Apparatus for controlled injection across a variety of material properties

Abstract

Described herein is a generalized injection device for delivering formulations with a variety of mechanical properties to precise locations. Of particular interest is the application of thermally responsive hydrogels to the manifestations of lacrimal ducts for occlusive purposes as a treatment for symptoms associated with dry eye. Further, a modular solution to the needs of injection devices across a variety of applications, mechanisms, and physical considerations is provided. The present disclosure provides examples of methods for precise injection of low volumes, moisture retention in pre-filled injection devices, and actuation of automatic or manual injections, to name a few.

Description

[0001] Cross-reference to related applications

[0002] This application claims priority and interest in co-pending U.S. provisional application No. 16 / 898,805, filed June 11, 2020, entitled “Apparatus for Controlled Injection Across a Variety of Material Properties,” the entire contents of which are hereby incorporated by reference. Background Technology

[0003] Many types of injection devices exist; some are for general purposes, while others are for specific applications. Their modes of action are also unique factors, often depending on the intended use. In clinical configuration, the interaction between human factors and device mechanisms ultimately affects the experience of both the user and the patient. Furthermore, injection dynamics arising from specific geometries, material properties, and mechanical forces can significantly influence the placement of the injected material and its overall efficacy.

[0004] In some cases, injection procedures are delicate and require both precision and speed. Similarly, the injected material may have properties that must be specially tailored, otherwise its intended function may be compromised if the rate of change of material properties or other effects exceeds the expected lifespan, administration rate, or other desired parameters. Summary of the Invention

[0005] This article describes examples of the assembly, performance, and usage of novel syringes. To distinguish this device from those strictly paired with pharmaceuticals, it is also commonly referred to as a device or applicator. The assembly and performance include various mechanical actuators and subtly differentiated design features, which are proportionally modular and enable user-friendly functionality that is most useful, but not exclusive, for single-use and low-volume applications, especially with the application of smart materials.

[0006] In one embodiment, the injection device particularly includes an injection port configured to deliver shape-adjustable material; a coupling assembly coupled to the body of the injection device and the injection port, the coupling assembly including a reservoir configured to contain the shape-adjustable material for ejection through the injection port; and an actuation mechanism including a stop that engages with and seals the reservoir, wherein activation of the actuation mechanism forces the stop into the reservoir, thereby controlling the ejection of the shape-adjustable material through the injection port. In one or more embodiments of these examples, the actuation mechanism may include a spring that forces the stop into the reservoir via a plunger. The spring may be a compression spring sized to provide an axial force based on the characteristics of the ejected shape-adjustable material. The spring may extend upon activation of the actuation mechanism. The spring may be compressed to a full-load length in the range of about 10% to about 50% of its free length before activation. The extension of the spring applies a force to the rear portion of the stop, causing the stop to extend radially, thereby increasing the interference fit with the inner surface of the reservoir. The extension of the spring applies a force to the rear portion of the stop, causing it to contract radially, thereby reducing interference with the inner surface of the reservoir. The spring can provide an injection force at approximately 30% compression or less, exceeding the resistance experienced by the stop during translation within the reservoir. The injection rate can be based on the spring compression.

[0007] In various formulations, the stop can be advanced a predefined length into the reservoir by actuating an actuation mechanism. Advancing the stop by the predefined length can deliver a volume of shape-adaptable material ranging from about 0.01 μL to about 10 mL, or from about 0.1 μL to about 1 mL, or from about 1 μL to about 100 μL, or from about 1 μL to about 20 μL. The predefined length can range from about 0.25 mm to about 60 mm, or from about 0.5 mm to about 10 mm, or from about 1 mm to about 5 mm. The advance of the stop into the reservoir can be limited to a stop distance from the distal end of the reservoir prior to injection. The reservoir may have an axial length (L) and the stop distance may be about 9 / 10 (0.9L) or less of the axial length. In some formulations, the stop may be coupled to the end of the plunger. Force transmission between the stop and the plunger can cause radial contraction of the stop. Force transmission between the stop and the plunger can cause radial expansion of the stop. The stop can be coupled to the plunger via a fork tip and a complementary cavity of the stop. The length of the fork tip can be greater than the length of the complementary cavity. Extension of the fork tip into the complementary cavity allows the stop to contract radially, thereby reducing interference fit with the inner surface of the reservoir. The length of the fork tip can be less than the length of the complementary cavity. One side of the plunger can contact the stop during plunger translation, and said contact can axially compress and radially expand the stop, thereby increasing interference fit with the inner surface of the reservoir. The stop can be an integrated part of the plunger. The stop can comprise a material having a Shore hardness in the range of 0 A to about 90 A. The Shore hardness can be in the range of about 30 A to about 75 A. The stop can comprise a material having a tensile modulus at 100% strain in the range of about 0.1 MPa to about 10 MPa. The tensile modulus can be in the range of about 1 MPa to about 4 MPa.

[0008] In many embodiments, the actuation mechanism can pneumatically force a stop into the reservoir. The stop can maintain an effective static seal by radial expansion in response to pneumatic forces applied to it. The actuation mechanism can release fluid to apply pneumatic forces to the stop. The actuation mechanism may include one or more elements that are manually operated to force the stop into the reservoir. One or more elements may include gears that convert rotation into axial movement of the stop within the reservoir. The actuation mechanism may include one or more elements that are deformed to expand axially to force the stop into the reservoir. In one or more embodiments, the shape-adaptable material may comprise a non-Newtonian material. The shape-adaptable material may have a viscosity of less than 5000 cp. The shape-adaptable material may be formulated for the dissolution of pharmaceutical, biological, or therapeutic substances. The volume of the shape-adaptable material present in the reservoir may be from about 110% to about 1000% of the injection volume delivered by the injection device. The injection volume can range from about 0.1 μL to about 250 μL. In some cases, the reservoir geometry allows air to be expelled from the reservoir during the introduction of the stop and the formation of a seal with the stop. The reservoir may have a geometry that promotes uniform fluid flow of shape-adaptive material through the injection port when the stop is forced into the reservoir. A coupling assembly may include a dispensing channel extending between the distal end of the reservoir and the injection port. The dispensing channel may be included in an intermediate chamber at the distal end of the reservoir. The intermediate chamber may have a barrel diameter ranging from about 25% to about 95% of the barrel diameter of the reservoir. The transition zone between the reservoir and the intermediate chamber may have a radius of curvature of about 20% to about 100% of the barrel diameter of the intermediate chamber.

[0009] In each configuration, the reservoir and the seal created by the stop and injection mask cap reduce the penetration of fluid or gas into or from the reservoir. The coupling assembly, stop, and / or injection mask cap have a water diffusivity of approximately 1 × 10⁻⁶. -6 cm 2 / s or less, or a wet vapor penetration rate of approximately 10 g / m 2Manufactured using low-permeability materials of / day or less. The bonding assembly may comprise glass, metal, cyclic olefin polymers or copolymers, or blends or layered materials of cyclic olefins or metals. The stop may comprise fluorocarbons, fluoroelastomers, or rubber. The injection port may comprise an injection port tube extending from the bonding assembly. The injection port tube may be assembled to deliver shape-adaptive material into the lacrimal duct. The injection port tube may comprise a blunt tip. The shape-adaptive material may modify its properties within the lacrimal duct to form an occlusive plug. The shape-adaptive material may change from a flowable liquid to a more viscous liquid or solid. The injection port tube may have an outer diameter ranging from about 0.3 mm to about 1.5 mm. The injection port tube may have a length ranging from about 0.5 mm to about 10 mm. The injection port tube may comprise polycarbonate, PEEK, polyimide, PEBAX, or stainless steel. The shape-adaptive material may be a polymeric hydrogel. The polymeric hydrogel may comprise NIPAM (N-isopropylacrylamide) monomer. The polymer hydrogel may contain one or more additional monomers. The polymer hydrogel may contain crosslinking monomers or excipients. The injection port may have a wall thickness to length ratio of about 0.005. The injection port may have a barrel diameter to length ratio in the range of about 1:1000 to about 4:1. The reservoir may contain a cavity assembled with a predefined volume of shape-adjustable material. The injection device may be a disposable device with a reservoir pre-filled with a predefined volume of shape-adjustable material. The coupling assembly may be a disposable assembly with a reservoir pre-filled with a predefined volume of shape-adjustable material. The body and actuation mechanism are reusable.

[0010] In many embodiments, the injection device may include an actuation trigger configured to activate an actuation mechanism. The actuation trigger may include a button configured to engage a plunger. The button may lock the plunger and stop assembly in a position within the reservoir, wherein the position determines a defined volume of shape-adjustable material for injection. The actuation trigger may include a lever configured to activate the actuation mechanism. The body may cover the actuation mechanism and may be sized to fit a user's hand. In one or more embodiments, a replaceable cartridge may be connected to or act as a reservoir, the replaceable cartridge containing shape-adjustable material. The replaceable cartridge may be a coupling assembly including seals at both ends. The coupling assembly may be integrated into the body. The coupling assembly may comprise polycarbonate, polypropylene, polyvinyl chloride, PET, PETG, cyclic olefin polymers or copolymers, or cyclic olefin or metal blends or layered materials, or other plastics, metals, or glass, or other materials suitable for manufacture. The stop and / or injection mask cap may comprise fluorocarbons, fluoroelastomers, rubber, silicone, polyurethane, TPE or TPV, and / or other flexible materials. In some cases, the reservoir may be pre-filled with shape-adaptive material in an injection volume ranging from about 0.01 μL to about 1 mL. At least 90% of the injection volume can be delivered to the target location within a predefined time of initiation of the injection device. The predefined time may be about 5 seconds or less. The injection volume may range from about 0.1 μL to about 250 μL. The reservoir may contain a volume greater than the injection volume. The volume contained in the reservoir may be about 5% to about 2000% of the injection volume. The shape-adaptive material may comprise a polymer hydrogel containing a concentration of 0.2% to 70% of a polymer or copolymer. The shape-adaptive material may have a viscosity of 5000 cp or higher. The injection device may be configured to provide an indication of the integrity or readiness of the shape-adaptive material or the injection device. The bonding assembly may be optically translucent or transparent. The injection device may contain a radiation-compatible material suitable for a cumulative radiation dose of about 100 kGy or less. The bonding assembly may include an activateable heating or cooling element for adjusting the shape-adjustable material prior to injection. The reservoir may include a barrier configured for removal, thereby allowing the mixture of materials prior to injection. The mixture of materials can form a shape-adjustable material.

[0011] Other systems, methods, features, and advantages of this disclosure will become apparent to those skilled in the art upon examination of the following drawings and detailed description. This disclosure is intended to include all such additional systems, methods, features, and advantages within this specification, the scope of this disclosure, and the protection afforded by the appended claims. Furthermore, all optional and preferred features and modifications of the described embodiments can be used in all variations of this disclosure taught herein. Moreover, the individual features of the disclosed variations, and all optional and preferred features and modifications, can be combined with and interchanged with each other.

[0012] The advantages will be set forth in part in the following embodiments, and in part will be apparent from the embodiments or may be learned by practice of the forms described below. The following advantages can be realized and obtained by means of the elements and combinations specifically pointed out in the appended claims. It should be understood that the foregoing general description and the following detailed description are illustrative and explanatory only and are not limiting. Attached Figure Description

[0013] The accompanying drawings, which are incorporated in and form part of this specification, illustrate several of the features described below:

[0014] Figure 1 Examples of injection devices according to various embodiments of the present disclosure are illustrated with various perspective views. This embodiment utilizes mechanical actuation, such that the pressurization assembly is controlled by releasing a load compression spring on the pressurization axis.

[0015] Figure 2 A table illustrating the components of an injection device according to various embodiments of the present disclosure.

[0016] Figure 3 Another example of an injection device according to various embodiments of the present disclosure is depicted in an exploded perspective view. This embodiment utilizes a manual actuation method, such as using a press plunger.

[0017] Figure 4 Another example of an injection device according to various embodiments of the present disclosure is illustrated with various perspective views. This embodiment utilizes another form of manual actuation, such that the pressurization component is controlled via sliding movement.

[0018] Figure 5 Another example of an injection device according to various embodiments of the present disclosure is depicted in various perspective views. This embodiment utilizes mechanical actuation to compress one or more rotating levers to control the pressurization assembly.

[0019] Figure 6 Various perspective views illustrate another example of an injection device according to various embodiments of the present disclosure. This embodiment utilizes mechanical actuation, such that squeezing one or more pressable buttons controls the pressurization components.

[0020] Figure 7 Various perspective views illustrate another example of an injection device according to various embodiments of the present disclosure. This embodiment utilizes mechanical actuation such that one or more rotating levers are used to induce deformation on a deformable feature of the lever or on a connecting assembly along the pressure axis in a manner that controls the injection.

[0021] Figure 8Various perspective views illustrate another example of an injection device according to various embodiments of the present disclosure. This embodiment utilizes mechanical actuation, such that the pressurization assembly is controlled via squeezing movement on a pressable button, a deformable body, a deformable button, or a rotating lever.

[0022] Figure 9 Examples of injection devices according to various embodiments of the present disclosure are shown in various perspective views. These embodiments utilize mechanical actuation, such that the pressurization assembly is controlled via squeezing movement on a pressable button, a deformable body, a deformable button, or a rotating lever.

[0023] Figure 10 Examples of injection devices according to various embodiments of the present disclosure are depicted in various perspective views. These embodiments utilize mechanical and / or pneumatic actuation, such that the pressurization assembly is controlled by compressing a flexible spherical assembly.

[0024] Figures 11A to 11H Examples of reservoir and stop interference and plunger assembly relative to the stop according to various embodiments of the present disclosure are described.

[0025] Figure 12 This describes one possible application of the apparatus according to various embodiments of the present disclosure. This example may include injecting a thermoreactive hydrogel into the lacrimal duct, where its state changes from fluid to solid or semi-solid, thus occluding the pathway.

[0026] Figure 13 and Figure 14 Examples of the use of the nasolacrimal anatomy structure and lacrimal duct embolization syringe according to various embodiments of the present disclosure are described.

[0027] Figure 15 Images illustrating flexible silicone lacrimal duct occlusion in a lacrimal duct model according to various embodiments of the present disclosure. Detailed Implementation

[0028] With the aid of the teachings presented in the foregoing description and associated drawings, those skilled in the art will recognize many modifications and other embodiments disclosed herein. Therefore, it should be understood that this disclosure is not limited to the specific embodiments disclosed, and that modifications and other embodiments are intended to be included within the scope of the appended claims. Those skilled in the art will recognize many variations and adaptations of the forms described herein. These variations and adaptations are intended to be included in the teachings of this disclosure and are covered by the claims herein.

[0029] Although specific terms are used in this article, they are used only in a general and descriptive sense and not for limiting purposes.

[0030] As will be apparent to those skilled in the art upon reading this disclosure, each of the various embodiments described and illustrated herein has its own components and features, which can be readily separated from or combined with the features of any of the other embodiments without departing from the scope or spirit of this disclosure.

[0031] Any described method and / or construction may be performed in the described order of assembly or in any other logically possible order. That is, unless expressly stated otherwise, no method or configuration described herein is intended to be construed as requiring its steps or construction to be presented in a particular order. Therefore, where the method or technical solution does not specifically state in the claims or embodiments that the steps are limited to a particular order, no inference of order is intended in any respect. This serves as the basis for any possible non-express interpretation, including logical matters, grammatical organization, or punctuation derived from the arrangement or flow of operations of steps, components, assemblies, or operations, or the number or type of configurations described in the specification.

[0032] All publications and patents cited in this specification are referenced to disclose and describe methods and / or materials relating to the cited publications. All such publications and patents are incorporated herein by reference as if each individual publication or patent were specifically and individually indicated as incorporated by reference. Such incorporation by reference is expressly limited to the methods and / or materials described in the cited publications and patents and does not extend to any dictionary definitions from the cited publications and patents. Any dictionary definitions from the cited publications and patents that are not expressly repeated in this application should not be treated as such and should not be construed as defining any terms appearing in the appended claims. References to any publication are made with respect to disclosures prior to the application date and should not be construed as an admission that this disclosure is not entitled to precede the stated publication by virtue of a previously disclosed disclosure. Furthermore, the publication date provided may differ from the actual publication date, which may require independent verification.

[0033] Although forms of this disclosure may be described and claimed in a particular statutory category, such as the systems statutory category, this is only for convenience, and those skilled in the art will understand that every form of this disclosure may be described and claimed in any statutory category.

[0034] It should also be understood that the terminology used herein is for descriptive purposes only and is not intended to be limiting. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the disclosed compositions and methods pertain. It should also be understood that terms, such as those defined in common dictionaries, should be interpreted as having the same meaning as in the context of this specification and related art, and should not be interpreted in an idealized or overly formal sense unless expressly defined herein.

[0035] As used herein, for convenience, multiple items, structural elements, composite elements, and / or materials may be presented in a common list. However, these lists should be understood as if each member of the list were individually identified as a separate and unique member. Therefore, in the absence of any indication otherwise, an individual member of this list should not be interpreted as substantially equivalent to any other member of the same list simply based on its presentation in the common group.

[0036] Geometric structures, dynamics, durations, quantities, and other numerical data may be expressed or presented in range format herein. It should be understood that such range format is for convenience and brevity and should be flexibly interpreted to include not only the numerical values ​​explicitly stated as range limits, but also all individual numerical values ​​or subranges encompassed within the range, as if each numerical value and subrange were explicitly stated. For example, a numerical range of "about 1" to "about 5" should be interpreted to include not only the explicitly stated values ​​of about 1 to about 5, but also the individual values ​​and subranges within the indicated range. Thus, included in this numerical range are individual values ​​such as 2, 3, and 4; subranges such as 1 to 3, 2 to 4, 3 to 5, about 1 to about 3, 1 to about 3, about 1 to 3, etc.; and individually 1, 2, 3, 4, and 5. The same principle applies to ranges describing only one numerical value as a minimum or maximum value. The range should be interpreted to include endpoints (e.g., when describing a range "from about 1 to 3," the range includes both endpoints 1 and 3, and the values ​​between the endpoints). Furthermore, this interpretation should be applied without taking into account the breadth or range of the characters being described.

[0037] The components, mechanisms, and materials disclosed herein are those that can be used, combined, or used in the preparation of the disclosed formulations and methods, or are products of the disclosed formulations and methods. These and other components are disclosed herein, and it should be understood that while specific references to every individual combination and arrangement of these components may not be explicitly disclosed when disclosing combinations, subsets, interactions, groups, etc., each is specifically covered and described herein. For example, if a type of mechanism is disclosed and discussed, and many different components are discussed, every possible combination of mechanisms and components is specifically covered unless specifically indicated to the contrary. For example, if categories of mechanisms A, B, and C and categories of components D, E, and F are disclosed, and example combinations of A+D are disclosed, then each is individually and collectively covered, even if not separately described. Therefore, in this example, each of the combinations A+E, A+F, B+D, B+E, B+F, C+D, C+E, and C+F is specifically covered, and the combinations should be considered in light of the disclosure of A, B, and C; D, E, and F; and the example combination A+D. Similarly, any subset or combination of these is also explicitly covered and disclosed. Thus, by way of example, subgroups of A+E, B+F, and C+E are specifically covered, and the disclosure should be considered in light of the example combinations of A, B, and C; D, E, and F; and A+D. This concept applies to all forms of this disclosure, including but not limited to components, assemblies, mechanisms, assemblies, constructions, and methods using the disclosed mechanical features. Therefore, if various additional assemblies exist that can be performed using any particular embodiment or combination of embodiments of the disclosed methods, each such assembly is specifically covered, and each such assembly should be disclosed.

[0038] In this specification and the following claims, reference will be made to several terms, which are defined to have the following meanings:

[0039] It must be noted that, unless the context clearly specifies otherwise, the singular forms "a(a)", "an(an)" and "the" as used in this specification and the appended claims include several indicators. Thus, by way of example, reference to "mechanism" or "component" includes combinations of two or more mechanisms or components and the like.

[0040] "Optional" or "optionally" means that the events or circumstances described below may or may not occur, and the description includes situations in which combinations or circumstances occur and situations in which combinations or circumstances do not occur.

[0041] Throughout this specification, unless the context otherwise requires, the phrase "comprise" or variations such as "comprises / comprising" should be understood to imply inclusion of the stated elements, integers, steps, features, or groups of elements, integers, steps, or features, but not to exclude any other elements, integers, steps, features, or groups of elements, integers, steps, or features.

[0042] As used herein, the term "about" is used to provide flexibility for the endpoints of a numerical range without affecting the desired result: a given numerical value may be "slightly above" or "slightly below" the endpoint. For the purposes of this disclosure, "about" means a range extending from 10% below the numerical value to 10% above the numerical value. For example, if the numerical value is 10, "about 10" means between 9 and 11, including the endpoints 9 and 11.

[0043] As used herein, unless otherwise specified to present a particular or significant difference, the term "injection" and its grammatically inferred configuration may refer to the physical transfer of material from a device to the site or location of interest and may be considered as any action that is interchangeable with similar descriptive redundancies, such as delivery, application, distribution, and the like.

[0044] As used herein, unless otherwise specified to present a particular or significant difference, the term "push" may refer to any substance that can be conceivably transferred from a reservoir to the location of interest via cannulation or outlet and can be considered interchangeable with similar descriptive redundancies in the appropriate context, such as fluids, solutions, formulations, liquids, gels, polymeric hydrogels, hydrogels, materials, substances and the like.

[0045] As used herein, unless otherwise specified to present a particular or significant difference, the term "applying device" may refer to any complete assembly that dispenses and can be considered interchangeable with similar descriptive redundancies, such as dispensers, syringes, injection devices, apparatuses, delivery systems and the like.

[0046] As used herein, the term "dose / dosage" may refer to the expected injection volume and / or mass, the concentration of a particular component, or a similar empirically measurable parameter.

[0047] As used herein, the term "reservoir" can refer to a cavity that holds fluid prior to injection. In some cases, this term may be used interchangeably with phrases such as "barrel," however, some distinctions may exist between these terms when used within the same description of a feature; for example, a reservoir may be an integral part of a material containing a geometric structure, while a barrel is a segment that contacts a stop. Furthermore, a reservoir and a barrel may be features present within another component, such as a hub, and in such cases, they are often referred to as interchangeable. The reservoir or the component containing the reservoir may be optically translucent or transparent to allow visual verification of the preservation of the material properties of the contained material and the device's readiness for use.

[0048] As used herein, unless otherwise specified to present a specific or significant distinction, the term "injection port" may refer to any outlet or channel through which an injection is ejected and can be considered interchangeable with similar descriptive redundancies, such as needle, tip, cannula, tube, outlet, dispensing port, dispensing site, and the like. While discussions of specific applications, such as those concerning dry eye, imply the benefits of blunt-tipped injection ports, such instances should not be construed as excluding the use of injection ports as subcutaneous or other sharp-tipped delivery systems (specifically, but not exclusively, used in pharmaceutical applications).

[0049] As used herein, the term "hub" can refer to any component or feature that serves as a container and / or connector for one or more directly responsible injections, particularly including reservoirs and injection ports. A hub can also be used to connect a feature to a body and an actuating element. Furthermore, a hub often refers to a feature that determines the depth of the injection port by acting as a physical interface and limiter based on the exposed length of the engagement component in question. Unless otherwise specified to present a specific or significant distinction, "hub" is to be considered interchangeable with similar descriptive and representative redundancies such as engagement component, interface, connector, barrel, barrel, limiter, reservoir (where appropriate), and the like.

[0050] As used herein, the term "pressurization assembly" may refer to any component or assembly directly responsible for pressurizing the reservoir. This may include stops and plungers as defined below, but should also be understood to apply to the broad scope discussed throughout this document.

[0051] As used herein, unless otherwise specified to present a particular or significant difference, the term "stop" may refer to any component or feature acting on a reservoir that directly causes an increase in pressure at the start of fluid distribution and may be considered interchangeable with similar descriptive redundancies, such as compressors and the like.

[0052] As used herein, unless otherwise specified to present a particular or significant difference, the term "plunger" may refer to any actuating component or rigid part that receives external force and acts on a stop to perform injection, and may be considered interchangeable with similar descriptive redundancies, such as shafts, rods, lead screws, cams, springs, compressors and the like.

[0053] It should be noted that in some cases, "plunger" and "stop" may be the same component, referring to any geometry that interfaces with the channels and compartments of the fluid reservoir and through which movement of this interface results in a reduction in volume and an increase in pressure. Unless otherwise specified to present a particular or significant distinction, in any context in which one, two, or a combination of these components performs this function, the components may be referred to (separately or jointly) and are considered interchangeable with reduplicated terms such as pressurizing assembly, compressor, stop, plunger, and the like, where appropriate.

[0054] As used herein, the term "body" may refer to the outer surface that gives the assembly structural integrity and general shape, while containing some or all other components within this housing so that they are not exposed. Unless otherwise specified to present a specific or significant distinction, "body" may be considered interchangeable with similar descriptive redundancies such as frame, housing, and the like.

[0055] As used herein, the term "activation trigger" can refer to any component that receives an external force or a specific signal initiated by a user, thereby triggering an event responsible for actuating the injection. This should be further extended to include components that support or enable the actual force-bearing component to be force-beared in an effective manner. Unless otherwise specified to present a specific or significant distinction, "activation trigger" may be considered interchangeable with similar descriptive and representative redundancies such as button, switch, trigger, dial, valve, spring, guide, and the like.

[0056] As used herein, the term "actuator" can refer to any component that applies or transmits force to the assembly responsible for pressurizing the reservoir. Unless otherwise specified to present a specific or significant distinction, "actuator" can be considered interchangeable with similar descriptive and representative terms such as actuator, spring, lever, cam, compressed gas, linear screw, worm gear, and the like. Actuators can also collectively refer to both the mode of force generation and the mode of force transmission.

[0057] As used herein, the term "fastening assembly" can refer to any assembly that holds one or more components together, thereby allowing them to form a secure joint, frame, and / or fit for the transmission of force. Unless otherwise specified to present a specific or significant distinction, "fastening assembly" may be considered interchangeable with similar descriptive and representative redundancies such as screw, snap-fit, press-fit, latch, clip, and the like.

[0058] As used herein, the term "injection mask cap" can refer to any component located directly above the injection port that provides a seal to prevent leakage or ingress of external substances, including but not limited to air and water. Figure 11C and Figure 11D Examples of the use of this component are described below. This component differs from a cap, which only provides protection against external forces; however, in some embodiments, the injection mask cap itself may have a rigid outer surface that provides protection for the contents of the capsule and / or for the user and patient. Unless otherwise specified to present a specific or significant difference, "injection mask cap" may be considered interchangeable with similar descriptive and representative redundancies, including all variations of the injection port, such as soft plastic (e.g., rubber) caps, seals, orifice / cannula / needle caps, and the like.

[0059] As used herein, the term "expander" can refer to any component that performs the function of dilating, opening, or widening the injection site. In some, but not all, forms, this feature is integrated into a protective cap that protects or covers sensitive components that need to be exposed during use. For the purposes of this document, unless otherwise specified to present a specific or significant distinction, "expander" may be considered interchangeable with similar descriptive and representative redundancies such as cap, expander cap, tear duct expander, and the like.

[0060] As used herein, the term "injection efficiency" can refer to the proportion of fluid volume or mass successfully dispensed relative to the total volume or mass of fluid present in the fluid reservoir prior to injection. In some cases, particularly where the intention is not to deliver all or even most of the fluid within the reservoir, injection efficiency can be considered as the ratio between the actual injected mass or volume and the theoretical injected mass or volume.

[0061] As used herein, the term "occlusion efficiency" refers to the proportion of the cross-sectional area of ​​a channel that is safely blocked by the injected material, relative to the total cross-sectional area of ​​the channel.

[0062] As used herein, the terms "individual," "person," or "patient" include mammals. Non-limiting examples of mammals include humans, rabbits, pigs, dogs, cats, and mice, including transgenic and non-transgenic mice. The methods described herein are applicable to both human treatment, preclinical applications, and livestock applications. In some embodiments, the individual is a mammal, and in some embodiments, the individual is a human.

[0063] As used herein, the term "shape-adjustable material" and equivalent terms can refer to any substance that is partially or completely formed into the shape of the delivery site by the device. The annotations as defined above can include such materials. Such substances include, but are not limited to, liquids, gels, elastomers, hydrogels and other aqueous solutions, gases, vapors, pastes, putties, and multiphase and property-modifying materials. For example, a shape-adjustable material can be a hydrogel based on N-isopropylacrylamide (NIPAM) comprising 0.2% to 70% of a polymer. Often throughout this disclosure, and particularly in relation to applicators for dry eyes, a shape-adjustable material can be a reactive substance that fills a passage (e.g., a lacrimal duct) before its properties are modified to become an occlusive plug. As another example, a shape-adjustable material can be formulated for the dissolution of a drug, biological, or therapeutic substance. The fluid and material can be biocompatible and / or medical-grade components. Examples of various fluids or materials that can be used with the disclosed injection device are provided in U.S. Patent Publication No. 2018 / 0360743 ("Thermoresponsive Polymers and Uses Thereof" by Bartynski et al.), which is hereby incorporated by reference in its entirety.

[0064] Basic structure and injection mechanism

[0065] This document describes a mechanical configuration for injecting boluses for clinical, therapeutic, or commercial purposes, such as cosmetics or manufacturing instruments. A preferred embodiment of this configuration is a pre-filled, single-use device, but this should not be construed as excluding reusability, which would be more common in non-medical applications. Upon trigger actuation, the bolus is pressurized within the device or, in some embodiments, within the cartridge. A preferred embodiment of this configuration relates to a single-trigger, instantaneous bolus injection, but this should not be construed as excluding variable dosing capabilities.

[0066] Embodiments of the device are shown in Figure 1 In this example, mechanical actuation is used to control the pressurization assembly by releasing the load compression spring on the pressurization axis. Figure 2 A table providing a description of the components. For example... Figure 1As seen, the embodiment comprises two halves of a body, which may contain components for performing injection: a pressable button (5A), exposed and substantially flush with the surface of the body (1), resting on top of a conical spring (5B) and constraining a plunger (4B). The plunger (4B) is compressed by a spring (6) along its longitudinal axis. The body halves (1) are fastened together using screws (8). Furthermore, this embodiment includes a connecting assembly (9) that connects to both the body (1) and the injection port (2). The connecting assembly (9) has an internal geometry designed to fill the injected fluid and a stop (4A) that is separate from the plunger (4B) and expels the fluid from the orifice during injection. Additionally, there is a soft plastic cover (10) resting above the orifice (2) which is removed before injection, and a cap (7) that snaps onto the top of the body (1) in a suitable position, thereby protecting the orifice (2) and covering the button (5A) to prevent accidental pressing.

[0067] This attachment (7) or a segment of the body (1) may include a long, thin, conical extruder that acts as a punctal dilator in cases where the physician determines the path is too small or constricted.

[0068] In some cases, the cap (7) can also be used to prevent unintended activation of the device by covering the part of the device that requires external force to perform the injection.

[0069] The activation trigger includes a pressable button (5A) as described above, which, depending on whether it is engaged, can be placed in one of two positions. When disengaged, the surface of the button rests approximately flush with the surface of the body (1), and the conical spring (5B) is subjected to a load equal to the weight of the button (5A), and the reaction force of the button (5A) is constrained by the body (1). The geometry of the button (5A) on the main longitudinal axis of the device is designed to interlock with the plunger (4B), thereby preventing its movement along the axis. For example, one or more tabs of the button (5A) may extend through corresponding recesses of the plunger (4B) to secure the plunger and stop (4A) in a first position. When engaged, the button (5A) further compresses the conical spring (5B). This geometry on the longitudinal axis changes with the depth of the button and ultimately becomes a shape that allows the plunger assembly (4A) to pass through the button (5A) without obstruction. For example, the tab of the button (5A) slides out of the corresponding recess, thereby allowing the plunger (4B) and the stop (4A) to advance through one or more openings in the button (5A) to a second position. When engaged, the interlocking geometry of the components (4B and 5A) prevents the button (5A) from being reset by the conical spring (5B). The plunger (4B) is subjected to a constant load from a compression spring (6), which is housed within the body (1) and further constrained by the geometry of the plunger (4B) itself. For example, the plunger (4B) may include a recess at one end, which is configured to receive one end of the spring (6) to prevent radial and lateral movement. When the feature preventing the plunger (4B) from advancing (e.g., the button 5A) is displaced, the spring will be released or extended, thereby translating the plunger (4B) until it reaches the free length of the spring (6) or until the plunger (4B) reaches the hard stop. The plunger (4B) advances along the longitudinal axis, and if decoupled, it contacts the stop (4A), which is also pushed in the direction of the internal geometry of the hub (9). If the stop (4A) is coupled to the plunger (4B), the pressurization assembly moves as a whole. The distal end of the stop (4A) creates a seal against the internal geometry of the hub (9) as it advances into the reservoir (3), thereby forcing fluid out of the distal end of the hub (9) and into and out of the injection port tip (2). In this embodiment, the injection occurs rapidly (or almost instantaneously), but this is not required for the overall operation of the device.

[0070] Figures 3 to 10 The description illustrates examples of alternative injection modalities. Injection can be actuated manually or mechanically, including but not limited to:

[0071] • Direct axial force on the plunger or any component connected to the fluid reservoir causes translation of these components and / or the reservoir, resulting in encroachment and overlap of the volume contained in the components and / or the reservoir.

[0072] • Rotation of gears, worm gears, or otherwise causes relative axial translation that acts on the plunger.

[0073] • The translation or rotation of levers, ramps, cams, or hinged assemblies, which tilt and gradually apply force to the plunger along the pressure axis.

[0074] • Translation, compression, or rotation of one or more components, which deforms itself or the interfering component on the pressure axis, thus translating the plunger.

[0075] • Compression or expansion of a flexible cavity having complete or partial sealing and / or paired compartments, such that the pressure generated by the volume change causes a corresponding pressure change on or around the plunger, resulting in a translational force perpendicular to the cross-sectional area exposed to the pressure change; this can be gradual or cause binary movement after reaching a certain threshold.

[0076] • Gradually or during bursting, release fluid or compressed gas to fill the cavity and act on the plunger (as described above), or directly on the fluid in the reservoir.

[0077] • The release of the compressed spring—either gradually or in a burst—acts on the plunger.

[0078] • Reactive materials, such as nitinol, gases, or foams, expand, contract, or reshape.

[0079] • Repulsion or attraction caused by exposure to magnetic force or application of electrical pulses.

[0080] In some configurations, the reservoir can be operated at constant pressure, where injection is achieved by removing the boundary between the reservoir and the outlet, such that a proper seal is placed at the junction where the boundary has been removed to prevent leakage anywhere except through the intended outlet. In some configurations, this method can be used in a cyclic manner, thus metering the outflow and effectively controlling the average injection rate over time.

[0081] While this disclosure is particularly concerned with applications involving low volume and the use of high-viscosity materials (e.g., >2000 cp), specifically (but not exclusively) due to the necessity of innovation in response to challenges in sensitivity and accuracy, this should not be construed as preventing any embodiment of this disclosure from being applied to larger volume or lower viscosity applications. In spirit, the embodiments of this disclosure are proportionally modular and character-independent, meaning they are considered applicable to a wide range of scales and material viscosities.

[0082] The structural functionality of the body can also be a factor in the efficient design of the injection device. In some versions, the internal geometry forms a structure for reinforcing and supporting the device relative to external forces. In some versions, these structures also serve to align internal assembly components with each other, such as placing the start button and providing grounding for components involved in actuation (such as the backplate of a spring). Furthermore, in some versions, the body exists as a joint of two halves, which better allows for assembly mounting and can be fastened together by features within the body (such as screw slots and snap-fit ​​mating).

[0083] refer to Figure 3 An example of an injection device is shown, which utilizes a manual actuation method, such as the use of a pressed plunger. The body (1) may include one or more components designed to form or house a reservoir (3), while providing functional shapes for manual operation. The plunger, which may provide part of both the actuation mechanism (5) and the actuation mechanism (6), may be directly actuated or may receive input force from some form of attachment (5) intended to simplify, increase stability, limit movement, and / or provide greater comfort to the user. A stop (4) at the end of the plunger may be gradually pressed to pressurize the reservoir (3), thereby causing fluid in the reservoir to drain through a dispensing orifice (2), which may be part of the attachment or an integrated element within the body (1). Hubs or interfacing components, such as Figure 2 As described in the table, but not in Figure 3 The explanation is as follows.

[0084] refer to Figure 4 An example of an injection device is shown, which utilizes another form of manual actuation, allowing control of the pressurization component via sliding movement. The body (1) may include one or more components designed to form or house a reservoir (3), while providing functional shapes for manual operation. A plunger that can provide part of both the actuation mechanism (5) and the actuation mechanism (6) may be directly actuated or may receive input force from some form of attachment (5) intended to simplify, increase stability, limit movement, and / or provide greater comfort to the user. In some cases, the plunger and the force or sliding input component are not a single element, but the force / sliding input element may also include a locking mechanism, requiring the element connected to the plunger to be pressed or switched before it can be translated. A stop (4) at the end of the plunger can be gradually pressed to pressurize the reservoir (3), thereby allowing internal fluid to drain through a dispensing orifice (2), which may be part of a hub (9) attachment or an integrated component within the body (1).

[0085] refer to Figure 5An example of an injection device is shown, which utilizes mechanical actuation to compress one or more rotating levers to control a pressurizing assembly. The body (1) may include one or more components designed to form or house a reservoir (3) while providing a functional shape for manual operation. One or more lever or trigger elements (5) may be raised from the surface of the body (1) and provide the user with an amplification mechanism for applying an actuating force. In some embodiments, the actuating mechanism (5) may interact directly with an actuating mechanism (6), such as a plunger and / or a stop (4). For example, the actuating mechanism (5) may cause movement of an intermediate assembly, which itself causes translation of the plunger, or may cause axial release of potential energy (e.g., from a spring). In some implementations, the lever may have a shape that allows it to move inward to move the plunger directly axially. In other implementations, inward movement may cause the element to deflect along a translational axis. The stop (4) at the end of the plunger can be pressed to pressurize the reservoir (3), thereby causing the internal fluid to be discharged through the distribution orifice (2), which may be a part attached to the hub (9) or an integrated element within the body (1).

[0086] refer to Figure 6 Examples of injection devices are shown, which utilize mechanical actuation to allow the squeezing of one or more pressable buttons to control a pressurizing component. The body (1) may include one or more components designed to form or house a reservoir (3) while providing a functional shape for manual operation. In some embodiments, the actuation mechanism (5) may include one or more pressable elements that are elevable from the surface of the body (1) and provide a force amplification mechanism for applying an actuating force to the user. In various embodiments, the pressable elements may provide a portion of both the actuation mechanism (5) and the actuation mechanism (6). For example, the actuation mechanism (5) may interact directly with the plunger and / or a stop. In some implementations, the actuation mechanism (5) may cause movement of one or more intermediate components, which themselves cause translation of the plunger or may cause axial release of potential energy (e.g., from a spring). For example, the element may have a shape that allows it to move inward, thereby directly moving the plunger axially. Inward movement may cause the element to deflect on a translational axis. In some configurations, these elements and / or the body (1) may be deformable and compressible to accumulate air (or other fluid) pressure within a container behind the plunger and / or stop. The stop (4) (e.g., at the end of the plunger) may then be pressed to pressurize the reservoir (3), thereby causing internal fluid to drain through a distribution orifice (2), which may be a portion attached to the hub (9) or an integrated element within the body (1).

[0087] refer to Figure 7An example of an injection device is shown, which utilizes mechanical actuation to cause one or more rotating levers to deform on a deformable feature of the lever or on a connecting component in a manner that controls the injection along the pressure axis. The body (1) may include one or more components designed to form or house a reservoir (3) while providing a functional shape for manual operation. The actuation mechanism (5) may include one or more lever or trigger elements that can be raised from the surface of the body (1) and provide a force amplification device for applying an actuating force to the user. In some embodiments, the actuation mechanism (5) may interact directly with the plunger and / or stop (4). For example, the actuation mechanism (5) may cause movement of an intermediate component that itself causes translation of the plunger, or may cause axial release of potential energy (e.g., from a spring). In some implementations, the lever may have a shape that allows it to move inward to move the plunger directly axially. In some embodiments, inward movement may cause the element to deflect along the translation axis. The stop (4) at the end of the plunger can be pressed to pressurize the reservoir (3), thereby causing the internal fluid to be discharged through the distribution orifice (2), which may be a part attached to the hub (9) or an integrated element within the body (1).

[0088] refer to Figure 8 Examples of injection devices are shown, which utilize mechanical actuation to control a pressurizing component via squeezing movement of a pressable button, deformable body, deformable button, or rotary lever. The body (1) may include one or more components designed to form or house a reservoir (3) while simultaneously providing a functional shape for manual operation. In some embodiments, one or more pressable elements (5) rise from the surface of the body (1) and provide the user with an amplification mechanism for applying an actuating force. The pressable elements may provide portions of both the actuation mechanism (5) and the actuation mechanism. In some embodiments, the actuation mechanism (5) may interact directly with the plunger and / or stop. For example, the actuation mechanism (5) causes movement of an intermediate component, which itself causes translation of the plunger, or may cause axial release of potential energy (e.g., from a spring). In some embodiments, the element has a shape that allows it to move inward to move the plunger directly axially. In other embodiments, inward movement may cause the element to deflect along a translational axis. In some configurations, these elements and / or the body (1) may be deformable and compressible to accumulate air pressure within a container behind the plunger and / or stop. The stop (4) (e.g., at the plunger end) may be pressed to pressurize the reservoir (3), thereby discharging internal fluid through a dispensing orifice (2), which may be a portion attached to the hub (9) or an integrated element within the body (1). A cap (7) may be included to cover and protect the injection end of the device (e.g., the dispensing orifice).

[0089] refer to Figure 9Examples of injection devices are shown, which utilize mechanical actuation to control a pressurizing component via squeezing movement of a pressable button, deformable body, deformable button, or rotary lever. The body (1) may include one or more components designed to form or house a reservoir (3) while providing a functional shape for manual operation. In some embodiments, one or more pressable elements (5) may provide a force amplification mechanism for applying an actuating force to the user. The pressable element may provide part of both the actuation mechanism (5) and the actuation mechanism. In some embodiments, the actuation mechanism (5) may interact directly with the plunger and / or stop (4). In some implementations, the actuation mechanism (5) may cause movement of an intermediate component, which itself causes translation of the plunger, or may cause axial release of potential energy (e.g., from a spring). In some embodiments, the element may have a shape that allows it to move inward to move the plunger directly axially. In other embodiments, inward movement may cause the element to deflect on a translational axis. For example, these components and / or the body (1) may be deformable and compressible to accumulate air pressure within a container behind the plunger and / or stop. The stop (4) (e.g., at the end of the plunger) may be pressed to pressurize the reservoir (3), thereby causing internal fluid to drain through a dispensing orifice (2), which may be a portion attached to the hub (9) or an integrated element within the body (1). A cap (7) may be included to cover and protect the injection end of the device (e.g., the dispensing orifice).

[0090] refer to Figure 10 Examples of injection devices are shown, which utilize mechanical and / or pneumatic actuation to control the pressurization assembly by compressing a flexible spherical component. The body (1) may include one or more components designed to form or house a reservoir (3) while providing functional shapes for manual operation. In some embodiments, one or more pressable elements (5) provide the user with a means of amplifying the application of actuation force. The pressable elements may provide portions of both the actuation mechanism (5) and the actuation mechanism (6). For example, the actuation mechanism (5) interacts directly with the plunger and / or stop (4). In some embodiments, the actuation mechanism causes movement of an intermediate component, which in turn causes translation of the stop (4). In some embodiments, the elements have a shape that allows them to move inward to move the stop directly axially via pneumatic pressure. In some implementations, these elements and / or the body (1) may be deformable and compressible to accumulate air pressure within a container behind the plunger and / or stop. The stop (4) can be pressed to pressurize the reservoir (3), thereby causing the internal fluid to drain through the dispensing orifice (2), which may be a portion attached to the hub (9) or an integrated element within the body (1). A cap (7) may be included to cover and protect the injection end of the device (e.g., the dispensing orifice).

[0091] Mechanical considerations, solutions and features

[0092] There are numerous combinations of mechanical pairings and procedural designs, the implementation of which can provide the desired characteristics for one or more applications. For example, an autoinjector allows for rapid and accurate dosing of pharmaceuticals or other fluids. This technology is typically implemented by healthcare professionals for the sake of simplicity and reliability, or for the widespread, rapid, and standardized administration of allergy-related treatments. The disclosed injection devices can be used in medical or healthcare applications and may contain biocompatible, medical-grade, or low-content materials containing harmful extractable or leached chemicals. Injection devices may also contain radiation-compatible materials that exhibit minimal degradation or discoloration upon exposure to a cumulative radiation dose of about 100 kGy or less. For example, the bonding components or other components may be designed to be irradiated while the reservoir is filled with polymers, hydrogels, pharmaceutical compounds, or biological compounds, and subsequently injected with such materials undergoing cross-linking or other mechanical property changes.

[0093] Certain product requirements may encourage a greater focus on static or steady-state characteristics. For example, in the case of a device pre-filled with a substance for later administration, the device can also be viewed as a storage unit for the substance, thus requiring consideration of the stability of the stored substance. These considerations may include material selection, substance composition, surface area exposure, and encapsulation, to name just a few. These elements that allow the device to reliably store pre-filled material are discussed in more detail throughout this disclosure.

[0094] In addition to supporting the precise and reliable delivery of materials with unique properties, there are applications that require the simplicity and speed of autoinjectors. In some cases, injection may need to target specific areas with particular access requirements. As previously described, the type of material being injected may also have specific requirements, where parameters such as injection rate and pressure are related to the material viscosity or, in the case of reactive materials, require reaching a certain depth before undergoing property changes. The latter can also be observed in cases such as with environmentally sensitive materials.

[0095] Such materials can respond to specific stimuli (such as temperature, pH, light, moisture, or other potential environmental differences following exposure), reversibly or permanently altering their mechanical or chemical properties. This dynamic behavior can lead to significant changes in viscosity, stiffness, liquid retention, pharmaceutical ingredient retention, adhesion, and other properties that make the material uniquely multifunctional. Therefore, there is a need for a drug delivery device capable of controlling the application of a variety of materials with diverse behaviors—pharmaceutical or otherwise chemically inert—with specificity, simplicity, speed, and reliability.

[0096] The mechanisms, features, assemblies, and functions provided herein are some of the ways to achieve desired device behavior parameters and human factor optimization. In one instance, the elements described herein are suitable for constructing devices that provide precise, rate-controlled delivery of substances, including but not limited to thermoreactive hydrogels, smart materials, polymer gels, polymers, elastomers, pharmaceutical compounds, adhesives, pharmaceutical dissolution compounds and formulations, aqueous solutions and other liquid formulations, and biological compounds for occluding biocontainers, delivering medicines or other types of therapies, adhesive elements, and elements for introducing conduction (electrically or otherwise) for flow.

[0097] The mechanisms, features, assemblies and functions provided herein are particularly applicable to viscous materials, both Newtonian and non-Newtonian, having a viscosity of about 500 cp to about 20,000 cp or about 3,000 cp to about 15,000 cp, but this should not be construed as excluding consideration of materials with lower or higher viscosity from this disclosure.

[0098] Ergonomics and human factors can play a significant role in the usability and effectiveness of devices across user groups; it is crucial and noteworthy that devices may incorporate certain features for this purpose. In some forms, the body may be small enough to fit the hands of most sizes of users, yet large enough to be easily manipulated and accessible while wearing disposable gloves. In some forms, the body is longer than wide, allowing it to be held like a pen or a wand. In some forms, the body may have sections that widen along an arc, providing a surface for gripping and may include features such as small, spaced extrusions, bumps, indentations, or soft, high-friction materials to serve as gripping surfaces. In some forms, this section may capture the center of mass and be used to bias the center of mass toward the distal half of the device. In some forms, the arousal point may be reached via a break in the continuity of the body and may occur at or near the center of mass. In some cases, the activation method is positioned such that it can be activated by the fingers of the hand holding the device in a manner comfortable for the user, such as by the thumb at the point where people would normally hold the pen, or by the index finger at the point where it is naturally located on the described structure.

[0099] The design, including features that allow the user to adjust the injection dose, can be useful. In some embodiments, this may include a rotating mechanism, such as a gear, that causes another component to travel distally or proximally, such that one of those directions is associated with a reduced dose and the other with an increased dose delivered. In some other embodiments, it may involve a sliding component that acts as a limiter for other moving components. In some embodiments, this may involve limiting the maximum travel distance of the plunger, thus producing a simulation or, in some embodiments, a stepped scale, where the plunger can only drive the stop into the fluid reservoir by a correspondingly limited distance, thereby producing a predetermined percentage of the maximum possible fluid delivery.

[0100] A single device containing multiple injection reservoirs can be useful. In some embodiments, this may include one reservoir at each end of the device. In another embodiment, it may include an assembly containing multiple reservoirs that can be accessed in large quantities by switching the microscope between focusing lenses. In yet another embodiment, it may include a rotatable assembly having several reservoirs that can be pre-filled and discharged with fluid after sufficient rotation to meet a certain geometry, or can receive fluid via rotational action, or a combination thereof. In some embodiments, these dosages may be the same, and in others they may be different, and in still others they may be completely different formulations or materials.

[0101] In some versions, the cylinder or replaceable component may contain a reservoir, thereby allowing circulation between unused pre-filled components. In some versions, this may also include a stop or plunger assembly. For example, the engagement assembly (9) may be detachably attached to the body (1) as a replaceable component. Figures 11A to 11F An example is described that includes a threaded end to the engagement assembly (9), which allows the engagement assembly (9) to be attached to or detached from the body (1) of the injection device. In some cases, there may be available cartridges with different volume injection sizes, wherein these volumes are predetermined, for example by a pre-set stop depth, for attachment to a reusable main device.

[0102] In some embodiments, as described in this disclosure, the cartridge is sealed using an injection mask cap and a stop, wherein the stop is set to a predefined depth and positioned in place during assembly to receive the plunger element. In some embodiments, the cartridge may be additionally or independently sealed with a plastic and / or foil cap, for example, by heat sealing in place, and said cap may be removable to access the reservoir or may be perforated by the device to allow direct access. The cartridge may also be encapsulated as discussed in the embodiments to reduce the potential environmental impact on material properties and device performance.

[0103] The device, in particular, exhibits reusability and may include easily accessible features for resetting the actuation mechanism. In some embodiments, this may include pushing, sliding, or pulling the plunger toward its initial position. In some embodiments, the plunger is moved until the component responsible for generating the geometric constraints can return to its interlocked, inactive position. In some embodiments, this may include a wound coil, a compressed spring, a toggle switch, or an action representing returning the system to an enable-ready state.

[0104] In some scenarios, injection efficiency is only a valuable parameter relative to cost savings, achieved by reducing the amount of wasted fluid or material. Injection may not need to be optimized for efficiency; in fact, a more valuable parameter is ensuring the system consistently injects a specific range of volumes. In other scenarios, injection efficiency is more valuable because the available dose and injection volume should be consistent when more complex user relationships, risk, and cost structures are involved. Where accurate injection is more valuable than efficiency, a design that eliminates variables and ensures consistency can be beneficial.

[0105] In some configurations, the design may include paired geometric considerations where the reservoir (3) and the stop (4A) do not interfere with each other until the stop (4A) is as close as possible to the filling point, thus allowing venting and preventing air trapping, which can cause leaks, fluid integrity problems, or injection inconsistencies. Examples are provided in Figure 11A and Figure 11B middle.

[0106] In some configurations, the reservoir (3) may be designed to be filled with a larger quantity than the intended injection volume. For example, the reservoir (3) may be filled with liquid such that the assembly allows the stop (4A) to penetrate the reservoir sufficiently (e.g., by a defined distance) to force some of the liquid or material out of the dispensing orifice (2), thus actuating the injection system. After actuation, the reservoir (3) may contain a volume greater than the intended injection volume, for example, about 5% to about 2000% or about 10% to about 50%. The presence of internal pressure may further help ensure that an airtight seal has been formed within the barrel (or inner surface) of the reservoir (3). In some configurations, the reservoir and stop geometry can be designed such that the stop (4A) forms a seal against the reservoir wall approximately at the top of the liquid filling level, thereby forcing the trapped air out of the rear of the reservoir (3), minimizing air contact with the fluid or material, which is beneficial for fluids or materials that react with air over time. In this method, or by using a stop designed to expel air during or after the formation of the seal, air expulsion from the system means that the reservoir volume displacement is directly converted into, for example, the volume of ejected fluid rather than compressed air. Furthermore, using a reservoir volume exceeding the intended injection volume allows for the use of extended channels (11) and geometries. These channels, which can help bridge larger changes in cross-sectional area, such as changes present when comparing the barrel (3) and the injection port (2), can improve laminar flow and injection accuracy. These features can be achieved through… Figures 11A to 11F It was observed in the geometric design of the stop (4A) and the reservoir (3).

[0107] Figures 11A to 11HExamples of possible combinations of the hub (9), stop (4A), and plunger (4B) are shown for purposes including but not limited to those discussed in more detail in the above paragraphs and throughout the document. Figure 11A and Figure 11B Examples of stoppers (4A) and hubs or coupling assemblies (9) configured to vent air during installation are described. Introducing a stopper (4A) into a reservoir (3) expels most or all of the air otherwise present in the reservoir (3). The reservoir geometry allows for the introduction of a stopper (4A) and the creation of a seal while expelling most of the air otherwise present, for example by establishing a fill level to approach or match the proximal cross-section of the reservoir (3) to the initial interference. In some embodiments, this air expelling can also be achieved by using a stopper (4A) designed to vent via its body. These examples present a solution and should not be construed as excluding, for example, an venting stopper (4A) based on considerations of this disclosure. Figure 11A This also illustrates the dual-discharge and sealing interference fit that is coordinated with the geometry of the reservoir (3). This element can also provide higher stability during translation.

[0108] Figures 11B to 11D These figures illustrate one possible configuration of the plunger and stop, such that a cavity exists within the hub to house both the plunger and stop. They also demonstrate how the positioning of the plunger and stop can be used to adjust the injection volume. Figure 11B and Figure 11E As shown, the ratio of the reservoir diameter (or width) D to the total barrel length L or to the actuation length should be taken into account for filling and actuation. This ratio may vary depending on, for example, the volume of fluid or material to be stored in the reservoir (3) and other operating characteristics of the injection device. In addition to sealing and venting air from the reservoir (3) during the insertion of the stop (4A), the additional reservoir length can assist in filling the reservoir (3) with fluid or material. Furthermore, this length provides the surface area required for the stop to create a seal. It should be noted that the length of the stop is also a factor in establishing the stop depth, as there exists a minimum depth required to create a seal. In one embodiment, the hub is a pre-filled element (made of, for example...) Figure 11D As described in the document, it is used in conjunction with a handheld rapid automated injection device for delivering approximately 0.1 μL to approximately 20 μL, wherein the total barrel length of the reservoir (3) may be approximately 1 mm to approximately 20 mm or approximately 3 mm to approximately 9 mm, the actuation length may be approximately 0.1 mm to approximately 5 mm or approximately 2 mm to approximately 3 mm, and the diameter may be approximately 0.1 mm to approximately 5 mm or approximately 0.5 mm to approximately 3 mm. In other cases, the ratio between D and L and between D and the actuation length may be approximately 1:1000 to approximately 10:1.

[0109] Figure 11E and Figure 11FFurther illustrating examples of designs considered in this disclosure, such that the stop (4A) interferes with the reservoir barrel, such that the diameter of the stop is larger than the diameter of the reservoir by, for example, within the range of about 0.1% to about 25%, about 1% to about 15%, or about 3% to about 9% of the diameter. These descriptions may also draw attention to the use of ridges on the circumference of the outer surface of the stop (4A) to reduce the contact surface area and friction, while providing stability and sealing assurance relative to leakage.

[0110] Figure 11G and Figure 11H Two examples illustrate how the combination of stop and plunger geometry during injection can affect the behavior of the stop (4A). These examples present only two possible combinations and should not be construed as excluding other geometries or pairings based on considerations of this disclosure.

[0111] In some configurations, the geometry of the stop and reservoir can be designed such that, prior to activation, the stop can only enter the reservoir by traveling a predetermined distance associated with the corresponding predetermined volume before reaching the stop. In some configurations, the actuation mechanism can also be designed to reach the travel limiter, causing the stop (4A) to travel a predetermined distance. For example, this could be a geometric constraint between the housing element and the actuation mechanism, but other suitable limiting mechanisms may be used depending on the actuation method. In some configurations, the stop (4A) may be designed to reduce lateral and / or radial movement, for example, by reducing the length-to-thickness ratio from, for example, about 10:1 or higher to, for example, about 4:1 or lower; by increasing the stiffness of the stop to, for example, about 1 MPa to about 3 MPa, or a tensile modulus of up to about 10 MPa (at 100% strain), depending on the degree of instability or undesirable movement; and / or by introducing features to provide support, such as rigid internal components or mating plungers (4B), as illustrated in the examples of 11C and 11D, or by assembling the reservoir barrel to interfere with the stop (4A) in multiple locations, as illustrated in the example of 11A.

[0112] In some cases, the sensitivity of volume to variations in axial position attributable to component and assembly tolerances can be reduced by controlling the reservoir dimensions. It can be demonstrated that reducing the reservoir width (or the diameter when assuming a cylindrical barrel, as shown below) while maintaining the specified volume by proportionally increasing the barrel length is beneficial for injection accuracy. The volume of the cylinder is given below: This indicates that volume is proportional to the square of the diameter (D), but only linearly proportional to the length (L). Therefore, for every unit increase in diameter, the total length needs to decrease by a larger amount, resulting in a larger fraction of the total volume being captured per unit of axial distance. This leads to higher sensitivity of volume to changes in axial position. Furthermore, in the system assembly of components, dimensional and mating tolerances, including the cumulative offset from nominal positioning, need to be considered. Given that the diameter of the reservoir barrel is fixed while the axial positioning of the stop remains variable, using a smaller diameter in volume-sensitive systems can reduce overall uncertainty and improve the accuracy of the injection volume per unit of axial distance traveled. This is particularly true for systems that rely on specific pre-start and post-start positioning to determine the dispensable volume.

[0113] The required fluid volume for filling or for use after filling but before use and for the initial volume of injection may vary depending on the application; however, certain relationships between the filling or initial volume, the injection volume, and the injection site may be applicable to arrive at an optimal solution. In some cases, the methods described above (e.g., paragraph

[0093] ) in which the filling or initial volume is larger than the expected injection volume may provide benefits for injection consistency and accuracy.

[0114] In some cases, the injection site can impose constraints on injection parameters, which can be advantageous to the designer. For example, when the injection scenario reflects a channel that is sealed at injection and has different internal volumes and a desired injection volume, there can be an advantage in characterizing the internal pressure of the channel generated by the injection. In some cases, a smaller channel can generate a larger internal pressure compared to a larger channel, thereby affecting the pressure of the dispensing fluid and reducing the total amount of fluid administered. However, due to the difference in fluid contact surface area, a smaller channel may require a smaller volume to be filled compared to a larger channel to be effective. In this case, it is possible to achieve similar desired results in both situations. In this way, the physical constraints that lead to natural self-regulation can become beneficial to the designer.

[0115] Limiting external exposure is crucial for the integrity of the injection. In some configurations, a stop (4A) may be placed in a position that fully seals the reservoir (3) to prevent, for example, the ingress of ambient air. In some configurations, this may also be addressed via a cap (threaded or otherwise) or membrane fastened to the opening, such as if applicable to refill or cartridges. In some configurations, the outlet may also be sealed to the external environment by using these elements or by using a tightly fitted flexible cover.

[0116] Diffusion mitigation can be important for maintaining a consistent solution composition within a pre-filled reservoir. In some cases, moisture content maintenance can be crucial for ensuring proper functioning of both the syringe and the injected substance. Inadequate moisture transfer can impair the effective lifespan of the device and the overall range of environmental conditions. Testing has shown that these can be particularly important when the solution volume is very small and therefore sensitive to even small amounts of moisture loss or increase caused by diffusion and / or evaporation over time or attributable to environmental conditions. By way of example, such low-volume cases can be considered to be within the range of dispensed volumes of about 0.01 μL to about 1 mL, or about 0.1 μL to about 100 μL, or about 0.5 μL to about 50 μL; however, such ranges should not be construed as excluding alternative definitions of "low volume," and furthermore, should not be construed as preventing any of the disclosed elements from providing benefits for applications utilizing larger volumes. Control can be achieved through physical design, material selection, and environmental control / manipulation. In some cases, ambient air diffusion can be important in preventing dehydration, oxidation, or other such effects. Regarding water loss, for example, the reservoir (3), the stop (4A), the injection mask cap (10) and / or the encapsulation can use low-permeability materials (e.g., a water diffusion coefficient of at most about 1×10⁻⁶). -6 cm 2 The maximum value of / s and / or the wet vapor penetration rate is at most about 10 g / m 2 The maximum value per day and appropriate thickness design are used to improve the retention of material properties over time. In other samples, the sensitivity of material properties to loss or ingress can also be reduced.

[0117] Various strategies for reducing sensitivity to moisture loss or other unwanted interactions can be used to improve the retention of material properties over time, including but not limited to using a solution present in the reservoir (3) with a volume increase of approximately 10% to approximately 1000%, enhanced molecular bonding to resist reactions with external factors, etc. In some cases, the concentration at manufacture or treatment can be selected based on the expected interactions by understanding the feasible range of solution concentrations; for example, a hydrogel that may undergo dehydration can be generated at the lowest feasible matrix concentration to maximize the time window in which dehydration may occur until the point at which the highest feasible concentration of solution is obtained due to moisture loss, assuming a water-permeable system. In some cases, a chain of treatment operation strategies can be used to enhance the effective storage duration; for example, by hydrating the dried matrix at subsequent time-sequential endpoints, by designs including but not limited to using a construction for hydration at the point of use, or by methods including but not limited to hydrating the dried matrix during device manufacture.

[0118] In some embodiments, the sealed reservoir includes a rigid barrel, a flexible pressurizing element and / or a barrel sealing element, an attached dispensing orifice, and a dispensing orifice cover. In some embodiments, additional secondary seals surround any of these elements to enhance their barrier effect and, in some cases, mitigate the potential effects of high moisture gradients between the reservoir and the environment. In some embodiments, materials including, but not limited to, cyclic olefin polymers and copolymers, cyclic olefin or metal blends or layered materials, polypropylene, glass, and other materials exhibiting low permeability can be used to enhance the reservoir element's ability to form an effective barrier, particularly for reducing moisture penetration. In some, but not all, forms, except for, but not limited to, fluorocarbons / fluoroelastomers, rubber; butyl rubber, EPDM, vulcanized rubber (such as Santoprene) or otherwise, combinations thereof; broadly including thermoplastic elastomers (TPEs) and thermoplastic vulcanized rubbers (TPVs); and other materials impregnated, coated, layered or loaded with any of the above materials or exhibiting similar properties, are considered for use in sealing elements (e.g., stops and injection mask caps), particularly in terms of the desired properties of physical flexibility and moisture impermeability.

[0119] The range of materials selected should be considered in relation to specific requirements; for example, in some samples, such as those involving oil or breathability, materials such as EPDM will be excluded as suboptimal candidates. In some samples, surface treatments or coatings (hydrophobic or other) may be applied to these materials or those that do not provide a suitable moisture barrier on their own. In some samples, the effectiveness of the moisture barrier may be specified by the diffusion coefficient, where the coefficient should be minimized. In some samples, testing and studies have shown that the range is from about 0 to about 1 × 10⁻⁶. -7 cm 2 The diffusion coefficient / s can be considered as a measure of permeability that will allow reliable moisture retention over extended periods of several months or more on a microliter scale, where a coefficient close to zero would be ideal. Similarly, if wet vapor penetration (or water vapor penetration) is used as a reference point, then 3.90 g / m 2 The rate per day can represent an upper limit indicator. Those skilled in the art will understand that such diagrams and parameters are intended for illustrative purposes only, and the specific application and combination of embodiments will affect how beneficial properties and associated values ​​are evaluated; including but not limited to the expected temperature range; where high temperatures lead to increased permeability and absorption levels, and parameters indicate the degree to which certain undesirable interactions are prevented, such as those with gases or oils (e.g., permeability coefficient).

[0120] Design and total exposure area are also important. A sufficiently small surface area with a high degree of permeability can still be feasible relative to the considerations described above. According to Fick's Law, diffusion is directly proportional to surface area exposure and inversely proportional to thickness. Those skilled in the art will understand that these considerations and the indicated choices reflect only a specific set of possible solutions to the conditions described above, and the indicated design parameters should not be interpreted as indicating that other ranges or quantitative property ranges of materials are not conceivable within the scope of this disclosure. In some embodiments, where the sensitivity level to these considerations is low, a higher permeability level may be permissible, while conversely, in cases of higher sensitivity, even tighter constraints may still exist compared to those levels outlined above.

[0121] This is considered applicable to one or more features that impose environmental control on the device and fluids. In some cases, this control will take the form of thermal, electrical, magnetic, moisture, or some other form of insulation. For example, in the case of thermally reactive hydrogels, insulation will prevent the fluid from reacting prematurely. In some cases, control over variable humidity may also be desirable; where a dry environment can accelerate drying, a humid environment can alter or degrade the function of the device or solution, or where a specific humidity range presents optimal storage conditions. In some cases, protection against environmental effects can be achieved via selective impermeability, which is influenced by the separating material and its thickness in the normal plane between the sensitive component and the environment. By selecting a material having, for example, a known water permeability and a desired water permeability over time, Fick's law can be used to estimate the thickness required to achieve the desired moisture retention. In some cases, this protective effect can be achieved by using containment units primarily for the device or secondarily as encapsulation. These elements may include barriers of metal, plastic, or metallized plastic, such as a combination of layered polyester and aluminum. For example, the injection device can be encapsulated in a container containing such a material that exhibits low water permeability.

[0122] According to Fick's law, where the diffusion rate is proportional to the gradient of the concentration of moisture (or conceivably, other substances), additional control can be permitted by using damp fabrics or other units or compartments capable of storing and releasing moisture to maintain relative humidity within an enclosed environment. Conversely, in some other, but not all, states, some characteristics of passively drying fluids will apply to maintaining the desired moisture content in, for example, water-absorbing gelling materials. In some states, this can manifest as cavities within the walls of reservoirs, which may contain air or some other insulating element, such as polyurethane foam. In some states, this concept is further extended by revealing features for active control, such as, for example, active cooling of thermoreactive hydrogels by means of an endothermic reaction or active heating by means of an exothermic reaction. The bonding assembly (9) may include elements that can activate heating or cooling to allow for conditioning of the thermoreactive material prior to injection.

[0123] In some configurations, user-selectable active cooling may involve cavities or chambers within the hub wall, for example, containing a barrier between two compartments that have mechanisms for the user to remove or dismantle the barrier, thus allowing the components to mix and react to draw heat from the surrounding area and ensuring that the thermally reactive hydrogel remains flowable, for example, during injection. The contents of the chambers may contain, for example, water and ammonium nitrate, or other combinations found in common commercial products that generate and endothermic reactions.

[0124] In some embodiments, user-selectable active heating may involve resistors within the hub or engagement assembly (9) that can be used to generate heat when connected to the battery. In some embodiments, for example, a cavity or chamber within the hub wall may contain a barrier between two compartments, the compartments containing and having mechanisms for the user to remove or disassemble the barrier, thus allowing mixing and reaction of these components to release heat to the surrounding area and to heat the injection during injection. The contents of the chamber may contain, for example, water and calcium oxide, magnesium sulfate, or other combinations found in common commercial products that generate and exothermic reactions.

[0125] In some configurations, the reservoir may contain a barrier between two compartments containing substances, which can be assembled prior to injection. The barrier can be removed to allow for the combination of multiple substances. The substances can be assembled to form shape-adaptable materials. For example, the substances may comprise a polymer and water, which, upon assembly, form a hydrogel.

[0126] A more natural transition between the reservoir (3) and the injection site prevents stagnation and backflow, and reduces the level of inertial forces, resulting in smoother fluid flow. Therefore, in some configurations, the geometry of the reservoir (3) can be optimized to minimize disruption to the fluid path. In some configurations, this may involve contouring and removing sharp angles and / or a gradual transition from a larger diameter channel to a smaller diameter channel. In some configurations, the required capacity of the reservoir is achieved by using a minimized cross-sectional area and a longer channel height compared to a short-width reservoir. This concept is also illustrated in… Figures 11A to 11F However, this should only be considered an example and not the only design concerning the concept of geometric transformation.

[0127] Figures 11B to 11F An example of the assembly of a distribution channel (11) between the reservoir (3) and the distribution orifice (2) is also illustrated. As shown, the distribution channel (11) may include multiple reduced diameters or widths to facilitate controlled supply of fluid or material from the reservoir (3) to the distribution orifice (2). The distribution channel may include one or more intermediate chambers or sections (12) with different barrel diameters or widths to reduce or minimize turbulence of the fluid or material as it is pressurized from the reservoir (3) by a stop (4A). The first intermediate chamber or section (12) at the distal end of the reservoir (3) may have a barrel diameter of about 25% to about 95% or about 45% to about 75% of the barrel diameter of the reservoir (3). The transition zone between the reservoir (3) and the first intermediate chamber (12) may have a radius curvature of about 20% to about 100% of the barrel diameter of the first intermediate chamber (12). This improves injection consistency and material integrity. The subsequent intermediate chamber may have a barrel diameter of about 25% to about 95% or about 45% to about 75% of the barrel diameter of the aforementioned intermediate chamber. The transition region between the aforementioned intermediate chamber and the subsequent intermediate chamber may have a radius of curvature of about 20% to about 100% of the barrel diameter of the subsequent intermediate chamber.

[0128] exist Figures 11B to 11F In this example, the end of the reservoir (3) smoothly transitions to an intermediate chamber (12) with a diameter smaller than that of the reservoir barrel, to reduce turbulence of the fluid or material as it is ejected from the reservoir (3) by force applied via a stop (4A) and a plunger (4B). The intermediate chamber (12) smoothly transitions to a portion of a distribution channel (11) that guides the fluid or material to a distribution orifice (2). Here, the distribution channel has substantially the same diameter as the distribution orifice (2). The smooth or gradually narrowing transition region reduces turbulence in the flow of the injected fluid or material and its resistance. Figures 11B to 11F In one example, the length of the intermediate chamber (12) may be about half (e.g., about 2 mm) of the total distribution channel length from the reservoir (3) to the inlet of the distribution orifice (2) (e.g., about 4 mm).

[0129] In some configurations, the stop (4A) is constructed in a form that imparts flexibility while maintaining sufficient rigidity to translate with minimal or no lateral strain when pushed over a relatively large surface area.

[0130] In some designs, the stop (4A) may be made of a lubricating material to reduce sliding friction. Furthermore, the thickness of the interface geometry may be non-uniform to reduce the amount of surface area in contact with the surrounding walls, or selectively thicker to generate a greater amount of friction when needed. In some designs, this non-uniform thickness allows for a greater degree of lateral deformation of the stop under axial compression, which can provide a more effective dynamic seal against the reservoir wall at the end of the injection stroke, providing additional protection against backflow.

[0131] In some configurations, the geometry will form a seal with the reservoir at its distal end, while the proximal end is used for stabilization and to ensure vertical translation, which may or may not involve a seal against the containment wall.

[0132] In some embodiments, the stop may have a thinned neck between the proximal base and the distal head, wherein a seal is formed. In some embodiments, the distal head and / or the proximal base may include a ridge surrounding the stop (4A), such as Figure 11B and Figure 11E As explained in the description. In other versions, it may have a gradual transition zone from a thicker body to a thinner head. In still other versions, the stop (4A) may have a uniform thickness. In some versions, the distal head may terminate with a curve or angle extending distally.

[0133] In some configurations, the stop (4A) may be decoupled and not connected to the plunger (4B) or influence assembly, while in others it may be paired by some internal features, such as complementary cavities or threads, as via Figure 11A The example of the stop cavity is illustrated in some cases. In some cases, the stop (4A) may have an inner cavity that preferably allows the plunger (4B) or realizing component to have a large interface area and allows such components to artificially increase the theoretical volume displacement by causing distal expansion from the head to the distal end of the reservoir at the end of the injection stroke.

[0134] The plunger length and / or distal geometry (e.g., fork tip) can be used to set the depth of the stop (4A) based on the distance traveled between the initial set depth and the translated distal position corresponding to the desired volume. The injection volume can be in the following ranges: about 0.1 μL to about 250 μL, or about 0.1 μL to about 200 μL, or about 1 μL to about 100 μL, or about 1 μL to about 50 μL, or about 1 μL to about 25 μL, or about 1 μL to about 10 μL, or about 2 μL to about 5 μL. For example, for similar to... Figures 11B to 11F For a given example, the barrel depth of approximately 1 mm to approximately 5 mm corresponds to a delivery volume of approximately 1 μL to approximately 16 μL. The injection volume can be freely manipulated depending on the length of the stop (4A), the plunger (4B), or a combination of both, thereby producing a delivery volume of approximately 1 μL to approximately 16 μL. The stop (4A) can be set to any number of distances as it moves from its proximal end position (towards the distal end) of the reservoir, wherein the travel distance is at most approximately 9 / 10 or less of the stop distance of the total length (or depth) of the reservoir barrel, depending on the sealing capability and requirements of the stop.

[0135] In some configurations, the specific construction, assembly, and mating of the stop (4A) and plunger (4B) can be designed to provide specific desired behavior. For example, the relative positions, geometry, and stiffness of these components can be used to selectively time and transmit the application of forces and cause movement and / or deformation. In some configurations, by means of non-exclusive instances, such as those by... Figure 11G As explained, the interaction between the plunger (4B) and the mating protrusion (where the length is greater than the depth of the mating cavity of the softer stop element) produces the utility of these behaviors; wherein the force applied results in deformation, beginning as a protrusion along the central axis, and further causing radial contraction of the stop (which can be described in part by Poisson's ratio of a given material), and wherein this reduced interference behavior can provide benefits relative to the degree of static interference, including but not limited to reduced "loosening" and "slipping" forces (broadly described as the forces required to initiate and maintain translation via the barrel). Therefore, such an assembly can present the opportunity to produce an improved static seal for purposes including but not limited to storage and disposal while maintaining the desired performance behavior.

[0136] In some configurations, the described assembly will exhibit different behaviors. For example, if the central contact point is located deeper within the stop, resulting in a greater longitudinal thickness and an initial contact position closer to the surface of the force-applying element, the level of the distal protrusion can be reduced and overcome by a higher degree of radial expansion, as by Figure 11HAs illustrated, this scenario is analogous to the contact between two flat surfaces of two components, where there is no cavity or mating protrusion at the insertion point. In this case, radial expansion can produce various utility effects, including but not limited to preventing leakage during injection by increasing the level of dynamic interference between the stop and the barrel. However, those skilled in the art will recognize that the interaction depends on a variety of variables, such as material stiffness, the rate of force applied, the degree of interference, the geometry of the outer surface and the radial cross section, and the specific mating geometry, to name just a few, but not all, of the factors to consider.

[0137] In some cases, the described behavior is also significantly influenced by the chosen material. Material properties such as stiffness, hardness, lubricity, and toughness will affect the stop (4A)'s ability to create a seal and determine how it responds to various rates of applied force. In the context of a rapid-actuation injection system considering the aforementioned potential component assemblies, low stiffness and hardness can lead to a greater degree of deformation relative to the force transmitted to movement. In other words, the stop (4B) will exhibit a greater degree of expansion or protrusion over the same amount of time when the material stiffness and hardness are lower. Low-stiffness materials—where a modulus of, for example, about 1.5 MPa or lower can be considered low-stiffness—are more easily deformed, meaning that, for the same contact area and coefficient of friction, the frictional resistance may be lower than that of higher-stiffness materials. However, the greater degree of deformation exhibited by lower-stiffness materials can also result in a larger contact surface area and / or compressive load depending on geometric constraints. Therefore, a balance needs to be struck between component geometry and material properties to achieve the desired performance; this is often indicated by consistently low loosening and slip forces and the absence of backflow or leakage.

[0138] In some configurations, the above considerations regarding the interaction between the stop (4A) and the plunger (4B) may be further influenced by the force transmission rate and mode. When considering the length of the fork tip relative to the length of the complementary cavity, the extension of the spring (6) can introduce, for example, a pulse force through the plunger (4B), which, upon first contacting the rear of the stop (4A) (e.g., where the fork tip length is less than the cavity length), causes the stop (4A) to expand radially, thereby increasing the interference fit with the reservoir (3) from about 1% to about 10% to about 2% to about 20%, thereby improving the dynamic seal and reducing translation. If the cavity allows for a distal protrusion of the stop (4A) (e.g., a fork tip length greater than the cavity length), it can contract radially, thereby reducing the originally higher level of interference from about 4% to about 20% to about 2% to about 10%, which enables the improvement of the static seal while reducing dynamic friction. There may also be some arrangements in which, for example, the rear of the stop is contacted first, followed by axial compression at the proximal end of the stop, and as an additional result, the fork tip contacts the distal end face of the cavity and causes radial contraction at the distal end of the stop.

[0139] To provide effective static and dynamic seals, the stop material should be flexible enough to fully adapt to the profile of the interference barrel. In some cases, the lubricating material itself is insufficient to guarantee adequate performance; in cases such as rapid injection actuation, due to the effects described above, a low-hardness material may perform worse than another material with higher hardness and lower inherent lubricity. In some cases, at a given initial spring force of approximately 2 lbf, materials with Shore hardness ratings in the range of about 0A to about 90A, about 40A to about 85A, about 30A to about 75A, or about 55A to about 75A (or equivalents in other rating systems) and tensile moduli (at 100% strain) in the range of about 0.1 MPa to about 100 MPa, about 0.5 MPa to about 20 MPa, about 1 MPa to about 10 MPa, about 1 MPa to about 5 MPa, or about 2 MPa to about 4 MPa are most favorable for rapid force transmission. Those skilled in the art will understand that the specified scope describes one possible embodiment and does not exclude consideration of other combinations from this disclosure. For example, these scopes may be significantly shifted depending on the applied force, the rate of application of the force, and the coefficient of friction of the material, to name several factors.

[0140] In many embodiments of the device, the presence of a rigid component is expected, which is used to pressurize the fluid reservoir. In some embodiments, this component is directly incorporated into the actuation mechanism, such that, for example, the component remains static under a constant force from a spring (6) in compression, but due to geometric constraints, and moves freely within the intended range of motion once released from those constraints. In some embodiments, this component may include features (e.g., fork tips) for mating with or otherwise interacting with a stop (4A) and features for mating with or otherwise supporting interactions with an actuation component (such as grooves for constraining the end faces of the spring). In some embodiments, this component is not affected by any external force before actuation, which may be rapid and continuous (as in the case of a spring) or subjective to external forces applied by the user (as in the case of manual injection).

[0141] The activation method is important when considering both the reliability and availability of activation. The method should be simple and offer minimal resistance to the intended activation, while protecting the device from malfunction. The button may be colored differently from the body to provide visual distinction. In some embodiments, this can be achieved by using a button that is approximately flush with the device surface when not pressed (e.g., to prevent accidental pressing), measuring about 9 mm or less to about 20 mm wide or greater, and which can activate the device with a force of about 2.8 N to about 11 N, where the pressed portion is about 3 mm to about 10 mm. In some embodiments, this can be achieved by selecting a spring that may be essentially conical (which, relative to its constant and compression distance, prevents pressing). In some embodiments, activation can be attributed to, for example, a geometric constraint between the button and a plunger, wherein the plunger passes through a segment of the button having openings at different depths and shaped in different ways, and wherein the two have interlocking geometry at the minimum depth and complementary non-contact geometry at the maximum depth. These depths may correspond to specific plunger (4B) positions that determine the depth of the stop (4A) inside the reservoir, where the injection volume is determined after the release mechanism is activated. In some configurations, this activation mechanism may be repeated using multiple depth ranges and a series of interlocking and complementary geometries along the movement axis, much like a key switch system. Such features will allow for measured activation amounts at various depths. In some configurations, this feature may conform to other activation mechanisms, such as constraints on geometric deformation. The above description should not be construed as excluding other methods for activation, including those suitable for the components described in this document.

[0142] Locking mechanisms provide a useful means of preventing unintentional or partial activation of a device. In some cases, this can be achieved by providing geometric constraints on the movement of the activating component until it is repositioned; as in the case of a switch.

[0143] It is anticipated that, for rapid injection, the applicable speed range will cover approximately 0.025 m / s to approximately 300 m / s. For non-rapid injection, the applicable speed range will cover approximately 0.25 mm / s to approximately 0.025 m / s, said applicable speed range being intended, for example, to help control the delivery of non-Newtonian fluids or reduce flow rates in sensitive applications.

[0144] In some, but not all, cases, the distance that the stop must travel to complete the injection is much smaller than the compression length of the spring (6) that provides the actuation force, where this ratio may be about 1:100 or less, or 1:25 or less, or 1:10 or less.

[0145] In some configurations, the compression spring (6) does not maintain continuous contact with the plunger or stop and can transmit force only after extending a certain distance.

[0146] When using a spring (6), the injection velocity can be characterized by the mass of the component under the force of a plunger, the spring constant (k), and the deflection; the two components of the force generated by the spring. The acceleration of the spring is equal to the force divided by the mass of interest. The velocity of the spring acting on another component (such as a stop) in the firing line is given as: The initial velocity is given as And d is the distance the spring travels before reaching the next resistance object without being loaded. Assuming the subsequent object provides constant resistance, then the mass v in motion... f It can be considered a variable that controls the injection rate.

[0147] In some cases, compression spring assemblies can be designed to meet the desired injection rate. For example, a strong spring (force, as defined by the spring strain rate (k) and the degree of compression it can be compressed to its free or rest length (L) relative to the known force required to complete the injection. F Approximately 10% to approximately 80% or approximately 20% to approximately 50% of the full-load length to maximize the available potential energy (at most k(0.8L)). F In one configuration of this example, the spring force is not transmitted to the stop (4A) until the spring extends to approximately 50% to approximately 100% or approximately 80% to approximately 95% of its free length, thereby applying approximately 0.5 kL when the spring velocity approaches its highest point. F or smaller or about 0.2kL F A smaller force can be used as a pulse, accelerating from the maximum compression state. In some cases, this pulse can also affect the rear of the stop and cause radial expansion, resulting in greater friction and resistance to translation, thereby further reducing the injection speed.

[0148] In another state, the spring (6) can be compressed to its free or rest length (L). F The spring can be selected to achieve an injection force (F) of approximately 50% or less, approximately 30% or less, or approximately 20% or less. i The injection force is greater than the maximum known resistance experienced during injection (e.g., the resistance that hinders the axial movement of the stop within the reservoir), thereby minimizing the chance of the spring accelerating while maintaining a sufficiently high force to complete the injection. Therefore, the injection force can be given, for example, k(0.3L). F )>F i or k(0.1L) F )>F i, where k is the spring strain rate and the resulting extension rate is proportional to this reduction in potential energy. The spring (6) described above can provide sufficient injection force at a controlled speed, which can be slow enough to be particularly effective for automated injection of non-Newtonian or other materials, including low-viscosity materials (e.g., <1000cp), thanks to a lower Reynolds number and improved resistance to turbulence.

[0149] For low-volume applications, including but not limited to dispensing volumes of about 0.01 μL to about 1 mL, about 0.1 μL to about 100 μL, or about 0.5 μL to about 50 μL, this disclosure provides examples of considered solutions exhibiting the ability to flow rates of about 0.01 μL / s to about 1 mL / s, or about 0.1 μL / s to about 100 μL / s, or about 1 μL / s to about 25 μL / s. In one example, where the device is intended for administering shape-adaptable, temperature-responsive materials for the treatment of symptoms associated with dry eye, flow rates of about 0.2 μL / s to about 50 μL / s or about 1 μL / s to about 10 μL / s are considered desirable; however, such ranges should not be construed as excluding other possible flow rates from the scope considered herein. Furthermore, the foregoing ranges provide examples of flow rates considered as averages and should not be construed as excluding variable flow rates from factors considered herein, as seen in some examples characterized by spring-actuated injections. This disclosure allows for design considerations that control the flow rate, including but not limited to injection port diameter, reservoir size, applied force, rate of application of force, and material properties such as viscosity.

[0150] In some configurations, the injection device can be configured to deliver approximately 90% or more of the injection volume within a defined time period (e.g., about 5 seconds or less) by pressing a button to initiate the injection.

[0151] For non-Newtonian fluids, the injection rate can be reduced to a level proportional to the rate of viscosity change. The applicable rate range varies depending on the individual properties of the fluid, but in some cases, it may include rates ranging from about 0.1 mm / s to about 0.5 m / s.

[0152] A key objective of injection tuning is to ensure laminar flow. The initiation of turbulence is another source of injection variability and a reduction in injection quality or fluid integrity. A common tool for assessing this quality is the Reynolds number. - Consider the relationship between inertial and viscous forces. In the case of non-Newtonian fluids, viscous forces are difficult to characterize because they are not constant in the pressurized cross-sectional region. One technique for addressing flow quality is to ensure that laminar flow is dominant at specific locations and times where the average velocity and channel diameter (D) are highest and the viscosity is lowest. It is assumed that velocity and viscosity variation curves can be derived from no-slip boundary conditions. Velocity is directly related to shear rate, a crucial parameter in viscosity variability; therefore, velocity and viscosity are paired, depending on the unique characteristics of each fluid. Due to the law of conservation of energy, it can be assumed that the effect of velocity is greater than the effect of viscosity along the variation curve, since the fluid's ability to absorb additional energy cannot exceed the change in input energy. Furthermore, the theoretical velocity at the boundary layer is 0 m / s, while the viscosity remains at a non-zero minimum equivalent to a stationary fluid. Therefore, it can be assumed that the worst-case scenario for achieving laminar flow occurs at the center of the channel where the highest velocity occurs. It is assumed that the precise fluid velocity at the interface between the fluid and the stop assembly is equal to the velocity of the stop assembly itself. Therefore, since velocity and cross-sectional area are conventionally proportional, the appropriate time and place for evaluating laminar systems is at the point of maximum diameter, where the component reaches its maximum velocity upon actuation. By further assuming that the system's viscosity and frictional resistance are negligible, an overestimation of the Reynolds number can be achieved, providing a basis for predicting which values ​​assigned to each parameter will prevent turbulence. Such considerations are more important for low-viscosity Newtonian fluids but remain worthwhile in other cases.

[0153] However, various tools exist for adjusting the speed along a given axis. In some cases, this can be analogous to a worm gear and its pairing, requiring a spring-acting object to follow a radial threaded path, such that the time for traveling a given distance increases proportionally to the number and spacing of the threads. In some cases, this scaled automatic injection speed can be achieved by using a torsion spring that causes the rotation of a worm gear, which in turn causes the linear movement of a third component. In some cases, the use of resistances such as friction or lateral compression can also be used to slow the movement of the pressurizing component. In some cases, a stop with a diameter larger than that of its containing barrel can be used, such that the material type and degree of interference determine the level of resistance to movement along an axis perpendicular to its cross-section.

[0154] Controlling injection speed is of particular interest when using reactive and multiphase materials and / or materials exhibiting non-Newtonian behavior, such as shear thickening. For example, when injecting a thermoreactive polymer hydrogel into the lacrimal duct, a balance needs to be struck so that the fluid reaches the desired depth before it solidifies at ambient body temperature. If the injection is too slow, the reaction will occur before the fluid reaches sufficient depth. If the injection is too fast, the fluid becomes more difficult to inject, disrupting the intended dynamics of the procedure.

[0155] Injections requiring greater injection force, particularly for high-viscosity (e.g., >2000 cp) injections, can benefit from pneumatic actuation to achieve constant pressure and force. In some embodiments, this mechanism utilizes a compressed air cylinder and regulator, where a valve on the cylinder opens, allowing air to escape at a rate controlled by the regulator. This pressurizes the air-filled chamber and maintains the same pressure regardless of plunger or other component movement, as the regulator releases more air to compensate, keeping the internal pressure of the chamber constant. In some other, but not all, embodiments, this pressurization can be achieved by manipulating a component that reduces the volume within the chamber at a rate corresponding to the volume gained through the movement of the plunger assembly. In some other embodiments, a spring system applying a constant force can also contribute to efficient injection.

[0156] In some embodiments, the injection port may comprise a self-attaching assembly or a hub-extending tube. The injection port tube may have a blunt or sharp tip and may be made of a variety of materials, including but not limited to polycarbonate, PEEK, polyimide, stainless steel, PEBAX, PTFE, and PET. The injection port may also be considered any attachment that allows the injected substance to be transferred from the reservoir to the site of interest. In this manner, the injection port may be a disposable component, such as a needle or catheter for subcutaneous delivery of substances, or for use at anatomical sites, for example, in common medical procedures.

[0157] The hub may feature custom or standardized connectors, such as Luer connectors, to facilitate the use of injection devices with consumable materials, including but not limited to needles, catheters, and reservoir cartridges. The device may be modular, allowing the reservoir to be connected to one or both of the body and actuation system and injection port.

[0158] In some cases, the shape-adjustable material may be thermally reactive and flowable at room temperature or lower, or about 25°C or lower, or about 32°C or lower, and its properties may change when heated above this threshold by body temperature. The coupling assembly or hub (9) may be configured to prevent changes caused by the user's body temperature before full delivery to the target location. The injection device may be configured to facilitate rapid injection of the shape-adjustable material into the subject and delivery to the target location before changes are caused by their body temperature. The shape-adjustable material may be a reactive material sensitive to environmental factors, and the injection device may be configured to isolate the material from conditions that would alter its properties.

[0159] All the mechanical modes described above should be considered as having been conceived in all possible combinations and permutations that can solve the desired characteristics described herein. Furthermore, well-known mechanisms, assemblies, and functional components should also be considered as having been conceived in these possible permutations and combinations for those skilled in the art.

[0160] Applications and Materials

[0161] The embodiments described above are generalized forms of common intradermal injection devices and are intended to expand the scope of feasible applications. They also anticipate the unique properties of the materials used in the device (such as hydrated or thermally reactive materials, but not exclusively). Some examples of applications and materials of interest are provided below.

[0162] Used to treat tear duct blockage in dry eye

[0163] Background of dry eye applications

[0164] A preferred pairing of materials and applications may be derived, for example, from U.S. Patent Application Publication No. 2018 / 0360743, which is hereby incorporated herein by reference in its entirety and is of particular interest in the use of thermoreactive hydrogels as occlusive agents for treating symptoms often associated with dry eye syndrome (also known as dry eye disease). The spirit of this disclosure is expressed for use with other materials at various anatomical locations and for feasible solutions with all feasible materials.

[0165] Dry eye occurs when the tear film, which normally covers the eye, fails to adequately protect it. Those with dry eye often report difficulties with activities such as reading, computer use, watching television, and driving. Current solutions suffer from significant discomfort that can be addressed by the device described.

[0166] Current technologies for treating dry eye include: over-the-counter (OTC) eye drops, pharmaceutical eye drops, rigid pre-molded emboli, and in-situ insertion and hydration emboli. Embolisms are typically installed using forceps and / or simple insertion tools, which, for example, present the embolus at the tip and then retract a retaining element. These emboli are further categorized by material and by occlusion site (punctate and tubular), but the focus of this section will be to demonstrate how current modalities, with their shared general form, address generally problematic characteristics.

[0167] This embodiment relates to a novel technology for using thermo-reactive hydrogels specifically designed for drug delivery to the lacrimal duct. Figure 12 and Figure 15 This section describes an example of injecting a hydrogel into the lacrimal duct. This example may include injecting a thermoreactive hydrogel into the lacrimal duct, where its state changes from fluid to solid or semi-solid, thus causing occlusion of the pathway. The hydrogel may be a viscous fluid upon injection, adapting to the internal shape of the lacrimal duct. The hydrogel may subsequently solidify as it reaches body temperature. Occlusion is achieved by creating a shape-fit occlusion within the duct, such as… Figure 12 and Figure 14 As shown, a larger amount of moisture is retained on the surface of the eye. Furthermore, the sensation of something blocking the inside of the eye is minimized. The table below describes the undesirable features of current treatments and how this disclosure presents a preferred experience.

[0168]

[0169]

[0170] The therapeutic benefits of this disclosure are as follows: by providing a pre-filled, disposable device with a single binary trigger for injecting shape-adjustable embolic material, both physicians and patients will benefit from a streamlined procedure that minimizes discomfort and risk of complications. This disclosure provides a universal solution and eliminates the need for physicians to perform anatomical measurements and selections between different embolization types and sizes.

[0171] The installation of alternative tear occlusion emboli may primarily involve: manual injection via a syringe and needle, forceps, or instrument, which presses in the fitted embolus and then releases it by contracting a retaining element. When presented for the same application, such devices require more skill and coordination and have a greater potential source of error compared to the disclosed devices.

[0172] Design considerations for dry eye applications

[0173] Figures 13 to 15 This diagram illustrates the anatomical structure of the nasolacrimal duct and examples of syringes that may be used for lacrimal duct occlusion. In some cases, the amount of injected fluid and the injection kinetics will produce a lacrimal occlusion efficiency of approximately 40% to 60%; in others, approximately 60% to 80% occlusion is desirable; in still others, approximately 80% to 100% occlusion is desirable; and in yet another case, complete 100% occlusion is desirable. It should be understood that occlusion efficiency can result from incomplete occlusion or the duct being completely filled with occlusion or from the porosity of the occlusion material. Furthermore, any substitution of the figures within and across the ranges described above can be considered a feasible range of possible occlusion efficiencies relative to the individual needs of the patient and healthcare professional.

[0174] In some configurations, the interface at the anatomical injection site does not create a strong or complete seal around the punctum, thus allowing fluid to exit the punctum around the dispensing cannula if a specific pressure threshold is met. In another configuration, a strong, complete seal can be implemented to ensure the lumen is filled to the maximum volume allowed by the compliance of the surrounding tissue and the depth of the fluid before it solidifies. In some configurations, features used to ensure a proper seal may involve a flexible sheath that contracts with the diameter of the punctum, but other features used to achieve this function are considered outside the examples above.

[0175] In some cases, the outer diameter of the injection port into the lacrimal punctum is small enough to allow for comfortable entry without dilation, such as... Figure 14As explained above. In this configuration, the outer diameter may be smaller than or slightly larger than the average lacrimal punctum diameter, taking into account tissue compliance. The injection port may be blunt-tipped and may be sized to have an outer diameter of approximately 0.3 mm to approximately 1.1 mm. In some configurations, there are injection port diameters or engagement components that are particularly large than the average lacrimal punctum diameter and may require expansion, such as injection port diameters or engagement components for creating a seal; in this case, the expected diameter will be in the range of approximately 0.6 mm to approximately 2.5 mm. It should be noted that the above ranges pertain only to applications of embolization to the lacrimal duct, and these figures do not indicate or exclude other use cases for similar devices.

[0176] In some embodiments, the injection port may be constructed to remain rigid and resistant to buckling, but elastic enough to bend and deflect from about 0° to about 90°. In some embodiments, but not all, this may involve biocompatible materials, including but not limited to polycarbonate, PEEK, polyimide, stainless steel (e.g., as a hypotube with smooth edges), PEBAX, PTFE, or other materials having a stiffness greater than about 0.5 GPa. In some embodiments, this may produce a ratio of exposed injection port length to wall thickness, determined by axial forces reasonably expected in a given application. For low-force scenarios, this may produce a ratio of about 0.005 or higher. It should be noted that the above ranges pertain only to applications of embolization to the lacrimal duct, and these figures do not represent or exclude other use cases for similar devices.

[0177] In some cases, hypodermic needles or similar structures may be involved to accommodate substances in different ways to provide benefits through alternative mechanisms. The injection device or cartridge may be assembled to achieve modularity in delivery methods and delivery sites through standardized fluid management fitting with hypodermic needles, blunt needles, tubes, catheters, etc.

[0178] In some embodiments, the inner diameter of the injection port into the lacrimal punctum may be as large as possible to achieve the desired mechanical and structural characteristics; it is expected to fit within the range of about 0.2 mm to about 1.0 mm, depending on the available support and the force applied to the injection port. In other embodiments, the inner diameter may be minimized as a means of controlling fluid flow as the fluid exits the cannula from the injection port. It should be noted that the above ranges pertain only to applications of embolization to the lacrimal duct, and these figures do not indicate or exclude other use cases for similar devices related to this disclosure. In some embodiments, the inner diameter is sufficiently small relative to the viscosity of the fluid such that the surface tension within the reservoir is sufficient to prevent excessive leakage via the cannula.

[0179] In some embodiments, the preferred exposure length of the injection port for applying the embolization to the lacrimal duct is such that it is easily observable and allows easy access to the lacrimal duct without entering the punctum, and allows the injection to be performed extremely deeply into the lacrimal duct to penetrate the tissue of the lacrimal duct, creating a sufficiently large gap between the device and the lacrimal duct that is negatively affected, or creating this long fluid delivery channel with an appropriate volume not distributed, excessive fluid retained, or distributed at an undesirable mass. The appropriate exposure tip length is expected to be in the range of about 0.5 mm to about 10 mm, or about 1 mm to about 5 mm, or about 2 mm to 4 mm. It should be noted that the above ranges pertain only to the application of the embolization to the lacrimal duct, and these figures do not represent or exclude other use cases for similar devices related to this disclosure, such as hypodermic needle-type injection ports, where the expected exposure length is in the range of about 0.5 mm to about 100 mm or about 5 mm to about 50 mm.

[0180] Preferably, the dispensed volume is large enough to completely occlude the maximum expected anatomical size (or within the expected range of occlusion efficiency) and remain constant under pressure, but small enough that the fluid does not overfill the minimum expected anatomical structure to the point that fluid enters the lacrimal sac or a large amount of fluid is wasted by returning to the lacrimal punctum. As described, the fluid flow depth needs to be deep enough to solidify or semi-solidify upon contact with sufficient surface area to be safely maintained under pressure, but not so deep as to penetrate the nasolacrimal sac, as this could increase the risk of health problems. It should be noted that depth is affected by anatomical size, tissue compliance, injection rate, back pressure, and the rate of phase transition. Therefore, in some cases, a volume larger than that that the static anatomical structure can accommodate can often be dispensed without the risk of entering the nasolacrimal duct and causing material to return from the lacrimal punctum, which can be wiped away to provide an embolism almost flush with the inlet point. Nevertheless, reducing the dispensed volume to what is possibly optimal can be considered beneficial in order to reduce the likelihood of complications and facilitate any potential need for removal. The expected range of dispensing volumes for achieving maximum safe depth relative to anatomical variability in most adults is approximately 1 μL to approximately 15 μL, or approximately 1.5 μL to approximately 8 μL, or approximately 2 μL to approximately 5 μL. Depending on the injection efficiency, the actual initial fluid volume is expected to range from approximately 1 μL to approximately 100 μL. In this case, a conservative injection efficiency of 50% is given as an example; however, this should not be construed as excluding the possibility of different volumes relative to different injection efficiencies. Furthermore, the above remains accurate when the system is designed to present a complete aspiration system, where the geometric constraints on the advance of the stop, reservoir overfilling, and fluid retention after injection are attributable to factors such as... Figure 11C and Figure 11D The examples in the text illustrate this.

[0181] In some configurations, the actuation mechanism and reservoir can be configured to deliver a volume of about 1 μL to about 20 μL or about 2 μL to about 5 μL into the lacrimal duct in about 5 seconds or less.

[0182] In some cases, the injection volume can be considered arbitrary. For example, when hydrogel is applied to a lacrimal duct sealed by an injection device, the resulting injection volume may self-regulate depending on the internal volume of the lacrimal duct and the resulting back pressure. In some cases, smaller channels may generate greater internal pressure compared to larger channels, thereby affecting the pressure of the dispensing fluid and reducing the total amount of fluid administered. However, due to the difference in the contact surface area of ​​the hydrogel, smaller channels may require a smaller volume to fill compared to larger channels to be effective. In this case, it is possible to achieve similar desired results in both cases, regardless of the selected injection volume.

[0183] In some configurations, the injection port is fastened to a hub assembly that acts as a fluid reservoir, thus forming a connection between the reservoir and the injection port, such as... Figure 11C and Figure 11D As described above. In some versions of this component, the distal surface is dome-shaped and smooth, allowing it to serve as a convenient and non-invasive interface when in contact with the patient. In some versions, the exposed tip length may be short enough that the hub can rest comfortably on the eyelid without forcefully pressing into the tissue within the lacrimal punctum; having this length as described above (e.g., paragraph

[0161] ), it has a relative... Figure 14 The lacrimal duct dimensions described herein are example lengths. In some versions, this hub may be connected to the structural body assembly via a snap-fit, thread, or other feature. In some versions, this may be a replaceable assembly, acting as a refill assembly for injection, and may include a stop that decouples from the plunger assembly. In some versions, when the hub and reservoir contact the stop, the contact material may be optimized to minimize friction by: using a low degree of diameter interference of about 0.1% to about 10%, or about 2% to about 8%; using a material with a low coefficient of friction of about 1.0% or less, or about 0.75 or less, or about 0.5 or less; or by reducing the contact surface area of ​​the two components (e.g., by using a ridge, such as by...). Figure 11E and Figure 11F(as illustrated in the examples above); as some examples, and optimized for minimum permeability by using the materials and techniques described above (e.g., paragraphs

[0106] and

[0107] ) and / or by using a thickness proportional to the desired permeability (e.g., paragraph

[0109] ). In some states, this component is transparent so that the interior of the fluid can be observed, which in some states may reflect information related to injection efficacy. An example of this observation is when a thermoreactive hydrogel becomes opaque and colored to, for example, a more solid state as it undergoes a change in properties, which would make it resistant to injection before it has cooled sufficiently to return to a fluid state.

[0184] In some cases, a device may be suitable for containing the dose necessary to treat both eyes.

[0185] All mechanical modes and considerations described above should be considered as having been conceived in all possible combinations and permutations, and also in the context of the following application areas.

[0186] Other applications

[0187] The injection device can be used in a wide range of applications, such as, but not limited to:

[0188] • Drug delivery using multiphase materials.

[0189] • Storage and / or administration of environmentally sensitive, low-volume materials.

[0190] • Electronic insulation, adhesion, or catalytic elements used in specific areas, channels, or occupied areas.

[0191] • For cosmetic or leisure applications, dyes, drugs, or pharmaceutical-like nutritional substances may be used.

[0192] • To deliver medication to the nasal passages to relieve symptoms of congestion or other ailments (e.g., via the nasolacrimal system or via the nasal cavity).

[0193] • For delivering solid cylinders, such as needles or plugs.

[0194] • Delivery of liquids, gels, aerosols, suspensions, and powders.

[0195] • Deliver materials intended to be kept for a period of time.

[0196] • Delivery of materials intended to be removed by rinsing, environmental consumption, or other means.

[0197] • Delivery of pharmaceutical agents or hydrogel mixtures or therapeutic drug release products.

[0198] • Materials intended to be delivered that always pass through an individual performing a certain function along the route (e.g., imaging contrast agents, diagnostic aids, drug delivery, etc.).

[0199] • Delivery of pharmaceutical, biological, or other therapeutic compounds subcutaneously or to specific internal anatomical structures.

[0200] The injection device may include mechanisms, components, assemblies, and / or features that enable the safe and efficient delivery of shape-adjustable materials to the lacrimal duct; material properties, protective materials, and design considerations; mechanical features that enable the controlled delivery of viscous and / or non-Newtonian fluids, formulations, and reactive materials; mechanical features that enable automated, speed-scaled injection; and / or mechanical features that enable precise and rapid delivery of extremely small volumes of approximately and including 1 mL or less. The speed can be controlled and scaled down by selecting spring parameters such as a constant (k), deflection, and permissible emission distance; or by using torsional springs, radial equivalents, and thread pitches in worm gear or gear ratio combinations. The pre-injected material (in a reservoir) may be insulated from and / or actively resist external factors that might otherwise affect the desired fluid properties for a given application. The injection device may include multiple reservoirs that allow for multiple injections from one or more locations on the device. The dose can be adjusted or delivered in defined steps up to the maximum dose. In some cases, these modular dosages can reflect occlusion levels ranging from approximately 40% to approximately 100%. The combination of reservoir and stop can be optimized to prevent trapped air. The injection system may include a main reusable device assembly and pre-filled, refilled / canister assemblies for injection. The injection device may be configured as a pre-filled unit or an aggregate of units, including a pre-filled canister, to store and deliver volumes of, for example, approximately 0.01 μL to approximately 10 mL, approximately 0.1 μL to approximately 1 mL, or approximately 1 μL to approximately 100 μL.

[0201] It should be emphasized that the above embodiments of this disclosure are merely possible examples of implementations set forth for the purpose of clearly understanding the principles of this disclosure. Many variations and modifications can be made to the above embodiments without substantially departing from the spirit and principles of this disclosure. All such modifications and variations are intended to be included within the scope of this disclosure and are protected by the following claims.

Claims

1. An injection device comprising: an injection port configured to deliver a shape-adaptable material, the injection port comprising a straight, blunt tip tube extending between an inlet at a proximal end and an outlet at a distal end, the injection port having a substantially constant diameter of 0.3 mm to 0.6 mm and a fixed exposure length of 1 mm to 5 mm along its length; a coupling assembly coupled to a body of the injection device and to the proximal end of the injection port, the coupling assembly comprising a reservoir configured to contain the shape-adaptable material for ejection through the injection port, the reservoir having a diameter ranging from 0.1 mm to 5 mm and having a ratio of the diameter to a priming length ranging from 1:1000 to 10:1, the coupling assembly further comprising a dispensing channel extending between a distal end of a barrel of the reservoir and the inlet of the injection port, the dispensing channel comprising an intermediate chamber adjacent to the distal end of the barrel, the intermediate chamber having a barrel diameter ranging from 25% to 95% of the barrel diameter of the reservoir, a transition zone between the barrel and the intermediate chamber having a radius of curvature ranging from 20% to 100% of the barrel diameter of the intermediate chamber; and an actuation mechanism comprising a stopper engaged with and sealing the reservoir, wherein activation of the actuation mechanism forces the stopper into the reservoir, thereby controlling ejection of the shape-adaptable material through the injection port, wherein the actuation mechanism ejects a defined injection volume of the shape-adaptable material from the reservoir through the injection port at a rate of 0.2 pL / sec to 50 pL / sec, the defined injection volume ranging from 0.1 pL to 20 pL of the shape-adaptable material having a viscosity greater than 3000 cp, the actuation mechanism ejecting the defined injection volume of the shape-adaptable material from the reservoir through the injection port by advancing the stopper a predefined length into the reservoir.

2. The injection device of claim 1, wherein the actuation mechanism comprises a spring forcing the stopper into the reservoir via a plunger.

3. The injection device of claim 2, wherein the spring is a compression spring sized to provide an axial force based on properties of the shape-adaptable material being ejected.

4. The injection device of claim 3, wherein the spring is extended when the actuation mechanism is activated.

5. The injection device of claim 4, wherein the spring is compressed to a full load length ranging from 10% to 50% of a free length of the spring prior to activation.

6. The injection device of claim 5, wherein during activation, active extension of the spring contacts the stopper and applies a force to a back portion of the stopper, causing the stopper to compress axially and expand radially, thereby increasing an interference fit with an inner surface of the reservoir as the stopper advances the predefined length.

7. The injection device of claim 5, wherein during activation, active extension of the spring or translation of the plunger contacts a distal surface of an internal cavity of the stopper and exerts a force along a central axis of the stopper causing the stopper to radially collapse, thereby reducing the interference fit with the internal surface of the reservoir.

8. The injection device of claim 4, wherein the spring provides an injection force at 30% compression or less of the free length of the spring, the injection force exceeding the unthreading slip force experienced by the stopper to initiate and maintain translation within the reservoir after activation.

9. The injection device of claim 8, wherein the injection rate is based on the amount of compression of the spring, the injection rate ranging from 0.2 to 50 pL / sec.

10. The injection device of claim 1, wherein the predefined length ranges from 0.25 to 10 mm.

11. The injection device of claim 1, wherein initial advancement of the stopper into the reservoir prior to injection is limited by the actuation mechanism or the reservoir to a defined length away from the distal end of the reservoir, wherein the stopper is prevented from advancing beyond the defined length until ejection of the shape-adaptable material is initiated.

12. The injection device of claim 11, wherein the reservoir has an axial length (L) between a proximal end and a distal end of the reservoir and the defined length is 9 / 10 (0.9L) or less from the distal end of the reservoir.

13. The injection device of claim 2, wherein the stopper is coupled to a distal end of the plunger.

14. The injection device of claim 13, wherein force transmission between the stopper and the plunger after activation causes the stopper to radially collapse, thereby reducing the interference fit with the internal surface of the reservoir.

15. The injection device of claim 13, wherein force transmission between the stopper and the plunger as the stopper advances the predefined length causes the stopper to radially expand.

16. The injection device of claim 13, wherein the stopper is coupled to the plunger via a prong and a complementary cavity of the stopper.

17. The injection device of claim 16, wherein the length of the prong is greater than the length of the complementary cavity, wherein the prong is not threadingly mated, the distal end of the prong initiates force transmission to the distal end of the complementary cavity.

18. The injection device of claim 17, wherein extension of the prong into the complementary cavity causes the stopper to radially collapse, thereby reducing the interference fit with the internal surface of the reservoir.

19. The injection device of claim 6, wherein the stopper is coupled to the plunger via a prong and a stopper complementary cavity, the prong extending an axial length from a distal end of the plunger, wherein the axial length of the prong is less than the axial length of the complementary stopper cavity, wherein the axial length is along a longitudinal axis of the plunger.

20. The injection device of claim 19, wherein after the distal end of the stopper contacts the distal end of the reservoir, a face of the plunger contacts the stopper from the proximal end, thereby causing the stopper to axially compress and radially expand, thereby increasing the interference fit with the inner surface of the reservoir.

21. The injection device of claim 2, wherein the stopper is an integral part of the plunger.

22. The injection device of claim 1, wherein the stopper comprises a material having a Shore hardness in a range from 0 A to 90 A.

23. The injection device of claim 22, wherein the Shore hardness is in a range from 55 A to 75 A, the interference of the stopper with the inner surface of the reservoir is 2% to 20%.

24. The injection device of claim 1, wherein the stopper comprises a material having a tensile modulus in a range from 0.1 MPa to 10 MPa at 100% strain.

25. The injection device of claim 24, wherein the tensile modulus is in a range from 1 MPa to 3 MPa.

26. The injection device of claim 1, wherein the actuation mechanism uses a pneumatic force applied to the stopper to move the stopper through the reservoir.

27. The injection device of claim 26, wherein the stopper maintains an effective static seal by radially expanding in response to the pneumatic force applied to the stopper.

28. The injection device of claim 26, wherein the actuation mechanism releases fluid to apply the pneumatic force to the stopper.

29. The injection device of claim 1, wherein the actuation mechanism comprises one or more elements that are manually manipulated to force the stopper into the reservoir.

30. The injection device of claim 1, wherein the actuation mechanism comprises a gear that converts rotation to axial movement of the stopper in the reservoir.

31. The injection device of claim 1, wherein the actuation mechanism comprises one or more elements that are deformed inward, pressurized, rotated, or translated to non-axially transmit a force to cause expansion or movement in an axial direction to force the stopper into the reservoir.

32. The injection device of claim 1, wherein the shape-adaptable material comprises a non-Newtonian material.

33. The injection device of claim 1, wherein the shape-adaptable material has a viscosity less than 20,000 cp.

34. The injection device of claim 1, wherein the shape-adaptable material is a non-Newtonian, multiphase hydrogel that is formulated for dissolution of a pharmaceutical, biological, or therapeutic substance.

35. The injection device of claim 1, wherein the volume of the shape-adaptable material present in the reservoir is 110% to 1000% of the total injectable volume delivered by the injection device.

36. The injection device of claim 1, wherein the reservoir geometry enables air displacement from the reservoir self-filling via or through the stopper during and with the stopper forming a seal with the reservoir or after.

37. The injection device of claim 1, wherein the reservoir has a geometry that facilitates laminar fluid flow of the shape-adaptable material via the injection port upon forcing the stopper into the reservoir by means of a dispensing channel extending between a distal end of a barrel of the reservoir and the inlet of the injection port.

38. The injection device of claim 37, wherein adjacent segments of the dispensing channel use curvature to smoothly transition into one or more intermediate segments of different diameters between the distal end of the barrel and the inlet of the injection port.

39. The injection device of claim 38, wherein the dispensing channel includes at least an intermediate chamber proximate a distal end of the barrel, and wherein the different diameters of the respective intermediate segments decrease between the distal end of the barrel of the reservoir and the inlet of the injection port.

40. The injection device of claim 1, wherein the reservoir and the seal created by the stopper and injection port cover reduce fluid penetration into and from the reservoir and the injection port.

41. The injection device of claim 1, wherein the reservoir and the seal created by the stopper and injection port cover reduce gas penetration into and from the reservoir and the injection port.

42. The injection device of claim 40, wherein the engagement assembly, the stopper, and the injection port cover are manufactured from a low permeability material having a water diffusivity of 1 x 10 -6 cm 2 / s, or less, or a moisture vapor transmission rate of 10 g / m 2 / day or less.

42. The injection device of claim 40, wherein the engagement assembly, the stopper, and the injection port cover are manufactured from a low permeability material having a water diffusivity of 1 x 10 -6 cm 2 / s, or less, or a moisture vapor transmission rate of 10 g / m 2 / day or less.

42. The injection device of claim 40, wherein the engagement assembly, the stopper, and the injection port cover are manufactured 43. The injection device of claim 40, wherein the interface assembly includes a metal, a cyclic olefin polymer, or a cyclic olefin or metal blend or layered material.

44. The injection device of claim 40, wherein the stopper includes a fluorocarbon or a thermoplastic elastomer.

45. The injection device of claim 40, wherein the stopper includes a fluoroelastomer or a thermoplastic vulcanizate.

46. The injection device of claim 1, wherein the injection port tube is configured to deliver the shape-adaptable material into a lacrimal duct, where it maintains its adapted shape to form an occlusive plug in the lacrimal duct.

47. The injection device of claim 1, wherein the injection port tube includes polycarbonate, PEEK, polyimide, PEBAX, or stainless steel.

48. The injection device of claim 1, wherein the shape-adaptable material is a polymeric hydrogel.

49. The injection device of claim 48, wherein the polymeric hydrogel includes NIPAM (N- isopropyl acrylamide) monomers.

50. The injection device of claim 49, wherein the polymeric hydrogel includes one or more additional monomers.

51. The injection device of claim 48, wherein the polymeric hydrogel comprises a cross- linking monomer or excipient.

52. The injection device of claim 1, wherein the injection port has a ratio of wall thickness to length of 0.005 or less.

53. The injection device of claim 1, wherein the injection port has a ratio of inner diameter to length in the range of from 1: 1000 to 4:

1.

54. The injection device of claim 1, wherein the reservoir comprises a cartridge configured to contain a predefined volume of the shape-adaptable material.

55. The injection device of claim 1, wherein the injection device is a disposable device having the reservoir pre-filled with the predefined volume of the shape-adaptable material.

56. The injection device of claim 54, wherein the engagement assembly is a disposable assembly having the reservoir pre-filled with the predefined volume of the shape- adaptable material.

57. The injection device of claim 56, wherein the body and the actuation mechanism are reusable.

58. The injection device of claim 1, comprising an activation trigger configured to activate the actuation mechanism.

59. The injection device of claim 58, wherein the activation trigger comprises a button configured to engage a plunger.

60. The injection device of claim 59, wherein the button arrests the plunger in combination with a stop at a location in the reservoir, wherein the location determines the defined injection volume of the shape-adaptable material for injection after activation.

61. The injection device of claim 58, wherein the activation trigger comprises a lever configured to activate the actuation mechanism.

62. The injection device of claim 1, wherein the body encases the actuation mechanism, the body sized to fit a user's hand.

63. The injection device of claim 1, comprising a cartridge connected to or serving as the reservoir, the cartridge containing a predefined volume of the shape-adaptable material, the cartridge replaceable after each use by an equivalent cartridge.

64. The injection device of claim 63, wherein the cartridge is the engagement assembly comprising a seal at both ends.

65. The injection device of claim 1, wherein the engagement assembly is integrated in the body.

66. The injection device of claim 1, wherein the engagement assembly comprises polycarbonate, polypropylene, polyvinyl chloride, PET, PETG, cyclic olefin polymer, or a cyclic olefin or metal alloyed or layered material, or metal.

67. The injection device of claim 1, wherein the stop and injection port cover comprise a fluorocarbon, silicone, polyurethane, or TPE.

68. The injection device of claim 1, wherein the stop and injection port cover comprise a fluoroelastomer or TPV.

69. The injection device of claim 1, wherein the reservoir is pre-filled with a predefined volume of the shape-adaptable material in a range from 0.01 μί to 1 mL.

70. The injection device of claim 69, wherein at least 90% of the predefined volume is delivered to a target site within a predefined time of activation of the injection device.

71. The injection device of claim 70, wherein the predefined time is 5 seconds or less.

72. The injection device of claim 69, wherein the predefined volume of the shape- adaptable material contained within the reservoir is greater than the defined injection volume, wherein remaining shape-adaptable material remains in both the injection port and a portion of the reservoir adjacent to the injection port after the stopper has traveled to the end of the reservoir.

73. The injection device of claim 72, wherein the predefined volume contained by the reservoir is 5% to 2000% greater than a total injection volume deliverable from the reservoir, independent of the amount of individual injections enabled by the delivery system.

74. The injection device of claim 73, wherein a portion of the shape-adaptable material remains in the reservoir after the defined injection volume is ejected.

75. The injection device of claim 1, wherein the shape-adaptable material comprises a polymer hydrogel comprising a polymer at a concentration of 0.2% to 70%.

76. The injection device of claim 1, wherein the shape-adaptable material has a viscosity of 5000 cp or greater.

77. The injection device of claim 1, wherein the injection device is configured to provide an indication of the shape-adaptable material or integrity or readiness of the injection device independent of a dose.

78. The injection device of claim 77, wherein the engagement assembly is optically translucent or transparent, providing visual access to the shape-adaptable material contained by the reservoir.

79. The injection device of claim 1, wherein the injection device comprises a radiation- compatible material suitable for radiation exposure above background radiation levels up to a cumulative radiation dose, wherein the cumulative radiation dose obtained during exposure to radiation is 100 kGy or less.

80. The injection device of claim 1, wherein the engagement assembly comprises an activatable heating or cooling element for conditioning the shape-adaptable material prior to injection.

81. The injection device of claim 1, wherein the reservoir comprises a barrier configured for removal, allowing a combination of substances spaced apart by the barrier to be mixed prior to injection.

82. The injection device of claim 81, wherein the mixing of the substances at the time of use forms the shape-adaptable material.

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