Assemblies for and methods of intraocular injection. An injector assembly includes a housing defining an internal chamber and having a slot on an external surface thereof; a cannula needle having a lumen and a cutout on an outer surface; a flexible arm having a proximal end affixed to the outer surface of the cannula needle and a distal end having a hook such that the hook is disposed within the cutout; a pushrod slidably disposed within the lumen; and a latch slidably disposed in the slot of the housing, the latch coupled to the pushrod such that translation of the latch causes translation of the pushrod to thereby eject an implant disposed within the lumen between the hook and pushrod.

FIELD OF THE INVENTION

Embodiments of the present disclosure relate to intraocular injectors.

BACKGROUND

The human eye is a highly evolved and complex sensory organ. Damage to any of its essential structures can result in impairment of vision. Treatments of various eye conditions and diseases often consist of applying doses of appropriate medications in aqueous suspension solutions or ointments. While such treatments are satisfactory for conditions that require only one or a few applications of the medicinal agents, certain conditions require more frequent doses and such treatments are inconvenient to patients. In contrast, ophthalmic medicinal agents in solid implant forms allow a high weight of drug per administered volume. This is particularly advantageous when a large amount of drug must be administered over a period of time per dose or when the volume is constrained, as in intraocular injections. Additionally, the solid state also renders the compound less sensitive to solution-mediated chemical degradation.

Direct injection into a sensitive and delicate structure like the eye has certain challenges and attendant difficulties. There are a number of procedures and devices that have been developed for the controlled injection of an implant into a tissue, such as an eye. However, improved procedures and devices would be beneficial.

BRIEF SUMMARY

According to embodiments of the present disclosure, assemblies for and methods of intraocular injection are provided. In various embodiments, an injector assembly includes a housing defining an internal chamber. The housing has a proximal end and a distal end including a distal opening. The housing has a slot on an external surface thereof between the proximal end and distal end. The injector assembly further includes a cannula needle having a proximal end disposed within the housing and extending at least partially through the distal opening to a distal end. The cannula needle has a lumen extending therethrough. The cannula needle has a distal bevel at the distal end and a proximal opening at the proximal end. The cannula needle has a cutout on an outer surface. The injector assembly further includes a flexible arm having a proximal end and a distal end, where the proximal end of the flexible arm is affixed to the outer surface of the cannula needle and the distal end of the flexible arm has a hook. In various embodiments, the hook prevents the payload (e.g., an implant) from falling out of the cannula needle prematurely. The hook is disposed within the cutout. The injector assembly further includes a pushrod slidably disposed within the lumen and the pushrod extends at least partially through the distal end of the cannula needle. The injector assembly further includes a latch slidably disposed in the slot of the housing. The latch is coupled to the pushrod such that translation of the latch causes translation of the pushrod.

In various embodiments, a needle subassembly includes a cannula needle having a proximal end, a distal end, and a lumen extending therethrough. The cannula needle has a distal bevel at the distal end and a proximal opening at the proximal end. The cannula needle has a cutout in an outer surface. The needle subassembly further includes a flexible arm having a proximal end and a distal end, where the proximal end of the flexible arm is affixed to the outer surface of the cannula needle and the distal end of the flexible arm has a hook. The hook is disposed within the cutout. The needle subassembly further includes a pushrod slidably disposed within the lumen and the pushrod extends at least partially through the distal end of the cannula needle. The needle subassembly further includes an implant disposed proximal to the hook and distal to the pushrod.

In various embodiments, a method of inserting an implant into an eye includes providing an injector assembly, inserting the distal end of the cannula needle into an eye, positioning the cannula needle at a target location within the eye, sliding the latch towards the distal end of the housing to thereby advance the pushrod against the implant, displacing the hook, until the implant is ejected from the needle cannula.

DETAILED DESCRIPTION

The assemblies, subassemblies, and methods described herein provide an injector device capable of delivering an implant into a tissue (e.g., ocular tissue). Traditional injector devices are uncomfortable to use due to a number of factors including size of the device and ergonomics of the control mechanism (e.g., button) that provides for ejection of an implant to be delivered. For example, the force to eject the implant may be enough that the process of ejection is uncomfortable for an average user (e.g., a healthcare provider) and/or the position of the ejection button makes use of the device uncomfortable for the user. Moreover, many commercial injectors have overly-complicated mechanisms which may cause issues at any time during the procedure, including during the critical time frame when the injector is inserted into the vitreous chamber of the eye, but prior to ejection of the implant at the target location. Additionally, many commercial injectors have issues with the payload (e.g., an implant) falling out of the cannula needle prior to insertion into the eye, which results in expensive monetary losses. Moreover, due to the small size of the payload, the physician may not notice if the payload is prematurely ejected (e.g., falls out) out of the device and may proceed with piercing the tissue thereby delivering nothing.

In certain embodiments, the injector device is fitted with a slidable latch coupled to a pushrod and a flexible arm having a hook that is disposed within a cutout of a needle cannula to thereby prevent premature ejection of the implant. When the latch is pushed forward by the force of a user's finger, the pushrod advances an implant through the cannula needle, displacing the hook out of the cutout, until the implant is ejected out of the cannula needle. It will be understood by one of ordinary skill in the art that the device and method described herein can be adapted and modified for other suitable applications and that such other additions and modifications will not depart from the scope hereof.

FIGS.1A-1Dillustrate an intraocular injector assembly100in accordance with an embodiment of the present disclosure. In various embodiments, the injector assembly100includes a housing102. In various embodiments, the housing102may be made from one or more (e.g., two) components. For example, in the embodiment shown inFIGS.1A-1D, the housing102includes two halves affixed to one another. In various embodiments, the housing102may be made from a polymer. In various embodiments, the housing102may be made by injection molding or 3D printing. In various embodiments, proximal and distal may be defined relative to the user such that distal is away from the user and proximal is closer to the user. Alternatively, in various embodiments, proximal and distal may be defined relative to the patient such that proximal is away from the user and distal is closer to the user. In various embodiments, the housing102includes a distal opening from which a cannula104needle may extend and a proximal end near the user.

In various embodiments, the cannula needle104extends at least partially out of the distal opening of the housing102to a distal end105which includes a beveled (e.g., sharpened) edge configured to pierce a tissue (e.g., sclera, conjunctival tissue, etc.). In various embodiments, the cannula needle104is fixed relative to the housing102; optionally, the cannula needle104can be adjustable in length relative to the housing102(e.g. the needle104can be retractable within the housing102). In various embodiments, the beveled edge may have an angle from the horizontal (i.e., longitudinal axis of cannula needle) of about 5 degrees to about 35 degrees. Preferably, the bevel has an angle from the horizontal of about 11 degrees. The angle can be constant, resulting in a linear edge, or non-linear with various points of inflection along the outer face of the needle. In various embodiments, as described with respect toFIG.2, the cannula needle104may be housed at least partially inside the housing102. In various embodiments, the cannula needle may have a length of about 20 mm to about 500 mm suitable for ejecting an implant at a target location within the eye (e.g., the vitreous chamber). In various embodiments, the length of the cannula needle may be any suitable length such that the cannula needle may be inserted at least 8 mm into the eye.

In various embodiments, the injector assembly100may further include a needle stop106positioned at the distal opening of the housing102. The needle stop106may extend at least partially out of the distal opening of the housing102and be configured to indicate to a user an optimal insertion depth for the cannula needle. In various embodiments, the optimal insertion depth of the cannula needle104may be about 3 mm to about 100 mm. Preferably, the optimal insertion depth may be about 3 mm to about 10 mm. Most preferably, the optimal insertion depth may be about 3 mm to about 8 mm. In various embodiments, the size of the cannula needle104may be about 21 gauge to about 28 gauge. Preferably, the size of the cannula needle104may be about 22 gauge to about 27 gauge.

In various embodiments, the injector assembly100includes a latch108extending from the housing102and configured to translate within a slot109formed in the housing102. In various embodiments, as described in more detail below, the latch108is coupled to a pushrod configured to advance an implant contained within the cannula needle104until the implant is ejected from the cannula needle104. In various embodiments, the latch108may be ergonomically designed to fit a particular finger of a user, such as the index finger. The latch108can move relative to the housing with a translational movement only, or can be depressed downward, and thereafter moved in a translational manner to advance/retract the pushrod.

FIG.1Billustrates the intraocular injector assembly100in use during an intraocular injection procedure. In various embodiments, the user (e.g., a healthcare provider) inserts the cannula needle104through the sclera of an eye150and into the posterior chamber151. In various embodiments, the user may insert the cannula needle104in a manner to avoid the various structures of the anterior segment of the eye (e.g., cornea, iris, ciliary body, and/or lens). The healthcare provider may position the distal end105of the cannula needle104at a target location within the eye150and proceed to eject an implant (e.g., a solid therapeutic drug) at the target location by pushing the latch108forward with a finger (e.g., an index finger). Similar toFIG.1B,FIG.1Cillustrates the intraocular injector assembly100in use during another injection procedure. In various embodiments, the user (e.g., a healthcare provider) inserts the cannula needle104through the sclera of an eye150and into the anterior chamber152. In various embodiments, when inserting the injector into the anterior chamber152, the healthcare provider may insert the cannula needle104parallel to the iris153so as not to damage the iris153or structures around the iris153(e.g., the lens capsule, the lens, etc.).

FIG.1Cillustrates a 3D model of an intraocular injector assembly100in accordance with an embodiment of the present disclosure. As shown inFIG.1C, the housing102may include one or more apertures103into which a fixation mechanism (e.g., a screw) is inserted to thereby affix one part of the housing102to another part of the housing102. In various embodiments, the housing parts may be joined without fixation mechanisms, such as by a snap-fit, welding, and/or bonding.

FIG.2illustrates a cross-section if an intraocular injector assembly100in accordance with an embodiment of the present disclosure. In various embodiments, the housing102defines an internal chamber107, which may house at least a part of various components of the injector assembly100, such as the cannula needle104, the needle stop106, the latch108, and a pushrod110coupled to the latch108. In various embodiments, as will be described in more detail below, the injector assembly includes a flexible arm114affixed to the cannula needle104.

As shown inFIG.2, the latch108is slidably disposed within a slot109formed in a surface (e.g., outer surface) of the housing and providing access to the internal chamber107. In various embodiments, the latch108includes a seating portion that is configured to contact the user's finger during use. In various embodiments, the seating portion of the latch108may be ergonomically-designed for a particular finger of a user, such as an index finger. In various embodiments, the seating portion may include one or more surface features configured to improve grip of the finger and reduce the chance that the finger slips during use. In various embodiments, the surface features may include any suitable structure that increases the friction between the user's finger and the latch thereby preventing slippage of the finger off of the latch108. In various embodiments, the seating portion may include a plurality of raised bumps. In various embodiments, the seating portion may include a plurality of raised bars.

In various embodiments, the latch108is coupled to a pushrod110. In various embodiments, the pushrod110is disposed entirely within the housing102. In various embodiments, the pushrod110is formed as a separate component from the latch108. In various embodiments, the pushrod is formed as an integral component with the latch108, i.e., both the latch108and the pushrod110are formed as one component. In various embodiments, at least a portion of the pushrod may extend into the distal opening of the cannula needle104. In various embodiments, the distal-most end of the latch108may be proximal to the distal-most end of the pushrod110. In this embodiment, the device may feel more comfortable to the user, as if they are holding a pen.

In various embodiments, the needle stop106may extend at least partially into the internal chamber107of the housing102. In various embodiments, the needle stop106may be configured as a bushing. In various embodiments, the needle stop106may be laser welded to the cannula needle104. In various embodiments, the needle stop106may be secured within the housing102by one or more alignment structures of the housing102.

FIGS.2B-2Gillustrates various mechanical drawings of an intraocular injector housing in accordance with an embodiment of the present disclosure. In various embodiments, the housing102may be formed of two components102aand102b(e.g., halves). In various embodiments, the components102a,102bmay be coupled together via an integral fastening element, such as a latch, hinge, and/or detent. In various embodiments, the components102a,102bmay be coupled together via a mechanical fastener, such as a screw, rivet, pin, nail, etc. In various embodiments, the components102a,102bmay be coupled together via a permanent joint, such as a weld (e.g., hot gas, vibration, ultrasonic, induction, dielectric, etc.) or bonding process (e.g., solvent, fusion, etc.).

FIG.3A-3Cillustrate a needle subassembly200in accordance with an embodiment of the present disclosure. The needle subassembly200includes the cannula needle104having a beveled distal end105, a cutout116disposed along the shaft of the cannula needle104at a distance d away from the distal end105of the cannula needle, an implant112, and a pushrod110. In various embodiments, the distanced may be about 5 mm to about 100 mm. Preferably the distanced may be about 10 mm to about 35 mm. As shown inFIG.3A, the needle subassembly200includes a flexible arm114affixed (e.g. welded) to the cannula needle104at a proximal end thereof; this can prohibit longitudinal movement of the flexible arm relative to the needle104. The flexible arm114includes a hook115having a first portion115aextending through the cutout116and into a lumen104aof the cannula needle104, and a second portion115bextending outwardly towards, and in some embodiments through, the cutout116. The cutout can be EDM skive cut to have rounded or chamfered edges (as best shown inFIG.4A) to prevent or inhibit risk of the hook115from engaging or “snagging” against the needle104when being displaced out of the lumen. Likewise, in some embodiments the edge or end of the hook can be formed with a rounded or bulbous shape to prevent snagging. In some embodiments a coating can be applied to the hook to reduce the frictional forces exhibited when the payload contacts (and displaces) the hook during deployment. This can be advantageous in that it reduces risk of damage to the payload. In various embodiments, the hook115may include a V-shape.

In various embodiments, the first portion115aof the hook115may be configured such that a (longitudinally applied) force of an implant112causes the hook115to displace out of the cutout116thereby allowing the implant112and the pushrod110to pass (over the hook115, as oriented inFIG.3A) through the lumen104a. The displacing force can be applied such that the hook is gradually displaced outside of the lumen104a. In some embodiments, the apex of the hook is displaced completely outside of the lumen104a. In various embodiments, the force necessary to displace the hook115is below (e.g., greater than a factor of safety of 1) a threshold that could damage the implant112. In various embodiments, the angle of the first portion115ais about 10 degrees to about 75 degrees from the horizontal (i.e., longitudinal axis of the cannula needle). Preferably, the angle of the first portion115ais about 65 degrees from the horizontal. In various embodiments, an angle between the first portion115aand the second portion115bis about 30 degrees to about 70 degrees. Preferably, the angle between the first portion115aand the second portion115bis about 50 degrees. In various embodiments, the second portion115bmay extend up to the outer surface of the cutout116. In various embodiments, the second portion115bmay extend no further, or less than the outer surface of the cutout116. In various embodiments, as shown inFIG.3A, the second portion115bmay extend beyond the outer surface of the cutout116. In various embodiments, the cutout116may be formed as a skive cut.

FIG.3Bshows a first step in ejecting the implant112where a user slides the latch108forward with their finger thereby causing the pushrod110to contact the proximal end of the implant112and advance the implant112through the lumen104a. As the implant112advances distally through the lumen104a, the distal end of the implant112contacts the first portion115aof the hook115. Because the first portion115ais disposed at a shallow angle relative to the horizontal, the force of the implant112contacting the first portion115adisplaces the hook115away from the lumen104aand out of the cutout116. InFIG.3B, the implant is directly under the hook115and the flexible arm114is acting as a cantilever beam (fixed at its proximal end) bending along its length. In various embodiments, the flexible arm114may undergo elastic deformation. In various embodiments, the flexible arm114may undergo plastic deformation (e.g., for a single-use device).

In various embodiments, a cushion may be provided between the pushrod110and the implant112to thereby protect the implant112from any potential damage. In various embodiments, the cushion may be placed at the proximal end of the implant112, the distal end of the implant112, or coat the implant112. In various embodiments, the cushion may include a liquid, a gas, a gel, and/or a lubricant.

FIG.3Cshows the last step in ejecting the implant112out of the cannula needle104where the latch108has translated about its maximum distance and the implant112is ejected from the distal end105of the cannula needle104. In particular, the pushrod110extends beyond the distal end105of the cannula needle104to ensure that the implant112is ejected therefrom. As shown inFIG.3C, the pushrod110continues to force the hook115out of the cutout116. In various embodiments, the pushrod110may include a pit (not shown) at a predetermined position along its length corresponding to a maximum translation of the latch108. In various embodiments, the pit may be sized such that the hook115of the flexible arm114snaps back into the cutout116and into the pit to thereby prevent retraction of the pushrod (e.g., for a single-use device). In various embodiments, the snapping motion of the hook115into the pit may provide an audible sound for the user to provide an indication to the user that the maximum translation has been reached and that the implant112has been ejected from the cannula needle104.

In various embodiments, the implant may be a therapeutic agent. In various embodiments, the implant may be a drug. In various embodiments, the implant may be a solid. In various embodiments, the drug may include at least one of: a steroid, an anti-vascular endothelial growth factor (anti-VEGF), a prostaglandin, a beta blocker, an alpha-2 agonist, cholinergic, carbonic anhydrase inhibitor, nucleoside reverse transcriptase inhibitor (NRTI), tyrosine kinase inhibitor, and rho kinase inhibitor. In various embodiments, the steroid may include dexamethasone. In various embodiments, the anti-VEGF may include bevacizumab, ranibizumab, or aflibercept. In various embodiments, the prostaglandin may be latanoprost, latanoprostene, tafluprost, bimatoprost, or travoprost. In various embodiments, the beta blocker may be timolol maleate, timolol hemihydrate, metipranolol, betaxolol, or levobunolol. In various embodiments, the alpha-2 agonist may be brimonidine tartrate or apraclonidine. In various embodiments, the cholinergic may be pilocarpine or carbachol. In various embodiments, the carbonic anhydrase inhibitor may be methazolamide, dorzolamide, brinzolamide, or acetazolamide. In various embodiments, the rho kinase inhibitor may be netarsudil. For example, the drug may be a solid dexamethasone implant.

FIG.4A-4Cillustrate various mechanical drawings of a needle subassembly in accordance with an embodiment of the present disclosure.

FIGS.5A-5Dillustrate various mechanical drawings of a needle stop106in accordance with an embodiment of the present disclosure. In various embodiments, the needle stop may be substantially cylindrical-shaped. In various embodiments, the needle stop106may include a distal bore106aconfigured to receive the cannula needle104. In various embodiments, the distal bore may have a diameter that is substantially similar (e.g., slightly larger than or equal) to the outer diameter of the cannula needle104. In various embodiments, the needle stop may be laser welded to the cannula needle104at the distal bore. In various embodiments, the needle stop106may include a cutout106b. In various embodiments, the cutout106bof the needle stop106may align substantially with the cutout116of the cannula needle104. In various embodiments, the cutout106bof the needle stop106may be sized (e.g., a larger cutout) to allow the motion of the flexible arm114and hook115to be displaced out of the cutout116of the cannula needle104. In various embodiments, the needle stop may include one or more positioning grooves106cconfigured to align the needle stop106within the housing102. In various embodiments, the needle stop106may having a proximal bore106dand a central chamber106ehaving a diameter that is larger than the diameter of the distal bore. In various embodiments, the cutout106bmay be formed as a skive cut.

FIG.6A-6Cillustrates a various mechanical drawings of a needle subassembly with needle stop in accordance with an embodiment of the present disclosure.

FIGS.7A-7Billustrate an exemplary pushrod and latch in accordance with an embodiment of the present disclosure.FIGS.7C-7Fillustrate mechanical drawings of an exemplary pushrod110and latch108in accordance with an embodiment of the present disclosure. In various embodiments, the latch108may be coupled to the pushrod110via a body111. In various embodiments, the body111may include a central bore111bout of which the pushrod110may extend. In various embodiments, at least a portion of the central bore111bmay include slot. In various embodiments, the proximal end of the pushrod110is affixed to a protrusion111aon the body111. In various embodiments, the proximal end of the pushrod110may be coiled around the protrusion111athereby creating a coil118. In various embodiments, the coil118may include an end119extending outward from the body111. In various embodiments, the end119of the coil118may extend perpendicularly outward from the body111. In various embodiments, the end119of the coil118may extend at an acute angle (i.e., less than 90 degrees) away from the body111. In various embodiments, the end119may extend beyond the outer surface of the body111such that the end119may engage a one-way catch on the body111(e.g., inside surface of the body111) while the body is permitted to slide within the housing unobstructed but for the end119of the coil118. In various embodiments, the end119of the coil118may extend at an obtuse angle (i.e., greater than 90 degrees) away from the body111. In various embodiments, the protrusion111amay be disposed within a recessed portion of the body111. In various embodiments, the central bore111bmay extend to the recessed portion of the body111. In various embodiments, the protrusion111aand/or the coil118may prevent the latch108from being pulled backwards after use thereby permitting only single use of the injector. In various embodiments, the end119of the coil118may catch on an interior portion of the injector housing102thereby preventing the latch108from being retracted after the latch108is advanced beyond a predetermined position (e.g., the position of the latch that causes the implant to be fully ejected). In various embodiments, the end119of the coil118may be advanced past a one-way catch inside the housing102that permits the end119to be advanced forward, but after the end119translates past the one-way catch in the forward direction, the end119is not capable of translating past the one-way catch in the reverse direction.

In various embodiments, the cannula needle104may be made of a metal. In various embodiments, the metal may be stainless steel. In various embodiments, the flexible arm may be made of a metal. In various embodiments, the metal may be stainless steel. In various embodiments, the needle stop106may be made of a metal. In various embodiments, the metal may be stainless steel.