Medical Penetration Devices and Systems

Abstract

The present invention discloses a medical puncture device and a system including a medical apparatus configured to be assembled into a medical puncture device, the device or system including a syringe barrel (1) including a distal closed end and a proximal open end, a resilient movement unit including an actuating member (2) and a floating seal (3) within the syringe barrel (1), the actuating member (2) and the floating seal (3) being capable of forming a resilient connection such that the actuating member (2) and the floating seal (3) can move back and forth relative to each other, a hollow puncture needle (6) fixedly connected to the actuating member (2) and proximal to the floating seal (3), the hollow puncture needle (6) including a needle distal opening (6a) and a needle body opening (6b), and a flowable composition lumen (7) enclosed by the distal closed end of the syringe barrel, the inner wall of the syringe barrel, and the floating seal (3). The device or system is configured to advance a hollow puncture needle (6) in a distal direction. Prior to use, the needle distal opening (6a) may be proximal to the floating seal (3), within the floating seal (3), between the floating seal (3) and the distal seal (8) at the distal closed end of the syringe barrel, within the distal seal (8), or distal to the distal seal (8). The hollow puncture needle (6) advances through the floating seal (3) and the distal closed end of the syringe barrel, thereby connecting the flowable composition lumen (7), the needle body opening (6b) and the needle distal opening (6a). The present invention allows for injection, access, expansion and / or device implantation into apparent or potential tissue voids, cavities or vessels, and is particularly useful for achieving precise control of puncture depth and needle placement, as well as stable injection and injection of a predetermined volume.

Description

[Technical Field]

[0001] [Cross-reference of related applications] This application claims priority to an international patent with application number PCT / CN2021 / 093646, filing date May 13, 2021, title of invention "Medical Penetration Device and System," the entire contents of said application are incorporated herein by reference in whole for all purposes.

[0002] In some embodiments, the present invention relates to the field of medical devices and apparatus, and more particularly to devices, kits, assemblies, or systems for medical penetration. [Background technology]

[0003] Existing treatments for the suprachoroid space (SCS) typically involve injecting medication into the SCS using a standard syringe. During puncture, the needle insertion depth must be manually controlled, and healthcare professionals must rely on experience to determine if the needle has entered the SCS. However, eye structure varies considerably from patient to patient, and the healthcare professional's determination of needle depth may not be accurate. Therefore, precise placement of the needle in the SCS cannot be guaranteed. Furthermore, the syringe plunger must always be manually pressed during medication injection. Stabilizing the injection rate and preventing fluctuations in flow rate requires skilled work from the healthcare professional. However, in practice, guaranteeing consistent injections each time is difficult. Improved devices and methods are needed for medical penetrations such as injections into the SCS. This invention addresses these and other needs. [Overview of the project]

[0004] In some embodiments, the present invention provides medical puncture devices and medical kits, assemblies, or systems that enable injection, access, expansion, and / or device implantation into the suprachoroidal space or other apparent or potential tissue cavities, cavities, or cavity systems and into blood vessels, in order to address at least one of the defects or shortcomings of existing devices and methods. The present invention is particularly useful for achieving precise control of puncture depth and needle placement, as well as stable injection and injection of a predetermined volume.

[0005] In some embodiments, the present invention provides a medical puncture device (e.g., a syringe) that enables precise placement of a needle into tissue, a system comprising a medical puncture device, a kit comprising components for assembling a medical puncture device, and a medical device assembly comprising one or more components.

[0006] In some embodiments, this specification discloses a system comprising a syringe barrel including a proximal end and a distal end; a floating seal within the syringe barrel; and a needle base located proximal to the floating seal (e.g., the needle base being closer to the practitioner and the floating seal being closer to the subject), configured such that the floating seal and the needle base elastically engage with each other. In some embodiments, the system further comprises a needle including a proximal end and a distal end, the proximal end of the needle engaging with the needle base. In any embodiment of this specification, the proximal end of the needle may be fixed to the needle base or may be assembled to the needle base in a dischargeable manner (e.g., for insertion). In any embodiment of this specification, the needle includes (i) a distal needle opening; (ii) a needle body opening between the proximal end of the needle and the distal end of the needle; and (iii) a needle body passage connecting the distal needle opening and the needle body opening. In any embodiment of this specification, the needle body opening may be located proximal to the distal needle opening. In any embodiment of this specification, the needle base may be configured to advance the needle distally toward the floating seal (for example, when the distal end of the needle is proximal to the floating seal) and / or through the floating seal (for example, when the distal end of the needle is entering or piercing the floating seal).

[0007] In any embodiment of this specification, the proximal lumen and the distal lumen may be located on opposite sides of the floating seal within the syringe barrel. In any embodiment of this specification, the floating seal may separate the proximal lumen and the distal lumen. The proximal lumen and the distal lumen may be sealed by the same syringe barrel or by different syringe barrels belonging to separate syringe units that can be assembled together. In any embodiment of this specification, the distal lumen may contain a fluid composition such as a liquid, solution, suspension, gel, oil, ointment, emulsion, cream, foam, lotion, paste, or any combination or mixture thereof.

[0008] In any embodiment of this specification, the needle body opening and the distal needle opening may be proximal to the floating seal before the needle advances. In any embodiment of this specification, the needle body opening and the distal needle opening may be in the proximal lumen. In any embodiment of this specification, the needle base may be configured to advance the needle distally toward the floating seal. For example, the needle may advance through the proximal lumen. In any embodiment of this specification, the needle base may be configured to further advance the needle distally through the floating seal. In any embodiment of this specification, the needle body opening may be in the proximal lumen and the distal needle opening may be in the distal lumen. In any embodiment of this specification, advancing the needle through the floating seal may include puncturing the floating seal with the distal end of the needle. In any embodiment of this specification, the floating seal may include a guide groove aligned with the needle to facilitate the puncture. In any embodiment of this specification, advancing the needle through the floating seal may include advancing the distal end of the needle through an existing hole or slit in the floating seal.

[0009] In any embodiment of this specification, the needle base may be configured to advance the needle distally such that both the needle body opening and the distal needle opening are distal to the floating seal. In any embodiment of this specification, the needle body opening and the distal needle opening may be located within the distal lumen, for example, in contact with a fluid composition. In any embodiment of this specification, the needle base may be configured to advance the needle distally through the distal lumen such that the needle body opening is within the distal lumen and the distal needle opening is outside the distal lumen. In any embodiment of this specification, when the distal needle opening is outside the distal needle lumen, the distal needle opening may be in contact with the distal seal of the syringe barrel (e.g., distal seal 8). In any embodiment of this specification, when the distal opening of the needle is outside the distal lumen, the distal opening of the needle may be in contact with a contact element (for example, a circular or any other suitable shape, which can be a contact element 1b) at the distal end of the syringe barrel. In any embodiment of this specification, the contact element may be distal to the distal seal and configured to be in contact with the subject. The contact element is optional, and the distal seal may be used here as the contact element. In any embodiment of this specification, the distal seal and / or contact element may be configured to prevent the fluid composition in the distal lumen from being discharged through the distal opening of the needle. In other words, the fluid composition does not flow out from the distal opening of the needle while the distal opening of the needle is in contact with the distal seal and / or contact element.

[0010] In any embodiment of this specification, when the needle body opening contacts the fluid composition in the distal lumen, the needle base may be configured to advance the needle distally so that the distal opening is within the first tissue of the subject. The first tissue can prevent the fluid composition in the distal lumen from being discharged through the distal opening. In any embodiment of this specification, the pressure at the needle body opening in the distal lumen is less than or equal to the pressure at the distal opening in the first tissue. In any embodiment of this specification, the distal lumen may be in fluid communication with the distal opening through the needle body opening and the needle body passage.

[0011] In any of the embodiments of this specification, the needle base may be configured to advance the needle in the distal direction such that the needle body opening is within the distal lumen and the needle distal opening is within the second tissue distal to the first tissue of the subject, or between the first tissue and the second tissue. In any of the embodiments of this specification, the first tissue may be a surface tissue, and the second tissue may be a deep tissue. In any of the embodiments of this specification, the needle distal opening may be present within an obvious or potential tissue void, cavity, or blood vessel that can exist within the second tissue or between the first tissue and the second tissue. In any of the embodiments of this specification, the pressure at the needle distal opening within the second tissue or between the first tissue and the second tissue may be lower than the pressure at the needle distal opening within the first tissue. In any of the embodiments of this specification, the pressure at the needle distal opening within the second tissue or between the first tissue and the second tissue may be lower than the pressure at the needle body opening within the distal lumen. In any of the embodiments of this specification, the distal lumen may be in fluid communication with an obvious or potential tissue void, cavity, or blood vessel via the needle distal opening, the needle body passage, and the needle body opening within the distal lumen. In any of the embodiments of this specification, the floating seal may be configured to move in the distal direction by elastic engagement without moving the needle base or the needle in the distal direction. In any of the embodiments of this specification, the elastic engagement may include one or more springs and / or one or more elastic sheaths. In any of the embodiments of this specification, the fluid composition within the distal lumen may be discharged into the second tissue via the needle distal opening or into a void formed between the first tissue and the second tissue. In any of the embodiments of this specification, the first tissue may be the sclera, the second tissue may be the choroid / ciliary body, and / or the void may be the suprachoroidal space.

[0012] In any of the embodiments of this specification, the fluid composition may include a liquid, a solution, a suspension, a gel, an oil, an ointment, an emulsion, a cream, a foam, a lotion, and / or a paste. In any of the embodiments of this specification, the space between the floating seal and the needle base may not include a fluid composition or a non-gaseous fluid composition. In any of the embodiments of this specification, the space between the floating seal and the needle base may include a gas such as sterile air. In any of the embodiments of this specification, the space between the floating seal and the needle base may be connected to the outside of the syringe barrel, for example, connected to the external environment, so that the space is not a sealed space. In any of the embodiments of this specification, when the needle is in the space between the floating seal and the needle base, the needle may be covered with an elastic sheath. The elastic sheath may seal the needle body opening and may prevent the fluid composition from leaking into the space between the floating seal and the needle base. In any of the embodiments of this specification, the distal lumen does not contain gas and may contain only a non-gaseous fluid composition, for example, a pharmaceutical composition and / or a pharmaceutically acceptable carrier or excipient in the form of a liquid, a solution, a suspension, a gel, an oil, an ointment, an emulsion, a cream, a foam, a lotion, and / or a paste.

[0013] In any of the embodiments of this specification, the system may further include a linear member configured to travel distally through the needle. Optionally, all or part of the linear member may be exposed at the distal end of the needle. In any of the embodiments of this specification, the linear member may include a wire, a tube, or any combination thereof. In any of the embodiments of this specification, the linear member may be selected from the group consisting of a guide wire, a sheath, a catheter, a cannula, a micro-needle, an electrode, and a sensor. In any of the embodiments of this specification, the system may further include a guiding member configured to guide the linear member towards the needle, into the needle, and / or through the needle.

[0014] In any embodiment of this specification, at least one component of the system may be provided separately from one or more other components. In any embodiment of this specification, two or more components of the system may be integrated or pre-assembled.

[0015] In some embodiments, this specification provides a syringe barrel having a proximal end (optionally, a proximal open end) and a distal end (optionally, a distal closed end), and an actuating unit within the syringe barrel, the actuating unit comprising a needle base and a floating seal elastically engaging with each other, the needle base being proximal to the floating seal, and a needle having a proximal end and a distal end engaging with the needle base, the needle comprising (i) a distal needle opening, (ii) a needle body opening between the proximal end and the distal end of the needle, the needle body opening being proximal to the distal needle opening, and (iii) a needle body passage connecting the distal needle opening and the needle body opening. In any embodiment of this specification, the device may further include a fluid composition lumen distal to the floating seal. In any embodiment of this specification, the actuating unit may be configured to advance the needle so that the proximal end and / or distal end of the needle are positioned within the fluid composition lumen.

[0016] In any embodiment of this specification, the fluid composition lumen may contain a fluid composition selected from the group consisting of liquids, solutions, suspensions, gels, oils, ointments, emulsions, creams, foams, lotions, pastes, and any combination thereof. In any embodiment of this specification, the fluid composition lumen may not contain gas. In any embodiment of this specification, the space between the floating seal and the needle base in the syringe barrel may not contain a fluid composition selected from the group consisting of liquids, solutions, suspensions, gels, oils, ointments, emulsions, creams, foams, lotions, pastes, and any combination thereof. In any embodiment of this specification, the space between the floating seal and the needle base in the syringe barrel may contain a gas such as sterile air. In any embodiment of this specification, the space between the floating seal and the needle base may be connected to the outside of the syringe barrel, for example, to the external environment, so that the space is not a sealed space.

[0017] In any embodiment of this specification, the needle base engages with an actuator (e.g., a retaining element) at the proximal open end of the syringe barrel, and the actuator (e.g., a retaining element) may be configured to advance the needle base and the needle distally. In any embodiment of this specification, the actuator unit may include an energy storage member that elastically engages with the needle base and the floating seal. In any embodiment of this specification, the energy storage member may be a first energy storage member, and the actuator unit may further include a second energy storage member that elastically engages with a slider and the floating seal, with a portion of the slider extending outside the syringe barrel. In any embodiment of this specification, the energy storage member may include a spring and / or an elastic sheath. In any embodiment of this specification, the energy storage member may be fixed to the needle base and / or the floating seal. In any embodiment of this specification, the energy storage member may be dischargeably connected to the needle base and / or the floating seal. In any embodiment of this specification, the energy storage member may be configured to apply force to the floating seal, which in turn applies force to the fluid composition within the lumen of the fluid composition. In any embodiment of this specification, the energy storage member may be configured to move the floating seal distally without moving the needle base or the needle.

[0018] In any embodiment of this specification, the device may include a sheath configured to enclose all or part of the needle. In any embodiment of this specification, the sheath may be configured to enclose the distal opening of the needle and / or the opening of the needle body. In any embodiment of this specification, the sheath may be configured to seal the opening of the needle body when enclosing it.

[0019] In any embodiment of this specification, the device may include a stopper in the lumen of the fluid composition, the stopper may be configured to prevent distal movement of the floating seal. In any embodiment of this specification, the stopper may be located on the inner wall of the syringe barrel enclosing the lumen of the fluid composition. In any embodiment of this specification, the device may include a distal seal located at the distal closed end of the syringe barrel. In any embodiment of this specification, the floating seal, syringe barrel, and distal seal may enclose the lumen of the fluid composition.

[0020] In any embodiment of this specification, the device may include a contact element located at the distal closed end of the syringe barrel.

[0021] In any embodiment of this specification, the device may include a guide structure configured to guide a linear member toward, into, and / or through a needle. In any embodiment of this specification, the guide structure may include an inclined guide groove on a floating seal. In any embodiment of this specification, the guide structure may include a valve and / or a removable plug in the inclined guide groove. In any embodiment of this specification, the valve may be a check valve configured to open toward the needle. In any embodiment of this specification, the inclined guide groove may extend from the proximal surface of the floating seal to the distal surface of the floating seal. In any embodiment of this specification, the inclined guide groove may not extend through the floating seal.

[0022] In any embodiment of this specification, the device may further include the linear member. In any embodiment of this specification, the linear member may be selected from the group consisting of guidewires, sheaths, catheters, cannulas, microneedles, electrodes, sensors, and any combination thereof.

[0023] In some embodiments, this specification includes (1) a first syringe unit, (2) a second syringe unit, and a third syringe unit, the first syringe unit including a first syringe barrel, a needle base in the first syringe barrel, and a needle including a proximal end and a distal end that engage with the needle base, the needle including (i) a distal opening, (ii) a needle body opening between the proximal end and the distal end of the needle, the needle body opening being proximal to the distal opening, and (iii) a needle body passage connecting the distal opening and the needle body opening, the second syringe unit The present invention discloses a device in which a syringe unit engages with the distal end of a first syringe unit and includes a second syringe barrel and a floating seal within the second syringe barrel, the floating seal being configured to elastically engage with the needle base when the first and second syringe units engage, and a third syringe unit engages with the distal end of the second syringe unit and includes a third syringe barrel containing a fluid composition, the needle base being configured to advance the needle so that the proximal and / or distal ends of the needle are placed in the fluid composition. In any embodiment of this specification, the device further includes one or more syringe units, optionally a fourth syringe unit configured to engage with the distal end of the third syringe unit.

[0024] In some embodiments, this specification includes (1) a first syringe unit and (2) a second syringe unit, the first syringe unit comprising a first syringe barrel, a needle base and a floating seal elastically engaging with each other within the first syringe barrel, the needle base being proximal to the floating seal, and a needle including a proximal end and a distal end that engage with the needle base, the needle comprising (i) a distal opening and (i The present invention discloses a device comprising: (i) a needle body opening between the proximal and distal ends of a needle, the needle body opening being located proximal to the distal end of the needle; and (iii) a needle body passage connecting the distal end of the needle and the needle body opening, wherein the second syringe unit engages with the distal end of the first syringe unit and includes a second syringe barrel containing a fluid composition, and the needle base may be configured to advance the needle to position the proximal and / or distal ends of the needle in the fluid composition. In any embodiment of this specification, the device may further comprise one or more syringe units, optionally, a third syringe unit configured to engage with the distal end of the second syringe unit.

[0025] In some embodiments, this specification includes (1) a first syringe unit and (2) a second syringe unit, the first syringe unit including a first syringe barrel, a needle base in the first syringe barrel and a needle including a proximal end and a distal end that engage with the needle base, the needle including (i) a distal opening, (ii) a needle body opening between the proximal end and the distal end of the needle, the needle body opening being proximal to the distal opening, and (iii) a needle connecting the distal opening and the needle body opening. A device is disclosed comprising a body passage, the second syringe unit engaging with the distal end of the first syringe unit, a second syringe barrel, a floating seal within the second syringe barrel configured to elastically engage with the needle base when the first syringe unit and the second syringe unit engage, and a fluid composition, the needle base may be configured to advance the needle so that the proximal and / or distal ends of the needle are placed in the fluid composition. In any embodiment of this specification, the device may further include one or more syringe units, optionally a third syringe unit configured to engage with the distal end of the second syringe unit.

[0026] In some embodiments, the present invention discloses a method comprising the step of positioning a distal needle opening in a desired subject using a system or device of any embodiment disclosed herein. In some embodiments, the method comprises the step of positioning the distal needle opening in a first tissue of the subject, the first tissue being able to prevent the fluid composition from being discharged through the distal needle opening. In any embodiment herein, the method may further comprise the step of positioning the distal needle opening in a second tissue of the subject, or between the first and second tissues. In any embodiment herein, the distal needle opening may be in an apparent or potential tissue void, cavity, or blood vessel that allows the fluid composition to be discharged through the distal needle opening. In any embodiment herein, the method may further comprise the step of delivering the fluid composition to an apparent or potential tissue void, cavity, or blood vessel in the subject via the distal needle opening. In any embodiment herein, the method may further comprise the step of implanting a wire or tube in an apparent or potential tissue void, cavity, or blood vessel in the subject via the distal needle opening. In any embodiment of this specification, apparent or potential tissue spaces, cavities, or blood vessels may include the suprachoroidal space, epidural space, pleural space, peritoneal space, or joint space.

[0027] In some embodiments, the present invention relates to a method for placing a needle inside the body of a subject, the steps being: (a) advancing the needle toward the subject to a first position, wherein the needle is contained within a syringe barrel including a proximal end and a distal end, the needle includes a needle proximal end and a needle distal end that engage with a needle base in the syringe barrel, the needle includes (i) a needle distal opening, (ii) a needle body opening between the needle proximal end and the needle distal end, the needle body opening being located proximal to the needle distal opening, and (iii) a needle body passage connecting the needle distal opening and the needle body opening, the needle base being the syringe A method is disclosed comprising the steps of (b) a first position of the needle, the distal opening of the needle being located proximal to the floating seal in a barrel, the floating seal and the needle base being configured to engage elastically with each other, the distal opening of the needle being located proximal to the floating seal, and the distal opening of the needle being located distal to the floating seal, and within a lumen containing a non-gasible fluid composition, wherein the non-gasible fluid composition is prevented from being discharged through the needle body opening.

[0028] In any embodiment of this specification, the method further includes the step of (c) advancing the needle toward the subject to a third position, wherein the needle body opening is distal to the floating seal and within the advancing lumen containing the non-gasile fluid composition, the distal opening of the needle is in contact with the distal seal, contact elements or the subject's tissue, and the advancing non-gasile fluid composition is prevented from being discharged through the distal opening of the needle.

[0029] In any embodiment of this specification, the method further includes (d) advancing the needle toward the subject to a fourth position, wherein the needle body opening is in the lumen containing the non-gasile fluid composition, the distal needle opening is in an obvious or potential tissue void, cavity or blood vessel of the subject, and the floating seal moves distally without further advancing the needle, thereby discharging the non-gasile fluid composition through the needle body opening, the needle body passage and the distal needle opening into the tissue void formed by the obvious tissue void, cavity or blood vessel or the potential tissue void. In any embodiment of this specification, the method further includes (e) stopping further distal movement of the floating seal. In any embodiment of this specification, further distal movement of the floating seal is stopped by the stopper, or when the pressure in the lumen is balanced with the pressure in the apparent tissue void, cavity or blood vessel, or the pressure in the tissue void formed by the potential tissue void, or when the needle body opening is sealed by the floating seal.

[0030] In some embodiments, the present invention discloses a system comprising: a syringe barrel including a proximal end and a distal end; a floating seal within the syringe barrel; a needle base located proximal to the floating seal; a piston rod between the floating seal and the needle base, wherein the needle base and the piston rod are elastically engaged with each other; and a needle in the piston rod including a proximal end and a distal end that engage with the needle base, wherein the needle comprises (i) a distal needle opening; (ii) a needle body opening between the proximal end and the distal end of the needle, wherein the needle body opening is located proximal to the distal needle opening; and (iii) a needle body passage connecting the distal needle opening and the needle body opening, wherein the needle base is configured to advance the needle distally through the piston rod toward and / or through the floating seal.

[0031] In any embodiment of this specification, the floating seal may be fixedly assembled to the distal end of the piston rod and form a sliding seal engagement with the inner surface of the syringe barrel. In any embodiment of this specification, the needle base may be fixedly engaged with an actuating member (e.g., a retaining element), and a spring may engage with the actuating member and the piston rod to provide an elastic engagement between the needle base and the piston rod.

[0032] In any embodiment of this specification, when the distal opening of the needle is in tissue, or in an apparent or potential tissue void, cavity, or blood vessel, if a pressure higher than the pressure at the needle body opening is provided at the distal opening of the needle, the floating seal can be advanced distally through the piston rod and through the floating seal without moving the floating seal distally. In some embodiments, tissue resistance or tissue pressure does not allow the fluid composition to be injected into the tissue through the distal opening of the needle, and the floating seal (and the piston rod in embodiments having a floating seal) does not move distally due to the force from the spring, even though the needle can be advanced distally by the force from the retaining shaft. For example, if tissue pressure does not allow injection, the distal opening of the needle is in tissue, while the needle body opening is distal to the floating seal and may be in contact with the fluid composition. As the needle advances further, the floating seal may maintain its axial position until the distal opening of the needle reaches an apparent or potential tissue void, cavity, or blood vessel.

[0033] In any embodiment of this specification, the floating seal may move distally when the distal opening of the needle is in tissue or in an apparent or potential tissue void, cavity, or blood vessel, and provides a lower pressure at the distal opening than at the needle body opening. In some embodiments, tissue resistance or tissue pressure allows the fluid composition to be injected into the tissue through the distal opening of the needle, and the floating seal (and the piston rod in embodiments having a floating seal) moves distally by force from a spring, and the needle does not need to advance distally. For example, when tissue pressure allows injection, the distal opening of the needle is in an apparent or potential tissue void, cavity, or blood vessel, while the needle body opening is distal to the floating seal and in contact with the fluid composition. The floating seal is movable distally, the fluid composition is discharged through the distal opening of the needle, and the needle does not advance further distally.

[0034] In some embodiments, the present invention discloses a method for delivering a fluid composition into the eye of a subject using the system disclosed herein, comprising inserting the distal opening of a needle into the eye and into a position between the sclera and choroid / ciliary body of the eye, thereby allowing the fluid composition to enter the body opening of the needle, pass through the body passage, and be discharged through the distal opening of the needle. In some embodiments, the fluid composition is discharged into the suprachoroidal space of the eye. In some embodiments, the method comprises inserting a cannula into the suprachoroidal space at the eye and advancing the distal tip of the cannula to the posterior part of the eye. In some embodiments, the method comprises advancing a microneedle through the cannula such that the distal end of the microneedle penetrates the choroid and / or ciliary body of the eye without penetrating the retina of the eye. In some embodiments, the method comprises delivering the composition into the subretinal space via the microneedle. [Brief explanation of the drawing]

[0035] The accompanying drawings illustrate only specific embodiments that possess the features and advantages of the present invention. These embodiments are not intended to limit the scope of the appended claims in any way. [Figure 1A] For example, a schematic diagram shows the various stages of operating an exemplary medical puncture device during puncture and injection into the suprachoroidal space (SCS) 14. Figure 1F shows a step of operating an exemplary medical puncture device without a contact member (e.g., 1b shown in Figures 1A-1E), where the distal seal (e.g., 8 shown in Figures 1A-1E) may be in direct contact with the tissue. [Figure 1B] For example, a schematic diagram shows the various stages of operating an exemplary medical puncture device during puncture and injection into the suprachoroidal space (SCS) 14. [Figure 1C] For example, a schematic diagram shows the various stages of operating an exemplary medical puncture device during puncture and injection into the suprachoroidal space (SCS) 14. [Figure 1D] For example, a schematic diagram shows the various stages of operating an exemplary medical puncture device during puncture and injection into the suprachoroidal space (SCS) 14. [Figure 1E] For example, a schematic diagram shows the various stages of operating an exemplary medical puncture device during puncture and injection into the suprachoroidal space (SCS) 14. [Figure 1F] For example, a schematic diagram shows the various stages of operating an exemplary medical puncture device during puncture and injection into the suprachoroidal space (SCS) 14. Figure 1F shows a step of operating an exemplary medical puncture device without a contact member (e.g., 1b shown in Figures 1A-1E), where the distal seal (e.g., 8 shown in Figures 1A-1E) may be in direct contact with the tissue. [Figure 2A] For example, a schematic diagram shows the various stages of operating an exemplary medical puncture device during puncture and injection into the suprachoroidal space (SCS) 14. [Figure 2B] For example, a schematic diagram shows the various stages of operating an exemplary medical puncture device during puncture and injection into the suprachoroidal space (SCS) 14. [Figure 2C]For example, a schematic diagram shows the various stages of operating an exemplary medical puncture device during puncture and injection into the suprachoroidal space (SCS) 14. [Figure 2D] For example, a schematic diagram shows the various stages of operating an exemplary medical puncture device during puncture and injection into the suprachoroidal space (SCS) 14. [Figure 2E] For example, a schematic diagram shows the various stages of operating an exemplary medical puncture device during puncture and injection into the suprachoroidal space (SCS) 14. [Figure 2F] For example, a schematic diagram shows the various stages of operating an exemplary medical puncture device during puncture and injection into the suprachoroidal space (SCS) 14. Figure 2F shows a step of operating an exemplary medical puncture device without a contact member (e.g., 1b shown in Figures 2A-2E), where the distal seal (e.g., 8 shown in Figures 2A-2E) may be in direct contact with the tissue. [Figure 2G] Figure 2G shows schematic diagrams of the various stages of operating an exemplary medical puncture device during, for example, puncture and injection into the suprachoroidal space (SCS) 14. Figure 2G shows the steps of operating an exemplary medical puncture device, which includes an additional actuation member 2' that engages with the floating seal 3 via another spring 4'. [Figure 3A] This is a partial structural diagram of an exemplary medical puncture device, including a floating seal 3, one or more needle body openings (6b or 6b1, 6b2 and / or 6b3), and a distal needle opening 6a. [Figure 3B] This is a partial structural diagram of an exemplary medical puncture device, including a floating seal 3, one or more needle body openings (6b or 6b1, 6b2 and / or 6b3), and a distal needle opening 6a. [Figure 3C] This is a partial structural diagram of an exemplary medical puncture device, including a floating seal 3, one or more needle body openings (6b or 6b1, 6b2 and / or 6b3), and a distal needle opening 6a. [Figure 3D] This is a partial structural diagram of an exemplary medical puncture device, including a floating seal 3, one or more needle body openings (6b or 6b1, 6b2 and / or 6b3), and a distal needle opening 6a. [Figure 3E]This is a partial structural diagram of an exemplary medical puncture device, including a floating seal 3, one or more needle body openings (6b or 6b1, 6b2 and / or 6b3), and a distal needle opening 6a. [Figure 3F] This is a partial structural diagram of an exemplary medical puncture device, including a floating seal 3, one or more needle body openings (6b or 6b1, 6b2 and / or 6b3), and a distal needle opening 6a. [Figure 4A] This is a partial structural diagram of an exemplary medical puncture device, including the floating seal 3 and the needle body opening 6b. [Figure 4B] This is a partial structural diagram of an exemplary medical puncture device, including the floating seal 3 and the needle body opening 6b. [Figure 4C] This is a partial structural diagram of an exemplary medical puncture device, including the floating seal 3 and the needle body opening 6b. [Figure 5A] This is a partial structural diagram of an exemplary medical puncture device, including floating seals 3a and 3b and one or more needle body openings (6b or 6b1 and / or 6b2). [Figure 5B] This is a partial structural diagram of an exemplary medical puncture device, including floating seals 3a and 3b and one or more needle body openings (6b or 6b1 and / or 6b2). [Figure 5C] This is a partial structural diagram of an exemplary medical puncture device, including floating seals 3a and 3b and one or more needle body openings (6b or 6b1 and / or 6b2). [Figure 5D] This is a partial structural diagram of an exemplary medical puncture device, including floating seals 3a and 3b and one or more needle body openings (6b or 6b1 and / or 6b2). [Figure 5E] This is a partial structural diagram of an exemplary medical puncture device, including floating seals 3a and 3b and one or more needle body openings (6b or 6b1 and / or 6b2). [Figure 5F]This is a partial structural diagram of an exemplary medical puncture device, including floating seals 3a and 3b and one or more needle body openings (6b or 6b1 and / or 6b2). [Figure 6] A partial structural diagram of an exemplary medical puncture device, including a through-slope guide groove 3a and a check valve 9, is shown. [Figure 7] A partial structural diagram of an exemplary medical puncture device, including a through-slope guide groove 3a and a check valve 9, is shown. [Figure 8] A partial structural diagram of an exemplary medical puncture device including a non-penetrating inclined guide groove 3a is shown. [Figure 9] A partial structural diagram of an exemplary medical puncture device, including an inclined guide needle hole 6c and a check valve 9, is shown. [Figure 10] A partial structural diagram of an exemplary medical puncture device, including an inclined guide needle hole 6c and a needle hole plug 10, is shown. [Figure 11A] A schematic diagram shows the implantation of the catheter 11 into the SCS 14 using an exemplary medical device assembly including a central guide groove 2c. Figure 11A shows the contact member 1b that comes into contact with the tissue. [Figure 11B] A schematic diagram shows the implantation of a catheter 11 into the SCS 14 using an exemplary medical device assembly including a central guide groove 2c. Figure 11B shows the distal seal 8 that contacts tissue without a contact member. The reference numerals and exemplary associated structures provided below are used only for illustrative purposes with reference to Figures 1A-1E to 11A-11B and should not be considered limiting. 1-Syringe barrel, 1a-Axial stopper, 1b-Circular contact element, 2-Pressing element, 2c-Central guide groove, 3-Floating seal, 3a-Inclined guide groove, 4-Elastic sheath, 5-Spring, 6-Hollow puncture needle, 6a-Distal needle opening, 6b-Needle body opening, 6c-Inclined guide needle hole, 7-Flow composition lumen, 8-Distal seal, 9-Check valve, 10-Needle hole plug, 11-Catheter, 12-Auxiliary guide needle, 13-Sclera, 14-Suprachoroidal space (SCS). [Figure 12]This is a schematic diagram of various elements and features of an exemplary medical puncture device. For example, the device may include a hollow housing 22 that engages with a proximal control knob 17. A presser / push shaft 2 slides through the control knob and engages with a guide tube 16 within the housing. The presser / push shaft 2 is configured to impart distal force to a compression spring 5, which functions as a force element configured to impart distal force to a piston rod 15. An oblique needle 6 is assembled and fixed to a needle base or base fixed to the presser / push shaft. The distal end of the needle 6 may be located within the lumen of the piston rod 15 and moves distally when a force is applied to move the presser / push shaft distally. The distal end of the needle may advance through a seal 3 at the distal end of the piston rod 15 into the lumen formed by the syringe barrel and distal seal 8 of the syringe 1. The gland 23 may engage with both the syringe 1 and the distal seal 8 to facilitate seal engagement. The distal seal 8 may interface with tissue, and the needle 6 may advance through the distal seal 8 to penetrate the tissue. The needle 6 may include a distal needle opening and a needle body opening, which are similar to 6a and 6b shown in Figures 1A-1E and 11A-11B, respectively. [Figure 13A] This diagram shows schematic representations of the various stages involved in operating an exemplary medical puncture device. [Figure 13B] This diagram shows schematic representations of the various stages involved in operating an exemplary medical puncture device. [Figure 13C] This diagram shows schematic representations of the various stages involved in operating an exemplary medical puncture device. [Figure 13D] This diagram shows schematic representations of the various stages involved in operating an exemplary medical puncture device. [Figure 13E] This diagram shows schematic representations of the various stages involved in operating an exemplary medical puncture device. [Figure 13F] This diagram shows schematic representations of the various stages involved in operating an exemplary medical puncture device. [Figure 14A]A schematic diagram of exemplary engagement features between a retaining shaft (e.g., retaining element 2 in Figures 1A-1E-11A-11B, or retaining shaft 2 in Figures 12 and 13A-13F) and a control knob or key is shown. Figure 14A shows an exemplary device including the device body and syringe and a distal seal at the distal end. [Figure 14B] A schematic diagram of exemplary engagement features between a retaining shaft (e.g., retaining element 2 in Figures 1A-1E-11A-11B, or retaining shaft 2 in Figures 12 and 13A-13F) and a control knob or key is shown. Figure 14B is an enlarged view of the gear meshing connecting the retaining shaft and the control knob or key via one or more gears (e.g., gear 25). The control knob or key may be in the form of a button or a scroll wheel. The button may be pressed, and the scroll wheel may roll or rotate around the shaft via one or more gears to actuate the retaining shaft and translate the syringe needle distally or proximal. [Figure 15A] A schematic diagram of the characteristics of an exemplary needle (for example, the hollow puncture needle 6 in Figures 1A-1E-11A-11B, or the syringe needle 6 in Figures 12 and 13A-13F) is shown. [Figure 15B] A schematic diagram of the characteristics of an exemplary needle (for example, the hollow puncture needle 6 in Figures 1A-1E-11A-11B, or the syringe needle 6 in Figures 12 and 13A-13F) is shown. [Figure 16A]A schematic diagram of the features of an exemplary seal (e.g., distal seal 8 in Figures 1A-1E-11A-11B, or distal seal tip 8 in Figures 12 and 13A-13F) is shown, which is configured to contact tissue such as the sclera of the eye. The seal may have a tapered distal end, a spherical distal end, or a flat distal end. The seal may have a distal portion having a flat distal surface, a convex, spherical, concave, or any other suitable distal surface shape. The reference numerals and exemplary related structures provided below are provided solely for illustrative purposes with reference to Figures 12-16A-16C and should not be considered limiting. 1- Syringe having a syringe barrel forming a lumen, 2- Retaining element (e.g., retaining shaft), 3- Floating seal (e.g., plunger seal), 5- Elastic element (e.g., spring), 6- Hollow puncture needle (distal opening of the needle and opening of the needle body are not shown), 8- Distal seal, 15- Piston rod (e.g., push rod), 16- Guide tube, 17- Control knob, 18- Limiter, 19- Ruler, 20- Adapter, 21- Handle, 22- Housing, 23- Gland, 24- Annular groove, 25- Gear. [Figure 16B] A schematic diagram of the features of an exemplary seal (for example, the distal seal 8 in Figures 1A-1E-11A-11B, or the distal seal tip 8 in Figures 12 and 13A-13F) is shown, and the seal is configured to contact tissue such as the sclera of the eye. The seal may have a tapered distal end, a spherical distal end, or a flat distal end. The seal may have a distal portion having a flat distal surface, a convex surface, a spherical surface, a concave surface, or any other suitable distal surface shape. [Figure 16C] A schematic diagram of the features of an exemplary seal (for example, the distal seal 8 in Figures 1A-1E-11A-11B, or the distal seal tip 8 in Figures 12 and 13A-13F) is shown, and the seal is configured to contact tissue such as the sclera of the eye. The seal may have a tapered distal end, a spherical distal end, or a flat distal end. The seal may have a distal portion having a flat distal surface, a convex surface, a spherical surface, a concave surface, or any other suitable distal surface shape. [Figure 17A]A schematic diagram shows the features of an exemplary container that can be pre-filled with a fluid composition and installed inside the device. [Figure 17B] A schematic diagram shows the features of an exemplary container that can be pre-filled with a fluid composition and installed inside the device. [Figure 18] A schematic diagram of an exemplary method disclosed herein for facilitating the delivery of a substance through the subretinal space of the choroid using a device is shown. [Modes for carrying out the invention]

[0036] The following is a detailed description of some embodiments of the present invention. It should be understood that the specific embodiments described herein are intended to illustrate and interpret embodiments of the present invention and should not be considered limiting.

[0037] Furthermore, the embodiments and features of the present invention can be combined in any appropriate manner, provided they do not contradict each other.

[0038] In some embodiments, descriptions of position such as "anterior," "posterior," "forward," "backward," "distal," and "proximal" are based on the perspective of the practitioner using the medical puncture device or medical device assembly. That is, when the practitioner uses the medical puncture device or medical device assembly, the direction away from the practitioner and relatively away is defined as the anterior direction, and the direction away from the practitioner and relatively closer is defined as the posterior direction.

[0039] As used herein, “proximal” and “distal” refer to the direction toward and away from the practitioner (e.g., surgeon, physician, nurse, technician, etc.) inserting the medical device into the patient’s body, respectively, with the tip of the device (distal end) being the first to be inserted into the patient’s body. Therefore, for example, the end of a needle described herein (e.g., a microneedle) that is first inserted into the patient’s body is the distal end, and the opposite end of the needle (e.g., the end of the medical device manipulated by the practitioner) is the proximal end of the needle.

[0040] As used herein, the singular forms “a,” “an,” and “the” refer to multiple objects unless the context explicitly specifies otherwise. For example, “a” and “an” mean “at least one” or “one or more.” Similarly, the term “component” means a single component or combination of components, and “material” means one or more materials or combinations thereof.

[0041] As used herein, the terms “about” or “approximately” refer to the normal range of error for each value, which is readily known to those skilled in the art. References to “about” a value or parameter herein include (and are described) embodiments relating to that value or parameter itself. For example, “about” may mean within or greater than one standard deviation, according to the practice of the art. Alternatively, “about” may mean a range of up to 20%, up to 10%, up to 5%, or up to 1% of a given value.

[0042] Throughout this disclosure, various aspects are presented in range form. It should be understood that the range form is for convenience and conciseness only and should not be interpreted as a flexible limitation of the scope of this disclosure. Therefore, the range description should be considered to specifically disclose all possible sub-ranges and the individual numerical values ​​within those ranges. For example, where a range of values ​​is provided, it should be understood that each intermediate value between the upper and lower limits of that range, and any other stated or intervening values ​​within that stated range, are included within this disclosure. These smaller upper and lower limits may independently be included within smaller ranges and are included within this disclosure, subject to any restrictions specifically excluded within the stated range. If a stated range includes one or both limits, the range excluding one or both of those limits is also included in this disclosure. This applies regardless of the breadth of the range.

[0043] The use of sequential numbering terms such as “first,” “second,” and “third” in a claim to modify a claim element does not imply priority, priority, or order of one claim element relative to other claim elements, or order in which method actions are performed, but is used solely as a label to distinguish one claim element having a specific name from other elements having the same name to distinguish the claim element (provided that sequential numbering terms are used). Similarly, the use of a), b), etc., or i), ii), etc., does not in itself imply priority, priority, or order of steps in the claims. Likewise, the use of these terms in this specification does not in itself imply a desired priority, priority, or order.

[0044] As used herein, the terms “puncture member” and “puncturing member” are interchangeable to refer to articles such as needles or microneedles configured to pierce a tissue layer and deliver a substance to a target tissue layer.

[0045] As used herein, the terms “medicinal container” and “medicinal chamber” are used interchangeably to refer to an article (e.g., a syringe) configured to contain a certain amount of substance (e.g., a pharmaceutical or drug).

[0046] All publications, including patent documents, scientific articles, and databases, referenced in this application are incorporated by reference in whole for any purpose to the same extent as individual publications are incorporated by reference individually. If any definition contained herein contradicts or is inconsistent with any definition contained herein in a patent, application, published application, or other publication incorporated herein by reference, the definition contained herein shall prevail over the definition incorporated herein by reference.

[0047] The section headings used herein are for organizational purposes only and should not be interpreted as limiting the subject matter being discussed. I. Overview

[0048] The medical puncture devices and medical device assemblies of the present invention can be used to penetrate, expand, and / or inject into cavities such as the suprachoroidal space of the eye, and to implant drugs, catheters, or other medical devices. Currently, the most commonly used intraocular injection method is intravitreous injection, but some drugs or gene therapy vectors have low efficiency in penetrating the posterior vitreous membrane and inner retinal layers to reach the outer retinal layer or retinal pigment epithelium layer. Also, because the vitreous cavity is a semi-open cavity, drugs injected into the vitreous cavity can flow out of the eyeball with aqueous humor circulation, affecting the local concentration and pharmacokinetics of the drug and potentially causing side effects such as increased intraocular pressure and cataracts. In some cases, a hollow puncture needle can be used to achieve an effective concentration of the drug or gene therapy vector in the outer retinal layer, retinal pigment epithelium, and / or choroid / ciliary body. The hollow puncture needle may penetrate the retina on the vitreous cavity side to reach the subretinal tissue, or it may penetrate the retina and retinal pigment epithelium to reach the subcutaneous space of the retinal pigment epithelium before injecting the drug or gene therapy vector. This type of injection is difficult and prone to failure. In contrast, suprachoroidal injection achieves high drug concentrations in the choroid / ciliary body, retinal pigment epithelium and / or outer retinal layers, while vitreous drug concentrations are low.

[0049] In some cases, targeted injection of therapeutic drugs is desirable. However, in this case, the relatively small anatomical structure of the eye often makes it difficult to position the needle in the desired location using known devices and methods, especially when it involves positioning the distal end of the needle to a desired depth within the eye. Many known methods for directly injecting drugs into the eye involve inserting a needle or cannula at an acute angle to the surface of the eye, making it difficult to control the insertion depth. For example, some such methods involve controlling the angular orientation of the needle so that the injected substance moves away from the needle at a specific location. Furthermore, some known methods for injecting substances into the tissues of the eye involve using complex visualization systems or sensors to control the positioning of the needle or cannula.

[0050] These shortcomings in known systems and methods are exacerbated because the size and thickness of the various layers contained in the eye can vary from person to person. For example, the thickness of the conjunctiva and sclera can vary substantially, and their true values ​​cannot be easily determined in advance by standard methods. Furthermore, the thickness of these layers can vary in different parts of the eye, and can also vary at different times of day, in the same eye and location. Therefore, it can be difficult to determine and / or adjust the length of the needle for puncturing the eye so that the needle tip reaches the desired depth, e.g., SCS, using known systems and methods.

[0051] In some cases, such as choroidal melanoma, precisely targeting and injecting therapeutic agents into the suprachoroidal space can improve therapeutic efficacy and reduce side effects. However, in the eye, due to its small structure, and especially for medical devices such as catheters, achieving penetration, dilation, injection, or catheter placement of the suprachoroidal space using existing devices or methods is quite difficult, particularly when the device needs to be positioned at a specific location in the suprachoroidal space.

[0052] One method of puncturing the suprachoroidal space involves making the length of the exposed puncture needle equal to the thickness of the sclera. After fully inserting the puncture needle into the sclera, the fluid is injected for suprachoroidal injection. A technical drawback of this puncture method is that the exposed length of the retained puncture needle may not perfectly match the thickness of the sclera. In practical applications, differences in scleral thickness between different people, between eyes, and between different parts of the same eye further amplify the aforementioned technical drawback. A needle that is too short may not penetrate the sclera, while a needle that is too long may penetrate the SCS and irritate and damage the retina of the eye. A convenient method is needed to detect the position of the needle tip within the eye.

[0053] Many known systems involve manual injection due to sensitivities associated with intraocular injection (e.g., tissue sensitivity, potential impact on intraocular pressure, etc.). More specifically, many known devices and methods involve the user manually applying force (e.g., pressing a plunger with the thumb or finger) to expel a fluid (e.g., drug) into the eye. Some of these devices and methods, due to the small size of the needle and / or the properties of the injectable drug, involve the use of a force level higher than what the user can comfortably apply, and in some cases, the user may not be able to accurately deliver the drug using the known systems and methods.

[0054] Furthermore, when injecting into different target layers of the eye, variations arise in the amount of force required for needle insertion and / or drug injection. Different layers of the eye can have different densities. For example, the sclera is usually denser than the conjunctiva or SCS. Differences in density of the target area or layer create different back pressures at the needle exit, such as at the needle tip from which the fluid flows. Therefore, injecting into relatively dense ocular materials such as the sclera requires greater kinetic pressure to expel the drug from the needle than injecting the drug into the SCS. Moreover, the injection force required to expel the drug also depends on the density and viscosity of the liquid drug, the length of the needle, and the diameter of the needle. Injecting a specific drug into the eye via a desired needle (e.g., 27 gauge, 30 gauge, or smaller) may require forces that are difficult to estimate and / or control in order to perform an accurate injection without risking damage to the eye tissue of a particular subject.

[0055] Given the relatively small anatomical structure of the eye, accessing certain internal areas of the eye remains challenging, for example, to minimally invasively place a tube (e.g., a catheter) or wire in a desired area.

[0056] Problems related to accessing ocular tissue may also apply to other tissues. Therefore, there is a need for improved devices and methods that can help determine whether the needle is at the correct depth, facilitate the injection of pharmaceuticals into tissues such as ocular tissue, and / or facilitate the implantation of certain structures into tissues such as ocular tissue. To achieve one or more of the above objectives, the present invention A syringe barrel including a distal closed end and a proximal open end, An operating unit (e.g., an elastic movement unit) including an operating member (e.g., a pressing element) and a floating seal, wherein the floating seal is positioned within the syringe barrel and elastically engageable with the operating member (e.g., a pressing element), A hollow puncture needle assembled to the aforementioned operating member (e.g., a pressing element), comprising a distal needle opening and a needle body opening, wherein the needle body opening is located proximal to the floating seal (the distal needle opening may also be located proximal to the floating seal, for example, the entire length of the needle is located proximal to the floating seal, or the needle passes through the floating seal such that the distal needle opening is located distal to the floating seal), A medical puncture device is provided, comprising a distal closed end of the syringe barrel, a luminal wall of the syringe barrel (e.g., a portion of the syringe barrel), and a fluid composition lumen (e.g., for a fluid or gel) formed by the floating seal.

[0057] In some embodiments, the medical puncture device is configured to move a hollow puncture needle forward by pressing an actuating member (e.g., a pressing element). In some embodiments, the hollow puncture needle sequentially protrudes the floating seal and the distal closed end of the syringe barrel, thereby connecting the lumen of the fluid composition, the needle body opening, and the distal needle opening. In some embodiments, the hollow puncture needle is pre-inserted into the floating seal. For example, the distal needle opening may be within the floating seal and be closed by the floating seal, and the needle may advance through the lumen of the fluid composition and pierce the distal closed end of the syringe barrel. In some embodiments, the hollow puncture needle is pre-inserted through the floating seal. For example, the distal needle opening may be within the lumen of the fluid composition, while the needle body opening may be proximal to or within the floating seal (e.g., the needle body opening may be closed by the floating seal shown in Figure 3E). The needle may then advance and pierce the distal closed end of the syringe barrel. In some embodiments, a hollow puncture needle is pre-inserted through a floating seal and then inserted through the distal closed end of the syringe barrel. For example, the distal opening of the needle may be within the distal seal of the distal closed end of the syringe barrel (e.g., the distal opening of the needle may be closed by the distal seal), or distal to the distal seal and / or the distal closed end of the syringe barrel, while the needle body opening may be proximal to the floating seal (e.g., see Figure 3D, 6b1), within the floating seal (e.g., the needle body opening may be closed by the floating seal shown in Figure 3D, 6b2), or within the lumen of the fluid composition (e.g., shown in Figure 3D, 6b3), after which the needle may be advanced through the distal closed end of the syringe barrel to expose the distal opening of the needle for tissue puncture.

[0058] Optionally, the medical puncture device includes a fluidized lumen, a needle body opening, and a distal needle opening. For example, in the fluidized state, the needle body opening may be proximal to the floating seal, while the distal needle opening may be distal to the floating seal and within the lumen of the fluidized lumen. In the fluidized state, the needle and / or floating seal are movable. For example, the floating seal can move under the elastic action between the floating seal and an actuating member (e.g., a retaining element) to seal or block the needle body opening, thereby preventing or stopping the discharge of the fluidized composition (e.g., gel) through the needle body opening and / or distal needle opening.

[0059] Optionally, in a fluid-connected state, the floating seal can move forward and, when in contact with the distal closed end of the syringe barrel, seal the needle body opening, thereby preventing or stopping the fluid composition (e.g., gel) from being discharged through the needle body opening and / or the distal needle opening.

[0060] Optionally, a stopper, such as an axial stopper, may be positioned distal to the floating seal within the syringe lumen. In some embodiments, the stopper may restrict the forward movement of the floating seal. In some embodiments, the medical puncture device includes a fluid communication state in which the fluid composition lumen is connected to the needle body opening and the distal needle opening. When the medical puncture device is in a fluid communication state, the needle body opening may be at the distal end of the stopper (see, for example, Figure 2D), and the floating seal may move forward by elastic engagement with an actuating member (e.g., a retaining element).

[0061] Optionally, the medical puncture device includes a manual control element that is mounted on a floating seal and extends outside the syringe barrel.

[0062] Optionally, the medical puncture device includes a preliminary puncture state after the hollow puncture needle has penetrated the distal closed end of the syringe barrel, a surface tissue puncture state, and a post-puncture fluid communication state. In the pre-puncture state, surface tissue puncture state, and fluid communication state, the range of lengths of the hollow puncture needle extending outside the distal closed end of the syringe barrel may correspond to the pre-puncture length range, the surface tissue puncture length range, and the fluid communication length range, respectively, where when the length of the hollow puncture needle extending outside the distal closed end of the syringe barrel is within the pre-puncture length range, the needle body opening is maintained above the lumen of the fluid composition (for example, the needle body opening may be within the floating seal proximal to the floating seal), and / or when the length of the hollow puncture needle extending outside the distal closed end of the syringe barrel is within the surface tissue puncture length range, at least a portion of the needle body opening is connected to the lumen of the fluid composition, and / or when the length of the hollow puncture needle extending outside the distal closed end of the syringe barrel is within the fluid communication length range, the needle body opening is located within the lumen of the fluid composition.

[0063] Optionally, a circular contact element extending in the axial direction is formed at the distal closed end of the syringe barrel, and the difference between the upper and lower limits of the preliminary puncture length range is equal to the axial length of the circular contact element.

[0064] Optionally, the elastic transfer unit includes an elastic sheath covering the outside of the hollow puncture needle. The elastic sheath can seal the needle body opening when the needle body opening is proximal to the floating seal. In some embodiments, if the fluid composition is a gel, it may not be necessary to seal the needle body opening when the needle body opening is proximal to the floating seal.

[0065] Optionally, the medical puncture device includes a catheter guide structure for guiding a catheter through the cavity of a hollow puncture needle (e.g., a needle body passage connected to the distal opening and / or the opening of the needle body).

[0066] Optionally, the catheter guide structure includes an inclined guide groove formed on a floating seal and extending at a certain angle toward a hollow puncture needle.

[0067] Optionally, the inclined guide groove is provided to penetrate the floating seal in the front-to-back direction. In some embodiments, the catheter guide structure further includes a check valve embedded in the inclined guide groove and openable and / or a guide groove plug inserted into the inclined guide groove.

[0068] Optionally, the inclined guide groove is provided on the upper surface of the floating seal and is a non-through groove.

[0069] Optionally, the needle body opening can be configured as an inclined opening that slopes backward.

[0070] Optionally, the catheter guide structure includes an inclined guide needle hole formed in the body wall of the hollow puncture needle and opening at a rearward inclination. In some embodiments, the medical puncture device includes a fluid communication state in which a fluid composition lumen is connected to the needle body opening and the needle distal opening. In the fluid communication state, the inclined guide needle hole is proximal to the floating seal.

[0071] Optionally, the catheter guide structure further includes a check valve embedded in the inclined guide needle hole and capable of opening and closing, or a guide groove plug inserted into the inclined guide needle hole.

[0072] Optionally, the catheter guide structure includes a puncturable central guide groove formed at the center of the proximal surface of the operating member (e.g., a retaining element). In some embodiments, the needle proximal opening is formed in a hollow puncture needle and is positioned to be axially aligned with the central guide groove.

[0073] Optionally, the medical puncture device includes a puncture control module and a fluid storage module that are independently manufactured and formed, wherein the puncture control module includes a first syringe unit, an elastic transfer unit formed inside the first syringe unit, and a hollow puncture needle, and the fluid storage module includes a second syringe unit, a fluid composition lumen formed inside the barrel of the second syringe unit, and a removable packaged module packaging component located proximal to the second syringe unit, wherein a removable connection structure is formed between the first syringe unit and the second syringe unit.

[0074] In a second aspect, the present invention provides a medical device assembly. In some embodiments, the medical device assembly includes a catheter and a medical puncture device including a catheter guide structure.

[0075] Optionally, the medical device assembly further includes a hollow auxiliary guide needle used in conjunction with the catheter guide structure. In some embodiments, when the auxiliary guide needle is connected to the catheter guide structure, the catheter can pass sequentially through the needle body passage of the auxiliary guide needle and the catheter guide structure, and then through the needle body passage of the hollow puncture needle.

[0076] In some embodiments, when using the medical puncture device of the present invention, the user can first apply pressure to an actuating member (e.g., a pressing element) to sequentially pass the hollow puncture needle through the floating seal and the distal closed end of the syringe barrel. When the distal opening of the hollow puncture needle reaches an apparent or potential tissue void, cavity system, or blood vessel, the needle body opening is positioned within the lumen of the fluid composition, and the floating seal is elastically engaged with the actuating member (e.g., a pressing element). In some embodiments, the fluid pressure within the lumen of the fluid composition may be higher than the pressure within an apparent or potential tissue void, cavity, or blood vessel.

[0077] In this case, the fluid in the lumen of the fluid composition may flow into apparent or potential tissue cavities, cavities, or blood vessels through the needle body opening and the distal needle opening. The fluid in the lumen of the fluid composition can flow into the needle body opening (and then flow out through the needle body passage and out the distal needle opening) during the injection process by elastic engagement between the floating seal and the actuating member (e.g., a retaining element), simply by maintaining the position of the actuating member (e.g., a retaining element), thereby achieving injection, penetration, and / or expansion into apparent or potential tissue cavities, cavities, or blood vessels. Furthermore, as described herein, the medical device assembly described in the present invention can achieve implantation of catheters and other medical devices via a medical puncture device, for example, via a catheter guide structure and the cavity of the needle described herein.

[0078] In some embodiments, before the hollow puncture needle penetrates an apparent or potential tissue void, cavity, or blood vessel, the external pressure at the distal opening of the needle is higher than the fluid pressure within the lumen of the fluid composition, and therefore the fluid cannot flow out from the distal opening of the needle. Thus, by observing whether the floating seal moves forward due to elastic engagement with the actuating member (e.g., a retaining element), it is possible to determine whether the hollow puncture needle has penetrated an apparent or potential tissue void, cavity, or blood vessel, thereby reminding the practitioner of the current puncture depth to ensure accurate puncture. Since the injection is controlled by changes in the fluid pressure within the lumen of the fluid composition, the practitioner does not need to manually apply thrust or force during the injection process, thereby preventing fluctuations in flow rate and achieving a stable injection.

[0079] Other features and advantages of the present invention are described in the following detailed description.

[0080] Some embodiments of the present invention will be described with reference to some of the figures in the accompanying drawings. II. Systems and Devices

[0081] In some embodiments, this specification describes systems and devices for assisting the insertion of a puncture member (e.g., a needle or microneedle) into the eye and / or for assisting the injection of a drug into target ocular tissue. In some embodiments, this specification describes systems and devices for controlling the depth to which a puncture member (e.g., a microneedle) is inserted into the eye to deliver a drug, for example, to the posterior region of the eye (e.g., via the suprachoroidal space). In some embodiments, this specification describes systems and devices for introducing an implant into tissue (e.g., an apparent or potential tissue cavity, or blood vessel).

[0082] In some embodiments, the Specified provides a system comprising a syringe barrel including a proximal end and a distal end; a floating seal within the syringe barrel; and a needle base located proximal to the floating seal (e.g., the needle base being closer to the practitioner and the floating seal being closer to the subject), configured such that the floating seal and the needle base elastically engage with each other. In some embodiments, the system further comprises a needle including a proximal end and a distal end, the proximal end of the needle engaging with the needle base. In any embodiment of the Specified, the proximal end of the needle may be fixed to the needle base or may be assembled to the needle base in a dischargeable manner (e.g., for insertion). In any embodiment of the Specified, the needle includes (i) a distal needle opening; (ii) a needle body opening between the proximal end of the needle and the distal end of the needle; and (iii) a needle body passage connecting the distal needle opening and the needle body opening. In any embodiment of this specification, the needle body opening may be located proximal to the distal needle opening. In any embodiment of this specification, the needle base may be configured to advance the needle distally toward the floating seal (for example, when the distal end of the needle is proximal to the floating seal), through the floating seal (for example, when the distal end of the needle is entered into or pierced by the floating seal), and / or through the distal end of the syringe barrel.

[0083] In any embodiment of this specification, the proximal and distal lumen may be located on opposite sides of the floating seal within the syringe barrel. In some embodiments, the distal lumen contains a fluid composition (e.g., a pharmaceutical, drug, and / or a pharmaceutically acceptable carrier or excipient such as saline solution), while the proximal lumen does not contain a non-gas fluid composition. The proximal lumen may be pre-filled with a gas such as sterile air and / or may communicate with an external environment such as air as the needle advances into and / or passes through the syringe barrel.

[0084] In some embodiments, the needles included in the embodiments described herein have an angled bevel that allows for easy penetration into tissues such as the sclera and / or suprachoroidal space while minimizing collateral damage. In some embodiments, the needles disclosed herein define a narrow lumen (e.g., gauge sizes greater than or equal to 30 gauge, 32 gauge, 34 gauge, 36 gauge, etc.) to allow drug delivery into the suprachoroidal space while minimizing the diameter of the needle trajectory due to needle insertion. In some embodiments, the aspect ratio of the lumen and angled bevel of the needles described herein is the same as or different from the standard 27 gauge and 30 gauge needles commonly used for intraocular injection.

[0085] In some embodiments, the needles included in the embodiments described herein are designed to rapidly penetrate dense tissue such as the sclera, positioning the needle tip between the dense tissue and adjacent less dense tissue. For example, the needle tip of this specification may be designed to rapidly and accurately reach the suprachoroidal lumen without the risk of overshoot. In some embodiments, the syringe needles included in the embodiments described herein may be between about 20 gauge (G) and about 34 G gauge, particularly between about 23 gauge (G) and about 30 G gauge, for example between about 25 G gauge and about 27 G gauge. In some embodiments, the syringe needles disclosed herein may be 22 G, 23 G, 24 G, 25 G, 26 G, 27 G, 28 G, 29 G, 30 G, or 31 G. Examples of needle sizes are shown in Table 1.

[0086] [Table 1]

[0087] In some embodiments, the needles disclosed herein include oblique angles of about 0 to about 40 degrees, particularly about 5 to about 30 degrees, for example, about 15 to about 25 degrees. In some embodiments, the syringe needles disclosed herein may include oblique angles of about 10 degrees, about 12 degrees, about 14 degrees, about 16 degrees, about 18 degrees, about 20 degrees, about 22 degrees, about 24 degrees, about 26 degrees, about 28 degrees, or about 30 degrees. In some embodiments, the needles disclosed herein include inclination angles of about 30 to about 95 degrees, particularly about 45 to about 90 degrees, for example, about 60 to about 75 degrees. In some embodiments, the needles disclosed herein include narrow angles of about 10 to about 90 degrees, particularly about 15 to about 60 degrees, for example, about 20 to about 45 degrees. Figure 15A shows the oblique angles, inclination angles, and narrow angles of the needle.

[0088] In some embodiments, the needles disclosed herein include a curved oblique surface. In some embodiments, the radius of curvature of the curved oblique surface is about 0.1 mm to about 4.0 mm, particularly about 0.2 mm to about 3.0 mm, for example, about 0.4 mm to about 2.0 mm. In some embodiments, the syringe needles disclosed herein may include an oblique surface having a radius of curvature of about 0.5 mm, about 0.75 mm, about 1.0 mm, about 1.25 mm, about 1.5 mm, about 1.75 mm, or 2.0 mm, or any of these values.

[0089] In some embodiments, the needles disclosed herein include multi-faceted blades such as double-sided blades, three-sided blades, four-sided blades, or five-sided blades.

[0090] In some embodiments, the devices disclosed herein include or are configured to be coupled to a pharmaceutical container containing a pharmaceutical, such as a solution, liquid, suspension, or gel. The pharmaceutical container may be formed at least partially as a syringe barrel.

[0091] Unlike some existing devices in which the needle is coupled to the distal end of a pharmaceutical container (e.g., as described in US9,180,047, US9,539,139, US9,572,800, US9,636,253, US9,636,332, US9,770,361, US9,937,075, US10,555,833, and US10,517,756, in which the needle is at the distal end of a syringe, and such patents are incorporated herein by all purposes), in some embodiments the present invention utilizes a needle coupled to an actuarial member within a syringe barrel. In some embodiments the needle disclosed herein is at least partially within the syringe barrel. In some embodiments the needle is not exposed to the distal end of the syringe barrel before use, nor is it directly engaged with the distal end of the syringe barrel.

[0092] In some embodiments, the device disclosed herein includes an energy storage member (e.g., one or more springs) configured to engage with the needle base and the floating seal. In some embodiments, the distal end of the energy storage member is located within the syringe barrel and configured to engage directly or indirectly with the floating seal. In some embodiments, the energy storage member is configured to generate a force at the proximal end of the floating seal. In some embodiments, if the distal tip of the needle is located within an apparent or potential tissue void, cavity, or blood vessel, the force is sufficient to move the floating seal within the syringe barrel to deliver at least a portion of a substance from a pharmaceutical container (e.g., the lumen of a fluid composition) through the needle. Furthermore, if the distal tip of the needle is adjacent to (e.g., above or below) an apparent or potential tissue void, cavity, or blood vessel, the force is not sufficient to move the floating seal within the syringe barrel. In some embodiments, the apparent or potential tissue void, cavity, or blood vessel has a first density, and the adjacent tissue has a second density higher than the first density. In some embodiments, apparent or latent tissue voids, cavities, or blood vessels generate a first back pressure, and adjacent tissue generates a second back pressure that is higher than the first back pressure.

[0093] In some embodiments, the devices disclosed herein include an energy storage member (e.g., one or more springs, such as spring 5 in Figures 1A-1E or Figure 12) configured to apply force to the floating seal directly (e.g., spring 5 in Figures 1A-1E or Figure 12) or indirectly (e.g., via a piston rod 15 as shown in Figure 12). In some embodiments, the energy storage member is configured to apply a force on the floating seal between the pressure in a first tissue and the pressure in a second, less dense tissue, or apparent or potential tissue voids, cavities, or blood vessels. In some embodiments, the energy storage member is configured to apply a force that is less than or equal to the pressure in the first tissue, but greater than the pressure in the second, less dense tissue, or apparent or potential tissue voids, cavities, or blood vessels. In some embodiments, the energy storage member is configured to apply force directly or indirectly to the floating seal, and this force is effective enough to overcome the pressure difference between the pressure at the distal needle opening in the sclera and the pressure at the distal needle opening in the suprachoroidal lumen. As the pressure difference causes the distal opening of the needle to advance and begin to enter the less dense second tissue through the first tissue, the energy stored in the energy storage member is automatically released, advancing the floating seal (for example, via the piston rod 15 in Figure 12), and a certain amount of fluid composition is discharged into the second tissue or into the void between the first and second tissues.

[0094] Unlike some existing devices in which the needle is coupled to a floating seal, in some embodiments the present invention utilizes a needle whose proximal end is coupled to an actuator in a syringe barrel, the actuator being separately located and proximal to the floating seal. In some embodiments, the proximal end of the needle disclosed herein is not connected to a floating seal. In some embodiments, before use, the needle disclosed herein may be distal to the floating seal or pass through the floating seal, but the proximal end of the needle is held distal to the floating seal and is not fixedly assembled to the floating seal.

[0095] In some existing devices, the drug container (e.g., containing liquid) is positioned between a proximal seal and a distal seal, and each seal is movable within the syringe barrel, as described, for example, in US 2020 / 0069883, which is incorporated herein by reference for all purposes. In these devices, force on the proximal side of the proximal seal is transmitted through the liquid to the distal seal connected to the needle. Assuming the liquid is generally incompressible, if the practitioner uses excessive force or applies sudden force to the proximal seal (e.g., via a stopper coupled to the proximal seal), the force will be transmitted to the needle. Because the liquid offers little compressibility to cushion the impact of the force, the needle may be inserted too deeply or too abruptly, damaging the target tissue (e.g., the suprachoroidal space) and / or surrounding tissue. Although the positions of the proximal and distal seals are observed during the injection process, they may be too slow to stop the needle movement when a force is applied that could cause the needle to overshoot, due to their insufficient ability to cushion the impact of the force.

[0096] Conversely, in some embodiments of the present invention, a pharmaceutical container (e.g., a fluid composition lumen) is positioned between the floating seal and the distal end of the syringe barrel (the distal end does not move relative to the syringe barrel). In some embodiments, the distal end of the syringe barrel includes a distal seal, and the fluid composition lumen is positioned between the floating seal and the distal seal. In some embodiments, the needle base is elastically connected to the floating seal (and thereby to the fluid composition), so the elastic connection is advantageous for the practitioner to apply the correct force and cushion the impact of that force. Furthermore, the practitioner can hold the needle base immobile relative to the syringe barrel and observe the movement of the floating seal to assess the depth to which the needle has been placed. Once fluid communication is established between the fluid composition and apparent or potential tissue voids, cavities, or blood vessels, and the pressure within the fluid composition becomes greater than the pressure within apparent or potential tissue voids, cavities, or blood vessels, the floating seal can move as the fluid composition enters the tissue without moving the needle and needle base. This allows for precise needle placement and stable injection, effectively reducing or eliminating the chance of needle overshoot.

[0097] In some embodiments of the present invention, a pharmaceutical container (e.g., a syringe configured to contain a fluid composition) may be set to have an adjustable volume, for example, between about 0 and about 0.2 ml, for example between about 0 and about 0.15 ml, particularly between about 0 and about 0.1 ml, for example between about 0.025 ml, about 0.05 ml, about 0.075 ml, about 0.1 ml, or any of the aforementioned values. The volume of the fluid composition delivered (e.g., by injection) using the devices disclosed herein may be selected based on the conditions of a particular subject and adjusted in response to changes in those conditions.

[0098] In some embodiments, the devices disclosed herein are provided and / or packaged as an integrated device comprising components that engage with each other. In some embodiments, the devices disclosed herein do not require the practitioner to assemble one or more components before use. In some embodiments, the devices disclosed herein include a pre-filled pharmaceutical container (e.g., a fluid composition lumen) containing a fluid composition such as a pharmaceutical in the form of a liquid, solution, suspension, gel, oil, ointment, emulsion, cream, foam, lotion, and / or paste.

[0099] Fluid compositions include liquids (e.g., solutions, suspensions, etc.) or semi-solid compositions (e.g., gels) that are easy to handle and can be injected, molded, and / or shaped at or near a target tissue site upon solidification. "Fluid" includes formulations with low viscosity or consistency, such as water, and formulations with high viscosity, such as viscoelastic or paste-like materials. In some embodiments, the methods disclosed herein involve injecting a viscoelastic material (e.g., a viscoelastic fluid) into the eye, for example, between the sclera and choroid / ciliary body of the eye, to form a choroidal space containing the viscoelastic material. In some embodiments, the viscoelastic fluid is a non-Newtonian fluid formed of a viscous component and an elastic component, for example, a mixture of a solvent and a polymeric material. Examples of viscoelastic materials usable in the present invention include sodium hyaluronate, Provisc (a 1% viscous transparent material which is a specific portion of sodium hyaluronate), Viscoat (a dispersed viscoelastic material containing sodium hyaluronate and chondroitin sulfate), Amvisc (a purified portion of sodium hyaluronate), Amvisc Plus (a 1.6% sodium hyaluronate product derived from chicken combs), sodium chondroitin sulfate / sodium hyaluronate, and DisCoVisc (4% sodium chondroitin sulfate and 1.65% sodium hyaluronate).

[0100] In various embodiments, the fluidity of the formulation allows it to conform to irregularities, gaps, cracks, and / or voids in tissue sites. For example, in various embodiments, the formulation can be used to fill one or more voids, expand tissue voids (e.g., obvious tissue voids), and / or generate tissue voids from potential tissue voids, and expand generated voids as needed. In some embodiments, the fluid composition may harden upon contact with an aqueous medium (e.g., body fluids, water, etc.) to form drug depots that control drug release.

[0101] In some embodiments, a therapeutic agent (e.g., a drug) is added to the fluid composition. Non-limiting examples of specific drugs and drug classes include β-adrenergic receptor antagonists (e.g., carteolol, cetamolol, betaxolol, levovunolol, metipranolol, timolol), miotics (e.g., pilocarpine, carbachol, physostigmine), sympathomimetic agents (e.g., adrenaline, dipivefrin), carbonic anhydrase inhibitors (e.g., acetazolamide, dorzolamide), anhydrase inhibitors (e.g., acetazolamide, dorzolamide), Topoisomerase inhibitors (e.g., topotecan, irinotecan, camptothecin, lamelalin D, etoposide, teniposide, doxorubicin, mitoxantrone, amsacrin), prostaglandins, antimicrobial compounds including antibacterial and antifungal agents (e.g., chloramphenicol, chlortetracycline, ciprofloxacin, furamycetin, fusidic acid, gentamicin, neomycin, norfloxacin, ofloxacin, polymyxin, propamidine, tetracycline) (e.g., tobramycin, quinoline), antiviral compounds (e.g., acyclovir, cidofovir, idoxuridine, interferon), aldose reductase inhibitors, anti-inflammatory agents and / or anti-allergic compounds (e.g., steroid compounds such as triamcinolone, betamethasone, clobetazone, dexamethasone, fluorometholone, hydrocortisone, prednisolone, and antazoline, bromfenac, diclofenac, indomethacin, rhodoxamide, saprofen), Examples include nonsteroidal compounds such as benzodiazepines and sodium cromoglycate, artificial tears and dry eye treatments, local anesthetics (e.g., ametokine, lignocaine, oxybuprocaine, proximetacaine), cyclosporine, diclofenac, urogastron, epidermal growth factor, mydriatics, cycloplegic agents, mitomycin C, growth factors such as collagenase inhibitors, and age-related macular degeneration treatments such as pegagtanib sodium, ranibizumab, aflibercept, and bevacizumab.

[0102] In one embodiment, the therapeutic agent is an integrin antagonist, a selectin antagonist, an adhesion molecule antagonist (e.g., intercellular adhesion molecule (ICAM)-1, ICAM-2, ICAM-3, platelet endothelial adhesion molecule (PCAM), vascular cell adhesion molecule (VCAM)), a leukocyte adhesion-inducing cytokine, or a growth factor antagonist (e.g., tumor necrosis factor-α (TNF-α), interleukin-1 β (IL-1 β), monocyte chemoattractant-1 (MCP-1), or vascular endothelial growth factor (VEGF)). In some embodiments, a vascular endothelial growth factor (VEGF) inhibitor is used in conjunction with one of the microneedles described herein. In some embodiments, the two drugs are delivered by the method described herein. The compound may be administered in one formulation or sequentially in two separate formulations. For example, both a VEGF inhibitor and VEGF are provided. In some embodiments, the VEGF inhibitor is an antibody, such as a humanized monoclonal antibody. In a further embodiment, the VEGF antibody is bevamab. In another embodiment, the VEGF inhibitor is ranibizumab, aflibercept, or pegaptanib. In other embodiments, the devices and methods described herein may be used to deliver one or more of the following VEGF antagonists: AL8326, 2C3 antibody, AT001 antibody, HyBEV, bevacizumab (Avastin), ANG3070, APX003 antibody, APX004 antibody, ponatinib (AP24534), BDM-E, VGX100 antibody (VGX100 CIRCADIAN), VGX200 (c-fosInducible growth factor monoclonal antibody), VGX300, COSMIX, DLX903 / 1008 antibody, ENMD2076, Sutent (sunitinib malate), INDUS815C, R84 antibody, KD019, NM3, allogeneic mesenchymal progenitor cells combined with anti-VEGF agents or antibodies, MGCD265, MG516, VEGF receptor kinase inhibitor, MP0260, NT503, anti-DLL4 / VEGF bispecific antibody, PAN90806, Paromide 529, BD0801 antibody, XV615, lucitanib (AL3810, E3810), AMG706 (motesanib diphosphate), AAV2-sFLT01, soluble Flt 1 receptor, cediranib (resentin), AV-951 (tivozanib, KRN-951), Stivarga (regorafenib), volasertib (BI6727), CEP11981, KH903, lenvatinib (E7080), telameprocol (EM1421), ranibizumab (Lucentis), Votrient (pazopanib hydrochloride), PF00337210, PRS050, SP01 (curcumin), orotinic acid carboxamide triazole, hydroxychloroquine, linifanib (ABT869, RG3635), Irbian (fluocinolone acetonide), ALG1001, AGN150998, DARPinMP0112, AMG386, ponatinib (AP24534), AVA101, vargatef (nintedanib), BMS690514, KH902, golbatinib (E7050), afinitor (everolimus), dovitinib lactate (TKI258, CHIR258), ORA101, ORA102, axitinib (Inrita, AG013736), pristicepsin (apridine), lenvatinib mesylate, P TC299, aflibercept (Zaltrap, Eylea), pegaptanib sodium (Macgen, LI900015), Visudyne (Verteporfin), bucillamine (Rimatil, Lamin, Brimani, Lamit, Boomiq), R3 antibody, AT001 / r84 antibody, troponin (BLS0597), EG3306, batalanib (PTK787), Bmab100, GSK21367 73, anti-VEGFR alterase, Avila, CEP7055, CLT009, ESBA903, HuMax-VEGF antibody, GW654652, HMPL010, GEM220, HYB6 76, JNJ17029259, TAK593, XtendVEGF antibody, Nova21012, Nova21013, CP564959, smart anti-VEGF antibody, AG028262, AG13958, CVX241, SU14813, PRS055, PG501, PG545, PT1101, TG100948, ICS283, XL647, Enzastaurin hydrochloride (LY317615), BC194, Quinoline, COT601M06.1, COT604M06.2, MabionVEGF, SIR-anti-VEGF or VEGF-R antibody-conjugated spheres, Apatinib (YN968D1), and AL3818. Furthermore, delivery of VEGF inhibitors or VEGF antagonists using the microneedle devices and methods disclosed herein may be combined with one or more of the agents described herein, or with other agents known in the art.

[0103] In some embodiments, one or more components of the systems or devices disclosed herein are configured to be assembled together. For example, the system or device may include one or more syringe barrels.

[0104] In some embodiments, the system or device may include two or more units, such as a first syringe unit including a first syringe barrel, a needle base in the first syringe barrel, and a needle including a proximal end and a distal end that engage with the needle base. In some embodiments, the system or device may include a second syringe unit configured to engage with the distal end of the first syringe unit, the second syringe unit including a second syringe barrel and a floating seal located in the second syringe barrel, the floating seal being configured to elastically engage with the needle base when the first syringe unit and the second syringe unit engage. In some embodiments, the system or device may include a third syringe unit configured to engage with the distal end of the second syringe unit, the third syringe unit including a third syringe barrel containing a fluid composition, the needle base being configured to advance the needle so that the proximal end and / or distal end of the needle are placed in the fluid composition. In any embodiment of this specification, the system or device may include one or more syringe units, the fourth syringe unit optionally configured to engage with the distal end of the third syringe unit.

[0105] In some embodiments, the system or device includes a first syringe unit, the first syringe unit includes a first syringe barrel, and a needle, which includes a needle base and a floating seal elastically engaging with each other within the first syringe barrel, the needle base being proximal to the floating seal, and a needle including a proximal end and a distal end that engage with the needle base, the needle including (i) a distal needle opening, (ii) a needle body opening between the proximal end and the distal end of the needle, the needle body opening being proximal to the distal needle opening, and (iii) a needle body passage connecting the distal needle opening and the needle body opening. In some embodiments, the system or device may further include a second syringe unit configured to engage with the distal end of the first syringe unit, and comprising a second syringe barrel containing a fluid composition, wherein the needle base may be configured to advance the needle, positioning the proximal and / or distal ends of the needle in the fluid composition. In any embodiment of this specification, the device may comprise one or more syringe units, and optionally include a third syringe unit configured to engage with the distal end of the second syringe unit. In some embodiments, the system or device may include a first syringe unit, the first syringe unit including a first syringe barrel, a needle base in the first syringe barrel, and a needle including a proximal end and a distal end that engage with the needle base, the needle including (i) a distal opening, (ii) a needle body opening between the proximal end and the distal end of the needle, the needle body opening being proximal to the distal opening, and (iii) a needle body passage connecting the distal opening and the needle body opening. In some embodiments, the system or device may further include a second syringe unit configured to engage with the distal end of the first syringe unit, and comprising a second syringe barrel, a floating seal in the second syringe barrel configured to elastically engage with the needle base when the first and second syringe units engage, and a fluid composition, wherein the needle base may be configured to advance the needle so that the proximal end and / or distal end of the needle are positioned in the fluid composition. In any embodiment of this specification, the device may comprise one or more syringe units, and optionally comprises a third syringe unit configured to engage with the distal end of the second syringe unit. III. Methods for Medical Penetration

[0106] In some embodiments, this specification describes methods for performing medical punctures, for example, in the eye or other organs or tissues.

[0107] As shown in Figures 1 to 11B, in some embodiments, the present invention provides a medical puncture or penetration device comprising a syringe barrel 1, an operating unit (e.g., an elastic moving unit for pushing the needle), a hollow puncture needle 6, and a fluid composition lumen 7.

[0108] In some embodiments, the syringe barrel 1 includes a distal closed end and a proximal open end. In some embodiments, the syringe barrel 1 may be designed to have two open ends in the axial direction, and sealing of the distal end can be achieved by attaching a distal seal 8 to the distal opening of the syringe barrel 1. In some embodiments, the distal seal 8 may be made of a material that can be punctured by a hollow puncture needle 6, such as rubber.

[0109] In some embodiments, the actuation unit (e.g., an elastic movement unit) includes an actuation member (e.g., a pressing element) 2 and a floating seal 3, the floating seal 3 being configured to seal and engage with the inner wall of the syringe barrel and to move axially, for example, toward the distal or proximal end of the syringe barrel. In some embodiments, the actuation member (e.g., a pressing element) 2 or a part thereof is located outside the proximal opening of the syringe barrel so that the practitioner can manually press the actuation member (e.g., a pressing element) or a part thereof. In some embodiments, the floating seal 3 is elastically engaged with the actuation member 2, and when pressure is applied to the actuation member 2, the floating seal 3 is movable forward or backward relative to the actuation member (e.g., a pressing element). In some embodiments, the floating seal 3 is configured to move toward the distal end of the syringe barrel. In some embodiments, the floating seal 3 is configured to move toward the proximal end of the syringe barrel. In some embodiments, the position of the operating member (e.g., a retaining element) relative to the syringe barrel remains stationary, and the floating seal 3 is configured to move elastically (e.g., distally) forward due to elastic engagement with the operating member (e.g., a retaining element).

[0110] In some embodiments, the hollow puncture needle 6 is fixedly connected to the actuator 2. When no pressure is applied to the actuator 2, the hollow puncture needle 6 is held proximal to the floating seal 3, and the two do not come into contact. In some embodiments, the hollow puncture needle 6 itself includes a distal needle opening 6a and a needle body opening 6b. In some embodiments, the distal needle opening 6a and the needle body opening 6b are connected via a needle cavity or needle body passage of the hollow puncture needle 6.

[0111] In some embodiments, the fluid composition lumen 7 is used to store, for example, pharmaceuticals and other fluid compositions such as liquids or gels. In some embodiments, the fluid composition lumen is sealed by the distal closed end of the syringe barrel, the inner wall of the syringe barrel, and the floating seal 3, i.e., the fluid composition lumen occupies the distal portion of the lumen of the syringe barrel. In some embodiments, the floating seal 3 is axially movable so that the fluid composition lumen 7 is configured to have a variable volume, and the fluid pressure within the fluid composition lumen 7 can change with the axial movement of the floating seal 3.

[0112] In some embodiments, using the medical puncture device disclosed herein involves applying pressure to the actuarial member 2 to advance the hollow puncture needle 6 distally, sequentially passing through the floating seal 3 (e.g., by puncturing the floating seal or by forcibly opening a conventional hole or slit that penetrates the floating seal) and the distal closed end of the syringe barrel (e.g., by puncturing the distal closed end or by forcibly opening a conventional hole or slit that penetrates the distal closed end). The conventional hole or slit may, for example, pass through the floating seal from the proximal surface to the distal surface of the floating seal, thereby creating a through hole in the floating seal. The conventional hole or slit does not have to pass through the entire floating seal, and advancing the distal end of the needle through the floating seal may include advancing through the conventional hole or slit and puncturing a portion of the floating seal, in any suitable combination. For example, the distal end of the needle can first advance from the proximal surface, pass through a conventional hole or slit, and then puncture the floating seal before being exposed from the distal surface of the floating seal, and vice versa. In some embodiments, the hollow puncture needle 6 is inserted into an apparent or potential tissue void, cavity, or blood vessel, thereby positioning the distal opening 6a of the needle within the apparent or potential tissue void, cavity, or blood vessel. In some embodiments, the needle body opening 6b is located within the fluid composition lumen 7, and the floating seal 3 elastically engages with the actuarial member 2. In some embodiments, the fluid pressure within the fluid composition lumen 7 is higher than the pressure within the apparent or potential tissue void, cavity, or blood vessel.

[0113] At this time, the fluid composition in the fluid composition lumen 7 can enter visible or latent tissue voids, cavities, or blood vessels through the needle body opening 6b and the distal needle opening 6a. In some embodiments, the user can easily maintain pressure in the actuator 2 during the injection process, for example, without further increasing the pressure. Due to the elastic engagement between the floating seal 3 and the actuator 2, the fluid composition (e.g., solution, suspension, or gel) in the fluid composition lumen 7 can enter the needle body opening 6b and, through the needle body passage, achieve injection, penetration, and / or expansion into visible or latent tissue voids, cavities, or blood vessels.

[0114] In some embodiments, before the hollow puncture needle 6 penetrates an exposed or potential tissue void, cavity, or blood vessel, the external pressure at the distal opening 6a of the needle is higher than the fluid pressure within the lumen of the fluid composition 7, for example, because the distal opening is located in tissue that is denser, harder, and / or less deformable than the exposed or potential tissue void, cavity, or blood vessel. Therefore, the fluid composition within the lumen of the fluid composition is present at the distal opening 6a of the needle and cannot enter the surrounding tissue. Taking the puncture process of the SCS of the eye as an example, if the hollow puncture needle 6 penetrates the sclera 13 but not the SCS 14, the fluid composition will not flow out from the distal opening 6a of the needle, regardless of whether the needle body opening 6b is in fluid communication with the lumen of the fluid composition 7. This is because the sclera 13 is relatively dense, and relatively high external pressure is applied to the distal opening 6a of the needle when it is located within the sclera 13. The external pressure is higher than the fluid pressure within the lumen 7 of the fluid composition, and dense tissues such as the sclera act as plugs that effectively prevent the outflow of the fluid composition.

[0115] In some embodiments, by observing whether the floating seal 3 moves forward due to elastic engagement when the actuator 2 is stationary under pressure, the practitioner can determine whether the hollow puncture needle 6 has penetrated an apparent or potential tissue void, cavity, or blood vessel, informing the practitioner of the current needle depth and / or the position of the distal opening of the needle, thereby ensuring accurate needle placement. In some embodiments, the injection can be controlled by changing the fluid pressure within the fluid composition lumen 7, so that the injection process does not require the manual application of force transmitted through a relatively rigid medium (e.g., solid or liquid) to advance the needle tip and precisely position it within an apparent or potential tissue void, cavity, or blood vessel. Rather, the elastic engagement between the actuator 2 and the floating seal 3 can buffer sudden forces applied to the actuator 2, allowing for more controllable and stable movement of the floating seal. In some embodiments, using the device disclosed herein can prevent or reduce fluctuations in flow velocity, resulting in a stable injection.

[0116] The apparent or potential tissue gaps, voids, cavities, cavity systems, or blood vessels of the present invention may include, but are not limited to, the SC, epidural space, pleural space, peritoneal space, arteries, veins, and joint spaces (e.g., knee joint space). Accordingly, the medical puncture devices disclosed herein also have the advantage of high versatility, as they can be used in any suitable apparent or potential tissue gaps, voids, cavities, cavity systems, or blood vessels. In some embodiments, the medical puncture devices can be used for SCS puncture and drug delivery, epidural puncture and drug delivery, pleural puncture and intrapleural drug delivery, peritoneal puncture and intraperitoneal drug delivery, or intra-articular injection. For example, it can be used for accessing the suprachoroid space (eye area), epidural injection (spinal cord access), accessing major blood vessels (arteries and veins), insertion of surgical wires (e.g., access to the heart via blood vessels), access to blood vessels for fistula access or catheter insertion, access to the heart wall without damaging the inner wall, access to the abdomen (e.g., access to minimally invasive surgical trocars), injection into subcutaneous fat, access to the inside of the amniotic sac without damaging the fetus, injection into the patella without damaging the cartilage, injection into the meninges without damaging brain tissue (by drilling a hole in the skull and using an autostop on the meninges), injection between the pericardium and the heart, injection between the fascia and the kidney, injection between the fibrous tissue layer and implants (e.g., breast implants), injection into other ocular spaces (e.g., use in deep anterior lamellar keratoplasty (DALK) to separate the epithelial cell layer from the collagen layer), or external injection into a collapsed lung. Furthermore, the system is useful for the delivery of gene therapy, including but not limited to viral vectors and / or transfected cells. In some embodiments, the fluid composition may contain multiple therapeutic agents. In non-limiting examples, the therapeutic agents may include mRNA, CRISPR reagents, RNAi, antibodies, nanoantibodies, nanoparticles, proteins, peptides, small molecules, aptamers, cells, extracellular vesicles, microRNAs, and the like.

[0117] In some embodiments, when the hollow puncture needle 6 is inserted into the distal closed end of the syringe barrel, the medical puncture device can be in at least three states, namely, a pre-puncture state, a surface tissue puncture state, and a fluid communication state.

[0118] In some embodiments, during the preliminary puncture state, the length range of the hollow puncture needle 6 extending from the distal closed end of the syringe barrel is the preliminary puncture length range. Within this range, the hollow puncture needle 6 has not yet initiated puncture into an organ or tissue.

[0119] In some embodiments, the system or device of the present invention includes a fluid composition lumen pre-filled with a fluid composition. In some embodiments, before using the system or device, the needle passes through a floating seal. In some embodiments, before using the system or device, the needle passes through a floating seal and a distal seal that seals the distal end of the syringe barrel, for example, the distal end of the syringe barrel.

[0120] In some embodiments, the fluid composition has a relatively high viscosity, such as a gel or paste-like material, with a viscosity higher than that of water. The elastic sleeve or sheath 4 shown in the drawings of the present invention is optional, especially when the viscosity of the fluid composition is sufficient to prevent discharge from the needle body opening and / or the distal needle opening, when the opening is located within the lumen of the fluid composition. For example, as shown in Figure 3A, the needle may pass through the floating seal such that the needle body opening 6b is proximal to the floating seal and the distal needle opening 6a is within the lumen of the fluid composition. Discharge of the fluid composition from the needle body opening can be prevented by the viscosity of the composition, and the elastic sheath is optional. Alternatively, as shown in Figure 3B, the needle body opening 6b may be within the lumen of the fluid composition and the distal needle opening 6a may be outside the lumen of the fluid composition. Discharge of the fluid composition from the distal needle opening can be prevented by the viscosity of the composition until the distal needle opening reaches a target tissue such as an apparent or potential tissue void, cavity, or blood vessel.

[0121] In some embodiments, for example, before or during use of the system or device, the distal opening 6a of the needle may be outside the lumen of the fluid composition, while the needle body opening 6b may be proximal to the floating seal (see, e.g., Figure 3C, 6b1) or inside the floating seal (see, e.g., Figure 3C, 6b2). Discharge of the fluid composition from the distal opening of the needle may be prevented by the viscosity of the composition until the distal opening of the needle reaches target tissue such as an apparent or potential tissue void, cavity, or blood vessel.

[0122] In some embodiments, for example, before or during use of the system or device, the distal needle opening 6a may be located within the distal seal of the distal closed end of the syringe barrel (for example, the distal needle opening may be occluded by the distal seal), and the needle body opening 6b may be located proximal to the floating seal (for example, see Figure 3D, 6b1), within the floating seal (for example, see Figure 3D, 6b2), or within the lumen of the fluid composition (for example, see Figure 3D, 6b3). This prevents the fluid composition from being discharged through the distal needle opening and the needle body opening.

[0123] In some embodiments, for example, before or during use of the system or device, the distal needle opening 6a may be within the lumen of the fluid composition, and the needle body opening 6b may be within the floating seal (see, for example, Figure 3E, 6b1) or within the lumen of the fluid composition (see, for example, Figure 3E, 6b2). This prevents the fluid composition from being discharged through the needle body opening.

[0124] In some embodiments, for example, before or during use of the system or device, the distal needle opening 6a may be located within the floating seal, and the needle body opening 6b may be located proximal to the floating seal (see, for example, Figure 3F, 6b). This prevents the fluid composition from being discharged through the needle body opening.

[0125] In some embodiments, in a surface tissue puncture state, the length range of the hollow puncture needle 6 extending from the distal closed end of the syringe barrel is the surface tissue puncture length range. In this range, the distal end of the hollow puncture needle 6 penetrates the surface tissue (e.g., pierces the sclera 13) but does not penetrate any apparent or potential tissue gaps, cavities, or blood vessels (e.g., does not pierce the SCS 14). In some embodiments, because the surface tissue is relatively dense, the external pressure at the distal opening 6a of the needle is higher than the fluid pressure in the fluid composition lumen 7, and therefore the fluid composition does not enter the needle body opening 6b or exit the distal opening 6a of the needle, regardless of whether the needle body opening 6b is connected to the fluid composition lumen 7.

[0126] In some embodiments, in the fluid-communication state, the length range of the hollow puncture needle 6 extending from the distal closed end of the syringe barrel is the fluid-communication length range. In this range, the distal end of the hollow puncture needle 6 is pierced into an apparent or potential tissue void, cavity, or blood vessel. In some embodiments, the device may be designed such that, in the fluid-communication state, the fluid pressure in the fluid composition lumen 7 is higher than the pressure in the apparent or potential tissue void, cavity, or blood vessel. In some embodiments, in the fluid-communication state, the needle body opening 6b is positioned within the fluid composition lumen 7, and due to the pressure difference between the inside (e.g., the apparent or potential tissue void, cavity, or blood vessel) and the outside (e.g., the fluid composition lumen 7), the fluid composition in the lumen 7 may flow into the apparent or potential tissue void, cavity, or blood vessel through the needle body opening 6b, the needle body passage, and then through the distal needle opening 6a.

[0127] In some embodiments, the floating seal 3 moves distally due to elastic engagement with the actuator 2 (for example, because the pressure in the lumen of the fluid composition is higher than the back pressure at the distal needle opening in apparent or potential tissue cavities or vessels) until the floating seal seals the needle body opening 6b (e.g., Figures 4A-4B). In some embodiments, the axial dimension of the needle body opening is less than or equal to the thickness of the floating seal. In some embodiments, the needle body opening may be completely sealed or occluded by the floating seal, in which case the fluid composition no longer enters tissue cavities from the distal needle opening 6a. In some embodiments, when the floating seal occludes the needle body opening, only a portion of the total volume of the fluid composition flows out from the distal needle opening 6a (see, for example, Figure 4A). In some embodiments, when the floating seal occludes the needle body opening, the entire volume of the fluid composition in the lumen flows out from the distal needle opening 6a (see, for example, Figure 4B).

[0128] In some embodiments, the needle body opening may be located within the distal seal or within the subject's tissue, and the fluid composition may stop the existing distal needle opening 6a (see, for example, Figure 4C). In some embodiments, the distance between the distal needle opening 6a and the needle body opening 6b may be kept constant. In some embodiments, the distance between the distal needle opening 6a and the needle body opening 6b may be variable. For example, a needle having an appropriate distance between the distal needle opening 6a and the needle body opening 6b may be selected based on the known or estimated depth of the tissue being accessed. In some embodiments, a stopper 1a may be located within the syringe lumen and used to restrict the forward movement of the floating seal 3 to enable precise injection, such as injection of a predetermined volume.

[0129] In some embodiments, when the floating seal 3 comes into contact with the stopper 1a, further distal movement of the floating seal 3 is restricted, stabilizing the floating seal for subsequent operations, as shown in Figures 6-11B, for example.

[0130] In some embodiments, the systems or devices disclosed herein include two or more floating seals. For example, as shown in Figure 5A, a first lumen is formed between floating seal 3b and the distal seal of the syringe barrel, and a second lumen is formed between floating seal 3a and floating seal 3b. In some embodiments, the first and second lumen contain the same fluid material. In some embodiments, the first and second lumen contain different fluid compositions. In some embodiments, the first and second lumen contain the same pharmaceutical product (e.g., active pharmaceutical ingredient) in the same or different fluid carrier or excipient. In some embodiments, the first and second lumen contain different pharmaceutical products (e.g., active pharmaceutical ingredients) in the same or different fluid carrier or excipient. In some embodiments, the first lumen contains the pharmaceutical product and the second lumen contains a pharmaceutically acceptable carrier or excipient, such as saline solution, and vice versa.

[0131] In some embodiments, the fluid compositions in the first and second lumens may be delivered sequentially into apparent or potential tissue cavities, cavities, or blood vessels. In some embodiments, the fluid compositions in the first and second lumens may be mixed into apparent or potential tissue cavities, cavities, or blood vessels. In some embodiments, the fluid composition in the first lumen may enter apparent or potential tissue cavities, cavities, or blood vessels for access to and / or expansion of the tissue cavities, cavities, or blood vessels. Subsequently, the fluid composition containing the pharmaceutical in the second lumen may enter apparent or potential tissue cavities, cavities, or blood vessels. For example, as shown in Figure 5A, when the distal opening 6a of the needle is in apparent or potential tissue cavities, cavities, or blood vessels, and the needle body opening 6b is in the first lumen (between the floating seal 3b and the distal seal of the syringe barrel), the fluid composition in the first lumen is delivered to the tissue. In Figure 5B, when the floating seal 3b moves distally and the needle body opening 6b contacts the second lumen (between the floating seals 3a and 3b), the distal needle opening 6a may remain stationary within an apparent or potential tissue void, cavity, or blood vessel. In this way, the fluid composition in the second lumen begins delivery to the tissue until a certain volume is delivered and / or until the floating seal 3a (or the floating seals 3a and 3b together) occludes the needle body opening 6b, as shown in Figure 5C. In some embodiments, a set (e.g., predetermined) volume of the fluid composition in the first lumen and / or a set (e.g., predetermined) volume of the fluid composition in the second lumen may be delivered to an apparent or potential tissue void, cavity, or blood vessel. In some embodiments, the dimension of the needle body opening 6b along the needle axis is greater than the thickness of the floating seal 3b so that the first fluid composition (between the floating seal 3b and the distal seal of the syringe barrel) and the second fluid composition (between the floating seal 3b and the floating seal 3a) can be sequentially and continuously delivered through the distal opening of the needle to apparent or potential tissue cavities, or blood vessels.In some embodiments, the dimension of the needle body opening 6b along the needle axis is less than or equal to the sum of the thicknesses of the floating seals 3a and 3b. In some embodiments, the dimension of the needle body opening 6b along the needle axis is greater than the thickness of the floating seal 3b and less than the sum of the thicknesses of the floating seals 3a and 3b. In some embodiments, the system or device disclosed herein includes one or more additional floating seals (e.g., a third floating seal 3c) proximal to the floating seal 3a, distal to the floating seal 3b, and / or between the floating seals 3a and 3b, so that the third fluid composition is delivered before the first fluid composition, after the second fluid composition, or between the first and second fluid compositions.

[0132] In some embodiments, the systems or devices disclosed herein include two or more needle body openings. In some embodiments, the systems or devices disclosed herein include two or more needle body openings and two or more floating seals. For example, as shown in Figure 5D, when the distal needle opening 6a is in an apparent or potential tissue void, cavity, or blood vessel, and the needle body opening 6b1 is in a first lumen (between the floating seal 3b and the distal seal of the syringe barrel), and the needle body opening 6b2 is occluded by the floating seal 3b, the fluid composition in the first lumen is delivered to the tissue. In Figure 5E, when the floating seal 3b moves distally to occlude the needle body opening 6b1, the distal needle opening 6a remains stationary in an apparent or potential tissue void, cavity, or blood vessel, allowing the needle body opening 6b2 to contact a second lumen (between the floating seals 3a and 3b). In this way, as shown in Figure 5F, the fluid composition in the second lumen begins delivery to the tissue until a predetermined volume is delivered and / or the floating seal 3a (or the floating seal 3a and floating seal 3b together) occludes the needle body opening 6b2 (and / or needle body opening 6b1). In some embodiments, a set (e.g., predetermined) volume of the fluid composition in the first lumen and / or a set (e.g., predetermined) volume of the fluid composition in the second lumen may be delivered to apparent or potential tissue voids, cavities, or blood vessels. In some embodiments, the distance along the needle axis between the needle body opening 6b1 and the needle body opening 6b2 is greater than the thickness of the floating seal 3b so that the first fluid composition (between the floating seal 3b and the distal seal of the syringe barrel) and the second fluid composition (between the floating seal 3b and the floating seal 3a) can be sequentially and continuously delivered through the distal needle opening to apparent or potential tissue voids, cavities, or blood vessels. In some embodiments, the distance along the needle axis between the needle body opening 6b1 and the needle body opening 6b2 is less than or equal to the sum of the thicknesses of the floating seals 3a and 3b.In some embodiments, the distance along the needle axis between the needle body opening 6b1 and the needle body opening 6b2 is greater than the thickness of the floating seal 3b and less than the combined thickness of the floating seals 3a and 3b. In some embodiments, the system or device disclosed herein includes one or more additional needle body openings (e.g., a third needle body opening 6b3) proximal to the needle body opening 6b2, distal to the needle body opening 6b1, and / or between the needle body openings 6b1 and 6b2, so that the third fluid composition is delivered before the first fluid composition, after the second fluid composition, or between the first and second fluid compositions.

[0133] Several embodiments of controlling the termination of an injection process using the medical puncture devices disclosed herein are described below.

[0134] In some embodiments, when the medical puncture device is in fluid communication, the floating seal 3 advances until it elastically engages with the actuarial member 2 and seals the needle body opening 6b. Once the needle body opening 6b is sealed, the injection process is complete. In some embodiments, the axial position of the needle body opening 6b within the fluid composition lumen 7 limits the maximum injection volume of the medical puncture device. In some embodiments, when the needle body opening 6b is closed or sealed by the floating seal 3, the floating seal 3 is not in contact with the wall of the distal closed end of the syringe barrel. In some embodiments, the fluid composition lumen 7 is not completely empty, and there is still fluid composition present between the floating seal 3 and the wall of the distal closed end of the syringe barrel.

[0135] In some embodiments, the floating seal 3 may be designed to seal the needle body opening 6b when the floating seal contacts the distal closed end of the syringe barrel, in cases where it is necessary to empty the fluid composition lumen 7. In some embodiments, the needle body opening 6b is located at the distal end of the fluid composition lumen 7. In some embodiments, the floating seal 3 contacts the wall of the distal closed end of the syringe barrel, and the needle body opening 6b is occluded or sealed by the floating seal 3 and / or the wall of the distal closed end of the syringe barrel. In some embodiments, the fluid composition lumen 7 is empty, and there is little to no fluid composition between the floating seal 3 and the wall of the distal closed end of the syringe barrel.

[0136] In some embodiments, as the fluid composition in the fluid composition lumen 7 gradually enters an apparent or potential tissue void, cavity, or blood vessel, there may be a state in which the fluid pressure in the fluid composition lumen 7 balances the pressure in the apparent or potential tissue void, cavity, or blood vessel. At this point, the floating seal 3 will not move due to the balance of forces. To continue the injection and / or empty the fluid composition lumen 7, additional force must be applied to the floating seal 3 to move it forward toward the distal closed end of the syringe barrel.

[0137] For example, as shown in Figures 2A to 2E, the main body wall of the syringe barrel 1 may be provided with one or more axially extending sliding grooves (not shown). A slider that fits into the sliding groove may be positioned on the actuator 2 (for example, the slider may include a portion of the actuator 2 that extends outside the syringe barrel 1), thereby increasing the upper limit of the travel distance or stroke of the actuator 2, as its movement is not restricted by the proximal end of the actuator 2. If the floating seal 3 cannot move any further due to a force imbalance (e.g., pressure between the fluid composition lumen 7 and apparent or potential tissue voids, cavities, or blood vessels), greater pressure can be applied to the slider of the actuator 2 to advance the actuator 2 toward the distal end, thereby increasing the elasticity between the floating seal 3 and the actuator 2, disrupting the force imbalance, and allowing the floating seal 3 to advance toward the distal end of the syringe barrel. This allows more fluid composition to be discharged from the fluid composition lumen 7, and in some embodiments, the fluid composition lumen 7 can be emptied.

[0138] In some embodiments, other drive structures may be used to further move the floating seal 3 until it contacts the wall of the distal closed end of the syringe barrel. Illustrative drive structures are described below.

[0139] In some embodiments, an axially extending sliding groove may be provided on the circumferential wall of the syringe barrel 1 and is located proximal to the floating seal 3. In some embodiments, the manual control unit may include an actuator 2' (which may be in the form of a slider) that slides into the sliding groove on the circumferential wall of the syringe barrel. In some embodiments, a portion of the actuator (e.g., slider) 2' extends through the sliding groove to the outside of the syringe barrel to facilitate user operation. In some embodiments, the floating seal 3 and the actuator (e.g., slider) 2' form an elastic connection. For example, the floating seal 3 and the actuator (e.g., slider) 2' may engage with each other by an elastic piece (e.g., spring) 4', as shown in step 1 of Figure 2G, or the floating seal 3 and the actuator (e.g., slider) 2 may engage with each other by an elastic piece (e.g., spring) 4. In some embodiments, the actuator 2 may include a rod configured to be inserted through the space between portions of the actuator 2' so that the actuators 2' and 2' do not interfere with each other. In some embodiments, the elastic piece (e.g., a spring) 4 and the elastic piece (e.g., a spring) 4' can operate independently and do not interfere with each other. In some embodiments, spring 4 may be smaller than spring 4', for example, the average diameter of spring 4 may be smaller than the average diameter of spring 4'. In some embodiments, elastic piece 4' is nested inside elastic piece 4. In step 2 of Figure 2G, force may be applied to the actuator 2 to move the needle distally while maintaining the position of the floating seal 3. In some embodiments, as shown in step 3 of Figure 2G, force may be applied to the actuator 2' to move distally along the axial direction of the sliding groove in the circumferential wall of the syringe barrel. This may cause the elastic piece (e.g., a spring) 4' between the floating seal 3 and the actuator (e.g., a slider) 2' to be elastically compressed. In some embodiments, the floating seal 3 may continue to move distally by an elastic force that disrupts the balance of forces while the position of the actuating member (e.g., slider) 2' remains constant, until the volume of the discharged fluid composition reaches a target volume.In some embodiments, the movable member (e.g., slider) 2' may move distally, as shown in step 4 of Figure 2G, to move the floating seal 3 further distally to discharge the movable composition from the needle.

[0140] In some embodiments, the medical puncture device includes an element configured to allow the practitioner to manually control the movement of the floating seal using one or both hands. In some embodiments, the manual control element can be moved using one or more fingers, for example, one finger of the same hand that grasps the syringe barrel. In some embodiments, the manual control element is fixed to the floating seal 3 and extends partially outside the syringe barrel. In some embodiments, if the volume of fluid composition injected into an apparent or potential tissue void, cavity, or blood vessel has not reached the target volume and the floating seal 3 no longer moves due to the balance of forces, the practitioner may drive the floating seal 3 further forward by moving the portion of the manual control element extending outside the syringe barrel until the volume of fluid composition discharged reaches the target volume. In some embodiments, the use of the manual control element facilitates emptying the fluid composition lumen 7. These embodiments are not limited to cases where it is necessary to empty the fluid composition lumen 7.

[0141] In some embodiments, the medical puncture device can precisely achieve (e.g., by injection) the delivery (of a fluid composition of a defined volume) and / or control the volume delivered. In some embodiments, the defined volume is a preset volume before delivery. In some embodiments, the defined volume is one of several volumes that the practitioner can select during delivery, and the volume delivered may be different from the preset volume. In some embodiments, as shown in Figures 1A-1F, 2A-2F, and 11, an axial stopper 1a is positioned distal to the floating seal 3 within the syringe lumen to restrict the forward movement of the floating seal 3. In some embodiments, when the medical puncture device is in fluid communication, the needle body opening 6b may be distal to the axial stopper 1a, and the floating seal 3 may elastically engage with the actuator 2 and move forward.

[0142] In some embodiments, the floating seal 3 is moved to a position limited by the axial stopper 1a. In some embodiments, while the floating seal 3 is moving to the position limited by the axial stopper 1a, the pressure within the fluid composition lumen 7 is not less than the pressure within obvious or potential tissue voids, cavities, or blood vessels. In some embodiments, the floating seal 3 may be biased forward to the position limited by the axial stopper 1a by an elastic restoring force between the floating seal 3 and the actuator 2, eliminating the need to rely on an additional drive structure or force to move the floating seal 3 to the position limited by the axial stopper 1a.

[0143] In some embodiments, the pressure within the fluid composition lumen 7 becomes equal to the pressure within apparent or potential tissue voids, cavities, or blood vessels (i.e., due to force balance, the floating seal 3 does not move before reaching the axial stopper 1a) by the elastic restoring force between the floating seal and the actuator 2. In this case, the elastic restoring force between the floating seal 3 and the actuator 2 alone is not enough to push the floating seal 3 forward to the position limited by the axial stopper 1a. Therefore, in some embodiments, one or more additional drive structures or mechanisms may be used to further advance the floating seal 3. For example, the additional drive structures or mechanisms may include manual control elements described herein (see, for example, Figures 2A-2E). In some embodiments, the axial stopper 1a provides a mechanism for achieving fluid injection of a set volume.

[0144] The following describes several embodiments of the puncture and injection timing of the medical puncture devices disclosed herein.

[0145] In some embodiments, when the medical puncture device is in a pre-puncture state, i.e., when the length of the hollow puncture needle 6 extending from the distal closed end of the syringe barrel is within the pre-puncture length range (or when the hollow puncture needle 6 is inserted into the distal closed end of the syringe barrel but has not yet begun to puncture an organ or its tissue), the needle body opening 6b is held above the fluid composition lumen 7 (e.g., at the proximal end). Such a configuration can prevent premature leakage from the distal opening 6a of the needle and can improve the reliability of the medical puncture device.

[0146] In some embodiments, corresponding structures(s) may be provided on the device to prevent premature leakage before the hollow puncture needle 6 punctures tissue and / or before the distal opening 6a of the needle reaches an apparent or potential tissue void, cavity, or blood vessel. For example, an axially extending circular contact element 1b may be formed at the distal closed end of the syringe barrel. In some embodiments, the axial length of the circular contact element 1b is set to be the same as the difference between the upper and lower limits of the pre-puncture length range of the hollow puncture needle 6 (i.e., the difference in the needle's pre-puncture length between when the hollow puncture needle 6 is inserted into the distal closed end of the syringe barrel and when it begins to puncture an organ or tissue). In this setting, premature leakage will not occur at the distal opening 6a of the needle as long as the distal end of the hollow puncture needle 6 is within the axial length range of the circular contact element 1b. During puncture, the circular contact element 1b may initially contact the surface of the organ or tissue to stabilize the medical puncture device. Subsequently, pressure may be applied to the operating member 2 to initiate the puncture operation.

[0147] In some embodiments, when the medical puncture device is in a surface tissue puncture state, i.e., when the length of the hollow puncture needle 6 extending from the distal closed end of the syringe barrel is within the surface tissue puncture length range (or when the distal end of the hollow puncture needle 6 is punctured into surface tissue but has not entered an obvious or potential tissue void, cavity, or blood vessel), the needle body opening 6b is at least partially connected to the fluid composition lumen 7. In some embodiments, fluid communication is established between the fluid composition lumen 7, the distal needle opening 6a, and the needle body opening 6b before the distal end of the hollow puncture needle 6 punctures into an obvious or potential tissue void, cavity, or blood vessel. In some embodiments, the fluid composition in the lumen 7 can enter the needle body passage of the hollow puncture needle 6 early (through the needle body opening 6b), removing at least some of the air that may be present in the needle body passage, thereby reducing the amount of air that enters an obvious or potential tissue void, cavity, or blood vessel.

[0148] In some embodiments, as the distal end of the hollow puncture needle 6 begins to penetrate surface tissue, the needle body opening 6b begins to connect to the lumen 7 of the fluid composition. In some embodiments, as the distal end of the hollow puncture needle 6 penetrates an apparent or potential tissue void, cavity, or blood vessel, the needle body passage of the hollow puncture needle 6 is filled with the fluid composition, thereby eliminating or reducing the possibility of air entering an apparent or potential tissue void, cavity, or blood vessel.

[0149] In some embodiments, when the medical puncture device is in fluid communication, i.e., when the length of the hollow puncture needle 6 extending from the distal closed end of the syringe barrel is within the fluid communication length range (or when the distal end of the hollow puncture needle 6 is inserted into an exposed or potential tissue gap, cavity or blood vessel), the needle body opening 6b is positioned within the fluid composition lumen 7, and the maximum flow rate is achieved at the needle body opening 6b, thereby increasing the injection speed.

[0150] The embodiments described herein may be implemented individually or in any suitable combination.

[0151] In some embodiments, the devices disclosed herein can prevent backflow and / or backflow of fluid through the needle body opening 6b.

[0152] In some embodiments, if the needle body opening 6b is still at the proximal end of the floating seal 3 while the distal needle opening 6b is connected to the lumen 7 of the fluid composition, there is a risk of backflow and / or backflow of fluid from the needle body opening 6a. In some embodiments, if the needle body opening 6b is still at the proximal end of the floating seal 3 while the distal needle opening 6a is in an apparent or potential tissue gap, cavity, or blood vessel, there is a risk of backflow and / or backflow of fluid from the needle body opening 6b. In some embodiments, the elastic sheath 4 covering the outside of the hollow puncture needle 6 may be located within an operating unit (e.g., an elastic moving unit), for example, between the needle base and the floating seal 3. In some embodiments, when the needle body opening 6b is located near the floating seal 3 (for example, when the needle body opening 6b is not connected to the lumen 7 of the fluid composition), the elastic sheath 4 can maintain the seal of the needle body opening 6b, effectively preventing backflow and / or backflow of the fluid composition, preventing contamination near the floating seal 3, reducing fluid loss, and improving product reliability.

[0153] In some embodiments, the elastic sheath 4 is not used to seal the needle body opening 6b, but simply functions as an elastic engagement between the floating seal 3 and the actuator 2. In some embodiments, moving the actuator 2 forward compresses the elastic sheath 4 between the floating seal 3 and the actuator 2, thereby creating an elastic restoring force between the floating seal 3 and the actuator 2, which allows the floating seal 3 to be driven forward. In some embodiments, the elastic engagement between the floating seal 3 and the actuator 2 comprises or can consist of springs 5 ​​assembled to the axial ends of the floating seal 3 and the actuator 2, respectively. Assembly at one or both ends of the springs can be done directly or indirectly. Assembly at one or both ends of the springs can be retractable or non-retractable. The springs, floating seal, and actuator (e.g., a retaining element) can be manufactured separately and then assembled in any suitable order. Alternatively, any two or more of the springs, floating seal, and actuator (e.g., a retaining element) can be integrated, for example, as a one-piece. The spring 5 and the elastic sheath 4 may be implemented individually or in combination.

[0154] In some embodiments, elastic engagement between the floating seal 3 and the actuating member 2 may be achieved by means other than providing one or more elastic engaging parts. For example, the floating seal 3 and the actuating member 2 may be arranged as a one-piece integrated actuating unit (e.g., an elastic moving unit).

[0155] In some embodiments, devices and methods are provided for implanting into apparent or potential tissue cavities, cavity systems, and blood vessels using the medical puncture devices disclosed herein. For ease of understanding, a catheter is used as an example of an implantable medical device. In some embodiments, the methods disclosed herein include using a catheter guide structure to guide a catheter 11 into the needle body passage of a hollow puncture needle 6. In some embodiments, a catheter guide structure is provided within the medical puncture device disclosed herein.

[0156] In some embodiments, as shown in Figures 6-8, the catheter guide structure is provided within or engages with the floating seal 3 and includes an inclined guide groove 3a that extends at an angle toward the hollow puncture needle 6. In some embodiments, the fluid composition can be expanded into an apparent or potential tissue cavity, or blood vessel when the fluid composition lumen 7, the needle body opening 6b, and the distal needle opening 6a are connected. In some embodiments, the catheter 11 may be implanted in the expanded apparent or potential tissue cavity, or blood vessel through the inclined guide groove 3a, the needle body opening 6b, the needle body passage 6 of the hollow puncture needle, and the distal needle opening 6a.

[0157] The inclined guide groove 3a may be a groove that penetrates the floating seal 3 in the proximal / distal direction, or it may be a non-penetrating groove formed on the near end surface of the floating seal 3.

[0158] In some embodiments, the inclined guide groove 3a is a through groove. In some embodiments, the catheter guide structure further includes a valve 9 positioned within or engaging with the inclined guide groove 3a, which may be a check valve configured to be openable and closable. In some embodiments, the valve includes a plurality of leaflets configured to open and close the valve. In some embodiments, in the absence of external force, the check valve 9 is closed to prevent the fluid composition in the fluid composition lumen 7 from leaking through the valve. In some embodiments, when an opening force is present, the plurality of leaflets of the valve can be forced open so that the catheter 11 passes through the valve to the needle body opening 6b. In some embodiments, the catheter guide structure further includes a guide groove plug configured to be removably inserted into the inclined guide groove 3a, and the guide groove plug may be withdrawn when it is necessary to implant the catheter 11.

[0159] In some embodiments, the inclined guide groove 3a is a non-penetrating groove. In some embodiments, the inclined guide groove is directly punctured by the implanted catheter 11. In some embodiments, the inclined guide groove is punctured by a puncture component other than the catheter, and the catheter 11 can enter the needle body opening 6b through the puncture opening.

[0160] In some embodiments, in order to align the guiding direction of the inclined guide groove 3a, the needle body opening 6b may be provided as an inclined opening that is tilted backward so as to align with the inclined guide groove 3a, thereby accurately guiding the catheter 11 through the inclined guide groove into the needle body opening.

[0161] In some embodiments, for example as shown in Figures 9 and 10, the catheter guide structure includes an inclined guide needle hole 6c formed or positioned in the body wall of the hollow puncture needle 6 and opening inclined toward the rear. In some embodiments, for example when the medical puncture device is in fluid communication, the inclined guide needle hole 6c is maintained proximal to the floating seal 3. In some embodiments, the catheter 11 may pass through the inclined guide needle hole 6c into the needle body passage of the hollow puncture needle 6. In some embodiments, the catheter 11 may be implanted through the distal needle opening 6a into an apparent or potential tissue void, cavity or blood vessel (or an apparent or potential tissue void, cavity or blood vessel expanded with a fluid composition).

[0162] In some embodiments, the catheter guide structure may further include a valve 9 positioned in or engaging with the inclined guide needle hole 6c, which may be a check valve configured to be openable and closable. In some embodiments, the valve includes a plurality of leaflets configured to open and close the valve. In some embodiments, in the absence of external force, the check valve 9 is closed to prevent the fluid composition in the fluid composition lumen 7 from leaking through the valve. In some embodiments, when an opening force is present, the plurality of leaflets of the valve may be forcibly opened so that the catheter 11 penetrates through the valve and the inclined guide needle hole 6c into the needle body passage (this passage may be connected to or separated from the needle body passage, connecting the needle body opening 6b and the distal needle opening 6a). In some embodiments, the catheter guide structure further includes a needle hole plug 10 configured to be removably inserted into the inclined guide needle hole 6c, which may be withdrawn to initiate the implantation operation of the catheter 11. In some embodiments, the guide needle hole 6c is connected to the distal needle opening 6a. The needle body passage connecting the distal needle opening 6a and the needle body opening 6b may be the same as, or separate from, the needle body passage connecting the distal needle opening 6a and the guide needle hole 6c. In some embodiments, the guide needle hole 6c is connected to a distal needle opening other than the distal needle opening 6a connected to the needle body opening 6b. The needle body passage connecting the needle body opening 6b to the distal needle end may be completely separate from the needle body passage connecting the guide needle hole 6c to the distal needle end. The needle body passage connecting the needle body opening 6b to the distal needle end may at least partially overlap with, or be in fluid communication with, the needle body passage connecting the guide needle hole 6c to the distal needle end.

[0163] In some embodiments, for example as shown in Figure 11, the catheter guide structure includes a central guide groove 2c formed or positioned on the proximal surface of the working member 2. In some embodiments, the central guide groove 2c may include a hole or a hole may be formed in the center of the proximal surface of the working member 2. In some embodiments, the central guide groove 2c may be punctured to create a hole. In some embodiments, the proximal needle opening is positioned on the hollow puncture needle 6 and aligned with the central guide groove 2c along its axis. In some embodiments, when it is necessary to implant the catheter 11, the central guide groove 2c can be punctured, and the catheter 11 can pass through the puncture opening of the central guide groove 2c and the proximal needle opening of the hollow puncture needle 6 into the needle body passage (this passage may be connected to or separate from the needle body passage that connects the needle body opening 6b and the distal needle opening 6a). In some embodiments, the catheter 11 may be implanted through a distal needle opening, such as the distal needle opening 6a or a different distal needle opening, into an apparent or potential tissue void, cavity, or blood vessel (or an apparent or potential tissue void, cavity, or blood vessel that has been expanded with a fluid composition).

[0164] In some embodiments, the Specified herein discloses a kit comprising components configured to be assembled to form a medical puncture device as disclosed herein.

[0165] In some embodiments, a kit for assembling a medical puncture device includes a puncture control module and a fluid composition storage module (e.g., a fluid storage module). In some embodiments, the puncture control module and the fluid composition storage module are manufactured and / or supplied independently. In some embodiments, the puncture control module includes a first syringe unit, an actuation unit (e.g., an elastic transfer unit), and a hollow puncture needle 6 disposed within the syringe barrel of the first syringe unit. Based on the embodiments disclosed herein, it can be seen that the puncture control module may further include other parts or components such as an elastic sheath 4 and a spring 5. In some embodiments, the fluid storage module includes a second syringe unit, a fluid composition lumen 7 formed within the syringe barrel of the second syringe unit, and a module packaging component detachably disposed at the proximal end of the second syringe unit. In some embodiments, a detachable connecting structure is formed between the first syringe unit and the second syringe unit. In some embodiments, the first syringe unit and the second syringe unit are connected to each other to form a syringe barrel 1. Based on the embodiments disclosed herein, it can be seen that the fluid storage module may further include other parts such as the distal seal 8.

[0166] In some embodiments, the puncture control module and the fluid storage module may be manufactured, assembled, and / or packaged separately and then assembled together, and optionally with other modules, components, and / or parts, to form the medical puncture device disclosed herein. In some embodiments, the module packaging component is used to seal the proximal end of the fluid composition lumen 7. In some embodiments, the module packaging component may be removed when assembling the puncture control module and the fluid storage module.

[0167] In some embodiments, medical device assemblies and systems comprising them are provided herein. As shown in Figures 7 and 11, in some embodiments, the medical device assembly comprises a catheter 11 and a medical puncture device including a catheter guide structure disclosed herein. In some embodiments, the catheter 11 may be implanted via the medical puncture device into an apparent or potential tissue gap, cavity, or blood vessel. The medical device assemblies described herein may have all the technical effects provided by the medical puncture device.

[0168] In some embodiments, the medical device assembly includes a hollow auxiliary guide needle 12 used in conjunction with a catheter guide structure. In some embodiments, the needle body passage of the auxiliary guide needle 12 has a diameter large enough to accommodate the catheter 11 and allow the catheter to penetrate. In some embodiments, during the procedure to implant the catheter 11, the auxiliary guide needle 12 is connected to the catheter guide structure so that the catheter 11 passes sequentially through the needle body passage of the auxiliary guide needle 12, the catheter guide structure, the needle body passage of the hollow puncture needle 6, and then through the distal opening 6a of the needle to enter an apparent or potential tissue cavity, or blood vessel. In some embodiments, before implanting the catheter, the apparent or potential tissue cavity, or blood vessel is expanded with a fluid composition using the medical puncture device disclosed herein. In some embodiments, when the apparent or potential tissue cavity, or blood vessel is expanded with a fluid composition using the medical puncture device disclosed herein, the catheter is implanted. In some embodiments, the catheter is implanted before a visible or potential tissue void, cavity, or blood vessel is expanded with a fluid composition using the medical puncture device disclosed herein.

[0169] In some embodiments, as shown in Figure 7, the catheter guide structure includes a through-angled guide groove 3a and a check valve 9 embedded in the angled guide groove 3a that can be opened and closed. In some embodiments, the needle body opening 6b is provided as an angled opening that is angled backward. In some embodiments, when the catheter 11 is implanted, the auxiliary guide needle 12 is used to open the check valve 9, allowing the auxiliary guide needle to be positioned within the angled guide groove 3a. In some embodiments, the distal end of the auxiliary guide needle 12 is advanced into the needle body opening 6b, and the catheter 11 may sequentially pass through the needle body passage of the auxiliary guide needle 12, the needle body passage of the hollow puncture needle 6, and the distal needle opening 6a, and then be implanted in an apparent or potential tissue gap, cavity, or blood vessel.

[0170] In some embodiments, as shown in Figure 11, the catheter guide structure includes a central guide groove 2c. In some embodiments, the proximal needle opening is formed in the hollow puncture needle 6 and is aligned with the central guide groove 2c along its axis. In some embodiments, when implanting the catheter 11, the central guide groove 2c can be punctured by the auxiliary guide needle 12 so that the auxiliary guide needle 12 is axially aligned with the proximal opening of the hollow puncture needle 6. In some embodiments, the catheter 11 is advanced into the needle body passage of the hollow puncture needle 6 by sequentially passing through the needle body passage of the auxiliary guide needle 12 and the proximal opening of the hollow puncture needle 6, and then implanted into an apparent or potential tissue gap, cavity, or blood vessel through a distal needle opening such as the distal needle opening 6a.

[0171] In some embodiments, the retaining shaft (e.g., retaining shaft 2 in Figure 12) includes a threaded portion configured to screw with a control knob 1 (e.g., control knob 17 in Figure 12). For example, the control knob may include an internal helical thread configured to engage with the threaded portion of the retaining shaft. In some embodiments, the control knob can rotate along a central axis, and the screwing may cause the rotation of the control knob to drive and translate the axial direction of the retaining shaft. In some embodiments, the retaining shaft moves axially relative to the housing (or shell) 22 along a helical path having rotational and translational components. In some embodiments, the translational motion of the retaining shaft may be distal (e.g., toward the subject's eyes) or proximal (e.g., toward the practitioner), depending on whether the control knob is rotated clockwise or counterclockwise. In some examples, clockwise rotation of the control knob advances the retaining shaft distally, while counterclockwise rotation of the control knob retracts the retaining shaft proximally. In another example, counterclockwise rotation of the control knob advances the retaining shaft distally, while clockwise rotation of the control knob retracts the retaining shaft proximally.

[0172] In some embodiments, a retainer shaft (e.g., retainer shaft 2 in Figure 12) is coupled to a syringe needle (e.g., syringe needle 6 in Figure 12) such that axial movement of the retainer shaft causes and / or allows movement of the syringe needle. In some embodiments, the retainer shaft is directly coupled to the syringe needle. In some embodiments, the retainer shaft is indirectly coupled to the syringe needle. In some embodiments, the retainer shaft is elastically coupled to the syringe needle. In some embodiments, the retainer shaft and the syringe needle elastically engage with each other. In some embodiments, the retainer shaft and the syringe needle are coupled via an elastic connection. In some embodiments, the retainer shaft and the syringe needle are fixedly or detachably coupled. In some embodiments, the retainer shaft and the syringe needle engage with each other fixedly or detachably. In some embodiments, the retainer shaft and the syringe needle are coupled by a fixed connection. In some embodiments, the connection between the retainer shaft and the syringe needle is sufficiently rigid so that the retainer shaft can drive the syringe needle forward or backward. In some embodiments, the syringe needle is part of the retainer shaft or is positioned on a needle base or seat directly or indirectly coupled to the retainer shaft. In some embodiments, the needle base or seat extends axially and has a smaller cross-sectional area than the portion of the retainer shaft directly adjacent to the needle base or seat. In some embodiments, the needle base or seat is fixedly coupled to the retainer shaft. In some embodiments, the needle base or seat is integrated with the retainer shaft. In some embodiments, the retainer shaft and the syringe needle are coupled by a needle base or seat that is at least sufficiently rigid in the axial direction so that the retainer shaft can be moved axially to its distal or proximal end to advance or retract the syringe needle relative to the housing or shell.

[0173] In some embodiments, the retainer shaft (e.g., retainer shaft 2 in Figure 12) and the piston rod (e.g., the push rod 15 in Figure 12) are connected by an elastic element or elastic piece, such as a spring (e.g., spring 5 in Figure 12). In some embodiments, the elastic element or elastic piece is directly or indirectly connected to the retainer shaft and / or the needle base or sheet or a part thereof. For example, a part of the elastic element or elastic piece (e.g., the proximal end) may directly or indirectly engage with the retainer shaft or a part of the needle base or sheet. The elastic element or elastic piece may be fixedly or detachably engaged with the proximal part of the needle base or sheet. In some embodiments, the elastic element or elastic piece is directly or indirectly connected to the piston rod. For example, a part of the elastic element or elastic piece (e.g., the distal end) may directly or indirectly engage with a part of the piston rod (e.g., the proximal end). In some embodiments, the elastic element or elastic piece is fixedly or detachably connected to the piston rod. In some embodiments, the retaining shaft is biased distally to the housing, applying force to an elastic element or elastic piece (e.g., a spring), which in turn applies force to the piston rod, while the syringe needle is simultaneously biased distally by the retaining shaft.

[0174] In some embodiments, the needle base or seat or a portion thereof extends axially, a space is provided between a portion of the retaining shaft and the piston rod, and the piston rod is configured to house one or more elastic elements or elastic pieces. In embodiments using multiple elastic elements or elastic pieces, any two or more elastic elements or elastic pieces can be arranged in series or in parallel. Each elastic element or elastic piece may be in the form of a flexible sheath or tube, a spring, an annular ring, an elongated rod or strip, or any combination thereof. The elastic elements or elastic pieces are arranged parallel to the needle base or seat and / or can pass through the needle base or seat. For example, the elongated needle base or seat may pass through a spring coil, with the proximal end of the spring engaging with the proximal part of the elongated needle base or seat and the distal end of the spring engaging with the proximal part of the piston rod. The distal part of the elongated needle base or seat may be inserted into the inner lumen of the piston rod, and all or part of the syringe needle may be housed in the inner lumen of the piston rod. In some embodiments, the syringe needle is positioned within the inner lumen without penetrating the distal end of the piston rod or a seal assembled to the piston rod (e.g., plunger seal 3 in Figure 12) before medical penetration using the syringe needle. Thus, in some embodiments, the retaining shaft (e.g., including or connected to an elongated needle base or seat) may be configured to elastically engage with the piston rod (e.g., by a spring 5 in Figure 12), allowing the distal end of the piston rod to engage with the seal and configure the seal as a floating seal.

[0175] In some embodiments, the piston rod (e.g., the push rod 15 in Figure 12) is configured to receive and / or house a syringe needle (e.g., the syringe needle 6 in Figure 12) or at least a portion thereof. In some embodiments, the piston rod is hollow. In some embodiments, the piston rod includes an inner lumen configured to receive and / or house a syringe needle or at least a portion thereof. The inner lumen of the piston rod may, but is not required, be configured to receive and / or house a fluid composition (e.g., a pharmaceutical composition). In some embodiments, the inner lumen of the piston rod contains a gas (e.g., air) and houses the syringe needle, but does not contain a liquid such as a drug solution. In some embodiments, the piston rod may be used to aspirate a fluid composition. In some embodiments, the piston rod may be pulled by a handle (e.g., the handle 21 in Figure 12) to aspirate the fluid composition into a syringe (e.g., the syringe 1 in Figure 12). In some embodiments, the piston rod may be used to inject the fluid composition. In some embodiments, the piston rod may be pressed by a retaining shaft (e.g., by spring 5 in Figure 12), and the syringe needle in the piston rod may pass through a seal at the distal end of the piston rod (e.g., plunger seal 3 in Figure 12). In some embodiments, there is a needle body opening between the proximal and distal ends of the syringe needle, and the fluid composition in the syringe can come into contact with the needle body opening when the needle body opening is distal to the seal. In some embodiments, a needle body passage connects the needle body opening to the distal needle opening, and the pressure difference between the needle body opening (e.g., when it is in the syringe and in contact with the fluid composition) and the distal needle opening drives the fluid composition through the needle body passage, thereby allowing the fluid composition to be injected (through the distal needle opening) into apparent or potential tissue cavities, or blood vessels.

[0176] In some embodiments, a portion of the piston rod (e.g., the push rod 15 in Figure 12) is configured to engage with a guide tube (e.g., the guide tube 16 in Figure 12). In some embodiments, the guide tube is a tube located inside the housing. In some embodiments, the guide tube is located inside another tube within the housing. In some embodiments, a portion of the piston rod slidably engages with the inner surface of the guide tube so that the piston rod can move axially relative to the guide tube. In some embodiments, a portion of the retainer shaft is configured to engage with the guide tube. In some embodiments, a portion of the retainer shaft slidably engages with the inner surface of the guide tube so that the retainer shaft can move axially relative to the guide tube to move the syringe needle. In some embodiments, the guide tube may include an inner surface structure (e.g., one or more axial ridges or grooves) that slidably engages with a corresponding structure (e.g., one or more axial ridges or grooves) located on the outer surface of the retainer shaft and / or on the piston rod. The corresponding structures (e.g., axial ridges and grooves) can allow axial sliding movement of the retaining shaft and / or piston rod while maintaining positional stability and / or minimizing movement of the syringe needle in other directions (e.g., radially). In some embodiments, the proximal portion of the piston rod includes projections (e.g., one or more annular ridges) that engage with the inner surface of the guide tube. Thus, in some embodiments, the piston rod is slidably engaged with the inner surface of the guide tube and can move axially relative to the guide tube by engaging with a spring, and can therefore be considered a floating structure. In some embodiments, the guide tube is fixed to the housing.

[0177] In some embodiments, the distal end of a piston rod (e.g., push rod 15 in Figure 12) is configured to engage with a seal (e.g., plunger seal 3 in Figure 12). In some embodiments, the piston rod is configured to slidably engage with the inner surface of a syringe (e.g., syringe 1 in Figure 12). In some embodiments, the seal is a floating seal that slidably and tightly engages with the inner surface of the syringe. In some embodiments, the seal separates the proximal and distal lumen formed by the syringe barrel of the syringe, and the distal lumen of the syringe is configured to aspirate and / or store the fluid composition. In some embodiments, the seal, together with the syringe barrel of the syringe, forms a lumen configured to aspirate and / or store the fluid composition. In some embodiments, the seal is located at the distal end of a piston rod inserted into the syringe.

[0178] In some embodiments, the syringe (e.g., syringe 1 in Figure 12) is configured to engage with a housing. In some embodiments, the proximal end of the syringe engages fixedly or detachably with the housing. In some embodiments, the distal end of the syringe engages fixedly or detachably with a distal seal (e.g., seal tip 8 in Figure 12). In some embodiments, the inner lumen of the syringe is configured to aspirate and / or store a fluid composition, such as a pharmaceutical composition. In some embodiments, the inner lumen, configured to contain the fluid composition, is located distal to a floating seal (e.g., a plunger seal) and proximal to the distal seal (or seal tip), and is formed by seal engagements between the syringe and the floating seal and between the syringe and the distal seal. In some embodiments, the distal seal seals and engages distally with the syringe. In some examples, the distal seal may be pressed against the distal end of the syringe to form a seal engagement. Exemplary configurations of distal seals are shown in Figures 16A to 16C, and distal seals may have a flat distal portion, a spherical distal portion, or a tapered distal portion. Distal seals may have a distal portion having a flat distal surface, a convex surface, a spherical surface, a concave surface, or any other suitable shape of distal surface.

[0179] In some examples, the distal seal may include a proximal portion that is inserted into the syringe to form a sealing engagement with the inner surface of the syringe. In some examples, the portion of the distal seal and the inner surface of the syringe may include corresponding structures that engage with each other (e.g., projections such as threads or ridges, such as annular ridges, and grooves, such as annular grooves). For example, the portion of the distal seal may include threads on its outer surface that engage with threads on the inner surface of the distal portion of the syringe. In some examples, the distal seal may include a portion that engages with the outer surface of the syringe. In some examples, the portion of the distal seal and the outer surface of the syringe may include corresponding structures that engage with each other (e.g., projections such as threads or ridges, and grooves, such as grooves). For example, the portion of the distal seal may include threads on its inner surface that engage with threads on the outer surface of the distal portion of the syringe.

[0180] In some examples, the distal seal may include a proximal portion that engages with a gland (e.g., gland 23 shown in Figure 12). In some examples, the inner surface of the gland and the outer surface of the syringe may include corresponding structures that engage with each other, for example, by threading (e.g., projections such as threads or ridges, such as annular ridges, and grooves such as annular grooves). In some examples, the gland engages with the distal seal at the annular groove 24, pressing the distal seal against the distal opening of the syringe barrel to form a seal engagement.

[0181] In some embodiments, the devices disclosed herein include a stopper such as the limiter 18 in Figure 12. In some embodiments, the stopper can limit the maximum length of axial movement of the retainer shaft, for example, to achieve precise injection. In some embodiments, the stopper may be used to limit the rotation and / or radial movement of the retainer shaft, for example, to prevent or minimize deviation of the retainer shaft (and the needle base and syringe needle connected thereto) from the central axis of the assembled device. In some embodiments, the stopper may engage with the guide tube. In some embodiments, the stopper may be fixedly or detachably engaged with the proximal end of the guide tube. In some embodiments, the guide tube may be used to guide the movement of the retainer shaft and piston rod, for example, by a corresponding structure of the component, to achieve precision in the axial movement of the retainer shaft and piston rod and precision in the movement of the syringe needle. In some embodiments, during transport and storage of the assembled device, and during use for medical penetration, the device prevents or minimizes rotation and / or displacement (e.g., from the central axis) of the retaining shaft, piston rod, needle base or seat, and / or syringe needle by a combination of features (e.g., stopper and guide tube).

[0182] In some embodiments, the devices disclosed herein include a ruler such as the ruler 19 in Figure 12. In some embodiments, the ruler may be used to measure, or otherwise determine, the distance between a penetration site (e.g., the site through which the syringe needle penetrates) and the corneal margin, which is the boundary between the cornea and the sclera. In some embodiments, the distal end of the ruler may be configured to contact a portion of the eye at the injection site. In some embodiments, projections of the ruler may be configured to leave a marker on a portion of the eye, such as the injection site. For example, the marker may indicate the injection site. For example, the marker may appear as parallel marker lines on the conjunctiva of the eye, indicating to the user that the injection should be performed in the area between the parallel marker lines. In some embodiments, the ruler may be detachably coupled to a delivery device, for example, at the distal end of the delivery device (e.g., to the distal seal 8 in Figure 12, or to the contact element 1b in Figure 1A). In such embodiments, the ruler may be removed from the delivery device after marking the injection site on the target tissue.

[0183] In some embodiments, the device disclosed herein includes an adapter such as adapter 20 in Figure 12. In some embodiments, the adapter may include a distal end including a plurality of distal petals and / or a proximal end including a plurality of proximal petals. In some embodiments, the adapter may include an adapter pin. In some embodiments, the adapter may be used to transfer a fluid composition from a container (e.g., a vial) to a syringe of the device disclosed herein. In some embodiments, the syringe may be inserted into the proximal end of the adapter. For example, a distal seal (e.g., seal tip 8 in Figure 12) may be inserted into the adapter so that the adapter needle contacts and penetrates the distal seal, establishing fluid communication with the inner lumen of the syringe, which is distal to the floating seal. The fluid communication can allow gas, liquid, or a mixture thereof to pass through. In some embodiments, for example, the adapter needle may be inserted into a container (e.g., a vial) containing a fluid composition (e.g., a drug solution) so that the adapter needle penetrates the seal of the container, thereby establishing fluid communication between the inner lumen of the syringe and the inside of the container. In some embodiments, a handle configured to engage with the proximal end of the piston rod (e.g., handle 21 in Figure 12) may be used to push and / or pull the piston rod axially relative to the syringe. For example, the handle may be pulled proximal to draw a fluid composition from a container into the inner lumen of the syringe via the adapter needle. In another example, the handle may be pushed distally to expel gas and / or liquid via the adapter needle. For example, by pulling the handle proximal, liquid (e.g., drug solution) and unwanted gas (e.g., air) can be drawn into the syringe, and then by pushing the handle distally (e.g., upward), the assembly including the syringe and adapter can be positioned on the adapter needle (e.g., vertically) so that the unwanted gas can be expelled via the adapter needle and the fluid composition can remain in the syringe.

[0184] In some embodiments, this specification provides a method for performing medical penetration using the devices described herein. In some embodiments, a pre-assembled device is provided, as shown in Figure 13A. In some embodiments, the housing of the pre-assembled device can be rotated to separate the syringe from the body of the device. In some embodiments, the proximal end of the syringe may screw onto the distal end of the housing. For example, as shown in Figure 13B, the proximal end of the syringe may include a thread groove on its inner surface configured to engage with threads on the outer surface of the distal end of the housing.

[0185] In some embodiments, after the syringe is separated, the proximal end of the piston rod is exposed. As shown in Figure 13C, the handle may be assembled to the piston rod, for example, by screwing it onto the proximal end of the piston rod. In some embodiments, an adapter containing an adapter needle may be assembled to the syringe. In some embodiments, the adapter includes a distal opening and a proximal opening. In some embodiments, the distal end of the syringe (e.g., where a distal seal is assembled) is inserted into the proximal opening of the adapter so that the adapter needle contacts the distal seal assembled to the syringe. In some embodiments, the proximal end of the adapter needle penetrates the distal seal assembled to the syringe so that the proximal opening of the adapter needle is located within the inner lumen of the syringe. In some embodiments, a container or part thereof containing a fluid composition (e.g., a pharmaceutical composition) is inserted into the distal opening of the adapter so that the adapter needle contacts the container. In some embodiments, the distal end of the adapter needle is inserted into the container such that the distal opening of the adapter needle is inside the container and a fluid communication can be established between the fluid composition and the inner lumen of the syringe. In some embodiments, unwanted gas can be discharged by pulling the handle to move the piston rod proximal, drawing the fluid composition into the inner lumen of the syringe through the adapter needle, and pushing the handle to move the piston rod distally. As shown in Figure 13D, by pulling and / or pushing the handle, the distal end of the piston rod and the seal inside the syringe can be positioned to set an appropriate volume of fluid composition in the syringe, for example, 0.1 ml or 0.05 ml, and the handle and adapter can be removed from the piston rod and syringe, respectively. As shown in Figure 13E, a syringe containing a fluid composition can be connected to the device body by, for example, inserting a syringe needle (e.g., 6 shown in Figure 13B) into a piston rod (e.g., 15 shown in Figure 13D), inserting the piston rod into a guide tube inside the housing, and screwing the proximal end of the syringe to the distal end of the housing.

[0186] After assembly, the retaining shaft can be biased to a distal position. In some embodiments, the position is predetermined. In some embodiments, the position may be adjusted as needed. In some embodiments, the retaining shaft is pressed to a position in which an elastic element or elastic piece (e.g., a spring) is compressed. In some embodiments, the seal tip may contact the eye, such as an area within the sclera of the eye, and maintain a stable position. In some embodiments, a control knob can be rotated to advance the retaining shaft distally, thereby advancing the syringe needle assembled to the retaining shaft distally toward and / or through the seal in the syringe. The seal may be a floating seal, and the syringe needle can penetrate the seal by piercing it or by inserting into a pre-existing hole in the seal. The syringe needle can advance further, passing the seal tip and piercing the sclera of the eye, as shown in Figure 13F. In some embodiments, because the sclera is a dense tissue, the pressure at the distal opening of the syringe needle is greater than the pressure at the body opening of the syringe needle, and the body opening may be in fluid communication with the fluid composition in the syringe, in which case the syringe needle may be advanced further into the sclera without changing the position of the floating seal in the syringe. In some embodiments, the position of the floating seal in the syringe is monitored when the practitioner presses the retaining shaft to advance the syringe needle. When the distal opening of the syringe needle is outside the sclera and enters the choroid / ciliary body, the pressure at the distal opening of the syringe needle decreases, and the pressure at the body opening of the syringe needle drives the fluid composition to be expelled through the needle body passage and through the distal opening of the syringe needle, thereby creating and expanding a suprachoroidal space containing a fluid composition that may include liquids, solutions, suspensions, gels, oils, ointments, emulsions, creams, foams, lotions, and / or pastes. As some of the fluid composition inside the syringe is discharged, the seal (along with the piston rod) moves to a more distal position within the syringe.Therefore, by observing the movement of the seal, the practitioner can determine whether the distal opening of the syringe needle has moved away from the first tissue and reached a less dense second tissue, for example, entering the choroid / ciliary body from the sclera. In some embodiments, once the seal has moved and passed a preset volume marker or indicator line (e.g., 0.1 ml or 0.05 ml), the distal advance of the syringe needle is stopped (e.g., by scrolling or pressing a control knob). In some embodiments, the position of the syringe needle is held for a period of time, e.g., 1s, 2s, 3s, 4s, 5s, 6s, 7s, 8s, 9s, 10s or longer, during which a spring acts on the piston rod, releasing the spring tension and allowing the seal to move distally. In some embodiments, the tension of the spring pushes the piston rod and the seal assembled thereto (e.g., not to move the position of the syringe needle in the tissue) to a predetermined more distal position in the syringe (e.g., the distal end of the syringe lumen), thereby sufficient to inject a predetermined volume of the fluid composition into the tissue (e.g., into the suprachoroidal lumen). In some embodiments, the predetermined volume is about 0.05 ml, about 0.075 ml, about 0.1 ml, about 0.125 ml, about 0.15 ml, about 0.175 ml, about 0.2 ml or more. In some embodiments, a handle and adapter are used to set the predetermined volume when the fluid composition is drawn into the syringe, for example, as shown in Figure 13D. After injection, the syringe needle can be removed from the tissue.

[0187] In some cases, as shown in Figures 13A-13F, for example, the syringe is not pre-filled with fluid material or composition, and the fluid material or composition is drawn from the container into the syringe before being delivered to tissue or visible or potential voids, cavities, or blood vessels within the tissue.

[0188] In some embodiments, the syringe of the device disclosed herein may be pre-filled with a fluid material or composition, for example, as shown in Figures 17A-17B. In some embodiments, the syringe (e.g., syringe 1 shown in Figure 12) may be provided in one or more parts. In some embodiments, as shown in Figures 17A-17B, for example, the container (e.g., syringe unit) may include a tubular wall that seals and engages with a fixed seal (which can be fixed to the container at the distal end of the container and is passable through the needle) and a floating seal (which is movable within the container and is passable through the needle), and the space enclosed by the tubular wall, the fixed seal and the floating seal may be pre-filled with a fluid material or composition. In some embodiments, the device or system may include a first syringe unit, and the container may be a second syringe unit configured to engage with the distal end of the first syringe unit. Before or after filling the container (e.g., syringe unit) with a fluid material or composition, the container (e.g., syringe unit) may be inserted into or assembled into the device body (e.g., first syringe unit). In some embodiments, a floating seal within the container (e.g., syringe unit) may contact the distal end of the piston rod to establish an engagement between the piston rod and the floating seal, and force is transmitted from this spring to the floating seal. A fixed seal at the distal end of the container (e.g., syringe unit) may contact a contact element at the distal end of the device, the contact element may be the distal seal of the syringe, as shown in Figure 17. In some embodiments, the fixed seal of the container (e.g., syringe unit) is also used as the distal seal and / or contact element of the syringe, as shown, for example, in Figure 17B. In some embodiments, the container (e.g., syringe unit) may be configured to be at least partially inserted into the syringe barrel, as shown, for example, in Figures 17A-17B. In some embodiments, a fixed seal seals and engages with a container (e.g., a syringe unit), which then engages with the inner wall of the syringe barrel.In some embodiments, the fixing seal seals and engages with both the container (e.g., syringe unit) and the inner wall of the syringe barrel. The engagement between the container (e.g., syringe unit) and the syringe barrel, and the engagement between the fixing seal and the container wall, may include any suitable engagement by insertion, screwing, unscrewing, clipping, glanding, or any combination thereof.

[0189] In some embodiments, the devices disclosed herein allow for precise control of the syringe needle as it passes through one or more tissues, and are particularly suitable for accessing apparent or latent tissue gaps, cavities, or blood vessels, such as potential spaces between two adjacent tissues of different densities. In some embodiments, the devices disclosed herein allow for precise access to the suprachoroidal space while reducing or minimizing the risk of insufficient penetration and / or overshoot, e.g., the risk of the needle penetrating too deeply into the choroid / ciliary body and / or damaging the retina. In some examples, the axial movement of the syringe needle can be controlled, and micron-level precision can be achieved as it advances through the tissue. In some examples, the axial movement of the syringe needle within the tissue can be set within any distance that satisfies the requirement for the tip of the syringe needle to penetrate from the ocular surface to the suprachoroidal space. In some examples, the axial travel distance of the syringe needle within the tissue can be set to a length between approximately 0 and approximately 4.0 mm, such as between approximately 0 and approximately 0.5 mm, between approximately 0 and approximately 1.0 mm, between approximately 0 and approximately 1.5 mm, between approximately 0 and approximately 2.0 mm, or between approximately 0 and approximately 2.5 mm. In some embodiments, the device disclosed herein includes a syringe needle of the size and configuration disclosed herein (e.g., 6 shown in Figure 12), for example, the syringe needle having an oblique angle of approximately 0 to approximately 40 degrees, particularly approximately 5 to approximately 30 degrees, for example, approximately 15 to approximately 25 degrees. In some embodiments, the volume of the fluid composition delivered using the device disclosed herein (e.g., by injection) may be selected based on the conditions of a particular subject and may be adjusted in response to changes in conditions. In some embodiments, energy stored in an energy storage member (e.g., a spring) is automatically released, advancing a floating seal (e.g., via a piston rod 15 in Figure 12), thereby releasing a predetermined volume of fluid composition into visible or potential tissue voids, cavities, or blood vessels.In view of the various combinations of features disclosed herein, the devices and methods disclosed herein can enable the precise, safe, and controllable delivery of drugs to the subject's tissue, such as the suprachoroidal space, or to other apparent or latent tissue cavities, cavities, or blood vessels.

[0190] In some embodiments, devices or systems are disclosed herein for delivering substances (e.g., herbal medicines) subretinally based on access to the suprachoroidal space and / or delivery of the composition between the sclera and choroid / ciliary body of the eye. In some embodiments, the devices or systems disclosed herein include a cannula (e.g., a microcannula), a microneedle, and an operating module (e.g., including a handle or knob configured to control the advancement or retraction of the microneedle and the advancement or retraction of a flexible cannula). In some embodiments, the cannula includes a distal tip, which may include a sharp tip, a stylet, an oblique face, or a blunt tip. In some embodiments, the cannula includes a flexible body. In some embodiments, the cannula is configured to be inserted into a vesicle or protrusion in the suprachoroidal space via a passage created by a syringe needle used to inject a viscoelastic composition into the suprachoroidal space. In some embodiments, the operating module is configured to control the positioning and transport of the cannula to enable minimally invasive surgery. In some embodiments, the microneedle has a curved tip and is configured to be housed within a cannula. In some embodiments, the microneedle is configured to advance and / or retract through the inner lumen of the cannula. After the cannula has advanced to a position between the choroid / ciliary body and the sclera of the patient's eye, the distal tip of the microneedle can be exposed, for example, by advancing the microneedle through the cannula. In some embodiments, since the microneedle has a curved distal tip, the distal tip can pierce the choroid / ciliary body at a specific angle to allow the composition to be delivered subretinate without removing the vitreous humor or performing a retinal incision (e.g., by piercing the retina). In some embodiments, the proximal end of the cannula is configured to engage with a distal connector of a manipulation module. In some embodiments, the manipulation module includes one or more elements configured to engage with the microneedle to control the movement of the microneedle within the inner lumen of the cannula.In some embodiments, the distal connector of the operating module is configured to engage with one or more syringes via one or more adapters. In some embodiments, each syringe is connected to an adapter connected to the operating module. In some embodiments, one or more syringes may contain one or more compositions, such as a fluid material, a viscoelastic material, or an infusion fluid, and the delivery of the composition via a microneedle can be controlled.

[0191] In some embodiments, a fluid composition, such as a viscoelastic composition, can be injected into the eye between the sclera and the choroid / ciliary body via the syringe needle of an injection device disclosed herein to form a suprachoroidal space containing the fluid composition. In some embodiments, the viscoelastic material forms a vesicle or protrusion between the sclera and the choroid / ciliary body. In some embodiments, the distal tip of a linear member, such as a flexible cannula, may be positioned within the vesicle. In some embodiments, the distal tip of the linear member is positioned within the vesicle and advances through the inner lumen of the syringe needle to further advance between the sclera and the choroid / ciliary body (e.g., to reach the posterior part of the eye). In some embodiments, the distal tip of the linear member is inserted through the penetration site of the syringe needle and advances toward the vesicle along the path created by the syringe needle. The linear member can be inserted through the path created by the syringe needle while the syringe needle is held in the eye. In some embodiments, the linear member is parallel to the syringe needle, and they are adjacent to each other in the path created by the syringe needle. In some embodiments, the linear member is located within the lumen of the syringe needle. In some embodiments, the syringe needle is located within the lumen of the linear member.

[0192] In some embodiments, a linear member such as a cannula is a thin, flexible, hollow tube having a smooth, rounded tip at its distal end, while the opposing proximal end may have a hub (e.g., a plastic hub) that can be attached to a syringe. In some embodiments, the cannula includes a sharp distal tip. In some embodiments, the cannula includes a blunt distal tip. In some embodiments, the distal end of the cannula opens a pathway between structures in the tissue, thereby facilitating the dissection of structures while reducing tissue damage. In some embodiments, the cannula may include an opening at its distal end, for example, the blunt tip of the cannula. In some embodiments, the cannula may include a lateral opening in the side wall of the cannula, while the distal end may or may not include an opening.

[0193] In some embodiments, the distal tip of a linear member (e.g., a flexible cannula) within a vesicle of the fluid composition may extend further into the interior of the eye, for example, between the sclera and the choroid / ciliary body, expanding the suprachoroidal space toward the posterior part of the eye. In some embodiments, the linear member is configured to conform to the contour of the eyeball, approach the posterior part of the eye, and target a posterior subretinal position. In some embodiments, the fluid composition, such as a viscoelastic composition, lubricates the distal tip of the linear member to allow it to slide along the boundary between the sclera and the choroid / ciliary body, reducing resistance during intubation and / or reducing the risk of choroidal perforation or unintended retinal damage caused by the linear member. In some embodiments, the viscoelastic composition may form a protective layer around the distal tip of the linear member, which provides lubrication and guides the direction of the cannula.

[0194] In some embodiments, after the distal end of the linear member reaches a target location, for example, a downstream subretinal location, a composition such as an infusion solution may be delivered to the target location. The composition such as an infusion solution may be delivered through one or more openings of the linear member. In some embodiments, the microneedle within one or more openings of the linear member may penetrate the choroid / ciliary body once it reaches the target location. In some embodiments, when the tip of the microneedle presses against the choroid / ciliary body, a tissue bulge is visualized, and the microneedle stops advancing through the flexible cannula. In some embodiments, the composition such as an infusion solution may be delivered into the subretinal space without penetrating the retina (for example, by applying pressure to a syringe connected to the microneedle and containing the infusion solution). In some embodiments, the composition such as an infusion solution may form an entrance vesicle in the subretinal space. In some embodiments, the entrance vesicle in the subretinal space is observed, and the size of the vesicle is monitored. In some embodiments, the microneedle and / or flexible cannula may retract after the vesicle reaches a certain size.

[0195] In some embodiments, a device or system for delivering a therapeutic agent to the eye is disclosed. In some embodiments, the device or system includes a control module and a cannula extending distally from the control module, the cannula being of a size and structure that allows insertion between the choroid / ciliary body and sclera of the patient's eye, and the cannula defining a longitudinal axis. In some embodiments, the device or system includes a hollow needle including a proximal end, the needle being slidable relative to the cannula. In some embodiments, the device or system includes an actuator coupled to the proximal end of the hollow needle to cause the hollow needle to translate. In some embodiments, the hollow needle is configured to translate relative to the cannula to drive the distal portion of the needle along an exit axis oriented obliquely to the longitudinal axis of the cannula.

[0196] In some embodiments, the device or system includes a fluid source in fluid communication with the proximal end of the hollow needle. In some embodiments, the needle includes a sharp distal tip. In some embodiments, the sharp distal tip of the needle includes a first bevel, a second bevel, and an optional third bevel, and the first bevel, the second bevel, and the optional third bevel are each oriented at an angle to each other. In some embodiments, the exit axis is oriented at an angle of about 5° to about 30° with respect to the longitudinal axis of the cannula. In some embodiments, the exit axis is oriented at an angle between about 7° and about 9° with respect to the longitudinal axis of the cannula. In some embodiments, the cannula includes an angled distal end having an angled corner with an angled corner of about 10° to about 30°. In some embodiments, the cannula defines a plurality of lumens extending longitudinally along the length of the cannula, and at least one of the plurality of lumens is configured to slidably receive the needle. In some embodiments, the cannula has a flexural rigidity of 0.5×10 -6 , <00{00008}, -6 , -6 , -6 , -6 , -6 , -6 , -6 , -6 , -6 , -6 , -6 , -6 , -6 , -6 , -6 , <00000{11}Nm<00{00002}~12×10<00{00003}Nm<00{00004}In some embodiments, the cannula has a flexural rigidity of 2.0×10<00{00005}Nm<00{00006}""~8.0×10<00{00{007}{END]]Nm<00{00008}In some embodiments, the cannula has a flexural rigidity of about 1.0×10<00{00009}about 1.5×10<00{00010}about 2.0×10<00{00011}about 2.2×10<00{00012}about 2.4×10<00{00013}about 2.6×10{0000014} about 2.8×10<00{00015}about 3.0×10<00{00016}about 3.2×10<00{00017}about 3.4×10<00{00018}about 3.6×10<00{00019}about 3.8×10<00{00020}about 4.0×10<00{00021}about 4.2×10<00{00022}about 4.4×10<00{00023}about 4.6×10<00{00024}, about 4.8×10 -6 , about 5.0×10 -6 , about 5.2×10 -6 , about 5.4×10 -6 , about 5.6×10 -6 , about 5.8×10 -6 , about 6.0×10 -6 , about 6.2×10 -6 , about 6.4×10 -6 , about 6.6×10 -6 , about 6.8×10 -6 , about 7.0×10 -6 , about 7.2×10 -6 , about 7.4×10 -6 , about 7.6×10 -6 , about 7.8×10 -6 , about 8.0×10 -6 , about 8.5×10 -6 , about 9.0×10 -6 , about 9.5×10 -6 , about 10.0×10 -6 , about 10.5×10 -6 , about 11.0×10 -6 , or approximately 11.5 × 10 -6 Nm 2 It has bending rigidity.

[0197] In some embodiments, this specification provides a method of using a device or system comprising a cannula and a hollow needle movable relative to the cannula. In some embodiments, the method comprises forming an incision in the patient's eye and inserting the cannula through the incision, which extends through the scleral layer of the eye and provides a passage to the suprachoroidal space of the eye. In some embodiments, the incision may be formed by a syringe needle of a device or system disclosed herein, such as the syringe needle 6 in Figures 1A-1E-11A-11B, or the syringe needle 6 in Figures 12 and 13A-13F.

[0198] In some embodiments, the method includes making an incision in at least a portion of the eye to provide access to the choroid / ciliary body of the eye. In some embodiments, the method includes guiding a cannula into the incision formed by making an incision in at least a portion of the eye. In some embodiments, the method includes advancing the cannula between the choroid / ciliary body and the sclera to position the distal end of the cannula in the posterior region of the suprachoroidal space. In some embodiments, at least a portion of the inserted cannula is flexible and conforms to the curvature of the eye during positioning of the distal end of the inserted cannula by advancing the cannula tangentially along at least one of the choroid / ciliary body layer or the scleral layer of the eye in the space between the choroid / ciliary body layer and the scleral layer of the eye, for example. In some embodiments, the method includes guiding the cannula to the injection site (e.g., downstream) by direct visualization of the pupil of the eye.

[0199] In some embodiments, the method includes advancing a needle through a cannula to penetrate the choroid / ciliary body. In some embodiments, the method includes advancing the needle relative to the cannula, passing through the choroid / ciliary body, and entering the subretinal space without penetrating the retina. In some embodiments, the needle advances from the distal end of a flexible cannula along a path across the longitudinal axis defined by the flexible cannula, with the distal end of the needle piercing the choroid / ciliary layer of the eye. In some embodiments, the method includes delivering a composition, such as a composition containing a therapeutic agent, to the subretinal space via the advanced needle. In some embodiments, the method includes delivering leading vesicles via the advanced needle before delivering the composition containing a therapeutic agent via the advanced needle.

[0200] For example, as shown in Figure 18, a method for delivering a fluid composition to a subject's eye using a device or system disclosed herein is disclosed. In some embodiments, a syringe needle is inserted into the eye, with the distal opening of the needle positioned between the sclera and the choroid / ciliary body of the eye. In some embodiments, the fluid composition enters the needle body opening and is discharged through the needle body passage (for example, by the force applied by the spring 5 to the piston rod 15 and floating seal 3, as shown in Figure 12) from the distal opening of the needle into the suprachoroidal space (SCS) within the eye. As shown in Figure 18, a viscoelastic material can be injected between the sclera and the choroid / ciliary body to form the SCS, and the viscoelastic material can facilitate the separation of the choroid / ciliary body from the sclera, further expanding the SCS. The viscoelastic material can also lubricate a flexible cannula inserted into the SCS, helping to direct the tip of the cannula towards the posterior part of the eye between the sclera and the choroid / ciliary body, while minimizing the risk of the distal tip of the cannula passing through the choroid / ciliary body and entering the retina. Therefore, as shown in Figure 18, in some embodiments, after the SCS is formed, the syringe needle can be removed, leaving the SCS filled with viscoelastic material and the injection site. It is possible, but not necessary, to enlarge the injection site, such as by creating a larger incision from the injection site. In some embodiments, as shown in Figure 18, a cannula is inserted through the injection site into the suprachoroid space and advances toward the posterior part of the eye. The cannula contains a microneedle, and the microneedle may be advanced and / or exposed such that the distal end of the microneedle penetrates the choroid / ciliary body without penetrating the retina. In some embodiments, as shown in Figure 18, the composition may be delivered via the microneedle to the subretinal space without removing the vitreous humor or passing the needle through the vitreous humor and retina.

[0201] Exemplary embodiments and optional implementations of the present disclosure have been described in detail above in conjunction with the drawings. However, the present invention is not limited to the details described in the embodiments described above. Simple modifications can be applied to embodiments of the present disclosure, all of which are within the scope of the present disclosure.

[0202] Furthermore, the technical features described in the above embodiments may be combined in any reasonable way, provided they do not conflict. To avoid unnecessary repetition, possible combinations are not described individually in the embodiments.

[0203] Furthermore, different implementations of the embodiments of the present invention can be freely combined. As long as they do not contradict the spirit of this disclosure, they should also be considered part of this disclosure.

Claims

1. It is a system, A syringe barrel including a proximal end and a distal end, The floating seal inside the syringe barrel, A needle base located proximal to the floating seal, wherein the needle base is configured to elastically engage with the floating seal and the needle base, A needle including a proximal end and a distal end that engage with the needle base, The needle includes a linear member configured to advance through the needle and be exposed at the distal end of the needle, the needle is (i) The distal opening of the needle, (ii) A needle body opening between the proximal end and the distal end of the needle, wherein the needle body opening is located proximal to the distal opening of the needle, (iii) including a needle body passage connecting the distal opening of the needle and the opening of the needle body, The needle base is configured to advance the needle distally toward and / or through the floating seal, in a system.

2. The floating seal separates the proximal lumen and distal lumen within the syringe barrel, and the distal lumen contains a fluid composition. The system according to claim 1, wherein the opening of the needle body and the distal opening of the needle are located within the proximal lumen.

3. The system according to claim 2, wherein before the needle advances, the needle body opening and the distal needle opening are located near the floating seal.

4. The needle base is configured to advance the needle distally toward the floating seal, The needle is configured to advance through the proximal lumen, The needle base is configured to advance the needle further distally through the floating seal, The opening of the needle body is located within the proximal lumen, and the distal opening of the needle is located within the distal lumen. Advancing the needle through the floating seal includes puncturing the floating seal with the distal end of the needle. The floating seal includes a guide groove aligned with the needle to facilitate the puncture. The system according to claim 2, wherein advancing the needle through the floating seal includes advancing the distal end of the needle through an existing hole or slit in the floating seal.

5. The needle base is configured to advance the needle distally such that both the needle body opening and the distal needle opening are distal to the floating seal. The opening of the needle body and the distal opening of the needle are located within the distal lumen. The needle base is configured to advance the needle distally through the distal lumen such that the opening of the needle body is inside the distal lumen and the distal opening of the needle is outside the distal lumen. When the distal opening of the needle is outside the distal lumen of the needle, the distal opening of the needle is in contact with the distal seal of the syringe barrel. When the distal opening of the needle is outside the distal lumen of the needle, the distal opening of the needle contacts the contact element at the distal end of the syringe barrel. The contact element is located distal to the distal seal and is configured to contact the subject. The system according to claim 2, wherein the distal seal and / or the contact element is configured to prevent the fluid composition in the distal lumen from being discharged through the distal opening of the needle.

6. The needle base is configured to advance the needle distally such that the distal opening of the needle is within the first tissue of the subject and the opening of the needle body is within the distal lumen. The first tissue can prevent the fluid composition in the distal lumen from being discharged through the distal opening of the needle. The distal lumen is in fluid communication with the distal opening of the needle via the needle body opening and the needle body passage. The needle base is configured to advance the needle distally such that the opening of the needle body is in the distal lumen and the distal opening of the needle is in the second tissue distal to the first tissue of the subject. The distal opening of the needle is located within an obvious or potential tissue void, cavity, or blood vessel in the second tissue. The pressure at the distal opening of the needle in the second tissue is lower than the pressure at the distal opening of the needle in the first tissue. The pressure at the distal opening of the needle in the second tissue is lower than the pressure at the opening of the needle body in the distal lumen. The floating seal is configured to move distally without moving the needle base or the needle distally due to the elastic engagement. The elastic engagement includes one or more springs and / or one or more elastic sheaths. The fluid composition in the distal lumen is discharged through the distal opening of the needle into the second tissue or into the space formed between the first tissue and the second tissue. The first tissue is the sclera, the second tissue is the choroid / ciliary body, and / or the space is the suprachoroidal space. The fluid composition includes liquids, solutions, suspensions, gels, oils, ointments, emulsions, creams, foams, lotions, and / or pastes. The system according to claim 2, wherein the space between the floating seal and the needle base does not contain a fluid composition.

7. The space between the floating seal and the needle base is filled with a gas such as sterile air. The system according to claim 6, wherein the needle is covered by the elastic sheath when the needle is in the space between the floating seal and the needle base.

8. The aforementioned system, The linear member includes a wire, a tube, or any combination thereof. The system according to claim 1, wherein the linear member is selected from the group consisting of a guidewire, sheath, catheter, cannula, microneedle, electrode, and sensor.

9. The system according to claim 8, further comprising a guide member configured to guide the linear member toward, into, and / or through the needle.

10. At least one component of the aforementioned system is provided separately from one or more other components. The system according to claim 1, wherein two or more components of the system are integrated or pre-assembled.

11. The system further includes a piston rod configured to elastically engage with the needle base, The piston rod is located between the floating seal and the needle base. The needle and the needle base within the piston rod are configured to advance the needle distally toward and / or through the floating seal via the piston rod. The floating seal is fixedly assembled to the distal end of the piston rod and forms a sliding seal engagement with the inner surface of the syringe barrel. The system according to claim 6, wherein the needle base is fixed to and engaged with an operating member (e.g., a pressing element), and the spring engages with the operating member and the piston rod, providing an elastic engagement between the needle base and the piston rod.

12. It is a device, A syringe barrel including a proximal open end and a distal closed end, The operating unit within the syringe barrel includes a needle base and a floating seal that elastically engage with each other, the needle base being located proximal to the floating seal, and the operating unit A needle including a proximal end and a distal end that engage with the needle base, The fluid composition lumen located distal to the floating seal, The needle includes a linear member configured to advance through the needle and be exposed at the distal end of the needle, the needle is (i) The distal opening of the needle, (ii) A needle body opening between the proximal end and the distal end of the needle, wherein the needle body opening is located proximal to the distal opening of the needle, (iii) a needle body passage connecting the distal opening of the needle and the opening of the needle body, wherein the actuation unit is configured to advance the needle so that the proximal end and / or distal end of the needle are positioned within the lumen of the fluid composition, The fluid composition lumen comprises a fluid composition selected from the group consisting of liquids, solutions, suspensions, gels, oils, ointments, emulsions, creams, foams, lotions, pastes, and any combination thereof. A device in which the space between the floating seal and the needle base within the syringe barrel is filled with a gas such as sterile air.

13. The device according to claim 12, wherein the needle base is engaged with an operating member (e.g., a retaining element) at the proximal open end of the syringe barrel, and the operating member (e.g., a retaining element) is configured to advance the needle base and the needle distally.

14. The operating unit includes an energy storage member that elastically engages with the needle base and the floating seal, The energy storage member is a first energy storage member, and the operating unit further includes a second energy storage member, the second energy storage member elastically engaging with the slider and the floating seal, and a portion of the slider extending outside the syringe barrel. The energy storage member includes a spring and / or an elastic sheath. The energy storage member is fixed to the needle base and / or the floating seal, The energy storage member is discharged to the needle base and / or the floating seal, The energy storage member is configured to apply force to the floating seal, and the floating seal then applies force to the fluid composition within the lumen of the fluid composition. The device according to claim 13, wherein the energy storage member is configured to move the floating seal distally without moving the needle base or the needle.

15. The device includes a sheath configured to enclose all or part of the needle, The sheath is configured to enclose the distal opening of the needle and / or the opening of the needle body, The device according to claim 13 or 14, wherein the sheath is configured to seal the needle body opening when the needle body opening is sealed.

16. The device includes a stopper in the lumen of the fluid composition, the stopper being configured to prevent distal movement of the floating seal, The device according to any one of claims 13 to 15, wherein the stopper is disposed on the inner wall of a syringe barrel that encloses the lumen of the fluid composition.

17. The device according to any one of claims 13 to 16, wherein the device includes a distal seal located at the distal closed end of the syringe barrel, and the floating seal, the syringe barrel, and the distal seal seal the lumen of the fluid composition.

18. The device according to any one of claims 13 to 17, wherein the device includes a contact element located at the distal closed end of the syringe barrel.

19. The device includes a guide structure configured to guide a linear member toward, into, and / or through the needle, The guide structure includes an inclined guide groove on the floating seal, The guide structure includes a valve and / or a removable plug in the inclined guide groove, The valve is a check valve configured to open toward the needle, The inclined guide groove extends from the proximal surface of the floating seal to the distal surface of the floating seal, The inclined guide groove does not extend through the floating seal, The device according to any one of claims 13 to 18, further comprising a linear member optionally selected from the group consisting of a guidewire, a sheath, a catheter, a cannula, a microneedle, an electrode, and a sensor.

20. It is a device, (1) a first syringe unit, (2) a second syringe unit, and a third syringe unit, The first syringe unit comprises a first syringe barrel and The needle base inside the first syringe barrel, A needle including a proximal end and a distal end that engage with the needle base, The needle includes a linear member configured to advance through the needle and be exposed at the distal end of the needle, the needle is (i) The distal opening of the needle, (ii) A needle body opening between the proximal end and the distal end of the needle, wherein the needle body opening is located proximal to the distal opening of the needle, (iii) including a needle body passage connecting the distal opening of the needle and the opening of the needle body, The second syringe unit engages with the distal end of the first syringe unit, The second syringe barrel, The floating seal in the second syringe barrel, The floating seal elastically engages with the needle base, The third syringe unit engages with the distal end of the second syringe unit and includes a third syringe barrel containing a fluid composition. The needle base is configured to advance the needle so that the proximal end and / or distal end of the needle are positioned in the fluid composition. The device further includes one or more syringe units, The device further includes a fourth syringe unit that engages with the distal end of the third syringe unit.

21. It is a device, (1) a first syringe unit, and (2) a second syringe unit, The first syringe unit comprises a first syringe barrel and A needle base and a floating seal elastically engage with each other within the first syringe barrel, wherein the needle base is located proximal to the floating seal, and the needle base and floating seal, A needle including a proximal end and a distal end that engage with the needle base, The needle includes a linear member configured to advance through the needle and be exposed at the distal end of the needle, the needle is (i) The distal opening of the needle, (ii) A needle body opening between the proximal end and the distal end of the needle, wherein the needle body opening is located proximal to the distal opening of the needle, (iii) including a needle body passage connecting the distal opening of the needle and the opening of the needle body, The second syringe unit engages with the distal end of the first syringe unit and includes a second syringe barrel containing a fluid composition. The needle base is configured to advance the needle so that the proximal end and / or distal end of the needle are positioned in the fluid composition. The device further includes one or more syringe units, The device further includes a third syringe unit that engages with the distal end of the second syringe unit.

22. It is a device, (1) a first syringe unit, and (2) a second syringe unit, The first syringe unit comprises a first syringe barrel and The needle base inside the first syringe barrel, A needle including a proximal end and a distal end that engage with the needle base, The needle includes a linear member configured to advance through the needle and be exposed at the distal end of the needle, the needle is (i) The distal opening of the needle, (ii) A needle body opening between the proximal end and the distal end of the needle, wherein the needle body opening is located proximal to the distal opening of the needle, (iii) including a needle body passage connecting the distal opening of the needle and the opening of the needle body, The second syringe unit engages with the distal end of the first syringe unit, The second syringe barrel, The floating seal in the second syringe barrel, wherein the floating seal elastically engages with the needle base, A fluid composition comprising, The needle base is configured to advance the needle so that the proximal end and / or distal end of the needle are positioned in the fluid composition. The device further includes one or more syringe units, The device further includes a third syringe unit that engages with the distal end of the second syringe unit.

23. A system according to any one of claims 1 to 11, used for the step of positioning the distal opening of a needle inside the body of a desired subject.

24. A device according to any one of claims 12 to 22, used for the step of positioning the distal opening of a needle inside the body of a desired subject.

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