Intracanalicular Depot Inserter Device

Abstract

In an embodiment, an intracanalicular injectate applicator device is disclosed that includes a body forming a cavity and a cannula coupled to a first distal end of the body. The cannula forms a channel that is aligned with the cavity of the body. The cannula is configured to store an intracanalicular injectate within the channel. The intracanalicular injectate applicator device further includes a tip structure coupled to the body. The tip structure is disposed about at least a portion of the cannula. A distal end of the tip structure is configured to dilate the canalicular punctum by inserting the distal end of the tip structure into the canalicular punctum through said punctum. The intracanalicular injectate applicator device further includes an actuation structure configured to push the intracanalicular injectate through the channel and the distal end of the tip structure into the canalicular punctum through the punctum.

Description

[Technical field]

[0001] Related Applications This application claims the benefit of U.S. Provisional Application No. 63 / 153,316, filed February 24, 2021, and U.S. Provisional Application No. 63 / 250,170, filed September 29, 2021, the entire contents of which are incorporated by reference in their entirety for all purposes.

[0002] FIELD OF THE DISCLOSURE Embodiments of the present disclosure relate to inserter devices, and more particularly to intracanalicular depot inserter devices. [Background technology]

[0003] The lacrimal puncta are tiny holes at the edge of the eyelid. The puncta open into the canaliculus. An intracanalicular filler may be inserted into the canaliculus via the puncta. The intracanalicular filler may be an injectable drug or an injectable biologic that is injected into the patient through the punctum by the physician. The intracanalicular filler may be a product that may be applied to prevent, treat, or cure a disease or condition of the patient's eye. Summary of the Invention

[0004] The present disclosure is illustrated by way of example, and not by way of limitation, in the figures of the accompanying drawings in which like reference numerals indicate like elements. It should be noted that separate references to "an" or "one" embodiment in the present disclosure are not necessarily to the same embodiment, and such references mean at least one. [Brief description of the drawings]

[0005] [Figure 1-1] 1A-1C illustrate an intracanalicular injectate applicator device according to certain embodiments. [Figure 1-2] 1A-1C illustrate an intracanalicular injectate applicator device according to certain embodiments. [Figure 2-1] 1A-1D show a main body of an intracanalicular injectate applicator device according to certain embodiments. [Figure 2-2]1A-1D show a main body of an intracanalicular injectate applicator device according to certain embodiments. [Figure 3-1] 1A-1C illustrate an actuation structure of an intracanalicular injectate applicator device according to certain embodiments. [Figure 3-2] 1A-1C illustrate an actuation structure of an intracanalicular injectate applicator device according to certain embodiments. [Figure 4] 1A-1C show a cannula of an intracanalicular injectate applicator device according to certain embodiments. [Figure 5-1] 1A-1C show a tip configuration of an intracanalicular injectate applicator device according to certain embodiments. [Figure 5-2] 1A-1C show a tip configuration of an intracanalicular injectate applicator device according to certain embodiments. [Figure 6] 1A-1C show a cap of an intracanalicular injectate applicator device according to certain embodiments. [Figure 7] 1A-1C illustrate a method of handling administration of an intracanalicular injectate using an intracanalicular injectate applicator device, according to certain embodiments. [Figure 8] 1A-1C illustrate an intracanalicular injectate applicator device according to certain embodiments. [Figure 9] 1A-1D show a main body of an intracanalicular injectate applicator device according to certain embodiments. [Figure 10] 1A-1C illustrate an actuation structure of an intracanalicular injectate applicator device according to certain embodiments. [Figure 11] 1A-1C show a tip configuration of an intracanalicular injectate applicator device according to certain embodiments. [Figure 12-1] 1A-1C show a cap of an intracanalicular injectate applicator device according to certain embodiments. [Figure 12-2] 1A-1C illustrate an intracanalicular injectate applicator device according to certain embodiments. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0006] The embodiments described herein relate to intracanalicular depot inserter devices (e.g., intracanalicular injectate applicator devices, punctal dilator applicators for delivering intracanalicular injectates, injectors, etc.) used to inject intracanalicular injectates (e.g., injectable drugs, injectable biologics, depots, etc.) into a patient.

[0007] Intracanalicular implants (e.g., polymeric intracanalicular inserts, depots) are used as a therapy to treat many conditions present in the eye. The puncta are tiny holes located at the inner corners of both the upper and lower eyelids. The puncta drain the tears that are constantly produced by the exocrine (lacrimal) glands of the eye. The intracanalicular implant (e.g., intracanalicular insert), which is usually cylindrical, can be placed through the puncta into the lower canaliculus or through the puncta into the upper canaliculus. The intracanalicular implant is generally large in diameter compared to the diameter of the punctal opening to aid in retention of the intracanalicular implant. The intracanalicular implant can be an injectable drug or an injectable biologic that is injected into the patient through the puncta by the physician. The intracanalicular implant can be a product that can be applied to prevent, treat, or cure a patient's eye disease or condition.

[0008] To allow the passage of intracanalicular fillers, an additional dilation procedure (e.g., punctal dilation) is used to enlarge the soft, delicate punctal tissue located around the punctum (e.g., the opening of the canalicularis). Punctal dilation is a daunting procedure because punctal dilation must be performed carefully to prevent damage to the surrounding tissue. This additional step of punctal dilation is also cumbersome and time-consuming. Because punctal diameters vary significantly between individuals and it can be difficult to know when punctal dilation is necessary, many physicians neglect to perform punctal dilation prior to injection (e.g., insertion) of intracanalicular fillers.

[0009] During injection (e.g., insertion) of the intracanalicular implant, hydrophilic polymer-based intracanalicular implants may absorb water from the ocular surface and surrounding tissues, causing the diameter of the intracanalicular implant to increase. This is favorable for retention of the implant. However, it presents a challenge to the procedure by limiting the amount of time available to successfully pass the intracanalicular implant through the punctum (e.g., punctal opening).

[0010] The small size of the intracanalicular injectate presents additional challenges because specialized instruments that are not standard for surgical procedures must be used for its insertion. Additionally, the intracanalicular injectate can be damaged if gripped too tightly or dropped if not held tight enough.

[0011] The variable patient-dependent nature and use of specialized instruments to perform the injection procedure (e.g., insertion procedure) may increase the likelihood of improper intracanalicular injection placement. The inferior canaliculus has two portions: a vertical portion approximately 2.5 millimeters (mm) long connected to a horizontal portion approximately 8 mm long via an angled ampulla. The effectiveness of the intracanalicular injection and its ability to be retained within the canaliculus (e.g., lacrimal canaliculus) depends on the initial placement of the intracanalicular injection during the injection procedure (e.g., insertion procedure). Also, the proximity of the injection to the punctal opening is important for delivery of the active ingredient (if present) from the injection to the tear fluid.

[0012] The combination of these factors increases the complexity of the procedure and can lead to failed injections (e.g., insertions), damage to the lacrimal tissue, dropout of the intracanalicular injection resulting in the need for another intracanalicular injection, and prolonged procedures. The amount of training and skill required to perform an injection procedure (e.g., insertion procedure) can discourage physicians from choosing to use intracanalicular injections and can create frustration when failures occur.

[0013] The devices, systems, and methods disclosed herein provide an intracanalicular injectate applicator device that simplifies and streamlines the injection procedure (e.g., insertion procedure) by protecting the intracanalicular injectate during storage and transport, and by easily and safely dilating the punctum so that it can receive the intracanalicular injectate, which is then placed into the canalicular cavity.

[0014] The intracanalicular injectant applicator device includes a body forming a cavity and a cannula coupled to a first distal end of the body. The cannula forms a channel aligned with the cavity of the body. The cannula is configured to store an intracanalicular injectant in the channel. The intracanalicular injectant applicator device further includes a tip structure coupled to the body. The tip structure is disposed about at least a portion of the cannula. The distal end of the tip structure is configured to dilate the punctum by inserting the distal end of the tip structure into the canalicular via the punctum (e.g., and rotating the distal end). The intracanalicular injectant applicator device further includes an actuation structure that may be partially disposed within the cavity of the body and partially disposed within the channel of the cannula. The actuation structure is configured to push the intracanalicular injectant through the channel and the distal end of the tip structure into the canalicular via the punctum while the distal end of the tip structure is inserted into the canalicular via the punctum.

[0015] The systems, devices, and methods disclosed herein have advantages over conventional solutions. The intracanalicular injectate applicator device can be used to safely dilate the punctum and insert the intracanalicular injectate more quickly than conventional solutions, thereby limiting the amount of moisture absorbed by the intracanalicular injectate and increasing the success rate of injection (e.g., insertion). The intracanalicular injectate applicator device avoids damage to the intracanalicular injectate and avoids dropping of the intracanalicular injectate compared to conventional solutions. The intracanalicular injectate applicator device has improved prospects for injection (e.g., insertion) and retention of the intracanalicular injectate in a precise location. The intracanalicular injectate applicator device reduces damage compared to conventional solutions.

[0016] Although certain embodiments of the present disclosure refer to intracanalicular implants, embodiments of the present disclosure may be used with one or more objects that are injected (e.g., inserted, placed) into the punctum and / or canaliculus. In some embodiments, the objects may include one or more of: an object that is injected (e.g., inserted, placed) into the canaliculus, an injectable drug, an injectable biologic, an object that delivers a drug (e.g., a pharmaceutical, a therapeutic agent), an object that occludes the punctum, a plug (e.g., a punctal plug, a hard plastic object shaped like a tether, an object with a head that is flush with the eyelid, etc.), an implant (e.g., located just below the punctum), an object made of hydrogel, an object made of poly(lactic acid) (PLA), an object made of poly(lactic-co-glycolic acid) (PLGA), a cylindrical object, a bioabsorbable object, an object that is subsequently physically removed, a polymeric object, an object that expands (e.g., expands to occlude the punctum), a polymeric object, an elastomeric object, etc.

[0017] Although certain embodiments of the present disclosure refer to an intracanalicular injectate applicator device used to dilate the punctum and place a single intracanalicular injectate within the canalicular region, embodiments of the present invention may be used to place multiple intracanalicular injectates (e.g., stacking intracanalicular injectates) into a single canalicular region (e.g., providing a first intracanalicular injectate into the canalicular region via a first intracanalicular injectate applicator device and a second intracanalicular injectate into the same canalicular region via a second intracanalicular injectate applicator device, providing first and second intracanalicular injectates into the same canalicular region via the same intracanalicular applicator device, etc.).

[0018] 1A-1G illustrate an intracanalicular injectate applicator device 100 (e.g., an applicator, a plunger-actuated intracanalicular injectate applicator device, a punctal dilator applicator for delivering an intracanalicular injectate, an injector, etc.) according to certain embodiments. The intracanalicular injectate applicator device 100 includes a body 110, an actuation structure 120, and a cannula 130 (e.g., an intracanalicular injectate is stored in the cannula 130).

[0019] The intracanalicular injectate application device 100 can be used to inject (e.g., place, insert, etc.) an intracanalicular injectate 160 (e.g., a depot) into a patient. The intracanalicular injectate 160 can be an injectable drug or an injectable biologic that is injected into a patient through a punctum by a physician. The intracanalicular injectate 160 can be a product that can be applied to prevent, treat, or cure a patient's ocular disease or condition. In some embodiments, the intracanalicular injectate 160 is a Dextenza® intracanalicular injectate. The intracanalicular injectate 160 may be referred to as an insert or an intracanalicular insert. The intracanalicular injectate application device 100 may be referred to as an intracanalicular insert application device, an injector, an inserter device (e.g., for dilating the punctum to deliver an intracanalicular injectate), an injector device for dilating the punctum to deliver an intracanalicular injectate, etc. In some embodiments, the intracanalicular injectate 160 includes one or more of travoprost, cyclosporine, or dexamethasone.

[0020] The body 110 forms a cavity (e.g., a hollow core, etc.). The cannula 130 is coupled (e.g., attached) to a distal end of the body 110. In some embodiments, the cannula 130 is secured to the body 110 by bonding (e.g., glue), insert molding, and / or the like. The cannula 130 forms a channel (e.g., lumen) that is aligned with the cavity of the body 110. The cannula 130 is configured to store an intracanalicular injectate within the channel. In some embodiments, the channel of the cannula 130 is configured to store, protect, and maintain alignment of the intracanalicular injectate. The actuating structure 120 is configured to be partially disposed within the cavity of the body 110 and partially disposed in the channel within the cannula 130. The actuating structure 120 is configured to push the intracanalicular injectate through the channel and into the canalicular canaliculus via the punctum.

[0021] The actuation structure 120 can include a plunger structure 122 and a push wire 124. The plunger structure 122 can be configured to be at least partially disposed within a cavity of the body 110. A first distal end of the plunger structure 122 is configured to receive a force (e.g., a user pushing the first distal end of the plunger structure 122 with a finger) to cause actuation of the actuation structure 120 (e.g., the plunger structure 122 and the push wire 124). A first distal end of the push wire 124 is attached to a second distal end of the plunger structure 122. In some embodiments, the second distal end of the plunger structure 122 forms a slot 128, and the first distal end of the push wire 124 is insert molded into the slot 128 of the plunger structure 122. The second distal end of the push wire 124 is disposed within a channel of the cannula 130 prior to actuation of the actuation structure 120. The push wire 124 is configured to push the intracanalicular injectate through the channel in response to actuation of the actuation structure 122. In some embodiments, the push wire 124 is a rod. In some embodiments, the push wire 124 is a metal wire. In some embodiments, the push wire 124 has a circular periphery that substantially matches the cylindrical shape of the channel of the cannula 130 (e.g., is cylindrical). In some embodiments, the outer diameter of the push wire 124 is substantially the same as the inner diameter of the channel of the cannula 130.

[0022] The plunger structure 122 may include a hooked clip 126 configured for insertion into a corresponding recess formed by the outer surface of the body 110 to prevent separation of the plunger structure 122 and the body 110 and to restrict movement of the intracanalicular injectate within the cannula 130.

[0023] In some embodiments, the portion of the plunger structure 122 disposed within the body cavity has a non-circular perimeter (e.g., elliptical; the portion of the plunger structure proximate the hooked clip 126), and a portion of the body 110 cavity has a non-circular (e.g., elliptical) contour that corresponds to the non-circular perimeter of that portion of the plunger structure 122. The actuation structure 120 may be rotated to align the non-circular perimeter of the portion of the plunger structure 122 with the non-circular contour of the portion of the body 110 cavity to actuate the actuation structure 120.

[0024] In some embodiments, the cavity of the body 110 and the outer contour of the plunger structure 122 are tapered to guide the push wire 123 into a channel of the cannula 130.

[0025] In some embodiments, the intracanalicular injectate applicator device 100 includes a cap 150 configured to be removably attached to the body 110 near a first distal end of the body 110 (e.g., near the cannula 130). The cap 150 may form an opening (e.g., a vent) that provides venting to the intracanalicular injectate.

[0026] The intracanalicular injectant applicator device 100 may include a tip structure 140 (e.g., a flexible tip, a dilator tip) coupled to the body 110. The tip structure 140 is disposed about at least a portion of the cannula 130. A distal end (e.g., a tip) of the tip structure 140 is configured to be inserted into the canalicular via the punctum. The actuation structure 120 is configured to push the intracanalicular injectant through the channel of the cannula 130 and the distal end of the tip structure 140 into the canalicular via the punctum while the distal end of the tip structure 140 is inserted into the canalicular via the punctum. In some embodiments, the distal end of the tip structure 140 is configured to dilate the punctum by inserting the distal end of the tip structure 140 into the canalicular via the punctum and rotating the intracanalicular injectant applicator device 100.

[0027] In some embodiments, at least a portion of the distal end (e.g., tip) of tip structure 140 has a durometer between 50 and 70. In some embodiments, the opening at the distal end of tip structure 140 has a diameter smaller than the outer diameter of the intracanalicular injectate. In some embodiments, the portion of the distal end of tip structure 140 comprises one or more of a flat tip, a beveled tip, a slit tip, a flat beveled tip, or a rounded beveled tip. The portion of the distal end of tip structure 140 is configured to be inserted entirely into the canaliculus via the punctum prior to injection (e.g., placement, insertion) of the intracanalicular injectate into the canaliculus.

[0028] In some embodiments, the tip structure 140 does not have a beveled tip. A punctum or punctum that is dilated (e.g., via cap 150 or a separate dilation component) may have a rest diameter (e.g., greater than the average rest diameter) that can accommodate the tip structure 140 (e.g., not having a beveled tip).

[0029] In some embodiments, the injectate applicator device 100 includes a collar structure disposed around a portion of the cannula 130 (e.g., in place of the tip structure 140). The collar structure limits the depth of insertion of the distal end of the cannula 130 into the canalicular via the punctum. The actuation structure 120 is configured to push the intracanalicular injectate through the channel and into the canalicular while the distal end of the cannula 130 is inserted into the canalicular via the punctum.

[0030] In some embodiments, the system includes the intracanalicular injectate applicator device 100 and an intracanalicular injectate (e.g., loaded into a channel of the cannula 130 of the intracanalicular injectate applicator device 100). In some embodiments, the kit includes a housing that houses the components (see, e.g., FIG. 12I). The components may include the intracanalicular injectate applicator device 100 and an intracanalicular injectate (e.g., the intracanalicular injectate loaded into the intracanalicular injectate applicator device 100 in the locked position and with the cap 150 on the body 110 in the kit, the intracanalicular injectate separate from the intracanalicular injectate applicator device 100 in the kit). The housing may be a foil pouch. The components in the kit may include a desiccant.

[0031] The intracanalicular injectate applicator device 100 can be economically manufactured using precision injection molded thermoplastics, thermoplastic resins, and / or machined metal components.

[0032] In some embodiments, the intracanalicular injectate applicator device 100 does not have an adhesive. The intracanalicular injectate applicator device 100 may be designed in a manner that eliminates the need for adhesives that may contribute to mechanical failure or moisture in the packaging. The cannula 130 (e.g., a textured subcutaneous cannula) may be insert molded into the body 110 (e.g., a plastic handle).

[0033] In some embodiments, the intracanalicular injectate is cylindrical in shape and is housed within a lumen (e.g., a channel) of the cannula 130 for protection and maintaining alignment during storage. A short length of the push wire 124 is also located within the lumen of the cannula 130 behind the intracanalicular injectate. The push wire 124 may restrain one end of the intracanalicular injectate (e.g., a cylindrical injectate) and prevent the intracanalicular injectate from moving toward the center. The push wire 124 may be insert molded into the plunger structure 122 without the use of adhesive and may be located at least partially within a cavity of the body 110 (e.g., within the hollow core of the handle). The plunger structure 122 may have a hooked clip 126 that is restrained by a recess in the body 110 to prevent the plunger structure 122 and the body 110 (e.g., the body assembly) from coming apart. This may further constrain the intracanalicular filler from migrating centrally and may maintain the positioning of the intracanalicular filler during storage.

[0034] The tip structure 140 may be a flexible tip that surrounds the cannula 130 (e.g., a subcutaneous cannula) that contains the intracanalicular injectate. The tip structure 140 has a distal end (e.g., a flexible tip) that has an inner diameter smaller than the diameter of the intracanalicular injectate, which prevents the intracanalicular injectate from migrating distally upon movement of the intracanalicular injectate applicator device 100 (e.g., during worst case shipping conditions). The material properties and flexibility of the distal end (e.g., flexible tip) of the tip structure 140 may allow the passage of the intracanalicular injectate when a threshold force (e.g., significant force) is applied.

[0035] Tip structure 140 may form an annular recess (e.g., formed by an inner surface of tip structure 140) that fits over a corresponding annular protrusion (e.g., formed by an outer surface of body 110) on body 110, thereby securing tip structure 140 (e.g., a flexible tip) in place. This may simplify the assembly procedure and improve consistent repeatability.

[0036] In some embodiments, the cap 150 (e.g., a protective cap) frictionally fits onto the body 110. A light press fit may be achieved via ridges that longitudinally line the inside diameter of the cap 150. The ridges may create an inside diameter that is smaller than the outside diameter of the body 110 (e.g., the ridges may be inset into the outside diameter of the body).

[0037] The inner circular core (e.g., hollow) of the body 110 and the circular shaft of the plunger structure 122 may be tapered to facilitate assembly. The tapered profile guides the push wire 124 into the cannula 130 as the plunger structure 122 is inserted into the body 110. The base of the inner core (e.g., hollow) of the body 110 may form a chamfer to guide the push wire 124 into the cannula 130 to prevent clogging during assembly.

[0038] The plunger structure 122 and the body 110 may form a "lock and key" type locking mechanism to prevent unintentional placement of an intracanalicular injectate during shipping and handling. The body 110 may be cylindrically tubular and may form a non-circular (e.g., elliptical) slot (e.g., a portion of the cavity may have a non-circular contour) that extends a distance into the cylindrical core of the body 110. The plunger structure 122 may have a corresponding non-circular (e.g., elliptical) periphery (e.g., protrusion) that extends a distance along the cylindrical axis of the plunger structure 122. The non-circular periphery of the plunger structure 122 should match the non-circular contour of the body 110 for axial advancement. If the non-circular perimeter and the non-circular contour (e.g., an elliptical feature) are not aligned, the maximum width of the non-circular perimeter of the plunger structure 122 (e.g., the elliptical protrusion of the plunger structure 122) will interfere with the minimum width of the non-circular contour of the body 110 (e.g., the oval slot of the body 110).

[0039] In addition to the "lock and key" mechanism preventing unintended forward actuation in the "locked position" (e.g., when the non-circular periphery of the plunger structure 122 is not aligned with the non-circular contour of the body 110), the intracanalicular injectate applicator device 100 may have another feature that prevents unintended rotation of the plunger structure 122. The plunger structure 122 may include two clips 126 (e.g., on either side of the plunger structure 122) that are spaced a set distance apart. The body 110 has a square contour where the clips 126 rest on the body 110. The square contour may be designed to prevent the plunger structure 122 from rotating until a threshold force (e.g., significant force) is applied to rotate the plunger structure 122. The width of the body at the location of the square contour may match the separation distance of the resting clips. As the plunger structure 122 is rotated 45 degrees, the clip 126 of the plunger structure 122 may flex to overcome the diagonal distance of the square contour of the body 110. The clip 126 of the plunger structure 122 may provide a spring force to prevent rotation as a result of any movement (e.g., worst case shipping conditions). The rotation force may be achieved with one finger.

[0040] The width of the square feature when the plunger structure 122 is disposed in the "unlocked position" may be larger (e.g., slightly larger) than the rest width of the clip 126 of the plunger structure 122, thereby bending the clip 126 and creating friction to prevent the plunger from moving in the "unlocked position" until a threshold force (e.g., significant force) is applied. The interface between the bending clip 126 of the plunger structure 122 and the square feature (e.g., square contour) of the body 110 may provide physical feedback to the end user while an intracanalicular injectate procedure is being performed.

[0041] The cap 150 may have a cutout window that allows for improved ventilation for the tip structure 140 (e.g., flexible tip) and the intracanalicular filler (e.g., polymer-based intracanalicular filler). In some embodiments, the intracanalicular filler and plastic material (e.g., of the tip structure 140) may have moisture removal by inert nitrogen pretreatment, and the cutout in the cap 150 (e.g., protective cap) may enhance the rate of potential moisture removal from the intracanalicular filler (e.g., polymer-based load) and surrounding materials contained therein. The plastic material (e.g., of the tip structure 140) may exhibit low H2O adhesion and cohesion properties.

[0042] The intracanalicular injectate applicator device 100 may be configured to dilate the punctum to a threshold diameter to receive the intracanalicular injectate and then inject (e.g., place, insert) the intracanalicular injectate into the vertical canaliculus through one streamlined procedure without additional actions. One or more warning indicators may be incorporated into the intracanalicular injectate applicator device 100 to provide one or more warnings to a user.

[0043] The distal end of tip structure 140 (e.g., a tubular flexible tip) may be beveled to allow just the tip of the bevel to come to an oval point having dimensions that allow for use with puncta of various sizes.

[0044] The distal end (e.g., tip) of tip structure 140 may be tubular in shape to allow for the passage of intracanalicular injectates and may have a beveled tip to initially find the punctal opening using only one wall, which allows for a larger wall thickness and therefore a stiffer tool to be used for dilating puncta of various sizes.

[0045] The distal end (e.g., tip) of tip structure 140 may have a bevel with a rounded tip and an oval profile, which prevents trauma and improves the user's ability to perform initial dilation of the punctum. The oval tip profile when inserted into a round punctal opening initially stretches the tissue in one plane. The oval tip can be rotated to dilate the entire circumference of the punctum. This may reduce the rate of dilation and allow successful use on patients with small punctal openings.

[0046] The tapered profile of the beveled tip at the distal end of tip structure 140 may allow tip structure 140 to gradually expand the punctal opening to a threshold diameter (e.g., a diameter large enough to accommodate an intracanalicular injectate). A slow and careful rate of expansion is used so as not to cause trauma to the fibroelastic tissue surrounding the punctal opening. The angle of the bevel at the distal end of tip structure 140 may optimize the rate of expansion as the bevel is inserted into the canalicular.

[0047] The flexibility and tubular structure of the distal end (e.g., expander tip) of tip structure 140 prevents forceful expansion. The distal end (e.g., tip) of tip structure 140 collapses when the distal end is first inserted to conform to the contours of the smaller canaliculus, and then slowly expands to its original shape while exerting an outward force that gradually expands the canalicular tissue.

[0048] When the entire bevel of the distal end (e.g., tip) of tip structure 140 is inserted inside the canaliculus, the outer diameter of tip structure 140 (e.g., dilator tip) suddenly increases to a diameter that prevents further insertion and overexpansion (e.g., tip structure 140 has a distal end configured to enter the canaliculus, the distal end having a larger diameter than the distal end adjacent a portion of tip structure 140 that is not configured to enter the canaliculus). Overexpansion of the punctal opening or canalicular diameter can damage the fibroelastic punctal tissue and / or create an opening that is too large to adequately retain an intracanalicular injectate.

[0049] Once a threshold dilation (e.g., sufficient dilation) is achieved, the intracanalicular injectate applicator device 100 can be used like a syringe to transmit an axial load along the push wire 124 to expel the intracanalicular injectate through the lumen of the tip structure 140 (e.g., a flexible tip). Placing a portion of the push wire 124 within the cannula 130 prior to actuation additionally maintains alignment of the push wire 124 and prevents the possibility of misfire. The inner wall of the cannula 130 (e.g., a subcutaneous cannula) prevents deflection of the wire and maintains a straight axial force vector that pushes the intracanalicular injectate into the canalicular canal.

[0050] A user can unlock and actuate the plunger with an index finger (e.g., based on the size of an average adult hand). The intracanalicular injectate applicator device 100 can remain in and function using one hand throughout the entire duration of the insertion procedure (e.g., one-handed insertion).

[0051] A non-circular (e.g., oval shaped) "lock and key" style locking mechanism can provide ambidextrous functionality. Utilizing a non-circular (e.g., oval shaped) can accomplish this by allowing the plunger structure 122 and body 110 to "unlock" and align when rotated 90 degrees clockwise and when rotated 90 degrees counterclockwise.

[0052] The sudden increase in outer diameter of the tip structure 140 (e.g., dilator tip) acts as a physical barrier and defines the location of the tip within the canalicular cavity prior to injection (e.g., placement, insertion) of the intracanalicular injectate. Accurate positioning of the distal end (e.g., tip) of the tip structure 140 within the canalicular cavity can result in accurate and consistent placement of the intracanalicular injectate (e.g., polymer-based load) regardless of human factors.

[0053] The injection (e.g., placement, insertion) depth of the intracanalicular injectate may be controlled by the depth of the non-circular portion of the cavity (e.g., elliptical cutout) inside the body 110. When the non-circular portion of the cavity (e.g., elliptical portion) transforms into a circular portion, the portion of the plunger structure 122 having the non-circular (e.g., oval) perimeter cannot advance any further.

[0054] The fixed stroke length of the plunger structure 122 and push wire 124 (e.g., plunger and push wire assembly), in combination with an insertion barrier at the distal end (e.g., tip) of the tip structure 140, allows the intracanalicular injectate to be injected (e.g., placed, inserted) to a consistent, predetermined depth. These features that define the injection (e.g., placed, inserted) depth may be selected to deliver the intracanalicular injectate to the vertical portion of the lower canaliculus.

[0055] A short push wire 124 can be used to deliver the intracanalicular injection to a maximum depth of 1 millimeter (mm) below the punctal opening, such that the intracanalicular injection is in the vertical portion of the lower canaliculus just above the angled ampulla. The short injection (e.g., placement, insertion) depth can be provided, in part, by the beveled distal end (e.g., beveled tip) of tip structure 140, which allows the intracanalicular injection to be expelled a shorter distance.

[0056] If the intracanalicular injectate is placed in the horizontal region of the lower canaliculus, the length of the push wire 124 may be increased to push the intracanalicular injectate past the ampulla. The flexibility of the distal end of the tip structure 140 (e.g., the dilator tip) can conform to the anatomy of the lacrimal gland and guide the intracanalicular injectate past the curved ampulla.

[0057] In some embodiments, the intracanalicular injectate applicator device 100 has an audible and / or physical feedback to signal the injection (e.g., placement, insertion) of the intracanalicular injectate. The audible and / or physical feedback may be caused by how the clip 126 of the plunger structure 122 interacts with the body 110 when the plunger structure 122 reaches a final "placed position," "injection position," or "insertion position." When the plunger structure 122 reaches the placed position, the clip 126 of the plunger structure 122 fits into a recess in the body 110, which generates an audible clicking sound. Clicking the plunger structure 122 into place at the placed position secures the push wire 124 in an exposed position (e.g., an extended position of the push wire 124) and allows the user to further push the intracanalicular injectate into place without the push wire 124 retracting (e.g., if applicable). The engagement of clip 126 of plunger structure 122 into the recess in body 110 may be physically felt through mechanical vibration of intracanalicular injectate applicator device 100 as clip 126 engages the recess.

[0058] The intracanalicular injectate applicator device 100 may include visual feedback indicia (e.g., in addition to or instead of audible and / or physical feedback). The plunger structure 122 may have indicia (e.g., red and green markings printed on the plunger). The actuation structure 120 may be the only moving component in the intracanalicular injectate applicator device 100. The indicia may be viewed through a cutout that peers into the cavity of the body 110. The position of the first indicia (e.g., red marking) when transitioning to the second indicia (e.g., green marking) may align when the intracanalicular injectate is fully injected (e.g., seated, inserted).

[0059] The dimensions of the push wire 124, the cannula 130 (e.g., a subcutaneous cannula), and the tip structure 140 (e.g., a flexible tip) can be adjusted to accommodate various sizes of intracanalicular injectates. The intracanalicular injectate applicator device 100 streamlines and reduces the complexity of the insertion procedure. By reducing the amount of time to perform the insertion procedure and preventing the intracanalicular injectate from expanding before being placed in the canalicular, the likelihood of an unsuccessful insertion can be reduced.

[0060] The design and construction of the intracanalicular injectate applicator device 100 may include a cannula 130 (e.g., a subcutaneous cannula) that is insert molded into the body 110 (e.g., a cylindrical tubular body) without the use of adhesive. The cannula 130 may constrain the intracanalicular injectate from moving laterally. The push wire 124 may be insert molded into the plunger structure 122 without the use of adhesive. The actuation structure 120 (e.g., a subassembly of the push wire 124 and the plunger structure 122) may be assembled within a cavity (e.g., a core) of the body 110. The push wire 124 may constrain the intracanalicular injectate from moving in a proximal direction. The plunger structure 122 may have a hooked clip 126 that interacts with the body 110 to prevent the plunger structure 122 and the body 110 (e.g., the plunger and body assembly) from coming apart. The tip structure 140 (e.g., a flexible tip) may surround the cannula 130 (e.g., a subcutaneous cannula) and may constrain the distal movement of the intracanalicular injectate. The tip structure 140 may have material properties and flexibility that allow the passage of the intracanalicular injectate when a threshold force is applied. The tip structure 140 may have an annular recess that fits into a corresponding annular protrusion on the body 110 to secure the tip structure 140 in place, which may reduce assembly time. A cap 150 (e.g., a protective cap) may frictionally fit over the body 110. The frictional fit may be created by ridges on the interior of the cap. A portion of the push wire 124 may be within the cannula 130 prior to actuation to maintain alignment of the push wire 124 and prevent possible misfire of the push wire 124. The body 110 may have a cavity (e.g., an internal circular core) and the shaft of the plunger structure 122 may be tapered to aid in aligning the push wire 124 during assembly. A space at the base of the cavity (e.g., internal core) of the body 110 may allow the push wire 124 to advance into the cannula 130.

[0061] The intracanalicular injectate applicator device 100 may prevent unintended placement of the intracanalicular injectate (e.g., via a locking feature that constrains the plunger structure 122). The body (e.g., a cylindrical tubular body) may include a non-circular (e.g., elliptical) slot extending into a cylindrical core. The plunger structure 122 having a substantially identical non-circular (e.g., elliptical) protrusion extends along the cylindrical axis of the plunger structure 122. The non-circular periphery of the plunger structure 122 should match the non-circular contour (e.g., elliptical slot) of the body 110 to advance distally. The placement or stroke depth may be directly dependent on the depth of the internal non-circular portion (e.g., oval-shaped cutout) relative to the body 110, which is also used as a locking feature. The plunger structure 122 may be rotated clockwise and counterclockwise to align with the body 110 for placement. The flexible clip 126 of the plunger structure 122 and the squared contour of the body 110 may interact with one another to prevent rotation of the plunger structure 122 until a threshold force is applied (e.g., via a single finger). The clip 126 of the plunger structure 122 may provide a spring force that can be applied (e.g., countered, overcome) by a single finger. The flexible clip 126 of the plunger structure 122 and the squared contour of the body 110 may interact to provide physical feedback in the form of resistance when the plunger structure 122 is actuated.

[0062] The cap 150 (e.g., protective cap) may have a cut-out window that allows for high HO diffusion rates for the polymer-based intracanalicular filler and components contained therein. To administer hygroscopic intracanalicular fillers that become unstable in the presence of HO, the plastic materials used to fabricate the intracanalicular filler applicator device 100 may have low moisture adhesion and cohesion. Mitigating exposure to HO within the intracanalicular filler packaging may help preserve the integrity of the intracanalicular filler during storage. In some embodiments, the intracanalicular filler applicator device 100 (e.g., loaded with intracanalicular filler) may be stored in a desiccant-lined foil pouch configured to remove internal moisture and prevent moisture ingress. The intracanalicular filler applicator device 100 loaded with intracanalicular filler may be stored in a foil pouch with a desiccant packet.

[0063] The distal end of the tip structure 140 may be a beveled tubular flexible tip so that just the tip of the bevel can come to an oval-shaped point with a circumference (e.g., perimeter) that can fit into puncta of various sizes. The bevel tip may be rounded at the end to prevent trauma. The bevel may allow for a larger wall thickness to increase tip stiffness while maintaining a small enough profile to dilate small punctal openings. The oval-shaped bevel tip profile may reduce the initial rate of expansion as the end first stretches the punctal opening in one direction, allowing the user to gradually expand in all directions when rotated. This allows for use with patients with small punctal openings. The bevel may be tapered to allow for a steady, gradual rate of punctal expansion without causing trauma to the punctal tissue. The flexible tubular tip may collapse when first inserted into the canaliculus and be allowed to gradually expand, resulting in a slower rate of expansion. The tip structure 140 (eg, a flexible dilating tip) may have a suddenly increasing outer diameter to prevent further insertion and overexpansion.

[0064] The intracanalicular injectate applicator device 100 may be used like a syringe to transmit an axial load along the push wire 124 to expel the intracanalicular injectate through the lumen of the tip structure 140 (e.g., a flexible, dilated tip). The intracanalicular injectate applicator device 100 is capable of storing the intracanalicular injectate, dilating the punctum, and subsequently injecting (e.g., placing, inserting) the intracanalicular injectate, and can be operated completely one-handed. The intracanalicular injectate applicator device 100 can be operated with completely ambidextrous functionality.

[0065] The intracanalicular injectate applicator device 100 can inject (e.g., place, insert) the intracanalicular injectate consistently into the vertical portion of the canaliculus. The beveled tip allows the intracanalicular injectate to be expelled from the beveled tip a shorter distance. The intracanalicular injectate applicator device 100 can inject (e.g., place, insert) the intracanalicular injectate across the vertical canaliculus and ampulla such that the intracanalicular injectate is placed in the horizontal portion of the canaliculus. The tip structure 140 can help guide the placement of the intracanalicular injectate across the curved ampulla.

[0066] The intracanalicular injectate applicator device 100 may have a feedback feature that can be audibly and / or physically detected when the intracanalicular injectate is fully seated. The clip 126 of the plunger structure 122 may snap into a recess in the body 110 when the plunger structure 122 is fully seated. The dimensions of the body 110 and the clip 126 of the plunger structure 122 may snap in a manner that can be felt (e.g., as a vibration) and heard as an audible click. The clip 126 of the plunger structure 122, which is held within the recess in the body 110, may only be moved by a threshold force (e.g., cannot be moved without the application of significant force).

[0067] The intracanalicular injectate applicator device 100 may have visual cue features that allow visual detection when the intracanalicular injectate is fully installed. In some embodiments, markers on the plunger structure 122 (e.g., red and green marks printed on the plunger structure 122) are visible through a cutout that looks into the cavity of the body 110. A first marker (e.g., a green marker) is visible through the cutout only when the intracanalicular injectate is fully installed. A second marker (e.g., a red marker) may only be visible when the intracanalicular injectate has been preloaded into the intracanalicular injectate applicator device 100 (e.g., and the plunger structure 122 has not yet been actuated).

[0068] In some embodiments, the actuation structure 120 includes a plunger structure 122 coupled to a push wire 124. In some embodiments, the actuation structure 120 includes a slider structure coupled to the push wire 124. An intracanalicular injectate applicator device 100 including the plunger structure 122 can be used like a syringe to deliver an axial load along the push wire 124 to inject (e.g., place, insert) an intracanalicular injectate. The force is applied to the plunger structure 122 at a distal end of the intracanalicular injectate applicator device 100. In the case of an intracanalicular injectate applicator device 100 including a slider structure, the slider structure travels laterally along the body to deliver the axial load.

[0069] In some embodiments, the intracanalicular injectant applicator device 100 includes a beveled cannula 130. The cannula 130 may be a subcutaneous metal cannula that is custom machined to have a blunt tip and a tapered bevel. The blunt tip prevents the intracanalicular injectant applicator device 100 from penetrating the lacrimal gland tissue and allows the intracanalicular injectant applicator device 100 to find the punctal opening where it begins to dilate. The tapered bevel may be configured to gradually dilate the punctum as it is inserted into the canalicular canal. The intracanalicular injectant is stored within the lumen of the cannula 130 and can be injected (e.g., placed, inserted) via the actuation structure 120 (e.g., a plunger structure or a slider structure). The beveled surface allows an appropriate amount of the intracanalicular filler to be exposed to the canalicular tissue so that when the cannula 130 is removed, the intracanalicular filler is held in place by friction between the intracanalicular filler and the canalicular tissue. This prevents the intracanalicular filler from being inadvertently removed along with the intracanalicular filler applicator device 100.

[0070] A collar (eg, a metal collar) may be provided around the cannula 130 to prevent overinsertion of the cannula 130 into the canaliculus.

[0071] In some embodiments, the intracanalicular injectate applicator device 100 includes a flexible tip structure 140. This tip structure 140 may be used similarly to the beveled cannula 130. The softness of the tip of the tip structure 140 reduces the risk of penetration into the lacrimal tissue, thereby increasing the safety of the intracanalicular injectate applicator device 100. The lumen of the tip structure 140 (e.g., flexible tip) may be undersized to hold the intracanalicular injectate during storage, and the flexibility of the tip material allows the intracanalicular injectate to pass when an actuation force is applied. The tip material is sufficiently rigid to sufficiently dilate the punctum.

[0072] Either a beveled cannula 130 or a flexible tip structure 140 may be used, both of which allow for punctal dilation (e.g., increasing the diameter of the punctum large enough to accept the intracanalicular injectate) and allow for the passage and placement of the intracanalicular injectate into the canalicular cavity.

[0073] One or more components of the intracanalicular injectate applicator device 100 may be three-dimensional (3D) printed. The intracanalicular injectate applicator device 100 may be used to insert an intracanalicular injectate (e.g., a polymeric insert) into the mammalian lacrimal canaliculus.

[0074] In some embodiments, the intracanalicular injectate applicator device 100 is used to store multiple intracanalicular injectates and insert multiple intracanalicular injectates into multiple canaliculi. In some embodiments, the intracanalicular injectate applicator device 100 is used to apply one or more products (e.g., liquids, solids, pharmaceuticals, etc.) to the punctum and / or canaliculi. In some embodiments, the intracanalicular injectate applicator device 100 is used to insert an intracanalicular injectate that includes a drug (e.g., to apply a drug). In some embodiments, the intracanalicular injectate applicator device 100 is used to insert an intracanalicular injectate that does not include a drug (e.g., to simply occlude).

[0075] FIG. 1A shows an exploded view of the intracanalicular injectate applicator device 100, including the body 110, the actuation structure 120 (e.g., the plunger structure 122 and the push wire 124), the cannula 130, the tip structure 140, and the cap 150. FIG. 1B shows the assembled intracanalicular injectate applicator device 100 (e.g., without the cap 150), including the body 110, the plunger structure 122, and the tip structure 140. FIG. 1C shows the assembled intracanalicular injectate applicator device 100 (e.g., without the cap 150) rotated 90 degrees compared to FIG. 1B. FIG. 1C shows a side view of the intracanalicular injectate applicator device 100 (e.g., without the cap 150). FIG. 1D shows a cross-sectional view of the intracanalicular injectate applicator device 100 (e.g., without the cap 150). FIGURE 1E shows a cross-sectional view of the tip structure 140 of the intracanalicular injectate applicator device 100 with an intracanalicular injectate 160 (e.g., Dextenza® intracanalicular injectate) not yet deployed (e.g., with the push wire 124 in a non-deployed position). FIGURE 1E shows a cross-sectional view of the tip structure 140 of the intracanalicular injectate applicator device 100 (e.g., with the intracanalicular injectate deployed and the push wire 124 in a deployed position). FIGURE 1G shows a perspective view of the intracanalicular injectate applicator device 100 with the tip structure 140 and cap 150 removed.

[0076] In some embodiments, the overall length of the intracanalicular injectant applicator device 100 (e.g., without the cap 150) is about 62-80 millimeters (mm). In some embodiments, the tip structure 140 is about 12 mm long. In some embodiments, the distal end (e.g., tip) of the tip structure 140 is about 1-5 mm long. In some embodiments, the width of the plunger structure 122 (e.g., from the outer surface of one clip 126 to the outer surface of the opposite clip 126) is about 9 mm. The maximum width of the body 110 is about 6 mm. The length of the central portion (e.g., gripping portion) of the body 110 is about 37 mm. The length of the portion of the intracanalicular injectant applicator device 100 between the central portion of the body 110 and the distal end (e.g., tip end) of the tip structure 140 is about 19 mm. In some embodiments, the cannula 130 is about 8-9 mm long.

[0077] In some embodiments, the cannula 130 is secured to the body 110 by insert molding with a minimum tensile strength of about 1 pound (lb). In some embodiments, the push wire 124 is secured to the plunger structure 122 by insert molding with a minimum tensile strength of about 1 lb. In some embodiments, the actuating structure 120 (e.g., the plunger structure 122 and the push wire 124) is placed within the body 110 and installed forward without obstruction. In some embodiments, the applicator assembly (e.g., the body 110, actuating structure 120, and cannula 130 assembled together), tip structure 140, and cap 150 are packaged separately.

[0078] 2A-2F show a body 110 of an intracanalicular injectate applicator device 100 according to certain embodiments. FIG. 2A shows a perspective view of the body 110. FIG. 2B shows a first side view of the body 110. FIG. 2C shows a second side view of the body 110 (e.g., rotated 90 degrees compared to FIG. 2B). FIG. 2D shows a first cross-sectional view of the body 110. FIG. 2E shows a second cross-sectional view of the body 110 (e.g., rotated 90 degrees compared to FIG. 2D). FIG. 2F shows a cross-sectional view of a non-circular portion of the body 110.

[0079] In some embodiments, the body 110 has a body tip 112 and an annular ridge 114. In some embodiments, the body 110 has no grease or release agent. In some embodiments, the cap 150 is lightly press-fit onto the body tip 112 (e.g., about 5 mm over the body tip 112). In some embodiments, the tip structure 140 is held in place by a protrusion (e.g., about 0.15 mm protrusion).

[0080] The body 110 may define a cavity having a first portion with a circular contour 116 and a second portion with a non-circular (e.g., elliptical) contour 118. The plunger structure 122 may be actuated by rotating 90 degrees into alignment with the non-circular contour 118 to expel the intracanalicular injectate from the intracanalicular injectate applicator device 100.

[0081] 3A-3F show actuation structure 120 of intracanalicular injectate applicator device 100, according to certain embodiments.

[0082] 3A-3D show an actuation structure 120 including a plunger structure 122. FIG 3A is a perspective view of the actuation structure 120. FIG 3B is a side view of the actuation structure 120. FIG 3C is a first cross-sectional view of the actuation structure 120. FIG 3D is a second cross-sectional view of the actuation structure 120.

[0083] The plunger structure 122 may be free of grease or mold release agents. The push wire 124 may be attached (e.g., glued), insert molded, and / or the like, into a slot in the plunger structure 122. A portion of the plunger structure 122 proximate the clip 126 may have a non-circular outer periphery that substantially matches the non-circular contour of a portion of the cavity of the body 110. To actuate the intracanalicular injectate applicator device 100, the plunger structure 122 is rotated such that the portion of the plunger structure 122 having the non-circular outer periphery is aligned with the non-circular contour of a portion of the cavity of the body 110.

[0084] Both distal ends of the push wire 124 may be cut, rounded and deburred. In some embodiments, the push wire 124 may undergo a passivation operation. The push wire 124 may be abrasive blasted (e.g., the entire outer length).

[0085] 3E shows clip 126 of plunger structure 122 interacting with body 110. A frictional interface between clip 126 of plunger structure 122 and body 110 may prevent plunger structure 122 from being installed without being physically actuated (e.g., a deflection of 0.2 to 0.5 on both clips 126 creates friction).

[0086] In some embodiments, the intracanalicular injectate applicator device 100 has a mounting mechanism (e.g., a thumb mounting mechanism) disposed on a side of the intracanalicular injectate applicator device 100 (e.g., a side of the body 110). For example, the intracanalicular injectate applicator device 100 may have one or more of a roller (e.g., a side rotation knob), a flexure push actuator, a slider, a living hinge, and / or the like. A living hinge may be a thin flexible hinge (e.g., a flexure bearing) made from the same material as the two rigid pieces it connects (e.g., plastic that is injection molded in the same orientation and crushed to mechanically move the intracanalicular injectate).

[0087] 3F-3G show an intracanalicular injectate applicator device 100 having an actuation structure 120 with a slider function. A user holds the body of the intracanalicular injectate applicator device 100 with the thumb and middle finger and actuates the slider function with the index finger. The slider function may be part of the actuation structure 120 with a push wire 124.

[0088] 4A-4I illustrate a cannula 130 of an intracanalicular injectate applicator device 100, according to certain embodiments. FIG. 4A illustrates a perspective view of the cannula 130. FIG. 4B illustrates a side view of the cannula 130 coupled (e.g., insert welded, injection molded, glued, pasted, insert molded) to the body 110. FIG. 4C illustrates a cross-sectional view of the cannula 130 coupled (e.g., insert welded, injection molded, glued, pasted, insert molded) to the body 110. The cannula 130 may be flush with a chamfer of the body 110.

[0089] In some embodiments, the cannula 130 is a 20 gauge thin-walled cannula 130. Both distal ends of the cannula 130 may be cut and deburred (e.g., inner and outer diameters). The cannula 130 may be abrasive blasted (e.g., entire outer length). The cannula 130 may undergo a passivation operation. In some embodiments, the cannula 130 is plastic. In some embodiments, the cannula 130 is metal.

[0090] Figures 4D-4I show a cannula 130 with a bevel. Figures 4D-4F show a cannula 130 with a rounded bevel (e.g., a rounded bevel cannula). Figures 4G-4I show a cannula 130 with a flat bevel (e.g., a flat bevel cannula). In some embodiments (e.g., instead of or in addition to having a tip structure 140), the intracanalicular injectate applicator device 100 has a collar 132 to prevent the cannula 130 from being overinserted into the punctum.

[0091] 5A-5I show tip structure 140 (e.g., a dilating tip, a flexible tip, a polymer tip, etc.) of intracanalicular injectate applicator device 100, according to certain embodiments. FIG. 5A shows a perspective view of tip structure 140. FIG. 5B shows a side view of tip structure 140. FIG. 5C shows a cross-sectional view of tip structure 140. FIG. 5D shows a side view of tip structure 140 prior to placement of intracanalicular injectate 160. FIG. 5E shows a side view of tip structure with intracanalicular injectate 160 placed thereon. FIGS. 5F-5H show the distal end (e.g., tip) of tip structure 140. FIG. 5I shows a cross-sectional view of tip structure 140.

[0092] The tip structure 140 is configured to dilate the punctum and place the intracanalicular injectate after dilating the punctum (e.g., dilating and placing occurs without removing the tip structure 140 from the punctum). In some embodiments, the tip structure 140 has a flexible, beveled tip configured to dilate the punctum and place the intracanalicular injectate at a location (e.g., a repeatable location) within the canalicular region.

[0093] In some embodiments, the punctum is 0.2-0.5 mm in diameter (e.g., this may be smaller than the intracanalicular injectate). The length of the vertical portion of the canalicular can be about 1.7-2 mm. The intracanalicular injectate may be about 2 mm in length (e.g., longer than the vertical portion of the canalicular canal). The intracanalicular injectate may hydrate over time, swell and retract into the vertical portion, where the intracanalicular injectate may remain while in use. In some embodiments, the diameter of the distal end (e.g., tip) of the tip structure 140 (e.g., distal end of the beveled end) may be about 0.1-0.4 mm. In some embodiments, the diameter of the distal end (e.g., tip) of the tip structure 140 (e.g., distal end of the beveled end) may be about 0.2-0.3 mm.

[0094] The material of tip structure 140 is strong (e.g., stiff) enough to dilate the punctum, yet flexible (e.g., mechanically soft) enough to allow intracanalicular injectate to pass through openings (e.g., to enter the canaliculus via the punctum) at the distal end of tip structure 140. In some embodiments, the distal end (e.g., tip) of tip structure 140 is radially flexible (e.g., bends outward, expands tip).

[0095] In some embodiments, the distal end (e.g., tip) of tip structure 140 has a beveled end (e.g., diagonal cut, truncated bevel, etc.). In some embodiments, the channel through the distal end of tip structure 140 is circular and the opening of the beveled end is oval shaped. The beveled end may allow the intracanalicular injectate to be placed in the canaliculus sooner and less deeply than a flat end. The beveled end may come to a smaller point than a flat end, which may allow for focusing force at the punctum to dilate the punctum.

[0096] The tip structure 140 may be made of one or more of medical grade silicone rubber, Class VI material, thermoplastic elastomer (TPE), fluorinated ethylene propylene (FEP), block copolymer, silicone. In some embodiments, the tip structure 140 has a Shore A durometer of about 50 to about 120. In some embodiments, the tip structure 140 has a Shore A durometer of about 50 to about 110. In some embodiments, the tip structure 140 has a Shore A durometer of about 50 to about 70. In some embodiments, the tip structure 140 has a Shore A durometer of about 85 to about 110. In some embodiments, the tip structure 140 has a Shore A durometer of about 90 to about 95. In some embodiments, the tip structure 140 has a Shore A durometer of about 95. The distal end of the tip structure 140 may facilitate delivery of an intracanalicular injectate (e.g., a cylindrical ocular insert having a diameter of about 0.45-0.54 mm and / or a length of about 2.92-3.08 mm) to the inferior canaliculus (e.g., lacrimal duct) or superior canaliculus (e.g., lacrimal duct). The lacrimal duct may have an average diameter of 0.4 mm and may expand to 0.7-0.9 mm when the distal end of the tip structure 140 is fully inserted. The distal end of the tip structure 140 may be sufficiently rigid to find the opening of the lacrimal duct and expand the opening by being inserted. The distal end of the tip structure 140 may remain within the lacrimal duct when the intracanalicular injectate is placed through the port (e.g., opening) of the distal end of the tip structure 140. The distal end of tip structure 140 may be flexible to allow an intracanalicular injectate of a first threshold diameter (e.g., 0.54 mm) to be pushed through, yet small enough to retain an intracanalicular injectate of a second threshold diameter (e.g., 0.45 mm) from falling out. Once placed, the intracanalicular injectate may be located 0.2-0.8 mm below the opening of the tear duct.

[0097] In some embodiments, the tip structure 140 has a silicone tip. After the entire tip is placed in the canalicular, the intracanalicular injectate is pushed through the elastic silicone opening. The intracanalicular injectate expands the canalicular as it approaches its final location. The diameter at the distal end of the tip structure 140 may be about 0.3-0.5 mm. The maximum diameter at the tip of the tip structure 140 may be about 0.7-0.9 mm. The maximum deployment depth may be about 1-5 mm. The hardness of the tip structure 140 may be stiff to find the punctum and anchor the tip of the tip structure. The hardness of the tip structure 140 may be flexible to place the intracanalicular injectate. In some embodiments, the distal end (e.g., tip) of the tip structure 140 has a flat tip (see FIG. 5F), a beveled tip (see FIG. 5G), and / or a slit tip (see FIG. 5H).

[0098] In some embodiments, the intracanalicular injectate applicator device 100 has a cannula 130 that is beveled. The cannula 130 may be rounded to locate the punctum and used to dilate the punctum to accept the cannula 130. The intracanalicular injectate may be placed once the bevel of the cannula 130 is no longer exposed. A metal collar may prevent overinsertion of the intracanalicular injectate applicator device 100 into the punctum. In some embodiments, the width of the cannula 130 at the tip is about 0.1-0.15 mm. In some embodiments, the outer diameter of the cannula is about .5-1.5 mm. In some embodiments, the maximum insertion depth is about 5-6 mm. In some embodiments, the flat tip of the cannula 130 creates a blunt surface to reduce possible tissue damage. In some embodiments, cannula 130 has a two-angled bevel design that allows the intracanalicular injectate to be placed close to the punctal opening (e.g., 0.5-0.75 mm deep).

[0099] 5I, tip structure 140 may include distal ends 510A and 510B, an outer surface 520, and an inner surface 530. Outer surface 520 may be sloped (e.g., curved, tapered, etc.) from distal end 510A to distal end 510B (e.g., this allows a user to view the punctum during use). Inner surface 530 may form an interior volume 540, a recess 542, and a channel 544. Inner surface 530 may include regions 532A-B that are one or more sloped, curved, tapered, funnel-shaped, etc., to go from a larger diameter near distal end 510A to a smaller diameter near distal end 510B.

[0100] In some embodiments, a first distal end of the cannula 130 is coupled to the body 110, and a second distal end of the cannula 130 is configured to be secured by the inner surface 530 within a channel 544 of the tip structure 140. In some embodiments, the region 532A guides the second distal end of the cannula 130 into the channel 544. In some embodiments, the second distal end of the cannula 130 abuts a portion of the region 532B. The region 532B may guide the intracanalicular injectate from the cannula 130 to an opening 546 (e.g., an elliptical opening) of the beveled edge 512. A portion of the inner surface 5530 is disposed over a portion of the body 110 (e.g., secured to the body 110 via a friction fit). In some embodiments, the recess 542 of the tip structure 140 interacts with (e.g., fits over) a protrusion (e.g., an annular ring) of the body 110.

[0101] In some embodiments, the tip structure 140 includes a distal end 510A configured to be attached to the body 110 of the intracanalicular injectate applicator device 100. The tip structure 140 may include an inner surface 530 that forms a recess (e.g., a channel 544) configured to receive the distal end of the cannula 130 (e.g., the other distal end of the cannula 130 is coupled to the body 110). The inner surface 530 of the tip structure 140 and the cannula 130 engage with one another (e.g., a friction fit) to prevent the cannula 130 from moving. The tip structure 140 may include a distal end 510B that includes a beveled edge 512 (e.g., a beveled tip) configured to be inserted into the punctum to dilate the punctum and place the intracanalicular injectate from the cannula 130 through the punctum and into the canaliculus.

[0102] 6A-6F show cap 150 of intracanalicular injectate applicator device 100 according to certain embodiments. FIG. 6A is a perspective view of cap 150. FIG. 6B is a bottom view of cap 150. FIG. 6C is a first side view of cap 150. FIG. 6D is a first cross-sectional view of cap 150. FIG. 6E is a second side view of cap 150 (e.g., rotated 90 degrees compared to FIG. 6C). FIG. 6F is a second cross-sectional view of cap 150 (e.g., rotated 90 degrees compared to FIG. 6D).

[0103] The cap 150 may include one or more (eg, two) openings 152 (eg, vents).

[0104] The cap 150 may be lightly press-fit onto the body 110. The cap 150 may be free of grease or release agents. The cap 150 may have one or more protrusions 154 (see, for example, FIGS. 6B, 6D, and 6F) from the interior surface that provide a press-fit with the body 110. In some embodiments, the cap 150 includes four protrusions 154 spaced 90 degrees apart from each other within the interior surface that provide a press-fit with the body.

[0105] 7 illustrates a method 700 for handling administration of an intracanalicular injectate using an intracanalicular injectate applicator device, according to certain embodiments. Although shown in a particular order or sequence, unless otherwise indicated, the order of operations may be modified. Thus, the illustrated embodiments should be understood as merely examples, and the illustrated operations may be performed in different orders, and some operations may be performed in parallel. Additionally, one or more operations may be omitted in various embodiments. Thus, not all operations are required in every embodiment.

[0106] At block 702, an intracanalicular injectate is loaded into a channel (e.g., lumen) formed by a cannula of an intracanalicular injectate applicator device. The channel is aligned with a cavity formed by a body of the intracanalicular injectate applicator device. An actuating structure of the intracanalicular injectate applicator device is disposed partially within the cavity of the body and partially within the channel of the cannula.

[0107] At block 704, a distal end of a tip structure (eg, a tip, a beveled tip, etc.) of an intracanalicular injectant applicator device is inserted into the canaliculus via the punctum to dilate the punctum.

[0108] At block 706, the intracanalicular injectate applicator device is rotated to further dilate the punctum to receive the intracanalicular injectate.

[0109] At block 708, the actuation structure is rotated to align a non-circular perimeter of the actuation structure (e.g., an elliptical shaped perimeter portion of the plunger structure) with a non-circular contour of the body cavity (e.g., an elliptical shaped portion of the body cavity).

[0110] At block 710, the actuation structure is actuated (eg, by pushing the distal end of the actuation structure) to inject (eg, place) the intracanalicular injectate into the canaliculus via the punctum.

[0111] In some embodiments, method 700 includes more or less operations than those shown in Figure 7. In some examples, method 700 may include the insertion of block 704 and the actuation of block 710 (e.g., an intracanalicular injectate applicator device is preloaded).

[0112] Figures 8A-12G show components of an intracanalicular injectate applicator device 100. The intracanalicular injectate applicator device 100 of Figures 8A-12G may have the same or similar functionality or structure as the intracanalicular injectate applicator device 100 illustrated in Figures 1A-7. Features in the figures may have the same or similar functionality as other features in other figures having like reference numbers.

[0113] 8A-8I illustrate an intracanalicular injectate applicator device 100 according to certain embodiments. FIG. 8A illustrates an exploded view of the intracanalicular injectate applicator device 100. FIG. 8B illustrates a side view of the actuating structure 120 inserted into the body 110 of the intracanalicular injectate applicator device 100. FIG. 8C illustrates a top view of the actuating structure 120 inserted into the body 110 of the intracanalicular injectate applicator device 100. FIG. 8D illustrates a side view of the assembled intracanalicular injectate applicator device 100. FIG. 8E illustrates a perspective view of the intracanalicular injectate applicator device 100. FIG. 8F illustrates a side view of the intracanalicular injectate applicator device 100. FIG. 8G illustrates a cross-sectional view of the intracanalicular injectate applicator device 100 (e.g., of FIG. 8F). Figure 8H shows a cross-sectional view of the distal end of the body 110 (e.g., detail of Figure 8G) with the intracanalicular injectate 160 installed. Figure 8I shows a cross-sectional view of the distal end of the body 110 with the intracanalicular injectate 160 in the loaded position (e.g., detail of Figure 8G).

[0114] Body 110 may have protrusions (eg, ridges) to prevent intracanalicular injectate applicator device 100 from slipping from a user's hand.

[0115] 9A-9I show the body 110 of the intracanalicular injectant applicator device 100 according to certain embodiments. FIG. 9A shows a perspective view of the body 110 of the injectant applicator device 100 coupled to the cannula 130. FIG. 9B shows a side view of the body 110 of the injectant applicator device 100 coupled to the cannula 130. FIG. 9C shows a top view of the body 110 of the injectant applicator device 100 coupled to the cannula 130. FIG. 9D shows a cross-sectional view of the body 110 of the injectant applicator device 100 coupled to the cannula 130 (e.g., cross-section AA in FIG. 9B). FIG. 9E shows a cross-sectional view of the body 110 of the injectant applicator device 100 coupled to the cannula 130 (e.g., cross-section BB in FIG. 9C). FIG. 9F shows a cross-sectional view of the distal end of the body 110 of the injectate applicator device 100 (e.g., detail C of FIG. 9D). FIG. 9G shows a cross-sectional view of the distal end of the body 110 of the injectate applicator device 100 (e.g., detail D of FIG. 9E). FIG. 9H shows a cross-sectional view of the distal end of the body 110 of the injectate applicator device 100 (e.g., detail E of FIG. 9E). FIG. 91 shows a cross-sectional view of the body 110 of the injectate applicator device 100 (e.g., section FF of FIG. 9B).

[0116] In some embodiments, the outer surface of cannula 130 may be roughened (e.g., by sandblasting) so that cannula 130 and body 110 are more secure to one another than if cannula 130 had a smoother outer surface. In some embodiments, cannula 130 may be attached to body 110 by bonding (e.g., glue), insert molding (e.g., injection molding), and / or the like.

[0117] 10A-10G illustrate an actuating structure 120 of an intracanalicular injectate applicator device 100 according to certain embodiments. FIG. 10A illustrates a perspective view of the actuating structure 120. FIG. 10B illustrates a top view of the actuating structure 120. FIG. 10C illustrates a cross-sectional view of the actuating structure 120 (e.g., section AA of FIG. 10B). FIG. 10D illustrates a side view of the actuating structure 120. FIG. 10E illustrates the push wire 124 of the actuating structure 120. FIG. 10F illustrates a cross-sectional view of the distal end of the actuating structure 120 (e.g., detail B of FIG. 10C). FIG. 10G illustrates a cross-sectional view of the distal end of the actuating structure 120 (e.g., section EE of FIG. 10D).

[0118] In some embodiments, the length of the push wire 124 is substantially straight (e.g., disposed about a longitudinal axis) and the distal end of the push wire 124 is curved (e.g., not disposed along a longitudinal axis). The curved distal end of the push wire 124 may be insert molded (e.g., injection molded) into the plunger structure 122 (e.g., such that the distal ends of the push wire 124 are more secure to one another than if the distal ends of the push wire 124 were not curved). In some embodiments, the push wire 124 may be roughened (e.g., by sandblasting) such that the push wire 124 and the plunger structure 122 are more secure to one another than if the push wire 124 had a smoother outer surface.

[0119] 11A-11E show a tip structure 140 of an intracanalicular injectate applicator device 100 according to certain embodiments. FIG. 11A is a perspective view of tip structure 140. FIG. 11B is a top view of tip structure 140. FIG. 11C is a cross-sectional view of tip structure 140 (e.g., section AA of FIG. 11B). FIG. 11D is a top view of the distal end of tip structure 140 (e.g., detail B of FIG. 11B). FIG. 11E is a cross-sectional view of the distal end of tip structure 140 (e.g., detail C of FIG. 11C).

[0120] In some embodiments, the tip structure 140 is made from a translucent (e.g., transparent, clear) material so that the user can visualize the intracanalicular injectate 160 as it advances from the tip structure 140 into the canalicular cavity (e.g., providing more user feedback and control).

[0121] 12A-12G illustrate cap 150 of intracanalicular injectate applicator device 100 according to certain embodiments. FIG. 12A is a perspective view of cap 150. FIG. 12B is a side view of cap 150. FIG. 12C is a top view of cap 150. FIG. 12D is a cross-sectional view of cap 150 (e.g., section AA of FIG. 12B). FIG. 12E is a top view of cap 150 (e.g., detail B of FIG. 12C). FIG. 12F is a rear view of cap 150. FIG. 12G is a rear view of cap 150 (e.g., detail C of FIG. 12F).

[0122] In some embodiments, the outer surface of cap 150 has protrusions (e.g., a series of small rectangular shaped protrusions along the face of cap 150) that provide an additional grip for the user when removing cap 150 from body 110. In some embodiments, body 110 has protrusions (e.g., a series of small rectangular shaped protrusions along the length of body 110) that provide additional grip to prevent finger slippage during expansion and injection (e.g., insertion).

[0123] In some embodiments, the cap 150 (e.g., cap expander, protective cap) has a tapered expander that faces distally and can be used to expand the punctal opening. The cap 150 can be used by a physician prior to an injection (e.g., insertion) procedure to widen the punctal opening and canaliculus prior to the injection (e.g., insertion) procedure. The cap 150 is attached (e.g., detachably coupled, detachably attached) to the body 110 so that the user can utilize the ergonomic body 110 to manipulate the expander to achieve expansion.

[0124] The small section (e.g., at the distal end) of the dilator tip of the cap 150 is tapered so that the distal end of the tip can be small enough (e.g., form a small enough point) to find and enter the punctum initially. Behind the tapered section is a straight section of uniform diameter (e.g., the diameter remains constant for a portion before subsequently tapering or becoming a larger diameter), which allows the dilator of the cap 150 to go deeper and dilate the entire length of the canaliculus where the intracanalicular injectate 160 will be placed (e.g., dilate the entire length of the canaliculus equal to the length of the intracanalicular injectate 160). The tip of the cap 150 may be referred to as the second tip structure, and the straight section of the cap 150 may be referred to as the substantially constant diameter section adjacent to the second tip structure of the cap 150. Conventional dilators have a single tapered section and dilate only the punctum. The cap 150 dilates both the punctum and the canaliculus. Expanding the longer section of the vertical tubule makes it easier for the user to advance the intracanalicular injectate 160 through the tubule.

[0125] In some embodiments, for puncta having widths less than the threshold width, the tip of the cap 150 is used for a first dilation procedure to partially dilate the punctum and canaliculus, and then the tip structure 140 is used for a second dilation procedure to finish dilating the punctum and / or canaliculus and inject (e.g., place, insert) the intracanalicular injectate 160 into the canaliculus. In some embodiments, for puncta having widths greater than the threshold width, the tip structure 140 is used for a dilation procedure to dilate the punctum and / or canaliculus and inject (e.g., place, insert) the intracanalicular injectate 160 into the canaliculus (e.g., without using the cap 150 to dilate the punctum and / or canaliculus).

[0126] 12H-12I illustrate an intracanalicular injectate applicator device 100 according to certain embodiments. FIG. 12H illustrates an exploded view of the intracanalicular injectate applicator device 100. FIG. 12I illustrates a kit 1200 including the intracanalicular injectate applicator device 100 disposed within a housing 1210. In some embodiments, the kit 1200 includes a housing 1210 that houses components. The components may include the intracanalicular injectate applicator device 100 and an intracanalicular injectate (e.g., an intracanalicular injectate loaded into the intracanalicular injectate applicator device 100 in a locked position and with the cap 150 attached to the body 110 within the kit 1200, an intracanalicular injectate separate from the intracanalicular injectate applicator device 100 within the kit 1200). The housing 1210 may be a foil pouch. The components within the kit 1200 may include a desiccant.

[0127] In some embodiments, the implant (e.g., intracanalicular implant 160, insert, depot, etc.) includes a therapeutic agent. In some embodiments, the implant (e.g., intracanalicular implant 160, insert, depot, etc.) is an injectable drug or injectable biologic administered by a physician to prevent, treat, or cure a disease or condition in a patient. The therapeutic agent can be a prostaglandin antagonist such as travoprost, bimatoprost, or latanoprost, a glucocorticoid such as dexamethasone or a pharma- ceutically acceptable salt thereof, a cyclosporine or cyclosporine derivative, or an adenine mimetic such as trabodenosone.

[0128] Therapeutic agents also include agents for treating conditions that may result from, for example, inflammatory or abnormal vascular conditions, occlusion of retinal veins, geographic atrophy, retinitis pigmentosa, retinoblastoma, etc. In the case of cancer, the agent may be, for example, an anti-cancer agent, an anti-VEGF, or a drug known for use in cancer treatment.

[0129] The therapeutic agent may be, for example, an anti-VEGF, a VEGFR1 inhibitor, a VEGFR2 inhibitor, a VEGFR3 inhibitor, an anti-PDGF, an angiogenesis inhibitor, sunitinib, E7080, Takeda-6d, tivozanib, regorafenib, sorafenib, pazopanib, axitinib, nintedanib, cediranib, vatalanib, motesanib, macrolides, sirolimus, everolimus, or a tyrosine kinase inhibitor. The drug (TKI) may be imatinib, gefitinib (Iressa), toceranib (Palladia), erlotinib (Tarceva), lapatinib (Tykerb), nilotinib, bosutinib, neratinib, lapatinib, vatalanib, dasatinib, erlotinib, gefitinib, imatinib, lapatinib, lestaurtinib, nilotinib, semaxanib, toceranib, or vandetanib.

[0130] The therapeutic agent may include a macromolecule, such as an antibody or an antibody fragment. The therapeutic macromolecule may include a VEGF inhibitor, such as ranibizumab, the active ingredient of the commercially available Lucentis™. VEGF (Vascular Endothelial Growth Factor) inhibitors can cause regression of abnormal blood vessels and improvement of vision when released into the vitreous humor of the eye. Examples of VEGF inhibitors include Lucentis™ (ranibizumab), Eylea™ (VEGF trap), Avastin™ (bevacizumab), and Macugen™ (pegaptanib). Also, platelet derived growth factor (PDGF) inhibitors, such as Fovista™ and anti-PGDF aptamers, may be delivered.

[0131] The therapeutic agent may include small molecules such as steroids or corticosteroids and their analogs. For example, the therapeutic corticosteroid may include one or more of the following: triamcinolone, triamcinolone acetonide, dexamethasone, dexamethasone acetate, fluocinolone, fluocinolone acetate, loteprednol etabonate, or analogs thereof. Alternatively or in combination, the therapeutic small molecule may include a tyrosine kinase inhibitor.

[0132] The therapeutic agent may include an anti-VEGF therapeutic agent. Anti-VEGF therapies and agents may be used to treat certain cancers and age-related macular degeneration. Examples of anti-VEGF therapeutic agents suitable for use in accordance with the embodiments described herein include one or more of the following: monoclonal antibodies, such as bevacizumab (Avastin™), or antibody derivatives, such as ranibizumab (Lucentis™), or small molecules that inhibit tyrosine kinases stimulated by VEGF, such as lapatinib (Tykerb™), sunitinib (Sutent™), sorafenib (Nexavar™), axitinib, or pazopanib.

[0133] The therapeutic agent may include a therapeutic agent suitable for treating dry AMD, such as one or more of Sirolim™ (rapamycin), Copaxone™ (glatiramer acetate), Othera™ complement C5aR inhibitor, ciliary neurotrophic factor, fenretinide, or Rheopheresis.

[0134] The therapeutic agent may include a therapeutic agent suitable for treating wet AMD, such as one or more of REDD14NP (Quark), Sirolimus™ (rapamycin), ATG003; EYELEA (VEGF trap), or a complement inhibitor (POT-4).

[0135] Therapeutic agents may include kinase inhibitors such as one or more of BIBW2992 (small molecule targeting EGFR / Erb2), imatinib (small molecule), gefitinib (small molecule), ranibizumab (monoclonal antibody), pegaptanib (small molecule), sorafenib (small molecule), dasatinib (small molecule), sunitinib (small molecule), erlotinib (small molecule), nilotinib (small molecule), lapatinib (small molecule), panitumumab (monoclonal antibody), vandetanib (small molecule) or E7080 (small molecule targeting VEGFR2, VEGFR3, and / or FGFR1, commercially available from Eisai Co., Ltd.). Therapeutic agents may include antibody drugs, such as bevacizumab, trastuzumab, cetuximab, and panitumumab.

[0136] Therapeutic agents may include a variety of classes of drugs, including, for example, steroids, nonsteroidal anti-inflammatory drugs (NSAIDS), anti-cancer drugs, antibiotics, anti-inflammatories (e.g., diclofenac), analgesics (e.g., bupivacaine), calcium channel blockers (e.g., nifedipine), antibiotics (e.g., ciprofloxacin), cell cycle inhibitors (e.g., simvastatin), and proteins (e.g., insulin). Therapeutic agents may include classes of drugs including, for example, steroids, NSAIDS, antioxidants, antibiotics, analgesics, inhibitors of vascular endothelial growth factor (VEGF), chemotherapeutic agents, and antiviral agents. Examples of NSAIDS are ibuprofen, meclofenamate sodium, mefenamic acid, salsalate, sulindac, tolmetin sodium, ketoprofen, diflunisal, piroxicam, naproxen, etodolac, flurbiprofen, fenoprofen calcium, indomethacin, celecoxib, ketorolac, and nepafenac.These drugs themselves can be small molecules, proteins, RNA fragments, proteins, glycosaminoglycans, carbohydrates, nucleic acids, inorganic and organic bioactive compounds, and specific bioactive substances include, but are not limited to, enzymes, antibiotics, antineoplastic agents, local anesthetics, hormones, angiogenic agents, antiangiogenic agents, growth factors, antibodies, neurotransmitters, psychotropic drugs, anticancer drugs, chemotherapeutic agents, drugs affecting the reproductive organs, genes, and oligonucleotides, or other structures.

[0137] Therapeutic agents may include proteins or other water-soluble biologics. These include peptides of various molecular weights. Peptides include therapeutic proteins and peptides, antibodies, antibody fragments, short chain variable fragments (scFv), growth factors, angiogenic factors, and insulin. Other water-soluble biologics are carbohydrates, polysaccharides, nucleic acids, antisense nucleic acids, RNA, DNA, short interfering RNA (siRNA), and aptamers.

[0138] The systems disclosed herein can be used to treat ocular diseases including, but not limited to, AMD, glaucoma, dry eye, allergic conjunctivitis, and pain and inflammation after cataract surgery.

[0139] The therapeutic agent may be used as part of a method to treat a presenting condition or to make a formulation to treat a presenting condition. For example, Azopt (Brinzolamide Ophthalmic Suspension) may be used to treat elevated intraocular pressure in patients with ocular hypertension and open angles. Betadyne in povidone-iodine eye drops may be used for preoperative disinfection of the periocular area and irrigation of the ocular surface. BETOPTIC (Betaxolol HCl) may be used to reduce intraocular pressure or for chronic open-angle glaucoma and / or ocular hypertension. CILOXAN (Ciprofloxacin HCl eye drops) may be used to treat infections caused by susceptible strains of microorganisms. NATACYN (Natamycin Ophthalmic Suspension) may be used to treat fungal blepharitis, conjunctivitis, and keratitis. NEVANAC (Nepafenac Ophthalmic Suspension) may be used to treat pain and inflammation associated with cataract surgery. TRAVATAN (Travoprost eye drops) may be used to reduce elevated intraocular pressure, open-angle glaucoma, or ocular hypertension. FML FORTE (Fluorometholone Ophthalmic Suspension) may be used to treat corticosteroid-responsive inflammation of the palpebral and bulbar conjunctiva, cornea, and anterior segment of the eye. LUMIGAN (Bimatoprost eye drops) may be used to reduce elevated intraocular pressure, open-angle glaucoma, or ocular hypertension. PRED FORTE (Prednisolone acetate) may be used to treat steroid-responsive inflammation of the palpebral and bulbar conjunctiva, cornea, and anterior segment of the eye. PROPINE (Dipivefrine hydrochloride) may be used to control intraocular pressure in chronic open-angle glaucoma. RESTASIS (Cyclosporine Ophthalmic Emulsion) is used to increase tear production in patients, such as those with ocular inflammation associated with keratoconjunctivitis sicca. ALREX (loteprednol etabonate ophthalmic suspension) may be used for the temporary relief of seasonal allergic conjunctivitis. LOTEMAX (loteprednol etabonate ophthalmic suspension) may be used to treat steroid-responsive inflammation of the palpebral and bulbar conjunctiva, cornea, and anterior segment of the eye. MACUGEN (pegaptanib sodium injection) may be used to treat neovascular (wet) age-related macular degeneration.OPTIVAR (azelastine hydrochloride) may be used to treat itchy eyes associated with allergic conjunctivitis. XALATAN (latanoprost eye drops) may be used to reduce elevated intraocular pressure in patients, such as those with open-angle glaucoma and ocular hypertension. BETIMOL (timolol eye drops) may be used to treat elevated intraocular pressure in patients with ocular hypertension and open-angle glaucoma. Latanoprost is a prodrug in the free acid form that is a prostanoid-selective FP receptor agonist. Latanoprost reduces intraocular pressure in patients with glaucoma with few side effects. Latanoprost is relatively insoluble in aqueous solutions, but is readily soluble in organic solvents that are commonly used to make microspheres using solvent evaporation.

[0140] Further embodiments of delivered therapeutic agents include those that specifically bind to target peptides in vivo to prevent interaction of the target peptide with its natural receptor or other ligands. For example, Avastin is an antibody that binds to VEGF. Also known are IL-1 traps that utilize the extracellular domain of the L-1 receptor, which prevents IL-1 from binding to and activating receptors on the surface of cells. Embodiments of delivered agents include nucleic acids, such as aptamers. For example, pegaptanib (MACUGEN) is a pegylated anti-VEGF aptamer. One advantage of the particle-hydrogel delivery method is that the aptamer is protected from the in vivo environment until it is released. Further embodiments of delivered agents include macromolecular drugs, a term that refers to drugs that are significantly larger than traditional small molecule drugs, i.e., drugs such as oligonucleotides (aptamers, antisense, RNAi), ribozymes, gene therapy nucleic acids, recombinant peptides, and antibodies.

[0141] One embodiment includes extended release of medication for allergic conjunctivitis. For example, ketotifen, antihistamines, and mast cell stabilizers may be provided as particles and released to the eye in effective amounts as described herein to treat allergic conjunctivitis. Seasonal allergic conjunctivitis (SAC) and perennial allergic conjunctivitis (PAC) are allergic conjunctival disorders. Symptoms include itchy and pink to reddish eyes. These two eye symptoms are mast cell mediated. Non-specific treatments to relieve symptoms traditionally include cold compresses, irrigating the eyes with tear substitutes, and avoiding allergens. Treatment traditionally consists of antihistamine mast cell stabilizers, dual mechanism antiallergic agents, or topical antihistamines. Corticosteroids can be effective but, due to side effects, are reserved for more severe forms of allergic conjunctivitis such as vernal keratoconjunctivitis (VKC) and atopic keratoconjunctivitis (AKC).

[0142] Moxifloxacin is the active ingredient of VIGAMOX, a fluoroquinolone approved for use in treating or preventing bacterial infections of the eye. VKC and AKC are chronic allergic diseases in which eosinophils, conjunctival fibroblasts, epithelial cells, mast cells, and / or TH2 lymphocytes cause inflammation in the biochemical and tissue structures of the conjunctiva. VKC and AKC can be treated by drugs used to suppress allergic conjunctivitis. Penetrating agents are drugs that may be included in gels, hydrogels, organogels, xerogels, and biomaterials as described herein. These are agents that help the drug penetrate into the target tissue. Penetrating agents may be selected as needed for the tissue, such as skin penetrating agents, tympanic membrane penetrating agents, and eye penetrating agents.

[0143] The agent may be a treatment for a disease of the rear of the eye, for example, where the disease of the rear of the eye is age-related macular degeneration (AMD), cystoid macular edema (CME), diabetic macular edema (DME), posterior uveitis, and diabetic retinopathy, or glaucoma.

[0144] Examples of drugs include anti-VEGF, VEGFR1 inhibitors, VEGFR2 inhibitors, VEGFR3 inhibitors, anti-PDGF, anti-PDGF-R, PDGFRβ inhibitors, and drugs including anti-angiogenic agents, sunitinib, E7080, Takeda-6d, tivozanib, regorafenib, sorafenib, pazopanib, axitinib, nintedanib, cediranib, vatalanib, motesanib, macrolides, sirolimus, everolimus, and tyrosine kinase The inhibitor may be a TKI, imatinib, gefitinib, toceranib, erlotinib, lapatinib, nilotinib, bosutinib, neratinib, lapatinib, vatalanib, a drug containing a low-solubility prostaglandin analogue for glaucoma, nepafenac, macrolides, rapamycin, sirolimus, tacrolimus, or a drug that acts to block the mTOR receptor for AMD (also called choroidal neovascularization (CNV)). mTOR refers to the mammalian target of rapamycin. The drug may be, for example, moxifloxacin, dexamethasone, travoprost, steroids, fluoroquinolones, prostaglandin analogues, prostamides.

[0145] Ocular diseases include ocular pathologies, where hyphema, ocular hypertension, and glaucoma are conditions that are treated with anterior chamber depots. Many drugs are suitable for delivery to the eye, for example, NSAIDs, steroids, antiglaucoma drugs, antivirals, antibiotics, mydriatics, and antifungals, which are administered by intracameral injection.

[0146] Some disease conditions are retrobulbar diseases. The term retrobulbar disease is recognized by those skilled in the art and generally refers to posterior ocular diseases that affect the vasculature and integrity of the retina, macula, or choroid, leading to impaired vision, loss of vision, or blindness. Posterior disease conditions may result from age, trauma, surgical intervention, and genetic factors. Some retrobulbar diseases are age-related macular degeneration (AMD), cystoid macular edema (CME), diabetic macular edema (DME), posterior uveitis, and diabetic retinopathy. Some retrobulbar diseases result from unwanted angiogenesis and blood vessel proliferation, such as macular degeneration and diabetic retinopathy. Drug treatment options for these and other ocular conditions may be provided by delivery of drugs from an implant.

[0147] The foregoing description sets forth numerous specific details, such as examples of specific systems, components, methods, and the like, to provide a good understanding of some embodiments of the present disclosure. However, it will be apparent to one of ordinary skill in the art that at least some embodiments of the present disclosure may be practiced without those specific details. In other instances, well-known components or methods have not been described in detail or have been presented in simple block diagram form to avoid unnecessarily obscuring the present disclosure. Thus, the specific details set forth are merely exemplary. It is contemplated that a particular implementation may vary from those example details and still be within the scope of the present disclosure.

[0148] References throughout this specification to "one embodiment," "one embodiment," or "some embodiments" mean that a particular feature, structure, or characteristic described in connection with that embodiment is included in at least one embodiment. Thus, the appearances of the phrases "in one embodiment," "in an embodiment," or "in some embodiments" in various places throughout this specification do not necessarily all refer to the same embodiment. In addition, the word "or" is intended to mean an inclusive "or" rather than an exclusive "or." When the word "about" or "approximately" is used herein, it is intended to mean that the nominal value presented is accurate to within ±10%.

[0149] Although the operations of the methods herein are illustrated and described in a particular order, the order of operations of each method may be changed, such as by performing certain operations in reverse order, such that certain operations are performed at least in part concurrently with other operations. In alternative embodiments, sub-operations of instructions or separate operations may be in an intermittent and / or alternating manner.

[0150] It is understood that the above description is illustrative and not restrictive. Many other embodiments will become apparent to those skilled in the art upon reading and understanding the above description. The scope of the present disclosure should therefore be determined with reference to the appended claims, along with the full scope of equivalents to which such claims are entitled. [Explanation of symbols]

[0151] 100 Intracanalicular Injection Applicator Device 110 Main unit 120 Operating Structure 130 Cannula 160 Intracanalicular injection 122 Plunger structure 124 Push Wire 128 Slot 126 clips 150 Cap 140 Tip structure 112 Main body tip 114 Annular ridge 132 Color 152 Opening 154 Protrusion 510A, 510B Distal end 512 Edge 520 outer surface 530 Inner surface 540 Internal Volume 542 Recess 544 Channels 532A~B area 546 Opening 5530 Inner surface 700 methods 1200 Kit 1210 Case

Claims

1. 1. An intracanalicular injectate applicator device comprising: A body forming a cavity; a cannula coupled to a first distal end of the body, the cannula forming a channel aligned with the cavity of the body, the cannula configured to store an intracanalicular injectate within the channel; a tip structure coupled to the body, the tip structure disposed about at least a portion of the cannula, a distal end of the tip structure configured to dilate the punctum by inserting the distal end of the tip structure through the punctum and into the canaliculus; an actuation structure configured to push the intracanalicular injectate through the channel and the distal end of the tip structure and into the canaliculus through the punctum while the distal end of the tip structure is inserted into the canaliculus through the punctum; 1. An intracanalicular injectate applicator device comprising:

2. 2. The intracanalicular injectate applicator device of claim 1, wherein the distal end of the tip structure has a Shore A durometer of about 50 to about 120, and the opening at the distal end of the tip structure has a diameter smaller than an outer diameter of the intracanalicular injectate.

3. 2. The intracanalicular injectate applicator device of claim 1, wherein a portion of the distal end of the tip structure comprises a beveled tip, the portion being configured to be fully inserted into the canalicular cavity through the punctum prior to injection of the intracanalicular injectate into the canalicular cavity.

4. The actuation structure comprises: a plunger structure configured to be disposed at least partially within the cavity of the body, a first distal end of the plunger structure configured to receive a force to cause actuation of the actuation structure; and a push wire, a first distal end of the push wire attached to a second distal end of the plunger structure, the second distal end of the push wire positioned within the channel of the cannula prior to the actuation of the actuation structure, the push wire configured to push the intracanalicular injectate through the channel in response to the actuation of the actuation structure; 10. The intracanalicular injectate applicator device of claim 1, comprising:

5. 5. The intracanalicular injectate applicator device of claim 4, wherein the plunger structure comprises a hooked clip configured for insertion into a corresponding recess formed by an outer surface of the body to prevent separation of the plunger structure and the body and to restrict movement of the intracanalicular injectate within the cannula.

6. a portion of the plunger structure located within the cavity of the body having a non-circular periphery; a portion of the cavity of the body having a non-circular contour corresponding to the non-circular perimeter; 5. The intracanalicular injectate applicator device of claim 4, wherein the actuation structure is rotated to actuate the actuation structure by aligning the non-circular outer periphery of the portion of the plunger structure with the non-circular contour of the portion of the cavity of the body.

7. 5. The intracanalicular injectate applicator device of claim 4, wherein the cannula is secured to the body by adhesive or insert molding, the second distal end of the plunger structure defines a slot, and the push wire is adhesively or insert molded into the slot.

8. 5. The intracanalicular injectate applicator device of claim 4, wherein the cavity of the body and the outer contour of the plunger structure are tapered to guide the push wire into the cannula.

9. 2. The intracanalicular injectate applicator device of claim 1, further comprising a cap configured to be removably attached to the body near the first distal end of the body, the cap defining a second tip structure and a substantially constant diameter section adjacent the second tip structure, the second tip structure and the substantially constant diameter section configured to pre-dilatate the punctum and at least a portion of the canaliculus by inserting the second tip structure and at least a portion of the substantially constant diameter section into the canaliculus via the punctum.

10. The intracanalicular injectate applicator device of claim 1 , wherein the channel of the cannula is configured to contain, protect and maintain alignment of the intracanalicular injectate.

11. A tip structure of an intracanalicular injectant applicator device, the tip structure comprising: a first distal end configured to be attached to a body of the intracanalicular injectate applicator device; an inner surface forming a recess configured to receive a first cannula distal end of a cannula of the intracanalicular injectate applicator device, a second cannula distal end of the cannula being coupled to the body; a second distal end including a beveled tip configured for insertion into a lacrimal punctum to dilate the punctum and to inject intracanalicular infusion from the cannula through the punctum and into the canaliculus; The advanced structure is provided with:

12. 12. The tip structure of claim 11, wherein the tip structure has a Shore A durometer of about 50 to about 120 and the opening at the second distal end of the tip structure has a diameter smaller than an outer diameter of the intracanalicular injectate.

13. The tip structure of claim 11, wherein the second distal end of the tip structure has a length of about 1-5 mm and a diameter of the second distal end of about 0.1-0.4 mm.

14. 1. A system including an intracanalicular injectate applicator device and an intracanalicular injectate, The intracanalicular injectate applicator device comprises: A body forming a cavity, a cannula coupled to a first distal end of the body, the cannula forming a channel aligned with the cavity of the body; a tip structure coupled to the body, the tip structure disposed about at least a portion of the cannula, a distal end of the tip structure configured to dilate the punctum by inserting the distal end of the tip structure through the punctum and into the canaliculus; and Operating structure, Equipped with the intracanalicular filler is loaded into the channel of the cannula of the intracanalicular filler applicator device, and the actuation structure is configured to push the intracanalicular filler through the channel and the distal end of the tip structure and into the canalicular through the punctum while the distal end of the tip structure is inserted into the canalicular through the punctum. The system.

15. A kit including a housing for housing a plurality of components, the plurality of components includes an intracanalicular injectate applicator device and an intracanalicular injectate; The intracanalicular injectate applicator device comprises: A body forming a cavity, a cannula coupled to the first distal end of the body, the cannula forming a channel aligned with the cavity of the body, the cannula configured to store an intracanalicular injectate within the channel; a tip structure coupled to the body, the tip structure disposed about at least a portion of the cannula, a distal end of the tip structure configured to dilate the punctum by inserting the distal end of the tip structure through the punctum and into the canaliculus; and an actuation structure configured to push the intracanalicular injectate through the channel and the distal end of the tip structure and into the canaliculus through the punctum while the distal end of the tip structure is inserted into the canaliculus through the punctum; Equipped with The kit.

16. 16. The kit of claim 15, wherein the housing is a foil pouch and the plurality of components further comprises a desiccant.

17. 16. The kit of claim 15, wherein the intracanalicular filler is loaded into the intracanalicular filler applicator device in the kit.

18. 1. An intracanalicular filler applicator device for use in a method of managing administration of an intracanalicular filler, said method comprising: loading the intracanalicular injectate into a channel formed by a cannula of an intracanalicular injectate applicator device, the channel being aligned with a cavity formed by a body of the intracanalicular injectate applicator device; inserting a distal end of a tip structure of the intracanalicular injectate applicator device into the canaliculus via a punctum to dilate the punctum; and actuating an actuating structure of the intracanalicular injectant applicator device while the distal end of the tip structure is inserted into the canalicular via the punctum to inject the intracanalicular injectant through the channel and the distal end of the tip structure into the canalicular via the punctum.

19. An intracanalicular injectate applicator device as described in claim 18, wherein the method further includes the step of rotating the actuating structure prior to said actuation of the actuating structure to align a non-circular outer periphery of the actuating structure with a corresponding non-circular contour of the cavity of the body.

20. 20. The intracanalicular injectate applicator device of claim 18, wherein the tip structure has a Shore A durometer of about 50 to about 120 and the opening at the distal end of the tip structure has a diameter smaller than an outer diameter of the intracanalicular injectate.

21. 1. An intracanalicular filler applicator device for use in a method for administering an intracanalicular filler, comprising: The method includes the steps of inserting a distal end of a tip structure of an intracanalicular injectate applicator device into the canalicular via a punctum to dilate the punctum, wherein an intracanalicular injectate is loaded into a channel formed by a cannula of the intracanalicular injectate applicator device, the channel being aligned with a cavity formed by a body of the intracanalicular injectate applicator device; and actuating an actuating structure of the intracanalicular injectant applicator device while the distal end of the tip structure is inserted into the canalicular via the punctum to inject the intracanalicular injectant through the channel and the distal end of the tip structure into the canalicular via the punctum.

22. An intracanalicular injectate applicator device as described in claim 21, wherein the method further includes the step of rotating the actuating structure prior to said actuation of the actuating structure to align a non-circular outer periphery of the actuating structure with a corresponding non-circular contour of the cavity of the body.

23. 22. The intracanalicular injectate applicator device of claim 21, wherein the tip structure has a Shore A durometer of about 50 to about 120, and the opening at the distal end of the tip structure has a diameter smaller than an outer diameter of the intracanalicular injectate.

24. 15. The system of claim 14, wherein the intracanalicular injectate comprises travoprost, cyclosporine, or dexamethasone.

25. 16. The kit of claim 15, wherein the intracanalicular injectate comprises travoprost, cyclosporine, or dexamethasone.

26. 20. The intracanalicular injectate applicator device of claim 18, wherein the intracanalicular injectate comprises travoprost, cyclosporine, or dexamethasone.

27. 22. The intracanalicular injectate applicator device of claim 21, wherein the intracanalicular injectate comprises travoprost, cyclosporine, or dexamethasone.

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