syringe

Abstract

The present invention relates to a syringe comprising an elongated housing having a proximal end and a distal end, wherein the proximal end comprises an actuation mechanism, wherein the elongated housing defines a lumen between the proximal and distal ends adapted to receive and hold a drug chamber to the actuation mechanism. The drug chamber also has corresponding proximal and distal ends and has a stop between its proximal and distal ends for holding the drug within the drug chamber. The actuation mechanism comprises an actuation housing having corresponding proximal and distal ends and a distal end adapted to engage with the proximal end and the elongated housing, wherein the actuation mechanism comprises a plunger, the distal end of which engages with or is adapted to engage with the stop. The plunger communicates with at least one drive spring which biases the plunger distally when the actuation mechanism has finished preparing for injection. Here, the plunger engages with an opposing second complementary surface to hold the plunger in a position against bias by at least one retaining arm or toggle having at least one first surface adapted to hold the plunger in a first non-operating position when the actuation mechanism has completed preparing for injection, the first and second surfaces are held in the engaged position by a restraint that, when induced, transitions from a non-operating position or configuration to an operating position or configuration, thereby disengaging the engagement between the first and second surfaces, allowing the plunger to be released and move distally. The present invention also relates to a needle hub, actuation mechanism, dosing mechanism, and assembled elongated housing for use in such a syringe, as well as a method of using such an instrument.

Description

Field

[0001] The present invention relates to an improvement of a syringe for delivering an active agent to a patient, and more particularly, although not exclusively, to an improvement of a syringe for intravitreal use. Background

[0002] Over the decades, a wide variety of syringes have been proposed. The most basic of such instruments is a basic syringe equipped with a needle, a barrel, and a plunger. The needle is optionally covered with a cap. The syringe may also be pre-filled with a drug. The needle may be an integral part with the syringe (i.e., integrally formed with the barrel), or may be separate and attached by a snap-type or screw-type mechanism such as a tight fit, a nest fit, or a luer lock attachment.

[0003] Such syringes are potentially dangerous because the patient and the syringe are exposed to the needle during administration. In order to ensure effectiveness, it is necessary to inject the correct amount of the active agent into the patient at the correct depth and, as in the case of intravitreal injection, to take care to avoid damage to other structures.

[0004] Recently, instruments with a protective sheath that always protects the needle when not in use have been developed. This sheath is biased to a shielding position and is pushed out so as not to interfere when the needle is pushed towards the subject. However, since such a sheath is usually not fixed in a predetermined position, pressing a used syringe against another surface may create a hole in that surface (which may also be the surface of the human body).

[0005] Auto-injectors that automatically release a predetermined amount of medication when pressed against a subject are also described. They may also feature a biased sheath to ensure the needle is shielded when not injecting. However, such syringes (e.g., Epi-pen®) are generally designed to release a specific amount regardless of the subject's age, build, health, and other physiological parameters, and typically spray the medication rapidly and briefly. This can be undesirable in many situations, such as injections into the eyes.

[0006] Optionally, electric syringes that dispense the desired amount of medication in a stepwise, continuous manner are also described. However, such syringes are very complex and expensive and are not suitable for single-use or disposable injection procedures.

[0007] Exemplary syringes for intraocular injections, including intravitreal injections, are known. Intravitreal injections, in particular, can be complex because the desired injection site is located in a flat area approximately 3-4 mm posterior to the limbus of the cornea. Furthermore, because the injection site is sensitive and delicate, the force required to inject the drug must be finely adjusted to reduce the risk of side effects. However, since many of the drugs typically used in ophthalmic procedures are biological formulations, such products may have higher viscosity than other drugs typically used in exemplary auto-injectors, making administration and delivery even more complex. Therefore, traditionally, such injections have been performed by physicians using standard syringes and measuring instruments (placed over the eye, surrounding the cornea, and with spaced holes for the needle).

[0008] Typical instruments specifically designed for intravitreal injection usually feature a spatial measuring device at the injection end to ensure the needle is properly positioned on the flattened surface. However, such instruments generally fail to adequately ensure the correct injection depth (which is crucial in intravitreal injection), cannot lock the sheath covering the used needle, or protect the needle's fluid pathway and injection site from contamination, are not suitable for easily adjustable and precise automated dosing, are complex and expensive, and are not readily suitable for single-use or disposable injection procedures, or a combination of these drawbacks.

[0009] The object of the present invention is to address these challenges and provide an improved auto-injector and system that offers precise and adjustable dosage and control of injection force and delivery force, thereby reducing risks to patients, improving clinical workflows, and enhancing the effectiveness of treatments. [Overview of the Initiative]

[0010] According to a first embodiment of the present invention, a syringe is provided comprising an elongated housing having a proximal end and a distal end, the proximal end of which is equipped with an actuation mechanism, wherein the elongated housing defines a lumen between the proximal and distal ends adapted to receive and hold a drug chamber to the actuation mechanism, the drug chamber also having corresponding proximal and distal ends and having a stop between its proximal and distal ends for holding the drug within the drug chamber, the actuation mechanism comprising an actuation housing having corresponding proximal and distal ends and a distal end adapted to engage with the proximal end and the elongated housing, wherein the actuation mechanism includes a plunger, the distal end of which engages with or is not engaged with the stop. Adapted to accommodate, the plunger communicates with at least one drive spring that biases the plunger distally when the operating mechanism has completed preparing for injection, wherein the plunger engages with an opposing second complementary surface to hold the plunger in a position against bias by at least one retaining arm or toggle having at least one first surface adapted to hold the plunger in a first non-operating position when the operating mechanism has completed preparing for injection, wherein the first and second surfaces are held in the engaged position by a restraint that, when induced, transitions from a non-operating position or configuration to an operating position or configuration, thereby disengaging the engagement between the first and second surfaces, allowing the plunger to be released and move distally.

[0011] In certain embodiments, the restraint may also transition from a non-operated position or configuration to an operated position or configuration by an activation mechanism that is activated when the needle connected to the syringe reaches a desired injection depth, or it may include a mechanism that moves the restraint proximal or distal as the needle is inserted into the subject and releases the retaining arm or toggle when the needle reaches a desired insertion depth. However, it is also conceivable that the restraint may transition from a position or configuration that restrains the retaining arm or toggle to a released position or configuration by a mechanism activated by a button that is pressed or slid when the needle is at a desired injection depth. Alternatively, after the restraint has transitioned from a position or configuration that restrains the retaining arm or toggle to a released position or configuration, the retaining arm or toggle may remain in the non-operated position until a mechanism is activated by a button that is pressed or slid by an operator.

[0012] In certain embodiments, the elongated housing also includes a sleeve that is slidable at least proximal to the drug chamber between the elongated housing and the drug chamber, and which slides proximal to the drug when the needle connected to the syringe is inserted into the subject. In certain embodiments, the sleeve is adapted to engage with the restraint, so that proximal movement of the sleeve causes proximal movement of the restraint, where operationally, when the needle connected to the syringe is inserted into the surface, the sleeve slides proximal to the restraint, and as a result the restraint moves proximal to the operating position or configuration, although it is also conceivable that the proximal movement of the sleeve may cause the restraint to move distally (e.g., by lever action or other opposing / complementary mechanism). In certain embodiments, when the restraint moves to a position that releases the retaining arm or toggle, the retaining arm or toggle is released, the plunger moves distally, and the drug is delivered to the subject. However, even if the restraint is in the released position / configuration, distal movement of the plunger may still be restrained until another mechanism is triggered to release mode, for example by a manually operated button. The sleeve may be located between the elongated housing and the drug chamber when housed within the elongated housing, outside the elongated housing, or a combination of both.

[0013] In certain embodiments, the restraint is in a non-operating position distally and in an operating position proximally. Therefore, when the sleeve is slid proximal to the elongated housing during operation, the restraint moves proximal, thereby releasing the retaining arm or toggle, disengaging the connection between the first and second surfaces, and allowing the drive spring to drive the plunger and stopper distally.

[0014] In certain embodiments, the retaining arm or toggle is a retaining toggle having a distal end and a proximal end, and is connected to the plunger by a pivot point located between the distal and proximal ends. In certain embodiments, the first surface of the toggle may be in the form of an outward projection adapted to engage with an opposing second complementary surface in the form of an inward projection on or connected to the operating housing, and the proximal end of the toggle includes a surface adapted to engage with a complementary surface of the restraint. In certain embodiments, the outward projection may be located between the pivot point and the proximal end of the toggle.

[0015] In certain embodiments, the restraint may be connected to the proximal end of the sleeve, or may form part of the proximal end of the sleeve. In other embodiments, the restraint may be separate from the sleeve.

[0016] In certain embodiments, at least during use, the distal end of the syringe may be provided with a sheath that encloses at least the distal portion of the needle assembly that is in fluid communication with the drug chamber, the sheath being an integral part of the sleeve or adapted to engage with the distal end of the sleeve and adapted to slide between the elongated housing and the drug chamber. The sheath is slidable at least proximal to the needle to withdraw the needle from the sheath when inserting the needle into a subject during injection, in which case the sleeve moves proximal, and as a result moves proximal to a position where the restraint releases the retaining arm or toggle, thereby enabling the release of the plunger.

[0017] In certain embodiments, the sleeve and sheath are held in a position surrounding the needle by a second spring pressurized between the operating housing or the plunger and the sleeve, and the sleeve is adapted to engage with the second spring.

[0018] In another embodiment, the sheath comprises a pressurized spring or other suitable biasing means between the distal portion of the sheath and the needle assembly so as to ensure that the sheath securely covers the tip of the needle.

[0019] In certain embodiments, the retaining arm or toggle is adapted to stop the proximal movement of the sleeve and sheath when released, so that the sleeve and sheath return to a position where they surround the needle.

[0020] In certain embodiments, at least one retaining arm or toggle may comprise at least one biasing arm, one end of which is connected to at least one proximal end of the actuation mechanism housing, or, in a preferred embodiment, to the proximal end of the plunger, and the other end of the at least one biasing arm comprises an inward projection adapted to engage with the plunger, or, in a preferred embodiment, a complementary outward projection provided on at least one of the actuation mechanism housings, the outward projection optionally formed as a groove in the plunger or a ridge on the plunger.

[0021] The configuration of the syringe's operating mechanism allows the force required to move the restraint proximal and release the retaining arm or toggle to be significantly reduced compared to a mechanism in which the retaining arm or toggle is biased inward relative to the plunger. According to a particular aspect of the present invention, the induced force required to release the engagement between the first surface and the second surface, and to release the plunger and move it distally, is inversely proportional to an a / b value, where a is the distance between the proximal end of the toggle and the pivot point, and b is the axial extension distance between the edge of the first surface and the pivot point, and the induced force can be adjusted by adjusting this a / b value.

[0022] The retaining arm or toggle may be equipped with a biasing means as an integrated component, or it may be biased by a biasing means attached to a separate component of the operating mechanism. In certain embodiments, the at least one retaining arm or toggle is biased by an integrated biasing means that applies force to the plunger or away from the plunger when the instrument is ready for injection. In other embodiments, the at least one retaining arm or toggle is biased by a biasing means connected to the plunger that applies force to the retaining arm or toggle away from the plunger when the instrument is ready for injection.

[0023] In certain embodiments, the operating mechanism housing and the elongated housing are detachable from each other, thereby allowing the drug chamber to be inserted into or removed from the elongated housing, detached, or replaced.

[0024] In certain embodiments, the drug chamber is pre-filled.

[0025] In other embodiments, the drug chamber is either vacuumed or filled without voids, in which case positive pressure is generated within the drug chamber by the engagement of the plunger and the stopper, the placement of the drug chamber within the elongated housing, and the connection between the operating housing and the elongated housing. This configuration offers the following advantages: When the needle is positioned in fluid communication with the distal end of the drug chamber, the positive pressure within the drug chamber causes a small amount of fluid to be expelled from the drug chamber through the needle, thereby filling the needle. This allows the instrument to automatically prepare the drug and further prevents air, other fluids, or contaminants from entering the drug chamber.

[0026] In certain embodiments, the needle assembly is attached to a drug chamber, and the distal end of the drug chamber is adapted for the attachment of the needle assembly.

[0027] In another aspect, the needle assembly is attached to the elongate housing, and the distal end of the elongate housing is adapted to allow fluid communication between the needle assembly and the drug chamber. This requires a bridge across the elongate housing between the sleeve lips, such that the sleeve is slidable between an outer portion of the elongate housing and an inner needle assembly engagement portion of the elongate housing. In certain aspects, the elongate housing includes a sleeve slidable at least proximally between the elongate housing and the drug chamber and adapted to engage the restraint, whereby proximal movement of the sleeve causes proximal movement of the restraint, and where, in operation, the distal end of the elongate housing includes a needle assembly having a sheath surrounding at least the distal portion of the needle in fluid communication with the drug chamber, where the sheath is slidable at least proximally relative to the needle to remove the needle from the sheath during insertion of the needle into the subject, such that the sleeve slides proximally and the restraint moves proximally to the actuated position.

[0028] In certain aspects, the needle assembly is attached to the distal end of the drug chamber or the elongate housing by means of a tight fit, snap, screw, or luer lock mechanism.

[0029] In an alternative aspect, the needle may form at least an integral part of the drug chamber or may be an integral part of the elongate housing.

[0030] In a specific embodiment, in a syringe according to the present invention, the elongated housing comprises a sleeve adapted to slide proximal between the elongated housing and the drug chamber, and adapted to engage with a restraint such that the proximal movement of the sleeve causes the restraint to move proximal; the distal end of the elongated housing is connected to or adapted to connect to a needle assembly including a sheath, wherein the sheath is slidable at least proximal to the needle to pull the needle out of the sheath during insertion of the needle into a subject, and to slide the sleeve proximal; and the connection As a result, the restraint moves proximal from a first non-operating position to a second operating position; the plunger is held in a position against the stress by a toggle having a distal end and a proximal end, connected to the plunger by a pivot point located between the distal end and the proximal end, wherein the first surface has the shape of an outward projection located between the pivot point and the proximal end, adapted to engage with the opposing second complementary surface provided on or connected to the operating housing in the form of a complementary inward projection, and the proximal end of the toggle has a surface adapted to engage with the complementary surface of the restraint when in the non-operating position.

[0031] According to another embodiment of the present invention, a syringe is provided comprising an elongated housing having a proximal end and a distal end, the proximal end of which is equipped with an operating mechanism, wherein the elongated housing defines a lumen between the proximal and distal ends, the lumen containing or adapted to receive and hold the drug chamber for the operating mechanism, the drug chamber also having corresponding proximal and distal ends and having a stopper between the proximal and distal ends for holding the drug in the drug chamber, the operating mechanism having corresponding proximal and distal ends, and , comprising an operating housing having a proximal end and a distal end adapted to engage with the elongated housing, wherein the operating mechanism includes a plunger, the distal end of which engages with or is adapted to engage with the stop, and the plunger is in communication with at least one drive spring which biases the plunger distally when the operating mechanism has completed preparing for injection, wherein the plunger is held in a position against bias by a toggle having a distal end and a proximal end, and a pivot point located between the distal end and the proximal end The toggle is connected to the plunger by a torch, and the toggle has an outward-facing projection located between the pivot point and the proximal end, adapted to engage with an inward-facing projection on the opposite side, which is on or connected to the operating housing, and holds the plunger in a first non-operating position when the operating mechanism has completed preparing for injection, the proximal end of the toggle includes a surface adapted to engage with a complementary surface of the restraint, thereby holding the toggle in a non-operating position, and thereby holding the outward-facing projection and the inward-facing projection on the opposite side in an engaged position, where the restraint The device, when triggered, moves from a non-operational position or configuration to an operational position or configuration, thereby allowing the toggle to flex to the operational position, thereby disengaging the engagement between the outward-facing projection and the inward-facing projection on the opposite side, disengaging the distal movement of the plunger, and the elongated housing comprises at least a sleeve adapted to slide proximal between the elongated housing and the drug chamber, and is adapted to engage with the restraint such that the proximal movement of the sleeve causes the proximal movement of the restraint, and also,The distal end of the elongated housing is connected to or adapted to be connected to the assembly of the needle including the sheath, and the sheath is an integral part of the sleeve or is adapted to engage the distal end of the sleeve, where the sheath is slidable at least proximally relative to the needle to draw the needle out of the sheath when inserting the needle into a subject and to slide the sleeve proximally, so that the restraint moves proximally from the non-activated position to the activated position, the engagement between the inward projection on the opposite side of the outward projection is released, and the plunger is released and moves distally.

[0032] In certain embodiments, the actuating housing includes a dosing mechanism adjustably coupled to the plunger at its proximal end, whereby the distance between the dosing mechanism and the actuating housing, and thus the allowable movement distance of the plunger, can be set to a predetermined value, and a selected volume of the drug can be manually released.

[0033] In an alternative embodiment, the plunger has a proximal end that extends proximally beyond the actuating housing and engages the cap or knob via an adjustable means such that the distance between the cap or knob and the actuating housing, and thus the allowable movement distance of the plunger, is controlled, whereby, in operation, by adjusting the cap, a selected volume of the drug can be delivered. In a particular embodiment, the dosing mechanism includes a first internal knob, a second external dosing setting knob, and a dosing delivery housing adapted to be placed on the proximal end of the actuating housing, where the proximal end of the plunger engages the first knob via a screw with an axial: longitudinal pitch X, and this first knob axially engages the second knob but does not longitudinally engage, and the second external dosing setting knob engages the dosing delivery housing via a screw with an axial: longitudinal pitch Y, where pitch Y is greater than pitch X, so that when the second external dosing setting knob is rotated axially, the same degree of axial rotation as that of the first knob occurs, but the longitudinal movement of the second external dosing setting knob is greater than that of the first knob.

[0034] In a particular embodiment of the syringe according to the present invention, the drive spring is positioned between the plunger and the proximal end of the operating mechanism housing. In other embodiments, the drive spring may be offset by the plunger and indirectly bias the plunger.

[0035] In certain embodiments, the syringe according to the present invention is for intravitreal injection and comprises a sheath enclosing at least the distal portion of a needle assembly that is in fluid communication with the drug chamber, the sheath being an integral part of the sleeve or adapted to engage with the distal end of the sleeve and adapted to slide between an elongated housing and a drug chamber, wherein the sheath is slidable at least proximal to the needle, so that during insertion of the needle into a subject the needle is dislodged from the sheath, the sleeve is pushed and moves proximal to a restraint, the restraint moves to a position where it releases a retaining arm or toggle, the sheath having a distal eye contact surface.

[0036] In certain embodiments, the eye contact surface has an outer circumference defining a circle or a deformed circle. The surface is annular, or a perforated concave disc, disc-shaped, or three-dimensional annular surface, in which case the needle defines the center of the circle. However, other shapes are also usable. When the eye contact surface is annular, or a perforated concave disc, disc-shaped, or three-dimensional annular surface, the diameter of the circle may be 4 to 10 mm, more preferably 6 to 8 mm. This allows for easy measurement of the distance from the limbus to the flattened portion of the cornea as 2 to 5 mm, preferably 3 to 4 mm, to ensure injection into the vitreous cavity of the eye. Even when other shapes of eye contact surfaces are used, at least one eye surface contact edge must be provided 2 to 5 mm, preferably 3 to 4 mm away from the needle, in order to properly position the needle for intravitreal injection.

[0037] In certain embodiments, the sheath has an external pad located substantially identical to the eye contact surface to apply pressure to a site adjacent to the injection site after injection. The external pad may extend along the periphery of the eye contact surface or extend from the outer surface of the sheath.

[0038] In certain embodiments, the syringe according to the present invention may be for single use or for multiple injections of either the same drug or different drugs. If the instrument is for multiple injections, the needle hub may be replaceable, the drug chamber may be replaceable, or the assembled elongated housing may have a drug chamber and a needle assembly (usually including a cap) that is replaceable. If the instrument is for single use, or if the assembled working housing with a drug chamber is for single use or limited multiple use, the drug chamber may be formed integrally with the elongated housing. If the instrument is for single use, the needle may also be integrated with the elongated housing or may be part of a separate replaceable needle assembly or hub. In certain embodiments, the elongated housing is adapted to house a filled drug chamber, where the needle assembly is formed integrally with the syringe body, or the elongated housing is adapted to have a needle assembly or needle hub attached thereto, thereby allowing the needle to fluidly communicate with the drug chamber.

[0039] According to another embodiment of the present invention, a needle hub is provided, adapted for attachment to a syringe according to any of the above-described embodiments of the syringe, and comprising a body from which a needle and the injection end of the needle protrude distally, wherein the proximal end of the needle hub is adapted to connect to an engagement portion so that the needle can operately communicate with the drug chamber, and the needle hub also comprises a sheath surrounding the distal needle and body, the proximal end of the sheath being operationally adapted to hold the body of the needle assembly within the sheath, engage with the sleeve of the syringe, and fit and slide against the syringe when the hub is attached to the syringe. The body of the needle assembly may be integrally molded or formed by injection molding technology, or may be a detachable or permanently attached part. The body may further have a proximal end from which the proximal end of the needle protrudes proximal and a body from which the injection end of the needle protrudes distally, the proximal end of the body being optionally adapted to engage with an elongated housing or drug chamber via a snap, tight-fit, screw, or Luer lock mechanism. The needle hub may optionally include a cap that completely encloses at least the distal end of the needle hub.

[0040] According to an alternative embodiment of the needle hub, a needle hub is provided which can be attached to a syringe according to any of the above embodiments of the syringe and comprises a body having a proximal body and a distal body, the body having a proximal end adapted to engage with the distal end of an elongated housing or drug chamber, the proximal body having a proximal needle extending in the proximal direction, the distal body having a distal needle extending in the distal direction, the proximal and distal bodies being adapted to connect to each other via a sealed filter between them and between the two needles, the needle hub also comprises a sheath surrounding the needle and body, the proximal end of the sheath being adapted to hold the body of the needle assembly within the sheath when not in use, to engage with the sleeve of the syringe, and to fit and slide within the elongated housing. Such embodiments make it possible to avoid particulate matter that may be present in the drug in the drug chamber and / or particulate matter that may be generated as a result of the proximal needle puncturing the distal seal of the drug chamber. The proximal and distal needles may or may not have the same gauge (outer diameter). The gauge of the proximal needle may be larger or smaller than that of the distal needle. However, since the proximal needle does not participate in the injection, it does not impose any limitations on comfortable intravitreal injection, and therefore can be any gauge. On the other hand, if the needle hub is for intravitreal injection, the distal needle may preferably have a gauge of 25 (outer diameter about 0.5 mm) or less, and preferably a gauge of 27 (outer diameter about 0.4 mm) or less. The needle hub may optionally be provided with a cap that completely encloses at least the distal end of the needle hub, and such a cap is usually provided at the time of distribution. Optionally, the cap may also include means to ensure that the cap does not rotate axially relative to the body when the needle hub is connected to the syringe.

[0041] In a particular embodiment, the needle hub is for intravitreal injection and has a distal eye contact surface as described above. In a particular embodiment, the sheath is substantially cylindrical for most of its length and has a frustoconical distal end.

[0042] The needle hub may include a sheath having an external pad that is substantially the same boundary as the eye contact surface in order to apply pressure adjacent to the injection site after injection. The external pad may extend around the eye contact surface or extend from the outer surface of the sheath.

[0043] The sheath may also include a characteristic component that prevents axial rotation of the sheath relative to the cap while fixing the needle hub to the syringe according to the present invention.

[0044] According to another embodiment of the present invention, a needle hub adapted for attachment to a syringe is provided, the syringe comprising a drug chamber and an engagement portion enabling connection to the drug chamber, the needle hub comprising a body with a needle and the injection end of the needle protruding distally, the proximal end of the needle hub being adapted for connection to the engagement portion so as to enable operational communication of the needle with the drug chamber, the needle hub also comprising a sheath covering the distal needle and body, the proximal end of the sheath being adapted for operational connection to the syringe sleeve and to fit and slide against the syringe when the hub is attached to the syringe, and the needle hub optionally also comprising a cap that completely covers at least the distal end of the needle hub.

[0045] According to another embodiment of the present invention, an operating mechanism for a syringe is provided, the mechanism having a plunger, the distal end of which is adapted to engage with a stopper, the plunger communicating with a drive spring which biases the plunger distally when the operating mechanism has completed preparing for injection, wherein the plunger is held in a position against the stress by a retaining arm or toggle having at least one first surface adapted to engage with an opposing second complementary surface in order to hold the plunger in a non-operating position when the operating mechanism has completed preparing for injection, the first and second surfaces are held in the engaged position by a restraint which, when induced, transitions from a non-operating position or configuration to an operating position or configuration, thereby disengaging the engagement between the first and second surfaces, and allowing the plunger to be released and move distally.

[0046] According to another embodiment of the present invention, an assembly of an elongated housing is provided for use with any one of the above embodiments of a syringe, the assembly of the elongated housing having a proximal end and a distal end defining a lumen between them, the assembly of the elongated housing including or adapted to house and hold a drug chamber relative to the operating mechanism, the drug chamber also having corresponding proximal and distal ends and having a stop between its proximal and distal ends for holding the drug in the drug chamber, wherein the elongated housing also comprises a sleeve adapted to engage with a restraint of the operating housing, and wherein when a needle connected to the elongated housing is inserted into a subject, the sleeve slides in the proximal direction.

[0047] According to another embodiment of the present invention, a dosage delivery mechanism for a syringe is provided, the syringe comprising a body having a distal end to which a needle assembly is attached, and a proximal end comprising an operating mechanism including a plunger having a distal end and a proximal end, the syringe further comprising a drug chamber also having a distal end and a proximal end, and comprising a stop between the distal end and the proximal end and the drug between the stop and the distal end of the drug chamber, wherein the distal end of the plunger is adapted to engage with the stop, and the dosage delivery mechanism is adjustablely coupled to the proximal end of the plunger, thereby setting a selected volume of drug for delivery by setting the distance between the delivery mechanism and the body of the instrument, and thus the allowable travel distance of the plunger, to a specific value.

[0048] According to another embodiment of the present invention, a method for operating a syringe is provided, the syringe comprising an elongated housing having a proximal end and a distal end, the proximal end having an actuation mechanism, and the distal end having or being adapted to have a needle. The syringe further comprises a drug chamber having a stopper, the actuation mechanism comprising a plunger, the distal end of the plunger being adapted to engage with the stopper, the plunger being biased toward the distal end when the actuation mechanism has completed preparation for injection, the plunger being held in a position against this bias by a retaining arm or toggle, thereby holding the plunger in a non-actuation position when the actuation mechanism has completed preparation for injection, the plunger being held in an engaged position by a restraint adapted to move from a non-actuation position or configuration to an actuation position or configuration when triggered. The method comprises placing the instrument in the actuation position, triggering the restraint to release the plunger from the engaged position, and then the plunger moving distally to deliver the drug from the drug chamber.

[0049] Accordingly, suitable embodiments of the present invention provide one or more of the following: reduced inducing force, more precise injection depth, accurate and adjustable dosage, protection of the needle and / or fluid pathway of the instrument including pre-injection preparation and post-injection needle lock protection, precise injection positioning (in the case of intravitreal injection), confirmation of dosage delivery, use of pre-filled syringes or cartridges, automated preparation, or any combination thereof. [Brief explanation of the drawing]

[0050] Exemplary embodiments of the present invention will be described with reference to the accompanying drawings.

[0051] Figure 1 shows an exploded view of the components of a syringe according to the first embodiment of the present invention.

[0052] Figure 2 shows a longitudinal cross-section of the exploded view shown in Figure 1.

[0053] Figure 3 shows a side view of a syringe according to the first embodiment of the present invention, in which a screw plug is provided instead of a needle hub (a separate plug may also be provided).

[0054] Figure 4 shows a longitudinal cross-section of the device illustrated in Figure 3.

[0055] Figure 5 shows a side view of a syringe according to a first embodiment of the present invention, which is provided with a needle hub, the needle hub also comprising a needle sheath with a flattened measuring rim and a protective cap that substantially covers the sheath and the needle.

[0056] Figure 6 shows a longitudinal cross-section of the device as illustrated in Figure 5.

[0057] Figure 7 shows a detailed longitudinal cross-section of the operating mechanism according to the first embodiment of the present invention, as well as its interaction with the rest of the syringe.

[0058] Figure 8 shows a detail of a longitudinal cross-section of the distal end of a syringe according to one embodiment of the present invention, which includes a detachable needle hub (with sheath and cover cap) and its interaction with the rest of the syringe.

[0059] Figures 9-11 show details and operation of longitudinal cross-sections during the injection process of a syringe according to a first embodiment of the present invention (Figure 9: Pressure is applied to the proximal end of the syringe to the injection subject; Figure 10: The injection depth is reached and the plunger is released; and Figure 11: Pressure is released from the proximal end and the sheath is returned to a position surrounding the needle and locked). Figure 9 shows a longitudinal cross-section rotated 90° longitudinally compared to Figures 10 and 11.

[0060] Figure 12 shows a detailed view of the longitudinal cross-section of the proximal end of the instrument shown in Figure 11, magnified at a slightly different angle for further detail.

[0061] Figure 13 shows external details of the operating mechanism housing according to the first embodiment of the present invention.

[0062] Figure 14 shows a magnified view of the longitudinal cross-section of the proximal end of the device according to the first embodiment of the present invention when it is ready for injection, detailing the interaction between the main body and the cap of the operating mechanism housing, as well as details of the retaining arm, restraint, and plunger when it is ready for injection.

[0063] Figure 15 shows details of the distal end of a preferred embodiment of intravitreous injection according to the present invention.

[0064] Figures 16 and 17 show details of the interaction between the retaining arm, restraint, plunger, and drive spring when the injection preparation is complete (Figure 16) and after the injection is complete (and after the plunger is released).

[0065] Figures 18-20 show the holding arm according to the present invention in magnified view from different angles.

[0066] Figure 21 shows an exploded view of the related components of a syringe according to a second embodiment of the present invention, and these components include parts that differ from those of the first embodiment shown in Figure 1.

[0067] Figure 22 shows a longitudinal cross-section of the exploded view shown in Figure 21.

[0068] Figures 23-25 ​​show longitudinal cross-sectional views of a syringe according to a second embodiment of the present invention: Figure 23 shows a figure in which a screw plug is provided instead of a needle hub (which may be provided separately). Figure 24 shows a figure in which a needle hub is attached, the needle hub also comprising a needle sheath with a flattened measuring rim and a pressure pad, and a protective cap that substantially covers the sheath and needle. Figure 25 shows the device of Figure 24 with the protective cap removed.

[0069] Figures 26-31 show details of the longitudinal cross-section and operation of the syringe during the injection process according to a third embodiment of the present invention. Figures 27 and 28: Pressure is applied to the proximal end of the syringe to the injection subject with the sleeve in contact with the restraint; Figure 28: Details of the physical interaction shown from a slightly different angle; Figure 29: The injection depth is reached and the plunger is released; Figures 30 and 31: Pressure is released from the proximal end and the sheath is returned to a position surrounding the needle and locked; Figure 31: Details of the physical interaction shown from a slightly different angle.

[0070] Figure 32 shows an operating mechanism housing according to a third embodiment of the present invention.

[0071] Figure 33 shows the dosage adjustment cap proximal to the operating mechanism housing according to a third embodiment of the present invention.

[0072] Figure 34 shows the proximal end of a plunger according to a third embodiment of the present invention.

[0073] Figure 35 shows an exploded view of the components of a syringe according to the fourth embodiment of the present invention.

[0074] Figure 36 shows a longitudinal cross-sectional view of the exploded view shown in Figure 35.

[0075] Figure 37 shows a longitudinal cross-sectional side view of a syringe according to a fourth embodiment of the present invention, in which a screw plug is provided instead of a needle hub. The components of the needle hub are shown below in a longitudinal cross-section.

[0076] Figure 38 shows a longitudinal cross-sectional side view of a syringe according to a fourth embodiment of the present invention with a needle hub attached. This needle hub also includes a needle sheath having an eye contact surface for measuring the flattened portion and a protective cap that substantially covers the sheath and needle. The shown cross-section is rotated 45° along its longitudinal axis compared to Figure 37 and shows a side view of the sleeve leaf. Figure 37, on the other hand, shows a longitudinal "rib" that extends inward beyond this sleeve leaf and engages with the drug chamber to hold it in place.

[0077] Figure 39 shows another longitudinal cross-sectional side view of the syringe illustrated in Figure 38, but rotated 90° along its longitudinal axis compared to Figure 38.

[0078] Figure 40 shows a side view of the syringe illustrated in Figures 37-39, but without a protective sheath cap or proximal cap.

[0079] Figures 41-43 show details of the longitudinal cross-section and operation of the syringe during the injection process according to the fourth embodiment of the present invention (Figure 41: Pressure is applied to the proximal end of the syringe to the injection subject, reaching the injection depth, and the drug is about to be released. Figure 42: The drug has been delivered. Figure 43: Pressure is released from the proximal end, and the sheath returns to a position surrounding the needle and is locked).

[0080] Figures 44-46 illustrate the details of the interaction between the retaining arm, sleeve / restraint, and plunger during the injection process (Figure 44: The operating mechanism is ready for injection, and the retaining arm and sleeve / restraint are in a position to restrain the drive component; Figure 45: The operating mechanism is triggered, and the retaining arm and sleeve / restraint are in a position to release the drive component; Figure 46: Pressure is released from the proximal end, the sleeve returns to its distal position, the retaining arm flexes fully outward, and the sleeve and sheath are locked in a position to surround the distal needle).

[0081] Figure 47 is a transparent view showing the operating housing and how it interacts with the retaining arm, drive spring, and plunger.

[0082] Figure 48 is a transparent view showing the operating housing and how it interacts with the retaining arm, the first spring, and the plunger. The plunger is equipped with a sleeve spring in a position to hold the sleeve / restrainer and the plunger.

[0083] Figure 49 is a transparent view showing the operating housing, how it interacts with the retaining arm, drive spring, plunger, sleeve / restraint, and sleeve spring in the position that holds the plunger, as well as the proximal cap located on top of the operating housing.

[0084] Figure 50 shows details of a preferred sleeve / restraint according to the present invention.

[0085] Figure 51 shows two detailed figures of an embodiment of the retaining arm according to the present invention.

[0086] Figures 52-56 show the details of the interaction between the retaining arm, plunger, proximal cap, and working housing during preparation, "zero" calibration, dosage setting, and "drug delivered" processes (Figure 52: Syringe is assembled but the needle is not in place and stress is applied to the drug chamber; Figure 53: The seal of the drug chamber is punctured by the needle, releasing some stress on the drug chamber and allowing the proximal cap to rest on the complementary surface of the working housing; Figure 54: The proximal cap rotates to release the remaining stress in the drug chamber, engaging the retaining projection of the retaining arm with the protruding part of the complementary plunger, thereby "zeroing" the administration system. The proximal cap is still resting on the complementary surface of the working housing; Figure 55: The proximal cap rotates further, lifting proximal to the complementary surface of the working housing, thereby enabling dosage setting determined by the distance the proximal cap lifts from the complementary surface of the working housing; Figure 56: The drug is delivered and the proximal cap rotates to rest on the complementary surface of the working housing).

[0087] Figures 57 and 58 show details of a preferred operating housing according to the present invention, with Figure 57 being a side view and Figure 58 being an internal view of the operating housing seen from the distal end.

[0088] Figure 59 shows a detailed view of the inside of the preferred proximal cap according to the present invention, seen from the distal end.

[0089] Figure 60 shows details of the interaction between the working housing, proximal cap, and plunger.

[0090] Figure 61 shows an exploded view of the components of a syringe according to the fifth embodiment of the present invention.

[0091] Figure 62 shows a longitudinal cross-section of the exploded view shown in Figure 61.

[0092] Figures 63-69 show details of a longitudinal cross-section of a syringe according to a fifth embodiment of the present invention, as well as its operation during preparation (Figures 63-65), dosage setting (Figure 66), and injection (Figure 67: pressure is applied to the distal end of the syringe to the injection subject, reaching the injection depth and delivering the medication; Figure 68: the medication has been delivered; and Figure 69: pressure is released from the proximal end, and the sheath is returned to a position surrounding the needle and locked).

[0093] Figure 70 shows a longitudinal cross-sectional side view of four main components of a syringe according to a fifth embodiment of the present invention. These include the operating mechanism 20d and its components, the drug cartridge 240 and its components, the elongated housing 10d and its components, and the needle hub 150d and its components.

[0094] Figure 71 is an exploded view of the operating mechanism 20d and its components, as shown in Figure 70.

[0095] Figures 72-76 show details of the restraint 130d, retaining toggle 120d, and plunger 80d according to a fifth embodiment of the present invention, and their interaction / connection.

[0096] Figures 77-79 show details of the interaction between the retaining toggle 120d, sleeve leaf 76d, restraint 130d, and plunger 80d during the injection process (Figure 77: The actuation mechanism is ready for injection, and the retaining toggle, sleeve, and restraint are in a position to hold the plunger; Figure 78: The actuation mechanism is about to be triggered, and the sleeve and restraint are in a position to release the drive component; Figure 79: The actuation mechanism is triggered, the toggle rotates around axis 121d, and the sleeve and restraint are in a position to release the drive component).

[0097] Figures 80-82 show details of the exterior and interior of the operating housing 110d according to the fifth embodiment of the present invention.

[0098] Figures 83 and 84 show external and internal details of the proximal cap 290d according to the fifth embodiment of the present invention.

[0099] Figure 85 shows an exploded view of the elongated housing 10d (as shown in Figure 70) and its components.

[0100] Figures 86 and 87 show details of the exterior and interior of the elongated housing 10d according to the fifth embodiment of the present invention.

[0101] Figures 88 and 89 show details of the exterior and interior of the sleeve 70d according to the fifth embodiment of the present invention.

[0102] Figures 90 and 91 show external and internal details of the cartridge centering / spring retaining plug 440 according to a fifth embodiment of the present invention.

[0103] Figure 92 shows a longitudinal cross-sectional side view of an elongated housing 10d according to a fifth embodiment of the present invention (as shown in Figure 70). Its components and the relative positions between components are shown.

[0104] Figures 93 to 95 show details of a needle hub according to another specific embodiment of the present invention.

[0105] Figures 96 and 97 illustrate in detail another specific embodiment of the dosage setting mechanism according to the present invention. Figure 96A: External details; Figure 96B: Longitudinal cross-sectional side view showing internal details; Figure 97: Partially cut section view showing further details.

[0106] Figure 98 shows details of an alternative dosage setting mechanism according to one embodiment of the present invention.

[0107] Figures 99 and 100 show details of a self-setting holding arm mechanism according to one embodiment of the present invention.

[0108] Figures 101 and 102 show the cam retaining arm (which does not require a biasing spring for operation) and details of its operation.

[0109] Figures 103-107 show details of alternative plunger drive mechanisms for use in various embodiments of the present invention.

[0110] Figure 108 shows details of the use of a multi-purpose syringe with an interchangeable elongated housing (including needle assembly and drug chamber) according to one embodiment of the present invention. Definition

[0111] As used herein, the term “axial” means toward or oriented toward an axis. The term “out-of-axis” means away from or oriented away from an axis.

[0112] As used herein, the term “distal” means the end or direction of the injection. The term “proximal” means the rear of the syringe, or the end or direction toward the rear of the injection component and / or the syringe and / or injection component.

[0113] As used herein, the term “engage” means that two or more elements interact with each other, with one element acting on one or more other elements that “engage,” and the “engage” elements may be connected to each other or simply in contact. Corresponding terms such as “engage,” “engaged,” and “engage” have corresponding meanings. Detailed explanation

[0114] The present invention will be described with reference to various specific embodiments illustrating the invention, but the invention is not limited to these embodiments. This is because the specific embodiments described herein can be modified in various ways without departing from the inventive concept shown therein. In particular, it will be understood that the various embodiments are intended to be illustrative and not limiting. In particular, it will be understood that this disclosure includes, for example, kinematic inversion, alternative biasing means, and substitution of equivalent mechanical structures such as changes in shape or material. It will also be understood that in instruments intended for injectable substances of different volumes or different viscosities or viscosities, corresponding adaptations to the structure and dimensions of the instrument may be necessary.

[0115] Referring to Figures 1-6, a first embodiment of the syringe according to the present invention includes a substantially hollow elongated housing 10 having a proximal and distal end, with an actuation mechanism 20 engaged at its proximal end. The actuation mechanism 20 comprises an actuation housing defined by a proximal cap 100 and a distal body 110. The elongated housing 10 includes longitudinal ribs 12 extending inward. These longitudinal ribs 12 define a lumen 30 adapted to house and secure a drug chamber 40 that contains or is adapted to contain an active drug for injection into a subject. The drug chamber also includes corresponding proximal and distal ends. At least the proximal portion of the chamber 40 is provided with a stop 50 for holding the active drug. The distal end contains or is adapted to fluidly communicate with a needle 60. The elongated housing also includes a sleeve 70 with leaves 74 positioned between the ribs, thereby allowing the sleeve 70 to slide at least proximal relative to the elongated housing 10.

[0116] In certain embodiments, the proximal cap 100 may engage with the body portion 110 via complementary threads 105 and 118 located on the proximal cap 100 and the body portion 110, respectively. This allows for adjustment of the drive component or plunger 80 (and stopper 50) relative to the drug barrel 42, and thus allows for adjustment of the preparation of the needle 60 and the dosage delivered.

[0117] The elongated housing 10, the actuation housing components 100 and 110, and the sleeve 70 may include any suitable material used in the art, including suitable polymer materials, metals, and / or metal alloys. In certain embodiments, the elongated housing 10, the actuation housing components 100 and 110, and the sleeve 70 may be constructed from polymer materials known to those skilled in the art, including but not limited to polycarbonate ("PC"), acrylonitrile, butadiene, and styrene ("ABS") blends, polyethylene, polystyrene, or polyvinyl chloride. The aforementioned components may be manufactured from such materials by suitable means known to those skilled in the art, such as molding.

[0118] Each of the elongated housing 10, sleeve 70, proximal cap 100, and body portion 110 is preferably having at least a hollow cylindrical internal profile (optionally having two or more stepped internal diameters and additional characteristic parts described later), and the elongated housing 10 and sleeve 70 are particularly preferred considering the cylindrical profiles of commercially available drug chambers. However, the external profile is not necessarily limited to this and may include shapes that make the syringe more ergonomic or easier to manufacture or package, and the internal profile may be a shape other than cylindrical, but may involve ease of manufacture, assembly, and / or functional complexity.

[0119] In the specific embodiments illustrated in Figures 1-14, the sleeve 70 comprises a hollow cylindrical proximal body 72 housed within an operating housing defined by a proximal cap 100 and a distal body portion 110. The sleeve leaf 74 extends distally from the body 72 into the lumen 30 of the elongated housing 10 through corresponding slots in the base plate 112 of the body portion 110 of the housing. One or more sleeve leaves 74 may be omitted, or a window 76 may be provided. This omission or window may coincide with a window 18 in the elongated housing 10. This allows for visualization of the contents of the drug chamber 40 (if installed). In another embodiment, the body or other parts of the elongated housing are made of a transparent or translucent material, thus allowing for easy visualization of the contents of the drug chamber or other internal components.

[0120] The elongated housing 10 and the operating mechanism 20 may be engaged with each other by any suitable means, such as means known in the art, that maintain a constant relative position to each other during use. For example, the mutually compatible surfaces may be welded together, crimped together, snapped together, screwed together, or bonded together.

[0121] According to one embodiment, the actuation mechanism 20 may include a drive component or a plunger 80. Its distal end engages with or is adapted to engage with a stop 50 of the drug chamber. In addition to interlock, overlap, screw in, or screw up, “engagement” and related terms may also include simply pushing, and as a result, the plunger 80 may be adapted to simply abut and push against the stop 50. The plunger 80 engages with the cap 110 of the actuation mechanism housing at its proximal end, in which case at least one drive spring 90 is positioned between the cap 100 and the plunger 80. The plunger 80 may include any suitable means for holding the drive spring 90 between the plunger 80 and the cap 100. For example, a spring retaining cup or a ridge 82 shown in Figures 1, 2, 4, and 6 (as well as Figures 7, 9-12, 16, and 17) is formed near the proximal end of the plunger 80.

[0122] Referring to Figures 4, 6, 7, 9-12, 14, 16, and 17, the syringe according to the present invention is assembled, that is, the drug chamber 40 is positioned in place, the plunger 80 is engaged with the stopper 50, and when the instrument is ready for injection, the drive spring 90 is subjected to stress, and the plunger 80 is held in place by the retaining arm 120. In order to optimally control the release force of the retaining arm (i.e., the force that needs to be applied to a surface such as the eye in order to operate the syringe), the retaining arm 120 is provided with an outward bias (i.e., in the direction away from the plunger 80), at which time, The retaining arm is held in the plunger engagement position against this bias by a restraint 130 that is at least proximal to the plunger engagement, and the restraint 130 is in a restrained position when distal (Figures 4, 6, 7, 9, 14, and 16) and in a released position when proximal (Figures 10, 11, 12, and 17). When in use, distal pressure is applied to the surface on which the syringe is injected, causing the sleeve 70 to slide proximal relative to the elongated housing 10. The restraint 130 is driven proximal by the sleeve 70, thereby releasing the retaining arm 120 and bending away from the plunger 80, allowing the drive spring 90 to drive the plunger 80 and the stopper 50 distally.

[0123] Referring to Figures 12, 14, 16-20, 41-47, and 51, preferred forms of the retaining arms 120, 120c and the restraints 130, 130c are illustrated. However, to those skilled in the art who benefit from this disclosure, other suitable means / configurations will be readily apparent, and the present invention should not be construed as being limited to the specific preferred forms of the illustrated retaining arms or toggles and restraints. Alternative retaining arms or toggles and complementary restraints may include, for example, different configurations. And / or, one or more retaining arms / toggles may be held against their bias by similar restraints such as the illustrated restraint 130, or by one or more different means other than the illustrated molded discs.

[0124] Referring to the retaining arms 120 shown in Figures 12, 14 and 16-20, each has an extended “arm” (like a shoulder) with a pivot / fulcrum 121 at its proximal end. This is adapted to engage with a pin or shaft 140 (shoulder joint) provided at the proximal end of the proximal cap 100. Alternatively, the pin or shaft 140 may be formed separately and form part of the retaining arm 120 to engage with the proximal cap 100 or a corresponding part of the operating mechanism housing via a corresponding joint or fulcrum. In one embodiment, a spring arm 123 with a corresponding recess 124 is axially positioned in the “underarm” portion of the retaining arm 120 (the spring arm 123 may be formed integrally with the retaining arm 120 or separately, and may be made of a rigid, viscoelastic, or resilient material, which may be the same material as or different from the rest of the retaining arm 120). In another embodiment, a spring or spring arm may be attached to the side of the plunger 80, integrated with the plunger 80, and press against the retaining arm 120, and in a particular embodiment, press against the surface of the retaining arm 120 corresponding to a recess 124. Moving distally along the “arm” of the retaining arm 120, there is a step or axially oriented “elbow,” which forms an inward projection 125. This projection 125 is substantially perpendicular to the axis of the plunger 80 when in the plunger engagement and retaining position and is adapted to engage with an opposite ridge or projection 86 formed on the plunger 80. It is also convenient that this projection 86 be the lower outer edge of the spring retaining cup 82. The retaining arm 120 extends distally beyond the inward projection 125 (thus forming a portion corresponding to the “forearm” in the analogue of the “arm”) and terminates with a “hand” including a concave flange 127 adapted to lean against the shaft of the plunger 80. The concave flange 127 has further flanges or tabs (retaining tabs) 128 extending outward on both sides, and one of the retaining tabs 128 (in this example, the tab on the right when viewed from the axial side) is provided with a flange / tab 129 ("sheath lock tab") that extends further distally.The retaining arm 120 may be made of any suitable material used in the art, including suitable polymer materials, metals and / or metal alloys, or any combination of such materials as described above. If the spring arm 123 is an integral part of the entire retaining arm 120, the retaining arm 120 may be made of a suitable rigid viscoelastic polymer material such as polycarbonate, polyoxymethylene, and nylon. The induced pressure when using such a retaining arm (i.e., the proximal force that the sleeve 70 must exert on the restraint 130, and consequently the distal force that must be exerted on the injection surface) is proportional to the ratio a:b of the distance "a" between the pivot point 121 and the proximal surface of the tab 128 and the axial extension distance "b" of the edge of the projection 125 compared to the pivot point 121. Therefore, given a predetermined biasing force provided by the spring arm 123, the longer "a" or the smaller "b" is, the less force is required to induce the device, thereby reducing discomfort for the subject being injected. Consequently, important in certain applications such as intraocular injection, the induced pressure can be adjusted by adjusting the ratio a:b in this particular embodiment, and by adjusting the ratio of equivalent mechanical advantages in other syringe embodiments described later.

[0125] Referring to the restraint 130 as shown in the figure, it is provided as a flat disc of any suitable thickness, which may be about 2 to 50 mm, typically about 5 to 20 mm, and can be made from any suitable material used in the art, including suitable polymer materials, metals and / or metal alloys. Referring to Figures 16 and 17, in one embodiment, the restraint 130 may have a suitable space cut into it. i) This holds a pair of opposing retaining tabs 128 facing the retaining channel 133, and when in the retaining position, holds a pair of retaining arms 120 against the plunger 80 and against the bias caused by the spring arm 123 being compressed into the recess 124. ii) This provides space for the retaining arms to flex away from the plunger 80 when the channel 136 is released and the restraint 130 slides proximal to release the retaining tabs 128. iii) A space is created in the cross-section of the opposing retaining channel 133, which releases the channel 136, allowing the restraint 130 to engage with the plunger 80 and move freely along the portion of the plunger 80 with which at least the lower part of the retaining arm 120 (below the projection 125) engages.

[0126] The embodiments illustrated in Figures 1-12 are adapted for use of a pre-filled, needleless drug chamber 40. This may optionally be filled under vacuum or filled without voids. Furthermore, a separately provided needle hub 150 may be attached via any suitable mechanism known in the art, such as a tight-fit, snap, Luer lock, bayonet, or screw mechanism. However, drug chambers with needles attached integrally or in other ways, whether pre-filled or not, are also available. In the embodiments illustrated in Figures 1-12, particularly with reference to Figures 1-4, the pre-filled drug chamber 40 may be provided separately, for example, or may form an integral part of a provided syringe. This comprises a cylindrical barrel 42 (which may be made of glass or a suitable polymer material, optionally silane-treated or silicone-treated) with a seal 44 and a barrel connector 46 (which, if made of a polymer material, may be formed integrally with the barrel 42, or may be formed separately and attached to the distal end of the barrel 42 by adhesive, snap fastening, crimping, or other suitable means), and a stop 50. The drug containing the active ingredient is contained within the barrel 43 between the seal 46 and the stop 50. A filled, needleless drug chamber, as illustrated in Figures 1-12, has a barrel flange projecting axially outward from the proximal end of the barrel 42. This is typically used to hold the syringe with the index and middle fingers and apply pressure to the proximal end of the plunger when administering an injection. However, in the embodiments shown in Figures 1 to 12, and particularly as shown in Figures 7 to 12, according to one embodiment, the drug chamber 40 is held within the syringe in a lumen formed by the elongated housing 10, and the barrel flange 49 at the proximal end of the barrel 42 fits into a recess 15 formed at the proximal end of the elongated housing 10, and together with the base plate 112 of the distal main body portion 110 of the operating housing, fixes the drug chamber 40 in a predetermined position within the syringe.The snug fit of the drug chamber 40 within the elongated housing 10 further enhances its retention within the syringe. Typically, a filled drug chamber 40 is fitted with a syringe cap 48 screwed onto the barrel connector 46, ensuring sterility and cleanliness within the barrel connector until the syringe cap 48 is removed before attaching the needle hub 150. In other embodiments, the plunger 80 may assist in holding the drug chamber 40 in place by applying pressure to the stopper 50.

[0127] Referring to the most recently described embodiment, Figures 1, 2, and 8, the needle hub 150 comprises needles 60 extending from both sides of an injection-molded body 160. The needles 60 have proximal connector ends 164 adapted for engaging and connecting with a barrel connector 46. The needles 60 also have a short end that extends sufficiently proximal to pierce the seal 44 when the hub 150 is fully connected to the barrel connector 46, and a substantially cylindrical body 168 adapted for sliding within a sheath 170 while remaining in close contact with it. The sheath 170 has a proximal end 175 adapted for clipping around the body 168, thereby holding the body 168 within the sheath 170, with the connector ends 164 protruding proximal to the sheath 170. In another embodiment, the needle hub 150 is manufactured from two parts, each part having injection-molded needles (a proximal needle for puncturing seals 44 or 246 and a distal needle for injection), which are coupled to each other (with the needles facing opposite directions) with a filter interposed between them. This allows for filtering and removal of any particles that may be generated when puncturing a filled cartridge or filled syringe, as well as any particulate matter present in the drug. The proximal end 175 is also adapted to engage with the sleeve 70 when the hub 150 is fully connected to the barrel connector 46. When not in use, the hub 150 may have a cap 180 ideally adapted to clip onto the sheath 170 (whether connected to the connector 46 or not). In certain embodiments, the cap 180 may have a guide 185 for securing and protecting the needle 60 within the needle hub. Alternatively, or additionally, the distal end or surface 173 of the sheath 170 may be provided with a guide for securing and protecting the needle 60 within the needle hub. Referring at least to Figures 1, 2 and 15, the distal surface 173 of the sheath 170 may function as a surface for contact with the subject or a part of their body for injection. In further embodiments, such contact surface of the sheath may be provided with a pad 177 made of a softer and / or spongy and / or adhesive material than the sheath 170, such as silicone, rubber, or an absorbent material.In further embodiments, the distal surface 173 of such a sheath 170 may be provided with characteristic features such as projections, protrusions, and / or other tactile elements. In even further embodiments, the contact surface of the distal surface of the sheath may include a combination of the aforementioned characteristic features or materials. Such materials and characteristic features may help to hold the distal surface in place during injection procedures (e.g., at the correct injection site on the ocular surface in the case of intraocular injection), and may also help the physician control or maintain the position of the eye in a desired position during injection. Although not shown, the needle hub 150 may include a biasing means such as a spring within the sheath 170. This biasing means pushes the sheath 170 distally relative to the body 168, and therefore the needle 60 also distally, maintaining the needle 60 in a retracted position within the sheath when not in use. The sheath 170 may be a cylindrical shape that is substantially hollow for its entire length or for most of its length, but other shapes are also possible. In certain embodiments, the sheath 170 may have a frustoconical distal end. If the sheath 170 and the corresponding cap 180 are substantially cylindrical, the sheath 170 or the cap 180 may be provided with means to prevent the cap 180 from rotating axially relative to the sheath 170, thereby allowing the needle hub 150 to engage with the barrel connector 46 by applying rotational pressure to the cap 180. Such means may include, for example, complementary longitudinal (i.e., extending distal to proximal) ridges and grooves, or the introduction of some asymmetry in the sheath 170 and the cap 180 sufficient to prevent axial rotation of the cap 180 relative to the sheath 170. Further alternatives include, for example, a pin or slip of rigid material passing through corresponding holes formed in the sheath 170 and the cap 180, or a rib extending from the hub body 168 through a corresponding slit in the sheath 170 and engaging with a corresponding slot in the cap 180. In certain embodiments, the cap 180 is adapted to firmly hold the remaining parts of the needle hub 150 together, thereby enabling handling and mounting of the hub to the barrel connector 46. Such adaptations include, for example, clippable flanges, interacting complementary fins and slots, or grooves and protrusions, biasing means, etc.In certain embodiments, the cap 180 may be closed and has a distal internal cavity of sufficient size to accommodate a preparation or dose adjustment amount of drug. This cavity may be provided with an absorbent pad to absorb that amount.

[0128] Instead of a needleless drug chamber 40 as illustrated in Figures 1-12, a drug chamber with a needle (integrated or disintegrated with the barrel) may be used. In such embodiments, a needle hub is not required. However, in certain embodiments, a sheath may be provided as an extension of the sleeve 70, which may include a cap that covers the end of the syringe when not in use.

[0129] Easily available drug chambers also include replaceable or disposable cartridges. These typically do not have a barrel connector; instead, a seal is provided at the distal end, which is held in place by a crimping ring or the like, and a stop is provided at the proximal end, and there is no barrel flange. Referring to Figures 21-25, a second embodiment of the syringe according to the present invention is shown. This involves the use of such replaceable or disposable cartridges with a modification of the configuration of the elongated housing 10. Figures 21-25 show details of these modifications. In particular, since the replaceable or disposable cartridges do not have a barrel connector, according to this embodiment, the needle hub connector 210 is provided as an internally threaded collar supported by radially indented extensions 220 of the elongated housing 10b. Between the radially indented extensions 220, there are slots corresponding to corresponding slots in the base plate 112 of the main body portion 110, in which the sleeve leaf 74 can move and use the same sleeve 70 as described above. The proximal end of the needle hub connector 210 is provided with a recessed sheet 230 for housing the distal end of a replaceable or disposable cartridge 240. The cartridge 240 comprises a barrel 243 made of glass (optionally silane-treated) or a suitable polymer material (optionally silicone-treated), a seal 246, typically made of synthetic rubber such as butyl rubber but not required, and a crimp ring 248, typically made of aluminum but not required, which holds the seal 246 in place relative to the distal edge of the barrel 243. Between the recessed sheet 230 and the hub connector 210 is a channel 250 that allows the proximal end of the needle 60 to pass from the connector hub 210 through the seal 246 into the lumen of the barrel 243. In one embodiment, in order to secure a replaceable or disposable cartridge 240 in a predetermined position within the elongated housing 10b, the main body portion of the operating housing may be modified to provide a main body portion 110b having a modified base plate 112b including a collar 119 that extends distally.The collar 119 surrounds the plunger 80 and extends into the lumen within the elongated housing 10b and sleeve 70. The collar extends by the correct distance into the lumen to ensure that the replaceable or disposable cartridge 240 is securely and substantially fixed within this lumen. Referring to Figures 23-25, the needle hub 150, syringe cap 48, and the rest of the operating mechanism 20 (except for the main body portion 110b) may be the same as or similar to those already described above. As shown in Figure 22, the elongated housing 10b may include an optional window 18b that matches the window 76 in the sleeve leaf 74, allowing for confirmation of the contents (if installed) of the replaceable or disposable cartridge 240.

[0130] Having described the main components of a specific syringe according to the present invention, the mechanism during its use will now be described.

[0131] First, referring to Figures 1-20, the device may be provided as a single-use sterile device pre-packaged in an injectable state, or it may be provided without a drug chamber. In either embodiment, the needle hub 150 (provided separately in sterile packaging) may be omitted. If the drug chamber 40 is provided separately and, ideally, filled, the operating mechanism 20 with the sleeve 70 is separated from the elongated housing 10, and the drug chamber 40 is inserted into the elongated housing 10 with the barrel flange 49 fitted into the recess 15. Next, the sleeve leaf 74 is positioned around the barrel 42 to integrate and fix the elongated housing 10 and the operating mechanism 20 in place, and at the same time engage the distal end of the plunger 80 with the stop 50. Next, the needle hub 150 is connected to the barrel connector 46 (if not already connected, or if the drug chamber integrated with the needle hub is not being used). At this time, the plug 48 is removed first. If the drug chamber is vacuum-filled, this assembly creates positive pressure within the drug chamber 40. When the proximal end of the needle 60 pierces the seal 44, the positive pressure within the drug chamber 40 causes the drug to be discharged from the barrel 42 into the needle 60, thus realizing a self-preparing system.

[0132] When the syringe is assembled, the restraint 130 is in a distal restraint position, and a pair of opposing retaining tabs 128 of the retaining arm 120 are held substantially together within the retaining channel 133 (against the out-of-axis bias caused by the compression of the spring arm 123 into the recess 124), substantially in contact with the plunger 80, and the inward projection 125 engages with the opposing ridge / projection 86 of the plunger 80, thereby holding the plunger in a "ready" position against the bias provided by the drive spring 90.

[0133] If the system is not self-prepared, according to one embodiment, the system may be prepared by adjusting the position of the proximal cap 100 relative to the body portion 110 by fully screwing the proximal cap 100 onto the body portion 110 and preparing the needle 60. In a particular embodiment, the dose delivered during injection may also be controlled by adjusting the position of the proximal cap 100 relative to the body portion 110 during injection, and thus by adjusting the travel distance of the plunger 80.

[0134] It will be understood that, either through the activation of the self-preparation mechanism or by adjusting the dosage by manipulating cap 100, a portion of the supplied dose in the drug chamber will be discharged from the syringe.

[0135] Once the system is prepared and the dosage is set as needed, the distal surface of the sheath 170 (or the pad 170, if provided) is brought into contact with the surface to be injected, and distal pressure is applied. This pressure causes the sheath 170 to slide proximal into the elongated housing 10 and contact the distal end of the sleeve leaf 74. Correspondingly, the sleeve 70 slides proximal into the operating housing defined by the proximal cap 100 and the distal body portion 110, and contacts the bias provided by at least one sleeve spring 190 between the operating housing and the spring engagement ridge or cup 78 on the outer edge of the sleeve body 72. As the sleeve 70 moves proximal into the operating housing, its proximal surface engages with the distal surface of the restraint 130, pushing the restraint 130 proximal. Once the restraint 130 has moved proximal by the required distance (as a result of the needle 60 reaching the desired injection depth), the retaining tab 128 is no longer held together and is no longer pressed against the plunger 80 in the channel 133. As a result, the bias provided by the spring arm 123 biases the “arm” of the retaining arm 120 away from the plunger 80 and into the space provided by the release channel 136 (the out-of-axis deflection of the distal end of the retaining arm 120 is limited by the inner wall of the sleeve 70). This disengages the projection 125 from the ridge / projection 86 and releases the plunger 80. The plunger 80 is driven distally by pressure from the first spring 90, as a result of the drug being discharged from the distal end of the needle 60.

[0136] In certain embodiments, the plunger 80 has a raised portion 84, and the base plate 112 of the main body portion 110 has a collar that extends proximally. This collar surrounds a portion of the length of the plunger 80 and provides an upper surface 115, and at the same time, the raised portion 84 and the surface 115 define the end movement of the plunger 80 during injection when the raised portion 84 reaches and stops on the surface 115. This allows the travel distance of the plunger 80, and therefore the stop portion 50, to be defined during injection, particularly by adjusting the proximal cap 100 relative to the main body portion 110, ensuring the delivery of a predetermined dose. In certain embodiments, the proximal cap 100 and / or the main body portion 110 may be provided with a calibrated dose scale 200 for a specific drug chamber.

[0137] When the injection is performed, the pressure applied distally is relieved or released. As a result, the sleeve spring 190 applies pressure to the protrusion or cup 78 of the sleeve 70 that is no longer facing it, pushing the sleeve 70 distally, and consequently the sheath 170 is pushed distally to cover the needle 60 again. Also, as a result of the sleeve 70 being pushed distally, its inner wall no longer restricts further distal out-of-axis movement of the retaining arm 120, and the retaining arm 120 then flexes further out-of-axis (and radially outward from the pivot point 121) toward the wall of the main body portion 110 of the operating mechanism housing, at which point the sheath lock tab 129 prevents proximal movement of the sleeve 70, and therefore prevents proximal movement of the sheath 170. This locks the sheath 170 in the position to cover the needle and secures the instrument (see Figures 11 and 12, and also 30 and 31). The proximal end of the sleeve may be adapted to enhance engagement with the sheath lock tab / surface of the retaining arm or toggle, and thus to more firmly lock the sleeve, and by extension the sheath, in the position covering the needle. Such adaptations may include, for example, a notch in the sleeve or a flexible finger on the proximal end of the sleeve for engaging with the sheath lock tab or the surface of the retaining arm or toggle, but several other such means will be readily apparent to those skilled in the art.

[0138] Referring particularly to Figures 12, 13, 16, and 17, a convenient application of the syringe according to the present invention is provided, which can detect when the injection mechanism has been induced. Specifically, the plunger 80 may include an extension 88 that extends proximally through a collar 107 at the proximal end of the working housing cap 100. When the syringe is activated, this extension 88 moves / retracts into the cap 100, providing a signal that the instrument has actually been activated. Alternatively, the extension 88 may include a ridge 89. The collar 107 may also include a thin flap, flap group, or ridge 109 of appropriate rigidity, viscoelasticity, or springiness (and may be formed integrally with the cap 100 or separately, and may be made of the same or different material as the cap 100). The flap extends axially within the diameter of the out-of-axial extension of the ridge 89, and when injection is performed, the plunger 80 is driven distally. The raised portion 89 is driven beyond the flap, flap group, or raised portion 109, resulting in the flap, flap group, or raised portion 109 bending and generating noise such as a "click" sound that indicates the injection mechanism has been activated.

[0139] A third embodiment of the syringe according to the present invention provides an alternative configuration for an actuation mechanism for controlling the dosage of drug released by the device during injection. Referring to Figures 26-34, this actuation mechanism housing is modified compared to the previously described embodiments so that it is defined by a body portion 110b comprising a proximal portion 260 and a distal portion 270. Here, the proximal portion 260 has a narrower diameter and inner diameter than the distal portion 270 and the housing retaining arm 120b. (This is identical to the retaining arm 120 described above and may be connected to the proximal end of the proximal portion 260 via a pin or shaft 140b as described above.) A restraint 130b is also slidably held within the proximal portion 260. The inner diameter of the proximal portion 160 is slightly larger than the outer diameter of the hollow cylindrical proximal body 72b of the sleeve 70b, so that the hollow cylindrical proximal body 72b can be slidably received by the proximal portion 260 during injection and drive the retaining component 130b in the proximal direction. The joint between the proximal portion 260 and the distal portion 270 forms an outer projection 273 and an inner projection 276, which, together with the spring-retaining ridge / cup 78b, hold the sleeve spring 190b in place within the distal portion 270. In addition to the modification of the operating mechanism housing, the plunger 80b is also modified compared to the plunger 80 described above. It has a threaded extension 280 that engages with a corresponding thread 293 in the cap 290, and this threaded extension 280 slides onto the proximal portion 260 of the main body portion 110b. The plunger 80b is substantially the same as the plunger 80 described above, except that it includes a spring-retaining cup 82b and a ridge / projection 86b. However, ridges such as the ridge 84 no longer serve a function. This is because the distance traveled by the plunger 80b, and consequently the amount of drug released during injection, is determined by the relationship between the plunger 88b, the cap 290, and the proximal portion 260 of the main body 110b. When the syringe according to this embodiment is assembled, the desired dosage can be adjusted by screwing the cap 290 proximal until the desired dosage scale 265 is visible through the window 296. This lifts the cap 290 proximal away from the projection 273.This distance is the distance between the lower surface of the cap 290 and the projection 273, and defines the travel distance of the plunger 80b, and therefore the amount of drug released during injection. When the operating mechanism is triggered as described above, the lower surface of the cap 290 is driven to the surface 275, providing a convenient indicator that the device has been successfully activated.

[0140] Referring to Figures 35-30, a fourth embodiment of the syringe according to the present invention is provided. This embodiment includes several modifications compared to the third embodiment described above, in particular, the use of a single retaining arm 120c and a restraining portion 130c which is an integral extension proximal to the sleeve 70c. This embodiment also includes the use of a replaceable or disposable cartridge.

[0141] The syringe comprises a substantially hollow elongated housing 10c having a proximal and distal end. An actuation mechanism 20c engages with the proximal end, which comprises an actuation housing 110c. The elongated housing 10c comprises a longitudinal rib 220c extending inward, which defines a lumen 30c adapted to house a drug cartridge 240 that contains or is adapted to house an active drug for injection into a subject. The drug chamber also comprises corresponding proximal and distal ends. At least the proximal portion of the cartridge 240 is provided with a stopper 50 for holding the active drug inside. Since the replaceable or disposable cartridge does not have a barrel connector, according to this embodiment, the needle hub connector 210c is provided as an internally threaded collar supported by the radially indented rib 220c of the elongated housing 10c. The radially indented extension 220c also provides a slot for a sleeve leaf 74c to slide inside. Compared to the previously described embodiment, the sleeve 70c comprises only two opposing sleeve leaves 74c, with a large opposing space between them. The elongated housing 10c may optionally be provided with a window 18c that coincides with one of the opposing spaces (or two windows corresponding to one of the opposing spaces between the sleeve leaves 74c), thereby allowing the contents of the cartridge 240 (if installed) to be seen. The proximal end of the needle hub connector 210c is provided with a radially recessed flange surface, and the force with which the plunger 80c pushes the stopper 50 allows the distal end of the cartridge 240 to be firmly fixed to this surface.

[0142] In the embodiments illustrated in Figures 35-60, the operating mechanism 20c may comprise an operating housing 110c, a proximal cap 290c, a proximal portion of a sleeve 70c (including a restraint 130c as an integral part of the sleeve 70c), and a plunger 80c. The distal end of the plunger 80c engages with or is adapted to engage with the stop portion 50 of the drug cartridge. The proximal end of the plunger 80c is threaded and extends proximal through a channel 263c beyond the operating housing 110c to engage with threads 293c in the proximal cap 290c. At least one drive spring 90 is positioned between the proximal end of the operating housing 110c and the plunger 80c. The plunger 80c may be provided with any suitable means for holding the drive spring 90 between the plunger 80c and the actuation housing 110c, such as a raised portion 82 / 86c formed near the proximal end of the plunger 80c as shown in Figures 41 and 44-47. The actuation mechanism 20c also includes at least a sleeve spring 190c and a longitudinal rib 330 extending inward from the actuation housing 110c and adapted to engage with the proximal end of the spring 190c. The distal end of this spring 190c is engaged with the proximal portion of the sleeve 70c. As a result, the spring 190c is pressurized between the rib 330 and the sleeve 70c, biasing the sleeve 70c toward its distal position.

[0143] The proximal cap 290c fits into the operating housing 110c but is not fixed. Therefore, the proximal cap 290c can be adjusted relative to the plunger 80c (and stop 50), and thus the dose delivered can be adjusted.

[0144] The elongated housing 10c and the operating housing 110c can be engaged with each other by any suitable means, such as means known in the art, that ensure that their relative positions are fixed during use. For example, the mutually compatible surfaces may be welded together, crimped together, snapped together, screwed together, or bonded together.

[0145] In the specific embodiments illustrated in Figures 35-60, and particularly in Figure 50, the sleeve 70c comprises a hollow cylindrical proximal body 72c and a restraint 130c formed as an integral part at its proximal end, and is housed within the operating housing 110c, in which two opposing sleeve leaves 74c extend distally from the body 72c through corresponding slots at the proximal end of the elongated body portion 10c, between the ribs 220c of the elongated housing 10c. The gap between the sleeve leaves 74c may coincide with a window 18c in the elongated housing 10c, thereby allowing the contents of the cartridge 240 (if installed) to be viewed. As described above, part or all of the sleeve 70c may optionally be constructed of a transparent material so that the contents of the cartridge 240 can be viewed through the window 18c. The sleeve 70c may optionally also include a surface 370 that engages with the retaining arm 120c to lock the sleeve 70c in the needle storage position, and / or an arm that extends proximally to interact with the proximal cap 290c to lock the syringe mechanism until the injection dose is set, as described later.

[0146] Referring to Figures 37-43, when the syringe according to the present invention is assembled, the cartridge 240 is placed in a predetermined position, the plunger 80c is engaged with the stopper 50, the dosage is set, and the device is ready for injection, the drive spring 90 is subjected to stress, and the plunger 80c is held in a predetermined position by the retaining arm 120c, which is an integral part of the sleeve 70c and is held in the plunger engagement position by a restraint 130c that is at least slidable in the proximal direction, the restraint 130c being in a restrained position when distal (Figures 39 and 44) ​​and in a released position when proximal (Figures 42 and 45). When in use, pressing the syringe against the injection surface and applying distal pressure causes the sleeve 70 to slide proximal relative to the elongated housing 10c, which in turn causes the restraint 130c to move proximal (as part of the sleeve 70), thereby releasing the retaining arm 120c and bending away from the plunger 80c, allowing the drive spring 90 to drive the plunger 80c and the stopper 50 distally.

[0147] Referring to Figures 35–60, particularly Figures 39, 41–47, 50, 51, and 57, retaining arms 120c and restraints 130c as used in the fourth embodiment are illustrated. In particular, the retaining arms or toggles 120c illustrated in Figures 39, 41–47, and 51 include a single extended “arm” having a pivot / fulcrum 121c at its proximal end (such as a shoulder portion) adapted to engage with a pin or shaft 140c (shoulder joint) provided at the proximal end of the operating housing 110c. Alternatively, the pin or shaft 140c may be formed separately or form part of the retaining arm 120c and engage with the corresponding portion of the operating housing 110c or the operating mechanism housing via a corresponding joint or fulcrum 390. As the “arm” of the retaining arm or toggle 120c moves distally, there is an axially oriented “elbow” step, forming an inward projection 125c. The projection 125c is substantially perpendicular to the axis of the plunger 80c when the plunger is engaged and retained, and is adapted to engage with the opposite ridge or projection 82 / 86c formed on the plunger 80c. The retaining arm 120c extends distally beyond the inward projection 125 (corresponding to the "forearm" in an analogue of an "arm") and terminates with a two-fingered "hand." This "hand" comprises a recess 127c and flanges 128c extending outward and distally on both sides thereof, with sleeve body engagement surfaces 129c provided at the distal end of each flange. A spring 360 (which may be made of a hard, viscoelastic, or resilient material, including steel) may be attached to the side of the plunger 80c, or may be integrated with the plunger 80c to push outward the recess at the distal end of the retaining arm 120c. The induced pressure using such a retaining arm (i.e., the amount of proximal force that needs to be applied to the restraint 130c by the sleeve 70c, and therefore the amount of distal force that needs to be applied to the injection surface) is proportional to the ratio a:b between the distance "a" between the pivot point 121c and the proximal surface of the tab 128c and the axial extension distance "b" of the end of the projection 125c compared to the pivot point 121.Therefore, given the predetermined biasing force provided by spring 360, the longer "a" or the smaller "b" is, the less force is required to trigger the device, resulting in less discomfort for the subject being injected.

[0148] Referring to the restraint 130c as shown in the illustration, it is provided as an integral part of the sleeve 70c in the form of two flanges extending inward from the proximal end of the sleeve body 72c. The two flanges are separated by a gap through which the “arm” body of the retaining arm 120c can pass, but the flange 128c cannot. However, other configurations will also be readily apparent to those skilled in the art.

[0149] Referring to Figures 37-43, the needle hub 150c, usable in any of the second, third, or fourth embodiments, may comprise a proximal body 168c1 attached by injection molding, bonding, or other means to a needle 62 extending proximal, and a distal body 168c2 attached by injection molding, bonding, or other means to a needle 64 extending distal. The needle 62 is used for puncturing the drug chamber seal 246, and the needle 64 is used for insertion into the subject to be injected. The proximal body 168c1 includes a connector end 164 (as described above) formed proximal to be adapted for engaging and connecting with the barrel connector 210c. The bodies 168c1 and 168c2 are adapted for connecting to each other (and may also be joined, for example, by bonding, welding, or other means). A filter 300 for filtering out particles that may be generated when puncturing a filled cartridge or filled syringe, or particulate matter present in the drug, is sealed between the two bodies. The entire body 168c is adapted to fit snugly yet slidably into the sheath 170c. The proximal end of the sheath 170c is adapted to engage with the sleeve 70c when the hub 150c is fully connected to the barrel connector 210c. When not in use, the hub 150c (whether connected to the connector 210c or not) may have a cap 180c adapted for clipping onto the sheath 170c. The distal end of the sheath 170c may have a guide 185c for securing and protecting the needle 64 within the needle hub during injection. The distal end of the sheath 170c may have a pad 177c made of a material softer than the sheath 170c and / or spongy and / or adhesive, such as silicone or rubber. Alternatively, (if some degree of precise positioning is required, such as in intravitreal injection) the distal end of the sheath 170c may have a rough or spiked surface to help hold the syringe in place during injection procedures. In further embodiments, the distal surface of the sheath 170c may be provided with characteristic components such as protrusions, bumps, and / or other tactile elements. In even further embodiments, the contact surface of the distal surface of the sheath may include a combination of the aforementioned characteristic components or materials.Such materials and characteristic components can help hold the distal surface in place during injection procedures (for example, at the correct injection site on the ocular surface in the case of intraocular injection) and can help the clinician control or hold the eye in a desired position during injection. Although not shown, the needle hub 150c may be equipped with a biasing mechanism, such as a spring, within the sheath 170c. This biasing mechanism biases the sheath 170c distally to the body 168c and, consequently, the needle 64, and holds the needle 64 within the sheath when not in use. The sheath 170c may be a cylindrical shape that is substantially hollow along its entire length or for most of its length. However, other shapes are also possible. In certain embodiments, the sheath 170c may have a substantially frustoconical distal end. If the sheath 170c and the corresponding cap 180c are substantially cylindrical, the sheath 170c or the cap 180c may include means to prevent the cap 180c from rotating axially relative to the sheath 170c and to engage the needle hub 150c with the barrel connector 210c by applying rotational pressure to the cap 180c. Such means may include, for example, complementary longitudinal (i.e., extending distal to proximal) ridges and grooves, or some asymmetrical introductions in the sheath 170c and cap 180c sufficient to prevent axial rotation of the cap 180c relative to the hub 150c, as described above herein. As shown in Figures 37-43, and in particular in Figure 40, such means may include fins 340 extending from the hub body 168c through a corresponding slit 350 in the sheath 170c and engaging with a corresponding slot in the cap 180c. In certain embodiments, the cap 180c is adapted to firmly hold the remaining components of the needle hub 150c together, thereby facilitating the attachment and handling of the hub to the barrel connector 210c. Such adaptations include, for example, clippable flanges, interacting complementary fins and slots (the illustrated fin 340 extends from the hub body 168c through a corresponding slit 350 in the sheath 170c and engages with a corresponding slot in the cap 180c), or grooves and protrusions, and biasing means, etc.In certain embodiments, the cap 180c may be closed and has a distal internal cavity of sufficient size to accommodate a preparation or dose adjustment amount of drug. This cavity may be provided with an absorbent pad to absorb that amount.

[0150] In certain embodiments, for example, a valve such as a duck valve and a filter 300 can be provided between the proximal body 168c1 and the distal body 168c2 of the needle hub. Such a valve may be advantageous in preventing undesirable leakage of the drug from the cartridge 240, for example, when there is residual pressure on the fluid or when other forces exist that could cause the fluid to leak from the needle at an undesirable moment during use of the device.

[0151] In certain embodiments, the needle 64 may be made as short as possible (while ensuring an appropriate injection depth) in order to reduce the resistance to drug flow.

[0152] (Referring to Figures 37-60) The syringe according to this fourth embodiment may be provided as a single-use sterile instrument pre-packaged in a ready-to-inject state during use, or without a drug chamber, and in any embodiment, optionally without a needle hub 150c (provided separately in sterile packaging). If the drug chamber 40 is provided separately (ideally pre-filled), the actuation mechanism 20c with sleeve 70c is separated from the elongated housing 10c, and the drug chamber 40 is inserted into the elongated housing 10c with the crimping ring 248 and seal 246 in contact with the radially indented flange surface provided by the proximal end of the needle hub connector 210c. The sleeve leaf 74c is then repositioned within the elongated housing 10c, and the actuation mechanism 20c and the elongated housing 10c are joined and fixed in place, while the distal end of the plunger 80c is engaged with the stop 50. If the drug chamber is filled under vacuum or without voids, this assembly creates positive pressure within the drug chamber 40. As a result, the proximal cap 290c is positioned higher than the operating housing 110c, and in a preferred embodiment, a gap "A" is created between the distal surface of the proximal cap 290c and the corresponding mounting surface of the operating housing 110c (Figures 52 and 37), and a gap "B" is created between the retaining arm surface 125c and the plunger protrusions 82 / 86c, with gap "A" being smaller than gap "B". Next, the needle hub 150c is connected to the needle hub connector 210c, the plug 48 is removed first, and the proximal end of the needle 62 pierces the seal 246, and the positive pressure in the drug chamber 40 causes the proximal cap 290c, connected to the plunger 80c, to move distally, causing the proximal cap 290c to contact the corresponding surface of the operating housing 110c (i.e., gap "A" is reduced to zero, gap "A" in Figure 53). This discharges the drug from the barrel 42 to the needles 62 and 64, and the system is self-prepared. Simultaneously, the gap "B" between the retaining arm surface 125c and the plunger protrusions 82 / 86c is also reduced to a smaller gap "B". Referring to Figure 54, the instrument is calibrated by slightly rotating the proximal cap B290c to reduce the gap "B" to 0.Referring to Figure 55, further rotation of the proximal cap 290c causes it to move proximal away from the complementary mounting surface on the operating housing 110c, forming a gap "A" and setting the dose travel distance. It is now ready to be induced and delivered at the set dose. A scale corresponding to the proximal extension of the proximal cap 290c relative to the operating housing 110c, and thus to the size of the gap "A" and the corresponding dose, may be provided on the outer surface of the operating housing 110c. Alternatively, as already described in the third embodiment, one or more windows for checking such scales and setting the dose may be optionally provided on the outer surface of the proximal cap 290c. The arbitrary dose scale may extend around the entire circumference of the outer surface of the operating housing 110c, and the accompanying standard dose scale assists in setting the dose while rotating the proximal cap 290c relative to the operating housing 110c.

[0153] This mechanism, applicable not only to the fourth embodiment but also to the third embodiment (i.e., an embodiment of the present invention utilizing an operating housing with a proximal cap, where the interaction between the proximal cap and the plunger determines the dosage), makes it possible to eliminate variations in tolerance in a particular instrument, and the accuracy of the travel distance for dosage release is greatly improved because variations in dimensional tolerance at the dosage setting point are minimized, resulting in a significant advantage in the dosage accuracy of the instrument. Furthermore, a spring may be provided between the proximal cap 290c and the plunger 80c, thereby absorbing the play between the proximal cap 290c and the plunger 80c and eliminating the resulting impact on dosage variations.

[0154] Once the syringe is prepared and the dosage is set, the restraint 130c is in the distal restraint position, the retaining arm 120c is held on the plunger 80c, and the inward projection 125c engages with the opposite protrusion / projection 82 / 86c of the plunger 80c, thereby holding the plunger in the "ready" position against the bias provided by the first spring 90.

[0155] Next, the eye contact surface 177c is brought into contact with the injection surface, and pressure is applied distally. This pressure causes the sheath 170c to slide proximal, enter the elongated housing 10c, and come into contact with the distal end of the sleeve leaf 74c. The sleeve 70c also slides proximal, enters the operating housing 110c, and moves against the biasing force of the second spring 190, which is pressurized between the operating housing rib 330 and the raised portion 78c that engages with the spring on the outer edge of the sleeve body 72c. As the sleeve 70c moves proximal into the operating housing, the restraint 130c also moves proximal. As the restraint 130c moves proximal to the required distance (resulting in the needle 64 reaching the desired injection depth), the retaining tab 128c is no longer held by the plunger 80c, and as a result, the bias provided by the spring 360 moves the “arm” of the retaining arm 120c away from the plunger 80c (the out-of-axis bias of the distal end of the retaining arm 120c is limited by the inner wall of the sleeve body 72). This disengages the projection 125c from the ridge / projection 82 / 86c, releasing the plunger 80c, which had been under pressure from the drive spring 90, and driving it distally. As a result, the drug is discharged from the distal end of the needle 64, and the proximal cap 290c once again contacts the corresponding surface of the operating housing 110c (i.e., the gap “A” in Figure 56 is reduced to zero).

[0156] When the injection is performed, the pressure applied distally is relieved or removed, and as a result the sleeve spring 190 applies pressure to the protrusion 78c of the sleeve 70c that is no longer facing it, pushing the sleeve 70c distally, and as a result the sheath 170c is pushed distally to cover the needle 64 again. Also, as a result of the sleeve 70c being pushed distally, its inner wall no longer restricts further out-of-axis movement of the retaining arm 120c, and the retaining arm 120c bends further out-of-axis toward the wall of the operating housing 110c (and radially outward toward the pivot point 390), and holds in place, at which point the distal end of the tab 129c engages with the sleeve body 72c, and in a preferred embodiment, engages with a corresponding recess / notch 370 formed on the outer edge of the distal end of the sleeve body 72c. This prevents proximal movement of the sleeve 70c and sheath 170c, locking the sheath 170c in the position covering the needle and securing the instrument (Figures 43 and 46). Instead of the recess / notch 370, the proximal surface of the sleeve body 72c may be provided with alternative means for engaging with the distal edge of the retaining tab 129c. For example, the proximal surface of the sleeve body 72c that contacts the distal edge of the retaining tab 129c may be provided with flexible fingers that engage more firmly with the distal edge of the retaining tab 129c than a smooth or notched surface. Other means for ensuring a firm engagement between the sleeve body 72c and the distal edge of the retaining tab 129c to securely fix the sheath in the position covering the needle will be readily apparent to those skilled in the art.

[0157] In the fifth embodiment illustrated in Figures 61-92, the actuation mechanism 20d may comprise an actuation housing 110d having a proximal portion 260d and a distal portion 270d, the proximal portion 260d having a narrower diameter and inner diameter than the distal portion 270d. The distal portion 270d of the actuation housing 110d is adapted to house a drive spring 90, the proximal half of a plunger 80d, most of a retaining toggle 120d, and a restraint 130d. The plunger 80d has a threaded extension 280d at its proximal end, which extends proximal beyond the actuation housing 110d through a channel 263d and engages with the threads 293d in the proximal cap 290d. At least one drive spring 90 is positioned between the proximal end of the actuation housing 110d and the plunger 80d. The plunger 80d may include any suitable means for holding the drive spring 90 between the plunger 80d and the distal surface 111d of the spring retaining flange of the operating housing 110d (Figures 81 and 82), such as a protrusion 82d shown in Figures 72 and 73. In this particular embodiment, the protrusion 82d is formed on about one-third of the proximal end of the plunger 80d. In the illustrated embodiment, referring particularly to Figures 63-69 and 80-82, the operating housing 110d also includes a retaining projection having a proximal surface 112d adapted to engage with the retaining surface 122d of the toggle 120d, and a distal surface 113d adapted to engage with the lockout surface 128d of the toggle 120d. The operating housing 110d may also include a lateral space extension 118d to provide space for the proximal end of the toggle 120d to move after release (see Figures 67-69 if the proximal end of the toggle 120d needs to be this lengthened). In certain embodiments, an opening may be provided on the proximal side of the extension 118d and / or the operating housing 110d. This allows the user to view the proximal end of the toggle 120d through the opening and confirm that the syringe has been activated.In certain embodiments, an indicator may be provided that is configured to indicate one or more of the following: operation of the syringe, completion of injection, confirmation of dosage setting, and / or "lockout" of the instrument, including a tactile indicator, an auditory indicator, another visual indicator, one or more electronic signals optionally configured to interface with one or more other instruments or applications, or other such indicators known to those skilled in the art.

[0158] In certain embodiments, the proximal cap 290d fits into the operating housing 110d but is not fixed; instead, it is screwed onto a thread 280d (protruding from the operating housing 110d) of the plunger 80d via a complementary thread 293d. This allows the proximal cap 290d to be adjusted relative to the plunger 80d (and a stop 50, not shown), and thus the dose delivered can be adjusted. Optionally, the dose is monitored via a scale 116d on the housing 110d, which is observed through a window 297d. The dose can be set, for example, by a dose setting snap provided by the interaction of a dose setting snap 114d with a dose setting snap recess 295d, or by axially extending grooves (e.g., one snap per dose setting) arranged radially and spaced on the inside of the proximal cap 290d. The proximal cap 290d is optionally provided with a window 298d through which the user can view the (optionally colored) indicator strip 117d when the syringe is prepared or when the medication is delivered.

[0159] In the embodiments illustrated in Figures 61-97, and particularly in Figures 85-92, the elongated housing 10d comprises a hollow cylindrical body with an external thread 210d at its distal end for engaging with a needle hub 50d. In yet another embodiment, centering ribs 220d are provided extending proximal from the distal end of the housing 10d over at least a portion of the length of the housing 10d, and these ribs are adapted to hold and center a drug chamber, a filled syringe, or a cartridge 240 within the elongated housing. One or more ribs 220d, preferably two or three ribs, support a cartridge seat 230d provided in the form of a centrally “floating” perforated disc, as shown in Figures 86 and 87. The elongated housing 10d houses a sleeve 70d, at least one sleeve spring 190, and (when installed) a drug chamber 240, all three of which are held in place within the elongated housing by a cartridge centering / spring retaining plug 440.

[0160] In the embodiments illustrated in Figures 90 and 91, the cartridge centering / spring retaining plug 440 includes, as described later, a slit 442 into which the leaf 76d of the sleeve 70d can extend proximally, a spring retaining / compression ring 444, a drug chamber centering rib and arm 446, and, in a preferred embodiment, a centering / positioning mechanism 447 and a snap mechanism 448 for fixing the plug 440 in a predetermined position within the elongated housing 10d, thereby fixing the spring 190 and drug cartridge 240 in a predetermined position. In certain embodiments, the plug 440 may be a separate component as shown in Figures 90 and 91, or it may be integrally formed as part of either the operating housing 110d or the elongated housing 10d, for example.

[0161] The elongated housing 10d and the operating housing 110d may be engaged with each other by any suitable means, such as means known in the art, that keep their relative positions constant during use. For example, the mutually compatible surfaces may be welded together, crimped together, snapped together, screwed together, or bonded together.

[0162] In certain embodiments illustrated in Figures 61–92, and particularly in Figures 88 and 89, the sleeve 70d comprises a hollow cylindrical central body 72d having two opposing sleeve leaves 74d. These sleeve leaves 74d extend distally from the body 72d between the ribs 220d (and, if present, between the housing 10d and the chamber 240). These sleeve leaves 74d have distal faces 73d adapted to interact with the complementary proximal faces of the needle sheath 170d. Optionally, the gap between the sleeve leaves 74d may coincide with a window in the elongated housing 10d (for example, as described in the third embodiment, window 18c). This allows for visualization of the contents of the drug chamber 240 (if present). Alternatively, the sleeve leaves 74d or the entire sleeve 70d may be transparent. In another embodiment, the elongated housing may be made of a transparent or translucent material to allow for visualization of the drug chamber and / or the internal mechanism contained within the elongated housing. In one embodiment, the sleeve 70d also includes a leaf 76d. The leaf 76d extends proximal from the body 72d between the elongated housing 10d and the chamber 240 (if in a predetermined position) through the corresponding slot 442 in the plug 440 (see Figures 91 and 92), and the leaf 76d has a proximal surface 78d that interacts with a complementary surface on the restraint 130d and is adapted to push the restraint 130d proximal when pressure is applied proximal to the distal surface 73d of the sleeve 70d by the sheath 170d.

[0163] Referring to Figures 63-69 and 77-79, when the syringe according to the present invention is assembled, the drug cartridge 240 is placed in a predetermined position, the plunger 80d is engaged with the stopper 50 (not shown), the dosage is set, and the device is ready for injection, the drive spring 90 is subjected to stress with the plunger 80d held in a predetermined position by the retaining toggle 120d, the retaining toggle 120d is held in the plunger engagement position by a restraining device 130d that is at least proximal to the plunger engagement position, the restraining device 130d is in the restraining position when distal (Figure 77) and in the release position when proximal (Figures 78 and 79).

[0164] Referring to Figures 61–92, and in particular Figures 72–76, retaining toggles 120d and restraints 130d as used in the fifth embodiment are illustrated. In particular, the retaining toggle 120d comprises a toggle with a pivot / fulcrum 121d adapted to engage with a pin or shaft 140c (shoulder joint) provided about one-third of the way from its tip. Alternatively, the pin or shaft 140d may be formed separately or form part of the toggle 120d. The pin / shaft 140d connects the toggle 120d to the plunger 80d via a corresponding joint or fulcrum 390d. The toggle 120d also comprises an outward-facing projection 122d located slightly proximal to the pivot / fulcrum 121d and adapted to engage with an opposing ridge or projection 112d formed on the operating housing 110d. The proximal end of the toggle 120d is provided with an axial inner surface 124d, which is adapted to engage with a complementary axial outer surface 132d on the restraint 130d in order to hold the toggle 120d in the actuation housing engagement position while the restraint 130d is in the restraint position. The induced pressure using such a retaining arm or toggle (i.e., the amount of proximal force that needs to be applied to the restraint 130d by the sleeve 70d, and therefore the amount of distal force that needs to be applied to the injection surface) is inversely proportional to a / b, where "a" is the distance between the pivot point 121d and the proximal surface 124d, and "b" is the out-of-axial extension distance of the end of the projection 122d compared to the pivot point 121d. Thus, for a given biasing strength provided by the spring 90, the longer "a" or the smaller "b", the less force is required to induce the device, resulting in less discomfort to the subject being injected. The distances "a" and "b" can be selected to suit a specific syringe for a particular application. For example, if the syringe is for intraocular injection, a low evoked pressure is desired, so it is desirable to set the a / b value such that "b" is equal to "a" or significantly smaller than "a". For example, the a / b value should be greater than 1, for example, in the range of 1 to 1000.The toggle 120d may also include a lockout projection 128d adapted to engage with the distal surface 113d of the retaining projection of the housing 110d, and may also include a surface 126d that engages with the surface 79d of the sleeve 70 to provide further lockout functionality. This causes the sleeve 70d to move proximal, causing the surface 79d to press against the surface 126d of the retaining toggle 120d, pressing it against the inner wall of the operating housing and securing it.

[0165] Referring to a restraint 130d, particularly illustrated in Figure 74, it is provided as one or more sleeve engagement surfaces 134d connected to a toggle retaining surface 132d. When in use, the sleeve 70d slides proximal to the elongated housing 10d by pressing the syringe against the injection surface and applying distal pressure, and the restraint 130d also moves proximal. This releases the toggle 120d, allowing the surface 122d to flex axially (biased by the spring 90) from the ridge or projection 112d of the operating housing 110d, and allows the drive spring 90 to drive the plunger 80d and the stopper 50 (not shown) distally. As illustrated in Figures 72-74, the restraint 130d may include means for holding the restraint in a slidably connected state with the plunger 80d. Such means include, for example, an arm 136d adapted for clipping onto a ridge 85d on the plunger 80d, as shown. This allows the restraint 130d to be held in a relationship that allows it to slide proximal and distally with respect to the plunger 80d. In certain embodiments, the restraint 130d may also include a projection 138d that is slidably positioned in a groove 138d in the plunger 80d and adapted to pass through an opening 119d in the housing 110d and engage with the transport lock bar 299d of the proximal cap 290d (to prevent unintended operation / movement) (Figures 71, 72, 81, and 84). In other embodiments, the restraint 130 may be formed as a ring that completely surrounds the plunger, eliminating the need for a clipping mechanism. In yet another embodiment, the restraint may have a projection, such as 138d, adapted to slide in a corresponding groove in the operating housing. Given the above description and illustrations of the intended purpose, many other options for positioning the locking projection will become apparent to those skilled in the art.

[0166] Referring to Figures 93-95, the needle hub 150d, which can be used in any of the second, third, fourth, or fifth embodiments, may comprise a body 168d having a proximal body 168d1 with a needle 62 extending proximal and a distal body 168d2 with a needle 64 extending distally. The needle 62 is for puncturing the drug cartridge seal 246 (if present; if a pre-filled syringe is used instead of a drug cartridge, there is no septum to penetrate), and the needle 64 is for insertion into the subject for injection. The distal body 168d2 is axially centered via a rib 164d in a connector 166d adapted to engage and connect with a barrel connector 210d. The bodies 168d1 and 168d2 are adapted to connect with each other (and may also be, for example, snap-fastened, bonded, or ultrasonically welded). A filter 300 is incorporated between the two bodies to filter out any particles that may be generated when puncturing a filled cartridge or filled syringe, or any particulate matter present in the drug. The sheath 170d has a distal subject contact surface 172d and a proximal leaf 174d. The proximal sheath leaf 174d slides through a slit 167d between the needle hub body 168d2 and the connector 166d, and the proximal end face of the leaf 174d is adapted to engage with the distal surface 73d of the leaf 74d of the sleeve 70d when the hub 150d is fully connected to the barrel connector 210d. The proximal sheath leaf 174d may be flexible and may also have a snap tab for securing the sheath in an interleaved relationship with the barrel connector 166d (see Figure 95). When not in use, the hub 150d (whether connected to the connector 210d or not) may have a removable cap 180d. The cap may be adapted to support, protect, or both support and protect the sheath (and patient contact surface) from contact with external surfaces in the extended position. In yet another embodiment, the detachable cap may further comprise a characteristic component adapted to surround the needle when connected to the needle hub. In certain embodiments, such a characteristic component may be further adapted to receive the volume of drug to be released when preparing the syringe for use.The distal end of the sheath 170d may be provided with a guide for securing and protecting the needle 64 within the needle hub during injection. The contact surface 172d may be provided with a pad made of a softer and / or spongy and / or adhesive material than the sheath 170d, such as silicone or rubber. Alternatively, the distal end of the sheath 170d may be provided with a rough or spiked surface to assist in holding the syringe in place during the injection procedure. In further embodiments, the distal surface of the sheath 170d may be provided with characteristic components such as protrusions, bumps, and / or other tactile elements. In even further embodiments, the contact surface of the distal surface of the sheath may include a combination of the aforementioned characteristic components or materials. Such characteristic components and materials may further assist the physician in controlling or maintaining the position of the eye in a desired position during the injection procedure (e.g., in the case of intraocular injection, in the correct injection position on the ocular surface). Although not shown, the needle hub 150d may be provided with biasing means such as a spring within the sheath 170d. This biasing mechanism presses the sheath 170d distally to the main body 168d and, consequently, to the needle 64, keeping the needle 64 stored inside the sheath when not in use.

[0167] As described above with respect to another embodiment of the needle hub, in certain embodiments, a one-way valve, such as a duck valve, may be provided between the proximal body 168d1 and the distal body 168d2 of the needle hub. Such a valve may be advantageous in preventing undesirable leakage of the drug from the cartridge 240 when positive pressure is present, for example, when residual pressure is acting on the fluid, or when other forces are present that could cause the fluid to leak out of the needle at an undesirable moment during use of the instrument.

[0168] In certain embodiments, the needle 64 may be made as short as possible (while ensuring the correct injection depth) to reduce drug flow resistance. In other embodiments, the space between needles 62 and 64 within the needle hub may be the same width and / or the same diameter as needle 62, or may have other geometric shapes configured to reduce drug flow resistance. In other embodiments, needle 62 may have a split channel to release air trapped within the needle hub during injection preparation and / or injection.

[0169] Any other characteristic components of the needle hub according to the present invention have already been described above with respect to at least the fourth embodiment and are similarly applicable to this embodiment.

[0170] When in use, the syringe according to this fifth embodiment may be supplied as a single-use sterile instrument ready for injection, or with a pre-filled syringe, or with a cartridge intended for use with multiple patients, equipped with a detachable needle hub, or without a drug chamber, as shown in Figures 61–95. In any embodiment, the needle hub 150d is optionally supplied without it (supplied separately in the form of a sterile package). A drug cartridge 240 is provided separately, and ideally pre-filled, the actuation mechanism 20d and an optional plug 440 (the cartridge centering arm 446 may be flexible enough to allow the cartridge 240 to pass through without the plug 440 needing to be removed) are separated from the elongated housing 10d, and the drug cartridge 240 is inserted into the elongated housing 10d with the crimping ring 248 and seal 246 (as shown in Figures 21 and 22) in contact with the sheet 230d. Subsequently, if the plug 440 has been removed, the plug 440 is reinserted into the proximal end of the elongated housing 10d (compressing the spring 190), the operating mechanism 20d and the elongated housing 10d are joined together and fixed in place, and at the same time the distal end of the plunger 80d is engaged with the stopper 50. If the drug cartridge is filled under vacuum or without air gaps, this assembly generates positive pressure inside the drug cartridge 240. As a result, the proximal cap 290d is positioned higher than the operating housing 110d, and in a preferred embodiment, this creates a gap "A" between the distal surface of the proximal cap 290d and the corresponding mounting surface of the operating housing 110d (Figure 63). Also, a gap "B" is created between the toggle surface 122d and the proximal surface 112d of the retaining projection of the operating housing 110d. Gap "A" is smaller than gap "B". Next, the needle hub 150d is connected to the needle hub connector 210d, the proximal end of the needle 62 pierces the seal 246, and the positive pressure in the drug cartridge 240 causes the plunger 80d and the proximal cap 290d connected to it to move distally, so that the proximal cap 290d comes into contact with the corresponding surface of the operating housing 110d and comes to rest (i.e., the gap "A" is reduced to zero - gap "A" in Figures 64 and 65).The drug is then dispensed from cartridge 240 into needles 62 and 64, and the system is prepared. Simultaneously, the gap "B" between the toggle surface 122d and the proximal surface 112d of the retaining projection on the operating housing 110d is also reduced to a small gap "B" (Figure 64). Referring to Figure 65, the instrument is calibrated by slightly rotating the proximal cap 290d to reduce gap "B" to 0. Referring to Figure 66, further rotation of the proximal cap 290d causes it to move proximal away from the complementary mounting surface on the operating housing 110d, forming gap "A" and setting the dose travel distance. This is induced, and the system is ready to deliver the set dose. The outer surface of the operating housing 110d may be provided with a scale that correlates with the proximal extension of the proximal cap 290d relative to the operating housing 110d. Thus, the size of gap "A" and the dose corresponding to that gap are indicated. Additionally, optionally, one or more windows may be provided on the outer surface of the proximal cap 290d for checking such markings and setting the dosage, as described in the third embodiment. To assist in setting the dosage while rotating the proximal cap 290d relative to the operating housing 110d, the dosage markings may extend along the circumference of the outer surface of the operating housing 110d.

[0171] This mechanism, applicable not only to this fifth embodiment but also to the fourth and third embodiments (i.e., embodiments of the present invention employing an operating housing with a proximal cap, in which the dosage is determined by the interaction between the proximal cap and the plunger), makes it possible to eliminate variations in tolerance in specific instruments, and the accuracy of the travel distance for dosage release is greatly improved because variations in dimensional tolerance at the dosage setting point are minimized, resulting in a significant advantage in the dosage accuracy of the instrument. Furthermore, a spring may be incorporated between the proximal cap 290d and the plunger 80d to absorb slack and counteract the play and its effect on dosage variations.

[0172] In an alternative embodiment of the preparation mechanism, the needle hub assembly 150d may also be provided with a preparation spring at the proximal end of the proximal body 168d1. The diameter of this spring is narrower than the opening of the seat 230d. This causes the cartridge 240 to be pressed proximal when the needle hub 150d is screwed into the barrel connector 210d. In such an embodiment, the plug 440 may also be provided with a cartridge stop that protrudes inward above the centering rib and arm 446 of the drug chamber. This causes the preparation spring to push the cartridge 240 toward the cartridge stop when the needle hub 150d is screwed into the barrel connector 210d. This also causes the stop 50 to move toward the distal surface of the plunger 80d and eventually engage with the distal surface of the plunger 80d before the proximal surface of the cartridge 240 reaches the cartridge stop, forming a gap "x". As the needle hub 150d is further screwed into the barrel connector 210d, the plunger 80d pushes against the stop 50, generating a positive "preparation" pressure within the cartridge 240 between the preparation spring and the plunger 80d (proportional to the spring force and the deflection of the preparation spring within the hub). As the needle hub 150d is further screwed into the barrel connector 210d, the preparation spring is further compressed, the needle 62 pierces the partition 44, and the drug passes through the needle hub, allowing for pressure equalization. This also causes the cartridge 240 to move further proximal until its proximal surface reaches the cartridge stop on the plug 440 (i.e., reducing the gap "x" to 0). At the same time, a certain amount of drug passes through the needle assembly, thereby preparing the needle hub 150d. In such a system, the positive pressure generated between the preparation spring and the plunger 80d within the cartridge 240 is smaller than the positive pressure applied by the spring 90 in the previously described embodiment, reducing delayed leakage (which can occur particularly with viscous drugs) caused by pressure generated after perforation of the partition wall 246, and preventing clogging of the stopper, thereby preventing pressurization of the fluid during storage and subsequent persistent clogging of the partition wall. In other embodiments, the needle 62 may have a split channel for releasing air trapped within the needle hub during preparation and / or injection.

[0173] Once the syringe is prepared and the dosage is set, the restraint 130d is in the distal restraint position, at which point the toggle 120d is held such that the toggle surface 122d engages with the proximal surface 112d of the retaining projection of the operating housing 110d. This holds the plunger 80d in the "ready" position against the biasing force of the first spring 90.

[0174] Next, the patient contact surface of the sheath 172d is placed against the injection surface, and distal pressure is applied. This pressure causes the sheath leaf 174d to slide proximal, into the elongated housing 10d, and contact the distal end 73d of the sleeve leaf 74d, causing the sleeve 70d and sleeve leaf 76d to slide proximal, into the operating housing 110d, and pressurized between the spring retaining ring 440 and the spring engaging protrusion 77d on the inner periphery of the sleeve body 72d, against the biasing force provided by the sleeve spring 190. As the sleeve 70d moves proximal into the operating housing, the proximal surface 78d of the sleeve leaf 76d also moves proximal into the operating housing 20d, finally engaging with the surface 134d of the restraint 130d, causing the sleeve 70d to slide proximal. When the restraint 130d moves the required distance proximal (as a result of the needle 64 reaching the desired injection depth), the retaining surface 132d disengages from the surface 124d of the toggle 120d, and the toggle 120d becomes able to rotate around the axis 121d (as a result of the bias applied by the spring 90), disengaging the surfaces 122d and 112d, thereby releasing the plunger 80d, which is driven distally by the bias applied by the spring 90, as a result of the drug being discharged from the distal end of the needle 64, and the proximal cap 290d comes to rest again in contact with the corresponding surface of the operating housing 110d (i.e., the gap "A" is reduced to zero - gap "A" in Figure 65).

[0175] When the injection is administered, the pressure applied distally is relieved or released. As a result, the sleeve spring 190 applies pressure to the raised portion 77d of the sleeve 70d, which is no longer facing it, pushing the sleeve 70d distally, and consequently the sheath 170d is pushed distally to cover the needle 64 again. Furthermore, as a result of the sleeve 70d being pushed distally, its inner wall no longer restricts further out-of-axis movement of the surface 126d of the toggle 120d under the bias of the spring 360d, and the surface 126d of the toggle 120d is further deflected out-of-axis by force toward the wall of the elongated housing 10d (and radially outward from the pivot point 121d), and then, if the sleeve 70d and sheath 170d are pushed proximal for any reason, the surface 126d engages with the surface 79d of the sleeve body 72d, locking the sheath 170d in a position that covers the needle, thereby reducing the risk of needle stick injury by preventing the distal needle from being exposed to the user again (Figure 69). Other means for ensuring a strong engagement between the sleeve body 72d and the distal end 126d of the toggle 120d and for more firmly fixing the sheath in a position that covers the needle have already been described above in relation to other embodiments and will be readily apparent to those skilled in the art.

[0176] Referring to Figures 96 and 97, an alternative embodiment of the dosage mechanism is illustrated that enables greater sensitivity and precision in setting small doses (e.g., doses of 100 μL or less). In this embodiment, the proximal cap 290d (described in the fifth embodiment) is replaced by an internal dosage setting knob 290e having threads 294e that screw onto threads 280e of a plunger 80e (which may be the same as the plunger 280d described above). The outer surface of the internal knob 290e may have an appropriate shape such that the external knob 500e slides on the internal knob 290e, but the internal knob 290e and the external knob 500e cannot rotate significantly axially relative to each other. Such a shape of the outer surface of the internal knob 290e may include a square or rectangular cross-section and / or may have splines, etc., that engage with a complementary inner surface in the external knob 500. The external knob 500e has an outer surface with threads complementary to thread 510e on the inner surface of the extension 115e of the operating housing 110e. The pitch of thread 510e is significantly larger than the pitch of threads 280e / 294e. As a result, when the knob 500e is rotated counterclockwise by one turn and the internal knob 290e is rotated by one turn, the knob 500e moves proximal a significantly longer distance than the internal knob 290e (compared to the rest of the operating housing 110e), thus resulting in a large proximal movement of the knob 500e. An advantage is that the large proximal movement of the knob 500e results in a small proximal movement of the internal knob 290e, which in turn slightly changes the dosage delivered by the device, making it visually easier to set small dosages for injections using the device according to the present invention. To further enhance convenience, as shown in Figure 97, the internal knob 290e may be equipped with a flexible extension arm 296e having a pip that engages with grooves 520e arranged radially and distally on the inner surface of the extension 115e. This enables stepwise dose measurement. As shown in Figure 96A, the extension 115e may be equipped with a window 530e on the outer surface of the external knob 500e for confirming the dose setting, and optionally a window 540e for visually confirming whether the internal knob 290e has returned to the resting position after operation.This allows confirmation that the device is functioning and that the dose has been delivered. To customize a given device to a specific dose, increment, and precision, all parameters such as the number of rotations of the dose setting knob to the maximum dose, the pitch of the internal screw of the dose setting knob, the diameter of the housing 115e, and the size and number of the stoppers 520e on the inner circumference of the housing 115e can be adjusted.

[0177] As an alternative to the embodiments illustrated in Figures 96 and 97, as shown in Figure 98, the extension 115e of the operating housing 110e is replaced by a separate dose delivery housing 115f, into which an external knob 500f is screwed via complementary threads, as described above for parts 115e and 500e, the knob 500f is adjusted until a reading of "0" is observed in the window 530f, and then the external knob 500f is attached to an internal knob 290f, which may be the same as the internal knob 290e, as described above. Alternatively, it may include a number of radially arranged proximal-distal extending splines 295f adapted to engage with one or more complementary surfaces, such as an inner ridge of the external knob 500f. The dose delivery housing 115f is then connected to the operating housing 110f in a fixed manner / position (i.e., so that the dose delivery housing 115f does not rotate or move significantly proximal or distally). An advantage of this embodiment is that when the delivery housing 115f is fixed in place on the actuation housing 110f, the external dosage knob 500f is set to the "0" setting. The "0" setting is achieved by engaging the retaining toggle surface 122d with the actuation housing surface 112f (i.e., there is no gap between them, and they are in contact). Next, the internal knob 290f is rotated until it contacts the actuation housing 110f or the nearest stopper (this may create a very small gap between 295f and 110f). Alternatively, a very small gap may exist between surfaces 122f and 112f (because the plunger 80f rises and the spring 90 is compressed, causing the retaining toggle 120e to rise from its projection). This gap can be arbitrarily controlled by the screw pitch on 290f. Next, since the spline pattern on 500f matches the spline pattern on 295f, assembly 115f / 500f is attached to internal knob 290f, and the system is correctly set to 0.

[0178] Referring to Figures 99 and 100, a self-setting retaining arm mechanism applicable to embodiments with a retaining toggle is described. In such embodiments, the slightly modified retaining toggle 120f has a beveled or rounded surface 125f and a slightly elongated surface 128f compared to the surface 128d of the retaining toggle illustrated in Figures 75 and 76. The restraint 130f also has a beveled / rounded surface 133f adapted to slidably engage with the surface 125f of the retaining toggle 120f, in addition to the retaining surface 132f (corresponding to the retaining surface 132d in Figure 74). When the operating mechanism is assembled, the proximal pressure applied to the plunger 80d / e / f pushes the surface 128f proximal until it engages with the surface 113d / e / f on the inside of the operating housing 110d / e / f. When proximal pressure is continuously applied to the plunger 80d / e / f, the retaining toggle rotates around the pivot axis 121f against the bias applied by the spring 360f, aligning the retaining toggle 120f with the plunger 80d / e / f and bringing the beveled / rounded surface 125f of the retaining toggle 120f into contact with the surface 133f of the restraint 130f. As a result, when proximal pressure is continuously applied to the plunger 80d / e / f, an out-of-axis pressure is applied from surface 125f to surface 133f. As a result, the restraint 130f is pushed proximal against the bias applied by the spring 90 (not shown) until surfaces 125f and 124f move distally relative to the retaining surface 132f. At this point, the restraint 130f is able to move freely distally due to its own weight (or, optionally, a bias applied to the proximal surface of the restraint 130f). The restraint 130f moves along its proximal surface until it stops on the complementary surface of the plunger 80d / e / f. Next, when the proximal pressure on the plunger 80d / e / f is released, pivotal pressure is applied to the retaining toggle 120f by the biasing forces of springs 360f and 90, which presses surface 124f against retaining surface 132f, stopping further pivoting of the retaining toggle 120f.Furthermore, the plungers 80d / e / f, the restraints 130f, and the retaining toggles 120f are biased by the spring 90 and become able to move distally, and the surface 122f of the retaining toggles 120f comes into contact with the surface 112f of the operating housing 110f, stopping further distal movement of the assembly, and the operating mechanism becomes active and ready to be triggered.

[0179] Referring to Figure 108, particularly Figure 108G', the self-setting holding arm mechanism shown in Figures 99 and 100 and described above, in the context of the administration mechanism illustrated in Figure 98 and described above, is suitable for a syringe that can be reset for multiple injections using the same operating mechanism, the same elongated housing (with or without drug chamber replacement), or replacement of the elongated housing (with or without drug chamber replacement). In the specific embodiment illustrated in Figure 108, the drug chamber 240f is integrally formed with the elongated housing 10f and connected to the inside of the wall of the elongated housing by ribs extending axially inward. However, the mechanism described herein can also operate in the aforementioned embodiments with separate drug chambers, such as replaceable syringes or cartridges. The sleeve 70f is slidably positioned between the drug chamber 240f and the wall of the elongated housing 10f, and the sleeve 70f is biased distally by a sleeve spring 190 (held in place relative to the sleeve 70f by a spring retaining ring 440) and adapted to engage with the distal end of the restraint 130f. The restraint 130f then engages with the proximal surface 124f of a toggle 120f connected to the plunger 80f via a pivot point 121f as described above. In a particular embodiment illustrated in Figure 108, the needle sheath 170f is formed separately from the sleeve 70f but adapted to engage with the distal end of the sleeve 70f. Therefore, when the sheath 170f is positioned at the target anatomical site to be injected and the syringe is pressed distally, the sheath 170f pushes the sleeve 70f, causing the sleeve 70f to slide proximal, pressing the restraint 130f proximal and releasing the proximal surface 124f or toggle 120f. The toggle 120f can freely rotate from a non-operating position to an operating position, thereby driving the plunger 80f distally by the spring 90, as described above. The embodiment specifically illustrated in Figure 108 has a sheath 170f formed separately from the sleeve 70f, but the mechanism described herein may also operate with a needle sheath formed integrally with the sleeve 70.Furthermore, while the embodiment specifically illustrated in Figure 108 has a integrally formed needle (bonded or injection-molded in place), the mechanism described herein may operate in a drug chamber with its own needle assembly, or in an elongated housing with a detachable / replaceable needle hub, as in any of the embodiments described above. Importantly, the syringe illustrated in Figure 108 is an improvement over the dose delivery mechanism illustrated in Figure 98. This improvement is that, compared to the dose delivery housing 115f illustrated in Figure 98, the dose delivery housing 115g has a flange 670 that extends outward in the circumferential direction. By pulling the dose delivery mechanism proximal to this flange, the toggle reset described in Figure 98 can be performed. Such a flange is not essential, and a different modification of the dose delivery housing 115f, or the dose delivery housing 115f illustrated in Figure 108, would be equally effective (for example, the dose delivery housing 115f only needs to be pulled proximal to assist this operation, and may have a rough outer surface). The dose delivery housing 115g may optionally include an extension 680 extending distally, as shown in the figure. This extension 680 is slidably mounted on the working housing and optionally clipped onto the extension housing, and is secured there via projections 690 extending inward from the dose delivery housing 115g and projections 700 extending outward from the working housing 110f (this prevents the dose delivery housing from being withdrawn from the syringe).

[0180] Instead of the flange 670 that extends circumferentially outward to pull the dose delivery housing proximal, the twist ring can be positioned beneath a modified 115g or 115f (held in place relative to the sleeve 70f by the spring retaining ring 440). This causes the dose delivery housing to rest on the twist ring, which engages with the actuating housing via a complementary thread system, so that when the twist ring rotates axially, it moves proximal, pushing the dose delivery housing proximal and activating the reset mechanism described above. When the twist ring is released, it returns to its starting position under pressure from the drive spring 90, or may remain in any position between the fully twisted position and the starting position if a non-zero dose is set in the dose delivery mechanism, but returns to the starting position when the actuating mechanism is triggered. Such a configuration allows the pitch of the actuating housing relative to the threads of the twist ring to be customized to move axially by a desired distance for each rotation angle. However, this pitch should not prevent the twist ring from returning to the starting position. Alternatively, or in addition to this, a spring can be provided to return the twist ring to its starting position after each reset operation.

[0181] Referring to the procedure illustrated in Figure 108, this relates to a multipurpose syringe adapted for the use and replacement of a pre-assembled elongated housing having a filled drug chamber (which may or may not be integrally formed with the elongated housing). As illustrated in Figures 108A and 108B (and the corresponding cross-sectional views in Figures 108A' and 108B'), a pre-assembled elongated housing 10f (including parts 70f, 190, 440, and 240) is mounted on a plunger 80f. The elongated housing is then joined with the working housing 20g (already adjusted to zero as described above in relation to the mechanism illustrated in Figure 98) and connected to it by any suitable means, such as a twist-lock mechanism as illustrated in Figure 108B. As a result, the plunger 80f contacts the stop portion of the drug chamber and pushes it distally, thereby preparing the distal needle 60 (see Figure 108B', downward-pointing white arrow). Next, the dosage setting knob is adjusted to 500g to set the dosage (Figures 108C and 108C'), the needle cap 180f is removed (Figures 108D and 108D'), the sheath 170f is placed against the injection surface (not shown), and distal pressure is applied to the syringe, causing the sheath 170f, sleeve 70f, and restraint 130f to slide proximal, the toggle 120f is released and rotated to the operating position, the plunger 80f is driven distally by the spring 90, and the drug is delivered from the drug chamber 240 (Figures 108E and 108E'). Once the injection is performed, the distal pressure on the syringe is released, and the sleeve spring 190 biases the sleeve 70f and sheath 170f distally so that the sheath 170f completely covers the needle 60 again (Figures 108F and 108F'). Simultaneously, the toggle 120f rotates further to its fully rotated position, causing its surface 126f to contact the inner wall of the extension housing 10f, and the surface 113g of the operating housing 20g (equivalent to the surface 113f shown in Figure 100) and the surface 128f of the toggle 120f to engage, thereby forcing a lockout. This prevents the sleeve 70f and sheath 170f from sliding proximal (and the exposure of the needle 60).Before or after disassembling an assembled but used extension housing, the operating housing may be reactuated as shown in Figures 108G, 108G', and 108G'', and also with reference to Figures 99 and 100, and the relevant description above regarding the mechanism. As shown in Figures 108G and 108G', proximal pressure on the optional flange 670 assists the proximal movement of the dose delivery housing 115g, sliding the plunger 80f proximal and returning the axial toggle 120f to the deacting position. Also, as shown in Figures 108G'' and 98, when the proximal pressure on the dose delivery housing 115g is released, the sleeve 70f slides distally, thereby allowing the restraint 130f to re-engage with the surface 124f of the toggle 120f, holding the toggle 120f in the deacting position, and consequently resetting the operating housing. If the elongated housing assembled before the operating housing was not removed, it can now be removed, and the operating mechanism is ready to be fitted with a new pre-assembled elongated housing with a newly pre-filled drug chamber, and is ready to perform the next injection following the procedure above.

[0182] Referring to Figures 108A–108C (and corresponding cross-sectional figures 108A'–108C'), an improved needle cap assembly is illustrated. This helps prevent drug loss from the drug chamber or engaged needle and supports and protects the needle when not in use. The needle illustrated in Figure 108 is integrated with the elongated housing (bonded to the elongated housing, injection molded, or otherwise secured), but the illustrated cap configuration may be used with other needle assemblies, including the aforementioned replaceable needle hub. Optionally, it may be used with a fitting to ensure secure attachment of the needle hub to the elongated housing (for example, to prevent the cap from axially slipping or sliding around the body of the needle assembly when the needle assembly is attached to the elongated housing by a twisting motion). The cap 180f, as illustrated in Figures 108A-108C (and Figures 108A'-108C'), has a tip 640 on the distal side of an elongated housing, and the tip 640 is held in a relationship that allows it to slide at least partially within the proximal part of the cap body 180f, so that the tip 640 can slide at least distally, if not proximal, within the cap body 180f. The tip 640 also has a seal 650 made of a perforable material such as a sponge-like, elastic, or rubber-like material, which is positioned inside so that the proximal end of the sheath 170f slides between the inner wall of the tip 640 and the seal 650. The seal 650 also engages with the needle 60 in a sealed state (for example, the needle 60 perforates the seal 650 at least partially) and at the same time helps to support the needle 60 when not in use. When the needle 60 is in fluid communication with the drug chamber under pressure (for example, when the stop portion of the drug chamber is biased distally by the plunger 80f during preparation), the drug is pushed out through the needle 60, which in turn pushes the seal 650 distally, causing the tip 640 to slide distally relative to the cap body 180f, thus preparing the needle 60. The seal 650 may optionally include a space 660 at its proximal end (which may remain within the distal end of the sheath 170f after preparation). This space 660 functions as a reservoir to receive fluid discharged from the needle 60 during preparation, etc.

[0183] Referring to Figures 101 and 102, a retaining toggle 120g with a cam is illustrated. This does not require a biasing spring 360d / e / f to rotate around axis 121g after being induced. The actuation mechanism is induced by the proximal movement of the restraint 130g, and as a result the coupling of surfaces 124g and 132g is released, the plunger 80g and the retaining toggle 120g connected to it are driven distally by spring 90, resulting in pressure between surface 123g of the retaining toggle 120g and surface 112g of the actuation housing 110g. As a result, due to the curvature of surface 123g, the retaining toggle 120g rotates around axis 121g until surface 123g rotates axially, allowing the plunger 80g to move freely distally. As a result of the retaining toggle 120g rotating around the axis 121g, the lockout extension 126g rotates outward and contacts and presses against the inner surface of the sleeve surface 79g. In one embodiment, the lockout extension is flexible or at least flexibly attached to the retaining toggle 120g. As a result, it can bend when pressed against the inner surface of the sleeve surface 79g, but when the induced pressure from the sleeve 70g is released, the surface 79g slides distally (as a result of biasing by the spring 190 on the sleeve 70g, not shown) and moves beyond the lockout extension 126g, and the lockout extension 126g flexes into the space left open by the surface 79g. When further proximal pressure is applied to the sleeve 70g, the surface 79g contacts the lockout extension 126g, and its proximal movement is stopped by the lockout extension 126g. Therefore, when a needle hub with a sheath is attached, the proximal movement of the sheath is also prevented by the lockout extension 126g, so that the needle 64 remains in the sheath even after this mechanism has been activated.

[0184] In all embodiments of the syringe according to the present invention, the drive spring 90 that biases the plunger / plunger 80 distally (and thus provides a force to expel the drug from the drug cartridge or chamber 40 or 240) may be replaced with another suitable biasing mechanism. For example, a torsion spring may be used instead, as shown in Figures 103 and 104. In such embodiments, the torsion spring 90h has a proximal pin 94h that engages with a complementary slot 111h at the proximal end of the operating housing 110h and a distal pin 92h that engages with a complementary slot 555 of a torque nut 550. The torque nut then engages with a thread 82h on the plunger 80h. When the operating mechanism is assembled and ready for activation, the torsion spring 90h is wound up and energy is stored. When the mechanism is activated as described above, the torsion spring 90h unwinds, the torque nut 550 rotates, and the plunger 80h is driven distally. The relationship between the torque diameter (defined by the position of slot 555 and the axis of rotation of torque nut 550) and the pitch of thread 82h determines the mechanical advantages of the system.

[0185] Figures 105-107 illustrate optional mechanisms for securing the device and / or reducing the load on the plunger until it is activated, and other possible mechanisms for pushing the plunger 80 distally.

[0186] For example, as shown in Figure 105, a spring or other elastic tensioning means (e.g., a constant-force spring 90b or a tension spring 90c) may be offset from the plunger 80i and exert a biasing force on the lever arm 560 via point 564. The lever arm may be fitted around the plunger 80i and connected to the operating housing via axis point 562. The lever arm 560 also has a recessed space 566 for engaging with the plunger pin 82i (this recessed space extends on both sides of the plunger 80i, and when the spring or other elastic tensioning means biases point 564 on the lever arm 560, the lever arm rotates distally around axis point 562, exerting distal pressure on the plunger pin 82i and thus distal pressure on the plunger 80i). The lever action or mechanical advantage obtained using such a mechanism is provided by the distance between 564 and 562, and the ratio of the distance between 566 / 82i and 562. Optionally, a removable tab 564 can hold the lever arm in place while the instrument is idle (e.g., during storage or transport), thereby suppressing the operation of the instrument and the action of pressure on the plunger 80i (and the drug cartridge 240, if installed) until needed.

[0187] As shown in Figure 106, the torsion spring 90d may be offset from the plunger 80j and bias the gear lever 580, which has a gear cog 585 at its axial end that interacts with the corresponding teeth on the plunger 80j. The torsion spring 90d has a body 92d that fits around the gear lever shaft 587, an arm 94d that engages with the axial side of the gear lever 580, and an opposite arm 94d that engages with a complementary surface, slot, or end on the operating housing opposite the connection point of the gear lever 580. The relationship between the arm contact distance from the shaft of the gear lever 580 and the diameter of the gear teeth that engage with the plunger 80j provides a mechanical advantage. When the torsion spring 90d biases the gear lever 580, and the gear lever 580 is biased axially as a result of rotation around the shaft 587, the teeth 585 of the gear lever engage with the corresponding teeth of the plunger 80i, pushing the plunger 80i distally. The out-of-axis biasing of the gear lever 580 also functions as a visual indicator that the device has been operated. When the syringe is assembled, the torsion spring 90d is already wound up and the gear lever 580 is biased by it, or optionally the device may be equipped with a switch such as a lever 590 that can be operated to wind up the torsion spring 90d when the syringe is ready to be used.

[0188] As shown in Figure 107, an alternative gear mechanism is shown in which a compression spring 90e, offset from the plunger 80k, engages with a rack 600 having teeth 605. The gear rack 600 engages with the outer side of a gear 610, which also has an outer side that engages with the plunger 80k. The outer side of the gear 610 engages with the gear rack having corresponding teeth 612, and the outer side of the gear 610 has teeth that engage with the corresponding teeth 82k on the plunger 80k. When the compression spring 90e biases the gear rack 600, it pushes the gear rack 600 proximal, which in turn pushes the distal side of the gear 610 proximal, causing the gear 610 to pivot around the axis 616, resulting in the distal side of the gear 610 and teeth 614 being pushed distally, and also pushing the plunger 80k distally. The compression spring may be already compressed during assembly (e.g., during storage), or optionally, the syringe may be equipped with a compression button 620 for compressing the spring 80k when ready for use.

[0189] The alternative biasing mechanisms illustrated in Figures 103-107 offer greater mechanical advantages, and therefore have the advantage of allowing greater injection force to be applied with smaller biasing devices such as springs, which can be particularly advantageous when injecting high-viscosity drugs.

[0190] In other specific embodiments of the syringe according to the present invention, unintended premature activation of the instrument can be prevented by a locking mechanism that interacts with the restraint described herein to stop the longitudinal movement of the restraint along the distal-proximal axis. Such a mechanism may include, for example, a pin or rigid slip that penetrates the operating mechanism housing and is inserted into a corresponding bed or slit formed on the side or other part of the restraint (e.g., the extension). Alternatively, the outer circumference of the restraint, or more preferably its distal extension within the diameter of the restraint, may have a partial ridge / flange with an outer out-of-axial groove that engages with a flange extending axially inward from the operating housing. In such embodiments, this relationship is released when the proximal cap is moved clockwise or counterclockwise, such as when setting the dosage, allowing the restraint to move freely. Exemplary locking mechanisms are illustrated in Figures 35-60. Therefore, the sleeve 70c has a rod 320 that extends proximal through a slot 380 at the proximal end of the operating housing 110c, and this rod 320 is blocked by a corresponding blocking surface 410 formed in the channel 420 on its lower surface when the proximal cap 290c is fitted. As described above, when the system is calibrated and the dosage is set by rotating the proximal cap 290c, the surface 410 no longer covers the proximal end of the rod, and the rod is able to move freely within the channel 420. This unlocks the device and allows the sleeve 70c to move proximal. Other such unlockable locking mechanisms would be readily conceivable to those skilled in the art.

[0191] In other embodiments, as illustrated in Figures 57-60 (which relate to the third embodiment as well as the fourth embodiment, i.e., embodiments of the present invention that use an operating housing with a proximal cap, where the dose is defined by the interaction between the proximal cap and the plunger), the relationship between the proximal cap 290c and the operating housing 110c may be stabilized so that the proximal cap 290c does not freely rotate on its axis relative to the operating housing 110c, and thus the dose can be prevented from being changed, for example, during the injection procedure. One means of achieving this is a ratchet mechanism, as illustrated in Figures 57-60. In this mechanism, biasing pawls 400 are provided around the operating housing 110c, and proximal-distal recesses 430 are provided on the inner surface of the proximal cap 290c. As a result, when the proximal cap 290c is positioned on the operating housing 110c (the proximal cap 290c and the operating housing 110c are in close contact with each other), the biasing claw 400 interacts with the recess 430 such that a sufficient force is required to overcome its interaction and rotate the proximal cap 290c relative to the operating housing 110c. Other mechanisms for stabilizing the relationship between the proximal cap 290c and the operating housing 110c will be obvious to those skilled in the art. These include, for example, friction fitting mechanisms.

[0192] In various embodiments / aspects of the syringe according to the present invention, the plunger may not be a single unit but may consist of two or more parts. For example, one part of the plunger in the device according to the present invention may be provided with a toggle and a dosage setting mechanism attached thereto, and a second part may be provided by a drug chamber (for example, attached to a stopper). Thus, it will be understood by those skilled in the art that "plunger" can be interpreted as meaning a plunger provided as a single unit, or a mechanism having multiple parts that are combined to form the plunger described in the present invention.

[0193] As described above, those skilled in the art may benefit from the above teachings and derive alternative embodiments, which include devising alternative operating mechanisms that function similarly using only materials and designs already well known in the field of syringes, or using only materials and designs that include only ordinary factory variations of those described above.

[0194] The apparatus according to the present invention can be used for injecting any drug, including liquids, solids (e.g., films, implants, gels, or particles), suspensions, or semi-solid or phase-transition drugs, and can be adapted for injecting any desired injectable therapeutic agent into any desired tissue or organ.

[0195] According to one particular embodiment of the present invention, a syringe for intravitreal injection is provided.

[0196] Intravitreal injection has been used to administer pharmacologically active ingredients into the eye to treat various eye diseases, including macular degeneration, diabetic retinopathy, retinal vein occlusion, and posterior uveitis. The active ingredients used are typically steroids, which can cause long-term systemic adverse effects if administered systemically, or antibodies such as anti-VEGF antibodies (bevacizumab, convercept, aflibercept, pegaptanib, and ranibuzumab), which have poor diffusion from the bloodstream into ocular tissue. Therefore, in such cases, intravitreal injection is sometimes preferred over systemic injection.

[0197] When administering intravitreal injections, care must be taken to avoid or minimize damage to other parts of the eye, including the lens, retina, ciliary body and muscle, suspension ligaments, and cornea.

[0198] The flattened area is an independent region of the sclera. This region is substantially concentric and is located 2–4 mm away from the limbus. The limbus is a 1–2 mm wide annular transitional region between the cornea and the sclera. This region lacks the inner retinal layer, is located almost behind the ciliary body and ciliary muscle, and allows direct access to the vitreous humor while avoiding the lens, making it a preferred target for intravitreal injection.

[0199] Accordingly, referring to Figures 1, 2, 5, 6, 8-11, 15, 24, 25, and Figures 35-43, 93, and 95, in one embodiment, a syringe according to one embodiment of the present invention comprises a sheath 170, 170c, or 170d (as part of a needle hub 150, 150c, or 150d, or as an extension of a sleeve 70, 70c, or 70d). Here, the sheath 170, 170c, or 170d has an eye contact surface at its distal end, or has a pad 177, 177c, or 172d at its distal end that functions as an eye contact surface. To better maintain position over the eye during injection, this eye contact surface may be padded or rough. In further embodiments, this eye contact surface may be provided with characteristic components such as protrusions, bumps, and / or other tactile elements. In yet another embodiment, the contact surface of the distal surface of the sheath may include a combination of the aforementioned characteristic components or materials. Such materials and characteristic components may help to hold the distal surface in place during injection procedures (for example, at the correct injection site on the ocular surface in the case of intraocular injection). They may also help the physician control or maintain the eye's position in a desired location during injection. The eye contact surface may have an outer circumference defining a circle or a deformed circle, and the surface may be annular, or a perforated concave disc, disc-shaped, or three-dimensional annular surface, with the needle defining the center of the circle. However, other shapes may also be used. When the eye contact surface is surface annular, or a perforated concave disc, disc-shaped, or three-dimensional annular surface (with the needle 60 / 64 passing through the perforation), the diameter of the circle may be 4–10 mm, more preferably 6–8 mm. This facilitates the measurement of 2–5 mm, preferably 3–4 mm, from the limbus to the flattened portion of the cornea to ensure injection into the vitreous cavity of the eye. Even when other eye contact surface shapes are used, it is necessary to provide at least one eye surface contact edge 2 to 5 mm, preferably 3 to 4 mm, away from the needle to ensure proper needle placement during intravitreal injection.If the eye contact surface is a pad 177, the pad 177 may be made of a material that is softer or spongy than the material constituting the sheath 170 or 170c and / or can grip the eye surface more firmly (to prevent the sheath from moving on the eye surface during the injection procedure), for example, silicone, rubber, or an absorbent material. In certain embodiments, the sheath 170, 170c, or 170d of the syringe for intravitreal injection according to the present invention may be substantially hollow cylindrical for most of its length, and optionally its distal end may be frustoconical (narrowing). When in use, the eye contact surface is positioned on the sclera of the eye surface, with one end of the eye contact surface positioned at the limbus (the boundary between the leucosclera and the cornea / iris) and the rest of the eye contact surface resting on the sclera (the side away from the cornea). This ensures that the needle 60 or 64 is reliably inserted into the eyeball from the area of ​​the flattened part of the eyeball, and the risk of damage to major structures of the eyeball such as the retina, lens, and ciliary body is greatly reduced. In certain embodiments, the eye contact surface, such as pad 177 or 177c, may be provided with a pad 179 extending circumferentially from it to help apply pressure near the injection site after injection to prevent post-wound leakage / backflow. A further advantage of pad 177 or 177c is that it introduces a large asymmetry between the sheath 170 or 170c and the cap 180, allowing the corresponding needle hub to be easily screwed into the barrel connector 46 or 210 or 210c with the cap 180 attached by applying axial rotational pressure to the cap 180. The sheath 170 or 170c may be provided with an axilla to engage with the eyelid during injection and keep it away from the injection site. This axilla may extend from the body of the sheath 170 or 170c, in which case the axilla contact means is in contact with the boundary of the eye contact surface 177 or 177c.

[0200] To avoid retinal damage, intravitreal injections should ideally aim to deliver the drug to the center of the vitreous cavity. Accordingly, in one embodiment, the intravitreal syringe according to the present invention may be configured to deliver the medicinal drug to a depth of about 4 to 10 mm, preferably 5 to 7 mm. The injection depth at which the plunger 80 or 80c is released by the interaction of the retaining arm or toggle 120 or 120c with the restraint 130 or 130c (i.e., the injection depth at which the injection is activated) can be predetermined based on the size of the retaining tab 128 or 128c (i.e., the length from proximal to distal) and the thickness of the restraint 130 or 130c, the "dead" space between the proximal surface of the sleeve body 72 or 72c and the bottom surface of the restraint 130 or 130c, and the "dead" space between the eye contact surface and the tip of the needle 60 when stationary.

[0201] The syringe according to the present invention may be disposable or may be configured for multiple uses by replacing the drug chamber. Alternatively, the instrument may be adapted for multiple injections from the same drug chamber using a replaceable disposable needle hub as described herein. In some embodiments, the syringe may be pre-assembled with the drug chamber and sterile-packaged for immediate use without additional assembly. In other embodiments, the syringe may not have a needle hub (although a syringe cap is provided on the barrel connector), and the needle hub may be provided separately, both sterile-packaged. Certain syringes according to the present invention are adapted to house standard drug chambers or cartridges that can be filled (including vacuum-filled), sealed and sterilized in a facility familiar with such procedures. On the other hand, the syringe and needle hub (if separate) may be manufactured in a separate facility familiar with their manufacturing procedures.

[0202] In certain embodiments, the syringe according to the present invention may be completely disposable or comprise a pre-assembled, disposable, single-use elongated housing (including a drug chamber, sleeve, needle assembly, and sheath). In this case, the pre-assembled elongated housing is detachable from a resettable working housing by a mechanism such as those described above and illustrated in Figures 99-100 and 108, thereby allowing for the replacement of the pre-assembled elongated housing (e.g., one per patient). In such embodiments, the drug chamber may be integrally formed with the elongated housing or adapted for the insertion of a syringe or cartridge. In such embodiments, the needle may be integrally formed with the elongated housing, for example, by bonding or injection molding during the formation of the elongated housing. Alternatively, the elongated housing may be adapted for the separate provision and attachment of a needle assembly such as a needle hub as described above. If an elongated housing is adapted to accommodate a drug cartridge (usually pre-filled), it may be advantageous to provide a spring at the proximal end of the needle assembly (whether detachable or not) to press the drug chamber proximal and against the plunger (to assist in needle preparation).

[0203] In configurations where an elongated housing is adapted to accommodate a filled syringe with a needle hub attached, the spring between the syringe and the needle assembly may be replaced by a spring between the proximal end of the elongated housing and the proximal end or flange of the syringe. This proximal spring pushes the syringe distally into contact with the needle assembly, sealing the two together as the needle hub is screwed in. When the needle hub is positioned at the distal end of the syringe, the plunger contacts the stop, pushing the stop forward and consequently preparing the needle. The proximal spring keeps the needle hub in contact with the tip of the syringe, allowing the preparation fluid to be expelled through the needle, and the system is ready when the needle hub is fully positioned.

[0204] In a particular aspect of the present invention, a syringe is provided having an elongated housing having a proximal end and a distal end, the proximal end being detachably attached to an operating mechanism. Here, The elongated housing defines a lumen between its proximal and distal ends, and this lumen is provided with a drug chamber integrally formed with the elongated housing, the drug chamber also having corresponding proximal and distal ends, and a stopper for holding the drug in the drug chamber is provided between the proximal and distal ends; The actuation mechanism comprises an actuation housing having corresponding proximal and distal ends, with the proximal end connected to a dose delivery mechanism and the distal end adapted to engage with the elongated housing. Here, the actuation mechanism includes a plunger. The distal end of the plunger engages with the stop, or is adapted to engage with the stop. The plunger also communicates with a drive spring positioned between it and the proximal end of the actuation housing, which biases the plunger distally when the actuation mechanism has completed preparation for injection. Here, the plunger is held in place against bias by a toggle having distal and proximal ends and is connected to the plunger by a pivot point located between the distal and proximal ends. The toggle has an outward-facing projection positioned between the pivot point and the proximal end, which is adapted to engage with an inward-facing projection on or connected to the actuation housing on the opposite side when the actuation mechanism has completed preparation for injection, and holds the plunger in a first non-actuated position. The proximal end of the toggle includes a surface adapted to engage with a complementary surface of the restraint to hold the toggle in a non-operating position, thereby holding the outward-facing projection and the inward-facing projection opposite to it in an engaged position. Here, when induced, the restraint transitions from a non-operating position or configuration to an operating position or configuration, thereby allowing the toggle to flex to the operating position, thereby disengaging the engagement between the outward-facing projection and the inward-facing projection opposite to it, and releasing the plunger so that it can move distally; The elongated housing comprises a sleeve, which is at least adapted to slide proximal between the elongated housing and the drug chamber, and is adapted to engage with the restraint such that the proximal movement of the sleeve causes the proximal movement of the restraint; The distal end of the elongated housing is provided with a needle assembly including a needle and sheath, which is bonded to or injection-molded to the distal end of a drug chamber integrally formed with the elongated housing. The sheath is adapted to engage with the distal end of the sleeve. Here, the sheath is slidable at least proximal to the needle, so that during insertion of the needle into a subject, the needle is disengaged from the sheath, the sleeve slides proximal, and as a result the restraint moves proximal from a non-operating position to an operating position, disengaging the engagement between the outward-facing projection and the opposite inward-facing projection, releasing the plunger so that it moves distally; Here, the dosage delivery mechanism comprises a first internal knob, a second external dosage setting knob, and a dosage delivery housing adapted for mounting on the proximal end of the operating housing, wherein the proximal end of the plunger engages with the first knob via a screw with an axial:longitudinal pitch X, the first knob engages with the second knob axially but not longitudinally, and the second external dosage setting knob engages with the dosage delivery housing via a screw with an axial:longitudinal pitch Y, where pitch Y is greater than pitch X, so that when the second external dosage setting knob is rotated axially, the axial rotation is the same as that of the first knob, but the longitudinal movement of the second external dosage setting knob is greater than that of the first knob; Here, the operating mechanism comprises a restraint and a restraint toggle having an interacting surface. The interacting surface is configured such that when the plunger is moved proximal against the biasing force of the drive spring and the first and second surfaces are again in the engaged position, the toggle returns to the deactivated position, and the restraint is configured to return to the deactivated position or configuration to restrain the toggle again in the deactivated position and be ready to be triggered again.

[0205] In another particular aspect of the present invention, a syringe is provided having an elongated housing having a proximal end and a distal end, the proximal end being detachably attached to an operating mechanism. Here, The elongated housing defines a lumen between its proximal and distal ends. This lumen contains a separately formed drug cartridge. The drug chamber also has corresponding proximal and distal ends, and a stopper between its proximal and distal ends for holding the drug in the drug cartridge; The actuation mechanism has corresponding proximal and distal ends and comprises an actuation housing having a proximal end connected to a dose delivery mechanism and a distal end adapted to engage with the elongated housing. Here, the actuation mechanism includes a plunger, the distal end of which engages with or is adapted to engage with the stop. The plunger is also positioned between the proximal end of the actuation housing and communicates with a drive spring that biases the plunger distally when the actuation mechanism has finished preparing for injection. Here, the plunger has a distal end and a proximal end and is held in a position against the bias by a toggle connected to the plunger by a pivot point located between the distal and proximal ends. The toggle has an outward projection positioned between the pivot point and the proximal end and is adapted to engage with an inward projection on or on the opposite side connected to the actuation housing in order to hold the plunger in a first non-actuated position when the actuation mechanism has finished preparing for injection. The proximal end of the toggle includes a surface adapted to engage with a complementary surface of the restraint to hold the toggle in a non-operating position, thereby holding the outward-facing projection and the opposite inward-facing projection in an engaged position. Here, when induced, the restraint transitions from a non-operating position or configuration to an operating position or configuration, thereby allowing the toggle to flex to the operating position, thereby disengaging the engagement between the outward-facing projection and the opposite inward-facing projection, releasing the plunger and allowing it to move distally; The elongated housing is at least adapted to slide proximal between the elongated housing and the drug cartridge, and includes a sleeve adapted to engage with the restraint such that the proximal movement of the sleeve causes the proximal movement of the restraint; The distal end of the elongated housing is provided with a needle assembly integrally formed with the elongated housing, and one or more needles are provided extending distally and proximal from the needle assembly, and the needle assembly is also provided with a sheath. The sheath is adapted to engage with the distal end of the sleeve. Here, the sheath is slidable at least proximal to the needle, so that the needle is released from the sheath during insertion of the needle into the subject, and so that the sleeve slides proximal. As a result the restraint moves proximal from a non-operating position to an operating position, disengaging the engagement between the outward projection and the inward projection on the opposite side, and releasing the plunger and moving it distally. Here, the needle assembly also has a spring at its proximal end adapted to push proximal to the distal end of the drug cartridge. As a result, when the needle assembly is attached to the elongated housing, the partition of the drug cartridge is pierced, the plunger engages with the stopper, and positive pressure is created between the plunger and the needle assembly, causing a small amount of fluid to be discharged from the drug chamber through the needle, thereby preparing the drug. Here, the dosage delivery mechanism comprises a first internal knob, a second external dosage setting knob, and a dosage delivery housing adapted for mounting on the proximal end of the operating housing. Here, the proximal end of the plunger engages with the first knob via a screw with an axial:longitudinal pitch X, which engages with the second external dosage setting knob axially but not longitudinally. The second external dosage setting knob engages with the dosage delivery housing via a screw with an axial:longitudinal pitch Y, where pitch Y is greater than pitch X. Therefore, when the second external dosage setting knob is rotated axially, it produces the same degree of axial rotation as the first knob, but the longitudinal movement of the second external dosage setting knob is greater than that of the first knob. Here, the actuation mechanism comprises a restraint and a restraint toggle having an interaction surface. The interaction surface is configured such that when the plunger is moved proximal against the biasing force of the drive spring and the first and second surfaces are again in the engaged position, the toggle returns to the deactivated position, and the restraint is configured to return to the deactivated position or configuration to restrain the toggle again in the deactivated position and be ready to be triggered again.

[0206] In other embodiments, the syringe according to the present invention can be adapted for multiple injections from the same drug chamber, adapted for injections of different drugs, or can be fully reusable (except for the drug chamber and needle). In such embodiments, the elongated housing needs to be adapted so that a needle assembly, such as the needle hub described above, can be interchangeably mounted, or so that syringes or cartridges, such as pre-filled syringes or cartridges, can be interchangeably inserted one at a time for each injection. In certain embodiments, such an elongated housing is pre-assembled with a large-capacity drug chamber (which may or may not be integrated), has a resettable operating mechanism, allows for multiple injections from a single drug chamber, and the needle hub is replaced only between injections. In other embodiments, the elongated housing is adapted to interchangeably house syringes, such as pre-filled syringes (which may have their own needles), or to house drug cartridges, to which a separately provided needle assembly, such as the needle hub described above, can be detachably mounted.

[0207] The components of the syringe according to the present invention may be sterilized by any method known in the art, such as autoclave sterilization, gamma irradiation sterilization, or ethylene oxide sterilization. Specifically, the needle assembly including the needle hub described herein, as well as the elongated housing (and its components) and plunger, may be sterilized and made from suitable materials known in the art. For example, but not limited to, springs, housings, plungers, and retaining arms / toggles intended for repeated reuse may be made from stainless steel, while most components may be made from suitable plastics such as polycarbonate (PC), acetonitrile butadiene styrene (ABS), PC / ABS composites, acetal (polyoxymethylene), or nylon. Certain needle hub components, such as the needle cap, may be made from similar plastics, or from polypropylene, polyisoprene, or thermoplastic viscoelastic materials. Needle valves, such as duck valves, are typically made of silicone. The filter used in the needle hub according to the present invention may be made from paper or other suitable polymer-insoluble porous material, as described above. Various drug chambers are typically made of glass (which may be spray-coated or baked with silicone) or heat-resistant plastic and usually feature a stopper or septum made of suitable rubber such as chlorobutyl rubber or brominated butyl rubber. When intended to integrally form the drug chamber within an elongated housing, these may be made, for example, from a cyclic olefin polymer.

[0208] Further aspects of the present invention are described below. Appearance 1. A syringe comprising an elongated housing having a proximal end and a distal end, wherein the proximal end is equipped with an operating mechanism, and here, The elongated housing defines a lumen between the proximal and distal ends, the lumen being adapted to receive and hold a drug chamber in a fixed position relative to the operating mechanism, the drug chamber containing or adapted to contain an active drug for injection into a subject, the drug chamber also having corresponding proximal and distal ends, and having a stopper between the proximal and distal ends for holding the drug in the drug chamber, and the distal end containing or adapted to fluid communication with a needle, The actuation mechanism also comprises a corresponding proximal and distal end, and an actuation housing having a proximal end and a distal end adapted to engage with the elongated housing, wherein the actuation mechanism comprises a plunger, the distal end of the plunger engaging with or adapted to engage with the stop, the proximal end of the plunger communicating with a first spring, the spring being positioned between the plunger and the proximal end of the actuation mechanism housing, and being under stress when the actuation mechanism is ready for injection. Herein, the plunger is held in a position against the stress by a retaining arm or toggle, the biasing force is directed outward from the plunger, the retaining arm or toggle has a plunger engaging means, where the retaining arm or toggle engages with the plunger when the operating mechanism has completed preparation for injection, and the retaining arm or toggle is held in the plunger engaged position against the biasing force by a restraint that, when triggered, moves from a restrained position or configuration to a released position or configuration, the syringe. Appearance 2. The syringe according to embodiment 1, wherein the restraint device transitions from a restraining position or configuration to a release position or configuration by a mechanism that is activated when the needle connected to the syringe reaches a desired injection depth. Appearance 3. A syringe according to embodiment 1 or embodiment 2, wherein the elongated housing is slidable at least in the proximal direction relative to the elongated housing, and also includes a sleeve that slides proximal when a needle connected to the syringe is inserted into a subject. Appearance 4. A syringe according to embodiment 3, wherein proximal movement of the sleeve results in proximal movement of the restraint. Appearance 5. Syringe according to embodiment 4, wherein the restraint is in a restrained position when distal and in a released position when proximal, and when the sleeve is slid proximal to the elongated housing during use, the restraint moves proximal, thereby releasing the retaining arm or toggle and bending away from the plunger, allowing the first spring to drive the plunger and stopper distally. Appearance 6. Syringe of Embodiment 5, wherein, at least when in use, the distal end of the syringe comprises a sheath enclosing at least the distal portion of a needle assembly that is in fluid communication with the drug chamber, the sheath being an integral part of the sleeve or adapted to engage with the distal end of the sleeve and adapted to slide between the elongated housing and the drug chamber, and wherein the sheath is slidable at least proximal to the needle to pull the needle out of the sheath when inserting the needle into a subject and to move the sleeve proximal, thereby moving proximal to a position where the retaining means releases the retaining arm or toggle. Appearance 7. A syringe according to embodiment 6, wherein the sleeve and sheath are held in a position surrounding the needle by a second spring pressurized between the operating housing and the sleeve, and the second spring is adapted to engage with the second spring. Appearance 8. A syringe according to embodiment 6, wherein the sheath is provided with a pressurized biasing means between the distal portion of the sheath and the needle assembly so that the sheath reliably covers the tip of the needle. Appearance 9. A syringe according to any one of embodiments 6 to 8, wherein the retaining arm or toggle, when released, is adapted to stop the proximal movement of the sleeve and sheath after the sleeve and sheath have returned to a position surrounding the needle. Appearance 10. A syringe according to any one of embodiments 1 to 9, wherein the retaining arm or toggle comprises at least one biasing arm, one end of the at least one biasing arm connected to the proximal end of the operating mechanism housing, and the other end of the at least one biasing arm comprises an inward projection adapted to engage with a complementary outward projection on the plunger, the outward projection optionally formed as a groove in the plunger or a ridge on the plunger. Appearance 11. A syringe according to any one of embodiments 1 to 10, wherein the operating mechanism housing and the elongated housing are detachable from each other, and a drug chamber can be placed in, removed from, or replaced in the elongated housing. Appearance 12. A syringe according to embodiment 11, wherein the drug chamber is pre-filled and optionally filled under vacuum or without voids. Appearance 13. A syringe according to embodiment 12, wherein positive pressure is generated in the drug chamber or operating mechanism by the engagement of the plunger and the stopper, the arrangement of the drug chamber in the elongated housing, and the connection of the operating housing to the elongated housing. Appearance 14. A syringe according to embodiment 13, wherein when the needle is positioned in fluid communication with the distal end of the drug chamber, the positive pressure causes a small amount of fluid to be discharged from the drug chamber through the needle, thereby filling the needle with the drug. Appearance 15. A syringe according to any one of embodiments 1 to 14, wherein the distal end of the drug chamber is adapted for the attachment of a needle assembly. Appearance 16. A syringe according to any one of embodiments 1 to 14, wherein the distal end of the elongated housing is adapted for mounting a needle assembly and allows for fluid communication between the drug chamber and the needle. Appearance 17. A syringe according to embodiment 15 or 16, wherein the needle assembly is attached to the distal end of the drug chamber or the elongated housing by screw means or a Luer lock mechanism. Appearance 18. The syringe according to any one of embodiments 1 to 14, wherein the needle forms at least an integral part of the drug chamber. Appearance 19. The needle forms an integral part of the elongated housing, and the syringe is according to any one of embodiments 1 to 14. Appearance 20. A syringe according to any one of the embodiments 1 to 17, An elongated housing including an inner sleeve (the housing and sleeve define a lumen adapted for receiving a drug chamber); An operating mechanism housing that can be attached to and connected to the proximal end of the elongated housing; and optionally, Assembly of a needle that can be detachably attached to and connected to the distal end of the elongated housing or the drug chamber. A syringe comprising, wherein the needle assembly comprises a sheath adapted to engage with the distal end of the sleeve and adapted to slide between the elongated housing and the drug chamber, wherein the sheath is slidable at least proximal to the needle to pull the needle out of the sheath when inserting the needle into a subject and to slide the sleeve proximal, thereby moving proximal to a position where the restraint releases the retaining arm or toggle. Appearance 21. A syringe according to any one of embodiments 1 to 20, wherein the operating housing comprises a proximal and distal portion engaged via adjustable means, thereby allowing the distance between the proximal and distal ends of the operating housing, and consequently the allowable travel distance of the plunger, to be set to a predetermined distance, thereby allowing a predetermined amount of drug to be released when the syringe is operated. Appearance 22. A syringe according to any one of embodiments 1 to 20, wherein the plunger extends proximal beyond the operating housing and has a proximal end that engages with the cap via an adjustable means, thereby allowing the distance between the cap and the operating housing, and consequently the allowable travel distance of the plunger, to be set to a predetermined distance, thereby allowing a predetermined amount of drug to be released when the syringe is operated. Appearance 23. A syringe according to any one of embodiments 1 to 22, comprising a mechanism for signaling the normal operation of the instrument by auditory, tactile, or visual means. Appearance 24. A syringe for intravitreal injection, comprising a sheath covering at least the distal portion of a needle assembly that is in fluid communication with the drug chamber, wherein the sheath is an integral part of the sleeve or is adapted to engage with the distal end of the sleeve and is adapted to slide between the elongated housing and the drug chamber, wherein the sheath is slidable at least proximal to the needle to withdraw the needle from the sheath and slide the sleeve when the needle is inserted into a subject, thereby moving the sleeve proximal to the restraint, which moves the restraint to a position that releases the retaining arm or toggle, wherein the sheath has a distal eye contact surface, according to any one of embodiments 1 to 23. Appearance 25. The eye contact surface has an outer circumference defining a circle or a deformed circle, and this surface is in the shape of an annular, perforated concave disc, disc-shaped, or three-dimensional annular surface, in which case the needle defines the center of the circle, where the diameter of the circle is 4 to 10 mm, and optionally 6 to 8 mm, in the syringe of embodiment 24. Appearance 26. A syringe according to embodiment 24 or 25, wherein the sheath comprises an external pad that is substantially identical to the eye contact surface for applying pressure adjacent to the injection site after injection. Appearance 27. A needle hub for attachment to a syringe having a needle and a body according to any one of embodiments 12-17 or 20, wherein the body comprises a proximal end from which the proximal end of the needle protrudes proximally and a body from which the injection end of the needle protrudes distally, the proximal end of the body being adapted to engage with the elongated housing or the drug chamber, the needle hub also comprising a sheath covering the needle and body, the proximal end of the sheath being adapted to hold the body of the needle assembly within the sheath, engage with the sleeve of the syringe, and fit and slide within the elongated housing, the needle hub optionally also comprising a cap that completely covers at least the distal end of the needle hub. Appearance 28. A needle hub for attachment to a syringe according to any one of embodiments 12-17 or 20, comprising a body having a proximal body and a distal body, wherein the proximal body is adapted to engage with the elongated housing or the drug chamber and a proximal needle extending therefrom in the proximal direction, the distal body comprises a distal needle extending therefrom in the distal direction, the proximal body and the distal body are adapted to be connected together by a filter enclosed between them and between the two needles, the needle hub also comprises a sheath surrounding the needle and the body, the proximal end of the sheath being adapted to hold the body of the needle assembly within the sheath when not in use, engage with the sleeve of the syringe and fit and slide within the elongated housing. Appearance 29. The needle hub of embodiment 28 wherein the proximal needle has a larger gauge than the distal needle. Appearance 30. The needle hub of embodiment 29, wherein the gauge of the distal needle is 25 (outer diameter approximately 0.5 mm) or less, preferably 27 (outer diameter approximately 0.4 mm) or less. Appearance 31. The needle hub according to any one of embodiments 27 to 30, wherein the sheath is substantially cylindrical for most of its length and has a frustoconical distal end. Appearance 32. A needle hub according to any one of embodiments 27 to 30, for intravitreal injection and having a distal eye contact surface. Appearance 33. The eye contact surface has an outer circumference defining a circle or a deformed circle, and this surface is in the shape of an annular, perforated concave disc, disc-shaped, or three-dimensional annular surface, in which case the needle defines the center of the circle, where the diameter of the circle is 4 to 10 mm, optionally 6 to 8 mm, in the needle hub of embodiment 32. Appearance 34. A needle hub according to embodiment 32 or 33, comprising a sheath having an external pad substantially identical to the eye contact surface for applying pressure adjacent to the injection site after injection. Appearance 35. A needle hub according to any one of embodiments 27 to 34, comprising a cap when not in use, the cap being adapted to completely cover at least the distal end of the needle hub, and optionally also comprising means for preventing the cap from rotating axially relative to the body when the needle hub is connected to the syringe. Appearance 36. A delivery device configured to deliver a drug to the anatomical region of a patient, wherein the delivery device is An elongated housing having a proximal end and a distal end, defining a lumen extending between the proximal and distal ends; Displaced within the lumen of the proximal end of the elongated housing and further having corresponding proximal and distal ends, at least one operating mechanism, at least one plunger, and at least one retaining means configured to hold at least one operating mechanism in a first preparatory configuration (wherein the at least one retaining means is in a first position corresponding to the first preparatory configuration, wherein the at least one retaining means restricts the movement of the at least one plunger on at least one operating axis, further wherein the at least one retaining means is configured to be movable to a second position corresponding to a second delivery configuration, further wherein the movement of the at least one plunger is no longer restricted by the at least one retaining means); A chamber configured to contain a drug, having corresponding proximal and distal ends; The device comprises at least one needle hub having at least one needle sheath that is slidable with respect to an axis substantially perpendicular to the patient's anatomical region, the at least one needle being connected to at least one chamber such that the at least one needle is in fluid communication with the at least one chamber, and further comprising at least one needle hub having at least one needle sheath that is slidable with respect to an axis substantially perpendicular to the patient's anatomical region (where this movement allows at least one needle sheath to move between a first non-retained configuration and a second retained configuration); At least one dose selection mechanism (wherein the dose selection mechanism is configured to select a desired dose of a drug) is coupled to the proximal end of the elongated housing and the proximal end of at least one operating mechanism; and The system comprises at least one triggering mechanism having a first non-operating position and a second operating position, configured to trigger a transition of at least one operating mechanism from a first ready configuration to a second delivery configuration, and further configured to communicate with at least one operating mechanism; Herein, when at least one triggering mechanism moves from a first non-operating position to a second operating position, at least one holding means moves from the first position to the second position, triggering the movement of at least one operating mechanism determined by at least one dose selection mechanism, and a corresponding desired dose of drug is discharged from at least one chamber through at least one needle into the patient's anatomical area, in a delivery device. Appearance 37. A delivery device according to embodiment 36, wherein the at least one triggering mechanism is guided to move from a first non-operating position to a second operating position by pressing at least one needle sheath of at least one needle hub against the anatomical area to be injected. Appearance 38. A delivery device according to embodiment 36 or 37, wherein the at least one chamber further has at least one stopper located at at least one of its proximal or distal ends. Appearance 39. The delivery device according to embodiment 38, wherein the at least one stopper is located at both the proximal and distal ends of the at least one chamber. Appropriate behavior 40. A delivery device according to embodiment 38 or 39, wherein the at least one stop portion located at the proximal end is coupled to the at least one plunger. Appearance 41. A delivery device according to any of embodiments 38 to 40, wherein at least one needle of the needle hub is configured to extend through at least one stop portion located at its distal end, thereby facilitating fluid communication between the at least one chamber and the at least one needle. Appearance 42. The delivery device according to embodiment 41, wherein the needle hub comprises at least two needles. Appearance 43. A delivery device according to embodiment 36, wherein the dosage selection mechanism is configured to select the distance between the at least one dosage selection mechanism and the housing, thereby limiting the distance that at least one plunger of the operating mechanism travels to deliver a correlated dose of drug. Appearance 44. The dose selection mechanism is configured to select individual doses, according to any of embodiments 36 to 43 of the delivery device. Appearance 45. The aforementioned at least one dose selection mechanism is A knob having an inner surface and at least one recess positioned on the inner surface and configured to be rotatable about the longitudinal axis of the delivery device; and A housing having at least one knob, having at least one projection distal to the lower surface of the at least one knob, and further having at least one finger configured to fit within a space defined by the inner surface of the at least one knob. The device comprises, wherein the at least one finger further has at least one projection corresponding to a set distance from the at least one projection, and is configured to be received in at least one recess of the at least one knob; Also, Hereinafter, the at least one knob is configured to rotate until at least one finger of the housing is received in at least one recess of the at least one knob, thereby moving the knob further axially away from at least one projection of the at least one housing, forming a distance between the lower surface of the knob and at least one projection of the housing corresponding to the dose of drug to be delivered, according to embodiment 44 of the delivery device. Appearance 46. The at least one operating mechanism is, At least one needle sheath that is slidable with respect to an axis substantially perpendicular to the patient's anatomical region (this sliding motion allows at least one needle sheath to move between a first non-retaining configuration and a second retaining configuration); At least one barrel sheath having a proximal end and a distal end (where at least one spring is located at the proximal end and coupled to the distal end of the at least one needle sheath, so that when the needle sheath moves from a first non-retracted configuration to its second retracted configuration, a corresponding movement of the at least one barrel sheath is induced, thereby compressing at least one of the at least one barrel springs); Having a proximal end and a distal end, and having at least one spring positioned adjacent to a collar located at the proximal end of at least one plunger, and having at least one plunger extending from its distal end into at least one chamber of the delivery device (the at least one plunger and the at least one chamber further extend through the at least one barrel sheath); At least one retaining arm coupled to at least one plunger at a point between the proximal and distal ends of the at least one plunger, and having a first non-operating position and a second operating position; and Coupled to the at least one plunger so as to be slidable along an axis substantially perpendicular to the patient's anatomical region, and having a first position configured to restrict the movement of the at least one retaining arm (thereby holding the at least one retaining arm in its first non-operating position), and further configured to contact the proximal end of the at least one barrel sheath (where such contact causes the at least one locking ring to slide to a second position, thereby abutting against a collar located at the proximal end of the at least one plunger, thereby the at least one plunger - At least one spring located at the proximal end is compressed, and further here the movement of the at least one retaining arm is not restricted, thereby allowing it to move to its second operating position; and further here, as the at least one retaining arm moves from its first non-operating position to its second operating position, at least one spring at the proximal end of the at least one plunger is compressed, and force is applied to the collar of the at least one plunger, thereby causing the distal end of the at least one plunger to move through the chamber and the drug to be discharged from the delivery device) at least one locking ring A delivery device further comprising any of embodiments 36 to 45. Appearance 47. A delivery device according to embodiments 36 to 46, wherein the dosage selection mechanism further incorporates at least one indicator configured to indicate a desired dosage. Appearance 48. A delivery device according to embodiment 47, wherein the at least one indicator is at least one of a visual indicator, a tactile indicator, an auditory indicator, or an electronic signal configured to interface with an application on another electronic device for a dosage located outside the delivery device. Appearance 49. The aforementioned needle sheath cannot be retracted after the dose has been delivered, according to any delivery device of embodiment 36 to 48. Appearance 50. The needle hub is configured to be detachably attached to the housing, a delivery device according to any of embodiments 36 to 49. Appearance 51. A delivery device according to any of embodiments 36 to 50, wherein at least one chamber is a separable cartridge. Appearance 52. The delivery device is a delivery device according to any of embodiments 36 to 51, configured for use with a high-viscosity fluid. Appearance 53. The delivery device is a delivery device according to any of embodiments 36 to 52, configured for use in ophthalmic procedures. Appearance 54. A delivery device configured for delivering a drug to the anatomical region of a patient, wherein the delivery device is An elongated housing having a proximal end and a distal end, and defining a lumen extending between the proximal end and the distal end; At least one chamber configured for containing a drug and located within the lumen of the elongated housing having corresponding proximal and distal ends; A needle hub having at least one needle sheath, coupled to the distal end of the elongated housing and configured for delivering a drug to the patient's anatomical region, wherein at least one needle is coupled to the at least one chamber such that the at least one needle is in fluid communication with the at least one chamber, and further having at least one needle sheath that is slidable with respect to an axis substantially perpendicular to the patient's anatomical region (where this movement allows the at least one needle sheath to move between a first non-retaining configuration and a second retaining configuration); Displaced within the lumen of the elongated housing and around the at least one chamber, at least one barrel sheath having a proximal end and a distal end (where at least one spring is located at the proximal end and coupled at the distal end to the at least one needle sheath, so that when the needle sheath moves from a first non-retained configuration to a second retained configuration, a corresponding axial movement of the at least one barrel sheath is induced, thereby compressing at least one spring of the at least one barrel spring); At least one plunger having a proximal end and a distal end, and positioned adjacent to a collar located at the proximal end of the at least one plunger, and having at least one spring extending into at least one chamber of the delivery device at its distal end (the at least one plunger and the at least one chamber further extend through the at least one barrel sheath); A retaining arm coupled to at least one plunger at a point between the proximal and distal ends of the at least one plunger, and having a first non-operating position and a second operating position; At least one locking ring coupled to the at least one plunger so as to be slidable along an axis substantially perpendicular to the patient's anatomical region, having a first position configured to restrict the movement of the at least one retaining arm (thereby holding the at least one retaining arm in its first non-operating position), and configured to contact the proximal end of the at least one barrel sheath (where such contact causes the at least one locking ring to slide to a second position, thereby contacting a collar located at the proximal end of the at least one plunger, compressing at least one spring located at the proximal end of the at least one plunger, and further here the movement of the at least one retaining arm is not restricted, thereby allowing it to move to its second operating position); At least one knob connected to the proximal end of the at least one plunger, having an inner surface and at least one recess positioned on the inner surface, and configured to be rotatable about the longitudinal axis of the delivery device; and A drug dispensing housing having at least one projection connected to the at least one knob, positioned around the at least one plunger, and distal to the lower surface of the at least one knob. Having; Herein, the at least one knob is configured such that, when rotated, it further moves the knob axially away from at least one projection of the at least one drug dispensing housing, forming a distance between the lower surface of the knob and the at least one projection of the drug dispensing housing corresponding to the dose of the drug to be administered; and further, herein, the at least one retaining arm moves from a first non-operating position to a second operating position, thereby compressing at least one spring at the proximal end of the at least one plunger, applying force to the collar of the at least one plunger, thereby moving the distal end of the at least one plunger through the chamber by a distance corresponding to the distance between the at least one projection of the at least one housing and the lower end of the at least one knob, and discharging the corresponding dose of drug into the patient's anatomical area through at least one needle; a delivery device. Appearance 55. A delivery device according to embodiment 54, wherein the at least one chamber further has at least one stopper at at least one of its proximal or distal ends. Appearance 56. The delivery device according to embodiment 55, wherein the at least one stopper is located at both the proximal and distal ends of the at least one chamber. Appearance 57. A delivery device according to embodiment 55 or 56, wherein at least one stop portion located at the proximal end is coupled to the at least one plunger. Appearance 58. A delivery device according to any of embodiments 56 to 57, wherein at least one needle of the needle hub is configured to extend through at least one stop portion located at the distal end, thereby facilitating fluid communication between the at least one chamber and the at least one needle. Appearance 59. The delivery device according to embodiment 58, wherein the needle hub comprises at least two needles. Appearance 60. The delivery device is configured for selecting individual doses, as described in any of embodiments 54 to 59. Appearance 61. The inner surface of the at least one knob is provided with at least one recess, and the at least one housing is provided with at least one finger configured to fit into a space defined by the inner surface of the at least one knob, wherein the at least one finger further has at least one projection corresponding to a set distance from the at least one projection and is configured to be received in the at least one recess of the at least one knob; also, A delivery device according to embodiment 60, wherein the at least one knob is configured to rotate until at least one finger of the housing is received in at least one recess of the at least one knob, thereby moving the knob further axially away from at least one projection of the at least one housing, forming a distance between the lower edge of the knob and the at least one projection of the housing corresponding to the dose of drug to be delivered. Appearance 62. A delivery device according to embodiments 54-61, further incorporating at least one indicator configured to indicate a desired dosage. Appearance 63. A delivery device according to embodiments 54-62, wherein the at least one indicator is at least one of a visual indicator, a tactile indicator, an auditory indicator, or an electronic signal configured to interface with an application on another electronic device for a dosage located outside the delivery device. Appearance 64. The aforementioned needle sheath cannot be retracted after the dose has been delivered, according to any delivery device of embodiment 54 to 63. Appearance 65. The needle hub is configured to be detachably attached to the housing, a delivery device according to any of embodiments 54 to 64. Appearance 66. A delivery device according to any of embodiments 54 to 65, wherein at least one chamber is a separable cartridge. Appearance 67. The delivery device is a delivery device according to any of embodiments 54 to 66, configured for use with a high-viscosity fluid. Appearance 68. The delivery device is a delivery device according to any of embodiments 54 to 67, configured for use in ophthalmic procedures. Appearance 69. An operating mechanism configured to deliver a selected dose of drug from at least one chamber of the delivery device to the patient's anatomical area via the delivery device, At least one needle sheath that is slidable with respect to an axis substantially perpendicular to the patient's anatomical region (this sliding motion allows at least one needle sheath to move between a first non-retaining configuration and a second retaining configuration); At least one barrel sheath having a proximal end and a distal end (where at least one spring is located at the proximal end and coupled to the distal end of the at least one needle sheath, so that when the needle sheath moves from a first non-retracted configuration to its second retracted configuration, a corresponding movement of the at least one barrel sheath is induced, thereby compressing at least one of the at least one barrel springs); Having a proximal end and a distal end, and having at least one spring positioned adjacent to a collar located at the proximal end of at least one plunger, and having at least one plunger extending from its distal end into at least one chamber of the delivery device (the at least one plunger and the at least one chamber further extend through the at least one barrel sheath); At least one retaining arm coupled to at least one plunger at a point between the proximal and distal ends of the at least one plunger, and having a first non-operating position and a second operating position; and Coupled to the at least one plunger so as to be slidable along an axis substantially perpendicular to the patient's anatomical region, having a first position configured to restrict the movement of the at least one retaining arm (thereby holding the at least one retaining arm in its first non-operating position), and further configured to contact the proximal end of the at least one barrel sheath (where such contact causes the at least one locking ring to slide to a second position, thereby contacting a collar located at the proximal end of the at least one plunger, thereby compressing the at least one spring located at the proximal end of the at least one plunger, and further hereby the movement of the at least one retaining arm is unrestricted, thereby allowing it to move to its second operating position; Here, as the at least one retaining arm moves from its first non-operating position to its second operating position, at least one spring at the proximal end of the at least one plunger is compressed, and force is applied to the collar of the at least one plunger, thereby causing the distal end of the at least one plunger to move through the chamber and the drug to be discharged from the delivery device.) An operating mechanism equipped with this. Appearance 70. A drug delivery mechanism configured to select an appropriate drug dose for delivering a drug to the anatomical region of a patient using a delivery device, At least one knob having an inner surface and at least one recess positioned on the inner surface, and configured to be rotatable about the longitudinal axis of the delivery device; and The present invention comprises at least one housing having at least one projection coupled to the at least one knob and positioned distal to the lower surface of the at least one knob, and further having at least one finger configured to fit within a space defined by the inner surface of the at least one knob; wherein the at least one finger further has at least one projection corresponding to a set distance from the at least one projection and is configured to be received in at least one recess of the at least one knob; Herein, the at least one knob is configured to rotate until at least one finger of the housing is received in at least one recess of the at least one knob, thereby moving the knob further axially away from at least one projection of the at least one housing, forming a distance between the lower surface of the knob and at least one projection of the housing corresponding to the dose of drug to be delivered, in a dosing mechanism. Appearance 71. A system for delivering medication to patients, A delivery device according to any of the embodiments 1 to 70; Electronic devices; and, An application configured to track and store information related to the provision of care. A system that includes these features. Appearance 72. A method for delivering a drug dose to a patient's anatomical region using a delivery device, a. Remove the needle cover from the delivery device; b. Rotate a knob located at the proximal end of the delivery device to select the dosage of the drug, thereby creating a distance between the knob and a projection located on the housing of the delivery device; c. Position the needle sheath adjacent to the surface of the patient's anatomical area; d. The needle sheath is retracted into the body of the delivery device, and the delivery device is pushed down so that the needle is exposed; e. Insert the needle to a depth determined by the retraction of the needle sheath into the body of the delivery device; f. Using the decrease in the distance between the knob and the projection as an indicator of progress, the device waits for the drug to be delivered; g. Remove the needle from the anatomical area of ​​the patient, thereby returning the needle sheath to its original, unretracted position. A method that includes steps.

[0209] Preferred embodiments of the present invention will be described below only as examples, with reference to comparative data, but these examples do not limit the scope or spirit of the present invention in any way. [Examples]

[0210] Example 1 - Method and Materials Experimental data regarding the accuracy of dose delivery and the dose-inducing power were obtained by filling drug cartridges with water or calibrated oil.

[0211] Experiments were conducted on the accuracy of dose delivery using a syringe according to the fifth embodiment, which had a dose delivery mechanism as illustrated in Figure 98. In this experiment, the three variations (IVAI 5.1, 5.2, and 5.3) differed in the threads between the inner knob and the plunger. As a result, in IVAI 5.1, one turn of the knob was required to administer 100 μL, in IVAI 5.2, two turns of the knob were required to administer 100 μL, and in IVAI 5.3, two turns of the knob were required to administer 20 μL. The drive springs of all instruments were the same (Century Springs A89, length 35.05 mm, 1.61 N / mm) and exerted a force of 34.7 N when assembled.

[0212] Experiments on the inducing force were conducted using a syringe according to the fifth embodiment, which has a dosage delivery mechanism as illustrated in Figure 98 or 71.

[0213] After assembling the instrument and attaching the needle hub, the needle was ready. Next, the external knob 500f was rotated to the appropriate position to select the desired dosage. When the test was ready, the instrument was mounted on the upper jaw of a universal (mechanical) testing machine (UTM), and a pre-weighted cup container was mounted on its lower jaw. Next, with the needle positioned to protrude from the hole in the lid, the instrument was lowered at a constant speed until the needle sheath contacted the hard lid of the cup. The UTM continued to press the needle hub against the lid, similar to how a clinician would press an instrument into the patient's sclera, and when the instrument was triggered, fluid was discharged from the cartridge through the needle into the cup. Subsequently, the upper jaw with the instrument mounted rose from the cup, and the needle sheath again covered the distal needle, resulting in a "lockout" state (where the sheath and sleeve could no longer slide proximally). The test instrument was further lowered to confirm that the "lockout" had been performed correctly.

[0214] By measuring the weight of the fluid and cup after injection and subtracting the weight of the cup before injection, the delivered dose and accuracy relative to the value selected by the external knob could be measured. The upper jaw of the UTM has a force sensor that can measure the force applied to the instrument throughout its movement within the UTM, thereby allowing identification of the moment of induction and the force applied at that time. The results obtained are well representative of what the user can obtain. Since all of this is automated, the user does not need to input information about fluid delivery and instrument operating force (other than setting the dose, which is part of this study protocol).

[0215] Example 2 - Dosage accuracy The results obtained are shown in Table 1. Table 1 JPEG2026514682000002.jpg65120

[0216] In comparison, the accuracy and consistency of dosage values ​​described in the literature are significantly inferior. Tables 2-4 show data from three different reports on injection reproducibility: Goldberg RA (Charters L, Ophthalmology Times, November 13, 2021, Report on RA Goldberg's presentation at the 2021 Annual Meeting of the American Ophthalmology Society held in New Orleans); Dingerkus et al. (Dingerkus VLS et al. (2002) Sci Rep. 12(1):18136); and Guest et al. (Guest JM et al. (2022), Int J Retina Vitreous, 8(1):27). Table 2 JPEG2026514682000003.jpg59130Table 3 JPEG2026514682000004.jpg70130

[0217] The Goldberg-1, 2, and 3 values ​​represent results from different methods of using pre-filled syringes (PFS), demonstrating that how the plunger / stop is aligned with the glass dose markings can significantly affect dose accuracy. The Dingerkus-1, 2, 3, and 4 values, from similar tests, also show that how firmly the plunger / stop is pressed at the end of the injection can affect dose accuracy. Table 4 shows estimated values ​​from Guest's publication for pre-filled syringes (PFS), Luer-lock syringes, and similar instruments.

[0218] Table 4 JPEG2026514682000005.jpg69125

[0219] As these data show, the accuracy and variability (standard deviation) of the dosage of the syringe according to the present invention are significantly better than the instruments tested in the papers by Goldberg, Dingerkus, and Guest.

[0220] Example 3 - Inducing force When dispensing water (viscosity 1 cP) or calibrated oil (viscosity 100 cP) using the dosage delivery mechanism illustrated in Figure 98, the average induced force of the syringe according to the fifth embodiment was 1.90 N (standard deviation 0.39 N). There was almost no difference in the induced force when dispensing water or calibrated oil. When dispensing water (viscosity 1 cP) or calibrated oil (viscosity 100 cP) using the dosage delivery mechanism illustrated in Figure 71 (having the same drive spring as IVAI 5.1, 5.2, and 5.3), the average induced force of the syringe according to the fifth embodiment was also very low, at 1.01 N when dispensing water (viscosity 1 cP) and 1.29 N when dispensing calibrated oil (viscosity 100 cP).

[0221] For illustrative purposes, specific embodiments of the present invention have been described herein, but it goes without saying that various modifications can be made without departing from the spirit and scope of the invention.

Claims

1. A syringe comprising an elongated housing having a proximal end and a distal end, wherein the proximal end is equipped with an operating mechanism, and here, The elongated housing defines a lumen between its proximal and distal ends, adapted for receiving and holding a drug chamber for the operating mechanism, and the drug chamber also has corresponding proximal and distal ends, and a stopper between its proximal and distal ends for holding the drug within the drug chamber; The actuation mechanism comprises an actuation housing having corresponding proximal and distal ends, and the proximal end having a distal end adapted to engage with the elongated housing, wherein the actuation mechanism includes a plunger, the distal end of which engages with or is adapted to engage with the stop, and the plunger communicates with at least one drive spring which biases the plunger distally when the actuation mechanism has finished preparing for injection. Herein, the plunger engages with an opposing second complementary surface to hold the plunger against the bias by at least one retaining arm or toggle having at least one first surface adapted to hold the plunger in a first non-operating position when the operating mechanism has completed preparing for injection, the first and second surfaces are held in the engaged position by a restraint that, when induced, transitions from a non-operating position or configuration to an operating position or configuration, thereby disengaging the engagement between the first and second surfaces and allowing the plunger to be released and move distally, in a syringe.

2. The syringe according to claim 1, wherein the restraint device transitions from a non-operating position or configuration to an operating position or configuration by an induction mechanism that is activated when the needle connected to the syringe reaches a desired injection depth.

3. The syringe according to claim 1 or 2, wherein the elongated housing comprises a sleeve that is slidable at least proximal to the slender housing and the drug chamber, and the sleeve is adapted to engage with the restraint such that proximal movement of the sleeve causes proximal movement of the restraint, where operationally, when a needle connected to the syringe is inserted into the surface, the sleeve slides proximal, and as a result the restraint moves proximal to the operational position or configuration.

4. The syringe according to claim 3, wherein the restraint is in the non-operating position distally and in the operating position proximally, so that when the sleeve is slid proximal to the elongated housing during operation, the restraint moves proximal, thereby releasing the retaining arm or toggle, disengaging the connection between the first surface and the second surface, and allowing the at least one drive spring to drive the plunger and stopper distally.

5. A syringe according to any one of claims 1 to 4, comprising a distal end and a proximal end, and a retaining toggle connected to the plunger by a pivot point located between the distal end and the proximal end.

6. The syringe of claim 5, wherein the first surface of the toggle is in the form of an outward projection adapted to engage with an opposing second complementary surface in the form of an inward projection on or connected to the operating housing, and the proximal end of the toggle includes a surface adapted to engage with a complementary surface of the restraint.

7. The syringe according to claim 6, wherein the outward projection is located between the pivot point and the proximal end of the toggle.

8. The syringe according to claim 6 or 7, wherein the induced force required to disengage the engagement between the first surface and the second surface and to release the plunger and move it distally is inversely proportional to an a / b value, where a is the distance between the proximal end of the toggle and the pivot point, and b is the distance between the first surface and the pivot point, and the induced force can be adjusted by adjusting this a / b value.

9. A syringe according to claim 8, configured such that b is substantially smaller than a, for use in injections exhibiting weak inducing force.

10. The syringe according to claim 8, wherein the value obtained by dividing a by b is 1 or greater.

11. The syringe according to any one of claims 1 to 10, wherein the elongated housing comprises a sleeve that is slidable at least proximal to the elongated housing and the drug chamber and is adapted to engage with the restraint, so that proximal movement of the sleeve causes proximal movement of the restraint, and wherein, operationally, the distal end of the elongated housing comprises a needle assembly having a sheath surrounding at least the distal portion of a needle that is in fluid communication with the drug chamber, the sheath being slidable at least proximal to the needle to dislodge the needle from the sheath during insertion of the needle into a subject, so that the sleeve slides proximal and the restraint moves proximal to the operating position.

12. The syringe according to claim 11, wherein the retaining arm or toggle in the operating position is adapted to prevent the sleeve and sheath from moving proximal after the sleeve and sheath have returned to a position where they surround the needle.

13. The elongated housing comprises a sleeve adapted to slide proximal between the elongated housing and the drug chamber, and adapted to engage with the restraint such that the proximal movement of the sleeve causes the proximal movement of the restraint; The distal end of the elongated housing is connected to or adapted to connect to a needle assembly with a sheath, wherein the sheath is slidable at least proximal to the needle to pull the needle out of the sheath during insertion of the needle into a subject and to slide the sleeve proximal, thereby causing the restraint to move proximal from the first non-operating position to the second operating position; The plunger is held in a position resistant to the stress by a toggle having a distal end and a proximal end, and is connected to the plunger by a pivot point located between the distal end and the proximal end, wherein the first surface has the shape of an outward projection located between the pivot point and the proximal end and is adapted to engage with the opposing second complementary surface provided on or connected to the operating housing in the form of a complementary inward projection, and the proximal end of the toggle has a surface adapted to engage with the complementary surface of the restraint when in the non-operating position. A syringe according to any one of claims 1 to 12.

14. The syringe according to any one of claims 11 to 13, wherein the sheath is an integral part of the sleeve.

15. The syringe according to claim 13 or 14, wherein the toggle is biased toward the operating position to ensure that the movement is completed.

16. The syringe according to any one of claims 11 to 15, wherein the sleeve and sheath are held in a position surrounding the needle by at least one sleeve spring that is pressurized against the proximal surface of the sleeve adapted to engage with the second spring.

17. The syringe according to any one of claims 11 to 15, wherein a spring is pressurized between the distal portion of the sheath and the needle assembly to ensure that the sheath covers the tip of the needle.

18. A syringe according to any one of claims 11 to 17, comprising a one-way valve and optionally a duckbill valve in the fluid path between the drug chamber and the distal end of the needle assembly.

19. The syringe according to any one of claims 11 to 18, wherein the sheath is provided with a distal anatomical contact surface that assists in positioning and holding the syringe in a predetermined position.

20. The syringe according to claim 19, wherein the anatomical contact surface comprises one or more of the following: a soft, spongy or rubbery material, an adhesive surface, a rough surface, a protrusion, a raised part or spike, or other tactile elements.

21. The syringe according to claim 19 or 20, wherein the sheath has a distal eye contact surface, and is adapted for intravitreal or suprachoroidal injection.

22. The syringe according to any one of claims 19 to 21, wherein the eye contact surface has an outer circumference defining a circle or a deformed circle, and the eye contact surface is in the shape of an annular, perforated concave disc, disc-shaped, or three-dimensional annular surface, in which case the needle defines the center of the circle, where the diameter of the circle is 4 to 10 mm, optionally 6 to 8 mm.

23. The syringe according to any one of claims 1 to 22, wherein the operating mechanism housing and the elongated housing are detachable from each other, and a drug chamber can be placed in, removed from, or replaced in the elongated housing.

24. The syringe according to any one of claims 1 to 22, wherein the operating mechanism housing and the elongated housing are detachable from each other, and after injection, the elongated housing and drug chamber can be replaced with a new elongated housing assembled with a new drug chamber.

25. The syringe according to any one of claims 1 to 24, wherein the distal end of the elongated housing is equipped with a needle assembly as an integrated part.

26. The syringe according to any one of claims 1 to 24, wherein the distal end of the elongated housing is adapted to be detachably attached by the needle assembly being directly attached to the drug chamber, or by the needle assembly being attached to the elongated housing in a manner that allows fluid communication with the drug chamber.

27. The syringe according to claim 26, wherein when the operating housing is connected to the elongated housing, the plunger engages with the stop portion of the drug chamber, resulting in positive pressure being generated in the drug chamber, its stop portion, the operating mechanism, or any combination thereof.

28. The syringe according to claim 27, wherein when the needle assembly is positioned in fluid communication with the distal end of the drug chamber, the positive pressure causes a small amount of fluid to be discharged from the drug chamber through the needle, thereby preparing the drug.

29. The syringe according to claim 26, wherein the needle assembly is equipped with a spring at its proximal end and is adapted to press proximal to the distal end of the drug chamber, so that when the needle assembly is mounted in the elongated housing, the plunger engages with the stopper, creating positive pressure between the plunger and the needle assembly, as a result a small amount of fluid is discharged from the drug chamber through the needle, thereby preparing the drug.

30. The syringe according to claim 29, wherein the amount of fluid discharged from the drug chamber is adjustable.

31. The syringe according to any one of claims 1 to 26, wherein the position of the plunger is adjustable, and as a result the plunger engages with the stopper, creating positive pressure between the plunger and the needle attached to the elongated housing, and as a result a small amount of fluid is discharged from the drug chamber through the needle, thereby preparing the drug.

32. The syringe according to any one of claims 28 to 31, wherein the needle is part of a needle assembly further comprising a needle cap having a reservoir for receiving excess drug discharged during the preparation of the needle.

33. The syringe according to any one of claims 1 to 32, wherein the dispensing mechanism is adjustablely connected to the plunger at the proximal end of the operating housing so that the distance between the dispensing mechanism and the operating housing, and therefore the allowable travel distance of the plunger, can be set to a specific value, thereby allowing a selected volume of drug to be released in operation.

34. The syringe according to claim 33, wherein the plunger has a proximal end that extends proximal beyond the operating housing and engages with the cap or knob such that the distance between the cap or knob and the operating housing, and therefore the allowable travel distance of the plunger, can be controlled, thereby allowing a selected volume of drug to be delivered by adjusting the cap in operation.

35. The syringe according to claim 33 or 34, wherein the administration mechanism comprises a first internal knob, a second external dose setting knob, and a dose delivery housing adapted for mounting on the proximal end of the operating housing, wherein the proximal end of the plunger engages with the first knob via a screw with an axial:longitudinal pitch X, the first knob engages with the second knob axially but not longitudinally, and the second external dose setting knob engages with the dose delivery housing via a screw with an axial:longitudinal pitch Y, where pitch Y is greater than pitch X, so that when the second external dose setting knob is rotated axially, the same degree of axial rotation occurs as with the first knob, but the longitudinal movement of the second external dose setting knob is greater than that of the first knob.

36. The syringe according to any one of claims 33 to 35, wherein the connection of the administration mechanism to the plunger is configured such that the administration mechanism is reliably set to the "0" setting when assembled and ready for injection.

37. The syringe according to any one of claims 1 to 36, wherein the at least one drive spring is located between the plunger and the proximal end of the operating mechanism housing.

38. The syringe of claim 37, wherein the at least one drive spring comprises a torsion spring pressurized between the operating housing and a torsion nut that engages the plunger with threads, the pitch of the threads defining a mechanical advantage with respect to the transmission of force from the spring to the plunger.

39. The syringe according to any one of claims 1 to 36, wherein the at least one drive spring is offset by and indirectly biases the plunger.

40. The syringe according to claim 39, wherein the offset spring biases the plunger via a lever or gear mechanism that provides a mechanical advantage in transmitting force from the spring to the plunger.

41. A syringe according to any one of claims 1 to 40, comprising a mechanism for signaling one or more of the following: operation of the instrument, completion of injection, confirmation of dosage setting, or lockout of the instrument after injection.

42. The syringe according to claim 41, wherein the signal is auditory, tactile, visual, or electronic, and is optionally configured to interface with one or more instruments or applications.

43. The apparatus of claim 42, wherein the signal is visual and is brought about by the movement of the retaining arm or toggle or the plunger from a non-operating position to an operating position.

44. An apparatus according to any one of claims 1 to 43, which is suitable for single use.

45. The apparatus according to claim 44, comprising an elongated housing having a needle assembly as an integrated component.

46. The apparatus of claim 44 or 45, wherein the operating housing and the elongated housing are adapted so that they cannot be separated once connected.

47. The apparatus according to any one of claims 44 to 46, wherein the operating mechanism, drug chamber, and elongated housing are provided as separate parts for assembly before use.

48. The apparatus according to any one of claims 44 to 46, wherein the drug chamber is an integral part of the elongated housing and is connected to the outer wall of the elongated housing by axially extending ribs, wherein a sleeve adapted for engaging with the restraint is slidably positioned between the chamber and the outer wall of the elongated housing.

49. The device according to any one of claims 1 to 43, adapted for use in multiple patients, multiple injections, or injections of different drugs.

50. The apparatus according to claim 49, comprising a restraint and a restraint arm / toggle configuration that allows the restraint and restraint arm / toggle to be reset to the non-operating position.

51. The device according to claim 49 or 50, comprising a dosing mechanism configured to be reset to a "0" setting after each injection.

52. The device according to any one of claims 49 to 51, wherein the distal end of the elongated housing is adapted to be detachably attached to the needle assembly by attaching the needle assembly to the elongated housing in a manner that the needle assembly is directly attached to the drug chamber or by fluid communication with the drug chamber, thereby allowing separate needle hubs to be used for different patients while injecting doses to different patients from the same drug chamber.

53. The apparatus according to any one of claims 49 to 52, wherein the operating housing and the elongated housing are adapted to be detachably connected, allowing for the insertion or replacement of the drug chamber, or the replacement of the elongated housing with an assembled elongated housing equipped with a new drug chamber.

54. A syringe comprising an elongated housing having a proximal end and a distal end, wherein the proximal end is equipped with an operating mechanism, and here, The elongated housing includes, or defines a lumen adapted to receive and hold, a drug chamber for the operating mechanism between its proximal and distal ends, the drug chamber also having corresponding proximal and distal ends, and having a stopper between its proximal and distal ends for holding the drug within the drug chamber; The actuation mechanism comprises an actuation housing having corresponding proximal and distal ends, and the proximal end having a distal end adapted to engage with the elongated housing, wherein the actuation mechanism includes a plunger, the distal end of which engages with or is adapted to engage with the stopper, and the plunger is in communication with at least one drive spring which biases the plunger distally when the actuation mechanism has completed preparing for injection, wherein the plunger is held in a position against bias by a toggle having a distal end and a proximal end, and is connected to the plunger by a pivot point located between the distal end and the proximal end, the toggle is located between the pivot point and the proximal end Having an outward-facing projection adapted to engage with an inward-facing projection on the opposite side, which is on or connected to the operating housing, the actuation mechanism holds the plunger in a first non-acting position when it has completed preparing for injection, the proximal end of the toggle includes a surface adapted to engage with a complementary surface of a restraint to hold the toggle in a non-acting position, thereby holding the outward-facing projection and the inward-facing projection on the opposite side in an engaged position, wherein, when induced, the restraint transitions from a non-acting position or configuration to an acting position or configuration, thereby allowing the toggle to flex to the acting position, thereby disengaging the outward-facing projection and releasing the distal movement of the plunger; The elongated housing comprises at least a sleeve adapted to slide proximal between the elongated housing and the drug chamber, and is adapted to engage with the restraint such that the proximal movement of the sleeve causes the proximal movement of the restraint; and, The distal end of the elongated housing is connected to or adapted to connect to a needle assembly with a sheath, the sheath being an integral part of the sleeve or adapted to engage with the distal end of the sleeve, wherein the sheath is slidable at least proximal to the needle in order to withdraw the needle from the sheath when inserting the needle into a subject and to slide the sleeve proximal, so that the restraint moves proximal from a non-operating position to an operating position, disengaging the engagement between the outward projection and the opposite inward projection, and the plunger is released and moves distally. syringe.

55. The syringe according to claim 54, wherein the induced force required to disengage the engagement between the first surface and the second surface and to release the plunger and move it distally is inversely proportional to an a / b value, where a is the distance between the proximal end of the toggle and the pivot point, and b is the distance between the first surface and the pivot point, and the induced force can be adjusted by adjusting this a / b value.

56. A syringe according to claim 55, configured such that b is substantially smaller than a, for use in injections exhibiting weak inducing force.

57. The syringe according to claim 56, wherein the value obtained by dividing a by b is 1 or greater.

58. The syringe according to any one of claims 54 to 57, wherein the toggle is biased toward the operating position to ensure that the movement is completed.

59. The syringe according to any one of claims 54 to 58, wherein the retaining arm or toggle in the second operating position is adapted to prevent the sleeve and sheath from moving proximal after the sleeve and sheath have returned to a position where they surround the needle.

60. The syringe according to claim 59, wherein the sleeve and sheath are held in a position surrounding the needle by at least one sleeve spring that is pressurized against the proximal surface of the sleeve, which is adapted to engage with the second spring.

61. The syringe according to claim 59, wherein a biasing means is provided to pressurize between the distal portion of the sheath and the needle assembly, ensuring that the sheath covers the tip of the needle.

62. A syringe according to any one of claims 54 to 61, comprising a one-way valve and optionally a duckbill valve in the fluid path between the drug chamber and the distal end of the needle assembly.

63. The syringe according to any one of claims 54 to 62, wherein the sheath is provided with a distal anatomical contact surface that assists in positioning and holding the syringe in a predetermined position.

64. The syringe according to claim 63, wherein the anatomical contact surface includes one or more of the following: a soft, spongy or rubbery material, an adhesive surface, a rough surface, a protrusion, a raised part or spike, or other tactile elements.

65. The syringe according to claim 63 or 64, wherein the sheath has a distal eye contact surface, and is adapted for intravitreal or suprachoroidal injection.

66. The syringe according to any one of claims 63 to 65, wherein the eye contact surface has an outer circumference defining a circle or a deformed circle, and the eye contact surface is in the shape of an annular, perforated concave disc, disc-shaped, or three-dimensional annular surface, in which case the needle defines the center of the circle, where the diameter of the circle is 4 to 10 mm, optionally 6 to 8 mm.

67. The syringe according to any one of claims 54 to 66, wherein the operating mechanism housing and the elongated housing are detachable from each other, allowing the drug chamber to be placed in, removed from, or replaced in the elongated housing.

68. The syringe according to any one of claims 54 to 67, wherein the operating mechanism housing and the elongated housing are detachable from each other, and after injection, the elongated housing and drug chamber can be replaced with a new elongated housing assembled with a new drug chamber.

69. The syringe according to any one of claims 54 to 68, wherein the distal end of the elongated housing is equipped with a needle assembly as an integrated part.

70. The syringe according to any one of claims 54 to 68, wherein the distal end of the elongated housing is adapted to be detachably attached by the needle assembly being directly attached to the drug chamber, or by the needle assembly being attached to the elongated housing in a manner that allows fluid communication with the drug chamber.

71. The syringe according to claim 70, wherein when the operating housing is connected to the elongated housing, the plunger engages with the stop portion of the drug chamber, resulting in positive pressure being generated in the drug chamber, its stop portion, the operating mechanism, or any combination thereof.

72. The syringe according to claim 71, wherein when the needle assembly is positioned in fluid communication with the distal end of the drug chamber, the positive pressure causes a small amount of fluid to be discharged from the drug chamber through the needle, thereby preparing the drug.

73. The syringe according to claim 70, wherein the needle assembly is equipped with a spring at its proximal end and is adapted to press proximal to the distal end of the drug chamber, so that when the needle assembly is mounted in the elongated housing, the plunger engages with the stopper, creating positive pressure between the plunger and the needle assembly, as a result a small amount of fluid is discharged from the drug chamber through the needle, thereby preparing the drug.

74. The syringe according to any one of claims 54 to 70, wherein the position of the plunger is adjustable, and as a result the plunger engages with the stopper, creating positive pressure between the plunger and the needle attached to the elongated housing, and as a result a small amount of fluid is discharged from the drug chamber through the needle, thereby preparing the drug.

75. The syringe according to any one of claims 72 to 74, wherein the needle is part of a needle assembly comprising a needle cap having a reservoir for receiving excess drug discharged during the preparation of the needle.

76. The syringe according to any one of claims 54 to 75, wherein the dispensing mechanism is adjustablely connected to the plunger at the proximal end of the operating housing so that the distance between the dispensing mechanism and the operating housing, and therefore the allowable travel distance of the plunger, can be set to a specific value, thereby allowing a selected volume of drug to be released in operation.

77. The syringe according to claim 76, wherein the plunger has a proximal end that extends proximal beyond the operating housing and engages with the cap or knob such that the distance between the cap and the operating housing and, therefore the allowable travel distance of the plunger is controlled, thereby allowing the cap to be adjusted operationally to deliver a selected volume of drug.

78. The syringe according to claim 77, wherein adjusting the cap or knob before operation sets the device to deliver a selected volume of drug when it is activated.

79. The syringe according to claim 78, wherein the selected volume can be adjusted in individual increments.

80. The syringe according to claim 76 or 77, wherein the administration mechanism comprises a first internal knob, a second external dose setting knob, and a dose delivery housing adapted for mounting on the proximal end of the operating housing, wherein the proximal end of the plunger engages with the first knob via a screw with an axial:longitudinal pitch X, the first knob engages with the second knob axially but not longitudinally, and the second external dose setting knob engages with the dose delivery housing via a screw with an axial:longitudinal pitch Y, where pitch Y is greater than pitch X, so that when the second external dose setting knob is rotated axially, the same degree of axial rotation occurs as with the first knob, but the longitudinal movement of the second external dose setting knob is greater than that of the first knob.

81. The syringe according to any one of claims 76 to 80, wherein the connection of the administration mechanism to the plunger is configured such that the administration mechanism is reliably set to the "0" setting when assembled and ready for injection.

82. The syringe according to any one of claims 54 to 81, wherein the at least one drive spring is located between the plunger and the proximal end of the operating mechanism housing.

83. The syringe of claim 82, wherein the at least one drive spring comprises a torsion spring pressurized between the operating housing and a torsion nut that engages the plunger with threads, the pitch of the threads defining a mechanical advantage in the transmission of force from the spring to the plunger.

84. The syringe according to any one of claims 54 to 81, wherein the at least one drive spring is offset by the plunger and indirectly biases the plunger.

85. The syringe according to claim 84, wherein the offset spring biases the plunger via a lever or gear mechanism that provides a mechanical advantage in transmitting force from the spring to the plunger.

86. A syringe according to any one of claims 54 to 85, comprising a mechanism for signaling one or more of the following: operation of the instrument, completion of injection, confirmation of dosage setting, or lockout of the instrument after injection.

87. The syringe according to claim 86, wherein the signal is auditory, tactile, visual, or electronic, and is optionally configured to interface with one or more instruments or applications.

88. The apparatus of claim 87, wherein the signal is visual and is brought about by the movement of the retaining arm or toggle or the plunger from a non-operating position to an operating position.

89. An apparatus according to any one of claims 54 to 88, which is suitable for single use.

90. The apparatus according to claim 89, comprising an elongated housing having a needle assembly as an integrated component.

91. The apparatus of claim 89 or 90, wherein the operating housing and the elongated housing are adapted so that they cannot be separated once connected.

92. The apparatus according to any one of claims 89 to 91, wherein the operating mechanism, drug chamber, and elongated housing are provided as separate parts for assembly before use.

93. The apparatus according to any one of claims 89 to 92, wherein the drug chamber is an integral part of the elongated housing and is connected to the outer wall of the elongated housing by axially extending ribs, wherein a sleeve adapted for engaging with the restraint is slidably positioned between the chamber and the outer wall of the elongated housing.

94. The device according to any one of claims 54 to 88, adapted for use in multiple patients, multiple injections, or injections of different drugs.

95. The apparatus according to claim 94, comprising a restraint and restraint arm / toggle configuration that allows the restraint and restraint arm / toggle to be reset to the non-operating position.

96. The device according to claim 94 or 95, comprising a dosing mechanism configured to be reset to a "0" setting after each injection.

97. The device according to any one of claims 94 to 96, wherein the distal end of the elongated housing is adapted to be detachably attached to the needle assembly by attaching the needle assembly to the elongated housing in a manner that the needle assembly is directly attached to the drug chamber or by fluid communication with the drug chamber, thereby allowing separate needle hubs to be used for different patients while injecting doses to different patients from the same drug chamber.

98. The apparatus according to any one of claims 94 to 97, wherein the operating housing and the elongated housing are adapted to be detachably connected, allowing for the insertion or replacement of the drug chamber, or the replacement of the elongated housing with an assembled elongated housing equipped with a new drug chamber.

99. The apparatus according to any one of claims 1 to 98, wherein the distal end of the elongated housing is connected to or adapted to connect to a needle assembly including a needle extending at least distally to the distal end, which is covered with a cap when not in use, the cap being adapted to completely cover the needle extending at least distally, and optionally also comprising means for ensuring that the cap does not rotate axially relative to the body when the needle assembly is connected to the syringe.

100. The device according to claim 99, wherein the cap is provided with a seal into which the distally extending needle is inserted.

101. The device of claim 100, wherein the cap comprises a tip portion held at least partially slidably within a proximal body connected to the elongated housing or needle assembly, wherein the tip portion may slide distally within or at least partially beyond the proximal body, wherein the seal is positioned at the tip portion, and wherein the needle is inserted into the seal before the needle is prepared, and the tip portion does not extend fully distally relative to the proximal body.

102. The apparatus according to claim 101, wherein, once the preparation of the needle is complete, the pressure from the preparation liquid pushes the seal and the tip distally.

103. A needle hub adapted for attachment to a syringe according to any one of claims 1 to 44, 46 to 89, or 91 to 102, and comprising a body from which a needle and the injection end of the needle protrude distally, wherein the proximal end of the needle hub is adapted for connection to an engagement portion so that the needle can be operationally communicated with the drug chamber, and the needle hub also comprises a sheath surrounding the distal needle and the body, the proximal end of the sheath being operationally adapted to hold the body of the needle assembly within the sheath, engage with the sleeve of the syringe, and fit and slide against the syringe when the hub is attached to the syringe.

104. The needle hub according to claim 103, further comprising a proximal end that protrudes in the proximal direction from the proximal end of the needle.

105. Needle hub according to claim 103 or 104, comprising a one-way valve, optionally a duckbill valve, in the fluid path within the body of the needle assembly.

106. A needle hub for attachment to a syringe according to any one of claims 1 to 44, 46 to 89, or 95 to 102, comprising a body having a proximal body and a distal body, wherein the body is connected to a component adapted to engage with the distal end of the elongated housing or drug chamber, or has a proximal end adapted to engage with the distal end of the elongated housing or drug chamber, the proximal body has a proximal needle extending therefrom in the proximal direction, the distal body has a distal needle extending therefrom in the distal direction, the proximal and distal bodies are adapted to be connected to each other by a filter enclosed between them and between the two needles, the needle hub also comprises a sheath surrounding the needle and body, the proximal end of the sheath being adapted to hold the body of the needle assembly within the sheath when not in use, to engage with the sleeve of the syringe, and to fit and slide within the elongated housing.

107. The needle hub of claim 106, wherein the proximal needle has a larger gauge than the distal needle.

108. The needle hub according to claim 107, wherein the gauge of the distal needle is 25 (outer diameter approximately 0.5 mm) or less, preferably 27 (outer diameter approximately 0.4 mm) or less.

109. A needle hub according to any one of claims 106 to 108, comprising a one-way valve and optionally a duckbill valve between the proximal and distal needles in the body of the needle assembly.

110. The needle hub according to any one of claims 106 to 109, wherein the sheath is provided with a distal anatomical contact surface that assists in positioning and holding the syringe in a predetermined position.

111. The needle hub of claim 110, wherein the anatomical contact surface comprises one or more of the following: a soft, spongy or rubbery material, an adhesive surface, a rough surface, a protrusion, a raised portion or spike, or other tactile elements.

112. The needle hub of claim 110 or 111, having a distal eye contact surface, is adapted for intravitreal or suprachoroidal injection.

113. The eye contact surface has an outer circumference defining a circle or a deformed circle, and this surface is in the shape of an annular, perforated concave disc, disc-shaped, or three-dimensional annular surface, in which case the needle defines the center of the circle, where the diameter of the circle is 4 to 10 mm, optionally 6 to 8 mm, a needle hub according to any one of claims 103 to 112.

114. A needle hub according to any one of claims 103 to 113, comprising a cap when not in use, the cap being adapted to completely cover at least the distal end of the needle hub, and optionally also comprising means for preventing the cap from rotating axially relative to the body when the needle hub is connected to the syringe.

115. The needle hub of claim 114, wherein the cap comprises a reservoir for receiving excess drug discharged during the preparation of the needle.

116. The needle hub according to claim 114 or 115, wherein the cap is configured to be detachably attached to the distal end of the needle hub, so that it is removed when the needle hub is operational and attached when the needle hub is not ready for operation.

117. The needle hub of claim 114 or 115, wherein the cap is configured to attach the needle hub to the elongated housing or drug chamber.

118. A needle hub adapted for attachment to a syringe, wherein the syringe includes a drug chamber and an engagement portion enabling connection to the drug chamber, the needle hub comprises a body from which a needle and the injection end of the needle protrude distally, the proximal end of the needle hub is adapted to connect to the engagement portion so that the needle can operately communicate with the drug chamber, the needle hub also includes a sheath surrounding the distal needle and body, the proximal end of the sheath being operationally adapted to hold the body of the needle assembly within the sheath, engage with the sleeve of the syringe, and fit and slide against the syringe when the hub is attached to the syringe, and the needle hub optionally also comprises a cap that completely surrounds at least the distal end of the needle hub.

119. The needle hub of claim 118, wherein the proximal end of the needle protrudes proximally from the proximal end.

120. The needle hub according to any one of claims 114 to 119, wherein the cap is provided with a seal into which the distally extending needle is inserted.

121. The needle hub of claim 120, wherein the cap comprises a tip portion held at least partially slidably within a proximal body connected to the elongated housing or needle assembly, wherein the tip portion may slide distally within or at least partially beyond the proximal body, wherein the seal is located at the tip portion, and wherein the needle is inserted into the seal before the needle is prepared, and the tip portion does not extend fully distally relative to the proximal body.

122. The needle hub according to claim 121, wherein, once the preparation of the needle is complete, the pressure from the preparation liquid pushes the seal and the tip distally.

123. An operating mechanism for a syringe, the operating mechanism having a plunger, the distal end of the plunger being adapted to engage with a stop, and the plunger communicating with at least one drive spring that biases the plunger distally when the operating mechanism has finished preparing for injection. Herein, the plunger is held in a position against the stress by a retaining arm or toggle having at least one first surface adapted to engage with an opposing second complementary surface in order to hold the plunger in a non-operating position when the actuation mechanism has completed preparation for injection, the first and second surfaces are held in the engaged position by a restraint that, when induced, transitions from a non-operating position or configuration to an operating position or configuration, thereby disengaging the engagement between the first and second surfaces, and allowing the plunger to be released and move distally.

124. The operating mechanism of claim 123, comprising a retaining toggle having a distal end and a proximal end, and connected to the plunger by a pivot point located between the distal end and the proximal end.

125. The actuation mechanism of claim 124, wherein the first surface of the toggle is in the form of an outward projection positioned between the pivot point and the proximal end and is adapted to engage with an opposing second complementary surface in the form of an inward projection on or connected to the actuation housing, and the proximal end of the toggle includes a surface adapted to engage with a complementary surface of the restraint.

126. The operating mechanism of claim 124 or 125, wherein the induced force required to disengage the engagement between the first surface and the second surface and to release the plunger and move it distally is inversely proportional to an a / b value, where a is the distance between the proximal end of the toggle and the pivot point, and b is the distance between the first surface and the pivot point, and the induced force can be adjusted by adjusting this a / b value.

127. An operating mechanism according to claim 126, configured such that b is substantially smaller than a, for use in injections exhibiting a weak inducing force.

128. A syringe according to claim 126, wherein the value obtained by dividing a by b is 1 or greater.

129. The operating mechanism according to any one of claims 123 to 128, wherein the arm or toggle is biased toward the operating position to ensure that the movement is completed.

130. The operating mechanism according to any one of claims 123 to 129, wherein the retaining arm or toggle and the operating mechanism housing in the operating position are adapted to prevent proximal movement of the plunger.

131. An operating mechanism according to any one of claims 123 to 130, wherein the dispensing mechanism is adjustablely connected to the plunger at the proximal end of the operating housing so that the distance between the dispensing mechanism and the operating housing, and therefore the allowable travel distance of the plunger, can be set to a specific value, thereby enabling the dispensing of a selected volume of drug in operation.

132. The actuation mechanism of claim 131, wherein the plunger has a proximal end that extends proximal beyond the actuation mechanism housing and engages with the cap such that the distance between the cap and the actuation housing and, therefore the allowable travel distance of the plunger is controlled, thereby allowing the cap to be adjusted operationally to deliver a selected volume of drug.

133. The administration mechanism comprises a first internal knob, a second external dose setting knob, and a dose delivery housing adapted for mounting on the proximal end of the operating housing, wherein the proximal end of the plunger engages with the first knob via a screw with an axial:longitudinal pitch X, the first knob engages with the second knob axially but not longitudinally, and the second external dose setting knob engages with the dose delivery housing via a screw with an axial:longitudinal pitch Y, where pitch Y is greater than pitch X, so that when the second external dose setting knob is rotated axially, it produces an axial rotation of the same degree as the first knob, but the longitudinal movement of the second external dose setting knob is greater than that of the first knob, the operating mechanism of claim 131 or 132.

134. The operating mechanism device according to any one of claims 131 to 133, wherein the connection of the administration mechanism to the plunger is configured such that the administration mechanism is reliably set to the "0" setting when assembled and ready for injection.

135. The actuation mechanism according to any one of claims 123 to 134, wherein the at least one drive spring is positioned between the plunger and the proximal end of the actuation mechanism housing.

136. The actuation mechanism of claim 135, wherein the at least one drive spring comprises a torsion spring pressurized between the actuation housing and a torsion nut that engages the plunger with threads, the pitch of the threads defining a mechanical advantage in the transmission of force from the spring to the plunger.

137. The operating mechanism according to any one of claims 123 to 134, wherein the drive spring is offset by the plunger and indirectly biases the plunger.

138. The actuation mechanism of claim 137, wherein the counteracting spring biases the plunger via a lever or gear mechanism that provides a mechanical advantage in transmitting force from the spring to the plunger.

139. An operating mechanism according to any one of claims 123 to 138, comprising a mechanism for signaling one or more of the following: operation of the device, completion of injection, confirmation of dosage setting, or lockout of the device after injection.

140. The operating mechanism of claim 139, wherein the signal is auditory, tactile, visual, or electronic, and is configured to interface with one or more devices or applications, of any choice.

141. The operating mechanism of claim 140, wherein the signal is visual and is brought about by the movement of the retaining arm or toggle or the plunger from a non-operating position to an operating position.

142. An operating mechanism according to any one of claims 123 to 141, comprising a configuration of a restraint and a restraint arm / toggle that allows the restraint and restraint arm / toggle to be reset to the non-operating position.

143. The actuation mechanism of claim 142, further comprising a retaining toggle configured to interact with complementary characteristic components on the inner wall of the actuation housing such that when the plunger is moved proximal against the biasing force of the drive spring, the toggle returns to its non-actuated position.

144. The actuation mechanism of claim 143, wherein the toggle and restraint are configured to allow the toggle to be re-held and re-restrained so that the toggle returns to its non-acting position and the first and second surfaces are again in the engaged position.

145. The operating mechanism of claim 143 or 144, wherein the interaction surfaces of the toggle, restraint, and operating housing are configured to allow the restraint and toggle to be reset to the non-operating position.

146. An assembly of an elongated housing for use with a syringe according to any one of claims 1 to 102, the assembly of the elongated housing having a proximal end and a distal end defining a lumen between them, wherein the assembly of the elongated housing includes or is adapted to house and hold a drug chamber for the operating mechanism, the drug chamber also having corresponding proximal and distal ends and having a stop between its proximal and distal ends for holding the drug in the drug chamber, wherein the elongated housing also comprises a sleeve that is slidable at least in the proximal direction between the elongated housing and the drug chamber and is adapted to engage with a restraint of the operating housing, wherein the assembly of the elongated housing slides in the proximal direction when a needle connected to the elongated housing is inserted into a subject.

147. Operationally, the distal end of the elongated housing comprises a needle assembly having a sheath that encloses at least the distal portion of the needle that is in fluid communication with the drug chamber, wherein the sheath is an integral part of the sleeve or adapted to engage with the distal end of the sleeve, and wherein the sheath is slidable at least proximal to the needle to dislodge the needle from the sheath during insertion of the needle into a subject, thereby causing the sleeve to slide proximal, according to claim 146.

148. The elongated housing of claim 147, wherein the distal end of the elongated housing is connected to or configured to be connected to the needle assembly.

149. An elongated housing according to any one of claims 146 to 148, suitable for single use.

150. The elongated housing according to claim 149, comprising an elongated housing having a needle assembly as an integrated component.

151. The elongated housing and the operating housing, once connected, are not separable, according to claim 149 or 150.

152. An elongated housing according to any one of claims 146 to 151, wherein the drug chamber is formed as an integral part of the elongated housing and is connected to the wall of the elongated housing by ribs extending inward in the axial direction, wherein the sleeve is slidably positioned between the chamber and the wall of the elongated housing.

153. An elongated housing according to any one of claims 146 to 152, adapted for use in multiple patients, multiple injections, or injections of different drugs.

154. The elongated housing of claim 153 is adapted to be detachably attached to a needle assembly by either attaching the needle assembly directly to the drug chamber or by attaching the needle assembly to the elongated housing in a manner that allows fluid communication between the needle assembly and the drug chamber, thereby enabling the use of separate needle hubs for different patients while injecting doses into different patients from the same drug chamber.

155. The elongated housing of claim 153 or 154 is adapted to be detachably connected to the operating housing, allowing for the insertion or replacement of the drug chamber, or the replacement of the elongated housing with an assembled elongated housing equipped with a new drug chamber.

156. The distal end of the elongated housing is connected to, or adapted to be connected to, a needle assembly including a needle that extends at least distally to the distal end, which is covered with a cap when not in use. The elongated housing of any one of claims 146 to 155, wherein the cap is adapted to completely cover a needle that extends at least distally, and optionally also includes means for ensuring that the cap does not rotate axially relative to the body when the needle hub is connected to the syringe.

157. The elongated housing of claim 156, wherein the cap is provided with a seal into which the distally extending needle is inserted.

158. The elongated housing of claim 157, wherein the cap comprises a tip portion held at least partially slidably within a proximal body connected to the elongated housing or needle assembly, wherein the tip portion may slide distally within or at least partially beyond the proximal body, wherein the seal is positioned at the tip portion, and wherein the needle is inserted into the seal before the needle is prepared, and the tip portion does not extend fully distally relative to the proximal body.

159. The elongated housing of claim 158, wherein, once the preparation of the needle is complete, the pressure from the preparation liquid pushes the seal and the tip distally.

160. A dosage delivery mechanism for a syringe, wherein the syringe comprises a body having a distal end to which a needle assembly is attached, and a proximal end comprising an operating mechanism including a plunger having a distal end and a proximal end, the syringe further comprising a drug chamber also having a distal end and a proximal end, and comprising a stop between the distal end and the proximal end and the drug between the stop and the distal end of the drug chamber, wherein the distal end of the plunger is adapted to engage with the stop, and wherein the dosage delivery mechanism is adjustablely connected to the proximal end of the plunger, thereby setting a selected volume of drug for delivery by setting the distance between the delivery mechanism and the body of the instrument, and thus the allowable travel distance of the plunger, to a specific value.

161. The dosage delivery mechanism of claim 160, wherein the plunger has a proximal end that extends proximal beyond the body of the instrument and is adjustablely engaged with the knob or cap so that the distance between the knob or cap and the body of the instrument can be adjusted, thereby controlling the allowable travel distance of the plunger, and by adjusting the knob or cap, a selected volume of drug for delivery can be set.

162. The dosage delivery mechanism according to claim 160 or 161, wherein the connection of the administration mechanism to the plunger is configured such that the administration mechanism is reliably set to an initial set value when assembled and ready for injection.

163. A dosage delivery mechanism according to any one of claims 160 to 162, comprising a first internal knob, a second external dose setting knob, and a dose delivery housing adapted for mounting on the proximal end of the body of the instrument, wherein the proximal end of the plunger engages with the first knob via a first screw with an axial:longitudinal pitch X, the first knob engages with the second knob axially but not longitudinally, and the second external dose setting knob engages with the dose delivery housing via a second screw with an axial:longitudinal pitch Y, where pitch Y is greater than pitch X, so that when the second external dose setting knob is rotated axially, it produces an axial rotation of the same degree as the first knob, but the longitudinal movement of the second external dose setting knob is greater than that of the first knob.

164. The dosage delivery mechanism according to claim 163, wherein the vertical position of the plunger is adjusted by the first knob until there is no substantial play between the first knob and the body of the injection device and between the operating mechanism and the plunger.

165. Operationally, the second knob is assembled to the dosage delivery housing via a second thread and adjusted to indicate an initial value in the window of the dosage delivery housing, and the assembled second knob and the dosage delivery housing are mounted on the first knob such that the initial value remains within the window of the dosage delivery housing and the first and second knobs are axially engaged, thereby positioning the dosage delivery mechanism to an initial state corresponding to the initial value, and preparing for dosage setting by adjusting the second knob within the dosage delivery housing, according to claim 164.

166. The dosage delivery mechanism of claim 165, wherein the initial value is zero.

167. The dosage delivery mechanism according to any one of claims 162 to 166, wherein assembling the second knob to the first knob such that the initial value is displayed in the window of the dosage delivery housing is independent of its rotational position about the longitudinal axis of the syringe.

168. The distal outer surface of the first knob is provided with a projection or protrusion that engages with a complementary protrusion or projection on the proximal surface of the body of the instrument, such that the axial rotation of the first knob is stepwise and not free, thereby allowing the dosage to be set in stepswise and individual amounts, and once the first knob is adjusted to the desired setting, it does not move freely in the axial direction, the dosage delivery mechanism according to any one of claims 163 to 167.

169. The dosage delivery mechanism according to any one of claims 163 to 168, wherein the syringe is the syringe according to any one of claims 1 to 102.

170. A method for operating a syringe, wherein the syringe comprises an elongated housing having a proximal end and a distal end, the proximal end having an operating mechanism, and the distal end having or being adapted to have a needle, and the syringe further comprises a drug chamber having a stopper, The actuation mechanism includes a plunger, the distal end of which is adapted to engage with the stopper, and when the actuation mechanism has completed preparation for injection, the plunger is biased toward the distal end, and the plunger is held in a position against this bias by a retaining arm or toggle, thereby holding the plunger in a non-actuated position when the actuation mechanism has completed preparation for injection, and the plunger is held in an engaged position by a restraint adapted to transition from a non-actuated position or configuration to an actuated position or configuration when triggered. The method includes placing the device in an operating position, inducing the restraint to release the plunger from the engaged position, and then moving the plunger distally to deliver the drug from the drug chamber. method.

171. The method of claim 170, wherein the apparatus further includes a needle, and the apparatus is prepared such that a drug is filled into the needle before inducing the restraint.

172. The method of claim 170 or 171, further comprising the step of selecting a desired dose by adjusting the proximal cap, wherein a selectively adjustable proximal cap is provided, before inducing the restraint.

173. The method of any one of claims 170 to 172, wherein the step of setting the instrument to the operating position further includes positioning the instrument adjacent to a desired anatomical location in the patient.

174. The method according to any one of claims 166 to 168, further comprising the step of aligning and engaging a positioning structure or alignment structure provided on the distal side of the syringe with respect to the anatomical features of the patient.

175. The method of any one of claims 170 to 173, wherein the syringe comprises a movable distal projection and a needle, and the step of inducing the restraint is initiated by engaging the distal projection with the surface of the patient.

176. The method of any one of claims 170 to 174, wherein the syringe further includes a delivered dose indicator, wherein the method further includes the step of activating the delivered dose indicator after the restraint has been induced.

177. The method of claim 170, further comprising the step of resetting the device for reuse after drug delivery.

178. The method according to any one of claims 170 to 177, wherein the restraint and restraint arm / toggle are configured to be reset to a non-operating position.

179. The method of claim 178, wherein the restraint arm / toggle is a toggle and further includes inducing the syringe to return the toggle to its deactivation position and then moving the plunger proximal against the bias of the drive spring, wherein the toggle is configured to return to its deactivation position by interacting with complementary characteristic components on the inner wall of the operating housing, and the toggle and the restraint are configured to re-hold and re-restrain the toggle so that the toggle returns to its deactivation position and the first and second surfaces are again in the engaged position.

180. The method of claim 179, wherein the interaction surfaces of the toggle, restraint and operating housing are configured to allow the restraint and toggle to be returned to a non-operating position.

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