disposed inside container inlet needle block 64, e.g., a rubber block, and is thus sealed. The user is thus unable to inject liquid 24 in syringe 22 via filling port 46 in the pre-activation state of therapeutic substance delivery device 20.

[0062] For some applications, therapeutic substance delivery device 20 includes dedicated control circuitry 66 (shown in Fig. 2A) which includes an indicator 67, e.g., a visible indicator, e.g., a color-changing LED that is visible through a hole 68 of housing 26, that indicates to the user when therapeutic substance delivery device 20 has finished performing the startup steps and the device is ready for the user to engage syringe 22 with filling port 46 and fill therapeutic substance container 28. For some applications, dedicated control circuitry 66 is also responsible for activating therapeutic substance delivery device 20, thus initiating the performance of the startup steps.

[0063] For some applications, the establishment of fluid communication between container inlet needle 40 and therapeutic substance container 28 is by therapeutic substance delivery device 20 transitioning from (i) a first state in which downstream end 42 of container inlet needle 40 is disposed within container inlet needle block 64 and outside of therapeutic substance container 28 (e.g., as shown in the top half of Fig. 3A) to (ii) a second state in which downstream end 42 of container inlet needle 40 is disposed outside of container inlet needle block 64 and within therapeutic substance container 28 (e.g., as shown in the bottom half of Fig. 3 A). Arrow 70 indicates the transition from the first state to the second state. For some applications, upon activation of therapeutic substance delivery device 20, control circuitry 50 actuates the disinfecting of disinfection chamber 60 including septum 62 of therapeutic substance container 28, e.g., by activating disinfection assembly 63 disposed within therapeutic substance delivery device 20, and subsequently to the disinfecting actuates the transition of therapeutic substance delivery device 20 from the first state to the second state.

[0064] For some applications, the establishment of fluid communication between container inlet needle 40 and therapeutic substance container 28, e.g., the transition between the first state and the second state as described above, is by container inlet needle 40 sliding from (i) a first position in which downstream end 42 of container inlet needle 40 is disposed within container inlet needle block 64 and outside of therapeutic substance container 28 (e.g., as shown in the top half of Fig. 3 A) to (ii) a second position in which downstream end 42 of container inlet needle 40 is disposed outside of container inlet needle block 64 and within therapeutic substance container 28 (e.g., as shown in the bottom half of Fig. 3 A). Arrow 71 indicates the sliding of container inlet needle 40 from the first position to the second position. Dashed lines, 72, 74, and 76 illustrate that the sliding of container inlet needle 40 is with respect to housing 26 of therapeutic substance delivery device 20 and with respect to container inlet needle block 64, i.e., container inlet needle block 64 remains stationary while container inlet needle 40 slides forward such that downstream end 42 of container inlet needle 40, initially disposed within container inlet needle block 64, pierces through container inlet needle block 64 on its way to penetrating therapeutic substance container 28. For some applications, upon activation of therapeutic substance delivery device 20, control circuitry 50 actuates the disinfecting of disinfection chamber 60 including septum 62 of therapeutic substance container 28, e.g., by activating disinfection assembly 63 disposed within therapeutic substance delivery device 20, and subsequently to the disinfecting actuates the sliding of container inlet needle 40 from the first position to the second position.

[0065] It is noted that, for some applications, the establishment of fluid communication between container outlet needle 32 and therapeutic substance container 28 may also occur in the same manner as the establishment of fluid communication between container inlet needle 40 and therapeutic substance container 28 as described hereinabove. As shown in Figs. 2-4, container inlet needle 40 and container outlet needle 32 are coupled to a common overmold 78, which slides forward as illustrated by arrow 71. This is by way of example and is not intended to be limiting. For some applications, container inlet needle 40 and container outlet needle 32 may be controlled via separate mechanisms and may penetrate therapeutic substance container 28 separately from each other.

[0066] For some applications, the container inlet needle block may itself be a sealing septum of therapeutic substance container 28 (configuration not shown). For example, the sealing septum may be thick enough, e.g., at least 2 mm thick and / or less than 10 mm thick, that downstream end 42 of container inlet needle 40 may initially start within the septum and subsequently penetrate through the septum upon activation of therapeutic substance delivery device 20.

[0067] As described hereinabove, during the filling of therapeutic substance container 28, sterile air from within therapeutic substance container 28 exits therapeutic substance container 28 via container outlet needle 32 and enters internal cavity 52 of housing 26. In order to prevent pressure from building up within housing 26, housing 26 typically includes a filter 80 (shown in Figs. 3A- B and 4). Filter 80 allows air to pass through it while maintaining internal cavity 52 a sterile environment. For some applications, filter 80 may be an air filtration membrane, e.g., made of a hydrophobic material such as PTFE. For some applications, a pore size of filter 80 may be at least 0.22 microns and / or less than 0.45 microns.

[0068] It is noted that everything described hereinabove with respect to Figs. 3A-B and 4 applies to both the configuration of therapeutic substance delivery device 20 as shown in Figs. 3A-B and the configuration of therapeutic substance delivery device 20 as shown in Fig. 4, mutatis mutandis.

[0069] Reference is now made specifically to Figs. 3A-B. For some applications, therapeutic substance container 28 is a therapeutic substance container having an interior volume that decreases as the therapeutic substance is drawn from the container. For example, therapeutic substance container 28 may be a therapeutic substance cartridge 29 that has a slidable plunger 82 which in a pre-liquid-injection state of therapeutic substance cartridge 29 is disposed at a distal end 84 of therapeutic substance cartridge 29, such as is shown in parts (i) and (ii) of Fig. 3A. Septum 62 of therapeutic substance cartridge 29 is disposed at a proximal end 86 of therapeutic substance cartridge 29 opposite distal end 84. As described hereinabove, container inlet needle 40 and container outlet needle 32 penetrate septum 62 in order to establish fluid communication with the interior of therapeutic substance cartridge 29. As illustrated by Fig. 3B, during delivery of the therapeutic substance to the subject, plunger 82 slides from distal end 84 of therapeutic substance cartridge 29 toward proximal end 86 of therapeutic substance cartridge 29 in response to pump 48 drawing the therapeutic substance from therapeutic substance cartridge 29.

[0070] Reference is now made specifically to Fig. 4. For some applications, therapeutic substance container 28 is a non-collapsible therapeutic substance container 88 having an internal volume that does not decrease as the therapeutic substance is drawn from the non-collapsible container, e.g., a therapeutic substance vial as shown in Fig. 4. Since the internal volume of a non-collapsible therapeutic substance container does not change when therapeutic substance is drawn from the container, air must be vented into non-collapsible therapeutic substance container 88 in order to prevent a vacuum from forming within the non-collapsible container. Thus, for some applications, therapeutic substance delivery device 20 includes a one-way air valve 90, e.g., a duckbill valve, disposed within internal cavity 52 of therapeutic substance delivery device 20 such that sterile air from within internal cavity 52 can flow through one-way valve 90. As described hereinabove, downstream end 42 of container inlet needle 40 penetrates septum 62 of non-collapsible therapeutic substance container 88. Upstream end 44 of container inlet needle 40 is disposed in fluid communication with both (i) one-way filling port 46 (as described hereinabove and shown in Fig. 2A), and (ii) one-way air-valve 90. Thus, one-way valve 90 allows air to flow from internal cavity 52 into container inlet needle 40.

[0071] During the filling of non-collapsible therapeutic substance container 88, liquid 24 flows from filling port 46 through container inlet needle 40 into non-collapsible therapeutic substance container 88. One-way valve 90 does not permit liquid 24 injected via filling port 46 to enter internal cavity 52. Once the user, e.g., the subject, has finished injecting liquid 24 from syringe 22 into non-collapsible therapeutic substance container 88, one-way filling port 46 (a) is disengaged from the syringe, e.g., by the user unscrewing the Luer Lock connection, and (b) selfseals subsequently to disengagement from syringe 22. For example, filling port 46 may be a selfsealing Luer Lock port that opens when syringe 22 is engaged with the Luer Lock port and closes automatically when syringe 22 is disengaged from the Luer Lock port. Thus, once the filling process is complete, container inlet needle 40 and one-way air valve 90 form an air-path to allow sterile air from within internal cavity 52 of therapeutic substance delivery device 20 to enter non- collapsible therapeutic substance container 88 as pump 48 draws the therapeutic substance from the non-collapsible container via container outlet needle 32. Filling port 46 being sealed (e.g., self-sealed) subsequently to the filling forces air to enter non-collapsible therapeutic substance container 88 from one-way valve 90 (and not directly from the outside environment), thus ensuring that the therapeutic substance remains sterile.

[0072] It is noted that filter 80 is a two-way filter and allows air to pass through it from internal cavity 52 to the outside environment and allows air to pass through it from the outside environment to internal cavity 52, while preventing the entrance of particles, e.g., dirt, bacteria, and / or virus particles to enter internal cavity 52. Thus, during the filling process of non-collapsible therapeutic substance container 88 filter 80 allows the extra air from within non-collapsible therapeutic substance container 88 to exit housing 26 so that pressure does not increase within housing 26. Subsequently, during the delivery of the therapeutic substance to the subject, the reduced pressure within non-collapsible therapeutic substance container 88 causes air within internal cavity 52 to flow into non-collapsible therapeutic substance container 88 via one-way valve 90. This in turn causes reduced pressure within housing 26 such that air from the outside environment flows into internal cavity 52 via filter 80.

[0073] For some applications, when a lyophilized therapeutic substance is reconstituted or two separate liquid parts of a therapeutic substance are brought together, the resulting therapeutic substance needs to be mixed, e.g., stirred or swirled. Thus, for some applications, mixing the therapeutic substance is the last step in the filling process that should be done prior to placement of therapeutic substance delivery device 20 on the subject's body for treatment. For example, the user, e.g., the subject, may receive instructions to move therapeutic substance delivery device 20 in a manner that mixes the therapeutic substance within therapeutic substance container 28 following the injection of liquid 24 into therapeutic substance container 28. In order to prevent the reconstituted or newly formed therapeutic substance (from separate parts) from being delivered to the subject prior to being mixed, for some applications therapeutic substance delivery device 20 has an accelerometer 92 (shown in Figs. 3A-B, and 4). Accelerometer 92 detects motion of therapeutic substance delivery device 20, and control circuitry 50 (shown in Fig. 2A) initiates driving pump 48 to draw the therapeutic substance from therapeutic substance container 28 in response to an indication from accelerometer 92 that therapeutic substance delivery device 20 has been moved in a manner that mixes the therapeutic substance within therapeutic substance container 28. Reference is again made to Fig. 2A. It is noted that although Fig. 2A depicts the configuration of therapeutic substance delivery device 20 when used with a non-collapsible container, this is not limiting and is just by way of example.

[0074] For some applications, alternatively or additionally to the user, e.g., the subject, moving therapeutic substance delivery device 20 in a manner that mixes the therapeutic substance, therapeutic substance delivery device 20 includes a vibration motor 94 that vibrates therapeutic substance container 28. Vibration motor 94 (shown in Fig. 2A) is typically built into a top shell 96 of housing 26 such that vibration motor 94 is in close proximity to, e.g., in contact with, therapeutic substance container 28 within housing 26. Vibration motor 94 may also be used to issue a tactile alert to the subject regarding a status of therapeutic substance delivery device 20. Thus, for some applications, control circuitry 50 may activate vibration motor 94 to (a) in a first mode, mix the therapeutic substance within therapeutic substance container 28, and (b) in a second mode, issue an alert to the subject regarding a status of therapeutic substance delivery device 20.

[0075] Typically, following the user, e.g., the subject, moving therapeutic substance delivery device 20 in a manner that mixes the therapeutic substance, therapeutic substance delivery device 20 is placed on the skin of the subject. For some applications therapeutic substance delivery device 20 has a delivery-initiating user interface 98, e.g., a button on top shell 96 of housing 26 such as is shown in Fig. 2A. Typically, following therapeutic substance delivery device 20 being been placed on the skin of the subject, the subject activates delivery-initiating user interface 98. It is possible however that a human error may occur and the subject may forget the step of moving therapeutic substance delivery device 20 in a manner that mixes the therapeutic substance and may instead proceed directly to placing therapeutic substance delivery device 20 on the skin and activating delivery-initiating user interface 98. In such an instance, in order to prevent the unmixed therapeutic substance from being delivered to the subject, control circuitry 50 issues an alert, e.g., using vibration motor 94, if delivery-initiating user interface 98 is activated prior to control circuitry 50 having received the indication from accelerometer 92 that therapeutic substance delivery device 20 has been moved in a manner that mixes the therapeutic substance within therapeutic substance container 28.

[0076] Another human error which may occur is the subject activating delivery-initiating user interface 98 prior to having placed therapeutic substance delivery device 20 on the skin of the subject. Thus, for some applications, therapeutic substance delivery device 20 has an on-body sensor 100 (shown in Figs. 3A-B and 4) that senses when therapeutic substance delivery device 20 is placed on the skin of the subject. Control circuitry 50 is configured to issue an alert, e.g., using vibration motor 94, if delivery-initiating user interface 98 is activated prior to control circuitry 50 having received an indication from on -body sensor 100 that therapeutic substance delivery device 20 has been placed on the skin of the subject.

[0077] For some applications, the therapeutic substance may be stored during shelf-life at a refrigerated temperature and may need to warm up prior to delivery to the subject. Thus, for some applications, therapeutic substance delivery device has a temperature sensor 102 (shown in Figs. 3A-B and 4) disposed within therapeutic substance delivery device 20 and arranged to sense the temperature of the therapeutic substance within therapeutic substance container 28. Control circuitry 50 initiates driving pump 48 to draw the therapeutic substance from therapeutic substance container 28 in response to an indication from temperature sensor 102 that the temperature of the therapeutic substance within therapeutic substance container 28 is above a threshold temperature.

[0078] For some applications, therapeutic substance delivery device 20 comprises an air-detector 104, e.g., an optical air-detector, disposed within therapeutic substance delivery device 20 in order to detect air in delivery fluid path 30 downstream of container outlet needle 32. Once control circuitry 50 has activated pump 48 to begin drawing therapeutic substance from therapeutic substance container 28 and deliver it to the subject, control circuitry 50 may assess a status of the injection of liquid 24 into therapeutic substance container 28 in response to an indication from airdetector 104 indicative of air within delivery fluid path 30. For example, if pump 48 is activated to begin drawing therapeutic substance from therapeutic substance container 28 and air-detector 104 detects that only air is flowing through delivery fluid path 30, it may be indicative that the user, e.g., subject, may have forgotten to inject liquid 24 into therapeutic substance container 28.

[0079] For some applications, once the entire dose of therapeutic substance has been delivered to the subject, an indication from air-detector 104 may be used by control circuitry 50 as an indication that the full dose has been delivered. Typically, the volume of the dose of therapeutic substance is known and thus control circuitry 50 "expects" to receive an indication from air-detector 104 once the dose has been delivered. In such a case, if air-detector 104 indicates the presence of air within delivery fluid path 30 prior to the expected end of the treatment, it may be an indication that the user, e.g., the subject, did not inject all of liquid 24 into therapeutic substance container 28, or in a case where a liquid part of the therapeutic substance is already in container 28 perhaps the user forgot to inject liquid 24 (entirely or in part). As such, in response to air-detector 104 indicating the presence of air within delivery fluid path 30 prior to the expected end of the treatment, control circuitry 50 may stop the operation of pump 48 and issue an alert to the subject.

[0080] It is noted that air-detector 104 and use of air-detector 104 may utilize techniques described in US Patent No. 11,357,909.

[0081] It will be appreciated by persons skilled in the art that the present invention is not limited to what has been particularly shown and described hereinabove. Rather, the scope of the present invention includes both combinations and subcombinations of the various features described hereinabove, as well as variations and modifications thereof that are not in the prior art, which would occur to persons skilled in the art upon reading the foregoing description.

Claims

CLAIMS1. A therapeutic substance delivery device for delivering a therapeutic substance to a subject, for use with a syringe containing a liquid, the therapeutic substance delivery device comprising:(a) a housing,(b) a therapeutic substance container disposed at least partially within the housing,(c) a delivery fluid path comprising a container outlet needle disposed at an upstream end of the delivery fluid path, the container outlet needle configured to penetrate the container,(d) a container inlet needle configured to penetrate the container, and(e) a one-way filling port coupled to the container inlet needle and configured to engage with the syringe,(i) the one-way filling port, the container inlet needle, and the container arranged such that the liquid from the syringe can be injected into the container via the one-way filling port and the container inlet needle, and(ii) the container and the container outlet needle arranged such that as the liquid is injected into the container, air within the container exits the container via the container outlet needle and enters an internal cavity of the therapeutic substance delivery device,(f) a pump configured to (i) draw therapeutic substance from the container via the container outlet needle following the injection of the liquid into the container and (ii) deliver the therapeutic substance to the subject, and(g) control circuitry configured to drive the pump.

2. The therapeutic substance delivery device according to claim 1, wherein the container is pre-filled with a lyophilized drug such that when the liquid is injected into the container the lyophilized drug is reconstituted.

3. The therapeutic substance delivery device according to claim 1, wherein the therapeutic substance delivery device is for use with a syringe containing a liquid therapeutic substance, and the container is empty when the therapeutic substance delivery device is packaged for commercial sale.

4. The therapeutic substance delivery device according to claim 1, wherein the therapeutic substance delivery device is for use with a syringe containing a first liquid, and the container ispartially filled with a second liquid when the therapeutic substance delivery device is packaged for commercial sale, such that when the first liquid is injected into the container the first liquid and the second liquid mix to form a therapeutic substance.

5. The therapeutic substance delivery device according to any one of claims 1-4, wherein: the delivery fluid path further comprises an injection assembly at a downstream end of the delivery fluid path, the injection assembly comprising an injection needle, the injection needle disposed, in a pre-subject-injection state of the therapeutic substance delivery device, within the internal cavity of the therapeutic substance delivery device, and the delivery fluid path is arranged such that the entering of the air into the internal cavity of the therapeutic substance delivery device is via the injection needle.

6. The therapeutic substance delivery device according to any one of claims 1-5, wherein the therapeutic substance delivery device is arranged to accommodate a range of volumes of the therapeutic substance container, the range including a volume of 0.8 ml and a volume of 50 ml, and wherein the therapeutic substance container has a volume that is within the range.

7. The therapeutic substance delivery device according to any one of claims 1-6, wherein: the container inlet needle comprises a downstream end that is configured to penetrate the container, and the therapeutic substance delivery device further comprises a container inlet needle block, and wherein the container inlet needle and the container inlet needle block are arranged such that in a pre-activation state of the therapeutic substance delivery device, the downstream end of the container inlet needle is sealed by the container inlet needle block.

8. The therapeutic substance delivery device according to claim 7, wherein the container inlet needle block comprises a sealing septum of the therapeutic substance container.

9. The therapeutic substance delivery device according to claim 8, wherein the sealing septum is 2-10 mm thick.

10. The therapeutic substance delivery device according to claim 7, wherein the therapeutic substance delivery device is configured to transition from (i) a first state in which the downstream end of the container inlet needle is disposed within the container inlet needle block and outside ofthe container to (ii) a second state in which the downstream end of the container inlet needle is disposed outside of the container inlet needle block and within the container.

11. The therapeutic substance delivery device according to claim 10, wherein the container comprises a septum and wherein the control circuitry is further configured to disinfect the septum of the container and to subsequently actuate the transition of the therapeutic substance delivery device from the first state to the second state upon activation of the therapeutic substance delivery device.

12. The therapeutic substance delivery device according to claim 7, wherein the downstream end of the container inlet needle is configured to penetrate the container by the container inlet needle sliding from (i) a first position in which the downstream end of the container inlet needle is disposed within the container inlet needle block and outside of the container to (ii) a second position in which the downstream end of the container inlet needle is disposed outside of the container inlet needle block and within the container.

13. The therapeutic substance delivery device according to claim 12, wherein the container comprises a septum and wherein the control circuitry is further configured to disinfect the septum of the container and to subsequently actuate the sliding of the container inlet needle from the first position to the second position upon activation of the therapeutic substance delivery device.

14. The therapeutic substance delivery device according to any one of claims 1-7, wherein the container is a therapeutic substance container having an interior volume that decreases as the therapeutic substance is drawn from the container.

15. The therapeutic substance delivery device according to claim 14, wherein: the container is a therapeutic substance cartridge comprising a slidable plunger which in a pre-liquid-injection state of the therapeutic substance cartridge is disposed at a distal end of the therapeutic substance cartridge, the cartridge comprises a septum at a proximal end of the cartridge opposite the distal end, the container inlet needle and the container outlet needle are configured to penetrate the septum, and the plunger is configured to slide from the distal end of the cartridge toward the proximal end of the cartridge in response to the pump drawing the therapeutic substance from the cartridge.

16. The therapeutic substance delivery device according to any one of claims 1-7, wherein: the therapeutic substance container is a non-collapsible therapeutic substance container having an internal volume that does not decrease as the therapeutic substance is drawn from the non-collapsible container, and the therapeutic substance delivery device further comprises a one-way air valve disposed within the internal cavity of the therapeutic substance delivery device, wherein: the non-collapsible container comprises a septum, and the container inlet needle comprises a downstream end and an upstream end, the downstream end of the container inlet needle configured to penetrate the septum, and the upstream end of the container inlet needle disposed in fluid communication with both (i) the one-way filling port and (ii) the one-way air valve, the one-way filling port (a) is disengageable from the syringe subsequently to the liquid from the syringe being injected into the non-collapsible container, and (b) is configured to self-seal subsequently to disengagement of the one-way filling port from the syringe, and the container inlet needle and the one-way air valve form an air-path to allow the air from within the internal cavity of the therapeutic substance delivery device to enter the non-collapsible container as the pump draws the therapeutic substance from the non- collapsible container via the container outlet needle.

17. The therapeutic substance delivery device according to claim 16, wherein the non- collapsible container is a therapeutic substance vial.

18. The therapeutic substance delivery device according to any one of claims 1-7, wherein the therapeutic substance delivery device further comprises an air-detector disposed within the therapeutic substance delivery device and configured to detect air in the delivery fluid path downstream of the container outlet needle, and wherein the control circuitry is configured to assess a status of the injection of the liquid into the container in response to an indication from the airdetector indicative of air within the delivery fluid path.

19. The therapeutic substance delivery device according to any one of claims 1-7, wherein the therapeutic substance delivery device further comprises a vibration motor configured to vibrate the container, and the control circuitry is configured to activate the vibration motor to:(a) in a first mode, mix the therapeutic substance within the container, and(b) in a second mode, issue an alert to the subject regarding a status of the therapeutic substance delivery device.

20. The therapeutic substance delivery device according to any one claims 1-7, wherein the therapeutic substance delivery device further comprises an accelerometer configured to detect motion of the therapeutic substance delivery device, and the control circuitry is further configured to initiate driving the pump to draw the therapeutic substance from the container in response to an indication from the accelerometer that the therapeutic substance delivery device has been moved in a manner that mixes the therapeutic substance within the container.

21. The therapeutic substance delivery device according to claim 20, wherein the therapeutic substance delivery device is configured to be placed on skin of the subject following the therapeutic substance delivery device being moved in a manner that mixes the therapeutic substance within the container, wherein: the therapeutic substance delivery device further comprises a delivery-initiating user interface configured to be activated by the subject following placement of the therapeutic substance delivery device on the skin of the subject, and the control circuitry is configured to issue an alert if the delivery-initiating user interface is activated prior to the control circuitry having received the indication from the accelerometer that the therapeutic substance delivery device has been moved in a manner that mixes the therapeutic substance within the container.

22. The therapeutic substance delivery device according to claim 21, wherein the therapeutic substance delivery device further comprises an on-body sensor configured to sense that therapeutic substance delivery device is placed on the skin of the subject, wherein the control circuitry is configured to issue an alert if the delivery -initiating user interface is activated prior to the control circuitry having received an indication from the on-body sensor that the therapeutic substance delivery device has been placed on the skin of the subject.

23. The therapeutic substance delivery device according to any one of claims 1-7, wherein the therapeutic substance delivery device further comprises a temperature sensor disposed within the therapeutic substance delivery device and arranged to sense the temperature of the therapeutic substance within the container, and the control circuitry is further configured to initiate driving thepump to draw the therapeutic substance from the container in response to an indication from the temperature sensor that the temperature of the therapeutic substance within the container is above a threshold temperature.

Images