Intratubular reservoir inserter device

Abstract

Disclosed in certain embodiments is an intratubular injection applicator device that includes a body forming a cavity and a cannula coupled to a first distal end of the body. The cannula forms a passageway that is aligned with the cavity of the body. The cannula is configured to store an intratubular injection within the passageway. The intratubular injection applicator device further includes a tip structure coupled to the body. The tip structure is disposed around at least a portion of the cannula. A distal end of the tip structure is configured to dilate a punctum by inserting the distal end of the tip structure through the punctum into the canaliculus. The intratubular injection applicator device further includes an actuating structure that is configured to push the intratubular injection through the passageway and through the distal end of the tip structure and into the canaliculus via the punctum.

Description

[0001] Related Applications

[0002] This application claims the benefit of U.S. Provisional Application No. 63 / 153,316, filed Feb. 24, 2021, and U.S. Provisional Application No. 63 / 250,170, filed Sep. 29, 2021, the entire contents of which are hereby incorporated by reference in their entirety for all purposes. Technical Field

[0003] Embodiments of the present disclosure relate to inserter devices, and more particularly to intratubular reservoir inserter devices. Background Art

[0004] The punctum is a tiny opening on the eyelid margin. The punctum leads to the canaliculus. Intratubular injectables can be inserted into the canaliculus via the punctum. Intratubular injectables can be injectable drugs or injectable biologics that are injected by a doctor into a patient via the punctum. Intratubular injectables can be products suitable for preventing, treating, or curing diseases or disorders of a patient's eye. Brief Description of the Drawings

[0006] The present disclosure is illustrated in the drawings by way of example and not limitation in the figures of the accompanying drawings, in which like reference numerals indicate like elements. It should be noted that different references to "an" or "one" embodiment in the present disclosure do not necessarily refer to the same embodiment, and such references mean at least one.

[0007] Figure 1A -G shows an intratubular injectable applicator device according to certain embodiments.

[0008] Figure 2A -F shows the body of an intratubular injectable applicator device according to certain embodiments.

[0009] Figure 3A -G shows the actuation structure of an intratubular injectable applicator device according to certain embodiments.

[0010] Figure 4A -I shows the cannula of an intratubular injectable applicator device according to certain embodiments.

[0011] Figure 5A -I shows the tip structure of an intratubular injectable applicator device according to certain embodiments.

[0012] Figure 6A -F shows the cap of an intratubular injectable applicator device according to certain embodiments.

[0013] Figure 7Disclosed is a treatment method for administering an intracanalicular injection using an intracanalicular injector device according to certain embodiments.

[0014] Figure 8A -I shows an intracanalicular injector device according to certain embodiments.

[0015] Figure 9A -I shows the body of an intracanalicular injector device according to certain embodiments.

[0016] Figure 10A -G shows the actuation structure of an intracanalicular injector device according to certain embodiments.

[0017] Figure 11A -E shows the tip structure of an intracanalicular injector device according to certain embodiments.

[0018] Figure 12A -G shows the cap of an intracanalicular injector device according to certain embodiments.

[0019] Figure 12H -I shows an intracanalicular injector device according to certain embodiments. Specific Embodiments

[0020] The embodiments described herein relate to intracanalicular reservoir inserter devices (e.g., intracanalicular injector devices, punctal dilator applicators for delivering intracanalicular injections, syringes, etc.) for injecting an intracanalicular injection (e.g., injectable drugs, injectable biologics, reservoirs, etc.) into a patient's body.

[0021] Intracanalicular injections (e.g., polymer-based intracanalicular inserts, reservoirs) are used as therapies for treating various conditions present in the eye. The punctum is a small hole located at the medial corner of both the upper and lower eyelids. The punctum drains the tears constantly produced by the exocrine (lacrimal) glands of the eye. An intracanalicular injection, typically cylindrical (e.g., an intracanalicular insert), can be placed into the lower lacrimal canaliculus or into the upper lacrimal canaliculus through the punctum. The diameter of the intracanalicular injection is typically larger than the diameter of the punctum opening to aid in the retention of the intracanalicular injection. The intracanalicular injection can be an injectable drug or injectable biologic that is injected by a doctor through the punctum into the patient's body. The intracanalicular injection can be a product suitable for preventing, treating, or curing a disease or condition of the patient's eye.

[0022] Additional dilation procedures (e.g., punctal dilation) are used to expand the soft and delicate punctal tissue (e.g., the opening of the canaliculus) located around the punctum to allow passage of the injectate within the canaliculus. Punctal dilation is a daunting procedure as it requires carefulness to prevent damage to the surrounding tissue. This additional punctal dilation step is also cumbersome and time-consuming. Many physicians neglect to perform punctal dilation prior to injecting (e.g., inserting) the injectate within the canaliculus as there is a large variation in punctum diameter size between individuals and it can be difficult to know when punctal dilation is required.

[0023] During the injection (e.g., insertion) procedure of the injectate within the canaliculus, a hydrophilic polymer-based injectate within the canaliculus can absorb moisture from the ocular surface and surrounding tissue, causing an increase in the diameter of the injectate within the canaliculus. This is beneficial for retention of the injectate. However, it limits the amount of time available for the injectate within the canaliculus to successfully pass through the punctum (e.g., punctal opening), posing a challenge to the procedure.

[0024] The small size of the injectate within the canaliculus presents additional challenges as specialized instruments that are not standard for surgical procedures are required to insert the injectate within the canaliculus. Additionally, if clamped too tightly, the injectate within the canaliculus may be damaged and if held not tightly enough, it may drop off.

[0025] Variable patient dependence and the use of specialized instruments for the injection procedure (e.g., insertion procedure) can increase the likelihood of incorrect placement of the injectate within the canaliculus. The inferior canaliculus has two segments: a vertical segment approximately 2.5 millimeters (mm) long that is connected to a horizontal segment approximately 8 mm long via an angled ampulla. The effectiveness of the injectate within the canaliculus and the ability of the injectate within the canaliculus to remain within the canaliculus (e.g., lacrimal canaliculus) depend on the initial placement of the injectate within the canaliculus during the injection procedure (e.g., insertion procedure). Also, the proximity of the injectate to the punctal opening is important for delivery of the active agent (if present) from the injectate to the tear fluid.

[0026] The combination of these factors increases the complexity of the procedure and can result in injection (e.g., insertion) failure, damage to the lacrimal tissue, the need for a second injectate within the canaliculus due to the injectate within the canaliculus dropping off, and prolonged procedures. The amount of training and skill required to perform the injection procedure (e.g., insertion procedure) may deter physicians from choosing to use the injectate within the canaliculus and can lead to frustration when failures occur.

[0027] The devices, systems, and methods disclosed herein provide an intratubular injector device. The intratubular injector device simplifies and improves the efficiency of injection procedures (e.g., insertion procedures). The intratubular injector device protects the intratubular injection material during storage and transportation, easily and safely dilates the lacrimal punctum to enable the intratubular injection material to be received, and then deploys the intratubular injection material into the tubule.

[0028] The intratubular injector 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 the intratubular injection material in the channel. The intratubular injector device further includes a tip structure coupled to the body. The tip structure surrounds at least a portion of the cannula. The distal end of the tip structure is configured to dilate the lacrimal punctum by inserting the distal end of the tip structure through the lacrimal punctum into the tubule (e.g., and rotating the distal end). The intratubular injector device further includes an actuation structure that may be partially disposed in the cavity of the body and partially disposed in the channel of the cannula. The actuation structure is configured to push the intratubular injection material through the channel and through the distal end of the tip structure and into the tubule through the lacrimal punctum while the distal end of the tip structure is inserted through the lacrimal punctum into the tubule.

[0029] The systems, devices, and methods disclosed herein have advantages over traditional solutions. The intratubular injector device can be used to safely dilate the lacrimal punctum and insert the intratubular injection material faster than conventional solutions, which limits the amount of moisture absorbed by the intratubular injection material and increases the success rate of the injection (e.g., insertion). Compared to traditional solutions, the intratubular injector device avoids damage to the intratubular injection material and avoids dropping of the intratubular injection material. The intratubular injector device increases the likelihood of injecting (e.g., inserting) and retaining the intratubular injection material in the correct position. Compared to traditional solutions, the intratubular injector device reduces injury.

[0030] Although certain embodiments of the present disclosure relate to intratubular injectables, embodiments of the present disclosure can be used with one or more objects to be injected (e.g., inserted, deployed) into the punctum and / or lacrimal duct. In some embodiments, the object can include one or more objects to be injected (e.g., inserted, deployed) into the duct, injectable drugs, injectable biologics, objects for delivering drugs (e.g., medical drugs, therapeutic drugs), objects for occluding the punctum, occluders (e.g., punctum occluders, hard plastic objects shaped like anchors, objects with heads flush with the eyelid, etc.), injectables (e.g., located directly below the punctum), objects made of hydrogel, objects made of poly(lactic acid) (PLA), objects made of poly(lactic-co-glycolic acid) (PLGA), cylindrical objects, bioabsorbable objects, objects to be physically removed, polymer-based objects, expanded objects (e.g., inflated to occlude the punctum), polymer objects, elastomeric objects, etc.

[0031] Although certain embodiments of the present disclosure relate to an intratubular injectable applicator device for dilating the punctum and deploying a single intratubular injectable into the duct, embodiments of the present disclosure can be used to deploy multiple intratubular injectables (e.g., stack intratubular injectables) into a single duct (e.g., providing a first intratubular injectable into the duct via a first intratubular injectable applicator device and providing a second intratubular injectable into the same duct via a second intratubular injectable applicator device, providing the first intratubular injectable and the second intratubular injectable into the same duct via the same intratubular applicator device, etc.).

[0032] Figure 1A -G shows an intratubular injectable applicator device 100 (e.g., applicator, plunger-actuated intratubular injectable applicator device, punctum dilation applicator for delivering an intratubular injectable, syringe, etc.) according to certain embodiments. The intratubular injectable applicator device 100 includes a body 110, an actuation structure 120, and a cannula 130 (e.g., the intratubular injectable is stored in the cannula 130).

[0033] The intratubular injectable application device 100 can be used to inject (e.g., deploy, insert, etc.) an intratubular injectable 160 (e.g., reservoir) into a patient. The intratubular injectable 160 can be an injectable drug or injectable biologic that is injected by a doctor into the patient via the punctum. The intratubular injectable 160 can be a product suitable for preventing, treating, or curing a disease or disorder of the patient's eye. In some embodiments, the intratubular injectable 160 is Intracanalicular injectate. The intracanalicular injectate 160 may be referred to as an insert or an intracanalicular insert. The intracanalicular injectate administration device 100 may be referred to as an intracanalicular insert administration device, a syringe, an inserter device (e.g., for dilating the punctum and delivering the intracanalicular injectate), an injection device for dilating the punctum and delivering the intracanalicular injectate, etc. In some embodiments, the intracanalicular injectate 160 includes one or more of travoprost, cyclosporine, or dexamethasone.

[0034] The body 110 forms a cavity (e.g., a hollow core, etc.). The cannula 130 is coupled (e.g., attached) to the distal end of the body 110. In some embodiments, the cannula 130 is fixed to the body 110 by adhesion (e.g., glue), insert molding, and / or similar means. The cannula 130 forms a channel (e.g., a lumen) that is aligned with the cavity of the body 110. The cannula 130 is configured to store the intracanalicular injectate within the channel. In some embodiments, the channel of the cannula 130 is configured to store the intracanalicular injectate, protect the intracanalicular injectate, and maintain the alignment of the intracanalicular injectate. The actuation structure 120 is configured to be partially disposed within the cavity of the body 110 and partially disposed within the channel of the cannula 130. The actuation structure 120 is configured to push the intracanalicular injectate through the channel via the punctum into the canaliculus.

[0035] The actuation structure 120 may include a plunger structure 122 and a push wire 124. The plunger structure 122 may be configured to be at least partially disposed within the cavity of the body 110. The first distal end of the plunger structure 122 is configured to receive a force (e.g., a user presses 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). The first distal end of the push wire 124 is attached to the second distal end of the plunger structure 122. In some embodiments, the second distal end of the plunger structure 122 forms a groove 128, and the first distal end of the push wire 124 is insert molded into the groove 128 of the plunger structure 122. Before actuation of the actuation structure 120, the second distal end of the push wire 124 is disposed within the channel of the cannula 130. 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 wire. In some embodiments, the push wire 124 has a circular perimeter 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.

[0036] The plunger structure 122 may include a hook-shaped clip 126 that is configured to be inserted 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 limit movement of the intracanalicular injectate within the cannula 130.

[0037] In some embodiments, a portion of the plunger structure 122 disposed within the cavity of the body has a non-circular perimeter (e.g., elliptical, the portion of the plunger structure near the hook-shaped clip 126), and a portion of the cavity of the body 110 has a non-circular profile (e.g., elliptical) corresponding to the non-circular perimeter of this portion of the plunger structure 122. The actuation structure 120 can be rotated to align the non-circular perimeter of this portion of the plunger structure 122 with the non-circular profile of this portion of the cavity of the body 110 to actuate the actuation structure 120.

[0038] In some embodiments, the outer profiles of the cavity of the body 110 and the plunger structure 122 are tapered to guide the push wire 123 into the channel of the cannula 130.

[0039] In some embodiments, the microintraocular injector device 100 includes a cap 150 configured to be removably attached to the body 110 near the first distal end of the body 110 (e.g., near the cannula 130). The cap 150 can form an opening (e.g., a vent) to provide ventilation for the microintraocular injection.

[0040] The microintraocular injector device 100 can include a tip structure 140 (e.g., a flexible tip, a dilator tip) connected to the body 110. The tip structure 140 is disposed around at least a portion of the cannula 130. The distal end (e.g., the tip) of the tip structure 140 is configured to be inserted into the canaliculus via the punctum. The actuation structure 120 is configured to push the microintraocular injection through the channel of the cannula 130 and the distal end of the tip structure 140 into the canaliculus while inserting the distal end of the tip structure 140 into the canaliculus 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 canaliculus via the punctum and rotating the microintraocular injector device 100.

[0041] In some embodiments, at least a portion of the distal end (e.g., the tip) of the tip structure 140 has a hardness between 50 and 70. In some embodiments, the opening at the distal end of the tip structure 140 has a diameter smaller than the outer diameter of the microintraocular injection. In some embodiments, a portion of the distal end of the tip structure 140 includes one or more of the following: a flat tip, a beveled tip, a slit tip, a flat beveled tip, or a rounded beveled tip. A portion of the distal end of the tip structure 140 is configured to be fully inserted into the canaliculus via the punctum before injecting (e.g., deploying, inserting) the microintraocular injection into the canaliculus.

[0042] In some embodiments, the tip structure 140 does not have a beveled tip. A punctum that has been dilated (e.g., by the cap 150 or a separate dilation assembly) or a punctum that may have a resting diameter (e.g., above the average resting diameter) can receive the tip structure 140 (e.g., without a beveled tip).

[0043] In some embodiments, the injectant delivery device 100 includes a collar structure (e.g., in place of the tip structure 140) disposed around a portion of the cannula 130. The collar structure limits the depth of insertion of the distal end of the cannula 130 into the canaliculus via the punctum. The actuation structure 120 is configured to push the injectant within the canaliculus through the passageway and into the canaliculus while inserting the distal end of the cannula 130 into the canaliculus via the punctum.

[0044] In some embodiments, the system includes an intraluminal injectant applicator device 100 and an intraluminal injectant (e.g., loaded in the passageway of the cannula 130 of the intraluminal injectant applicator device 100). In some embodiments, the kit includes a housing that houses the components (e.g., see Figure 12I ). These components can include the intraluminal injectant applicator device 100 and the intraluminal injectant (e.g., loading the intraluminal injectant into the intraluminal injectant applicator device 100 in a locked position and having a cap 150 placed on the body 110 in the kit, the intraluminal injectant being separated from the intraluminal injectant applicator device 100 in the kit). The housing can be a foil pouch. The components in the kit can include a desiccant.

[0045] The intraluminal injectant applicator device 100 can be economically and precisely injection molded using thermoplastics, thermosetting materials, and / or machined metal components.

[0046] In some embodiments, the intraluminal injectant applicator device 100 does not have an adhesive. The intraluminal injectant applicator device 100 can be designed in a manner that eliminates the need for an adhesive that can cause mechanical failures and moisture in the packaging. The cannula 130 (e.g., a textured subcutaneous cannula) can be insert molded to the body 110 (e.g., a plastic handle).

[0047] In some embodiments, the shape of the intratubular injection is cylindrical and is stored within the lumen (e.g., channel) of the cannula 130 for protection and alignment maintenance during storage. Further, there is a short length of push wire 124 within the lumen of the cannula 130, which is located behind the intratubular injection. The push wire 124 can limit one end of the intratubular injection (e.g., the cylindrical injection) and can prevent the intratubular injection from moving in the inward direction. The push wire 124 can be insert molded onto the plunger structure 122 without using an adhesive and can rest at least partially within the cavity of the body 110 (e.g., within the hollow core of the handle). The plunger structure 122 can have a hooked clip 126 that is restricted by a notch in the body 110 to prevent separation of the plunger structure 122 and the body 110 (e.g., the body assembly). This can further limit the movement of the intratubular injection in the inward direction and can maintain the positioning of the intratubular injection throughout storage.

[0048] The tip structure 140 can be a flexible tip surrounding the cannula 130 (e.g., subcutaneous cannula) containing the intratubular injection. The tip structure 140 has a distal end (e.g., the flexible tip) that has an inner diameter smaller than the diameter of the intratubular injection, which prevents the intratubular injection from migrating in the distal direction during movement of the intratubular injection applicator device 100 (e.g., under worst-case shipping conditions). When a threshold force (e.g., a significant force) is applied, the material properties and flexibility of the distal end (e.g., the flexible tip) of the tip structure 140 allow the intratubular injection to pass through.

[0049] The tip structure 140 can form an annular recess (e.g., formed by the inner surface of the tip structure 140) that snaps onto a corresponding annular protrusion on the body 110 (e.g., formed by the outer surface of the body 110) to secure the tip structure 140 in place. This can simplify the assembly process and can enhance consistent repeatability.

[0050] In some embodiments, the cap 150 (e.g., protective cap) is friction fit onto the body 110. A light press fit can be achieved by ridges lining the inner diameter of the cap 150 in the longitudinal direction. The ridges can form an inner diameter smaller than the outer diameter of the body 110 (e.g., the ridges can be slotted onto the outer diameter of the body).

[0051] The inner circular core (e.g., cavity) of the body 110 and the circular shaft of the plunger structure 122 can have a taper to facilitate assembly. When the plunger structure 122 is inserted into the body 110, the tapered profile guides the push wire 124 into the cannula 130. The base of the inner core (e.g., cavity) of the body 110 can be chamfered to funnel the push wire 124 into the cannula 130 to prevent clogging during assembly.

[0052] The plunger structure 122 and the body 110 can form a "lock and key" locking mechanism to prevent the inadvertent deployment of the intratubular injection during transportation and operation. The body 110 can be a cylindrical tube and can form a non-circular (e.g., oval) groove (e.g., a part of the cavity can have a non-circular profile) that extends a certain distance into the cylindrical core of the body 110. The plunger structure 122 can have a corresponding non-circular (e.g., oval) perimeter (e.g., an extrusion) that extends a distance along the cylindrical axis of the plunger structure 122. The non-circular perimeter on the plunger structure 122 aligns with the non-circular profile of the body 110 to travel in the axial direction. If the non-circular perimeter and the non-circular profile (e.g., oval features) are not aligned, the maximum width of the non-circular perimeter of the plunger structure 122 (e.g., the oval extrusion of the plunger structure 122) will block the minimum width of the non-circular profile of the body 110 (e.g., the oval groove of the body 110).

[0053] In addition to the "lock and key" mechanism that prevents inadvertent forward actuation at the "locked position" (e.g., when the non-circular perimeter of the plunger structure 122 is not aligned with the non-circular profile of the body 110), the intratubular injection applicator device 100 can have another feature that prevents the plunger structure 122 from rotating inadvertently. The plunger structure 122 can include two clips 126 that appear to be spaced a set distance apart (e.g., on opposite sides of the plunger structure 122). The body 110 has a square profile where the clips 126 rest on the body 110. The square profile can be designed to prevent the plunger structure 122 from rotating until a threshold force (e.g., a significant force) is applied to rotate the plunger structure 122). The width of the body at the square profile location can match the stationary clip spacing distance. In response to the plunger structure 122 rotating 45 degrees, the clips 126 of the plunger structure 122 can bend to overcome the diagonal distance of the square profile of the body 110. The clips 126 of the plunger structure 122 can provide a resilient force that prevents rotation due to certain movements (e.g., worst-case transportation conditions). The rotational force can be achieved with one finger.

[0054] When the plunger structure 122 is positioned at the "unlocked position", the width of the square feature can be greater than (e.g., slightly greater than) the stationary width of the clips 126 of the plunger structure 122, which can cause the clips 126 to bend and create friction to prevent the plunger from moving at the "unlocked position" until a threshold force (e.g., a significant force) is applied. When the intratubular injection procedure is in progress, the interface between the bent clips 126 of the plunger structure 122 and the square feature (e.g., square profile) of the body 110 can provide physical feedback to the end user.

[0055] The cap 150 may have a cutout window, which enhances ventilation of the tip structure 140 (e.g., flexible tip) and the intratubular injectate (e.g., polymer-based intratubular injectate). In some embodiments, the intratubular injectate and the plastic material (e.g., the plastic material of the tip structure 140) will have moisture removed by inert nitrogen conditioning, and the cutout in the cap 150 (e.g., protective cap) can increase the rate of potential moisture removal from the internally stored intratubular injectate (e.g., polymer-based insert) and the surrounding materials. The plastic material (e.g., the plastic material of the tip structure 140) may exhibit low H 2 O adhesion and cohesion properties.

[0056] The intratubular injectate applicator device 100 may be configured to dilate the punctum to a threshold diameter to receive the intratubular injectate and then inject (e.g., deploy, insert) the intratubular injectate into the vertical lacrimal canaliculus through a smooth process without using additional maneuvers. One or more alert indicators may be incorporated into the intratubular injectate applicator device 100 to provide one or more alerts to the user.

[0057] The distal end (e.g., tubular flexible tip) of the tip structure 140 may be beveled such that the very tip of the bevel reaches an oval point, the size of which allows for use on puncta of different sizes.

[0058] The distal end (e.g., tip) of the tip structure 140 may be tubular to allow the intratubular injectate to pass through and may have a beveled tip such that initially only one wall is used to find the punctum opening. This allows for a greater wall thickness, resulting in a stiffer tool being used for dilation of puncta of different sizes.

[0059] The distal end (e.g., tip) of the tip structure 140 may have a bevel with a rounded tip and an oval profile, which can prevent trauma and enhance the user's ability to initially dilate the punctum. When inserted into a round punctum opening, the oval tip profile first elongates the tissue in one plane. The oval tip can be rotated to expand the entire circumference of the punctum. This can reduce the dilation speed and allow for successful use in patients with smaller punctum openings.

[0060] The tapered profile of the beveled tip at the distal end of the tip structure 140 may enable the tip structure 140 to gradually dilate the punctum opening to a threshold diameter (e.g., a diameter large enough to receive the intratubular injectate). A slow and delicate dilation speed is used to avoid trauma to the fibroelastic tissue surrounding the punctum opening. The angle of the bevel at the distal end of the tip structure 140 can optimize the dilation rate when the bevel is inserted into the canaliculus.

[0061] The flexibility and tubular structure of the distal end of the tip structure 140 (e.g., the dilating tip) prevent violent dilation. When the distal end begins to be inserted, the distal end of the tip structure 140 (e.g., the tip) can collapse and conform to the smaller profile of the small tube, and then slowly expand to the original shape of the distal end while exhibiting an outward force that causes the gradual expansion of the small tube tissue.

[0062] Once the entire bevel of the distal end of the tip structure 140 (e.g., the tip) is inserted inside the small tube, the outer diameter of the tip structure 140 (e.g., the dilating tip) suddenly increases to a diameter that prevents further insertion and over-dilation (e.g., the tip structure 140 has a distal end configured to enter the small tube, and the portion of the tip structure 140 adjacent to the distal end has a larger diameter than the distal end and is not configured to enter the small tube). Over-dilation of the punctum opening or the diameter of the small tube may damage the fibroelasticity of the lacrimal duct tissue and / or cause the orifice to be too large to properly retain the intratubular injectate.

[0063] Once threshold dilation (e.g., sufficient dilation) is achieved, the intratubular injectate applicator device 100 can be used in a syringe-like manner to transmit an axial load along the push wire 124, thereby ejecting the intratubular injectate through the lumen of the tip structure 140 (e.g., the flexible tip). A portion of the push wire 124 is rested inside the cannula 130 prior to actuation to additionally maintain the alignment of the push wire 124 and prevent the possibility of ineffectiveness. The inner wall of the cannula 130 (e.g., the subcutaneous cannula) prevents wire deflection and maintains a linear axial force vector for pushing the intratubular injectate into the small tube.

[0064] The user (e.g., based on the average size of an adult hand) can unlock and actuate the plunger with the index finger. During the entire insertion procedure (e.g., one-handed insertion), the intratubular injectate applicator device 100 can be held in one hand and operated with one hand.

[0065] A non-circular (e.g., oval) "key-lock" locking mechanism can provide a universal two-handed function. This can be achieved by using a non-circular (e.g., oval) shape that allows the plunger structure 122 and the body 110 to "unlock" and align when rotated 90 degrees clockwise and 90 degrees counterclockwise.

[0066] The sudden increase in the outer diameter of the tip structure 140 (e.g., the dilating tip) acts as a physical barrier and determines the position of the tip in the small tube prior to injecting (e.g., deploying, inserting) the intratubular injectate. The ability to accurately position the distal end of the tip structure 140 (e.g., the tip) in the small tube can provide accurate and consistent placement of the intratubular injectate (e.g., polymer-based insert) regardless of human factors.

[0067] The injection (e.g., deployment, insertion) depth of the intratubular injection can be controlled by the depth of the non-circular portion of the cavity (e.g., oval incision) inside the body 110. Once the non-circular portion of the cavity (e.g., oval portion) transitions to a circular portion, the portion of the plunger structure 122 having a non-circular (e.g., oval) perimeter can no longer travel forward.

[0068] The fixed stroke length of the plunger structure 122 and the pusher wire 124 (e.g., plunger and pusher wire assembly) in combination with the insertion of the distal end (e.g., tip) of the tip structure 140 into the barrier results in the intratubular injection being consistently injected (e.g., deployed, inserted) to a predetermined depth. These features that determine the injection (e.g., deployment, insertion) depth can be selected to deliver the intratubular injection to the vertical segment of the inferior lacrimal duct.

[0069] A shorter pusher wire 124 can be used to deliver the intratubular injection to a maximum depth of 1 millimeter (mm) below the punctal opening such that the intratubular injection is just above the angled ampulla in the vertical segment of the inferior lacrimal duct. The short injection (e.g., deployment, insertion) depth can be provided in part by the beveled distal end (e.g., beveled tip) of the tip structure 140, which allows the intratubular injection to be released over a shorter distance.

[0070] To place the intratubular injection in the horizontal region of the inferior lacrimal duct, the length of the pusher wire 124 can be increased to push the intratubular injection past the ampulla. The flexibility of the distal end of the tip structure 140 (e.g., dilating tip) can conform to the lacrimal duct anatomy and can guide the intratubular injection past the curved ampulla.

[0071] In some embodiments, the intratubular injection applicator device 100 has auditory and / or physical feedback indicating the injection (e.g., deployment, insertion) of the intratubular injection. Once the plunger structure 122 reaches the final “deployment position,” “injection position,” or “insertion position,” the auditory and / or physical feedback can be generated by how the clip 126 of the plunger structure 122 engages with the body 110. Once the plunger structure 122 reaches the deployment position, the clip 126 of the plunger structure 122 snaps into a recess in the body 110, producing an audible click. Snapping the plunger structure 122 into place in the deployment position also secures the pusher wire 124 in an exposed position (e.g., extended position of the pusher wire 124) and allows the user to further push the intratubular injection into place (e.g., if applicable) while the pusher wire 124 does not retract. When the clip 126 snaps into the recess, the snapping of the clip 126 of the plunger structure 122 into the recess in the body 110 can be physically felt through the mechanical vibration of the intratubular injection applicator device 100.

[0072] The intratubular injection applicator device 100 may include a visual feedback indicator (e.g., in addition to or instead of auditory and / or physical feedback). The plunger structure 122 may have an indicator (e.g., red and green markings printed on the plunger). The actuation structure 120 may be the only moving component in the intratubular injection applicator device 100. The indicator may be observable through a cutout hole that peeks into the cavity of the body 110. The position of the first indicator (e.g., red marking) may align when the intratubular injection has been fully injected (e.g., deployed, inserted) when transitioning to a second indicator (e.g., green marking).

[0073] The sizes of the push wire 124, cannula 130 (e.g., subcutaneous cannula), and tip structure 140 (e.g., flexible tip) may be adjusted to accommodate different sized intratubular injections. The intratubular injection applicator device 100 simplifies the process of the insertion procedure and reduces complexity. The amount of time taken to perform the insertion procedure may be reduced to prevent the intratubular injection from swelling before being placed into the tubule to reduce the likelihood of an unsuccessful insertion.

[0074] The design and composition of the intratubular injection applicator device 100 can include a cannula 130 (e.g., a subcutaneous cannula) that is insert-molded onto a body 110 (e.g., a cylindrical tubular body) without an adhesive. The cannula 130 can restrict the lateral movement of the intratubular injection. A push wire 124 can be insert-molded onto a plunger structure 122 without an adhesive. An actuation structure 120 (e.g., a push wire 124 and plunger structure 122 subassembly) can be assembled within a cavity (e.g., a core) of the body 110. The push wire 124 can restrict the proximal movement of the intratubular injection. The plunger structure 122 can have a hooked clip 126 that engages with the body 110 to prevent the plunger structure 122 and the body 110 (e.g., the plunger and body assembly) from separating. A tip structure 140 (e.g., a flexible tip) can surround the cannula 130 (e.g., a subcutaneous cannula) and can restrict the distal movement of the intratubular injection. When a threshold force is applied, the tip structure 140 can have material properties and flexibility that allow the intratubular injection to pass through. The tip structure 140 can have an annular recess that snaps onto a corresponding annular protrusion on the body 110 to hold the tip structure 140 in place and this can reduce the assembly time. A cap 150 (e.g., a protective cap) can be friction-fitted onto the body 110. The friction fit can be created by ridges inside the cap. A portion of the push wire 124 can rest within the cannula 130 prior to actuation to maintain the alignment of the push wire 124 and prevent the possibility of the push wire 124 from malfunctioning. The body 110 can have a cavity (e.g., an inner circular core) and the shaft of the plunger structure 122 can be tapered to assist in the alignment of the push wire 124 during assembly. A chamber at the bottom of the cavity (e.g., the inner core) of the body 110 can funnel the push wire 124 into the cannula 130.

[0075] The intratubular injection applicator device 100 can prevent the unintentional deployment of the intratubular injection (e.g., by restricting the locking features of the plunger structure 122). The body (e.g., a cylindrical tubular body) can include a non-circular (e.g., oval) slot that extends into the cylindrical core. The plunger structure 122 having a substantially identical non-circular (e.g., oval) extrusion extends along the cylindrical axis of the plunger structure 122. The non-circular perimeter of the plunger structure 122 aligns with the non-circular profile (e.g., oval slot) of the body 110 to travel in the distal direction. The deployment depth or stroke depth can directly depend on the depth of the non-circular portion (e.g., ovoid cutout) inside the body 110, which also serves as a locking feature. The plunger structure 122 can be rotated clockwise and counterclockwise to align with the body 110 for deployment. The flexible clip 126 of the plunger structure 122 and the square profile of the body 110 can engage with each other to prevent the rotation of the plunger structure 122 until a threshold force (e.g., via one finger) is applied. The clip 126 of the plunger structure 122 can provide an elastic force that can be applied (e.g., resisted, overcome) with one finger. When the plunger structure 122 is actuated, the flexible clip 126 of the plunger structure 122 and the square profile of the body 110 can engage to provide physical feedback in the form of resistance.

[0076] The cap 150 (e.g., a protective cap) can have a cutout window that enables a higher H 2 O diffusion rate of the internally stored polymer-based intratubular injection and components. For administering a hygroscopic intratubular injection that is unstable in the presence of H 2 O, the plastic material used to fabricate the intratubular injection applicator device 100 can have properties of low moisture cohesion and adhesion. Reducing the exposure of H 2 O inside the intratubular injection package may help maintain the integrity of the intratubular injection during storage. In some embodiments, the intratubular injection applicator device 100 (e.g., loaded with the intratubular injection) can be stored in a foil bag lined with a desiccant, which is configured to remove internal moisture and prevent moisture from entering. The intratubular injection applicator device 100 loaded with the intratubular injection can be stored in a foil bag with a desiccant packet.

[0077] The distal end of the tip structure 140 can be a beveled tubular flexible tip such that the very tip of the bevel reaches the oval point, which has a perimeter (e.g., circumference) that can be inserted into lacrimal puncta of different sizes. The beveled tip can be rounded at the end to prevent trauma. The bevel can allow for a greater wall thickness to increase tip stiffness while maintaining a profile small enough to dilate small lacrimal punctum openings. The oval beveled tip profile can reduce the rate of initial dilation when the tip first elongates the lacrimal punctum opening in one direction and allows the user to gradually dilate in all directions when rotated. This allows for use with patients with smaller lacrimal punctum openings. The bevel can be tapered to allow for a stable and progressive rate of lacrimal punctum dilation without traumatizing the lacrimal punctum tissue. When initially inserted into the small tube, the flexible tubular tip is capable of collapsing and gradually expanding, occurring at a slower rate of dilation. The tip structure 140 (e.g., flexible dilation tip) can have a suddenly increased outer diameter to prevent further insertion and over-dilation.

[0078] The intratubular injector device 100 can be used in a syringe-like manner to deliver an axial load along the push wire 124 to eject the intratubular injectant through the lumen of the tip structure 140 (e.g., flexible dilation tip). The intratubular injector device 100 can store the intratubular injectant, dilate the lacrimal punctum, and then inject (e.g., deploy, insert) the intratubular injectant and can be fully operated with one hand. The intratubular injector device 100 can be operated with a fully ambidextrous function.

[0079] The intratubular injector device 100 can consistently inject (e.g., deploy, insert) the intratubular injectant into the vertical section of the small tube. The beveled tip allows the intratubular injectant to be released from the beveled tip over a shorter distance. The intratubular injector device 100 can inject (e.g., deploy, etc.) the intratubular injectant through the vertical small tube and the ampulla such that the intratubular injectant resides in the horizontal section of the lacrimal duct. The tip structure 140 can assist in guiding the deployment of the intratubular injectant through the curved ampulla.

[0080] The intratubular injector device 100 can have a feedback feature that can be detected auditorily and / or physically once the intratubular injectant has been fully deployed. Once the plunger structure 122 has been fully deployed, the clip 126 of the plunger structure 122 can snap into a recess in the body 110. The body 110 and the clip 126 of the plunger structure 122 can be sized to snap in a way that can be felt (e.g., as a vibration) and an audible click can be heard. The clip 126 of the plunger structure 122 held in the recess of the body 110 can only be moved by a threshold force (e.g., cannot be moved without applying significant force).

[0081] The intratubular injection applicator device 100 may have a visual cue feature that can be visually detected once the intratubular injection is fully deployed. In some embodiments, markings on the plunger structure 122 (e.g., red and green markings printed on the plunger structure 122) can be observed through the cutout hole that peeks into the cavity of the body 110. A first marking (e.g., green marking) can be seen through the cutout only when the intratubular injection is fully deployed. A second marking (e.g., red marking) is visible only when the intratubular injection is pre-loaded into the intratubular injection applicator device 100 (e.g., and the plunger structure 122 has not been actuated).

[0082] 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. The intratubular injection applicator device 100 including the plunger structure 122 can be used in a syringe-like manner to transmit an axial load through the push wire 124 to inject (e.g., deploy, insert) the intratubular injection. The force is applied to the plunger structure 122 located at the distal end of the intratubular injection applicator device 100. For the intratubular injection applicator device 100 including a slider structure, the slider structure travels laterally along the body to transmit the axial load.

[0083] In some embodiments, the intratubular injection applicator device 100 includes a beveled cannula 130. The cannula 130 can be a subcutaneous metal cannula that is custom machined to have a blunt tip and a tapered bevel. The blunt tip prevents the intratubular injection applicator device 100 from piercing the lacrimal gland tissue and allows the intratubular injection applicator device 100 to locate the lacrimal punctum opening to begin dilation. The tapered bevel can be configured to gradually dilate the lacrimal punctum when the tapered bevel is driven into the canaliculus. The intratubular injection is stored within the lumen of the cannula 130 and can be injected (e.g., deployed, inserted) via the actuation structure 120 (e.g., plunger structure or slider structure). The bevel can expose a sufficient amount of the surface of the intratubular injection to the canaliculus tissue such that when the cannula 130 is removed, the intratubular injection remains in place by the frictional force between the intratubular injection and the canaliculus tissue. This prevents the intratubular injection from being inadvertently removed by the intratubular injection applicator device 100.

[0084] A collar (e.g., metal collar) can be provided around the cannula 130 to prevent the cannula 130 from being over-inserted into the canaliculus.

[0085] In some embodiments, the intratubular injector device 100 includes a flexible tip structure 140. The tip structure 140 can be used similarly to the beveled cannula 130. The softness of the tip of the tip structure 140 can reduce the risk of perforating the lacrimal gland tissue, thereby increasing the safety of the intratubular injector device 100. The inner lumen of the tip structure 140 (e.g., the flexible tip) can be smaller than normal size to retain the intratubular injectant during storage, and the flexible nature of the tip material allows the intratubular injectant to pass through when an actuating force is applied. The tip material is hard enough to adequately dilate the lacrimal punctum.

[0086] Either the beveled cannula 130 or the flexible tip structure 140 can be used. Both can provide lacrimal punctum dilation (e.g., increasing the diameter of the lacrimal punctum to be large enough to receive the intratubular injectant) and allow the intratubular injectant to pass through and be retained in the tubule.

[0087] One or more components of the intratubular injector device 100 can be 3D printed. The intratubular injector device 100 can be used to insert an intratubular injectant (e.g., a polymer insert) into the lacrimal tubule of a mammal.

[0088] In some embodiments, the intratubular injector device 100 stores multiple intratubular injectants and is used to insert multiple intratubular injectants into multiple tubules. In some embodiments, the intratubular injector device 100 is used to administer one or more products (e.g., liquids, solids, drugs, etc.) to the lacrimal punctum and / or lacrimal tubule. In some embodiments, the intratubular injector device 100 is used to insert an intratubular injectant comprising a drug (e.g., to administer the drug). In some embodiments, the intratubular injector device 100 is used to insert an intratubular injectant that does not include a drug (e.g., for occlusion only).

[0089] Figure 1A An exploded view of the intratubular injector device 100 is shown, which includes a body 110, an actuating structure 120 (e.g., a plunger structure 122 and a push wire 124), a cannula 130, a tip structure 140, and a cap 150. Figure 1B An assembled intratubular injector device 100 (e.g., without the cap 150) is shown, which includes a body 110, a plunger structure 122, and a tip structure 140. Figure 1C Shown in comparison with Figure 1B The assembled intratubular injector device 100 (e.g., without the cap 150) that has been rotated 90 degrees. Figure C shows a side view of the intratubular injector device 100 (e.g., without the cap 150). Figure 1D A cross-sectional view of the intratubular injector device 100 (e.g., without the cap 150) is shown. Figure 1EShows a cross-sectional view of the tip structure 140 of the intratubular injection applicator device 100, which has an intratubular injection 160 that has not been deployed (e.g., the push wire 124 is in the undeployed position) (e.g., intratubular injection). Figure 1E Shows a cross-sectional view of the tip structure 140 of the intratubular injection applicator device 100 (e.g., the intratubular injection has been deployed and the push wire 124 is in the deployed position). Figure 1G Shows a perspective view of the intratubular injection applicator device 100 with the tip structure 140 and the cap 150 removed.

[0090] In some embodiments, the overall length of the intratubular injection applicator device 100 (e.g., without the cap 150) is about 62 to 80 millimeters (mm). In some embodiments, the tip structure 140 is about 12 mm long. In some embodiments, the distal end (e.g., the tip) of the tip structure 140 is about 1 to 5 mm long. In some embodiments, the width of the plunger structure 122 (e.g., 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., the gripping portion) of the body 110 is about 37 mm. The length of the portion of the intratubular injection applicator device 100 between the central portion of the body 110 and the distal end (e.g., the end of the tip) of the tip structure 140 is about 19 mm. In some embodiments, the length of the cannula 130 is about 8 mm to 9 mm.

[0091] In some embodiments, the cannula 130 is fixed 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 fixed to the plunger structure 122 by insert molding with a minimum tensile strength of about 1 lb. In some embodiments, the actuation structure 120 (e.g., the plunger structure 122 and the push wire 124) is placed in the body 110 and deployed forward unobstructed. In some embodiments, the applicator assembly (e.g., the body 110, the actuation structure 120, and the cannula 130 assembled together), the tip structure 140, and the cap 150 are packaged separately.

[0092] Figure 2A -F shows the body 110 of the intratubular injection applicator device 100 according to certain embodiments. Figure 2A Shows a perspective view of the body 110. Figure 2B Shows a first side view of the body 110. Figure 2B Shows a first side view of the body 110. Figure 2C Shows a second side view of the body 110 (e.g., rotated 90 degrees compared to Figure 2B ). Figure 2DShows a first cross-sectional view of the body 110. Figure 2E Shows a second cross-sectional view of the body 110 (e.g., Figure 2D rotated 90 degrees compared to Figure 2F Shows a cross-sectional view of the non-circular portion of the body 110.

[0093] In some embodiments, the body 110 has a body tip 112 and an annular ridge 114. In some embodiments, the body 110 does not have a lubricant or a release agent. In some embodiments, the cap 150 is gently press-fitted onto the body tip 112 (e.g., on the body tip 112 of about 5 mm). In some embodiments, the tip structure 140 is held in place by a protrusion (e.g., a bump of about 0.15 mm).

[0094] The body 110 can form a cavity having a first portion with a circular profile 116 and a second portion with a non-circular (e.g., elliptical) profile 118. The plunger structure 122 can be rotated 90 degrees to align with the non-circular profile 118 to actuate and push the in-tube injectant out of the in-tube injectant applicator device 100.

[0095] Figure 3A -F shows the actuation structure 120 of the in-tube injectant applicator device 100 according to certain embodiments.

[0096] Figure 3A -D shows the actuation structure 120 including the plunger structure 122. Figure 3A Is a perspective view of the actuation structure 120. Figure 3B Is a side view of the actuation structure 120. Figure 3C Is a first cross-sectional view of the actuation structure 120. Figure 3D Is a second cross-sectional view of the actuation structure 120.

[0097] The plunger structure 122 may not have a lubricant or a release agent. The push wire 124 can be adhered (e.g., glued), insert molded, and / or similar ways into the groove of the plunger structure 122. The portion of the plunger structure 122 near the clip 126 can have a non-circular perimeter that substantially matches the non-circular profile of a portion of the cavity of the body 110. To actuate the in-tube injectant applicator device 100, the plunger structure 122 will be rotated so that the portion of the plunger structure 122 having a non-circular perimeter aligns with the non-circular profile of a portion of the cavity of the body 110.

[0098] The two distal ends of the push wire 124 can be cut, rounded, and polished. In some embodiments, the push wire 124 can undergo a passivation operation. The push wire 124 can be abrasive jet (e.g., the entire outer length).

[0099] Figure 3EA clip 126 that engages with the plunger structure 122 and the body 110 is shown. The friction interface between the clip 126 on the plunger surface 122 and the body 110 can prevent the deployment of the plunger structure 122 without being physically actuated (e.g., a 0.2 - 0.5 deflection on the two clips 126 generates friction).

[0100] In some embodiments, the intratubular injector device 100 has a deployment mechanism (e.g., a thumb deployment mechanism) disposed on the side of the intratubular injector device 100 (e.g., the side of the body 110). For example, the intratubular injector device 100 can have one or more of a roller (e.g., a side - rolling knob), a curved push actuator, a slider, a living hinge, and / or the like. The living hinge can be a thin flexible hinge (e.g., a flexure bearing) made of the same material as two rigid members connected to the living hinge (e.g., plastic injection - molded in the same direction to mechanically move the intratubular injection).

[0101] Figure 3F -G shows the intratubular injector device 100 having an actuation structure 120 with a slider block feature. The user grasps the body of the intratubular injector device 100 with the thumb and middle finger and actuates the slider block feature with the index finger. The slider block feature can be part of the actuation structure 120 having a push wire 124.

[0102] Figure 4A -I shows the cannula 130 of the intratubular injector device 100 according to certain embodiments. Figure 4A A perspective view of the cannula 130 is shown. Figure 4B A side view of the cannula 130 coupled (e.g., insert - welded, injection - molded, adhered, glued, insert - molded) to the body 110 is shown. Figure 4C A cross - sectional view of the cannula 130 coupled (e.g., insert - welded, injection - molded, adhered, glued, insert - molded) to the body 110 is shown. The cannula 130 can be flush with the chamfer of the body 110.

[0103] In some embodiments, the cannula 130 is a 20 - gauge thin - wall cannula 130. The two distal ends of the cannula 10 can be cut and polished (e.g., inner diameter and outer diameter). The cannula 130 can be abrasive - jet (e.g., the entire outer length). The cannula 130 can undergo a passivation operation. In some embodiments, the cannula 130 is plastic. In some embodiments, the cannula 130 is metal.

[0104] Figure 4D -I shows the cannula 130 having a bevel. Figure 4D -F shows the cannula 130 having a circular bevel (e.g., a circular bevel cannula).Figure 4G -I shows the cannula 130 with a flat bevel (e.g., a flat bevel cannula). In some embodiments (e.g., instead of having the tip structure 140 or in addition to having the tip structure 140), the microtubule injectant applicator device 100 has a collar 132 to prevent the cannula 130 from being inserted too far into the lacrimal punctum.

[0105] Figure 5A -I shows the tip structure 140 (e.g., a dilating tip, a flexible tip, a polymeric tip, etc.) of the microtubule injectant applicator device 100 according to certain embodiments. Figure 5A is a perspective view of the tip structure 140. Figure 5B is a side view of the tip structure 140. Figure 5C is a cross-sectional view of the tip structure 140. Figure 5D is a side view of the tip structure 140 before deploying the microtubule injectant 160. Figure 5E is a side view of the tip structure with the deployed microtubule injectant 160. Figure 5F -H shows the distal end (e.g., the tip) of the tip structure 140. Figure 5I is a cross-sectional view of the tip structure 140.

[0106] The tip structure 140 is configured to dilate the lacrimal punctum and deploy the microtubule injectant after dilating the lacrimal punctum (e.g., dilating and deploying without removing the tip structure 140 from the lacrimal punctum). In some embodiments, the tip structure 140 has a flexible bevel tip that is configured to dilate the lacrimal punctum and deploy the microtubule injectant to a location (e.g., a repeatable location) in the microtubule.

[0107] In some embodiments, the diameter of the lacrimal punctum is 0.2 mm to 0.5 mm (e.g., it can be smaller than the microtubule injectant). The length of the vertical portion of the microtubule can be about 1.7 mm to 2 mm. The length of the microtubule injectant can be about 2 mm (e.g., it can be longer than the vertical cross-section of the microtubule). The microtubule injectant can hydrate and expand over time to retract and move into the vertical segment, where it can remain when in use. In some embodiments, the diameter of the distal end (e.g., the tip) (e.g., the distal end of the beveled end) of the tip structure 140 can be about 0.1 mm to 0.4 mm. In some embodiments, the diameter of the distal end (e.g., the tip) (e.g., the distal end of the beveled end) of the tip structure 140 can be about 0.2 mm to 0.3 mm.

[0108] The material of the tip structure 140 can be strong enough (e.g., hard) to dilate the punctum and flexible enough (e.g., mechanically soft) to allow the intratubular injectate to pass through an opening in the distal end of the tip structure 140 (e.g., enter the canaliculus through the punctum). In some embodiments, the distal end (e.g., tip) of the tip structure 140 has radial flexibility (e.g., bends outward, expands the tip).

[0109] In some embodiments, the distal end (e.g., tip) of the tip structure 140 has a beveled end (e.g., diagonal cut, cut bevel, etc.). In some embodiments, the channel through the distal end of the tip structure 140 is circular and the opening at the beveled end is oval. The beveled end can allow the intratubular injectate to be deployed into the canaliculus faster than a flat end and not as deep as a flat end. The beveled end can achieve a smaller point than a flat end, and the smaller point can allow the force to be concentrated on the punctum to dilate the punctum.

[0110] The tip structure 140 can be made of one or more of medical-grade silicone rubber, Class VI materials, thermoplastic elastomer (TPE), fluorinated ethylene propylene (FEP), block copolymer, silicone resin, etc. In some embodiments, the tip structure 140 has a Shore A hardness of about 50 to about 120. In some embodiments, the tip structure 140 has a Shore A hardness of about 50 to about 110. In some embodiments, the tip structure 140 has a Shore A hardness of about 50 to about 70. In some embodiments, the tip structure 140 has a Shore A hardness of about 85 to about 110. In some embodiments, the tip structure 140 has a Shore A hardness of about 90 to about 95. In some embodiments, the tip structure 140 has a Shore A hardness of about 95. The distal end of the tip structure 140 can facilitate delivery of an intratubular injectate (e.g., a cylindrical eye insert having a diameter of about 0.45 mm to 0.54 mm and / or a length of about 2.92 mm to 3.08 mm) to the lower canaliculus (e.g., lacrimal duct) or upper canaliculus (e.g., lacrimal duct). The lacrimal duct can have an average diameter of 0.4 mm and can expand to 0.7 mm to 0.9 mm once the distal end of the tip structure 140 is fully inserted. The distal end of the tip structure 140 can be hard enough to find and pass through the opening that dilates the lacrimal duct by insertion. When the intratubular injectate is deployed through the mouth (e.g., opening) of the distal end of the tip structure 140, the distal end of the tip structure 140 can remain in the lacrimal duct. The distal end of the tip structure 140 can be flexible to allow an intratubular injectate of a first threshold diameter (e.g., 0.54 mm) to be advanced through and also small enough to keep an intratubular injectate of a second threshold diameter (e.g., 0.45 mm) from falling off. The intratubular injectate can be placed 0.2 mm to 0.8 mm below the opening of the lacrimal duct after deployment.

[0111] In some embodiments, the tip structure 140 has a silicone tip. After the entire tip is fixed in the small tube, the injectate within the small tube is pushed through the elastic silicone opening. The injectate within the small tube expanding the small tube means that the injectate within the small tube approaches its final position. The diameter at the distal end of the tip structure 140 can be about 0.3 mm to 0.5 mm. The maximum diameter of the tip of the tip structure 140 can be about 0.7 mm to 0.9 mm. The maximum placement depth can be about 1 mm to 5 mm. The tip structure 140 can be firm in hardness for finding the lacrimal punctum and anchoring the tip of the tip structure. The tip structure 140 can be flexible in hardness for deploying the injectate within the small tube. In some embodiments, the distal end (e.g., the tip) of the tip structure 140 has a flat tip (see Figure 5F ), beveled tip (see Figure 5G ), and / or slit tip (see Figure 5H ).

[0112] In some embodiments, the injectate applicator device 100 has a beveled cannula 130. The cannula 130 can be circular for finding the lacrimal punctum and dilating the lacrimal punctum to receive the cannula 130. Once the bevel of the cannula 130 is no longer exposed, the injectate within the cannula can be deployed. A metal collar can prevent the injectate applicator device 100 from being inserted too far into the lacrimal punctum. In some embodiments, the width of the cannula 130 at the tip is about 0.1 mm to 0.15 mm. In some embodiments, the outer mouth mold diameter of the cannula is about 0.5 mm to 1.5 mm. In some embodiments, the maximum insertion depth is about 5 mm to 6 mm. In some embodiments, the flat tip of the cannula 130 forms a blunt surface to reduce potential tissue damage. In some embodiments, the cannula 130 has a two-angle bevel design that allows the injectate to be placed closer to the lacrimal punctum opening (e.g., 0.5 mm to 0.75 mm deep).

[0113] Reference Figure 5I , the tip structure 140 can include distal ends 510A and 510B, an outer surface 520, and an inner surface 530. The outer surface 520 can be inclined (e.g., curved, tapered, etc.) from the distal end 510A to the distal end 510B (e.g., to allow the user to view the lacrimal punctum during use). The inner surface 530 can form an internal volume 540, a recess 542, and a channel 544. The inner surface 530 can include regions 532A - B that are one or more of inclined, curved, tapered, funnel-shaped, etc., to form a larger diameter near the distal end 510A to a smaller diameter near the distal end 510B.

[0114] In some embodiments, a first distal end of cannula 130 is coupled to body 110, and a second distal end of cannula 130 is configured to be secured by an inner surface 530 within a channel 544 of tip structure 140. In some embodiments, region 532A guides the second distal end of cannula 130 into channel 544. In some embodiments, the second distal end of cannula 130 abuts a portion of region 532B. Region 532B may guide an intracanalicular injection from cannula 130 to an opening 546 (e.g., an oval opening) in bevel edge 512. A portion of inner surface 5530 is disposed on a portion of body 110 (e.g., secured to body 110 by a friction fit). In some embodiments, recess 542 of tip structure 140 engages (e.g., snaps onto) a protrusion (e.g., an annular ring) of body 110.

[0115] In some embodiments, tip structure 140 includes a distal end 510A configured to be attached to body 110 of an intracanalicular injection applicator device 100. Tip structure 140 may include an inner surface 530 that forms a recess (e.g., channel 544) configured to receive a distal end of cannula 130 (e.g., another distal end of cannula 130 is coupled to body 110). Inner surface 530 of tip structure 140 and cannula 130 may cooperate with each other (e.g., a friction fit) to prevent movement of cannula 130. Tip structure 140 may include a distal end 510B that includes a bevel edge 512 (e.g., a beveled tip) configured to be inserted into a punctum to dilate the punctum and deploy an intracanalicular injection from cannula 130 to a canaliculus via the punctum.

[0116] Figure 6A -F shows cap 150 of an intracanalicular injection applicator device 100 according to certain embodiments. Figure 6A is a perspective view of cap 150. Figure 6B is a bottom view of cap 150. Figure 6C is a first side view of cap 150. Figure 6D is a first cross-sectional view of cap 150. 6E is a second side view of cap 150 (e.g., rotated 90 degrees compared to Figure 6C ). Figure 6F is a second cross-sectional view of cap 150 (e.g., rotated 90 degrees compared to Figure 6D ).

[0117] Cap 150 may include one or more (e.g., two) openings 152 (e.g., vents).

[0118] Cap 150 may be press-fit onto body 110. Cap 150 may not have a lubricant or a release agent. Cap 150 may have one or more protrusions 154 from an inner surface (e.g., see Figure 6B, 6D and 6F), which provides a press fit with the body 110. In some embodiments, the cap 150 includes four protrusions 154, each spaced 90 degrees in the inner surface, providing a press fit with the body.

[0119] Figure 7 A treatment method 700 for administering an intracanalicular injection using an intracanalicular injection applicator device according to certain embodiments is shown. Although shown in a particular order or sequence, the order of operations may be modified unless otherwise stated. Accordingly, the illustrated embodiments should be understood only as examples, and the illustrated operations may be performed in a different order and some operations may be performed in parallel. Additionally, one or more operations may be omitted in various embodiments. Thus, not all embodiments require all operations.

[0120] At block 702, an intracanalicular injection is loaded into a channel (e.g., lumen) formed by a cannula of the intracanalicular injection applicator device. The channel is aligned with a cavity formed by the body of the intracanalicular injection applicator device. The actuation structure of the intracanalicular injection applicator device is partially disposed within the cavity of the body and partially disposed within the channel of the cannula.

[0121] At block 704, the distal end (e.g., tip, beveled edge, etc.) of the tip structure of the intracanalicular injection applicator device is inserted through a punctum into the canaliculus to dilate the punctum.

[0122] At block 706, the intracanalicular injection applicator device is rotated to further dilate the punctum to receive the intracanalicular injection.

[0123] At block 708, the actuation structure is rotated to align a non-circular perimeter (e.g., an elliptical perimeter portion of a plunger structure) of the actuation structure with a non-circular profile (e.g., an elliptical portion of the body cavity) of the cavity of the body.

[0124] At block 710, the actuation structure is actuated (e.g., by pressing the distal end of the actuation structure) to inject (e.g., deploy) the intracanalicular injection through the punctum into the canaliculus.

[0125] In some embodiments, method 700 includes more or fewer operations than Figure 7 shown. In some examples, method 700 may include the insertion of block 704 and the actuation of block 710 (e.g., preloading the intracanalicular injection applicator device).

[0126] Figures 8A - 12G Components of an intracanalicular injection applicator device 100 are shown. Figures 8A - 12G The intracanalicular injection applicator device 100 of Figures 1A - 7The same or similar functions or structures as those of the intratubular injector device 100 described in [reference]. The features in the figures may have the same or similar functions as other features with similar markings in other figures.

[0127] Figure 8A -I shows an intratubular injector device 100 according to certain embodiments. Figure 8A A exploded view of the intratubular injector device 100 is shown. Figure 8B A side view of an actuation structure 120 to be inserted into a body 110 of the intratubular injector device 100 is shown. Figure 8C A top view of an actuation structure 120 to be inserted into a body 110 of the intratubular injector device 100 is shown. Figure 8D A side view of an assembled intratubular injector device 100 is shown. Figure 8E A perspective view of the intratubular injector device 100 is shown. Figure 8F A side view of the intratubular injector device 100 is shown. Figure 8G A cross-sectional view of the intratubular injector device 100 is shown (e.g., Figure 8F [specific cross-section]). Figure 8H A cross-sectional view of a distal end of the body 110 deploying an intratubular injection 160 is shown (e.g., Figure 8G a detailed view of [specific part]). Figure 8I A cross-sectional view of a distal end of the body 110 including an intratubular injection 160 in a loading position is shown (e.g., Figure 8G a detailed view of [specific part]).

[0128] The body 110 may have a protrusion (e.g., a ridge) to prevent the intratubular injector device 100 from slipping out of the user's hand.

[0129] Figure 9A -I shows the body 110 of the intratubular injector device 100 according to certain embodiments. Figure 9A A perspective view of the body 110 of the injector device 100 coupled to a cannula 130 is shown. Figure 9B A side view of the body 110 of the injector device 100 coupled to a cannula 130 is shown. Figure 9C A top view of the body 110 of the injector device 100 coupled to a cannula 130 is shown. Figure 9D A cross-sectional view of the body 110 of the injector device 100 coupled to a cannula 130 is shown (e.g., Figure 9B section A-A). Figure 9E A cross-sectional view of the body 110 of the injector device 100 coupled to a cannula 130 is shown (e.g., Figure 9C section B-B).Figure 9F Shows a cross-sectional view of the distal end of the body 110 of the injectant applicator device 100 (e.g., Figure 9D detail C). Figure 9G Shows a cross-sectional view of the distal end of the body 110 of the injectant applicator device 100 (e.g., Figure 9E detail D). Figure 9H Shows a cross-sectional view of the distal end of the body 110 of the injectant applicator device 100 (e.g., Figure 9E detail E). Figure 9I Shows a cross-sectional view of the body 110 of the injectant applicator device 100 (e.g., Figure 9B section F-F).

[0130] In some embodiments, the outer surface of the cannula 130 is roughened (e.g., by sandblasting) such that the cannula 130 and the body 110 are fixed to each other more strongly than when the cannula 130 has a smoother outer surface. In some embodiments, the cannula 130 is adhered (e.g., glued), insert molded (e.g., injection molded), and / or the like to the body 110.

[0131] Figure 10A -G shows the actuation structure 120 of the intratubular injectant applicator device 100 according to certain embodiments. Figure 10A Shows a perspective view of the actuation structure 120. Figure 10B Shows a top view of the actuation structure 120. Figure 10C Shows a cross-sectional view of the actuation structure 120 (e.g., Figure 10B section A-A). Figure 10D Shows a side view of the actuation structure 120. Figure 10E Shows the push wire 124 of the actuation structure 120. Figure 10F Shows a cross-sectional view of the distal end of the actuation structure 120 (e.g., Figure 10C detail B). Figure 10G Shows a cross-sectional view of the distal end of the actuation structure 120 (e.g., Figure 10D section E-E).

[0132] In some embodiments, the length of the push wire 124 is substantially straight (e.g., disposed around the longitudinal axis), and the distal end of the push wire 124 is curved (e.g., not disposed along the longitudinal axis). The curved distal end of the push wire 124 can be insert molded (e.g., injection molded) to the plunger structure 122 (e.g., to be fixed to each other more strongly than when the distal end of the push wire 124 is not curved). In some embodiments, the push wire 124 is roughened (e.g., sandblasted) such that the push wire 124 and the plunger structure 122 are fixed to each other more strongly than when the push wire 124 has a smooth outer surface.

[0133] Figure 11A-E shows the tip structure 140 of the intratubular injection applicator device 100 according to certain embodiments. Figure 11A is a perspective view of the tip structure 140. Figure 11B is a top view of the tip structure 140. Figure 11C is a cross-sectional view of the tip structure 140 (e.g., Figure 11B section A-A of Figure 11D is a top view of the distal end of the tip structure 140 (e.g., Figure 11B detail B of Figure 11E is a cross-sectional view of the distal end of the tip structure 140 (e.g., Figure 11C detail C of

[0134] In some embodiments, the tip structure 140 is made of a translucent (e.g., transparent, clear) material to allow the user to visualize the intratubular injection 160 as it enters the tubule from the tip structure 140 (e.g., to provide more user feedback and control).

[0135] Figure 12A -G shows the cap 150 of the intratubular injection applicator device 100 according to certain embodiments. Figure 12A is a perspective view of the cap 150. Figure 12B is a side view of the cap 150. Figure 12C is a top view of the cap 150. Figure 12D is a cross-sectional view of the cap 150 (e.g., Figure 12B section A-A of Figure 12E is a top view of the cap 150 (e.g., Figure 12C detail B of Figure 12F is a rear view of the cap 150. Figure 12G is a rear view of the cap 150 (e.g., Figure 12F detail C of

[0136] In some embodiments, the outer surface of the cap 150 has protrusions (e.g., a series of small rectangular-shaped protrusions along the face of the cap 150). The protrusions provide additional grip for the user when removing the cap 150 from the body 110. In some embodiments, the body 110 has protrusions (e.g., a series of small rectangular-shaped protrusions along the length of the body 110) that provide additional grip to prevent finger slippage during dilation and injection (e.g., insertion).

[0137] In some embodiments, the cap 150 (e.g., cap dilator, protective cap) has a conical dilator that can be used to dilate the punctal opening facing the distal direction. 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). Since the cap 150 is attached (e.g., detachably coupled, detachably attached) to the body 110, the user can utilize the ergonomic body 110 to manipulate the dilator to effect the dilation.

[0138] A small section of the dilator tip of the cap 150 (e.g., the distal end of the dilator tip of the cap 150) is conical such that the distal end of the tip can be small enough (e.g., form a small enough point) to locate and begin entry into the punctum. Behind the conical section is a straight section of uniform diameter (e.g., a portion of the diameter remains constant before continuing to taper conically to a larger diameter), which allows the dilator of the cap 150 to advance deeper and dilate the entire length of the canaliculus in which the intratubular injectate 160 resides (e.g., dilate the entire length of the canaliculus to be equal to the length of the intratubular injectate 160). The tip of the cap 150 can be referred to as a second tip structure, and the straight section of the cap 150 can be referred to as a section of substantially constant diameter adjacent to the second tip structure of the cap 150. Conventional dilators have a single taper and only dilate the punctum. The cap 150 dilates the punctum and the lacrimal canaliculus. Dilating a longer section of the vertical canaliculus makes it easier for the user to advance the intratubular injectate 160 through the canaliculus.

[0139] In some embodiments, for puncta having a width less than a 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 complete the dilation of the punctum and / or canaliculus to inject (e.g., deploy, insert) the intratubular injectate 160 into the canaliculus. In some embodiments, for puncta having a width greater than the threshold width, the tip structure 140 is used for a dilation procedure to dilate the punctum and / or canaliculus to inject (e.g., deploy, insert) the intratubular injectate 160 into the canaliculus (e.g., without using the cap 150 to dilate the punctum and / or canaliculus).

[0140] Figure 12H -I shows an intratubular injectate applicator device 100 according to certain embodiments. Figure 12H An exploded view of the intratubular injectate applicator device 100 is shown. Figure 12IShown is a kit 1200 that includes an intratubular injector device 100 disposed within a vial in a housing 1210. In some embodiments, the kit 1200 includes a housing 1210 for containing components. These components can include an intratubular injector device 100 and an intratubular injectate (e.g., loading the intratubular injectate into the intratubular injector device 100 in a locked position and having a cap 150 placed on a body 110 in the kit 1200, the intratubular injectate separated from the intratubular injector device in the kit 1200). The housing 1210 can be a foil pouch. The components in the kit 1200 can include a desiccant.

[0141] In certain embodiments, the injectate (e.g., intratubular injectate 160, insert, reservoir, etc.) contains a therapeutic agent. In some embodiments, the injectate (e.g., intratubular injectate 160, insert, etc.) is an injectable drug or an injectable biologic administered by a physician for preventing, treating, or curing a disease or disorder in a patient. The therapeutic agent can be a prostaglandin antagonist, such as travoprost, bimatoprost, or latanoprost; a glucocorticoid, such as dexamethasone or a pharmaceutically acceptable salt thereof; cyclosporine or a cyclosporine derivative or an adenine mimetic, such as trabodenoson.

[0142] The therapeutic agent also includes, for example, an agent for treating a condition that may be caused by an inflammatory or abnormal vascular condition, retinal vein occlusion, geographic atrophy, retinitis pigmentosa, retinoblastoma, etc. For cancer, the agent can be, for example, an anti-cancer drug, an anti-VEGF drug, or a drug known for cancer treatment.

[0143] The therapeutic agent can be, for example, anti-VEGF, blocking VEGFR1, blocking VEGFR2, blocking VEGFR3, anti-PDGF, anti-angiogenic, sunitinib, E7080, Takeda-6d, tivozanib, regorafenib, sorafenib, pazopanib, axitinib, nintedanib, cediranib, vatalanib, motesanib, macrolides, sirolimus, everolimus, tyrosine kinase inhibitor (TKI), 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.

[0144] The therapeutic agent can contain macromolecules, such as an antibody or an antibody fragment. The therapeutic macromolecule can contain a VEGF inhibitor, such as ranibizumab, which is commercially available as Lucentis TMActive ingredients therein. When released into the vitreous humor of the eye, VEGF (vascular endothelial growth factor) inhibitors can cause regression of abnormal blood vessels and improve vision. Examples of VEGF inhibitors include Lucentis TM (ranibizumab), Eylea TM (VEGF Trap), Avastin TM (bevacizumab), Macugen TM (pegaptanib). Platelet-derived growth factor (PDGF) inhibitors can also be delivered, such as Fovista TM , an anti-PGDF aptamer.

[0145] Therapeutic agents can include small molecules, such as steroids or corticosteroids and their analogs. For example, therapeutic corticosteroids can include one or more of triamcinolone, triamcinolone acetonide, dexamethasone, dexamethasone acetate, fluocinolone acetonide, fluocinolone acetonide acetate, loteprednol etabonate or their analogs. Alternatively or in combination, small molecule therapeutic agents can include tyrosine kinase inhibitors.

[0146] Therapeutic agents can include anti-VEGF therapeutic agents. Anti-VEGF therapies and agents can be used to treat certain cancers and age-related macular degeneration. Examples of anti-VEGF therapeutic agents suitable for use according to the embodiments described herein include one or more monoclonal antibodies such as bevacizumab (Avastin TM ) or antibody derivatives such as ranibizumab (Lucentis TM ), or small molecules that inhibit VEGF-stimulated tyrosine kinase, such as lapatinib (Tykerb TM ), sunitinib (Sutent TM ), sorafenib (Nexavar TM ), axitinib or pazopanib.

[0147] Therapeutic agents can include therapeutic agents suitable for treating dry AMD, such as Sirolimus TM (rapamycin), Copaxone TM (glatiramer acetate), Othera TM complement C5aR blocker, ciliary neurotrophic factor, tretinoin amide or Rheopheresis, one or more of them.

[0148] Therapeutic agents can include therapeutic agents suitable for treating wet AMD, such as REDD14NP (Quark), Sirolimus TM (rapamycin), ATG003; EYLEA (VEGF Trap) or complement inhibitor (POT-4), one or more of them.

[0149] The therapeutic agent may comprise a kinase inhibitor, such as one or more of BIBW 2992 (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 (targeting VEGFR2, VEGFR3, and / or FGFR1, a small molecule commercially available from Esai, Co.). The therapeutic agent may comprise antibody drugs, such as bevacizumab, trastuzumab, cetuximab, and panitumumab.

[0150] The therapeutic agent may comprise various classes of drugs. Drugs include, for example, steroids, non-steroidal anti-inflammatory drugs (NSAIDs), anti-cancer drugs, antibiotics, anti-inflammatory drugs (such as diclofenac), painkillers (such as bupivacaine), calcium channel blockers (such as nifedipine), antibiotics (such as ciprofloxacin), cell cycle inhibitors (such as simvastatin), proteins (such as insulin). The classes of drugs comprised by the therapeutic agent include, for example, steroids, NSAIDs, antioxidants, antibiotics, painkillers, vascular endothelial growth factor (VEGF) inhibitors, chemotherapeutic drugs, antiviral drugs. Examples of NSAIDs are ibuprofen, sodium meclofenamate, mefenamic acid, salsalate, sulindac, tolmetin sodium, ketoprofen, diflunisal, piroxicam, naproxen, etodolac, flurbiprofen, calcium fenoprofen, indomethacin, celecoxib, ketorolac, and nepafenac. The drug itself may be a small molecule, protein, RNA fragment, protein, glycosaminoglycan, carbohydrate, nucleic acid, inorganic and organic bioactive compounds, where specific bioactive agents include, but are not limited to: enzymes, antibiotics, anti-tumor agents, local anesthetics, hormones, angiogenic agents, anti-angiogenic agents, growth factors, antibodies, neurotransmitters, psychotropic drugs, anti-cancer drugs, chemotherapeutic drugs, drugs affecting the reproductive organs, genes, and oligonucleotides or other configurations.

[0151] The therapeutic agent may comprise proteins or other water-soluble biological agents. These include peptides of various molecular weights. Peptides include therapeutic proteins and peptides, antibodies, antibody fragments, single-chain variable fragments (scFv), growth factors, angiogenic factors, and insulin. Other water-soluble biological agents are carbohydrates, polysaccharides, nucleic acids, antisense nucleic acids, RNA, DNA, small interfering RNA (siRNA), and aptamers.

[0152] The system disclosed herein can be used to treat eye diseases, including but not limited to AMD, glaucoma, dry eye, allergic conjunctivitis, and pain and inflammation after cataract surgery.

[0153] Therapeutic agents can be used as part of a method for treating a specified disorder or formulated into a composition for treating a specified disorder. For example, AZOPT (brinzolamide ophthalmic suspension) can be used to treat elevated intraocular pressure in patients with ocular hypertension or open-angle glaucoma. BETADINE in povidone-iodine ophthalmic solution can be used for the preparation of the periorbital area and irrigation of the ocular surface. BETOPTIC (betaxolol HCl) can be used to reduce intraocular pressure, or for chronic open-angle glaucoma and / or ocular hypertension. CILOXAN (ciprofloxacin HCl ophthalmic solution) can be used to treat infections caused by susceptible microbial strains. NATACYN (natamycin ophthalmic suspension) can be used to treat fungal blepharitis, conjunctivitis, and keratitis. NEVANAC (nepafenac ophthalmic suspension) can be used to treat pain and inflammation associated with cataract surgery. TRAVATAN (travoprost ophthalmic solution) can be used to reduce elevated intraocular pressure - open-angle glaucoma or ocular hypertension. FML FORTE (fluorometholone ophthalmic suspension) can be used to treat corticosteroid-responsive inflammation of the palpebral and bulbar conjunctiva, cornea, and anterior segment of the globe. LUMIGAN (bimatoprost ophthalmic solution) can be used to reduce elevated intraocular pressure - open-angle glaucoma or ocular hypertension. PRED FORTE (prednisolone acetate) can be used to treat corticosteroid-responsive inflammation of the eyelids and bulbar conjunctiva, cornea, and anterior segment of the globe. PROPINE (dipivefrin HCl) can be used to control intraocular pressure in chronic open-angle glaucoma. RESTASIS (cyclosporine ophthalmic emulsion) can be used to increase tear production in patients, such as those with ocular inflammation associated with keratoconjunctivitis sicca. ALREX (loteprednol etabonate ophthalmic suspension) can be used to temporarily relieve seasonal allergic conjunctivitis. LOTEMAX (loteprednol etabonate ophthalmic suspension) can be used to treat corticosteroid-responsive inflammation of the eyelids and bulbar conjunctiva, cornea, and anterior segment of the globe. MACUGEN (pegaptanib sodium injection) can be used to treat neovascular (wet) age-related macular degeneration. OPTIVAR (azelastine HCl) can be used to treat ocular pruritus associated with allergic conjunctivitis. XALATAN (latanoprost ophthalmic solution) can be used to reduce elevated intraocular pressure in patients (such as those with open-angle glaucoma or ocular hypertension). BETIMOL (timolol ophthalmic solution) can be used to treat elevated intraocular pressure in patients with ocular hypertension or open-angle glaucoma. Latanoprost is a prodrug in the free acid form and is a selective FP receptor agonist of prostaglandins. Latanoprost can reduce intraocular pressure in glaucoma patients with few side effects. Latanoprost has relatively low solubility in aqueous solution but is readily soluble in organic solvents commonly used for manufacturing microspheres by solvent evaporation.

[0154] Further embodiments of therapeutic agents for delivery include those that specifically bind to a target peptide in vivo to prevent the target peptide from interacting with its natural receptor or other ligands. For example, AVASTIN is an antibody that binds VEGF. IL-1 traps that utilize the extracellular domain of the IL-1 receptor are also known. The trap can prevent IL-1 from binding and activating the receptor on the cell surface. Embodiments of the reagent for delivery include nucleic acids, such as aptamers. For example, pegaptanib (MACUGEN) is a pegylated anti-VEGF aptamer. An advantage of the particulate and hydrogel delivery processes is that the aptamer is protected from the in vivo environment until they are released. Further embodiments of the reagent for delivery include macromolecular drugs, a term that refers to drugs that are significantly larger than classical small molecule drugs, i.e., for example, oligonucleotides (aptamers, antisense, RNAi), ribozymes, gene therapy nucleic acids, recombinant peptides, and antibodies.

[0155] One embodiment includes extended release of a drug for allergic conjunctivitis. For example, ketotifen (an antihistamine and mast cell stabilizer) can be provided in particulate form and released in an effective amount to the eye as described herein to treat allergic conjunctivitis. Seasonal allergic conjunctivitis (SAC) and perennial allergic conjunctivitis (PAC) are both allergic conjunctival disorders. Symptoms include itching and the eyes being pink to slightly red. These two eye conditions are mediated by mast cells. Nonspecific measures to relieve symptoms typically include: cold compresses, eye washes with tear substitutes, and avoidance of allergens. Treatment usually consists of antihistamine mast cell stabilizers, dual-mechanism antiallergic agents, or topical antihistamines. Corticosteroids may be effective, but due to side effects, they are reserved for more severe forms of allergic conjunctivitis, such as vernal keratoconjunctivitis (VKC) and atopic keratoconjunctivitis (AKC).

[0156] Moxifloxacin is the active ingredient in VIGAMOX, a fluoroquinolone drug approved for the treatment or prevention of ocular bacterial infections. VKC and AKC are chronic allergic diseases in which eosinophils, conjunctival fibroblasts, epithelial cells, mast cells, and / or TH2 lymphocytes exacerbate the biochemistry and histology of the conjunctiva. VKC and AKC can be treated with drugs for anti-allergic conjunctivitis. Penetrants are reagents and can also be included in the gels, hydrogels, organogels, xerogels, and biomaterials described herein. These are reagents that help the drug penetrate into the intended tissue. Penetrants can be selected according to the needs of the tissue, for example, penetrants for the skin, penetrants for the tympanic membrane, penetrants for the eyes.

[0157] The agent can treat posterior eye diseases, for example, where the posterior eye disease is age-related macular degeneration (AMD), cystoid macular edema (CME), diabetic macular edema (DME), posterior uveitis, and diabetic retinopathy or glaucoma.

[0158] The agent can be, for example, one that includes anti-VEGF, blocks VEGFR1, blocks VEGFR2, blocks VEGFR3, anti-PDGF, anti-PDGF-R, blocks PDGFRβ, anti-angiogenic agent, sunitinib, E7080, Takeda-6d, tivozanib, regorafenib, sorafenib, pazopanib, axitinib, nintedanib, cediranib, vatalanib, motesanib, macrolides, sirolimus, everolimus, tyrosine kinase inhibitor (TKI), imatinib, gefitinib, toceranib, erlotinib, lapatinib, nilotinib, bosutinib, neratinib, lapatinib, vatalanib, including low-solubility prostaglandin analogs for glaucoma, nepafenac, macrolides, rapamycin, sirolimus, tacrolimus, or an agent for blocking the mTOR receptor (also known as choroidal neovascularization (CNV)) for AMD. mTOR refers to the mammalian target of rapamycin. The agent can be, for example, moxifloxacin, dexamethasone, travoprost, steroids, fluoroquinolones, prostaglandin analogs, and prostanamides.

[0159] Ocular diseases include ocular lesions, and hyphema, ocular hypertension, and glaucoma are conditions treated with an anterior chamber reservoir. Many agents are suitable for ocular delivery, such as NSAIDs, steroids, antiglaucoma drugs, antivirals, antibiotics, mydriatics, and antifungals administered by anterior chamber injection.

[0160] Some disease states are posterior segment eye diseases. The term posterior segment eye diseases is recognized by those skilled in these fields and generally refers to any posterior segment ocular disease that affects the vasculature and integrity of the retina, macula, or choroid, resulting in visual impairment, loss of vision, or blindness. Disease states in the posterior segment can be caused by age, trauma, surgical intervention, and genetic factors. Some posterior segment eye diseases are: age-related macular degeneration (AMD), cystoid macular edema (CME), diabetic macular edema (DME), posterior uveitis, and diabetic retinopathy. Some posterior segment eye diseases are caused by unwanted angiogenesis or vascular proliferation, such as macular degeneration or diabetic retinopathy. Pharmaceutical treatment options for these and other ocular conditions can be provided by delivering agents from implants.

[0161] The foregoing description sets forth numerous specific details, such as examples of specific systems, components, methods, etc., in order to provide a good understanding of several embodiments of the present disclosure. However, it will be apparent to those skilled in the art that at least some embodiments of the present disclosure may be practiced without these specific details. In other instances, well-known components or methods have not been described in detail or are presented in the form of a simple block diagram to avoid unnecessarily obscuring the present disclosure. Accordingly, the specific details set forth are merely exemplary. The specific embodiments may vary from these exemplary details and still be contemplated within the scope of the present disclosure.

[0162] References throughout this specification to "one embodiment", "an embodiment", or "some embodiments" mean that a particular feature, structure, or characteristic described in connection with the embodiment is included in at least one embodiment. Thus, the appearances of the phrases "in one embodiment", "in an embodiment", or "in some embodiments" throughout this specification are not necessarily all referring to the same embodiment. Additionally, the term "or" is intended to mean an inclusive "or" rather than an exclusive "or". When the term "about" or "approximately" is used herein, it is intended to mean that the recited nominal value is precisely within ±10%.

[0163] Although the operations of the methods herein are shown and described in a particular order, the order of operations of each method may be altered so that certain operations may be performed in the reverse order, so that certain operations may be performed at least in part concurrently with other operations. In another embodiment, the instructions or sub-operations of the different operations may be in an intermittent and / or alternating manner.

[0164] It should be understood that the foregoing description is intended to be illustrative and not restrictive. After reading and understanding the foregoing description, many other embodiments will be apparent to those skilled in the art. Accordingly, the scope of the present disclosure should be determined with reference to the appended claims and the full scope of equivalents to which such claims are entitled.

Claims

1. A device for administering an intratubular injection, which comprises: a body forming a cavity; a cannula connected to a first distal end of the body, wherein the cannula forms a channel aligned with the cavity of the body, and wherein the cannula is configured to store an intratubular injection in the channel; a tip structure connected to the body, wherein the tip structure surrounds at least a portion of the cannula, wherein a distal end of the tip structure is configured to dilate a punctum by inserting the distal end of the tip structure into the punctum via the punctum, the distal end of the tip structure further comprising a Shore A hardness of about 50 to about 120, and wherein an opening at the distal end of the tip structure has a diameter smaller than an outer diameter of the intratubular injection; and an actuating structure configured to push the intratubular injection through the channel and through the distal end of the tip structure and into the punctum via the punctum while inserting the distal end of the tip structure into the punctum via the punctum.

2. The device for administering an intratubular injection according to claim 1, wherein the actuating structure comprises: a plunger structure configured to be at least partially disposed in the cavity of the body, wherein a first distal end of the plunger structure is configured to receive a force to cause actuation of the actuating structure; and a push wire, wherein a first distal end of the push wire is attached to a second distal end of the plunger structure, wherein a second distal end of the push wire is disposed in the channel of the cannula before actuation of the actuating structure, and wherein the push wire is configured to push the intratubular injection through the channel in response to actuation of the actuating structure.

3. The device for administering an intratubular injection according to claim 2, wherein the plunger structure comprises a hook-shaped clip configured to be inserted into a corresponding recess formed by an outer surface of the body to prevent separation of the plunger structure and the body and to limit movement of the intratubular injection in the cannula.

4. The device for administering an intratubular injection according to claim 2, wherein: a portion of the plunger structure disposed in the cavity of the body has a non-circular perimeter; a portion of the cavity of the body has a non-circular profile corresponding to the non-circular perimeter; and rotating the actuating structure to align the non-circular perimeter of the portion of the plunger structure with the non-circular profile of the portion of the cavity of the body to actuate the actuating structure.

5. The device for administering an intratubular injection according to claim 2, wherein the cannula is fixed to the body by adhesion or insert molding, wherein a second distal end of the plunger structure forms a groove, and wherein the push wire is adhesively or insert molded into the groove.

6. The device for administering an intratubular injection according to claim 2, wherein the cavity of the body and an outer profile of the plunger structure are tapered to guide the push wire into the cannula.

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