Fluid flow path for injector

Abstract

In some examples, a tubing assembly for an injection device includes a tubing having a first end and a second end, the tubing defining a lumen having a constant inner diameter and a constant outer diameter from the first end to the second end, a first connector coupled to the first end, the first connector having a first enlarged section, a first tapered section and a first narrowed section, and a second connector coupled to the second end, the second connector having a second enlarged section, a second tapered section and a second narrowed section.

Description

FLUID FLOW PATH FOR INJECTOR CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of priority to U.S. Provisional Applications No. 63 / 606,469, filed December 5, 2023, the disclosure of which is incorporated herein by reference in its entirety. FIELD OF THE DISCLOSURE

[0002] The present disclosure relates generally to medical devices for delivery of drugs. More specifically, the present disclosure relates to tubing assemblies for use with pumps, injectors and other medical devices. BACKGROUND OF THE DISCLOSURE

[0003] External drug pumps are typically used to deliver substances (e.g., large molecules which cannot be digested when administered orally) to patients. For example, such devices are commonly used to infuse a basal rate of insulin to subjects suffering from diabetes, as an alternative to insulin injections by an insulin syringe or an insulin pen. Typically, the pump is adhered to the abdomen of the patient and delivers the substance to the patient via a cannula that is inserted into the patient's skin. Traditional pumps or injectors are limited. For examples, the injection forces of traditional injectors may be suboptimal or injection time may be too long. This may be particularly an issue with highly viscous substances.

[0004] Thus, there exists a need for devices that work with and advance the methods of safely using injectors to ensure proper delivery of high viscosity medicaments. SUMMARY OF THE DISCLOSURE

[0005] In some examples, a tubing assembly for an injection device includes a tubing having a first end and a second end, the tubing defining a lumen from the first end to the second end, the tubing having a first terminal portion, a first tapered portion, a central portion, a second tapered portion, and a second terminal portion.

[0006] In some examples, a tubing assembly for an injection device includes a tubing having a first end and a second end, the tubing defining a lumen having a constant inner diameter and a constant outer diameter from the first end to the second end, a first connector coupled to the first end, the first connector having a first enlarged section, a first tapered section and a first narrowedsection, and a second connector coupled to the second end, the second connector having a second enlarged section, a second tapered section, and a second narrowed section. BRIEF DESCRIPTION OF THE DRAWINGS

[0007] Various embodiments of the presently disclosed devices are disclosed herein with reference to the drawings, wherein:

[0008] FIG.1A is a schematic illustration of apparatus for administering a substance to a subject, in accordance with an embodiment of the present disclosure;

[0009] FIG.1B is a schematic illustration of the apparatus of FIG.1A on a subject's body, a sensor for use with the apparatus being disposed inside the subject's body, in accordance with an embodiment of the present disclosure;

[0010] FIG.2 is a schematic exploded view of the apparatus of FIG.1, in accordance with an embodiment of the present disclosure;

[0011] FIG.3 is a schematic illustration of a housing base of the apparatus of FIG.1, in accordance with an embodiment of the present disclosure;

[0012] FIG.4 is a schematic illustration of a vial being inserted into the housing base of FIG. 3, in accordance with an embodiment of the present disclosure;

[0013] FIG.5A is a schematic illustration of a vial inserted in the housing base, in accordance with an embodiment of the present disclosure;

[0014] FIG.5B is a schematic illustration of a housing top coupled to the housing base, in accordance with an embodiment of the present disclosure;

[0015] FIGS.6A, 6B, 6C, and 6D are schematic cross-sectional illustrations, taken along line VI of FIG.5A, of the vial at respective stages of use of the apparatus, in accordance with an embodiment of the present disclosure;

[0016] FIG.6E is a force vector diagram showing the forces acting on a stopper during operation of the apparatus, in accordance with an embodiment of the present disclosure;

[0017] FIGS.7A, 7B, and 7C are schematic cross-sectional illustrations, taken along line VII of FIG.5A, of an activation mechanism of the apparatus at respective stages of operation of the apparatus, in accordance with an embodiment of the present disclosure;

[0018] FIGS.8A-8B are schematic illustrations of a vial, in accordance with an embodiment of the present disclosure;

[0019] FIG.9 is a schematic illustration of apparatus including a vial housing unit and a separate needle housing unit, in accordance with an embodiment of the present disclosure;

[0020] FIG.10A-10B are a schematic representation and a photograph of a common tubing assembly used with an apparatus for administering a substance to a subject;

[0021] FIG.11 is a schematic representation of a tubing assembly according to a first embodiment;

[0022] FIG.12 is a chart showing potential dimensions for components of an apparatus for administering a substance to a subject including a tubing assembly according to the first embodiment;

[0023] FIGS.13-14 are photographs and schematic representations of a tubing assembly according to another embodiment.

[0024] FIG.15 is a chart showing potential dimensions for a tubing assembly according to another embodiment;

[0025] FIGS.16, 17A, and 17B are schematic representations of a tubing assembly having connectors according to another embodiment;

[0026] FIG.17C is a photograph of a tubing assembly having connectors being coupled to cannulas according to one embodiment;

[0027] FIG.18 is a photograph of a testing assembling to perform experiments on the tubing assembly; and

[0028] FIG.19 is a graph showing results of the experiments performed by the testing assembly of FIG.18.

[0029] Various embodiments are described below with reference to the appended drawings. It is to be appreciated that these drawings depict only some embodiments of the disclosure and are therefore not to be considered limiting of its scope. DETAILED DESCRIPTION OF THE DISCLOSURE

[0030] Despite the various improvements that have been made to injectors, conventional methods suffer from some shortcomings as discussed above. Specifically, conventional methods and devices may require longer than desired injection times, particularly when used with high viscosity substances. The long injection times lead to the device being applied and / or attached to the patient for longer than necessary, which may lead to patient discomfort and dissatisfaction. Patient discomfort and dissatisfaction may also lead to noncompliance.25880

[0031] Therefore, there is a need for further improvements to the devices and methods used to deliver medication, particularly for high viscosity medicaments. Among other advantages, the present disclosure may address one or more of these needs.

[0032] As used herein, the term “proximal,” when used in connection with a component of an injector, refers to the end of the component closest to the injector; whereas the term “distal,” when used in connection with a component of an injector, refers to the end of the component closest to the needle insertion site during use. The terms “trailing” and “leading” are to be taken as relative to the operator’s fingers (e.g., physician) of the injector. “Trailing” is to be understood as relatively close to the operator’s fingers, and “leading” is to be understood as relatively farther away from the operator’s fingers. Moreover, as used herein, the terms “medicament,” “medication,” and “drug” are used generically interchangeably and it will be understood that the ampoules described herein may be used to store, deliver or administer vaccines, biologics, therapeutic, medicaments, topical ointments, and the like.

[0033] Certain terminology is used in the following description for convenience only and is not limiting. The words “right,” “left,” “lower” and “upper” designate directions in the drawings to which reference is made. The words “inwardly” and “outwardly” refer to directions toward and away from, respectively, the geometric center of the device and designated parts thereof. Unless specifically set forth herein, the terms “a”, “an” and “the” are not limited to one element but instead should be read as meaning “at least one”. The terminology includes the words noted above, derivatives thereof and words of similar import.

[0034] Reference is now made to FIGS.1A-1B and 2, which are schematic illustrations of apparatus 20 for administering a substance, for example, insulin, to a subject, in accordance with an embodiment of the present disclosure. Typically, apparatus 20 comprises a vial 22 that contains the substance to be administered to a subject. Vial 22 is sealed at its proximal end by a stopper 24. A first threaded element 26 (e.g., a screw, as shown) is disposed at least in part within the vial, and a second threaded element 28 (e.g., a nut, as shown) is also disposed within the vial, threadedly coupled to the first threaded element. The distal end of the second threaded element defines a coupling portion 30 that couples the second threaded element to the stopper. The first threaded element is rotated by a rotation mechanism (e.g., motor 50), and by rotating, linearly advances the second threaded element and the stopper toward a distal end of the vial, without substantially rotating the second threaded element or the stopper.

[0035] In some embodiments, first threaded element 26 is a nut and second threaded element 28 is a screw disposed at least in part inside the nut. The nut is configured to rotate and to cause the screw and the stopper to advance toward a distal end of the vial due to the rotation of the nut. Alternatively, the first threaded element is a first screw and the second threaded element is a second screw. The first screw is configured, by rotating, to advance the second screw and the stopper toward the distal end of the vial. In general, apparatus 20 comprises a first threaded element that rotates, but is substantially immobile linearly during rotation of the first threaded element, and a second threaded element that (a) is substantially non-rotatable, (b) moves linearly toward the distal end of the vial in response to the rotation of the first threaded element, and (c) is coupled to the stopper. The first threaded element is rotated, causing the second threaded element and the stopper to advance distally.

[0036] Typically, vial 22 is inserted into a housing base 32. In some embodiments, portion 34 of the housing base is configured to impede proximal linear motion of first threaded element 26. (In the context of the present patent application and in the claims, the term “proximal” denotes a position toward an end 38 of the vial. The term “distal” denotes a position toward an end 36 of the vial, out of which the substance is administered to the subject.) In some embodiments, during rotation of first threaded element 26, stopper 24 is configured to impede rotation of second threaded element 28. Typically, friction of the stopper against the inside of the vial impedes rotational motion of the stopper, and element 28 being coupled to the stopper is similarly impeded. Thus, as first threaded element 26 is rotated, second threaded element 28 and the stopper advance linearly toward distal end 36 of the vial. In some embodiments, a standard, commercially-available vial and stopper are used as vial 22 and stopper 24. For some applications, the first and second threaded elements are standard, commercially-available threaded elements, e.g., a standard commercially-available screw and nut. Friction between the stopper and the vial impedes rotation of the stopper, while allowing distal movement of the stopper within the vial, as described in further detail herein below, with reference to FIGS.6C and 6E.

[0037] For some applications, rotation of the second threaded element is impeded by other means, for example, as described herein below.

[0038] For some applications, the initial position of stopper 24 in vial 22 is in accordance with the amount of the substance that is contained within the vial and that is to be administered to the subject. The lengths of first and second threaded elements 26 and 28 are typically such that whenthe threaded portions of the elements are maximally overlapping (i.e., fully screwed together), and the elements are disposed within the vial, coupling portion 30 couples the second threaded element to the stopper. For example, the lengths of the screw and the nut, shown in FIG.2, are typically such that when the screw is maximally inserted within the nut, and the screw and nut are disposed within the vial, coupling portion 30 of the nut couples the nut to the stopper. For example, if the vial contains a small amount of the substance prior to administering the substance, then stopper is disposed toward distal end 36 of the vial. In such a case, a relatively long screw / nut assembly (or screw / screw assembly) is designated to be disposed within the vial, so that coupling portion 30 couples the nut to the stopper. If, on the other hand, a large volume of the substance is contained within the vial, then a relatively short screw / nut assembly (or screw / screw assembly) is typically disposed within the vial. For some applications, screw / nut assemblies (or screw / screw assemblies) are color-coded or otherwise marked to indicate which screw / nut assembly (or screw / screw assembly) is suitable for use with which initial volume of substance.

[0039] In an alternative embodiment, first and second threaded elements 26 and 28 are placed in the vial, without being selected based on the initial volume of substance, and the elements are unscrewed from each other a suitable amount in order to facilitate the coupling of coupling portion 30 to the stopper.

[0040] Typically, a distal end 40 of the first threaded element 26 is configured to remain proximal to the stopper, or proximal to distal end 43 of the stopper, at all times during the rotating of the first threaded element. Further typically, the distal end of the second threaded element remains proximal to the distal end of the stopper at all times during the rotation of the first threaded element. The stopper typically provides a seal between a first portion of the vial, which is distal to the stopper, and a second portion of the vial, which is proximal to the stopper. In some embodiments, the sterility of the substance disposed in the first portion is maintained by the stopper providing a seal between the first portion and the second portion, threaded elements being disposed in the second portion. The first and second threaded elements assembly may be viewed as a shaft that converts the rotational motion of motor 50 to distal advancement of stopper 24. Typically, at all times during the rotating of the shaft, (a) the distal end of the shaft (i.e., the distal end of the second threaded element) is configured to remain proximal to a distal end of the stopper, and (b) the proximal end of the shaft (i.e., the proximal end of the first threaded element) is configured to remain distal to a proximal end of the rotation mechanism.25880

[0041] For some applications, a vial piercing mechanism 44 is movably (e.g., rotatably) coupled to housing base 32. As part of the insertion of vial 22 into the housing base, a seal 46 at distal end 36 of the vial is pierced by pressing the seal against the piercing mechanism. The substance is configured to subsequently flow through a tube 53 toward an activation mechanism 56, which is typically coupled to the housing base, and is configured to insert a cannula and / or a needle through the subject's skin and to deliver the substance via the cannula and / or the needle.

[0042] Although first and second threaded elements 26 and 28 have been described as being within vial 22 (e.g., the apparatus may be bought by the subject with the threaded elements already within the vial), in some embodiments, the threaded elements are inserted into the vial and are coupled to stopper 24 by the subject and / or by a healthcare provider. In some embodiments, vial 22 and stopper 24 are a standard, commercially-available vial and stopper, for example, the vial may be a circular barrel with a smooth inner wall. The first and second threaded elements are inserted into the vial and coupled to the stopper, and the apparatus dispenses the substance, in accordance with the techniques described hereinabove. The friction between the standard stopper and the standard vial prevents the second threaded element from rotating due to the coupling of the second threaded element to the stopper, as described hereinabove. For some applications, providing the apparatus described herein for use with standard, commercially-available vials and stoppers provides a commercial advantage.

[0043] For some applications, the threaded elements are coupled to housing base 32, and the subject and / or a healthcare provider moves the vial with respect to the housing base in order to couple the stopper to the second threaded element. For example, a standard, commercially- available vial and stopper may be moved with respect to the housing base, in order to couple the stopper to the second threaded element, the threaded elements being coupled to the housing base.

[0044] In some embodiments, a housing top 48 is coupled by the subject to housing base 32. The housing top typically comprises a motor 50 and a battery 58. (In an embodiment, the battery is coupled to housing base 32.) For some applications, a first cog 52 is coupled to housing base 32. The motor is configured to rotate the cog, and the cog is configured to rotate first threaded element 26. Typically, first cog 52 engages a second cog 54, the second cog being coupled to the proximal end of threaded element 26, and / or comprising the proximal portion of threaded element 26. In some embodiments, only a single cog is used, the single cog being coupled to and / or comprising a proximal portion of threaded element 26, and the single cog being rotateddirectly by the motor. Alternatively, or additionally, other techniques known in the art are used for converting motion from a motor to rotational or linear motion.

[0045] For some applications, the subject reversibly couples the housing top to housing base 32. Following the termination of the delivery of the substance to the subject from vial 22, the subject and / or a healthcare provider decouples the housing top from the housing base. In some embodiments, the housing top is configured to be re-used with another housing base, and the housing base is configured to be discarded after a single use. For some applications, the housing top and the housing base comprise magnetic materials 59 that are configured to releasably couple the housing top to the housing base when the top and the base are aligned.

[0046] For some applications, a control unit 51 is coupled to motor 50. In some embodiments, the control unit administers a basal rate of the substance to the subject by controlling the motor. Alternatively, or additionally, the control unit is configured to receive an input and to administer a bolus of the substance to the subject responsively to the input. For example, housing top 48 may comprise two buttons. When both buttons are pressed at the same time, the control unit is configured to administer a bolus of the drug. Alternatively, a button 80 associated with activation mechanism 56 may be configured to cause the control unit to administer a bolus of the drug, when pushed subsequent to the insertion mechanism having been activated. Further alternatively or additionally, a sensor 57 (shown in FIG.1B) is configured to detect one or more physiological parameters of the subject. The control unit is configured to control the administering of the substance in response to the detected parameters. In some embodiments, the sensor is configured to be implanted in the subject. For some applications, the sensor transmits the detected parameters to the control unit wirelessly.

[0047] Reference is now made to FIGS.3 and 4, which are respectively a schematic illustration of housing base 32, and a schematic illustration of vial 22 being inserted into the housing base, in accordance with an embodiment of the present disclosure. The housing base, as shown in FIG.3, is prepared for the insertion of vial 22. The distal end of the vial is inserted into vial piercing mechanism 44, which pierces the seal at the distal end of the vial. The vial is then lowered into the housing base. Typically, opposing resilient arms 70 support the vial upon the housing base.

[0048] In some embodiments, as vial 22 is lowered into housing base 32, first cog 52 engages second cog 54. For some applications, as the vial is lowered, portion 34 of the housing base automatically displaces first and second threaded elements 26 and 28 (and therefore stopper 24) toward distal end 36 of the vial. In some embodiments, the stopper is disposed within the vialsuch that before the insertion of the vial into the housing, first threaded element 26 protrudes a distance h from the proximal end of the vial. The proximal end of the first threaded element (or of second cog 54) comprises a rounded portion 74. Portion 34 of the housing base comprises an angled face 76. As rounded portion 74 slides past the angled face, the first threaded element is pushed the distance h inside the vial. As a result, the threaded elements and the stopper are displaced toward the distal end of the vial.

[0049] In some embodiments, apparatus 20 comprises alternative means of pushing threaded elements 26 and 28 inside vial 22 during the insertion of the vial into housing base 32. For example, the proximal end of first threaded element 26 may comprise an angled face and portion 34 of the housing base may comprise a rounded portion. Alternatively, both the proximal end of the first threaded element and portion 34 of the housing may comprise an angled face and / or a rounded portion.

[0050] For some applications, portion 34 of housing base 32 is configured to apply a sufficient force, in displacing threaded elements 26 and 28 and stopper 24, to overcome friction between stopper 24 and vial 22 that is due to prolonged storage of the stopper in contact with the vial. For example, the stopper may have been stored in contact with the inner surface of the vial for a period of at least one week or longer, as a result of which the stopper may have a higher effective static friction than would have existed if the stopper had been recently moved with respect to the vial. Alternatively, or additionally, apparatus 20 comprises a cannula 100 and / or a needle 102 (as shown in FIGS.7A-C), configured to be inserted in the subject's skin. Portion 34 of the housing base, by displacing the threaded elements and the stopper, is configured to expel gas through a distal end of the cannula and / or needle. In some embodiments, in addition to expelling the gas, portion 34 is configured to expel at least some of the substance therefrom, as a result of displacing the threaded elements and the stopper. Typically, the expelling of the substance from the distal end of the cannula before the cannula is inserted into the subject's skin increases the accuracy of the first dosage administered, because the initial activation of the motor essentially immediately administers the substance, without previously ejecting gas stored in the vial or conduits of apparatus 20.

[0051] Reference is now made to FIGS.5A and 5B, which are respectively a schematic illustration of vial 22 inserted in housing base 32, and of housing top 48 coupled to housing base 32, in accordance with an embodiment of the present disclosure. Housing top 48 is shaped such25880 that when it is coupled to the housing base, button 80 of activation mechanism 56 is accessible to be pressed by the subject.

[0052] Reference is now made to FIGS.6A-E. FIGS.6A-D are schematic cross-sectional illustrations of vial 22 at respective stages of use of apparatus 20, in accordance with an embodiment of the present disclosure. FIG.6E is a force vector diagram showing the forces acting on stopper 24 during rotation of first threaded element 26, in accordance with an embodiment of the present disclosure.

[0053] FIG.6A shows vial 22 before its insertion into housing base 32. First threaded element 26 (e.g., a screw, as shown) protrudes by distance h from proximal end 38 of the vial. Second threaded element 28 (e.g., a nut, as shown) is threadedly coupled to the first threaded element and is coupled to stopper 24 via coupling portion 30. For example, coupling portion 30 may be shaped to define teeth 90, which are inserted into the stopper. Or, coupling portion 30 may be a flat surface that is flush with a proximal end 42 of stopper 24, or that is otherwise in contact with the stopper.

[0054] During insertion of the vial into the housing base, the first and second threaded elements and the stopper are displaced toward distal end 36 of the vial, as shown in FIG.6B.

[0055] First threaded element 26 rotates during administration of the substance to the subject. Rotational motion of second threaded element 28 is impeded (even if not necessarily eliminated) by stopper 24 to which the second threaded element is coupled, and / or rotational motion of the second threaded element is impeded by alternative means, for example, as described with reference to FIGS.8A-B. Additionally, proximal linear motion of the first threaded element with respect to the vial is impeded (by portion 34 of housing base 32, not shown) during rotation of the first threaded element. The rotation of the first threaded element combined with the impeded rotation of the second threaded element results in the second threaded element and the stopper advancing toward distal end 36 of vial 22, as shown in FIGS.6C and 6D.

[0056] Typically, due to the rotation of the first threaded element, a linear force FL and a rotational force FR act on stopper 24, as shown in FIG.6E. A linear friction force FFL between the stopper and vial 22 acts to oppose the linear advancement of the stopper, and a rotational friction force FFR between the stopper and the vial acts to oppose rotation of the stopper. Further typically, and as described in detail in the following paragraphs, friction between the stopper and the vial acts to oppose rotation of the stopper to a greater extent than it acts to oppose linear advancement of the stopper through the vial. In particular, in this embodiment, rotation of the25880 stopper by (for example) a full rotation is impeded to a much greater extent than forward motion of the stopper by the pitch of the threaded elements is impeded, because significantly more friction must be overcome to produce a full rotation of the stopper than would need to be overcome in order for the stopper to advance the distance of the pitch of the threaded elements. As a result, friction generally acts to impede rotation of the stopper, while allowing distal movement of the stopper within the vial.

[0057] In a more detailed analysis of this effect, it is noted that, in some embodiments, friction between the stopper and the vial has the aforementioned effect due to selection of a suitable ratio of (a) the maximal diameter D of the first threaded element (shown in FIG.6C) to (b) the pitch P of the first threaded element. Typically, the ratio of the maximal diameter D to the pitch P is 3:1 to 30:1, for example, 6:1 to 20:1, or 8:1 to 15:1. In some embodiments, the ratio is 6:1 to 15:1, for example, 10:1. The pitch of the second threaded element is equal to the pitch of the first threaded element. Proximal linear motion of the first threaded element is impeded (as described hereinabove). Therefore, when the first threaded element rotates and the second threaded element unscrews from the first threaded element, the second threaded element must either rotate, advance distally, or both rotate and advance distally.

[0058] By way of example, the first threaded element may have a maximal diameter of 8 mm and a pitch of 1 mm (i.e., a ratio of maximal diameter to pitch of 8:1). Accordingly, the outer perimeter of the first threaded element is greater than 25 mm (pi multiplied by the maximal diameter). As the first threaded element rotates through 360 degrees, if the second threaded element were to unscrew from the first threaded element by rotating, the second threaded element would rotate through a distance of more than 25 mm, around the perimeter of the first threaded element. Accordingly, the outer surface of the stopper would rotate in contact with the inner surface of the vial through an even greater distance, such as 40 mm (since the outer diameter of the stopper is greater than that of the first threaded element, as seen, for example, in any of FIGS.6A-D). Alternatively, if the second threaded element unscrews from the first threaded element by advancing linearly through the vial, it advances by a distance of 1 mm, i.e., by a distance that is equal to the pitch of the threaded elements. Accordingly, in the presence of significant, intentionally-generated friction, the stopper advances substantially only linearly (in contact with the inner surface of the vial) by a distance of 1 mm, while rotating only to a relatively small extent.25880

[0059] It is noted that in some embodiments, friction between the stopper and the vial acts to impede rotation of the stopper, while allowing distal movement of the stopper within the vial, generally irrespective of the ratio of the maximal diameter D to the pitch P of the first threaded element.

[0060] As disclosed hereinabove, in some embodiments, friction acts to impede rotation of the stopper, while allowing distal movement of the stopper within the vial, even when the apparatus disclosed herein is used in conjunction with standard, commercially-available vials, stoppers, and threaded elements.

[0061] Reference is now made to FIGS.7A-C, which are schematic illustrations of activation mechanism 56 of apparatus 20 at respective stages of operation of the apparatus, in accordance with an embodiment of the present disclosure. Typically, following the insertion of vial 22 into housing base 32, and the coupling of housing top 48 to the housing base, the bottom surface of the housing base is adhered to the subject's skin (e.g., with an adhesive), as shown in FIG.1B. Subsequently, the activation mechanism is activated.

[0062] FIG.7A shows activation mechanism 56 before the activation mechanism has been activated. Needle 102 is disposed within the activation mechanism, and cannula 100 is disposed around the outside of the needle. When the bottom surface of housing base 32 is adhered to the subject's skin, the subject pushes button 80, which is accessible through housing top, as shown in FIG.5B. Until the force of the pushing of the button exceeds a threshold force, friction between a protrusion 104 of a structural element 103 and force receiving element 106 prevents the button and the needle being pushed down. (Force receiving element 106 is typically a surface of a holding portion 108, described herein below.) When the button is pushed by the subject with a force that exceeds the threshold force, force receiving element 106 is suddenly and rapidly pushed aside by protrusion 104. Typically, by applying sufficient force to the button to overcome the resistive force of force receiving element 106, the subject applies a level of force which is sufficient to suddenly and rapidly insert the needle and cannula into the subject's skin. FIG.7B shows the needle and cannula having been advanced due to button 80 having been pushed with a force that exceeds the threshold force.

[0063] The pushing of button 80 with sufficient force causes structural element 103 to advance toward the subject's skin. When the structural element arrives at the end of its travel, it is held in place by holding portion 108. For example, a proximal portion of protrusion 104 may be secured by a distally-directed force applied thereto by a distal portion of force receiving element 106,25880 constituting holding portion 108, as shown in FIG.7B. When the subject releases button 80, as shown in FIG.7C, a spring 110 pushes the button up, which retracts needle 102 back inside housing base 32. Cannula 100 is coupled to structural element 103, which is held in place by holding portion 108. Therefore, the cannula remains inserted in the patient's skin. The substance is administered to the subject via the cannula.

[0064] In an alternative embodiment, the substance is administered to the subject via needle 102, the needle remaining inserted in the subject's skin for the duration of the administration. In such an embodiment, apparatus 20 is typically configured to administer substantially all of the substance to the subject in less than one hour. For example, Copaxone® (or another drug) may be administered to the subject in this manner over the course of approximately one-half hour.

[0065] In some embodiments, needle 102 comprises a plurality of microneedles, which are inserted into the subject's skin, and the substance is administered to the subject via the microneedles. Typically, the diameter of each of the microneedles is about 50-150 microns, e.g., about 100 microns, and the length of each of the microneedles is about 200-1000 microns.

[0066] In an embodiment, control unit 51 is configured to receive an indication, on vial 22, first threaded element 26, second threaded element 28, or another element, which indicates a characteristic of the contents of vial 22. For example, a barcode, RFID, mechanical code, or other code may indicate to the control unit the type of pharmaceutical product in the vial, the quantity of the substance, or a dosage schedule for administration of the substance. Typically, when the subject first receives the vial, stopper 24 is already in place within the vial at the correct position for initiating delivery of the substance.

[0067] Reference is now made to FIGS.8A-B, which are schematic illustrations of respective views of vial 22, in accordance with an embodiment of the present disclosure. For some applications, a protrusion 120 protrudes from inner surface 122 of the vial, and second threaded element 28 is a nut that is shaped to define a groove 124 on its outer surface. As the nut advances toward the distal end of the vial, groove 124 slides along protrusion 120, preventing the nut from rotating. Alternatively, or additionally, stopper 24 is shaped to define a groove on its outer surface, the groove preventing the stopper, and therefore the second threaded element, from rotating. In some embodiments, inner surface 122 of vial 22 is not round, but, for example, is square, oval, or rectangular. The outer surface of the second threaded element, and / or the stopper, is shaped similarly to the inner surface of the vial. The shapes of inner surface 122, and25880 the outer surface of the second threaded element and / or the stopper, prevent the second threaded element from rotating.

[0068] In some embodiments, vial 22 contains (for example, the vial may be composed of) a cyclic olefin polymer, such as Crystal Zenith®. In some embodiments, manufacturing the vial using a cyclic olefin polymer facilitates the molding of protrusion 120. For some applications, stopper 24 is coated with a fluoropolymer. Typically, using a vial that contains a cyclic olefin polymer, and / or a stopper that is coated with a fluoropolymer maintains the stability of a substance that is disposed within the vial. For example, the vial may be used to administer a monoclonal antibody to the subject, and the composition of the vial, the stopper, and / or the second threaded element may maintain the stability of the monoclonal antibody.

[0069] In some embodiments, the proximal end of vial 22 is shaped to define two or more flanges 123. Typically, the flanges facilitate the filling of the vial. For example, during the filling of the vial, the vial may be placed inside a hole of a tray, and the flanges may support the vial inside the hole. In some embodiments, the flanges are configured to hold the vial in a fixed position inside housing base 32.

[0070] Reference is now made to FIG.9, which is a schematic illustration of apparatus 20 including a vial housing unit 170 and a separate needle housing unit 172, in accordance with an embodiment of the present disclosure. The apparatus shown in FIG.9 is generally similar to the apparatus shown in FIGS.1 and 2, except for the differences described herein below.

[0071] In some embodiments, activation mechanism 56 is housed in needle housing unit 172. The activation mechanism, as described hereinabove, inserts cannula 100 and / or needle 102 through the subject's skin and delivers the substance via the cannula and / or the needle. Vial 22 and control components, such as motor 50 and battery 58, are housed separately in vial housing unit 170. In some embodiments, needle housing unit 172 is adhered to the subject’s skin, and vial housing unit 170 is not adhered to the subject's skin. Typically, the needle housing unit and the vial housing unit are not rigidly connected to each other. For example, vial housing unit 170 may be worn on the subject's belt, or elsewhere on the subject's clothing. Typically, vial housing unit 170 is coupled to needle housing unit 172 via tube 53, via which the substance flows from the vial toward activation mechanism 56.

[0072] It is noted that, although a specific configuration of activation mechanism 56 is shown, in some embodiments, needle housing unit 172 houses an activation mechanism having a different configuration. For example, needle housing unit 172 may house only cannula 10025880 and / or needle 102. The subject inserts the needle into the subject's skin by adhering the needle housing unit to the skin.

[0073] As noted above, the injection force required to utilize the device may be significantly high for viscous drugs with conventional tubing configurations, such as tube 53. Meanwhile, patients desire quicker injections (e.g., injections quicker than 11 minutes). Thus, it would be desirable to reduce the injection force required, especially for high viscosity drugs while minimizing impact to device design and assembly process. In some examples, a delivery tubing may be configured to transfer drug from the container to the patient, maintain an aseptic fluid path and maintain drug integrity without any leakage.

[0074] To better illustrate the problems associated with conventional delivery tubing, FIGS. 10A-10B show an example of a tubing assembly 1000 that includes a cartridge needle hub 1020a that terminates in a cartridge needle or cartridge cannula 1022a for piercing a medicament container or vial V1, and a patient needle hub 1020b that terminates in a patient needle or patient cannula 1022b. A hollow tubing 1010 extends between cartridge needle hub 1020a and patient needle hub 1020b and connects the two components to create a fluid path P1 from cartridge cannula 1022a to patient cannula 1022b as shown in FIG.10A.

[0075] The pressure drop in a fluid pipe or tubing assembly may be governed by the Hagen Poiseuille equation show below: where ^^ isL is Length of the pipe, Q is Volumetric Flow rate, R is Radius of the pipe (or tubing), and ∆^^ is Pressure difference between two ends. It will be appreciated from this equation that radius has the highest impact on pressure drop and that increasing the radius of the tubing may substantially reduce pressure drop.

[0001] For the present purposes, total pressure drop in the fluid path may be calculated as: where Pcto the cartridge cannula, and Tu refers to the tubing connecting both cannulas. From this equation, it is apparent that several options are available to reduce the pressure drop and the corresponding injection force. For example, modifying one or more of the cannulas may achieve certain gains, but involves changing multiple25880 parts and complex capital equipment. Alternatively, increasing the tubing diameter may have a large impact on the pressure drop. Specifically, the tubing may be modified without altering the remaining structure of the tubing assembly (e.g., with modifying the cannulas).

[0076] Turning to FIG.11, in a first embodiment, tubing 1100 may be provided that has a central portion 1110, two tapered portions 1115a,1115b and two terminal portions 1116a,1116b, with a continuous lumen L1 extending between terminal portions 1116a,1116b. As shown, tubing 1100 maybe between 40 mm and 65 mm (e.g., between 50 mm and 60 mm, or approximately 56 mm) in length from the end of terminal portion 1116a to the end of terminal portion 1116b. Tubing 1100 may be configured in a such way that it has a larger diameter at central portion 1110 and smaller diameters at the terminal portions 1116a,1116b. In some examples, central portion 1110 has an inner diameter of approximately 0.5 mm. In some examples, terminal portions 1116a,1116b have the same inner diameter of approximately 0.29 mm. It will be understood that the terminal portions 1116a,1116b may instead have unequal inner diameters, if desired. The tapered portions 1115a,1115b may transition the tubing 1100 from the relatively larger inner diameter at central portion 1110 to the relatively smaller diameter at terminal portions 1116a,1116b. In at least some examples, tapered portions 1115a,1115b may be between 2 mm and 8 mm in length, and may transition the inner diameter (i.e., the diameter of the lumen) from 0.5 mm to 0.29 mm.

[0077] In some examples, tubing 1100 may be formed using molding techniques, such as dip molding. Specialized extrusion techniques, such as bump extrusion techniques, may also be used. In some examples, tubing 1100 may be formed of one or more materials, including various polymers or thermoplastic elastomers (TPE). FIG.12 is a chart showing certain dimensions of components of an exemplary injector system that include a cartridge, plunger, cartridge needle, patient needle, and proposed tubing dimensions in the last two rows.

[0078] In a variation of this embodiment, tubing 1200 may be extruded and a secondary operation may be performed to create a shape that has a gradually increasing inner diameter between two sections following by a gradually decreasing inner diameter. In the example shown in FIGS.13-15, tubing 1200 may be divided into three portions at locations 12-1, 12-2 and 12-3, and the tubing 1200 may be connected to a cartridge needle hub 1220a that terminates in a cartridge needle or cartridge cannula 1222a, and a patient needle hub 1220b that terminates in a patient needle or patient cannula 1222b. FIG.15 is a chart showing certain dimensions of examples of such a tubing. As shown, it may be difficult to achieve consistent dimensions (e.g.,25880 tapering) using this secondary operation. Without being bound to any particular theory, it is believed that initial testing reveals that the use a varying-diameter tube reduced the injection force by 25%.

[0079] In another embodiment, shown in FIG.16, tubing assembly 1600 including a large diameter tubing 1610 having a constant inner diameter from one end to the other. The inner diameter of tubing 1610 may be similar to the central portions described above for other embodiments (e.g., between 0.4 mm and 0.6 mm, or about 0.5 mm) and the outer diameter may be between 1.6 mm and 2.0 mm, or about 1.74 mm. Two molded connectors 1620 may be coupled to opposing ends of tubing 1610 and configured to receive ends of the tubing. In some examples, molded connectors 1620 may be friction fit onto tubing 1610, although other coupling means are possible. As shown in FIGS.17A-17B, each connector 1620 may include an enlarged section 1622, a tapered section 1624 and a narrowed section 1626. Enlarged section 1622 may have a first inner diameter, D1, configured to receive the outer diameter of tubing 1610 (e.g., enlarged section 1622 may define an inner diameter of approximately 1.8 mm). Tapered section 1624 may have a series of gradually decreasing inner diameters D2 that reduce the inner diameter to an inner diameter D3 of narrowed section of approximately 0.28 mm. In some examples, inner diameters D2 in the tapered section begin with an inner diameter of 1.8 mm and linearly decrease to an inner diameter for 0.28 mm. Non-linear transitions are also possible in the tapered sections. Connectors 1620 may be coupled to ends of tubing 1610 and a cannula may be disposed within the narrowed section 1626 of each connector, one to the patient and another to the vial. Without being bound to any particular theory, it is believed that initial testing reveals that the use of connectors in this manner reduced the injection force by approximately 40%.

[0080] FIG.18 shows a system for empirically testing the various tubing assemblies. In this example, various tubings were tested at a constant rate on an INSTRON® machine and the force output was measured utilizing BLEF test setup. In one example, the test speed was 4.5 mm / min or equivalent to 1.2 mL / minute, and the test fluid was N10 (mineral oil) with a viscosity of ~19cP at 20 degrees Celsius. Cartridges were filled to 5 mL. Although the test fluid was N10 with a viscosity of approximately 19 cP, substances contemplated for use with tubing according to the present disclosure may vary. In some examples, substances to be used with the present disclosure may have a viscosity of 0-5 cP, 5-10 cP, 10-15 cP, 15-20 cP, 20-25 cP, 25-30 cP, 30- 35 cP, 35-40 cP, 40-45 cP, 45-50 cP, 50-55 cP, 55-60 cP, 60-65 cP, 65-70 cP, 70-75 cP, 75-8025880 cP, or 80-90 cP, 90-100 cP, or 100 cP or more. These substances may be administered at 15-20 degrees C, 20-25 degrees C, or 25 or more degrees C.

[0002] FIG. 19 illustrates results according to the tested protocol. Several curves are shown illustrating the force in Newtons against the displacement in mm for three different sets. Curve 1900 represents the baseline tubing having a constant diameter, which shows a measured force between 90N and 100N. Curve 1910 represents the first embodiment in which a tubing is manufactured to include varying diameters according to the embodiments described with respect to FIGS.11-15, and it shows a decrease in the force of approximately 25%. Curve 1920 represents the second embodiment in which a tubing is used in conjunction with molded connectors according to the embodiments described with respect to FIGS. 16-17C, and a decrease in the force of approximately 40% was observed.

[0081] It is to be understood that the embodiments described herein are merely illustrative of the principles and applications of the present disclosure. For example, the materials and configurations of the tube may be varied. Moreover, certain components or steps of a method of using the device are optional, and the disclosure contemplates various configurations and combinations of the steps disclosed herein. It is therefore to be understood that numerous modifications may be made to the illustrative embodiments and that other arrangements may be devised without departing from the spirit and scope of the present disclosure as defined by the appended claims.

[0082] It will be appreciated that the various dependent claims and the features set forth therein can be combined in different ways than presented in the initial claims. It will also be appreciated that the features described in connection with individual embodiments may be shared with others of the described embodiments.

Claims

25880 CLAIMS 1. A tubing assembly for an injection device comprising: a tubing having a first end and a second end, the tubing defining a lumen from the first end to the second end, the tubing having a first terminal portion, a first tapered portion, a central portion, a second tapered portion and a second terminal portion.

2. The tubing assembly of claim 1, wherein the central portion has an inner diameter of 0.5 mm.

3. The tubing assembly of claim 1, wherein the first terminal portion and the second terminal portion have a same inner diameter.

4. The tubing assembly of claim 1, wherein the first terminal portion and the second terminal portion both have an inner diameter of 0.29 mm.

5. The tubing assembly of claim 1, wherein the first tapered portion is disposed between the first terminal portion and the central portion, and the second tapered portion is disposed between the second terminal portion and the central portion.

6. The tubing assembly of claim 1, wherein the tubing is between 40 mm and 65 mm in length from the first end to the second end.

7. The tubing assembly of claim 1, wherein the tubing is formed of a polymer.

8. The tubing assembly of claim 1, wherein the tubing is formed of a thermoplastic elastomer.

9. A delivery system comprising: the tubing assembly of claim 1; a first cannula coupled to the first end of the tubing; and a second cannula coupled to the second end of the tubing.25880 10. A tubing assembly for an injection device comprising: a tubing having a first end and a second end, the tubing defining a lumen having a constant inner diameter and a constant outer diameter from the first end to the second end; a first connector coupled to the first end, the first connector having a first enlarged section, a first tapered section and a first narrowed section; and a second connector coupled to the second end, the second connector having a second enlarged section, a second tapered section and a second narrowed section.

11. The tubing assembly of claim 10, wherein the first connector and the second connector have equal dimensions.

12. The tubing assembly of claim 10, wherein the first connector is configured to accept the outer diameter of the first end of the tubing, and the second connector is configured to accept the outer diameter of the second end of the tubing.

13. The tubing assembly of claim 10, wherein the first narrowed section and the second narrowed section have a same inner diameter.

14. The tubing assembly of claim 10, wherein the first narrowed section and the second narrowed section have an inner diameter of 0.28 mm.

15. The tubing assembly of claim 10, wherein the first tapered section is disposed between the first enlarged section and the first narrowed section, and the second tapered section is disposed between the second enlarged section and the second narrowed section.

16. The tubing assembly of claim 10, wherein the first enlarged section and the second enlarged section have a same inner diameter.

17. The tubing assembly of claim 10, wherein the first enlarged section and the second enlarged section have an inner diameter of 1.8 mm.25880 18. A delivery system comprising: the tubing assembly of claim 10; a first cannula coupled to the first narrowed section of the first connector; and a second cannula coupled to the second narrowed section of the second connector.

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