Patent Application
20250009972
Systems, devices, and methods described herein generally relate to fluidic throttle control for the delivery of therapeutic substances in needle-based delivery systems. In some embodiments, the present disclosure relates to the delivery of standard therapies, while in other embodiments, the present disclosure relates to the delivery of rheologically challenging therapies, such as viscous, shear sensitive, or non-Newtonian therapies. A needle-based delivery system can be used to deliver such therapies. In some embodiments, the needle-based delivery system can include a fluidic throttle that interacts with an intermediary fluid. The fluidic throttle can act as a rate limiter, providing a throttled rate and constant force of drug extrusion, regardless of the force applied by the stored energy system. The fluidic throttle can also enable different forces to be applied for controlling needle ejection and drug extrusion.
Devices have been used to administer therapies under emergency conditions, such as, for example, administering epinephrine to counteract the effects of a severe allergic reaction (e.g., anaphylaxis) or naloxone for opioid overdose. Devices have also been described for use in administering therapies to treat disease, such as, for example, anti-arrhythmic medications and selective thrombolytic agents during a heart attack. One common type of delivery device is an auto-injector. Auto-injectors offer an alternative to syringes manually operated by patients for administering therapeutic agents into subjects in need thereof by allowing subjects in need thereof to self-administer medications.
Auto-injectors can be the preferred method of delivery for many therapeutics due to their ease of use by both trained and untrained professionals. Additionally, the speed of delivery and dose accuracy can be desired for quick administration. With auto-injectors, a small needle may be desirable to reduce pain associated with needle insertion. However, the small inner diameter and length of a needle acts to create a restricted fluid flow, which is an undesirable condition that becomes more restrictive as needle inner diameter size decreases. This limiting condition acting on the fluid flow through the restrictive needle can limit or prevent fluid flow of a therapy. The slowdown or stalling of the fluid in the needle can be exacerbated in viscous, shear sensitive or non-Newtonian pharmaceutical therapies, such as proteins and monoclonal antibodies.
In attempts to overcome the restrictive inner diameter of the needle, higher pressures may be applied. Such higher pressures, however, may generate high pressures in the primary drug container and in the needle, which can increase the risk of cartridge rupture or stack clogging in the needle. This is a phenomenon that is inherent in needle-based injection systems, because the needle acts as the primary restrictive orifice. High initial forces can result in blockage or exponential increases in apparent viscosity of a therapy to be extruded, due to the needle acting as a block in the system. This can result in undelivered or, in some cases, a damaged therapeutic due to shear forces. Compared to standard therapies, rheologically-challenging therapies can present more challenges. For example, such therapies can require higher forces to extrude the therapy through small needles, but are also more likely to clog in the needles. As an alternative, larger needles in conjunction with less powerful energy systems can be used, but while such needles may avoid clogging due to restricted flow, they can cause more patient discomfort, do not have the power to deliver larger volume doses, and cannot regulate dose over time.
To provide high enough pressures that can overcome stalling given a small needle, a powerful single energy force, such as a spring, may be used to deploy a therapy. The forces generated by these powerful energy sources, however, can exacerbate the risk of system failure. Specifically, the high speeds and impact forces experienced during auto-injector activation can result in mechanical damage on the surface of a cartridge, such as a glass cartridge, which can fracture, as the cartridge can come into contact with a needle hub, interior components, and/or interior walls of the auto-injector.
Alternatively, multiple or variable stored energy systems can be used, but these add significant complexity to the delivery system design. This added complexity can fail to meet regulated reliability demands. In particular, needle ejection, dose accuracy, and time to deliver a therapy are required to have a reliability of 99.99%. Multiple energy sources, such as a two-spring system with one spring to eject the needle and another to extrude the drug, add to the complexity and may reduce reliability to unacceptable levels. Therefore, there remains a need for a drug delivery system that can meet current reliability standards and avoid the downsides of existing single stored energy delivery systems.
Systems, devices, and methods described herein relate to needle-based injection systems including fluidic throttle elements for the delivery of therapeutic substances. Such delivery systems can have advantages over manual drug delivery systems (e.g., manually actuated syringes) and advantages over traditional auto-injectors that use a single stored energy system. In some embodiments, delivery systems described herein may use a intermediary fluid (e.g., a hydraulic or pressurized fluid) that interacts with a fluidic throttle to deliver a therapeutic fluid that is located within a drug container (e.g., a glass cartridge). The fluidic throttle may enable a single stored energy device to be used to eject a needle and to deliver a therapeutic fluid, without the risk of generating forces that would result in failures during delivery.
In some embodiments, a drug delivery system can be an auto-injector that provides a driving force source (e.g., spring, liquid or gas fluids, or other mechanism(s)), which apply pressure to a plunger of a drug container (e.g., a glass cartridge). The drug container can include a glass container, a crimp cap with a seal, and the plunger. Initially, the drug container can be driven forward toward a needle sub-assembly, puncturing the seal and/or a needle sheath and driving the needle into the patient. The plunger, internal to the glass container, can then be driven forward to extrude a therapeutic fluid located within the drug container. In drug delivery systems without a fluidic throttle, the rate that the needle is driven at and the rate of drug extrusion can be the same, e.g., as a result of being driven by the same driving force of a stored energy device. In such systems, the flow of the therapeutic fluid is rate restricted by needle fluid flow characteristics.
Given the drawbacks of existing needle-based drug delivery systems, there is a continuing need for a throttle using an intermediary fluid to replace the needle as the fluid restriction point and enables an extrusion rate control that provides a constant drug extrusion rate. Gas pressure driven systems suffer from effects of temperature change as well as pressure decrease as the gas is exhausted. Spring driven systems suffer from force reduction as the spring force is released. A throttle as disclosed herein can directly control, and maintain consistently, the desired internal pressure in a drug container and therefore a rate of drug extrusion, e.g., as driven by a stored energy component. The throttle can allow the stored energy component to apply sufficient pressure to a plunger of a drug container while avoiding drug stalling in the needle or rupture of the drug container. The throttle can work in tandem with a working or intermediary fluid having desired densities and/or vapor pressures to provide a constant transfer of force from the stored energy component to the drug cartridge.
Therapy or drug delivery systems as described herein enable one to separate the force driving needle insertion from the force driving a cartridge plunger. Embodiments of the present technology specifically apply to drug delivery devices that use a single stored energy source with an intermediary fluid flowing through a throttle before being applied to a plunger for extrusion of therapeutic fluid. A cartridge, such as a glass container, typically includes a bottom heel at the base of a barrel that extends to a shoulder and a neck. In embodiments, the bottom heel of the cartridge can be fitted with a fluidic throttle, which can include an orifice configured to modulate a speed of fluid flow, e.g., to thereby modulate a pressure applied to the cartridge plunger. The throttle on the bottom heel of the cartridge therefore acts as a throttle controlling the flow of fluid to the cartridge plunger and thereby controlling the velocity of the plunger and the rate of drug extrusion. Throttling in this case is associated with a choked condition or choked flow, as commonly associated with the venturi effect. Choking occurs when a working fluid either approaches the speed of sound or changes phase. Under such conditions, the flow rate does not increase with an increase in driving pressure. In some embodiments, the throttle can also define an effective piston size for driving a needle forward. Since the throttle is coupled to the bottom heel of the cartridge, a surface area of the backside of the throttle (or outer diameter of the backside of the throttle, in the case of a circularly shaped throttle backside) can form the effective piston size for driving the entire cartridge and therefore the needle forward. This backside surface area of the throttle and the configuration of the throttle orifice allow for separate and discrete modulation of the rate of drug extrusion and the rate or force of needle ejection.
In some embodiments, the intermediary fluid or drive fluid can be either liquid or gaseous, e.g., with vapor points and density designed to work in tandem with the throttle to maintain pressure applied to the drug container. In particular, the intermediary fluid and the throttle orifice work in tandem to prevent the needle from acting as the restrictive orifice in the system.
The throttle may be positioned at any point between the stored energy device and the plunger of a drug container or cartridge. In some embodiments, the throttle can be positioned on a bottom heel of the drug cartridge, while in other embodiments, the throttle can be positioned separately or apart from the drug cartridge. When positioned over the drug cartridge, the throttle may or may not contact the inner surface of the drug cartridge. In some embodiments, the throttle can have an initial inner diameter such that it can be sleeved over the bottom heel of a drug cartridge and a recovered inner diameter to secure itself on the cartridge. In some embodiments, the throttle can be coupled to the drug cartridge, e.g., by chemically adhering the throttle to the cartridge. In some embodiments, the throttle can be under compression to secure the throttle around at least a portion of the drug cartridge.
In some embodiments, an apparatus includes: a needle having a proximal end and a distal end; a cartridge having a body, a plunger, and a seal, the body, the plunger, and the seal collectively defining a reservoir configured to contain a therapeutic agent; a stored energy device configured to apply pressure to an intermediary fluid; a throttling assembly disposed on the body of the cartridge upstream of the plunger, the throttling assembly including a restrictor configured to limit a flow of the intermediary fluid therethrough; and an activation device configured to activate the stored energy device to apply pressure to the intermediary fluid such that the intermediary fluid acts on the throttling assembly to: initially drive a movement of the cartridge and the needle to insert the distal end of the needle into tissue and the proximal end of the needle through the seal and into the reservoir; and subsequently drive a movement of the plunger to extrude the therapeutic agent out through the needle.
In some embodiments, a method includes activating, by pressing an activation device, a stored energy device of a therapeutic delivery system; in response to activating the stored energy device, applying pressure on an intermediary fluid to cause the intermediary fluid to act on a throttling assembly of the therapeutic delivery system; in response to the intermediary fluid acting on the throttling assembly, driving movement of a cartridge and a needle of the therapeutic delivery system toward the skin of a patient to insert the needle into the skin; in response to the intermediary fluid acting on the throttling assembly, driving movement of the cartridge toward the needle such that the needle punctures through a seal of the cartridge to be in fluid communication with a therapeutic agent within the cartridge; in response to the intermediary fluid acting on the throttling assembly, generating a throttled flow of intermediary fluid via the throttling assembly; and driving movement of a plunger of the cartridge to extrude an amount or volume of the therapeutic agent in response to the throttled flow of the intermediary fluid acting on the plunger.
In some embodiments, an apparatus includes: a cartridge having a plunger and a reservoir configured to contain a therapeutic agent; a needle configured to extrude the therapeutic agent; a stored energy device configured to apply pressure to an intermediary fluid; a throttling assembly disposed upstream of the plunger in a pathway of the intermediary fluid; and an activation device configured to activate the stored energy device to apply pressure to the intermediary fluid such that the throttling assembly generates a flow of the intermediary fluid that applies a constant pressure on the plunger to extrude the therapeutic agent through the needle.
The drawings described herein are for illustrative purposes only of selected embodiments and not all possible implementations, and are not intended to limit the scope of the present disclosure.
Systems, devices, and methods are described herein for delivering a therapeutic substance to a patient, e.g., via a needle-based delivery system such as an auto-injection system.
As schematically illustrated in
The housing 102 can include one or more sections. In some embodiments, the housing 102 can include a main body and a removable cap that is configured to cover at least a portion of the main body. The removable cap can be configured to cover the portion of the main body so that a needle contained within the main body is shielded, e.g., to maintain sterility of the needle prior to use and/or to avoid accidental needle ejection. In some embodiments, the removable cap can also be placed over the main body such that an activation device or actuator for activating the therapeutic delivery system 100 is covered, e.g., to avoid accidental activation. In use, the removable cap of the housing 102 can be removed to enable the needle to be ejected into a patient's body. In some embodiments, the portion of the main body that is exposed once the removable cap is removed can be pressed or placed against a tissue surface, and an activation device (e.g., a button, switch, slider, knob, etc.) can be activated to cause the needle to eject out of the main body and through the tissue surface.
The needle assembly 140 can include a needle or cannula and a needle hub. The needle can include a sharp distal end that extends from the hub and is configured to penetrate through tissue. The needle hub can support the needle, e.g., relative to the cartridge 110, housing 102, and/or other portions of the therapeutic delivery system 100. In some embodiments, the needle may be held within the housing 102 (e.g., held within a main body of the housing 102) until an activation element is activated (e.g., a button, switch, or other activation device is pressed or actuated). In some embodiments, the needle can be a double-ended needle and include a proximal end that is also sharp. In use, the proximal end of the needle can be configured to puncture through a septum, membrane, or other seal 118.
The cartridge 110 can include a septum 118, a reservoir 112 that contains a therapeutic agent 114, and a plunger 116. In some embodiments, the cartridge 110 can include a body that is formed of a rigid material, such as, for example, glass, plastic, metal, or some combination of such materials. For example, the cartridge 110 can include a glass container, e.g., formed of borosilicate glass. In some embodiments, the body can include a bottom heel and a barrel that extends to a shoulder and a neck. The body can have an inner surface and an outer surface, with a wall thickness extending between the inner and outer surfaces. The reservoir 112 can be bounded on one end by the septum 118 and on the other end by the plunger 116. When not in use, the septum 118, plunger 116, and body of the cartridge 110 contain the therapeutic agent 114 within the reservoir 112.
The therapeutic agent 114 can include at least one of a drug, a vaccine, a protein, a peptide, a gene, a compound or another pharmaceutically active ingredient. Examples of therapeutic agents suitable for use in the system 100 include glucagon, insulin, adrenaline, epinephrine, anti-venom, atropine, antibody formulations, antidotes to chemical agents, and the like. In some embodiments, the medication suitable for use in the device of the present invention is at least one medication selected from the group of medications identified by tradenames consisting of Acthar, Actimmune, Apokyn, AquaMephyton, Aranesp, Arixtra, Avonex, Betaseron, Bravelle, Butorphanol, Byetta, Calcijex, Calcitonin, Caverject, Cetrotide, Chorionic Gonadotropin, Cimzia, Copaxone, Copegus, DDAVP, D.H.E-45, Delatestryl, Delestrogen, Depo-Estradiol, Depo-Provera 150, Depo-SubQ Provera 104, Depo-Testosterone, Desmopressin, Dihydroergotamine, Edex, Eligard, Enbrel, Epipen, Epogen, Exjade, Faslodex, Fertinex, Follistim, Forteo, Fragmin, Fuzeon, Ganirelix acetate, Genotropin, Gleevec, Glucagon, Gonal, Heparin, Humatrope, Humira, Imitrex, Increlex, Infergen, Innohep, Insulin, Intron A, iPlex, Ketorolac, Kestrone, Kineret, Kuvan, Leukine, Leuprolide Acetate, Lovenox, Lupron, Luveris, Medroxyprogesterone, Menopur, Methotrexate, Miacalcin, Muse, Neumega, Neulasta, Neupogen, Nexavar, Norditropin, Novarel, Nutropin, NuvaRing, Omnitrope, Orfadin, Ovidrel, Pegasys, Peg-Intron, Pregnyl, Procrit, Profasi, Progesterone, Pulmozyme, Raptiva, Rebetol, Rebif, Repronex, Revlimid, Ribasphere, Ribavirin, Saizen, Sandostatin, Sensipar, Serostim, Somatuline, Sprycel, Somavert, Stadol, Sumatriptan, Supprelin, Sutent, Symlin, Tarceva, Testosterone, Temodar, Tev-Tropin, Thalomid, Tobi, Tykerb, Vitamin B12, Vitamin D, Vitamin K, Xeloda, Zemplar, and Zorbtive. In some embodiments, the system 100 is capable of delivering highly viscous therapeutic agents (e.g., having a kinetic viscosity greater than that of water, having a kinetic viscosity greater than 30 centipoise, having a kinetic viscosity between 30 centipoise and 1500 centipoise, etc.), such as biologicals, flowable tissues, connective tissue matrixes or monoclonal antibodies. It will be apparent to those of skill in the art that the therapeutic agents listed above are only exemplary and that the system 100 is equally suitable for use in connection with practically any other injectable therapeutic agent not specifically listed herein.
The septum or seal 118 can function as a partition, enclosing or sealing off the therapeutic agent 114 from an external environment. In some embodiments, septum 118 can be implemented as a crimp cap seal or septum (e.g., a crimp camp combi-seal) that is to the body of the cartridge 110. The septum 118 can be formed of a flexible material, e.g., silicone, rubber, or other type of elastomer. The septum 118 can be disposed at a distal or dispensing end of the cartridge 110. The dispensing end of the cartridge 110 can be configured to receive a needle hub of the needle assembly 140 thereon, such as, for example, the needle hub of a double-ended needle. The needle hub can be coupled to the dispensing end by any known technique, such as threaded connection or snap fit configurations. Once advanced onto the cartridge 110, the double-ended needle can pierce the septum 118 to dispense the therapeutic agent 114 from the cartridge 110.
In use, one end of a needle of the needle assembly 140 can be placed within the reservoir 112, e.g., after puncturing through the septum 118, and another end of the needle can be inserted into a patient's body. Fluid communication of the therapeutic agent 114 can then be established through the needle into the patient's body. The plunger 116 can slide along a length of the body of the cartridge 110, e.g., by sliding along the inner surface of the body of the cartridge 110. As the plunger 116 moves distally toward the needle, the plunger 116 can extrude an amount or volume of the therapeutic agent 114 through the needle and into the patient's body. The amount or volume extruded can be a predetermined or preset amount, e.g., dependent on the therapy or treatment being delivered to the patient.
The plunger 116 can be driven by energy imparted by a stored energy device 130. In some embodiments, the plunger 116 can be driven hydraulically, e.g., by an intermediary fluid 132 (e.g., a hydraulic or pressurized liquid and/or gas). Alternatively or additionally, the plunger 116 can be driven manually, e.g., via a user pressing down on a shaft, slider, or other mechanical actuator that is coupled to the plunger 116. Still alternatively or additionally, the plunger 116 can be driven mechanically, e.g., using a spring.
The stored energy device 130 can be configured to supply energy, e.g., to drive movement of the needle, the plunger 116, or other components of the therapeutic delivery system 110. In some embodiments, the stored energy device 130 can be configured to supply energy in response to being released or activated. For example, an activation device such as a button, tab, slider, knob, or other mechanism can be coupled to the stored energy device 130, and upon actuation of such device, the stored energy device 130 can be configured to deliver stored energy to drive the delivery of the therapeutic agent 114. In some embodiments, the stored energy device 130 can include a power or deployment spring that drives a piston, which then delivers intermediary fluid 132 to the plunger 116. The deployment spring can be locked in a compressed configuration, and can be released upon actuation of an activation device. Alternatively, in some embodiments, the stored energy device 130 can include an electric motor to drive the piston. Still alternatively, in some embodiments, the stored energy device 130 can include pressurized fluid containers that can open to release an intermediary fluid 130. It can be appreciated that other suitable forms of energy storage and release can be used with the stored energy device 130 without departing from the scope of the present disclosure.
In some embodiments, the energy provided by a single stored energy device 130 can be used to drive needle ejection or insertion (e.g., via movement of the needle assembly 140) and to drive drug extrusion (e.g., via movement of the plunger 116). Alternatively, multiple stored energy devices 130 can be used, with each stored energy device 130 being used to drive a different component of the therapeutic delivery system 100, serially or in parallel. For example, a first stored energy device 130 can be configured to supply energy for driving needle ejection, while a second stored energy device 130 can be configured to supply energy for driving drug extrusion or plunger movement.
In some embodiments, a throttling element 120 can be used to restrict a portion of the flow of intermediary fluid 132 to the plunger 116. The throttling element 120 can be disposed between a source of the intermediary fluid 132 and the plunger 116. In some embodiments, the throttling element 120 can be coupled to the cartridge 110. For example, the throttling element 120 can extend over a bottom heel of the cartridge 110. In some embodiments, the throttling element 120 can be formed of one or more medical grade elastomers, such as, for example, liquid silicone rubber (LSR), fluoroelastomers (FKM), perfluoroelastomers (FFKM), and ethylene-propylene diene monomer (EPDM). In some embodiments, the throttling element 120 can have a minimum Shore hardness of 40A.
The throttling element 120 can be configured to replace the needle as the fluid rate limiting orifice in a hydraulically driven therapeutic delivery system. In particular, the throttling element 120 can include an opening or orifice having a small cross-sectional area, thereby limiting the fluid flow of the intermediary fluid 132 to the plunger 116 and the rate of drug extrusion. In some embodiments, the throttling element 120 can include a single opening having a circular cross-sectional area. In some embodiments, the circular cross-sectional area can have a diameter of less than about 5 mm, less than about 4 mm, less than about 3 mm, less than about 2 mm, less than about 1 mm, or less than about 0.5 mm, including all values and sub-ranges therebetween (e.g., between about 0.5 mm and about 5 mm, or between about 0.5 mm and about 2 mm). In some embodiments, throttling element 120 and include multiple openings. In some embodiments, the multiple openings can have a combined cross-sectional area that is equal to the cross-sectional area of a single opening having a circular cross-sectional area with a diameter of less than about 5 mm, less than about 4 mm, less than about 3 mm, less than about 2 mm, less than about 1 mm, or less than about 0.5 mm, including all values and sub-ranges therebetween. In some embodiments, the throttling element 120 can include a single or multiple openings with different cross-sectional shapes, e.g., circular, oval, square, rectangular, etc.
By replacing the needle as the rate limiting orifice, the throttling element 120 can prevent or mitigate pressures during therapeutic delivery that can result in a blockage in the needle and/or breakage of the cartridge 110, especially with a more viscous, shear sensitive, or non-Newtonian fluid. The throttling element 120 also serves as an intermediary component between the stored energy device 130 and the cartridge 110, which can alleviate direct forces being applied to the cartridge. In some embodiments, the throttling element 120 can be of monolithic construction. Alternatively, the throttling element 120 can be formed of multiple parts, e.g., which can be joined together during assembly.
The restrictive orifice or opening of the throttling element 120 can be varied, e.g., to control the rate of drug extrusion. For example, the restrictive orifice of the throttling element 120 can be reduced to reduce the rate of drug extrusion below the restrictive limitations of a given needle gauge. The throttling element 120 can be configured to provide a flowrate for the intermediary fluid that remains constant or substantially constant, which in turn allows for constant or substantially constant therapeutic delivery rates. As such, the therapy delivery time can be controlled by adjusting the restrictive orifice of the throttling element 120. In some embodiments, the intermediary fluid can be a Newtonian fluid, such as, for example, water, oil, alcohol, or combination thereof. In some embodiments, the intermediary fluid can be a non-Newtonian fluid, such as a slurry, a gel, a colloid, etc.
In some embodiments, the system 100 including the throttling element or assembly 120 can be for discretely and/or separately controlling the forces applied to the cartridge during forward advancement and needle insertion and the forces applied to the plunger for drug extrusion using a single stored energy device (e.g., power spring). The throttling assembly is configured to allow for the rate of insertion of the needle into the tittle (due to the pressure applied to the cartridge and needle hub assembly) to be greater or less than the pressure applied to on the plunger of the cartridge to determine the rate of drug extrusion. The purpose being to protect the cartridge from initial high force impacts or high internal pressures that are generated from high initial autoinjector spring forces, while still being able to generate pressure required to extrude a therapeutic substance such as a viscous drug.
While a single throttling element 120 and a single cartridge 110 are depicted in
In some embodiments, certain components of needle-based injection systems as described herein can be similar to those described in U.S. Patent Application Publication No. 2021/0386932, published Dec. 16, 2021, titled “Miniaturized wearable medication administration device,” this disclosure of which is incorporated herein by reference.
In some embodiments, the throttling element 220 can be configured to control the rate of needle ejection. In particular, the body 221 of the throttling element 220 can have a proximal end with an area A1. When a stored energy device (e.g., stored energy device 130) drives an intermediary fluid toward the cartridge, the intermediary fluid can act on the area A1 to drive movement of the entire cartridge 210. The cartridge 210, by moving, can then engage with a needle hub of a needle assembly (e.g., needle assembly 140), thereby driving movement of a needle into a patient. The throttling element 220, by being coupled to the proximal end of the cartridge 210, therefore functions as an actuator that drives the ejection of the needle. As such, the rate of needle ejection can be controlled by setting the area A1. In some embodiments, the area A1 can be a circular cross-section having a diameter of between about 20 mm and about 50 mm, including all values and sub-ranges therebetween.
Additionally or alternatively, the throttling element 220 can be configured to control the rate of drug extrusion or delivery. As depicted in
As shown in
In the case of a gaseous intermediary fluid, the physical point at which choked flow occurs for adiabatic conditions is when the exit plane velocity is at sonic conditions at or above a Mach number of 1, and is therefore dependent on fluid density. In the case of a liquid intermediary fluid, the physical point at which choked flow occurs for adiabatic conditions is when the pressure drop across the constriction is such that the pressure at the constriction's exit is below the vapor pressure of the intermediary fluid. As such, beyond a certain pressure difference ΔP CHOKED, the mass flow rate through the throttling element cannot be exceeded, which thereby limits the pressure action on the plunger of the cartridge and the drug extrusion rate.
In some embodiments, variable density intermediary fluids or other fluid modifications can also be used to further adjust or control the flow rate of the intermediary fluid and, consequently, the rate of drug extrusion. In some embodiments, the intermediary fluid can be a Newtonian fluid, such as, for example, water, oil, alcohol, or combination thereof. In some embodiments, the intermediary fluid can be a non-Newtonian fluid, such as a slurry, a gel, a colloid, etc. Depending on the flow rate desired (e.g., due to the needle gauge, properties of the therapeutic agent, etc.), the throttling element 220 can be selected to operate with a Newtonian or non-Newtonian fluid.
In therapeutic delivery systems, it can be desirable to use a single stored energy source for both needle ejection and drug extrusion. This can reduce the manufacturing costs as well as allow for smaller profile devices (e.g., with less components). With a single stored energy source and no throttling element, the same pressure would be applied for needle ejection and drug extrusion. This can lead to complications, especially with non-Newtonian fluids being delivered and small needle gauges. In particular, it can be desirable to have needles with small profiles to reduce patient discomfort. But small needles can result in greater pressures, especially with non-Newtonian fluids, and therefore cause cartridge failure (e.g., breaking of the cartridge body) and stalling of therapy delivery. The risk of cartridge failure also increases with larger size cartridges, which may be needed for delivering larger doses of a therapeutic agent. With a throttling element, these issues can be avoided as different pressures can be applied for needle ejection and drug extrusion, e.g., due to the different sizes of areas A1 and A2, as described above with reference to
As depicted in
The needle 340 and the needle hub 342 may be held in position within the housing 302 by a support 344. The support 344 can be, for example, an elastic or a deformable element. In an embodiment, the support 344 can be a spring. The needle 340 can be a double-sided needle, e.g., having a distal end 340a and a proximal end 340b that are sharp and can puncture through tissue or other surfaces. When the flow 352 of the intermediate fluid acts on the throttling element and the cartridge, this drives the distal end of the cartridge into the needle hub 342, which then pushes against the support 344. The stored energy device can be configured to generate the flow 352 such that sufficient force is applied on the cartridge and therefore on the needle hub 352 to overcome the force of the support 344 that holds the needle 340 and needle hub 342 in place. Once this force of the support 344 is overcome, the distal end 340a of the needle 340 can extend out of the housing 302 and into the tissue, as depicted in
Once the needle 340 has extended into the tissue and punctured into the reservoir 312, the needle 340 can act as a fluid passageway for delivering a therapeutic agent disposed within the reservoir 312 into the tissue. As depicted in
Once the dose of the therapeutic agent has been delivered, the stored energy device can stop generating the flow 342 of the intermediary fluid. In
Optionally, at 402, a distal or dispensing end of the therapeutic delivery system can be placed against a skin surface of the patient. The dispensing end of the therapeutic delivery system can include a surface for resting against the skin surface. In some embodiments, the surface of the dispensing end of the therapeutic delivery system can have a shape designed for mating against or engaging with the skin surface, such as, for example, a curved or concave shape.
At 403, the therapeutic delivery system can be activated, e.g., by actuating an activation device. As described with reference to
In response to the activation of the device, and consequently the generation of the flow of intermediary fluid, a needle of the therapeutic delivery system can be inserted into the patient through the skin surface, at 404. As described with reference to
At 405, a therapeutic substance or agent can be extruded from the cartridge of the therapeutic delivery system and into the patient. The therapeutic substance extrusion can occur at a second predetermined rate that is different from the first predetermined rate associated with the needle ejection. For example, the second predetermined rate can be less than the first predetermined rate. In particular, the therapeutic substance extrusion can be driven by the movement of a plunger. The plunger can move in response to a flow of the intermediary fluid acting on the proximal side of the plunger. The plunger can be disposed downstream of a throttling element (e.g., throttling element 320), which can be configured to reduce the flow of the intermediary fluid that acts on the plunger. In some embodiments, the throttling element can include a restriction that is configured to generate a choked flow of the intermediary fluid. The choked flow can be associated with a constant flow rate, which exerts less pressure or force on the plunger than the full force of the intermediary fluid. The choked flow at this constant flow rate then acts on the plunger to drive the extrusion of the therapeutic substance at a second predetermined rate that is less than the first predetermined rate of needle ejection.
After the appropriate dose of the therapeutic substance has been delivered to the patient, the needle optionally can be retracted from the skin, at 406. In some embodiments, the therapeutic delivery system can include a retraction spring that is coupled to the needle hub, and once the flow of intermediary fluid halts, this retraction spring can be configured to pull or push the needle (e.g., depending on spring configuration) back into the housing of the therapeutic delivery system. In such embodiments, the power spring compresses the retraction spring during delivery of the drug, and once the pressure to the intermediary fluid is removed, the retraction spring is able to retract the needle.
The barrel 513 can include an inner surface, an outer surface, and a wall thickness extending between the inner and outer surfaces. In some embodiments, the wall of the barrel 513 can be formed of glass, such as, for example, borosilicate glass. The barrel 513, together with the plunger 512 and the crimp cap 517 can define a reservoir for containing a therapeutic agent. The therapeutic agent can be extruded from the reservoir via the needle 519. The crimp cap 517 can be a crimp cap combi-seal, although in other embodiments, other types of seals can be used. The distal end 516 of the cartridge 510 can be configured to receive the needle hub 518 thereon. The needle hub 518 can be coupled to the distal end 516 of the cartridge 510 by any known technique, such as a threaded connection or snap fit configuration. The needle hub 518 can support the needle 519. The needle 519 can be a double-ended needle with a proximal end that can pierce through the crimp cap 517 and a distal end that can puncture into tissue. In use, the needle 519 can move relative to the cartridge 510 such that the proximal end of the needle 519 pierces through the crimp cap 517 and gains access to the reservoir containing the therapeutic agent. The distal end of the needle 519 can also puncture into tissue, thereby establishing a fluid pathway between the reservoir and the tissue for delivery of the therapeutic agent.
The plunger 512 of the cartridge 510 can be configured to advance distally to extrude the therapeutic agent contained within the reservoir. The plunger 512 can advance distally in response to a pressure applied by a stored energy device (not depicted).
In some embodiments, the proximal end or heel 511 of the cartridge 510 can be coupled to (e.g., fitted with) a fluidic throttling element (e.g., throttling element 120), e.g., for facilitating delivery of constant pressure to the cartridge 510 and for controlling a drug extrusion rate. The throttling element can be configured to provide drug extrusion with constant pressure despite variable or decreasing force applied by the stored energy device. The throttling element can be configured to deliver a throttled and constant (or substantially constant) flow of an intermediary fluid to the plunger 512, e.g., thereby driving a constant rate of advancement of the plunger 512 and therefore a constant rate of therapeutic agent delivery or extrusion. In embodiments, the throttling element includes an opening or orifice that replaces the needle 519 as the fluid rate limiting orifice, thus modulating the flow rate of drug extrusion.
The throttling element 720 can be fitted to the back or heel of a cartridge.
As depicted in
The size of the restrictive orifice of a throttling element can be varied, e.g., to increase or decrease the rate of drug extrusion given needle gauge, therapeutic substance sensitivities or properties, etc.
In some embodiments, a throttling element can also be used to control the rate of needle insertion. In particular, the outer diameter of the proximal end of a throttling element can be varied to control the initial rate that the needle is ejected from a therapeutic delivery system and into a patient.
Referring now to
As depicted in
Prior to use, the cap 1104 can be removed from the housing 1102 to expose the activation device 1136 and the needle ejection point. The housing 1102 can then be pressed against an injection site (e.g., against skin or against clothing overlaying the injection site) so as to position the needle for insertion into the injection site.
The activation device 1136 can be a button or trigger. The activation device 1136, when pressed or actuated as shown in
In some embodiments, the needle hub 1142 and the needle 1140 can be spaced from the septum 1145 (and therefore held within the housing 1102) by a compression spring 1144 (e.g., a retraction spring). Therefore, to be able to eject the needle 1140 from the housing 1102, the spring 1134 of the stored energy device must be configured to generate sufficient energy via the flow 1132a of the intermediary fluid 1132 to overcome the force of the spring 1144. In some embodiments, the spring 1134 can be a compression spring with a spring rate of between about 1 N/mm and about 3 N/mm, including all values and sub-ranges therebetween, including, for example, about 1.50 N/mm, about 1.55 N/mm, about 1.60 N/mm, about 1.65 N/mm, about 1.70 N.mm, about 1.75 N/mm, about 1.80 N/mm, about 1.85 N/mm, about 1.90 N/mm, about 1.95 N/mm, or about 2.00 N/mm. In some embodiments, the spring 1144 can be a compression spring with a spring rate that is less than the spring rate of the spring 1134. In some embodiments, the spring 1144 can be a compression spring with a spring rate of between about 0.5 N/mm and about 2 N/mm, including all values and sub-ranges therebetween, including, for example, about 1.0 N/mm, about 1.1 N/mm, etc. In some embodiments, the spring 1134 and/or the spring 1144 can be formed of a metal or metal composite. In some embodiments, the spring 1134 can have an outside diameter of between about 5 mm and about 15 mm, including all values and sub-ranges therebetween, including, for example, between about 8.5 mm and about 9.5 mm. In some embodiments, the spring 1144 can have an outside diameter that is the same or substantially the same as the spring 1134, while in other embodiments, the spring 1144 can have an outside diameter that is less than or greater than the spring 1134.
The piston 1138 can continue to move, driving the movement of the cartridge 1110 and therefore the needle hub 1142 and the needle 1140 until the needle hub 1142 engages with a portion of the housing 1102 that prevents further movement of the needle hub 1142 and/or the spring 1144 is fully compressed. At this point, the sharp distal end of the needle 1140 has pierced through the septum 1145 and can be in a fully extended position.
The throttling element 1121, similar to other throttling elements described herein, can be configured to determine the rate of needle ejection. In particular, the area of the proximal side of the throttling element 1121 upon which the intermediary fluid acts can be sized to produce a predetermined force for driving the movement of the cartridge 1110 and the needle 1140. This area can be increased to increase the force and therefore the ejection rate of the needle 1140 or decreased to decrease the force and therefore the ejection rate of the needle 1140. The throttling element 1121, similar to other throttling elements described herein, can also include a restrictor such as, for example, an opening or orifice. The restrictor can be configured to reduce the flow of the intermediary fluid that acts on the plunger 1116 of the cartridge. More specifically, the restrictor can be configured to generate a throttled or constant flow of the intermediary fluid. As described above, this throttled flow of the intermediary fluid can drive the therapeutic extrusion rate while avoiding failure of the delivery system, e.g., by avoiding high pressures from being generated in the cartridge 1110 and/or blockage in the needle 1140.
As the piston 1138 moves to the position shown in
Once pressure applied by the intermediary fluid has abated, the spring 1144 can force the needle hub 1142, the cartridge 1110, and the needle 1140 away from the septum 1145, thereby retracting the needle 1140 to a position that is entirely within the housing 1102. In some embodiments, the spring 1144 is selected so as to be strong enough to provide an immediate or near-immediate retraction of the needle 1140 once the piston 1138 has moved pass the pressure relief point 1139 and the pressure has abated.
The deployment spring 1134 and the retraction spring 1144 are configured (e.g., selected to have an appropriate spring rate) such that the entire process of activation, deployment, administration of the therapeutic agent, and retraction is performed within a predefined period of elapsed time. The predefined period of elapsed time is selected to be a clinically acceptable time period. In some embodiments, the period of elapsed time is between about 0.1 seconds and 2.0 seconds, including all values and sub-ranges therebetween, including, for example between about 0.1 sections and about 0.5 seconds.
While a spring-loaded piston system is described with reference to
While the throttle elements described herein are primarily described with reference to auto-injectors or automatic drug delivery devices, it can be appreciated that the throttle elements are not limited to auto-injector systems. For example, a fluidic throttle as described herein can be incorporated into any needle-based injector, e.g., to replace the needle as the restrictive orifice, including hand-held syringes. With a manually actuated syringe, the throttle can be affixed in the fluid path before the plunger applies the driving pressure to a therapeutic fluid. The throttle can then allow for constant drug extrusion from a manually applied force. Precise administration of therapy from prefilled syringes is critical to provide the highest level of care. Break-loose and glide forces of the driving plunger are carefully considered when developing these systems. The fluidic throttle, by delivering a constant force to the plunger, can allow for a uniform delivery of therapy. This is expected to reduce the need for chemical surface treatments for uniform glide forces. This is particularly useful in therapeutics that are sensitive to surface treatments during administration or storage.
While various inventive embodiments have been described and illustrated herein, those of ordinary skill in the art will readily envision a variety of other means and/or structures for performing the function and/or obtaining the results and/or one or more of the advantages described herein, and each of such variations and/or modifications is deemed to be within the scope of the inventive embodiments described herein. More generally, those skilled in the art will readily appreciate that all parameters, dimensions, materials, and configurations described herein are meant to be exemplary and that the actual parameters, dimensions, materials, and/or configurations will depend upon the specific application or applications for which the inventive teachings is/are used. Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, many equivalents to the specific inventive embodiments described herein. It is, therefore, to be understood that the foregoing embodiments are presented by way of example only and that, within the scope of the appended claims and equivalents thereto; inventive embodiments may be practiced otherwise than as specifically described and claimed. Inventive embodiments of the present disclosure are directed to each individual feature, system, article, material, kit, and/or method described herein. In addition, any combination of two or more such features, systems, articles, materials, kits, and/or methods, if such features, systems, articles, materials, kits, and/or methods are not mutually inconsistent, is included within the inventive scope of the present disclosure.
Also, various inventive concepts may be embodied as one or more methods, of which an example has been provided. The acts performed as part of the method may be ordered in any suitable way. Accordingly, embodiments may be constructed in which acts are performed in an order different than illustrated, which may include performing some acts simultaneously, even though shown as sequential acts in illustrative embodiments.
All definitions, as defined and used herein, should be understood to control over dictionary definitions, definitions in documents incorporated by reference, and/or ordinary meanings of the defined terms.
As used herein, the terms “about” and/or “approximately” when used in conjunction with numerical values and/or ranges generally refer to those numerical values and/or ranges near to a recited numerical value and/or range. In some instances, the terms “about” and “approximately” may mean within ±10% of the recited value. For example, in some instances, “about 100[units]” may mean within ±10% of 100 (e.g., from 90 to 110). The terms “about” and “approximately” may be used interchangeably.
“A” and “an” as used herein indicate “at least one” of the item is present; a plurality of such items may be present, when possible. Except where otherwise expressly indicated, all numerical quantities in this description are to be understood as modified by the word “about” and all geometric and spatial descriptors are to be understood as modified by the word “substantially” in describing the broadest scope of the technology.
Although the open-ended term “comprising,” as a synonym of non-restrictive terms such as including, containing, or having, is used herein to describe and claim embodiments of the present technology, embodiments may alternatively be described using more limiting terms such as “consisting of” or “consisting essentially of.” Thus, for any given embodiment reciting materials, components, or process steps, the present technology also specifically includes embodiments consisting of, or consisting essentially of, such materials, components, or process steps excluding additional materials, components or processes (for consisting of) and excluding additional materials, components or processes affecting the significant properties of the embodiment (for consisting essentially of), even though such additional materials, components or processes are not explicitly recited in this application. For example, recitation of a composition or process reciting elements A, B and C specifically envisions embodiments consisting of, and consisting essentially of, A, B and C, excluding an element D that may be recited in the art, even though element D is not explicitly described as being excluded herein.
As referred to herein, disclosures of ranges are, unless specified otherwise, inclusive of endpoints and include all distinct values and further divided ranges within the entire range. Thus, for example, a range of “from A to B” or “from about A to about B” is inclusive of A and of B. Disclosure of values and ranges of values for specific parameters (such as amounts, weight percentages, etc.) are not exclusive of other values and ranges of values useful herein. It is envisioned that two or more specific exemplified values for a given parameter may define endpoints for a range of values that may be claimed for the parameter. For example, if Parameter X is exemplified herein to have value A and also exemplified to have value Z, it is envisioned that Parameter X may have a range of values from about A to about Z. Similarly, it is envisioned that disclosure of two or more ranges of values for a parameter (whether such ranges are nested, overlapping or distinct) subsume all possible combination of ranges for the value that might be claimed using endpoints of the disclosed ranges. For example, if Parameter X is exemplified herein to have values in the range of 1-10, or 2-9, or 3-8, it is also envisioned that Parameter X may have other ranges of values including 1-9, 1-8, 1-3, 1-2, 2-10, 2-8, 2-3, 3-10, 3-9, and so on.
When an element or layer is referred to as being “on,” “engaged to,” “connected to,” or “coupled to” another element or layer, it may be directly on, engaged, connected or coupled to the other element or layer, or intervening elements or layers may be present. In contrast, when an element is referred to as being “directly on,” “directly engaged to,” “directly connected to” or “directly coupled to” another element or layer, there may be no intervening elements or layers present. Other words used to describe the relationship between elements should be interpreted in a like fashion (e.g., “between” versus “directly between,” “adjacent” versus “directly adjacent,” etc.). As used herein, the term “and/or” includes any and all combinations of one or more of the associated listed items.
Although the terms first, second, third, etc. may be used herein to describe various elements, components, regions, layers and/or sections, these elements, components, regions, layers and/or sections should not be limited by these terms. These terms may be only used to distinguish one element, component, region, layer or section from another region, layer or section. Terms such as “first,” “second,” and other numerical terms when used herein do not imply a sequence or order unless clearly indicated by the context. Thus, a first element, component, region, layer or section discussed below could be termed a second element, component, region, layer or section without departing from the teachings of the example embodiments.
Spatially relative terms, such as “inner,” “outer,” “beneath,” “below,” “lower,” “above,” “upper,” and the like, may be used herein for ease of description to describe one element or feature's relationship to another element(s) or feature(s) as illustrated in the figures. Spatially relative terms may be intended to encompass different orientations of the device in use or operation in addition to the orientation depicted in the figures. For example, if the device in the figures is turned over, elements described as “below” or “beneath” other elements or features would then be oriented “above” the other elements or features. Thus, the example term “below” can encompass both an orientation of above and below. The device may be otherwise oriented (rotated 90 degrees or at other orientations) and the spatially relative descriptors used herein interpreted accordingly.
This application is a continuation of International Patent No. PCT/US2023/061093, filed Jan. 23, 2023, and titled “SYSTEMS, DEVICES, AND METHODS FOR FLUIDIC THROTTLE CONTROL OF THE DELIVERY OF THERAPIES IN NEEDLE-BASED DELIVERY SYSTEMS,” which claims priority to pending U.S. Provisional Patent Application No. 63/412,109, filed Sep. 30, 2022, and titled “SYSTEMS, DEVICES, AND METHODS FOR FLUIDIC THROTTLE CONTROL OF THE DELIVERY OF THERAPIES IN NEEDLE-BASED DELIVERY SYSTEMS,” and U.S. Provisional Patent Application No. 63/301,864, filed Jan. 21, 2022, and titled “FLUIDIC THROTTLE CONTROL FOR THE DELIVERY OF STANDARD AND RHEOLOGICALLY CHALLENGING THERAPIES IN NEEDLE-BASED DRUG DELIVERY SYSTEMS,” the disclosures of each of which are incorporated by reference in their entireties.
| Number | Date | Country | |
|---|---|---|---|
| 63412109 | Sep 2022 | US | |
| 63301864 | Jan 2022 | US |
| Number | Date | Country | |
|---|---|---|---|
| Parent | PCT/US2023/061093 | Jan 2023 | WO |
| Child | 18779996 | US |
