Intratubule reservoir inserter device

Abstract

Disclosed in certain embodiments is a cannular injection applicator device comprising a body forming a cavity and a cannula coupled to a first distal end of the body. The cannula forms a channel aligned with the cavity of the body. The cannula is configured to store an intra-cannular injection in the channel. The intra-cannular injection applicator device further includes a tip structure coupled to the body. A tip structure is disposed about at least a portion of the cannula. The distal end of the tip structure is configured to dilate the punctum by inserting the distal end of the tip structure into the tubule via the punctum. The intra-cannular injection applicator device further includes an actuation structure configured to push an intra-cannular injection through the channel and the distal end of the tip structure into the tubule via the punctum.

Description

[0001] This application is a divisional application of the Chinese invention patent application with the application date of February 23, 2022, application number 202280030054.5, and invention name “Intratubular Reservoir Inserter Device”.

[0002] Related applications

[0003] This application claims the benefit of U.S. Provisional Application No. 63 / 153,316, filed on February 24, 2021, and U.S. Provisional Application No. 63 / 250,170, filed on September 29, 2021, the entire contents of which are incorporated by reference in their entirety and for all purposes. Technical Field

[0004]

[0014] Embodiments of the present disclosure relate to inserter devices, and in particular to intratubular reservoir inserter devices. Background Art

[0005] The punctum is a tiny opening on the edge of the eyelid. The punctum leads to the canaliculus. Intracanalicular injections can be inserted into the canaliculus via the punctum. Intracanalicular injections can be injectable drugs or injectable biologics that a doctor injects into the patient through the punctum. Intracanalicular injections can be products used to prevent, treat, or cure a disease or condition of the patient's eye. Summary of the Invention

[0006] According to one embodiment of the present disclosure, an intratubular injection applicator device is provided, comprising: a main body forming a cavity; a sleeve connected to a first distal end of the main body, wherein the sleeve forms a channel aligned with the cavity of the main body, and wherein the sleeve is configured to store intratubular injection in the channel; a tip structure connected to the main body, wherein the tip structure is arranged around at least a portion of the sleeve, wherein the distal end of the tip structure is configured to dilate the lacrimal punctum by inserting the distal end of the tip structure into the canaliculus through the lacrimal punctum; and an actuating structure configured to push the intratubular injection through the channel and the distal end of the tip structure into the canaliculus through the lacrimal punctum while inserting the distal end of the tip structure into the canaliculus through the lacrimal punctum.

[0007] In some examples of the device, the distal end of the tip structure has a Shore A durometer of about 50 to about 120, and wherein the opening of the distal end of the tip structure has a diameter smaller than an outer diameter of the injectable within the cannula.

[0008] In some examples of the device, a portion of the distal end of the tip structure comprises a beveled tip, wherein the portion is configured to be fully inserted into the canaliculus via the punctum prior to injecting the intracanalicular injectable into the canaliculus.

[0009] In some examples of the device, the actuation structure includes: a plunger structure configured to be at least partially disposed in a cavity of the body, wherein a first distal end of the plunger structure is configured to receive a force to cause actuation of the actuation structure; and a push wire, wherein the first distal end of the push wire is attached to the second distal end of the plunger structure, wherein the second distal end of the push wire is disposed in a channel of the sleeve prior to actuation of the actuation structure, wherein the push wire is configured to push the intratubular injection through the channel in response to actuation of the actuation structure.

[0010] In some examples of the device, the plunger structure includes a hook-shaped clip configured to be inserted into a corresponding recess formed by the outer surface of the body to prevent the plunger structure and the body from separating and limit the movement of the intratubular injection in the cannula.

[0011] In some examples of the device, a portion of the plunger structure disposed in the cavity of the body has a non-circular periphery; a portion of the cavity of the body has a non-circular contour corresponding to the non-circular periphery; and the actuating structure is rotated to align the non-circular periphery of the portion of the plunger structure with the non-circular contour of the portion of the cavity of the body to actuate the actuating structure.

[0012] In some examples of the device, the cannula is secured to the body via bonding or insert molding, wherein the second distal end of the plunger structure forms a groove, wherein the push wire is bonded or insert molded into the groove.

[0013] In some examples of the device, the cavity of the body and the outer profile of the plunger structure are tapered to guide the push wire into the cannula.

[0014] In some examples of the device, the intratubular injection applicator device further includes a cap configured to be removably attached to the body near a first distal end of the body, wherein the cap forms a second tip structure and a substantially constant diameter segment adjacent to the second tip structure, wherein the second tip structure and the substantially constant diameter segment are configured to pre-dilate the punctum and at least a portion of the canaliculus by inserting the second tip structure and at least a portion of the substantially constant diameter segment into the canaliculus through the punctum.

[0015] In some examples of the device, the channel of the cannula is configured to store the intracanalicular injectable, protect the intracanalicular injectable, and maintain alignment of the intracanalicular injectable.

[0016] According to another embodiment of the present disclosure, a tip structure of an intratubular injection applicator device is also provided, wherein the tip structure includes: a first distal end, which is configured to be attached to the main body of the intratubular injection applicator device; an inner surface forming a recess, which is configured to receive the first sleeve distal end of the sleeve of the intratubular injection applicator device, wherein the second sleeve distal end of the sleeve is connected to the main body; and a second distal end including a beveled tip, which is configured to be inserted into the lacrimal punctum to dilate the lacrimal punctum and inject the intratubular injection from the sleeve via the lacrimal punctum into the tubule.

[0017] In some examples of the tip structure, the tip structure has a Shore A hardness of about 50 to about 120, and wherein the opening of the second distal end of the tip structure has a diameter that is smaller than an outer diameter of the injectable within the cannula.

[0018] In some examples of the tip structure, the second distal end of the tip structure has a length of about 1 mm to 5 mm, and a diameter of the second distal end is about 0.1 mm to 0.4 mm.

[0019] According to another embodiment of the present disclosure, a system is also provided, which includes: an intratubular injection applicator device, which includes: a body forming a cavity; a sleeve connected to a first distal end of the body, wherein the sleeve forms a channel aligned with the cavity of the body; a tip structure connected to the body, wherein the tip structure is arranged around at least a portion of the sleeve, wherein the distal end of the tip structure is configured to expand the lacrimal punctum by inserting the distal end of the tip structure into the tubule through the lacrimal punctum; and an actuating structure; and an intratubular injection, which is loaded in the channel of the sleeve of the intratubular injection applicator device, wherein the actuating structure is configured to push the intratubular injection through the channel and the distal end of the tip structure into the tubule through the lacrimal punctum while inserting the distal end of the tip structure into the tubule through the lacrimal punctum.

[0020] In some examples of the system, the intratubular injection comprises travoprost, cyclosporine, or dexamethasone.

[0021] According to yet another embodiment of the present disclosure, a kit is provided, comprising: a housing for accommodating a plurality of components, the plurality of components comprising: an intratubular injection applicator device comprising: 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 is disposed around at least a portion of the cannula, wherein the distal end of the tip structure is configured to dilate the lacrimal punctum by inserting the distal end of the tip structure into the cannula through the lacrimal punctum; and an actuation structure configured to push the intratubular injection through the channel and the distal end of the tip structure into the cannula through the lacrimal punctum while inserting the distal end of the tip structure into the cannula through the lacrimal punctum; and the intratubular injection.

[0022] In some examples of the kit, the intravascular injection comprises travoprost, cyclosporine, or dexamethasone.

[0023] In some instances of the kit, the housing is a foil pouch, and wherein the plurality of components further comprises a desiccant.

[0024] In some examples of the kit, the intratubular injection is loaded into the intratubular injection applicator device in the kit.

[0025] According to still another embodiment of the present disclosure, a treatment method for administering an intratubular injection is provided, the method comprising: loading the intratubular injection into a channel formed by a sleeve of an intratubular injection applicator device, wherein the channel is aligned with a cavity formed by a body of the intratubular injection applicator device; inserting the distal end of the tip structure of the intratubular injection applicator device into the tubule via the lacrimal punctum to dilate the lacrimal punctum; and actuating the actuating structure of the intratubular injection applicator device to inject the intratubular injection into the tubule through the channel and the distal end of the tip structure via the lacrimal punctum while inserting the distal end of the tip structure into the tubule via the lacrimal punctum.

[0026] In some examples of the method, the method further includes rotating the actuation structure to align a non-circular perimeter of the actuation structure with a corresponding non-circular contour of the cavity of the body before actuating the actuation structure.

[0027] In some examples of the method, the tip structure has a Shore A hardness of about 50 to about 120, and wherein the opening at the distal end of the tip structure has a diameter smaller than an outer diameter of the injectable within the cannula.

[0028] According to another embodiment of the present disclosure, a treatment method for administering an intratubular injection is also provided, the method comprising: inserting the distal end of the tip structure of an intratubular injection applicator device into the canaliculus via the lacrimal punctum to dilate the lacrimal punctum, wherein the intratubular injection is loaded into a channel formed by a sleeve of the intratubular injection applicator device, wherein the channel is aligned with a cavity formed by a body of the intratubular injection applicator device; and actuating the actuating structure of the intratubular injection applicator device to inject the intratubular injection into the canaliculus through the channel and the distal end of the tip structure via the lacrimal punctum while inserting the distal end of the tip structure into the canaliculus via the lacrimal punctum.

[0029] In some examples of the method, the method further includes rotating the actuation structure to align a non-circular perimeter of the actuation structure with a corresponding non-circular contour of the cavity of the body before actuating the actuation structure.

[0030] In some examples of the method, the tip structure has a Shore A hardness of about 50 to about 120, and wherein the opening at the distal end of the tip structure has a diameter smaller than an outer diameter of the injectable within the cannula.

[0031] In some instances of the method, the intravascular injection comprises travoprost, cyclosporine, or dexamethasone. BRIEF DESCRIPTION OF THE DRAWINGS

[0032] The present disclosure is illustrated by way of example and not limitation in the figures of the accompanying drawings in which like reference numerals designate elements. It should be noted that different references in this disclosure to "an" or "one" embodiment are not necessarily to the same embodiment, and such references mean at least one.

[0033] Figures 1A to 1G An intratubular injectable applicator device according to certain embodiments is shown.

[0034] Figures 2A to 2F The body of an intracanalicular injectable applicator device according to certain embodiments is shown.

[0035] Figures 3A to 3G An actuation structure of an intracanalicular injection applicator device according to certain embodiments is shown.

[0036] Figures 4A to 4I A cannula of an intratubular injectable applicator device is shown, according to certain embodiments.

[0037] 5A to 5I Shown is a tip structure of an intratubular injection applicator device according to certain embodiments.

[0038] Figures 6A to 6F A cap of an intratubular injection applicator device is shown, according to certain embodiments.

[0039] Figure 7 A method of treating an intracanalicular injection using an intracanalicular injection applicator device according to certain embodiments is shown.

[0040] Figures 8A to 8I An intratubular injectable applicator device according to certain embodiments is shown.

[0041] 9A to 9I The body of an intracanalicular injectable applicator device according to certain embodiments is shown.

[0042] Figures 10A to 10G An actuation structure of an intracanalicular injection applicator device according to certain embodiments is shown.

[0043] Figures 11A to 11E Shown is a tip structure of an intratubular injection applicator device according to certain embodiments.

[0044] Figures 12A to 12G A cap of an intratubular injection applicator device is shown, according to certain embodiments.

[0045] FIG. 12H to FIG. 12I An intratubular injectable applicator device according to certain embodiments is shown. DETAILED DESCRIPTION

[0046] The embodiments described herein relate to intracanalicular reservoir inserter devices (e.g., intracanalicular injectable applicator devices, punctum dilator applicators for delivering intracanalicular injectables, syringes, etc.) for injecting intracanalicular injectables (e.g., injectable drugs, injectable biologics, reservoirs, etc.) into a patient.

[0047] Intraductal injections (e.g., polymer-based intraductal inserts, reservoirs) are used as a therapy for a variety of conditions present in the eye. The lacrimal punctum is a tiny hole located at the medial corner of the upper and lower eyelids. The lacrimal punctum drains the tears that are continuously produced by the exocrine (tear) glands of the eye. Intraductal injections (e.g., intraductal inserts), which are typically cylindrical, can be placed in the lower lacrimal canaliculus through the lacrimal punctum or in the upper lacrimal canaliculus through the lacrimal punctum. The diameter of the intraductal injection is typically larger than the diameter of the lacrimal punctum opening to help retain the intraductal injection. The intraductal injection can be an injectable drug or injectable biologic that is injected into the patient's body by a doctor through the lacrimal punctum. The intraductal injection can be a product that is suitable for preventing, treating, or curing a disease or condition of the patient's eye.

[0048] An additional dilation procedure (e.g., punctal dilation) is used to enlarge the soft and fragile punctal tissue (e.g., the opening of the canaliculus) located around the lacrimal punctum to allow passage of intracanalicular injections. Punctal dilation is a daunting procedure because it needs to be performed carefully to prevent damage to surrounding tissue. This additional punctal dilation step is also tedious and time-consuming. Many doctors neglect to perform punctal dilation before injecting (e.g., inserting) intracanalicular injections because the diameter of the punctum varies greatly between individuals, and it is sometimes difficult to know when punctal dilation is needed.

[0049] During the injection (e.g., insertion) procedure of an intracanalicular injectable, a hydrophilic polymer-based intracanalicular injectable can absorb water from the ocular surface and surrounding tissues, resulting in an increase in the diameter of the intracanalicular injectable. This facilitates the retention of the injectable. However, it limits the amount of time available to successfully pass the intracanalicular injectable through the lacrimal punctum (e.g., the lacrimal punctum opening), thereby posing a surgical challenge.

[0050] The small size of the intravaginal syringe presents additional challenges because specialized instruments that are not standard for surgical procedures are used to insert the intravaginal syringe. Furthermore, the intravaginal syringe may be damaged if clamped too tightly and may fall out if not gripped tightly enough.

[0051] The variable patient dependency and the use of specialized instruments for injection procedures (e.g., insertion procedures) can increase the likelihood of incorrect placement of the intracanalicular injection. The lower canaliculus has two segments: a vertical segment approximately 2.5 millimeters (mm) long connected to a horizontal segment approximately 8 mm long by an angled ampulla. The effectiveness of the intracanalicular injection and the ability of the intracanalicular injection to remain in the canaliculus (e.g., the lacrimal canaliculus) depend on the initial placement of the intracanalicular injection during the injection procedure (e.g., insertion procedure). Furthermore, the proximity of the injection to the lacrimal punctum opening is important for delivering the active agent (if present) from the injection to the tear fluid.

[0052] The combination of these factors increases the complexity of the procedure and may result in failed injections (e.g., insertions), damage to tear duct tissue, loss of the intracanalicular injectable requiring a second intracanalicular injectable, and prolonged surgery. The amount of training and skill required to perform an injection procedure (e.g., insertion) may prevent a physician from choosing to use an intracanalicular injectable and may lead to frustration when failure occurs.

[0053] The devices, systems, and methods disclosed herein provide an intratubular injection applicator device. The intratubular injection applicator device simplifies and improves the efficiency of injection procedures (e.g., insertion procedures). The intratubular injection applicator device protects the intratubular injection during storage and transportation, easily and safely dilates the lacrimal punctum to enable the lacrimal punctum to accept the intratubular injection, and then deploys the intratubular injection into the canaliculus.

[0054] The intratubular injection applicator device includes a main body forming a cavity and a sleeve connected to the first distal end of the main body. The sleeve forms a channel aligned with the cavity of the main body. The sleeve is configured to store the intratubular injection in the channel. The intratubular injection applicator device further includes a tip structure connected to the main body. The tip structure is arranged around at least a portion of the sleeve. The distal end of the tip structure is configured to expand the lacrimal punctum by inserting the distal end of the tip structure into the tubule via the lacrimal punctum (for example, and rotating the distal end). The intratubular injection applicator device further includes an actuating structure, which can be partially arranged in the cavity of the main body and partially arranged in the channel of the sleeve. The actuating structure is configured to push the intratubular injection through the channel and the distal end of the tip structure into the tubule via the lacrimal punctum while the distal end of the tip structure is inserted into the tubule via the lacrimal punctum.

[0055] The systems, devices and methods disclosed herein have advantages over conventional solutions. The intratubular injection applicator device can be used to safely dilate the lacrimal punctum and insert the intratubular injection faster than conventional solutions, which limits the amount of water absorbed by the intratubular injection and increases the success rate of injection (e.g., insertion). Compared to conventional solutions, the intratubular injection applicator device avoids damage to the intratubular injection and avoids the intratubular injection from falling. The intratubular injection applicator device increases the likelihood that the intratubular injection will be injected (e.g., inserted) and retained in the correct position. Compared to conventional solutions, the intratubular injection applicator device reduces injuries.

[0056] 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 lacrimal punctum and / or lacrimal canaliculus. In some embodiments, the objects can include one or more objects to be injected (e.g., inserted, deployed) into the canaliculus, injectable drugs, injectable biologics, objects that deliver drugs (e.g., medical drugs, therapeutic drugs), objects that block the lacrimal punctum, obstructions (e.g., lacrimal punctum obstructions, hard plastic objects shaped like anchors, objects with heads that are flush with the eyelids, etc.), injectables (e.g., located just below the lacrimal punctum), objects made of hydrogels, 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., that swell to block the lacrimal punctum), polymeric objects, elastomeric objects, etc.

[0057] Although certain embodiments of the present disclosure relate to intracanalicular injectable applicator devices for dilating a lacrimal punctum and deploying a single intracanalicular injectable into a canaliculus, embodiments of the present disclosure can be used to deploy multiple intracanalicular injectables (e.g., stacking intracanalicular injectables) into a single canaliculus (e.g., providing a first intracanalicular injectable into a canaliculus via a first intracanalicular injectable applicator device and providing a second intracanalicular injectable into the same canaliculus via a second intracanalicular injectable applicator device, providing the first intracanalicular injectable and the second intracanalicular injectable into the same canaliculus via the same intracanalicular applicator device, etc.).

[0058] Figures 1A to 1G An intracanalicular injection applicator device 100 (e.g., an applicator, a plunger-actuated intracanalicular injection applicator device, a punctum dilator applicator for delivering an intracanalicular injection, a syringe, etc.) according to certain embodiments is shown. The intracanalicular injection applicator device 100 includes a body 110, an actuating structure 120, and a cannula 130 (e.g., the intracanalicular injection is stored in the cannula 130).

[0059] The intratubular injection administration device 100 can be used to inject (e.g., deploy, insert, etc.) an intratubular injection 160 (e.g., a reservoir) into a patient. The intratubular injection 160 can be an injectable drug or injectable biologic that is injected into the patient's body via the lacrimal punctum by a physician. The intratubular injection 160 can be a product suitable for preventing, treating, or curing a disease or condition of the patient's eye. In some embodiments, the intratubular injection 160 is an intratubular injection. The intratubular injection 160 can be referred to as an insert or an intratubular insert. The intratubular injection administration device 100 can be referred to as an intratubular insert administration device, a syringe, an inserter device (e.g., for dilating the lacrimal punctum and delivering an intratubular injection), an injection device for dilating the lacrimal punctum and delivering an intratubular injection, etc. In some embodiments, the intratubular injection 160 includes one or more of travoprost, cyclosporine, or dexamethasone.

[0060] 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 the like. The cannula 130 forms a channel (e.g., a lumen) aligned with the cavity of the body 110. The cannula 130 is configured to store intratubular injections within the channel. In some embodiments, the channel of the cannula 130 is configured to store intratubular injections, protect intratubular injections, and maintain alignment of intratubular injections. The actuating structure 120 is configured to be partially disposed in the cavity of the body 110 and partially disposed in the channel of the cannula 130. The actuating structure 120 is configured to push the intratubular injections through the channel via the lacrimal punctum into the canaliculus.

[0061] 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 in 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 pressing 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. Prior to actuation of the actuation structure 120, the second distal end of the push wire 124 is disposed in the channel of the cannula 130. The push wire 124 is configured to push the intratubular injection through the channel in response to actuation of the actuation structure 122. In some embodiments, the push wire 124 is a rod. In some embodiments, the push wire 124 is a metal wire. In some embodiments, the push wire 124 has a circular perimeter (e.g., is cylindrical) that substantially matches the cylindrical shape of the channel of the cannula 130. 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.

[0062] The plunger structure 122 may include a hook clip 126 configured to be inserted into a corresponding recess formed by the outer surface of the body 110 to prevent the plunger structure 122 and the body 110 from separating and restricting movement of the intratubular injection in the cannula 130 .

[0063] In some embodiments, a portion of the plunger structure 122 disposed in the cavity of the body has a non-circular perimeter (e.g., an oval shape, a portion of the plunger structure proximate the hook-shaped clip 126), and a portion of the cavity of the body 110 has a non-circular profile (e.g., an oval shape) that corresponds to the non-circular perimeter of the portion of the plunger structure 122. The actuation structure 120 can be rotated to align the non-circular perimeter of the portion of the plunger structure 122 with the non-circular profile of the portion of the cavity of the body 110 to actuate the actuation structure 120.

[0064] In some embodiments, the cavity of the body 110 and the outer profile of the plunger structure 122 are tapered to guide the push wire 123 into the channel of the cannula 130 .

[0065] In some embodiments, the intracanalicular injection applicator device 100 includes a cap 150 configured to be detachably 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 intracanalicular injection.

[0066] The intratubular injection applicator device 100 may 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., tip) of the tip structure 140 is configured to be inserted into the cannula via the lacrimal punctum. The actuation structure 120 is configured to push the intratubular injection through the channel of the cannula 130 and the distal end of the tip structure 140 into the cannula while inserting the distal end of the tip structure 140 into the cannula via the lacrimal punctum. In some embodiments, the distal end of the tip structure 140 is configured to dilate the lacrimal punctum by inserting the distal end of the tip structure 140 into the cannula via the lacrimal punctum and rotating the intratubular injection applicator device 100.

[0067] In some embodiments, at least a portion of the distal end (e.g., tip) of the tip structure 140 has a hardness between 50 and 70. In some embodiments, the opening of the distal end of the tip structure 140 has a diameter that is smaller than the outer diameter of the intratubular injectable. 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 bevel tip, a slit tip, a flat bevel tip, or a rounded bevel tip. A portion of the distal end of the tip structure 140 is configured to be fully inserted into the tubule via the lacrimal punctum prior to injecting (e.g., deploying, inserting) the intratubular injectable into the tubule.

[0068] In some embodiments, the tip structure 140 does not have a beveled tip. A punctum that has been expanded (e.g., by the cap 150 or a separate expansion component) or a punctum that may have a resting diameter (e.g., a higher than average resting diameter) can receive the tip structure 140 (e.g., without a beveled tip).

[0069] In some embodiments, the injectable 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 to which the distal end of the cannula 130 can be inserted into the cannula via the lacrimal punctum. The actuation structure 120 is configured to push the injectable substance within the cannula through the channel and into the cannula while the distal end of the cannula 130 is inserted into the cannula via the lacrimal punctum.

[0070] In some embodiments, the system includes an intracanalicular injection applicator device 100 and an intracanalicular injection (e.g., loaded in a channel of a cannula 130 of the intracanalicular injection applicator device 100). In some embodiments, the kit includes a housing containing the components (e.g., see Figure 12I). These components may include an intracanalicular injection applicator device 100 and an intracanalicular injection (e.g., the intracanalicular injection is loaded into the intracanalicular injection applicator device 100 in a locked position and has the cap 150 placed on the body 110 in the kit, and the intracanalicular injection is separated from the intracanalicular injection applicator device 100 in the kit). The housing may be a foil bag. The components in the kit may include a desiccant.

[0071] The intracanalicular injectable applicator device 100 can be economically precision injection molded from thermoplastics, thermosets, and / or machined metal components.

[0072] In some embodiments, the small tube injection applicator device 100 does not have an adhesive. The small tube injection applicator device 100 can be designed in a manner that eliminates the need for adhesives that may cause mechanical failure 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).

[0073] In some embodiments, the intratubular injection is cylindrical in shape and is stored in the lumen (e.g., channel) of the sleeve 130 for protection and alignment during storage. In addition, there is a short length of push wire 124 in the lumen of the sleeve 130, which is located behind the intratubular injection. The push wire 124 can limit one end of the intratubular injection (e.g., cylindrical injection) and prevent the intratubular injection from moving in the inward direction. The push wire 124 can be insert-molded onto the plunger structure 122 without the use of an adhesive and can be at least partially placed in the cavity of the body 110 (e.g., in the hollow core of the handle). The plunger structure 122 can have a hook-shaped clip 126 that is limited by a notch in the body 110 to prevent the plunger structure 122 and the body 110 (e.g., body assembly) from separating. This can further limit the movement of the intratubular injection in the inward direction and can maintain the positioning of the intratubular injection throughout the storage period.

[0074] The tip structure 140 may be a flexible tip surrounding a cannula 130 (e.g., a subcutaneous cannula) containing an intratubular injection. The tip structure 140 has a distal end (e.g., a flexible tip) having an inner diameter smaller than that of the intratubular injection, which prevents the intratubular injection from migrating distally during movement of the intratubular injection applicator device 100 (e.g., under worst-case shipping conditions). The material properties and flexibility of the distal end (e.g., the flexible tip) of the tip structure 140 may allow the intratubular injection to pass when a threshold force (e.g., a significant force) is applied.

[0075] The tip structure 140 may form an annular recess (e.g., formed by the inner surface of the tip structure 140) that snaps into 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 may simplify the assembly process and may enhance consistent repeatability.

[0076] In some embodiments, the cap 150 (e.g., a 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 that is smaller than the outer diameter of the body 110 (e.g., the ridges can be grooved into the outer diameter of the body).

[0077] The inner circular core (e.g., cavity) of the body 110 and the circular shaft of the plunger structure 122 can be tapered to facilitate assembly. When the plunger structure 122 is inserted into the body 110, the tapered profile guides the push wire 124 into the sleeve 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 sleeve 130 to prevent clogging during assembly.

[0078] The plunger structure 122 and the body 110 can form a "lock and key" locking mechanism to prevent inadvertent deployment of the intratubular injection during transport and operation. The body 110 can be cylindrical and can form a non-circular (e.g., oval) groove that extends a certain distance into the cylindrical core of the body 110 (e.g., a portion of the cavity can have a non-circular profile). The plunger structure 122 can have a corresponding non-circular (e.g., oval) perimeter (e.g., extrusion) that extends a distance downward along the cylindrical axis of the plunger structure 122. The non-circular perimeter on the plunger structure 122 is aligned with the non-circular profile of the body 110 so as to travel in the axial direction. If the non-circular perimeter and the non-circular profile (e.g., the oval feature) 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 hinder the minimum width of the non-circular profile of the body 110 (e.g., the oval groove of the body 110).

[0079] In addition to the "lock and key" mechanism that prevents unintentional forward actuation in 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 may have another feature that prevents the plunger structure 122 from being accidentally rotated. The plunger structure 122 may 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, with the clips 126 resting 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 body width at the square profile position can match the static 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 clip 126 of the plunger structure 122 can provide a spring force that prevents rotation due to certain movements (eg, worst case shipping conditions). The rotational force can be achieved with one finger.

[0080] The width of the square feature can be greater (e.g., slightly greater) than the rest width of the clip 126 of the plunger structure 122 when the plunger structure 122 is positioned in the "unlocked position," which can cause the clip 126 to flex and create friction to prevent the plunger from moving in the "unlocked position" until a threshold force (e.g., a significant force) is applied. The interface between the curved clip 126 of the plunger structure 122 and the square feature (e.g., a square profile) of the body 110 can provide physical feedback to the end user while an intratubular injection procedure is being performed.

[0081] The cap 150 may have a cutout window that allows for enhanced ventilation of the tip structure 140 (e.g., a flexible tip) and the intratubular injectable (e.g., a polymer-based intratubular injectable). In some embodiments, the intratubular injectable and the plastic material (e.g., the plastic material of the tip structure 140) will be conditioned with inert nitrogen to remove moisture, and the cutout in the cap 150 (e.g., a protective cap) can increase the rate of potential moisture removal from the intratubular injectable (e.g., a polymer-based insert) and surrounding materials stored inside. The plastic material (e.g., the plastic material of the tip structure 140) can exhibit low H2O adhesion and cohesion properties.

[0082] The intracanalicular injection applicator device 100 can be configured to dilate the lacrimal punctum to a threshold diameter to receive the intracanalicular injection and then inject (e.g., deploy, insert) the intracanalicular injection into the vertical lacrimal canaliculus through a smooth process without using additional manipulations. One or more warning indicators can be incorporated into the intracanalicular injection applicator device 100 to provide one or more warnings to the user.

[0083] The distal end of the tip structure 140 (eg, a tubular flexible tip) can be beveled such that the extreme point of the bevel reaches an oval point sized to allow for use on puncta of varying sizes.

[0084] The distal end (e.g., tip) of the tip structure 140 can be tubular to allow passage of small intratubular injectables and can have a beveled tip so that only one wall is initially used to find the punctal opening. This allows for a greater wall thickness, resulting in a stiffer tool, to be used to dilate puncta of varying sizes.

[0085] The distal end (e.g., tip) of the tip structure 140 can have a beveled surface 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 punctal opening, the oval tip profile initially stretches the tissue in one plane. The oval tip can be rotated to expand the entire circumference of the punctum. This can reduce the rate of dilation and allow successful use in patients with smaller punctal openings.

[0086] The tapered profile of the beveled tip at the distal end of the tip structure 140 can enable the tip structure 140 to gradually dilate the lacrimal opening to a threshold diameter (e.g., a diameter large enough to receive an intracanalicular injection). A slow and delicate dilation rate is used to avoid trauma to the fibroelastic tissue surrounding the lacrimal 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 canalicular cavity.

[0087] The flexibility and tubular structure of the distal end (e.g., the expansion tip) of the tip structure 140 prevents abrupt expansion. When the distal end is initially inserted, the distal end (e.g., the tip) of the tip structure 140 can collapse and conform to the smaller tubule contour, and then slowly expand to the original shape of the distal end while exerting an outward force that causes the tubule tissue to gradually expand.

[0088] Once the entire bevel of the distal end (e.g., tip) of the tip structure 140 is inserted into the interior of the canaliculus, the outer diameter of the tip structure 140 (e.g., expanded tip) suddenly increases to a diameter that prevents further insertion and overexpansion (e.g., the tip structure 140 has a distal end configured to enter the canaliculus, and a 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 canaliculus). Overexpansion of the diameter of the punctal opening or canaliculus may damage the fibroelasticity of the canaliculus tissue and / or result in an orifice that is too large to properly retain the intracanalicular injection.

[0089] Once a threshold expansion (e.g., sufficient expansion) is achieved, the intratubular injectable substance 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 injectable substance through the lumen of the tip structure 140 (e.g., a flexible tip). Prior to actuation, a portion of the push wire 124 is placed within the cannula 130 to additionally maintain alignment of the push wire 124 and prevent the possibility of misfiring. The inner wall of the cannula 130 (e.g., a subcutaneous cannula) prevents the wire from deflecting and maintains a linear axial force vector that pushes the intratubular injectable substance into the cannula.

[0090] The user (e.g., based on the average size of an adult's hand) can unlock and actuate the plunger with an index finger. During the entire insertion procedure (e.g., one-handed insertion), the small tube intratubular injection applicator device 100 can be kept in one hand and work with one hand.

[0091] A non-circular (e.g., oval) "lock and key" locking mechanism can provide ambidextrous functionality. This can be achieved by allowing the plunger structure 122 and body 110 to "unlock" and align when rotated 90 degrees clockwise and 90 degrees counterclockwise.

[0092] The sudden increase in the outer diameter of the tip structure 140 (e.g., the flared tip) acts as a physical barrier and determines the position of the tip within the cannula prior to injection (e.g., deployment, insertion) of the intracanalicular injectable. The ability to accurately position the distal end (e.g., the tip) of the tip structure 140 within the cannula can provide accurate and consistent placement of the intracanalicular injectable (e.g., a polymer-based insert) regardless of human factors.

[0093] The injection (e.g., deployment, insertion) depth of the intracanalicular injectable can be controlled by the depth of the non-circular portion of the cavity (e.g., elliptical cutout) inside the body 110. Once the non-circular portion (e.g., elliptical portion) of the cavity is transformed into a circular portion, the portion of the plunger structure 122 having a non-circular (e.g., oval) perimeter can no longer advance.

[0094] The fixed stroke length of the plunger structure 122 and the push wire 124 (e.g., plunger and push wire assembly) combined with the distal end (e.g., tip) insertion barrier of the tip structure 140 results in the intracanalicular injectable 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 intracanalicular injectable to the vertical segment of the inferior lacrimal canaliculus.

[0095] The shorter push wire 124 can be used to deliver the intracanalicular injection to a maximum depth of 1 millimeter (mm) below the lacrimal punctum opening so that the intracanalicular injection is located just above the angled ampulla in the vertical segment of the inferior lacrimal canaliculus. 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 intracanalicular injection to be released over a shorter distance.

[0096] To place the intracanalicular injection in the horizontal region of the inferior canaliculus, the length of the push wire 124 can be increased to push the intracanalicular injection through the ampulla. The flexibility of the distal end of the tip structure 140 (e.g., a flared tip) can conform to the lacrimal duct anatomy and guide the intracanalicular injection through the curved ampulla.

[0097] 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," 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 at the deployment position also secures the push wire 124 in an exposed position (e.g., an extended position of the push wire 124) and allows the user to further push the intratubular injection into place (e.g., if applicable) without retracting the push wire 124. The snapping of the clip 126 of the plunger structure 122 into the recess in the body 110 can be physically felt by the mechanical vibration of the intratubular injection administration device 100 when the clip 126 snaps into the recess.

[0098] The intratubular injection applicator device 100 may include a visual feedback indicator (e.g., in addition to or in place of auditory and / or physical feedback). The plunger structure 122 may have an indicator (e.g., red and green marks 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 observed by peering through the cutout hole of the cavity of the body 110. When transitioning to the second indicator (e.g., green mark), the position of the first indicator (e.g., red mark) may be aligned when the intratubular injection is fully injected (e.g., deployed, inserted).

[0099] The sizes of the push wire 124, the cannula 130 (e.g., a subcutaneous cannula), and the tip structure 140 (e.g., a flexible tip) can be adjusted to accommodate different sizes of intratubular injections. The intratubular injection applicator device 100 simplifies the insertion procedure and reduces complexity. The time required for the insertion procedure can be reduced to prevent the intratubular injection from expanding before being placed in the cannula, thereby reducing the possibility of unsuccessful insertion.

[0100] The design and composition of the intratubular injection applicator device 100 may include a cannula 130 (e.g., a subcutaneous cannula) that is insert-molded onto the body 110 (e.g., a cylindrical tubular body) without the need for adhesive. The cannula 130 can limit the lateral movement of the intratubular injection. The push wire 124 can be insert-molded onto the plunger structure 122 without the need for adhesive. The actuation structure 120 (e.g., the push wire 124 and the plunger structure 122 subassembly) can be assembled within the cavity (e.g., the core) of the body 110. The push wire 124 can limit the proximal movement of the intratubular injection. The plunger structure 122 can have a hook-shaped 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 limit the distal movement of the intratubular injection. When applying threshold force, tip structure 140 can have the material characteristic and flexibility that allow small tube intramedullary injection thing to pass through.Tip structure 140 can have annular recess, and this annular recess snaps onto the corresponding annular protrusion on main body 110 so that tip structure 140 is fixed in place and this can reduce assembly time.Cap 150 (for example, protective cap) can be friction fit on main body 110.Friction fit can be produced by the ridge inside cap.A part of push line 124 can be placed in sleeve 130 before actuation, to keep the alignment of push line 124 and prevent the possibility that push line 124 does not work.Main body 110 can have cavity (for example, inner circular core) and the axis of plunger structure 122 can be tapered, to help the alignment of push line 124 during assembly.The chamber at cavity (for example, inner core) bottom of main body 110 can pass through funnel and enter sleeve 130 with push line 124.

[0101] The small tube injection applicator device 100 can prevent the unintentional deployment of the small tube injection (for example, by limiting the locking feature of the plunger structure 122). The main body (for example, a cylindrical tubular body) can include a non-circular (for example, an oval) groove extending into the cylindrical core. The plunger structure 122 having substantially the same non-circular (for example, an oval) extrusion extends downward along the cylindrical axis of the plunger structure 122. The non-circular periphery of the plunger structure 122 is aligned with the non-circular profile of the main body 110 (for example, an oval groove) to travel in the distal direction. The deployment depth or stroke depth can be directly dependent on the depth of the non-circular portion (for example, an oval cutout) inside the main body 110, which also serves as a locking feature. The plunger structure 122 can be rotated clockwise and counterclockwise to align with the main body 110 for deployment. The flexible clip 126 of the plunger structure 122 and the square profile of the main body 110 can engage with each other to prevent the plunger structure 122 from rotating until a threshold force is applied (for example, via a finger). The clip 126 of the plunger structure 122 can provide a spring 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.

[0102] The cap 150 (e.g., a protective cap) can have a cutout window that allows a higher rate of H2O diffusion for the polymer-based intratubular injection and components stored inside. In order to administer hygroscopic intratubular injections that are unstable in the presence of H2O, the plastic material used to manufacture the intratubular injection applicator device 100 can have low moisture cohesion and adhesion properties. Reducing the exposure of H2O within the intratubular injection packaging may help maintain the integrity of the intratubular injection during storage. In some embodiments, the intratubular injection applicator device 100 (e.g., which is loaded with 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 intratubular injection can be stored in a foil bag with a desiccant pack.

[0103] The distal end of the tip structure 140 can be a tubular, flexible tip with a bevel so that the tip of the bevel reaches an oval point, which has a perimeter (e.g., circumference) that can be inserted into puncta of varying sizes. The beveled tip can be rounded at the end to prevent trauma. The bevel allows for a greater wall thickness to increase tip rigidity while maintaining a sufficiently small profile to dilate small punctal openings. The oval, beveled tip profile can slow the rate of initial expansion, as the tip initially elongates the punctal opening in one direction and allows the user to gradually expand in all directions as the tip is rotated. This allows for use in patients with smaller punctal openings. The bevel can be tapered to allow for a steady and gradual rate of punctal expansion without causing trauma to the punctal tissue. When initially inserted into the cannula, the flexible tubular tip can collapse and gradually expand, occurring at a slower rate of expansion. The tip structure 140 (e.g., a flexible, expanding tip) can have an abruptly increasing outer diameter to prevent further insertion and over-expansion.

[0104] The intratubular injection 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 injection through the lumen of the tip structure 140 (e.g., a flexible expansion tip). The intratubular injection applicator device 100 can store the intratubular injection, expand the lacrimal punctum, and then inject (e.g., deploy, insert) the intratubular injection and can be operated entirely with one hand. The intratubular injection applicator device 100 can be operated with full ambidextrous functionality.

[0105] The intracanalicular injection applicator device 100 can consistently inject (e.g., deploy, insert) the intracanalicular injection into the vertical section of the canaliculus. The beveled tip allows the intracanalicular injection to be released from the beveled tip over a shorter distance. The intracanalicular injection applicator device 100 can inject (e.g., deploy, etc.) the intracanalicular injection through the vertical canaliculus and ampulla so that the intracanalicular injection resides in the horizontal section of the lacrimal canaliculus. The tip structure 140 can help guide the deployment of the intracanalicular injection through the curved ampulla.

[0106] The intratubular injection applicator device 100 can have a feedback feature that can be detected audibly and / or physically once the intratubular injection is fully deployed. Once the plunger structure 122 is 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 are sized to snap in a manner that can be felt (e.g., as a vibration) and heard as an audible click. The clip 126 of the plunger structure 122, which is retained in the recess of the body 110, can only be moved by a threshold force (e.g., cannot be moved without applying significant force).

[0107] The small tube injection applicator device 100 can have a visual cue feature that can be visually detected once the small tube injection is fully deployed. In some embodiments, the markings on the plunger structure 122 (e.g., red and green markings printed on the plunger structure 122) can be observed by peeking through the cutout hole of the cavity of the body 110. The first mark (e.g., green mark) can only be seen through the cutout when the small tube injection is fully deployed. The second mark (e.g., red mark) can only be seen when the small tube injection is preloaded into the small tube injection applicator device 100 (e.g., and the plunger structure 122 has not yet been actuated).

[0108] 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 manner similar to a syringe 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 on the distal end of the intratubular injection applicator device 100. For the intratubular injection applicator device 100 including the slider structure, the slider structure travels laterally along the body to transmit the axial load.

[0109] In some embodiments, the intratubular injection applicator device 100 includes a cannula 130 with a bevel. 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 find 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 canal. The intratubular injection is stored in the inner cavity of the cannula 130 and can be injected (e.g., deployed, inserted) via an actuating structure 120 (e.g., a plunger structure or a slider structure). The bevel can expose a sufficient amount of the surface of the intratubular injection to the canal tissue so that when the cannula 130 is removed, the intratubular injection is held in place by the friction between the intratubular injection and the canal tissue. This prevents the intratubular injection from being inadvertently removed by the intratubular injection applicator device 100.

[0110] A collar (eg, a metal collar) may be provided around the cannula 130 to prevent over-insertion of the cannula 130 into the small tube.

[0111] In some embodiments, the intracanalicular injection applicator 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 perforation of the lacrimal gland tissue, thereby increasing the safety of the intracanalicular injection applicator device 100. The inner lumen of the tip structure 140 (e.g., the flexible tip) can be smaller than typical to retain the intracanalicular injection during storage, and the flexible nature of the tip material allows the intracanalicular injection to pass through when an actuation force is applied. The tip material is sufficiently hard to fully dilate the lacrimal punctum.

[0112] Either a beveled cannula 130 or a flexible tip structure 140 can be used. Both can provide punctal dilation (eg, increasing the diameter of the punctum large enough to receive the intracanalicular injection) and allow the intracanalicular injection to pass through and remain in the canaliculus.

[0113] One or more components of the intracanalicular injectable applicator device 100 may be three-dimensionally (3D) printed.The intracanalicular injectable applicator device 100 may be used to insert an intracanalicular injectable (eg, a polymer insert) into a mammalian lacrimal canaliculus.

[0114] In some embodiments, the intratubular injection applicator device 100 stores a plurality of intratubular injections and is used to insert a plurality of intratubular injections into a plurality of tubules. In some embodiments, the intratubular injection applicator device 100 is used to administer one or more products (e.g., liquids, solids, drugs, etc.) to the lacrimal puncta and / or lacrimal canaliculi. In some embodiments, the intratubular injection applicator device 100 is used to insert an intratubular injection comprising a drug (e.g., to administer a drug). In some embodiments, the intratubular injection applicator device 100 is used to insert an intratubular injection that does not comprise a drug (e.g., for obstruction only).

[0115] Figure 1A An exploded view of the intracannula injectable applicator device 100 is shown, which includes a body 110 , an actuation structure 120 (eg, a plunger structure 122 and a push wire 124 ), a cannula 130 , a tip structure 140 , and a cap 150 . Figure 1B The assembled intratubular syringe applicator device 100 is shown (eg, without the cap 150 ), including the body 110 , the plunger structure 122 , and the tip structure 140 . Figure 1C Shown with Figure 1B Compare the assembled intracanalicular syringe applicator device 100 (eg, without the cap 150 ) that has been rotated 90 degrees. Panel C shows a side view of the intracanalicular syringe applicator device 100 (eg, without the cap 150 ). Figure 1D A cross-sectional view of the intratubular syringe applicator device 100 (eg, without the cap 150 ) is shown. Figure 1EA cross-sectional view of the tip structure 140 of the intracanalicular injectable applicator device 100 is shown with the intracanalicular injectable 160 (eg, intracanalicular injectable) not yet deployed (eg, with the pushwire 124 in an undeployed position). Figure 1E A cross-sectional view of the tip structure 140 of the intracanalicular injectable applicator device 100 is shown (eg, the intracanalicular injectable has been deployed, with the pushwire 124 in the deployed position). Figure 1G A perspective view of the intracannula injectable applicator device 100 is shown with the tip structure 140 and cap 150 removed.

[0116] In some embodiments, the total length of the small tube 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 small tube 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 to 9 mm.

[0117] In some embodiments, the cannula 130 is secured to the body 110 by an insert molding having a minimum tensile strength of about 1 pound (lb). In some embodiments, the push wire 124 is secured to the plunger structure 122 by an insert molding having a tensile strength of about 1 lb min. In some embodiments, the actuation structure 120 (e.g., the plunger structure 122 and the push wire 124) are placed in the body 110 and deployed forward without obstruction. In some embodiments, the applicator assembly (e.g., the assembled body 110, the actuation structure 120, and the cannula 130), the tip structure 140, and the cap 150 are packaged separately.

[0118] Figures 2A to 2F Shown is a body 110 of an intracanalicular injectable applicator device 100 according to certain embodiments. Figure 2A A perspective view of the main body 110 is shown. Figure 2B A first side view of the body 110 is shown. Figure 2B A first side view of the body 110 is shown. Figure 2C A second side view of the body 110 is shown (e.g., with Figure 2B compared to a 90 degree rotation). Figure 2D A first cross-sectional view of the body 110 is shown. Figure 2E A second cross-sectional view of the body 110 is shown (eg, with Figure 2D compared to a 90 degree rotation). Figure 2F A cross-sectional view of a non-circular portion of the body 110 is shown.

[0119] 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 mold release agent. In some embodiments, the cap 150 is lightly press-fitted onto the body tip 112 (e.g., about 5 mm of the body tip 112). In some embodiments, the tip structure 140 is held in place by a protrusion (e.g., a bump of about 0.15 mm).

[0120] 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 for actuation to push the intracannula injection out of the intracannula injection applicator device 100.

[0121] Figures 3A to 3F An actuation structure 120 of the intracannula injectable applicator device 100 is shown, according to certain embodiments.

[0122] Figures 3A to 3D An actuation structure 120 including a plunger structure 122 is shown. 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 .

[0123] The plunger structure 122 may not have lubricant or release agent. The push wire 124 may be adhered (e.g., glued), insert molded, and / or similarly entered into a groove of the plunger structure 122. The portion of the plunger structure 122 adjacent the clip 126 may have a non-circular periphery that substantially matches the non-circular contour of a portion of the cavity of the body 110. To actuate the intratubular injection applicator device 100, the plunger structure 122 will be rotated so that the portion of the plunger structure 122 having the non-circular periphery is aligned with the non-circular contour of a portion of the cavity of the body 110.

[0124] 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-blasted (e.g., the entire outer length).

[0125] Figure 3EThe clips 126 of the plunger structure 122 are shown engaged with the body 110. The friction interface between the clips 126 and the body 110 of the plunger surface 122 can prevent the plunger structure 122 from deploying without being physically actuated (e.g., 0.2-0.5 deflections on both clips 126 to generate friction).

[0126] In some embodiments, the intratubular injection applicator device 100 has a deployment mechanism (e.g., a thumb deployment mechanism) disposed on a side of the intratubular injection applicator device 100 (e.g., a side of the body 110). For example, the intratubular injection applicator device 100 may have one or more of a roller (e.g., a side rolling knob), a bend-press actuator, a slider, a living hinge, and / or the like. The living hinge may be a thin, flexible hinge (e.g., a flexible bearing) made of the same material as the two rigid pieces connected to the living hinge (e.g., plastic injection molded in the same direction to squeeze to mechanically move the intratubular injection).

[0127] Figures 3F to 3G The device 100 for administering intracanalicular injections is shown with an actuation structure 120 having a slider feature. The user grasps the body of the device 100 with the thumb and middle finger and actuates the slider feature with the index finger. The slider feature may be part of the actuation structure 120 having a push wire 124.

[0128] Figures 4A to 4I The cannula 130 of the intracannula injectable applicator device 100 is shown, according to certain embodiments. Figure 4A A perspective view of the sleeve 130 is shown. Figure 4B A side view of the sleeve 130 is shown coupled (eg, insert welded, injection molded, adhered, glued, insert molded) to the body 110 . Figure 4C A cross-sectional view of a sleeve 130 is shown coupled (eg, insert welded, injection molded, adhered, glued, insert molded) to the body 110. The sleeve 130 may be flush with a chamfer of the body 110.

[0129] In some embodiments, the cannula 130 is a 20-gauge thin-walled cannula 130. Both distal ends of the cannula 130 may be cut and polished (e.g., inner and outer diameters). The cannula 130 may be abrasive-blasted (e.g., the entire outer length). The cannula 130 may undergo a passivation operation. In some embodiments, the cannula 130 is plastic. In some embodiments, the cannula 130 is metal.

[0130] Figures 4D to 4I A cannula 130 is shown having a beveled surface. Figures 4D to 4F A cannula 130 having a rounded bevel (eg, a rounded bevel cannula) is shown. Figures 4G to 4IA cannula 130 having a flat bevel (e.g., a flat bevel cannula) is shown. In some embodiments (e.g., instead of or in addition to having a tip structure 140), the intratubular injectable applicator device 100 has a collar 132 to prevent over-insertion of the cannula 130 into the lacrimal punctum.

[0131] 5A to 5I A tip structure 140 (eg, a flared tip, a flexible tip, a polymer tip, etc.) of an intracanalicular injectable applicator device 100 is shown, 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 prior to deployment of the intratubular injectate 160. Figure 5E is a side view of the tip structure with the intratubular injectable 160 deployed. Figures 5F to 5H The distal end (eg, tip) of the tip structure 140 is shown. Figure 5I is a cross-sectional view of the tip structure 140 .

[0132] The tip structure 140 is configured to dilate the punctum and deploy the intracanalicular injectable substance after dilating the punctum (e.g., dilating and deploying without removing the tip structure 140 from the punctum). In some embodiments, the tip structure 140 has a flexible beveled tip that is configured to dilate the punctum and deploy the intracanalicular injectable substance to a location (e.g., a repeatable location) in the canaliculus.

[0133] In some embodiments, the diameter of the punctum is 0.2 mm to 0.5 mm (e.g., it can be smaller than the intratubular injection). The length of the vertical portion of the tubule can be about 1.7 mm to 2 mm. The length of the intratubular injection can be about 2 mm (e.g., it can be longer than the vertical section of the tubule). The intratubular injection can be hydrated and expanded over time to retract and move into the vertical section, and when used, the intratubular injection can remain in the vertical section. In some embodiments, the diameter of the distal end (e.g., the tip) of the tip structure 140 (e.g., the distal end of the bevel end) can be about 0.1 mm to 0.4 mm. In some embodiments, the diameter of the distal end (e.g., the tip) of the tip structure 140 (e.g., the distal end of the bevel end) can be about 0.2 mm to 0.3 mm.

[0134] 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 intracanalicular injection to pass through the opening in the distal end of the tip structure 140 (e.g., through the punctum into the canaliculus). In some embodiments, the distal end (e.g., tip) of the tip structure 140 has radial flexibility (e.g., bends outward, expands the tip).

[0135] In some embodiments, the distal end (e.g., tip) of the tip structure 140 has a beveled end (e.g., diagonally cut, cut beveled, etc.). In some embodiments, the passage 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 injectable to be deployed into the tubule faster than a flat end and not as deep as a flat end. The beveled end can reach a smaller point than a flat end, and the smaller point can allow force to be concentrated on the tear punctum to dilate the tear punctum.

[0136] The tip structure 140 can be made of one or more of medical grade silicone rubber, Class VI material, thermoplastic elastomer (TPE), fluorinated ethylene propylene (FEP), block copolymers, 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 intracanalicular injectable (e.g., a cylindrical ocular insert having a diameter of approximately 0.45 mm to 0.54 mm and / or a length of approximately 2.92 mm to 3.08 mm) to the lower canaliculus (e.g., the tear duct) or the upper canaliculus (e.g., the tear duct). The tear duct may have an average diameter of 0.4 mm, and once the distal end of the tip structure 140 is fully inserted, the tear duct may expand to 0.7 mm to 0.9 mm. The distal end of the tip structure 140 can be sufficiently rigid to locate and dilate the opening of the tear duct through insertion. When the intracanalicular injectable is deployed through the orifice (e.g., opening) of the distal end of the tip structure 140, the distal end of the tip structure 140 can remain in the tear duct. The distal end of the tip structure 140 can be flexible to allow an intracanalicular injectable of a first threshold diameter (e.g., 0.54 mm) to be advanced therethrough, and also small enough to prevent an intracanalicular injectable of a second threshold diameter (e.g., 0.45 mm) from being dislodged. The intracanalicular injection can be placed 0.2 mm to 0.8 mm below the tear duct opening after deployment.

[0137] In some embodiments, the tip structure 140 has a silicone tip. After the entire tip is fixed in the tubule, the intratubular injection is pushed through the elastic silicone opening. The intratubular injection dilates the tubule means that the intratubular injection approaches the final position of the intratubular injection. The diameter at the distal end of the tip structure 140 can be about 0.3mm to 0.5mm. The maximum diameter of the tip of the tip structure 140 can be about 0.7mm to 0.9mm. The maximum placement depth can be about 1mm to 5mm. The hardness of the tip structure 140 can be firm for finding the tear point and anchoring the tip of the tip structure. The hardness of the tip structure 140 can be flexible for deploying the intratubular injection. In some embodiments, the distal end (e.g., the tip) of the tip structure 140 has a flat tip (see Figure 5F ), bevel tip (see Figure 5G ) and / or slit tip (see Figure 5H ).

[0138] In some embodiments, the intratubular injection applicator device 100 has a beveled cannula 130. The cannula 130 can be rounded to find the lacrimal punctum and expand the lacrimal punctum to receive the cannula 130. Once the bevel of the cannula 130 is no longer exposed, the cannula intratubular injection can be deployed. The metal collar can prevent the intratubular injection applicator device 100 from being over-inserted into the lacrimal punctum. In some embodiments, the width of the cannula 130 at the tip is about 0.1mm to 0.15mm. In some embodiments, the outer die diameter of the cannula is about 0.5mm to 1.5mm. In some embodiments, the maximum insertion depth is about 5mm to 6mm. 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, which allows the intratubular injection to be placed closer to the lacrimal punctum opening (e.g., 0.5mm to 0.75mm deep).

[0139] refer to Figure 5I , the tip structure 140 may include distal ends 510A and 510B, an outer surface 520, and an inner surface 530. The outer surface 520 may be inclined (e.g., curved, tapered, etc.) from the distal end 510A to the distal end 510B (e.g., allowing the user to view the tear point during use). The inner surface 530 may form an interior volume 540, a recess 542, and a channel 544. The inner surface 530 may 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.

[0140] In some embodiments, the first distal end of the cannula 130 is coupled to the body 110, and the second distal end of the cannula 130 is configured to be secured by the inner surface 530 in the channel 544 of the tip structure 140. In some embodiments, the region 532A guides the second distal end of the cannula 130 into the channel 544. In some embodiments, the second distal end of the cannula 130 is adjacent to a portion of the region 532B. The region 532B can guide the intratubular injection from the cannula 130 to the opening 546 (e.g., an oval opening) in the beveled edge 512. A portion of the inner surface 5530 is disposed on a portion of the body 110 (e.g., secured to the body 110 by a friction fit). In some embodiments, the recess 542 of the tip structure 140 engages with (e.g., snaps onto) a protrusion (e.g., an annular ring) of the body 110.

[0141] In some embodiments, the tip structure 140 includes a distal end 510A configured to be attached to the body 110 of the intracanalicular injectable applicator device 100. The tip structure 140 may include an inner surface 530 forming a recess (e.g., a channel 544) configured to receive the distal end of the cannula 130 (e.g., the other distal end of the cannula 130 is coupled to the body 110). The inner surface 530 of the tip structure 140 and the cannula 130 may mate with each other (e.g., a friction fit) to prevent movement of the cannula 130. The tip structure 140 may include a distal end 510B including a beveled edge 512 (e.g., a beveled tip) configured to be inserted into the lacrimal punctum to dilate the lacrimal punctum and deploy the intracanalicular injectable from the cannula 130 via the lacrimal punctum into the cannula.

[0142] Figures 6A to 6F The cap 150 of the intracanalicular injectable applicator device 100 is shown, according to certain embodiments. Figure 6A is a perspective view of the cap 150 . Figure 6B is a bottom view of the cap 150 . Figure 6C is a first side view of cap 150 . Figure 6D 6E is a second side view of the cap 150 (e.g., Figure 6C compared to a 90 degree rotation). Figure 6F is a second cross-sectional view of the cap 150 (e.g., with Figure 6D compared to a 90 degree rotation).

[0143] The cap 150 may include one or more (eg, two) openings 152 (eg, vents).

[0144] The cap 150 may be lightly press-fitted onto the body 110. The cap 150 may not have a lubricant or release agent. The cap 150 may have one or more protrusions 154 from the inner surface (e.g., see Figure 6B、 6D and 6F), which provide a press fit with the body 110. In some embodiments, the cap 150 includes four protrusions 154, each spaced 90 degrees apart in the inner surface, providing a press fit with the body.

[0145] Figure 7 A method of treating an intraductal injection using an intraductal injection applicator device 700 is shown according to certain embodiments. Although shown in a particular order or sequence, the order of operations may be modified unless otherwise indicated. Therefore, the illustrated embodiments should be understood as examples only, and the illustrated operations may be performed in a different order, and some operations may be performed in parallel. In addition, one or more operations may be omitted in various embodiments. Therefore, not all operations are required in all embodiments.

[0146] At block 702, an intratubular injection is loaded into a channel (e.g., lumen) formed by a cannula of an intratubular injection applicator device. The channel is aligned with a cavity formed by a body of the intratubular injection applicator device. An actuating structure of the intratubular injection applicator device is partially disposed within the cavity of the body and partially disposed in the channel of the cannula.

[0147] At block 704, the distal end of the tip structure (eg, tip, beveled edge, etc.) of the intracanalicular injectable applicator device is inserted into the canaliculus through the lacrimal punctum to dilate the lacrimal punctum.

[0148] At block 706 , the intracanalicular injectate applicator device is rotated to further dilate the punctum to receive the intracanalicular injectate.

[0149] At block 708 , the actuation structure is rotated to align the non-circular perimeter of the actuation structure (eg, the elliptical perimeter portion of the plunger structure) with the non-circular contour of the cavity of the body (eg, the elliptical portion of the body cavity).

[0150] At block 710 , an actuation structure is actuated (eg, by depressing a distal end of the actuation structure) to inject (eg, deploy) an intracanalicular injectable into the canaliculus via the lacrimal punctum.

[0151] In some embodiments, method 700 includes comparing Figure 7 More or fewer operations may be shown. In some examples, method 700 can include inserting at block 704 and actuating at block 710 (eg, preloading a small intratubular injectable applicator device).

[0152] Figures 8A to 12G Components of an intracanalicular syringe applicator device 100 are shown. Figures 8A to 12G The intratubular injection applicator device 100 may have Figures 1A to 7The features in the figures may have the same or similar functions as other features with similar numbers in other figures.

[0153] Figures 8A to 8I An intratubular injectable applicator device 100 is shown, according to certain embodiments. Figure 8A An exploded view of the intratubular syringe applicator device 100 is shown. Figure 8B A side view of the actuation structure 120 is shown about to be inserted into the body 110 of the intracannula injectable applicator device 100 . Figure 8C A top view of the actuation structure 120 is shown to be inserted into the body 110 of the intracannula injectable applicator device 100 . Figure 8D A side view of the assembled intratubular syringe applicator device 100 is shown. Figure 8E A perspective view of the intratubular syringe applicator device 100 is shown. Figure 8F A side view of the intratubular syringe applicator device 100 is shown. Figure 8G A cross-sectional view of a small tube injection applicator device 100 is shown (eg, Figure 8F of). Figure 8H A cross-sectional view of the distal end of the body 110 is shown deploying an intratubular injectable 160 (eg, Figure 8G Detailed view of the . Figure 8I A cross-sectional view of the distal end of the body 110 including the intratubular injectable 160 is shown in a loaded position (eg, Figure 8G Detailed view of the .

[0154] The body 110 may have protrusions (eg, ridges) to prevent the intratubular syringe applicator device 100 from slipping out of the user's hand.

[0155] 9A to 9I Shown is a body 110 of an intracanalicular injectable applicator device 100 according to certain embodiments. Figure 9A A perspective view of the body 110 of the injectable applicator device 100 coupled to the cannula 130 is shown. Figure 9B A side view of the body 110 of the injectable applicator device 100 coupled to the cannula 130 is shown. Figure 9C A top view of the body 110 of the injectable applicator device 100 coupled to the cannula 130 is shown. Figure 9D A cross-sectional view of the body 110 of the injectable applicator device 100 coupled to the cannula 130 is shown (eg, Figure 9B Section AA). Figure 9E A cross-sectional view of the body 110 of the injectable applicator device 100 coupled to the cannula 130 is shown (eg, Figure 9C cross-section BB). Figure 9F A cross-sectional view of the distal end of the body 110 of the injectable applicator device 100 is shown (eg, Figure 9D Details C). Figure 9G A cross-sectional view of the distal end of the body 110 of the injectable applicator device 100 is shown (eg, Figure 9E Details D). Figure 9H A cross-sectional view of the distal end of the body 110 of the injectable applicator device 100 is shown (eg, Figure 9E Details E). Figure 9I A cross-sectional view of the body 110 of the injectable applicator device 100 is shown (eg, Figure 9B Cross-section FF).

[0156] In some embodiments, the outer surface of the sleeve 130 is roughened (e.g., by sandblasting) so that the sleeve 130 and the body 110 are more strongly secured to each other than if the sleeve 130 had a smoother outer surface. In some embodiments, the sleeve 130 is adhered (e.g., glued), insert molded (e.g., injection molded), and / or the like to the body 110.

[0157] Figures 10A to 10G An actuation structure 120 of the intracannula injectable applicator device 100 is shown, according to certain embodiments. Figure 10A A perspective view of the actuation structure 120 is shown. Figure 10B A top view of the actuation structure 120 is shown. Figure 10C A cross-sectional view of the actuation structure 120 is shown (eg, Figure 10B AA section). Figure 10D A side view of the actuation structure 120 is shown. Figure 10E The push wire 124 of the actuation structure 120 is shown. Figure 10F A cross-sectional view of the distal end of the actuation structure 120 is shown (eg, Figure 10C Details B). Figure 10G A cross-sectional view of the distal end of the actuation structure 120 is shown (eg, Figure 10D EE cross section).

[0158] In some embodiments, the length of the push wire 124 is substantially straight (e.g., disposed about a longitudinal axis), and the distal end of the push wire 124 is curved (e.g., not disposed along 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 secure the push wire 124 to the plunger structure 122 more strongly than if the distal end of the push wire 124 were 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 more secure to each other than if the push wire 124 had a smooth outer surface.

[0159] Figures 11A to 11EThe tip structure 140 of the intracanalicular injectable applicator device 100 is shown, 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 (eg, Figure 11B AA section). Figure 11D is a top view of the distal end of the tip structure 140 (e.g., Figure 11B Details B). Figure 11E is a cross-sectional view of the distal end of the tip structure 140 (eg, Figure 11C Details C).

[0160] 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 injectable 160 as it enters the tubule from the tip structure 140 (e.g., providing more user feedback and control).

[0161] Figures 12A to 12G The cap 150 of the intracanalicular injectable applicator device 100 is shown, 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 (eg, Figure 12B AA section). Figure 12E is a top view of the cap 150 (eg, Figure 12C Details B). Figure 12F is a rear view of the cap 150 . Figure 12G is a rear view of the cap 150 (eg, Figure 12F Details C).

[0162] 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 the user with additional grip 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 when performing expansion and injection (e.g., insertion).

[0163] In some embodiments, the cap 150 (e.g., a cap expander, a protective cap) has a tapered expander that can be used to expand the distal-facing punctal opening. The cap 150 can be used by a physician prior to an injection (e.g., insertion) procedure to widen the punctal opening and canaliculus prior to an injection (e.g., insertion) procedure. Because the cap 150 is attached (e.g., detachably coupled, detachably attached) to the body 110, the user can manipulate the expander using the ergonomic body 110 to achieve expansion.

[0164] A small section of the dilator tip of cap 150 (e.g., the distal end of the dilator tip of cap 150) is tapered so that the distal end of the tip can be small enough (e.g., forming a small enough point) to find and begin entering the lacrimal punctum. The tapered section is followed by a straight section of uniform diameter (e.g., a portion of the diameter remains constant before continuing to taper to a larger diameter), which allows the dilator of cap 150 to advance deeper and expand the entire length of the canaliculus where the intracanalicular injection 160 resides (e.g., expanding the entire length of the canaliculus to equal the length of the intracanalicular injection 160). The tip of cap 150 can be referred to as a second tip structure, and the straight section of cap 150 can be referred to as a substantially constant diameter section adjacent to the second tip structure of cap 150. Conventional dilators have a single taper and only expand the lacrimal punctum. Cap 150 expands both the lacrimal punctum and the lacrimal canaliculus. The longer section that expands the vertical canaliculus makes it easier for the user to advance the intracanalicular injection 160 through the canaliculus.

[0165] In some embodiments, for a punctum having a width less than a threshold width, the tip of the cap 150 is used in a first dilation procedure to partially dilate the punctum and canaliculus, and then the tip structure 140 is used in a second dilation procedure to complete the dilation of the punctum and / or canaliculus to inject (e.g., deploy, insert) the intracanalicular injectable 160 into the canaliculus. In some embodiments, for a punctum having a width greater than the threshold width, the tip structure 140 is used in a dilation procedure to dilate the punctum and / or canaliculus to inject (e.g., deploy, insert) the intracanalicular injectable 160 into the canaliculus (e.g., without using the cap 150 to dilate the punctum and / or canaliculus).

[0166] FIG. 12H to FIG. 12I An intratubular injectable applicator device 100 is shown, according to certain embodiments. Figure 12H An exploded view of the intratubular syringe applicator device 100 is shown. Figure 12IA test kit 1200 is shown, which includes an intracanalicular injection applicator device 100 disposed in a housing 1210. In some embodiments, the test kit 1200 includes a housing 1210 for accommodating components. These components may include the intracanalicular injection applicator device 100 and an intracanalicular injection (e.g., an intracanalicular injection loaded into the intracanalicular injection applicator device 100 in a locked position and having a cap 150 placed on the body 110 in the test kit 1200, an intracanalicular injection separated from the intracanalicular injection applicator device in the test kit 1200). The housing 1210 may be a foil pouch. The components in the test kit 1200 may include a desiccant.

[0167] In certain embodiments, the injection (e.g., intratubular injection 160, insert, reservoir, etc.) contains a therapeutic agent. In some embodiments, the injection (e.g., intratubular injection 160, insert, etc.) is an injectable drug or injectable biological product administered by a physician for the prevention, treatment, or cure of a patient's disease or condition. 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.

[0168] Therapeutic agents also include, for example, agents used to treat conditions that may be caused by inflammation or abnormal blood vessel conditions, retinal vein occlusion, geographic atrophy, retinitis pigmentosa, retinoblastoma, etc. For cancer, the agent can be, for example, an anticancer drug, an anti-VEGF drug, or a drug known to be used in cancer treatment.

[0169] The therapeutic agent can be, for example, an anti-VEGF, a VEGFR1 blocker, a VEGFR2 blocker, a VEGFR3 blocker, an anti-PDGF, an anti-angiogenic, sunitinib, E7080, Takeda-6d, tivozanib, regorafenib, sorafenib, pazopanib, axitinib, nintedanib, cediranib, vatalanib, motesanib, a macrolide, sirolimus, everolimus, a tyrosine kinase inhibitor (TKI), imatinib, gefitinib (Iressa), toceranib (Paladin), erlotinib (Tarceva), lapatinib (Taricar), nilotinib, bosutinib, neratinib, lapatinib, vatalanib, dasatinib, erlotinib, gefitinib, imatinib, lapatinib, lestaurinib, nilotinib, semaxanib, tolanib, or vandetanib.

[0170] The therapeutic agent may comprise a macromolecule, such as an antibody or antibody fragment. The therapeutic macromolecule may comprise a VEGF inhibitor, such as ranibizumab, which is the active ingredient in the commercially available Lucentis™. When released into the vitreous humor of the eye, VEGF (vascular endothelial growth factor) inhibitors can cause abnormal blood vessels to regress and improve vision. Examples of VEGF inhibitors include Lucentis™ (ranibizumab), Eylea™ (VEGF Trap), Avastin™ (bevacizumab), and Macugen™ (pegaptanib). Platelet-derived growth factor (PDGF) inhibitors, such as Fovista™, an anti-PGDF aptamer, may also be delivered.

[0171] The therapeutic agent may comprise a small molecule, such as a steroid or corticosteroid and its analogs. For example, the therapeutic corticosteroid may include one or more of triamcinolone, triamcinolone acetonide, dexamethasone, dexamethasone acetate, fluocinolone acetonide, fluocinolone acetonide, loteprednol etabonate, or their analogs. Alternatively or in combination, the small molecule therapeutic agent may comprise a tyrosine kinase inhibitor.

[0172] The therapeutic agent may include an anti-VEGF therapeutic agent. 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™) or antibody derivatives such as ranibizumab (Lucentis™), or small molecules that inhibit VEGF-stimulated tyrosine kinases, such as lapatinib (Tykerb™), sunitinib (Sutent™), sorafenib (Nexavar™), axitinib, or pazopanib.

[0173] The therapeutic agent may include a therapeutic agent suitable for treating dry AMD, such as one or more of Sirolimus™ (rapamycin), Copaxone™ (glatiramer acetate), Othera™ complement C5aR blocker, ciliary neurotrophic factor, retinamide, or rheopheresis.

[0174] The therapeutic agent may include a therapeutic agent suitable for treating wet AMD, such as one or more of REDD14NP (Quark), Sirolimus™ (rapamycin), ATG003; EYELEA (VEGF trap), or a complement inhibitor (POT-4).

[0175] The therapeutic agent may comprise a kinase inhibitor, such as one or more of BIBW 2992 (a small molecule targeting EGFR / Erb2), imatinib (a small molecule), gefitinib (a small molecule), ranibizumab (a monoclonal antibody), pegaptanib (a small molecule), sorafenib (a small molecule), dasatinib (a small molecule), sunitinib (a small molecule), erlotinib (a small molecule), nilotinib (a small molecule), lapatinib (a small molecule), panitumumab (a monoclonal antibody), vandetanib (a small molecule), or E7080 (a small molecule targeting VEGFR2, VEGFR3, and / or FGFR1, commercially available from Esai, Co.). The therapeutic agent may comprise an antibody drug, such as bevacizumab, trastuzumab, cetuximab, and panitumumab.

[0176] Therapeutic agents can include various classes of medicine. Medicine includes, for example, steroids, nonsteroidal anti-inflammatory drugs (NSAIDs), anticancer drugs, antibiotics, anti-inflammatory drugs (such as diclofenac), analgesics (such as bupivacaine), calcium channel blockers (such as nifedipine), antibiotics (such as ciprofloxacin), cell cycle inhibitors (such as simvastatin), proteins (such as insulin). The categories of medicines included in the therapeutic agent include, for example, steroids, NSAIDS, antioxidants, antibiotics, analgesics, vascular endothelial growth factor (VEGF) inhibitors, chemotherapeutics, antiviral drugs. The example of NSAID is ibuprofen, meclofenamic acid sodium, mefenamic acid, salsalate, sulindac, tolmetin sodium, ketoprofen, diflunisal, piroxicam, naproxen, etodolac, flurbiprofen, fenoprofen calcium, indomethacin, celecoxib (celoxib), ketorolac and nepafenac. The drug itself can be a small molecule, protein, RNA fragment, protein, glycosaminoglycan, carbohydrate, nucleic acid, inorganic and organic biologically active compound, where specific biologically active 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 reproductive organs, genes and oligonucleotides or other configurations.

[0177] Therapeutic agents may include proteins or other water-soluble biologics. These include peptides of various molecular weights. Peptides include therapeutic proteins and peptides, antibodies, antibody fragments, short chain variable fragments (scFv), growth factors, angiogenic factors, and insulin. Other water-soluble biologics are carbohydrates, polysaccharides, nucleic acids, antisense nucleic acids, RNA, DNA, small interfering RNA (siRNA), and aptamers.

[0178] The systems disclosed herein can be used to treat ocular diseases including, but not limited to, AMD, glaucoma, dry eye, allergic conjunctivitis, and pain and inflammation following cataract surgery.

[0179] The therapeutic agents can be used as part of a method of treating a given condition or in a composition for treating a given condition. 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 preparation of the periocular 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 strains of microorganisms. 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) is used to treat corticosteroid-responsive inflammation of the palpebral and bulbar conjunctiva, cornea, and anterior segment of the globe. LUMIGAN (bimatoprost ophthalmic solution) is used to reduce elevated intraocular pressure (IOP)—open-angle glaucoma or ocular hypertension. PRED FORTE (prednisolone acetate) is used to treat steroid-responsive inflammation of the palpebral and bulbar conjunctiva, cornea, and anterior segment of the globe. PROPINE (dipifrine hydrochloride) is used to control IOP in chronic open-angle glaucoma. RESTASIS (cyclosporine ophthalmic emulsion) is used to increase tear production in patients, such as those with ocular inflammation associated with keratoconjunctivitis sicca. ALREX (loteprednol etabonate ophthalmic suspension) is used for the temporary relief of seasonal allergic conjunctivitis. LOTEMAX (loteprednol etabonate ophthalmic suspension) is used to treat steroid-responsive inflammation of the palpebral and bulbar conjunctiva, cornea, and anterior segment of the globe. MACUGEN (pegaptanib sodium injection) is used to treat neovascular (wet) age-related macular degeneration. OPTIVAR (azelastine hydrochloride) is used to treat ocular itching associated with allergic conjunctivitis. XALATAN (latanoprost ophthalmic solution) is used to reduce elevated intraocular pressure in patients, such as those with open-angle glaucoma or ocular hypertension. BETIMOL (timolol ophthalmic solution) is used to treat elevated intraocular pressure in patients with ocular hypertension or open-angle glaucoma. Latanoprost is a prodrug in the free acid form that is a selective FP receptor agonist of the prostaglandin class. Latanoprost reduces intraocular pressure in patients with glaucoma with minimal side effects. Latanoprost has relatively low solubility in aqueous solutions but is readily soluble in organic solvents that are commonly used to manufacture microspheres by solvent evaporation.

[0180] Further embodiments of therapeutic agents for delivery include those that specifically bind to the target peptide in vivo to prevent the target peptide from interacting with its natural receptor or other ligand. For example, AVASTIN is an antibody that binds to VEGF. IL-1 traps that utilize the extracellular domain of the IL-1 receptor are also known. This trap can prevent IL-1 from binding to and activating receptors on the cell surface. Embodiments of agents for delivery include nucleic acids, such as aptamers. For example, pegaptanib (MACUGEN) is a pegylated anti-VEGF aptamer. One advantage of particle and hydrogel delivery processes is that aptamers are protected by the in vivo environment until they are released. Further embodiments of agents for delivery include macromolecular drugs, which term refers to drugs that are significantly larger than classic small molecule drugs, i.e., drugs such as oligonucleotides (aptamers, antisense, RNAi), ribozymes, gene therapy nucleic acids, recombinant peptides, and antibodies.

[0181] One embodiment includes the extended release of a drug for allergic conjunctivitis. For example, ketotifen (an antihistamine and mast cell stabilizer) can be provided in granular form and released into the eyes in an effective amount as described herein to treat allergic conjunctivitis. Seasonal allergic conjunctivitis (SAC) and perennial allergic conjunctivitis (PAC) are allergic conjunctival disorders. Symptoms include itching and pink to reddish eyes. Both of these eye conditions are mediated by mast cells. Non-specific measures to alleviate symptoms typically include: cold compresses, washing the eyes with tear substitutes, and avoiding allergens. Treatment typically 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).

[0182] Moxifloxacin is the active ingredient of VIGAMOX, a fluoroquinolone drug approved for the treatment or prevention of bacterial eye infections. VKC and AKC are chronic allergic diseases in which eosinophils, conjunctival fibroblasts, epithelial cells, mast cells and / or TH2 lymphocytes aggravate the biochemistry and histology of the conjunctiva. VKC and AKC can be treated with drugs for allergic conjunctivitis. Penetrants are reagents and can also be included in gels, hydrogels, organogels, xerogels and biomaterials described herein. These are reagents that help drugs 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.

[0183] The agent can treat a posterior ocular disease, for example, wherein the posterior ocular disease is age-related macular degeneration (AMD), cystoid macular edema (CME), diabetic macular edema (DME), posterior uveitis and diabetic retinopathy or glaucoma.

[0184] The agent can be, for example, an anti-VEGF, a VEGFR1 blocker, a VEGFR2 blocker, a VEGFR3 blocker, an anti-PDGF, an anti-PDGF-R blocker, a PDGFRβ blocker, an anti-angiogenic agent, sunitinib, E7080, Takeda-6d, tivozanib, regorafenib, sorafenib, pazopanib, axitinib, nintedanib, cediranib, vatalanib, motesanib, a macrolide, sirolimus , everolimus, tyrosine kinase inhibitors (TKI), imatinib, gefitinib, tolanib, erlotinib, lapatinib, nilotinib, bosutinib, neratinib, lapatinib, vatalanib, including low-soluble prostaglandin analogs for glaucoma, nepafenac, macrolides, rapamycin, sirolimus, tacrolimus, or agents for blocking the mTOR receptor (also known as choroidal neovascularization (CNV)) of AMD. mTOR refers to the mammalian target of rapamycin. The agent can be, for example, moxifloxacin, dexamethasone, travoprost, steroids, fluoroquinolones, prostaglandin analogs, prostaglandin.

[0185] Ocular diseases include eye disorders, and hyphema, ocular hypertension, and glaucoma are conditions treated with anterior chamber reservoirs. Many pharmaceutical agents are suitable for ocular delivery, such as NSAIDs, steroids, anti-glaucoma drugs, antivirals, antibiotics, mydriatics, and antifungals administered by intracameral injection.

[0186] Some disease states are posterior ocular diseases. The term posterior ocular disease has been recognized by those skilled in the art and generally refers to any posterior ocular disease that affects the vasculature and integrity of the retina, macula, or choroid, resulting in visual impairment, loss of vision, or blindness. The posterior segment disease state may be caused by age, trauma, surgical intervention, and genetic factors. Some posterior ocular diseases are: age-related macular degeneration (AMD), cystoid macular edema (CME), diabetic macular edema (DME), posterior uveitis, and diabetic retinopathy. Some posterior ocular diseases are caused by unwanted angiogenesis or vascular proliferation, such as macular degeneration or diabetic retinopathy. Drug treatment options for these and other eye conditions can be provided by delivering medicaments from implants.

[0187] The foregoing description sets forth many 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 cases, well-known components or methods are not described in detail or are presented in the form of simple block diagrams to avoid unnecessarily obscuring the present disclosure. Therefore, the specific details set forth are merely exemplary. Specific embodiments may differ from these exemplary details and are still contemplated to be within the scope of the present disclosure.

[0188] 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, appearances of the phrases "in one embodiment," "in an embodiment," or "in some embodiments" in various places 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, this is intended to mean that the nominal value presented is accurate to within ±10%.

[0189] Although the operation of the method herein is shown and described in a particular order, the order of operation of each method can be changed so that some operations can be performed in reverse order, so that some operations can be performed at least in part, simultaneously with other operations. In another embodiment, the instructions or sub-operations of different operations can be intermittent and / or alternating modes.

[0190] It should be understood that the above description is intended to be illustrative, rather than restrictive. After reading and understanding the above description, many other embodiments will be apparent to those skilled in the art. Therefore, the scope of the present disclosure should be determined with reference to the complete scope of the equivalents enjoyed by the appended claims and these claims.

Claims

1. An intratubular injection applicator device comprising: a body forming a cavity; a cannula connected to the first distal end of the body, wherein the cannula forms a passageway aligned with the cavity of the body, and wherein the cannula is configured to store an intratubular injectable substance in the passageway; a tip structure connected to the body, wherein the tip structure is disposed around at least a portion of the cannula, wherein a distal end of the tip structure is configured to dilate the punctum by inserting the distal end of the tip structure into the canaliculus through the punctum; as well as An actuation structure is configured to simultaneously push the intracanalicular injectable through the channel and the distal end of the tip structure into the canaliculus via the punctum while inserting the distal end of the tip structure into the canaliculus via the punctum.

2. A tip structure of an intratubular injection applicator device, wherein the tip structure comprises: a first distal end configured to be attached to a body of the intratubular injectable applicator device; forming an inner surface of a recess configured to receive a first cannula distal end of a cannula of the intratubular injectable applicator device, wherein a second cannula distal end of the cannula is coupled to the body; and A second distal end including a beveled tip is configured to be inserted into a lacrimal punctum to dilate the punctum and inject an intracanalicular injectable from the cannula through the punctum into the canaliculus.

3. A system comprising: An intratubular injection applicator device, comprising: a body forming a cavity; a cannula coupled to the first distal end of the body, wherein the cannula forms a passage aligned with the cavity of the body; a tip structure coupled to the body, wherein the tip structure is disposed around at least a portion of the cannula, wherein a distal end of the tip structure is configured to dilate the punctum by inserting the distal end of the tip structure through the punctum into the canaliculus; and an actuating structure; and An intratubular injection is loaded in a channel of a cannula of the intratubular injection applicator device, wherein the actuating structure is configured to push the intratubular injection through the channel and the distal end of the tip structure into the cannula via the lacrimal punctum while inserting the distal end of the tip structure into the cannula via the lacrimal punctum.

4. A kit comprising: A housing for accommodating a plurality of components, the plurality of components comprising: An intratubular injection applicator device comprising: a body forming a cavity; a cannula coupled to the first distal end of the body, wherein the cannula forms a passageway aligned with the cavity of the body, and wherein the cannula is configured to store an intratubular injectable substance in the passageway; a tip structure coupled to the body, wherein the tip structure is disposed around at least a portion of the cannula, wherein a distal end of the tip structure is configured to dilate the punctum by inserting the distal end of the tip structure through the punctum into the canaliculus; and an actuation structure configured to simultaneously push the intracanalicular injectable through the channel and the distal end of the tip structure into the canaliculus via the punctum while inserting the distal end of the tip structure into the canaliculus via the punctum; and Intraductal injection.

5. A method of treating with an intravascular injection, the method comprising: loading the intratubular injection into a channel formed by a cannula of an intratubular injection applicator device, wherein the channel is aligned with a cavity formed by a body of the intratubular injection applicator device; inserting the distal end of the tip structure of the intracanalicular injection applicator device into the canaliculus through the lacrimal punctum to dilate the lacrimal punctum; as well as The actuating structure of the intracanalicular injectable applicator device is actuated to inject the intracanalicular injectable into the canaliculus through the channel and the distal end of the tip structure via the punctum while inserting the distal end of the tip structure into the canaliculus via the punctum.

6. A method of treating with an intravascular injection, the method comprising: inserting a distal end of a tip structure of an intracanalicular injection applicator device into a canaliculus through the lacrimal punctum to dilate the lacrimal punctum, wherein an intracanalicular injection is loaded into a channel formed by a cannula of the intracanalicular injection applicator device, wherein the channel is aligned with a cavity formed by a body of the intracanalicular injection applicator device; as well as The actuating structure of the intracanalicular injectable applicator device is actuated to inject the intracanalicular injectable into the canaliculus through the channel and the distal end of the tip structure via the punctum while inserting the distal end of the tip structure into the canaliculus via the punctum.

Images