Ophthalmic injection assembly, injection device and method of use

Abstract

The present invention relates to the field of ophthalmic treatment, and in particular to an ophthalmic injection assembly, an injection device and a method of use. The ophthalmic injection assembly includes a sleeve and a needle. The needle is fittable into the sleeve. An end of the sleeve is provided with a clamping port. In use, the tip of the needle can penetrate the clamping port. When using the ophthalmic injection assembly, the clamping port of the sleeve is brought into contact with and pressed against the ocular tissue at the injection site, causing the ocular tissue at the injection site to protrude into the sleeve, which can significantly improve the success rate of injection.

Description

[Technical field]

[0001] The present invention relates to the field of ophthalmic treatments, and in particular to ophthalmic injection assemblies, injection devices and methods of use. [Background technology]

[0002] The eye is a very complex organ. As a visual organ, the eye contains three parts: the eyeball, the visual pathway, and the appendages, which complete the visual function. The eyeball is roughly spherical and has a highly complex structure consisting of the ocular wall and the ocular contents. The ocular wall is divided into three layers: the outer layer is the fibrous membrane, the middle layer is the uvea, and the inner layer is the retina. The fibrous membrane is mainly composed of fibrous tissue and is the outer membrane of the eyeball, mainly the cornea and sclera, of which the sclera accounts for 5 / 6. The sclera is made up of tough, dense, intersecting fibers. The thickness of the sclera varies depending on the area and is individual specific. The arrangement of scleral collagen fiber bundles is different in different age groups, such as children, adults, and the elderly, and in different parts of the eye. The uvea lies between the sclera and the retina and is divided into three contiguous parts from anterior to posterior: the iris, the ciliary body, and the choroid. The choroid is a highly vascularized and pigmented tissue composed of fibrous tissue, small blood vessels, and capillaries, containing one large branching small artery and a network of small arterial and venous passageways; its thickness varies with vascular congestion and decreases with age.

[0003] As an exposed organ, the eye is susceptible to various types of injury, including conjunctival and corneal damage caused by pathogens. The conjunctiva is a thin, transparent, highly vascular mucous membrane that covers the inner surface of the eyelid and the front of the eyeball and helps protect the eye from injury due to foreign bodies and infection. However, the conjunctiva itself is not only very sensitive, but also susceptible to irritation by chemicals or allergens, or infection by viruses or bacteria, which can lead to conjunctivitis. Furthermore, the abundant vascularity induces a large amount of drug (>60%) to enter the systemic circulation, resulting in unnecessary tissue toxicity, etc.

[0004] Currently, ocular fundus diseases are one of the leading causes of irreversible vision impairment and loss. These ocular diseases include neovascular age-related macular degeneration, diabetic retinopathy, diabetic macular edema, central retinal vein occlusion, and branch retinal vein occlusion. In the treatment of ocular diseases, ocular drug delivery devices play a very important role because drug delivery to the fundus is restricted by tissue barriers (such as the cornea, conjunctiva, blood-aqueous humor barrier, and blood-retina barrier). Although traditional delivery methods such as ocular surface administration and intravitreal injection (IVT) are convenient, it is difficult to efficiently and safely deliver drugs to the fundus lesion site. Ocular injections can cause complications if the injection is made at an incorrect location or angle, such as intraocular bleeding or retinal damage, which can lead to cataracts and retinal detachment. If the medication leaks, it can also cause infection of other tissues in the eye.

[0005] The prior art discloses devices for injecting drugs into the choroidal space, but all have the side effect of causing eye damage. For example, CN112165923A discloses a device for injecting a substance into the middle layer of a body tissue or organ, the injection needle of which is composed of a two-layer needle including an outer 27G stainless steel short needle and an inner blunt separation needle. First, a 27G tunneling needle is inserted obliquely from the limbus into the sclera, keeping the needle parallel to the ocular surface. The control button on the syringe is pressed to extend the separation needle and dissect the tissue, creating an intrascleral passageway that connects to the suprachoroidal space. Then, the blunt separation needle is withdrawn by pressing the control button of the syringe. Finally, the drug solution in the syringe is injected into the suprachoroidal space through the passageway shot out by the tunnel needle to complete the injection. However, this device causes significant damage to the eye and is prone to bleeding. The insertion angle is very important, and it is difficult to precisely control and isolate the passageway leading to the suprachoroidal space. It is easy to penetrate the vitreous body or break through the conjunctiva.

[0006] CN107223042B discloses a therapeutic agent delivery device. When performing an ocular injection, first, the sclera is incised behind the corneal limbus. An arc-shaped cannula is inserted between the sclera and the choroid and advanced to the suprachoroidal space, after which the injection needle is pushed in until it penetrates under the retina and the injection is complete. However, this delivery device requires incision of the sclera and driving the cannula through the wall of the eye, which is traumatic and abrades large areas of the choroid and sclera. The injection needle then needs to be thrust to a precisely controlled depth, otherwise it may easily penetrate the retina, which is very difficult to control. [Prior art documents] [Patent documents]

[0007] [Patent Document 1] Chinese Patent Publication No. 112165923 [Patent Document 2] Chinese Patent Registration No. 107223042 Summary of the Invention [Problem to be solved by the invention]

[0008] In order to solve the above problems, it is necessary to provide a simple and convenient device that can effectively deliver drugs to target tissues in the eye while solving the problem of eye damage caused by injection.

[0009] The present invention provides an ocular injection assembly, which uses a clamping port to press the conjunctival tissue around the injection point to form a protrusion facing the clamping port, which can not only effectively deliver drugs to the target eye tissue, but also solve the problem of eye damage caused by injection. [Means for solving the problem]

[0010] To achieve the above object, the present invention includes the following. 1. An ophthalmic injection assembly comprising: a sleeve; and a needle that can be fitted into the sleeve, the sleeve having an end with a clamping port through which a tip of the needle can pass, the clamping port of the sleeve being brought into contact with and pressed against ocular tissue at an injection site when the ophthalmic injection assembly is used, causing the ocular tissue at the injection site to protrude into the sleeve.

[0011] Preferably, the minimum inner diameter of the clamping opening is 1 mm to 3 mm. The needle is inserted into the injection point to perform the injection, and the minimum inner diameter of the clamping hole refers to the length of a line segment that passes through the injection point and has both ends located inside the clamping hole. The injection point is located in the center of the line segment. Experimental results showed that when the inner diameter is 1 to 3 mm, the area of ​​the eye tissue within the clamping opening is appropriate, and obvious protrusions are formed on the eye tissue within the clamping opening, making the injection operation easier.

[0012] Preferably, the jaw has an annular end surface. The periphery of the clamping opening forms an annular end surface, capable of forming annular surface contact with the ocular tissue surrounding the injection point.

[0013] Preferably, the annular end surface is planar and said needle is perpendicular to said annular end surface. That is, the axial direction of the needle is perpendicular to the plane in which the annular end face lies.

[0014] Preferably, the jaws are circular, elliptical or polygonal in shape. Different shapes of jaws, such as circular, elliptical, hexagonal, octagonal, rectangular or irregular, can all achieve pressure of the jaws against the conjunctival tissue. When the clamping opening is circular, the annular end surface is a circular end surface, which is not only more advantageous for avoiding damage to the ocular tissue, but also more advantageous for the recovery of the ocular tissue during the injection process.

[0015] Preferably, the end of the sleeve is a constricted portion and the clamping opening is located at a distal end of the constricted portion. The cross-sectional size of the contracted portion gradually increases in the direction away from the clamping opening, which is advantageous for containing the backflowing medicinal solution within the contracted portion when backflow occurs.

[0016] Preferably, the side wall of the sleeve is provided with a viewing window of transparent material or the sleeve is a member of transparent material. By providing a viewing window or using a sleeve made of a transparent material, it becomes easier to observe the reflux state of the medicinal solution, allowing a quick judgment as to whether the injection was successful or not.

[0017] Preferably, the viewing window is provided with volume graduations or the transparent sleeve is provided with volume graduations, the volume graduations extending along the axial direction of the sleeve. By providing a scale line, the backflow amount of the medicinal liquid can be observed in real time, and if the warning limit is exceeded, it is convenient to notify the operator of the failure of the injection and stop the injection.

[0018] Preferably, the length of the blade surface at the tip of the needle is less than 1100 μm, preferably less than 900 μm, further preferably less than 700 μm, more preferably 550 μm or less, and most preferably 250 to 550 μm.

[0019] Preferably, when the needle is engaged with the sleeve, the length of the tip of the needle beyond the clamping opening is 500 to 2000 μm, preferably 700 to 1350 μm, and more preferably 700 to 1100 μm.

[0020] Preferably, in the case of suprachoroidal injection, the length of the portion of the tip of the needle beyond the clamping opening is 500 to 1100 μm.

[0021] Preferably, the sleeve is provided with a flow passage and the needle is movably connected within the flow passage. The needle is connected to the sleeve via a flow passage, which is advantageous in that the needle maintains its position relative to the jaw of the sleeve when puncturing to reach the injection site.

[0022] Preferably, the needle has a hub connected to one end opposite the tip, and an adjustment assembly is provided between the sleeve and the hub for adjusting the length of the tip of the needle that extends beyond the clamping mouth portion, making it convenient to adjust the length of the needle tip that extends beyond the clamping mouth to control the puncture depth. It can be applied to different patients or puncture different locations of the eye, for example, to the eye wall tissue in patients with abnormal scleral thickness.

[0023] Preferably, the hub and the sleeve are connected via the adjustment assembly. A needle hub is provided to facilitate connection to a syringe. By locating the adjustment assembly between the needle hub and the sleeve, adjustment of the needle length is less susceptible to interference from other components, such as a syringe.

[0024] Preferably, the adjustment assembly includes a male threaded portion provided on the needle hub and a corresponding female threaded portion provided on the sleeve, the male threaded portion and the female threaded portion being capable of being matingly connected to each other. By fitting the male and female threads together, the needle base and sleeve can be rotated relative to each other to adjust the length of the needle.

[0025] Preferably, the needle hub includes a guide tube, and the guide tube is provided with the male thread portion. The guide tube is connected to the front end of the needle base, and the guide tube is fitted and connected to the needle, thereby enhancing the strength of the needle and preventing the needle from bending or shaking during the puncture process.

[0026] The thread pitch is preferably 50 to 200 μm, and more preferably 50 to 150 μm.

[0027] Another method of setting the adjustment assembly is as follows. Preferably, a hub is connected to the rear end of the sleeve, and an adjustment assembly including a telescopic rod assembly and a drive mechanism is provided within the hub. The telescopic rod assembly includes an outer tube and an inner tube, one end of the outer tube is connected to the rear end of the needle hub and the other end is fitted into the inner tube, and the other end of the inner tube is connected to the rear end of the needle. The outer tube, the inner tube and the needle are connected in sequence, or the rear end of the needle passes through the inner tube and the outer tube in sequence and beyond the outer tube. The drive mechanism is connected to the inner tube and can drive the inner tube to move relative to the outer tube along the axial direction, and the inner tube can move the needle in conjunction with the inner tube. The rear end of the needle sequentially penetrates the inner tube and the outer tube and extends beyond the outer tube means that the needle is fixed to the inner tube, and the rear end of the needle extends beyond the inner tube into the outer tube and then to the other end of the outer tube.

[0028] Preferably, a guide tube is fitted outside the needle, both ends of the needle are exposed from the guide tube, and the front end of the needle hub is fitted outside the guide tube, so that the guide tube and the needle hub are slidable relative to each other. The guide tube is fitted into the needle, thereby increasing the strength of the needle and reducing shaking and deformation of the needle that occurs during the process of puncturing eye tissue.

[0029] Preferably, the drive mechanism includes a drive housing, a rack guide, a drive gear, and an operating rod. A drive housing has one end connected to the outer tube and an other end slidably connected to the inner tube. The rack guide is connected to the inner tube and is disposed along the axial direction. The drive gear is hingedly connected to the drive housing and meshed with the rack guide. One end of the operating rod is connected to the drive gear, and the other end passes through a through hole in the drive housing and a through hole in the hub to reach the outside of the hub. By rotating the operating rod, the drive gear can be rotated in conjunction with the rotation of the operating rod. The driving gear is rotated by the operating rod in the rotary driving mechanism, and the driving gear moves in conjunction with the rack guide, the inner tube moves together with the rack guide, and further the needle is moved axially in conjunction with the rack guide, thereby adjusting the needle position.

[0030] Another method of setting the adjustment assembly is to use it in combination with a release assembly.

[0031] Preferably, a hub is connected to the rear end of the sleeve, and a release assembly including an elastic member and a first stopper is provided between the sleeve and the hub, the sleeve is connected to the hub via the elastic member, one end of the first stopper is detachably connected to the sleeve, and / or the other end of the first stopper is detachably connected to the hub, and when the first stopper is connected to the sleeve and the hub, the elastic member is in an extended state and can provide a tensile force in the axial direction, extending the elastic member to increase the distance between the hub and the sleeve, and engaging the first stopper between the hub and the sleeve to maintain the distance between the hub and the sleeve. At this time, the elastic member is in an extended state and the front end of the needle is withdrawn into the sleeve. In use, the clamping opening is kept in contact with the ocular tissue, and after the first stopper is removed, the needle base is moved forward so that the front end of the needle protrudes from the clamping opening and is punctured into the ocular tissue.

[0032] Preferably, the elastic member is a return spring, a compressed gas container, or a container containing a propellant, and the first stopper is a locking piece, a locking groove, a locking ring, or a pawl.

[0033] Preferably, an adjustment assembly including a telescopic rod assembly and a drive mechanism is provided between the sleeve and the needle hub, the telescopic rod assembly including an outer tube and an inner tube, one end of the outer tube is connected to the front end of the needle hub and the other end is fitted into the inner tube, and the other end of the inner tube is connected to the rear end of the needle. The outer tube, the inner tube and the needle are connected in sequence, or the rear end of the needle penetrates the inner tube and the outer tube in sequence and passes beyond the outer tube, and a driving mechanism is connected to the inner tube to drive the inner tube to move relative to the outer tube along the axial direction, and the inner tube can move the needle in conjunction with the inner tube. In this embodiment, the structure of the adjustment assembly may be consistent with that of the previous embodiment, and the adjustment assembly may be located outside the hub and in the center of the elastic member.

[0034] Preferably, the drive mechanism includes a drive housing, a rack guide, a drive gear, and an operating rod, one end of the drive housing is connected to the outer tube and the other end is slidably connected to the inner tube, the rack guide is connected to the inner tube and is arranged along the axial direction, the drive gear is hingedly connected within the drive housing and meshingly connected to the rack guide, and the operating rod has one end connected to the drive gear and the other end passing through a through hole of the drive housing and a through hole of the needle hub to reach the outside of the needle hub. By rotating the operating rod, the drive gear can be rotated in conjunction with the operating rod. The operating rod and the drive gear are detachably connected. When the operating rod is separated from the hub, the first stopper can be interlocked to separate the first stopper from the sleeve and / or the hub. By disposing the operating rod outside the needle base, the operating rod can be removed by pulling it out after the needle length is adjusted using the operating rod, which makes observation convenient. The operating rod then cooperates with the first stopper to separate the sleeve and the hub, facilitating one-handed operation by the operator.

[0035] Preferably, when the clamping opening of the sleeve comes into contact with and is pressed against ocular tissue, the clamping opening is closed and a protrusion directed toward the inside of the sleeve is formed on the ocular tissue.

[0036] Preferably, when the jaws are closed, the chamber within the sleeve forms a sealed chamber. If backflow occurs, the backflowing medicinal solution is contained in the sealed chamber, and when the clamping mouth is separated from the ocular tissue, the medicinal solution is less likely to leak from the sealed chamber, and dripping of the medicinal solution onto the ocular tissue can be prevented. This is advantageous in determining the volume of refluxed medication accurately and estimating the amount of medication injected.

[0037] The present invention further provides an ophthalmic injection device comprising a syringe and the above-described ophthalmic injection assembly attachable to the syringe.

[0038] Preferably, the syringe includes a drug container and a push rod slidable within the drug container, the drug container being used for storing a drug solution and being matingly connected to a needle.

[0039] Preferably, a thrust assembly is provided between the distal end of the push rod and the medication container for generating a constant thrust on the push rod.

[0040] Preferably, the thrust assembly is a spring ball mechanism, a spring pin, a cylinder, or a container containing a propellant.

[0041] Preferably, the constant thrust threshold generated by the thrust assembly is less than or equal to 6 N. When the thrust assembly generates a constant thrust, it means that the thrust assembly cannot propel when the thrust received by the thrust assembly is less than the threshold. When the thrust is greater than the threshold, the thrust assembly can counteract the thrust to maintain the thrust at the threshold. For example, if the threshold is 5N, a force of 4N will not be able to propel the thrust assembly, and if the thrust is 7N, the thrust assembly will be able to hold the thrust at 6N.

[0042] Preferably, the injection device further includes a second stopper disposed between the push rod and the drug container for limiting the magnitude of the push stroke of the push rod.

[0043] Preferably, the second stopper is a locking piece, a locking groove, a locking ring, or a pawl.

[0044] Preferably, the injection device further includes a needle protection cap engageable with the needle.

[0045] The present invention further provides a method of using the above-mentioned ocular injection device, which includes a step of using the ocular injection device to contact and press the clamping mouth of the sleeve against ocular tissue at the injection site, causing the ocular tissue at the injection site to protrude into the sleeve.

[0046] Preferably, the clamping mouth of the sleeve is brought into contact with and pressed against the ocular tissue at the injection site, causing the tip of the needle to pierce the ocular tissue at the injection site so that the distal end of the needle reaches the ocular target tissue at the injection site after the ocular tissue at the injection site forms a protrusion within the sleeve.

[0047] Preferably, the clamping mouth of the sleeve is brought into contact with and pressed against the ocular tissue at the injection site, causing the ocular tissue at the injection site to form a protrusion within the sleeve and causing the tip of the needle to pierce the ocular tissue at the injection site so that the distal end of the needle reaches the ocular target tissue at the injection site.

[0048] Preferably, before the clamping opening of the sleeve is brought into contact with and pressed against the ocular tissue at the injection site, the length of the needle tip exposed from the clamping opening is adjusted according to the thickness of the ocular tissue at the injection site. The adjustment can be performed using an adjustment assembly in the injection device.

[0049] Preferably, one side of the sleeve clamping opening is first brought into contact with the ocular surface, the sleeve is then inverted about this contact point to insert the needle into the ocular tissue at the injection site, and the inversion is continued to bring the other side of the clamping opening into contact with the ocular surface, such that the ocular tissue forms a protrusion within the sleeve. The ocular surface may be an ocular surface such as conjunctival tissue or other ocular tissue.

[0050] Preferably, the thickness of the ocular tissue at the injection site is detected using one or more detection means including optical coherence tomography (OCT), enhanced optical coherence tomography (EDI-OCT), sweeping optical coherence tomography (SS-OCT) or ultrasound biomicroscopy (UBM).

[0051] Preferably, the push rod is pressed to inject at least a portion of the substance in the drug container through the needle and into the ocular target tissue.

[0052] Preferably, the amount of refluxed medicinal fluid within the sleeve is observed as the push rod is pushed to deliver at least a portion of the substance within the medicinal container through the needle and into the target ocular tissue. An injection device with a visible window or a clear sleeve may be used.

[0053] Preferably, when the ophthalmic injection assembly presses against and punctures ocular tissue, the thrust assembly cooperates with the syringe to apply force to the clamping port at the distal end of the sleeve, causing ocular tissue around the injection site to protrude into the sleeve.

[0054] Preferably, when the ophthalmic injection assembly presses against and punctures eye tissue, the force that the thrust assembly applies to the distal end clamping port of the sleeve in cooperation with the syringe is 0.4 N to 6 N or less, more preferably 1 N to 6 N, and more preferably 1 to 3 N.

[0055] Preferably, when the push rod is pressed to deliver at least a portion of the substance in the drug reservoir through the distal end of the needle to the ocular target tissue, the injection pressure in the drug reservoir is less than 500 kPa.

[0056] Preferably, when the push rod is pushed to deliver at least a portion of the substance in the drug container through the distal end of the needle to the target ocular tissue, the increase in intraocular pressure is 30 mmHg or less, more preferably 20 mmHg or less, and more preferably 10 mmHg or less.

[0057] Alternatively, the present invention provides an ocular injection device which includes a syringe 1, a needle 2, and a sleeve 3, with a clamping opening 31 provided at the distal end of the sleeve 3, and which, when injecting into the eye, can bring the clamping opening 31 into close contact with the ocular tissue, causing the ocular tissue to form a protrusion toward the inside of the sleeve 1.

[0058] The syringe 1 further includes a drug container 11 and a push rod 12, the drug container 11 is connected to the proximal end of the needle 2 and coupled to the push rod 12, the distal end of the push rod 12 is disposed in the drug container 11, and after the proximal end portion of the push rod 12 is subjected to a force, the distal end portion of the push rod 12 is moved within the drug container 11 to transport at least a portion of the substance in the drug container 11 through the needle 2, the sleeve 3 is provided with a flow path 32 and is movably connected to the proximal end of the needle 2, and the distal end of the needle 2 is configured to pass through the flow path 32 of the sleeve 3 and pierce the eye tissue via the clamping port 31.

[0059] When the ocular injection device performs a clamping action, the sleeve 3 forms a bottom sealed chamber 33 with the clamped ocular tissue.

[0060] The shape of the clamping opening 31 is circular, hexagonal, octagonal, rectangular or irregular, preferably circular, and the minimum inner diameter of the clamping opening 31 is 0.5 mm to 10 mm, preferably 1 mm to 6 mm, and more preferably 1 mm to 3 mm.

[0061] The length of the blade surface at the distal end of needle 2 is less than 1100 μm, preferably less than 900 μm, further preferably less than 700 μm, more preferably 550 μm or less, and most preferably 250 to 550 μm.

[0062] The puncture force of the distal end of the needle 2 is 0.7N or less, more preferably 0.5N or less.

[0063] The force applied by the ocular injection device to the ocular tissue can cause elastic deformation of the ocular tissue, and is preferably 0.4N to 10N, more preferably 2N to 6N, and most preferably 3N to 5N.

[0064] The needle 2 of the ophthalmic injection device includes a needle base 21, the proximal end of which is connected to the distal end of the drug container 11 and the distal end of which is connected to the proximal end of the needle 2, and an adjustment assembly 4 is provided between the proximal and distal ends of the needle base 21 which cooperates with the sleeve 3 to adjust the length of the needle 2 exposed from the clamping opening 31 at the distal end of the sleeve 3.

[0065] An adjustment release member 5 configured to adjust the length of the needle 2 exposed from the distal end clamping port 31 of the sleeve 3 is provided between the needle base 21 and the sleeve 3, and is configured to push the needle 2 so that it is inserted into the eye tissue through the distal end clamping port 31 of the sleeve 3 when the ophthalmic injection device performs a puncture operation.

[0066] The injection device includes a thrust assembly 6 configured to generate a constant thrust force at a proximal end portion of a push rod 12 .

[0067] The injection device further includes a second stopper 7 configured to selectively limit the movement of the push rod 12 relative to the drug container 11 and release the thrust assembly 6 upon performance of a drug injection.

[0068] The sleeve 3 is a transparent sleeve and is configured to allow observation of the length of the needle 2 exposed from the distal end clamping opening 31 of the sleeve 3 and / or to allow observation of the amount of medicinal solution reflux in the chamber 33.

[0069] Alternatively, the sleeve 3 may have a visible window 34 configured to observe the length of the needle 2 exposed from the distal end clamping opening 31 of the sleeve 3 and / or configured to observe the amount of medicinal solution reflux in the chamber 33. Effect of the Invention

[0070] As described above, by adopting the above technical means, the present invention has the following beneficial effects. 1. The ophthalmic injection device of the present invention has a clamping port set as an annular end surface, so that the area of ​​the ocular tissue within the clamping port is appropriate and an obvious protrusion can be formed within the clamping port, thereby improving the success rate of injection, smoothly delivering the drug solution to the target site, and effectively preventing backflow and subconjunctival diffusion of the drug solution. 2. The ocular injection assembly of the present invention is convenient to adjust the length of the needle tip beyond the clamping port to control the puncture depth by installing an adjustment assembly. By controlling the effective length of the needle, the effective dose of the drug is accurately delivered to the target tissue through the needle. It can be applied to different patients and can puncture different positions of the eye. For example, it can be applied to the eye wall tissue in patients with abnormal scleral thickness. 3. In the ophthalmic injection assembly of the present invention, the operating rod in the adjustment assembly is detachably connected, and the first stopper in the release assembly can be interlocked and separated, which facilitates one-handed operation by the operator and makes the operation more convenient. 4. The ophthalmic injection device of the present invention uses an ophthalmic injection assembly to cooperate with the syringe, making operation more convenient. 5. The method of using the ocular injection device of the present invention can select different injection assemblies of injection devices according to different patient conditions. During implementation, the tissue around the injection point forms a protrusion in the sleeve before the needle punctures, which is favorable for the needle to reach the predetermined position and ensure the injection effect. 6. The ocular injection assembly of the present invention can effectively prevent the drug from leaking from the insertion site, improving the success rate of one-time puncture at a specified position. Even if reflux occurs due to operation or other reasons, the refluxed drug solution will flow back into the sleeve through the clamping port, effectively avoiding the refluxed drug from spreading on the ocular surface due to failed injection. 7. The chamber in the sleeve forms a sealed chamber. When reflux occurs, the refluxed medicinal solution is contained in the sealed chamber. When the clamping mouth is separated from the ocular tissue, the medicinal solution is less likely to leak from the sealed chamber, and the medicinal solution can be prevented from dripping onto the ocular tissue. By using a transparent window, a scale mark, and other means, it is more convenient to accurately judge the situation of refluxed medicinal solution, observe the volume of refluxed medicinal solution, and estimate the amount of injected medicinal solution. [Brief description of the drawings]

[0071] [Figure 1] 1 is a cross-sectional view of the human eye. [Figure 2A] This is a diagram of the state where there is no liquid under the conjunctiva. [Figure 2B] This is a diagram of the state where there is liquid under the conjunctiva. [Figure 3A] FIG. 13 is a diagram showing the effect of no liquid in the suprachoroidal space. [Figure 3B] FIG. 1 is a diagram showing the effect of having liquid in the suprachoroidal space. [Figure 4] ~ [Figure 18] 1 is a diagram in Examples 1 to 9. [Figure 4] FIG. 1 is a diagram illustrating the configuration of an ocular injection device. [Figure 5A] FIG. 5 is a front view of the sleeve shown in FIG. [Figure 5B] FIG. 5 is a plan view of the sleeve shown in FIG. [Figure 5C] FIG. 5 shows a bottom view of the sleeve shown in FIG. [Figure 6] FIG. 5 is a schematic diagram of a protruding front surface and protruding ocular tissue structure formed by the ocular syringe and ocular tissue of FIG. [Figure 7A] FIG. 5 is a front view of the distal end blade face of the needle shown in FIG. 4. [Figure 7B] FIG. 13 shows a side view of the distal blade face of the needle. [Figure 8] FIG. 1 is a structural schematic diagram of an ocular injection device with a bottom sealed chamber and a viewing window. [Figure 9A] FIG. 9 is a schematic diagram of a sleeve with a viewing window and a bottom sealed chamber shown in FIG. 8. [Figure 9B] FIG. 9 is a schematic diagram of a sleeve with volume graduation lines as shown in FIG. 8. [Figure 10] FIG. 2 is a structural schematic diagram of an ophthalmic injection device including a needle hub. [Figure 11] FIG. 1 is a structural schematic diagram of an ophthalmic injection device with a screw adjustment assembly. [Figure 12A] FIG. 2 is a structural schematic diagram of a female-threaded sleeve. [Figure 12B] FIG. 2 is a schematic diagram of the structure of a needle hub provided with a male thread. [Figure 12C] FIG. 13 is a schematic diagram of a distal end of a needle with volume graduations. [Figure 13] FIG. 1 is a structural schematic diagram of an ophthalmic injection device with a telescopic rod adjustment assembly. [Figure 14A] FIG. 13 is a structural schematic diagram of a needle with a telescopic rod adjustment assembly. [Figure 14B] FIG. 2 is a structural schematic diagram of a telescopic rod adjustment assembly. [Figure 14C] FIG. 4 is a schematic diagram of the internal structure of the telescopic rod adjustment mechanism. [Figure 14D] FIG. 2 is a structural schematic diagram of a needle hub sleeve assembly with volume graduation lines; [Figure 15] 1 is a structural schematic diagram of an ophthalmic injection device with an adjustable release assembly. [Figure 16A] FIG. 1 is a structural schematic diagram of a needle with an adjustable release assembly. [Figure 16B] FIG. 4 is a schematic diagram showing the structure of a first stopper. [Figure 17] 1 is a structural schematic diagram of an ophthalmic injection device including a thrust assembly. [Figure 18] FIG. 4 is a schematic diagram showing the structure of a second stopper. [Figure 1] ~ [Figure 18]The signs are as follows: e1-eye e2-lens e3-cornea e4-sclera e5-iris e6-anterior chamber e7-posterior chamber e8-corneal limbus e9-conjunctiva e10-choroid e11-retina e12-vitreous body e13-ciliary body e14-suprachoroidal space e15-fluid layer 1-syringe 11-drug container 12-push rod 2-needle 21-needle base 211-passage 212-flange 213-connection 214-rib 3-sleeve 31-clamping port 32-fluid passage 33-chamber 34-visible window 35-volume scale mark 36-limit hole 4-adjustment assembly 41-screw 42-telescopic rod assembly 421-outer tube 422-inner tube 423-guide rail 424-drive mechanism 43-first operating rod 5-adjustment release member 51-telescopic assembly 52-release assembly 53—second operating rod; 54—first stopper; 6—thrust assembly; 7—second stopper; 8—needle protection cap [Figure 19] FIG. 13 is a structural schematic diagram of the ocular injection assembly in Example 10. [Figure 20] FIG. 13 is an assembly diagram of the ocular injection assembly in Example 10. [Figure 21] FIG. 13 is a front view of the ophthalmic injection assembly of Example 10. [Figure 22] 22 is a cross-sectional view taken along line AA in FIG. 21. [Figure 23] This is an enlarged view of circle O in Figure 22. In the figure, d is the length of the tip of the needle beyond the clamping mouth portion. [Figure 24] 1 is a schematic diagram of a circular clamping mouth and an annular end surface. [Diagram 25] FIG. 2 is a schematic diagram of an elliptical clamping mouth and an annular end surface. [Figure 26] FIG. 2 is a schematic diagram of a polygonal clamping mouth and an annular end surface. [Figure 27] FIG. 1 is a schematic diagram of the relationship between the jaw and the ocular surface when the ocular injection assembly is in use. [Figure 28] FIG. 13 is a schematic diagram of the relationship between the clamping port and the ocular surface when reflux occurs during use of the ophthalmic injection assembly. [Figure 29] FIG. 16 is a schematic diagram of the cross-sectional structure of the needle hub and needle of the injection assembly in Example 11. [Diagram 30]FIG. 16 is a schematic cross-sectional view of the sleeve of the injection assembly in Example 11. [Diagram 31] FIG. 13 is a schematic cross-sectional view of a sleeve of another embodiment of the injection assembly in Example 11. [Diagram 32] FIG. 15 is a schematic cross-sectional view of the injection assembly in Example 12. [Diagram 33] FIG. 16 is a schematic cross-sectional view of another embodiment of the injection assembly in Example 12. [Diagram 34] FIG. 16 is a structural schematic diagram of the adjustment assembly of the injection assembly in Example 12. [Diagram 35] FIG. 16 is a schematic cross-sectional view of the adjustment assembly of another embodiment of the injection assembly in Example 12. [Diagram 36] FIG. 36 is a schematic diagram of a cross-sectional structure taken along line BB in FIG. 35. [Figure 37] FIG. 16 is a schematic cross-sectional view of another embodiment of the injection assembly in Example 12. [Figure 38] FIG. 13 is a schematic cross-sectional view of the injection assembly in Example 13. [Figure 39] FIG. 13 is a schematic cross-sectional view of the injection assembly in another state according to the thirteenth embodiment. [Diagram 40] FIG. 23 is a structural schematic diagram of a first stopper in the thirteenth embodiment. [Diagram 41] FIG. 17 is a structural schematic diagram of the injection device in Example 14. [Diagram 42] FIG. 21 is an exploded view of the injection device in Example 14. [Diagram 43] FIG. 15 is a structural schematic diagram of the injection device in Example 15. [Diagram 44] 1 is a photograph of a section of fundus tissue in Test Example 1. [Diagram 45] 1 shows ICGA angiography results and OCT scan results in Test Example 3. [Diagram 46] 13 shows the results of fundus fluorescence detection in Test Example 3. [Figure 47] 1 shows the expression results of the injected reagent in retinal epithelial cells and photoreceptor cells in Test Example 3. [Figure 48]1 shows ICGA angiography results and OCT scan results in Test Example 4. [Figure 49] 1 shows ICGA angiography results and OCT scan results in Test Example 5. [Figure 50] 1 shows ICGA angiography results and OCT scan results in Test Example 6. [Figure 51] 13 shows an OCT scan result in Test Example 7. [Figure 52] 13 shows the expression results of the injected reagent in retinal epithelial cells and photoreceptor cells in Test Example 7. [Diagram 53] 13 shows an OCT scan result in Test Example 8. [Figure 54] 13 shows the expression results of the injected reagent in retinal epithelial cells and photoreceptor cells in Test Example 8. [Figure 55] 1 is a photograph of a fundus tissue section in Comparative Example 2. [Figure 19] ~ [Figure 55] Reference numerals: 101 - female thread portion 102 - male thread portion 200 - projection 2 - needle 21 - needle base 211 - guide tube 3 - sleeve 31 - clamping port 32 - contraction portion 33 - annular end face 34 - chamber 35 - viewing window 351 - volumetric graduations 4 - adjustment assembly 41 - drive mechanism 411 - drive housing 412 - drive gear 413 - rack guide 414 - operating rod 42 - telescopic rod assembly 421 - outer tube 422 - inner tube 5 - release assembly 51 - elastic member 52 - first stopper 6 - thrust assembly 7 - second stopper 8 - needle protection cap DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0072] Hereinafter, embodiments of the present invention will be described in detail with reference to the drawings.

[0073] The injection site, needle size, blade length, puncture force of the blade, constant thrust and puncture biasing force of the thrust assembly, and needle size are described below.

[0074] <1. Injection site> Injection sites as described in the text: any area of ​​the conjunctiva, including the supranasal, subnasal, supratemporal, or subtemporal; At any point on any area of ​​the conjunctiva between the iris edge and the limbus, such as the supranasal, infranasal, supratemporal, or infratemporal, approximately 3 to 9 mm from the limbus, approximately 4 to 8 mm from the limbus, approximately 4 to 7 mm from the limbus, approximately 6 to 8 mm from the limbus, approximately 7 to 8 mm from the limbus, and approximately 4 to 5 mm from the limbus. The distance may be selected to be about 3 mm, or about 4 mm, or about 5 mm, or about 6 mm, or about 7 mm, or about 8 mm from the limbus.

[0075] <2. Needle specifications> You can choose from conventional injection needles available on the market, such as 28G, 30G, 31G, 32G, 33G, and 34G needles, or you can customize and process them using conventional needle manufacturing processes. Needle Effective Length: The effective length of the needle is the length exposed from the sleeve clamping opening, and is about 1400 μm or less, about 1300 μm or less, about 1200 μm or less, about 1100 μm or less, about 1000 μm or less, about 900 μm or less, about 800 μm or less, about 850 μm or less, about 700 μm or less, about 650 μm or less, about 500 μm or less, or about 450 μm or less. In some embodiments, the effective length of the needle may be about 700 μm, hi other embodiments, the effective length of the needle may be about 750 μm, or about 800 μm, or about 850 μm, or about 900 μm, or about 950 μm, or about 1000 μm, or about 1100 μm, or about 1350 μm.

[0076] <3. Length of the blade> The linear distance from the inner proximal edge of the needle wall at the distal fluid outlet of the needle to the distal edge of the outer wall of the needle at the distal fluid outlet of the needle is about 800 μm or less, about 700 μm or less, about 650 μm or less, about 600 μm or less, about 550 μm or less, about 500 μm or less, about 450 μm or less, about 400 μm or less, about 350 μm or less, about 300 μm or less, about 250 μm or less. In some embodiments, the length of the distal blade face of the needle is about 550 μm. In other embodiments, the length of the needle distal blade face is about 700 μm, or about 650 μm, about 600 μm, about 500 μm, about 450 μm, about 300 μm, or about 250 μm.

[0077] <4.Blade surface piercing force> To limit the reach to a desired location within the target tissue (e.g., the suprachoroidal space and / or the vitreous body) and form a drug delivery passage, the blade penetration force of the distal end outlet of the needle is about 0.7 N or less, about 0.65 N or less, about 0.5 N or less, about 0.4 N or less, or about 0.3 N or less. In some embodiments, the blade face puncture force may be about 0.5N, and in other embodiments, the blade face puncture force may be about 0.7N, or about 0.65N, about 0.4N, about 0.3N.

[0078] <5. Needle specifications> Needle Standards: The distal end of the needle is generally sharpened, beveled, or otherwise configured to pierce the ocular surface (eg, the sclera). The needle used can be of any suitable gauge, for example, about 25G, about 26G, about 27G, about 28G, about 29G, about 30G, about 31G, about 32G, about 33G, about 34G, about 35G, about 36G, etc. The wall of the needle can be of any suitable thickness. For example, in addition to normal wall thickness (RW), the needle wall thickness can be designed as thin wall (TW), extremely / ultra thin wall (XTW / UTW), or extremely thin wall (XXTW). These names are well known to those skilled in the art. For example, the needle may be a fine gauge intubation or needle. In some variations, the needle can have a gauge of about 25G to about 36G. In other variations, the needle can have a gauge of about 27G to about 35G. In another variation, the needle can have a gauge of about 30G to about 33G.

[0079] The above embodiments relate to systems and devices for delivering fluids (eg, drugs) to ocular tissue. Additionally, the above embodiments relate to systems, devices and methods that aid in inserting a delivery object (e.g., a needle) into the eye at a predetermined injection site and / or aid in effectively metering a drug into a targeted ocular tissue. The above embodiments also relate to systems, devices and methods that avoid the gap between the conjunctiva and the sclera from spreading during penetration by a delivery object (e.g., a needle) to prevent diffusion of substances and / or ocular fluids under the conjunctiva, thereby forming a subconjunctival leakage pathway. The above embodiments also relate to systems, devices and methods in which a delivery object (eg, a needle) forms a sealed chamber during puncture to prevent diffusion of substances and / or ocular fluids around the ocular surface. The above embodiments also relate to systems, devices, and methods in which the sleeve is made of a transparent construction or has a viewing window to allow an operator to quickly and intuitively observe needle length adjustment or reflux status of substances and / or ocular fluids.

[0080] The "syringe" of the present invention is a conventional ophthalmic syringe assembly, mainly comprising a drug container 11 and a push rod 12, the drug container 11 being connected to the proximal end of the needle 2 and coupled to the push rod 12, the distal end of the push rod 12 being disposed within the drug container. The proximal end portion of the push rod 12 receives a force, causing the distal end portion of the push rod 12 to move within the drug container 11 and deliver at least a portion of the substance within the drug container 11 through the needle 2 .

[0081] <Eye structure> 1 to 3 are diagrams of the human eye (of which Figs. 2 and 3 are cross-sectional views). Although the drawings in this specification relate to specific regions of the eye, those skilled in the art will understand that the illustrations of specific regions of the eye in the drawings in this specification do not constitute the entire eye, but are used only as specific examples applicable to the present invention so that those skilled in the art will understand the technical solution. Here, eye e1 includes an anterior stage (the portion of the eye in front of the lens e2 (including the lens e2)) and a posterior stage (the portion of the eye behind the lens e2). The anterior section is bounded by the cornea e3 and the crystalline lens e2, while the posterior section is bounded by the sclera e4 and the crystalline lens e2. The anterior section is further divided into the anterior chamber e6 between the iris e5 and the cornea e3, and the posterior chamber e7 between the crystalline lens e2 and the iris e5. The cornea e3 and the sclera e4 together form the limbus e8 at their joint. The exposed part of the sclera e4 in the anterior section is the conjunctiva e9, which protects the eye. Below the sclera e4 are the choroid e10 and retina e11, collectively known as the retina-choroidal tissue. The vitreous body e12 is located between the ciliary body e13 and the retina e11. The loose connective tissue or potential space between the choroid e10 and the sclera e4 is called the suprachoroidal space e14. As shown in Figure 2, the conjunctiva e9 is specifically a single layer of soft, smooth, and elastic mucous membrane that covers the upper and lower eyelids and the front of the eyeball.It is a transparent thin film consisting of multi-layered columnar epithelium and a small amount of connective tissue, and has a small number of mucous glands that can secrete mucus, making the ocular surface smoother. The sclera e4 is divided into three layers: the superficial layer, the stroma, and the lamina fusca. The superficial layer is made of loose connective tissue, while the stroma and brown lamina are made of dense connective tissue and elastic fibers. Therefore, the sclera e4 is dense and strong. During injection, if there is leakage of the drug, it will easily flow back under the conjunctiva and diffuse to form a liquid layer e15, as shown in Figures 2A and 2B.

[0082] As shown in FIG. 3A, the suprachoroidal space e14 is a potential small space between the sclera e4 and the choroid e10, in the absence of any apparent gap in the absence of fluid and / or tissue separation. As shown in FIG. 3B, when fluid e16 is present in the suprachoroidal space e14, a clear gap appears, with the sclera e4 above and the choroid e10 below. Thus, if fluid or other material accumulates between the choroid e10 and the sclera e4, a suprachoroidal space e14 can appear in this region. Thus, by delivering, injecting, and / or injecting a drug formulation into the suprachoroidal space, an accumulation of flow is intentionally created to further create and / or expand the suprachoroidal space formed by the separation of the choroid and sclera.

[0083] The injection locations for any of the ocular injection devices and / or methods of the present invention are all in the region of 6-8 mm from the limbus, for example, supranasal, subnasal, supratemporal, subtemporal, etc. The operator can measure the distance using ophthalmic calipers to confirm the injection site (7-8 mm from the limbus). In this way, they can introduce the drug into the suprachoroidal space from the injection site (e.g., via a needle) and push the drug into the suprachoroidal space away from the insertion site.

[0084] As shown in FIG. 7, the length of the distal blade surface of the needle in the present invention is the maximum distance from the opening in the inner wall of the needle to the tip of the needle.

[0085] As used herein, the term "distal end" or "front end" refers to the end closest to the ocular tissue, and the term "proximal end" or "rear end" refers to the end closest to the operator (such as a doctor or nurse).

[0086] <Specific Examples> <<Example 1>> The ophthalmic injection device of this embodiment is as shown in FIGS. The ophthalmic injection device comprises a syringe 1 , a needle 2 and a sleeve 3 . The distal end of the sleeve 3 is provided with a clamping opening 31. When injecting into the eye, the clamping opening 31 is brought into close contact with the eye tissue, and the eye tissue can form a protrusion inwardly of the sleeve 3.

[0087] Here, the syringe 1 comprises a drug container 11 and a push rod 12 . The proximal ends of the drug container 11 and needle 2 are connected to a push rod 12 , the distal end of which is disposed within the drug container 11 . The proximal end portion of the push rod 12 receives a force, causing a distal end portion of the push rod 12 to move within the drug container 11 to deliver at least a portion of the substance within the drug container 11 through the needle 2 .

[0088] Here, the sleeve 3 is provided with a flow passage 32 and is movably connected to the proximal end of the needle 2 . The distal end of needle 2 is positioned to pass through passage 32 in sleeve 3 and penetrate eye tissue via clamping port 31 .

[0089] The ocular injection method of this embodiment mainly includes the following steps: Step 1: Measure the distance with an ophthalmic caliper and identify the injection site. Step 2: A force is applied to the clamping opening 31 side of the sleeve 3 via the syringe 1 so that the clamping opening 31 side of the sleeve 3 forms a fulcrum on the conjunctival surface. Step 3: The clamping mouth 31 is inverted to the other side with one side as a fulcrum, and the distal end of the needle 2 is inserted into the conjunctival tissue at the injection site. Step 4: Continue inversion via the fulcrum, clamp the other side of the clamping mouth 31 of the sleeve 3 onto the conjunctival surface, clamp the conjunctival tissue with the clamping mouth 31 of the sleeve 3 to form a protrusion within the sleeve 3, and press the distal end of the needle 2 into the ocular target tissue at the injection site. Step 5: Administer the injection so that the drug reaches the administration site.

[0090] This embodiment provides another method of ocular injection, which includes the following steps. Step 1: Measure the distance with an ophthalmic caliper and identify the injection site. Step 2: The clamping opening 31 of the sleeve 3 is aligned perpendicular to the ocular surface at the injection site. Step 3: The distal end of needle 2 is inserted into the conjunctival tissue at the injection site, and the clamping opening 31 of sleeve 3 is brought into contact with the ocular surface at the injection site. Step 4: Cooperation between the syringe 1 and sleeve 3 of the ocular injection device applies force to the ocular tissue at the injection site, causing the held conjunctival tissue to form a protrusion within the sleeve 2, pressing the distal end of the needle 2 into the ocular target tissue at the injection site. Step 5: Administer the injection so that the drug reaches the administration site.

[0091] The needle 2 in this embodiment can be selected from commercially available conventional ophthalmic needles such as 31G and 32G needles, or can be customized and processed by conventional processes for injection needles.

[0092] In this embodiment, the needle and sleeve can be produced as a set. Depending on the thickness from the injection site ocular surface to the suprachoroidal space of drug delivery, the length of the needle 2 exposed from the clamping port 31 can be 500 to 2000 μm, for example, 700 μm, 800 μm, 900 μm, 1000 μm, 1100 μm, 1200 μm, 1300 μm, etc., and needle sleeve assemblies of different specifications can be customized and produced for the operator to select.

[0093] In order to prevent the distal end of the needle 2 from being worn down or piercing the operator, the ocular injection device provided by this embodiment further includes a needle protection cap 8 configured to be movably connected to the sleeve 3 and the needle base 21. The operator removes the needle protection cap 8 during use, replaces it after use, and disposes of it together with the other assemblies of the injection device.

[0094] A 700 μm needle sleeve assembly was selected to inject into the suprachoroidal space of the rabbit's eye according to the ocular injection method of this embodiment. As a result, it was found that the ocular injection device provided by this embodiment not only succeeded in puncturing in one go, but also successfully delivered the drug to the target tissue of the eye, and the leakage of the drug solution under the conjunctiva was significantly reduced.

[0095] The present invention was developed as a result of research into the application of force to eye tissue by an ocular injection device, and discovered that the force applied to eye tissue by an ocular injection device should not be too large or too small. If the size is too small, the conjunctival tissue cannot elastically deform to form a protrusion, whereas if the size is too large, the conjunctival tissue of the eye may be destroyed. When the applied force is between 0.4N and 10N, the conjunctival tissue can form a protrusion within the sleeve 3, and the protruding conjunctival tissue can automatically recover after the injection is completed, ensuring a significant reduction in the leakage of drug solution under the conjunctiva. When the applied force is controlled to 2N to 6N, the drug solution does not leak under the conjunctiva.

[0096] After studying the shape of the clamping port 31, the present invention has found that the objective of the present invention can be achieved by selecting a clamping port 31 of different shapes for the ophthalmic injection device, such as a circular, hexagonal, octagonal, rectangular or irregular shape. Here, if the clamping port 31 of the ocular injection device is circular, it is not only advantageous to avoid damage to the conjunctiva of the eye, but also advantageous to the recovery of ocular tissue during injection. When the inner diameter of clamping port 31 is controlled to 0.5 mm to 10 mm, the conjunctival tissue forms an arch-shaped protrusion structure, and the needle of the ocular injection device is inserted through the protrusion apex of the ocular tissue to reach the administration site in the eye, thereby further fixing the needle to the conjunctival tissue at the injection site, making the injection at the confirmed injection site easier. When the inner diameter of the clamping opening 31 is controlled to 1-6 mm, the arch-shaped protrusion structure formed is better, and when the inner diameter of the clamping opening 31 is 1-3 mm, the injection effect is the best.

[0097] <<Example 2>> Details of the ocular injection device of this example are shown in Figures 7A-7B, in which the blade face at the distal end of needle 2 has a length of 700 µm.

[0098] The needle of this embodiment can be manufactured by the following steps. Step 1: Using a seamless welding machine, the stainless steel strip is wound into a tube by laser welding, and then passed through equipment such as a thinning machine, a tube drawing machine, and a distortion straightening machine to be thinned into a stainless steel capillary with a diameter of 31G. Step 2: Use a tube cutter to cut the capillary to length. Step 3: Use a needle placement machine to align and fix the capillaries. Step 4: Use the grinding machine to set the angle at 18° for the first grinding, and the rotation angle for the second and third grinding is 35°. Grinding is stopped when the cutting edge length reaches 700 μm. Step 5: Wash. Step 6: The needles are then moved to the 100,000-class workshop for assembly.

[0099] The results of the needle puncture experiment showed that the blade puncture force of the needle manufactured by the above process was 0.4N or less.

[0100] <<Example 3>> Details of the ocular injection device of this example are shown in Figures 7A-7B, in which the cutting edge at the distal end of needle 2 is 550 μm long.

[0101] The needle of this embodiment can be manufactured by the following steps. Step 1: Using a seamless welding machine, the stainless steel strip is wound into a tube by laser welding, and then passed through equipment such as a thinning machine, a tube drawing machine, and a distortion straightening machine to be thinned into a stainless steel capillary with a diameter of 31G. Step 2: Use a tube cutter to cut the capillary to length. Step 3: Use a needle placement machine to align and fix the capillaries. Step 4: Use the grinding machine to set the angle at 22° for the first grinding, and the rotation angle for the second and third grinding is 35°. Grinding is stopped when the cutting edge length reaches 550 μm. Step 5: Wash. Step 6: The needles are then moved to the 100,000-class workshop for assembly.

[0102] The results of the needle puncture experiment showed that the blade puncture force of the needle manufactured by the above process was 0.5N or less.

[0103] <<Example 4>> Details of the ocular injection device provided by this embodiment are shown in Figures 7A-7B, in which the cutting edge at the distal end of needle 2 is 250 μm long.

[0104] The needle of this embodiment can be manufactured by the following steps. Step 1: Using a seamless welding machine, the stainless steel strip is wound into a tube by laser welding, and then passed through equipment such as a thinning machine, a tube drawing machine, and a distortion straightening machine to be thinned into a stainless steel capillary with a diameter of 32G. Step 2: Use a tube cutter to cut the capillary to length. Step 3: Use a needle placement machine to align and fix the capillaries. Step 4: Use the grinding machine to set the angle at 30° to perform the first grinding, and the second and third grinding rotation angles are 35°. Grinding is stopped when the cutting edge length reaches 250 μm. Step 5: Wash. Step 6: The needles are then moved to the 100,000-class workshop for assembly.

[0105] The results of the needle puncture experiment showed that the blade puncture force of the needle manufactured by the above process was close to 0.7N.

[0106] The ophthalmic injection device provided in Examples 2 to 4 of the present invention was used to perform suprachoroidal injection according to the injection method of Example 1. As a result, it was discovered that in Examples 2 to 4, not only was there no backflow of the medicinal solution, but the puncture force applied by the operator was further reduced, making the operation more convenient and further reducing the safety risk caused by puncture faced by the patient's ocular tissues.

[0107] The blade surface of the distal end of the needle 2 of the present invention can not only be processed into a three-sided structure by the triple-cut process provided by the above-mentioned embodiments, but can also be processed into the distal end of the needle 2 of embodiments 2 to 4 by one or more cuts.

[0108] <<Example 5>> As shown in Figures 8 and 9, when the ophthalmic injection device of this embodiment performs a clamping operation, sleeve 3 and the clamped eye tissue form a chamber 33 with a sealed bottom.

[0109] Here, the sleeve 3 has a transparent structure or has a viewing window 34 on the tube wall of the sleeve 3, and the operator observes the reverse osmosis status of the chemical solution through the transparent sleeve 3 or the viewing window 34.

[0110] Injection is performed according to the suprachoroidal injection method of Example 1, and the reflux medicinal solution produced by the ophthalmic injection device of this example is automatically refluxed into the bottom sealed chamber 33 formed between the sleeve 3 and the clamped ocular tissue through an injection port formed at the injection position. The operator can observe the reverse osmosis status of the medicinal liquid through the sleeve 3 or the viewing window 34 on the sleeve 3, quickly determine whether the injection is successful or not, and quickly take corrective measures based on the result. For example, the operator can increase the puncture force so that the distal end of the needle 2 penetrates the sclera without removing the needle 2, or can adjust the length of the needle 2 exposed from the distal end clamping opening 31 of the sleeve 3 using the adjustment assembly 4 of the present invention so that the distal end of the needle 2 penetrates the sclera without removing the needle 14.

[0111] At the same time, the ocular injection device of this embodiment collects the refluxed medicinal solution in a concentrated manner within chamber 33, thereby preventing the refluxed medicinal solution from diffusing to the surrounding area on the ocular surface, and greatly reducing the difficulty of cleaning the ocular surface during and after the injection is completed.

[0112] In this embodiment, to facilitate the operator in judging the amount of refluxed fluid and assessing whether the injection was successful, a volumetric scale 35 for the amount of refluxed fluid is provided in the visible window 34 or transparent sleeve 3, and a warning limit is provided on the scale to warn the operator that the injection has failed and that the injection should be stopped.

[0113] <<Example 6>> This embodiment provides an ophthalmic injection device including a needle hub 21 whose proximal end is connected to the distal end of a drug container 11 and whose distal end is connected to the proximal end of a needle 2, as shown in FIG. The needle hub 21 is provided with a passage 211 for conveying at least a portion of the substance from the drug container 11 via the passage 211 to the needle 2 . The needle base 21 is provided with flanges 212 at its proximal and distal ends, which are arranged to connect with the sleeve 3 .

[0114] A connection part 213 is provided at the distal end of the needle base 21 and is fixedly connected to the proximal end of the needle 2 . In this embodiment, the proximal end of the needle 2 can be inserted and passed through the connecting portion 213, and the space between the connecting portion 313 and the proximal end of the needle 2 can be sealed and fixed by a dispensing method.

[0115] The flange 212 is provided with a rib 214 so that the operator can easily grip the hub 21 when attaching it.

[0116] In the ophthalmic injection device of this embodiment, by fixing the needle to the connection portion 213, not only is it possible to prevent the distal end of the needle 2 from swinging and bending during puncture, but it also becomes easier for the operator to install, and it becomes even easier for the adjustment assembly 4 of the present invention to adjust the length of the distal end of the needle 2 exposed from the clamping opening 31 of the sleeve 3.

[0117] <<Example 7>> As shown in Figures 11 to 14, the ophthalmic injection device of this embodiment has an adjustment assembly 4 between the proximal and distal ends of the needle base 31, which cooperates with the sleeve 3 to adjust the length of the needle 2 exposed from the clamping opening 31 of the sleeve 3.

[0118] The adjustment assembly 4 is provided with a screw thread that is used on the outer wall of the distal end portion of the needle base 21 and on the inner wall of the sleeve 3, and the screw thread 41 is used to rotate the sleeve 3 and adjust the length of the distal end of the needle 2 exposed from the clamping opening 31 of the sleeve 3.

[0119] The adjustment assembly 4 is provided with a telescopic rod assembly 42 and a first operating rod 43. The telescopic rod assembly 42 includes an outer tube 422, an inner tube 422, a guide rail 423, and a drive mechanism 424. The outer tube 421 is connected to the needle hub 21 , and the inner tube 422 is connected to the connection portion 313 . The guide rail 423 is attached inside the outer tube 421 , and the inner tube 422 moves axially on the guide rail 423 by being driven by a driving mechanism 434 .

[0120] The first operating rod 431 has one end movably connected to a drive mechanism 434 and the other end fixed to the outside of the sleeve 3 . The first operating rod 43 acting on the outside of the sleeve 3 is used to operate the drive mechanism 434 in conjunction with the inner tube 422 to move axially on the guide rail 423, thereby enabling free adjustment of the length of the needle 2 exposed from the clamping opening 31 of the sleeve 3.

[0121] The drive mechanism 434 of the telescopic rod assembly 42 is a linear drive mechanism, and the length of the needle 2 exposed from the clamping opening 31 of the sleeve 3 can be adjusted by driving the drive mechanism 434 of the telescopic rod assembly 42 with the first operating rod 43 using conventional methods such as a lead screw, rack and pinion, ball screw, or cylinder.

[0122] The operator can measure the length of needle 2 exposed through clamping opening 31 of sleeve 3, adjusted by adjustment assembly 4, with an ophthalmic caliper. The adjustment assembly 4 of this embodiment has the advantage of allowing the exposed length of the distal end of the needle 2 to be flexibly adjusted, making it suitable for use with eye wall tissues such as patients with abnormal scleral thickness.

[0123] At the same time, in order to facilitate the operator to more accurately observe the length of the needle 2 being adjusted, this embodiment further provides volume graduations of different variables on the outer wall of the transparent sleeve 3 and on the visible window 34. When manufacturing the adjustment assembly 4 of this embodiment, a start line for adjusting the length of the needle 2 can be provided on the male thread of the connection part 313 and aligned with a scale start line provided on the outer wall of the transparent sleeve or the visible window, and the distal end of the needle 2 can be aligned with the sleeve clamping port. By actuating the adjustment assembly to move the distal end of the needle axially into the sleeve clamping opening, the operator can precisely adjust the length of the needle 2 exposed from the clamping opening 31 of the sleeve 3, eliminating the need to measure using ophthalmic calipers.

[0124] In this embodiment, the distal end of the needle 2 is further provided with volume graduations for different variables. The volume graduation lines can be marked by a laser marking method. When the volume graduation marks on the distal end of the needle 2 are aligned with the clamping opening of the sleeve, the length of the distal end of the needle 2 exposed from the clamping opening 31 of the sleeve 3 can be measured without the need to use ophthalmic calipers to measure.

[0125] <<Example 8>> The ophthalmic injection device of this embodiment is as shown in Figures 15 to 16. An adjustment release member 5 is provided between the needle base 21 and the sleeve 3, and the adjustment release member 5 is configured to adjust the length of the needle 2 exposed from the distal end clamping port 31 of the sleeve 3, and pushes the distal end of the needle 2 so that it is inserted into the target tissue of the eye through the distal end clamping port 31 of the sleeve 3.

[0126] The adjustment release member 5 includes a telescopic assembly 51 , a release assembly 52 , and a second operating rod 53 . The telescopic assembly 51 of this embodiment is the same as the telescopic rod assembly of the eighth embodiment, and the second operating rod 53 is the same as the first operating rod of the eighth embodiment.

[0127] The release assembly 521 has one end connected to the flange 312 of the needle hub 21 and the other end connected to the proximal end of the sleeve 2 . A first stopper 54 is provided at the other end of the second operating rod 53 connected to the sleeve, and a regulating hole 36 provided through the sleeve 3 is engaged between the needle base 21 and the sleeve 3. The second operating rod 53 and its first stopper are pulled out to release the release assembly 52, thereby pushing the distal end of the needle 2 so as to be inserted into the eye tissue through the clamping port 31 of the sleeve 3.

[0128] The release assembly 52 is either a return spring, a compressed gas container, or a container containing a propellant.

[0129] When manufacturing the adjustment release member 5 of this embodiment, the first stop piece 54 can be manufactured into a locking piece, a locking groove, a locking ring, a pawl, etc. This allows the release assembly 52 to release the pulling force of the sleeve on the proximal end of the needle base, driving the distal end of the needle 2 to move towards the clamping opening 31 at the distal end of the sleeve 3, limiting its insertion into the eye tissue. When it is necessary to release the pulling force of the release assembly 52, the operator can remove the first stopper 54 by pulling out the second operating rod 53.

[0130] By operating the second operating rod 53, the operator can adjust the length of the needle 2 exposed from the clamping opening 31 of the sleeve 3, and by pulling out the second operating rod 53 having the first stopper 54, the release assembly 52 can push the needle 2 so that the distal end of the needle 2 is inserted into the target eye tissue through the distal end clamping opening 31 of the sleeve 3.

[0131] The present embodiment further provides another method for injecting eye tissue, which includes the following steps. Step 1: The length of the needle 2 exposed from the clamping opening 31 at the distal end of the sleeve 3 is adjusted by the adjustment release member 5 of the ophthalmic injection device of this embodiment. Step 2: Measure the distance with an ophthalmic caliper and confirm the injection site. Step 3: The clamping opening 31 of the sleeve 3 of the ophthalmic injection device is aligned perpendicular to the injection site, the conjunctiva. Step 4: The syringe 1 and sleeve 3 of the ophthalmic injection device cooperate to apply force to the conjunctival tissue at the injection site, bringing the clamping opening 31 of the sleeve 3 into close contact with the conjunctival tissue to clamp it, and protruding the clamped conjunctival tissue toward the sleeve 3. Step 5: Release the release assembly 52 by removing the first stopper 54 via the second operating rod 53, and drive the distal end of the needle 2 to be inserted through the clamping port 31 at the distal end of the sleeve 3 from the protruding conjunctival tissue into the target tissue of the eye. Step 6: Administer the injection so that the drug reaches the administration site.

[0132] As a result of the suprachoroidal injection using the ophthalmic injection device and ophthalmic injection method of this embodiment, it can be seen that the distal end of needle 2 of the ophthalmic injection device of this embodiment forms an arch structure with the protrusion formed by the transocular tissue, and needle 2 of the ophthalmic injection device is inserted into the target ocular tissue through the upper part of the ocular tissue protrusion, making it easier to inject at the confirmed injection site.

[0133] When industrially manufacturing the ocular injection device of this embodiment, the stroke length adjusted by the release assembly 52 is the distance from the distal end of the needle 2 to the clamping port 31 of the sleeve 3 when the first stopper 54 limits the release assembly 52 from releasing the thrust.

[0134] <<Example 9>> The ophthalmic injection device of this embodiment includes a thrust assembly 6, as shown in FIGS. The thrust assembly 6 is configured to generate a constant thrust on the proximal end portion of the push rod 12, pushing the distal end of the push rod 12 in the drug chamber 11 to move toward the needle 2, causing at least a portion of the drug in the drug chamber 11 to be injected through the injection site into the ocular target tissue and reach the administration site.

[0135] In manufacturing the thrust assembly 6 of the ocular injection device of this embodiment, any of the mechanical structures of the prior art spring ball mechanism, spring pin, cylinder, or reservoir containing the propellant may be used.

[0136] When the operator performs a drug injection after completing the puncture, the operator can use the thrust assembly 6 to generate a constant thrust at the proximal end portion of the push rod 12, thereby injecting the drug into the target eye tissue at a constant speed, thereby avoiding the operator applying too much force or pushing the push rod 12 too fast, which would result in excessive local injection pressure and damage to the eye tissue at the drug administration site.

[0137] The injection device of this embodiment further includes a second stopper 7 configured to selectively limit the movement of the push rod 12 relative to the medication container. When manufacturing the second stopper 7 of the ophthalmic injection device of this embodiment, any mechanical structure capable of limiting the movement of the push rod 12 relative to the drug container is used, such as a locking ring, a locking groove, a pawl, or the like commonly used in the prior art. When the operator is ready to perform a drug injection, he or she simply pulls out the second stopper 7 to release the thrust assembly 6 .

[0138] The ophthalmic injection device and method of use provided by the present invention can be widely applied to ophthalmic and related diseases. Ophthalmic diseases include, but are not limited to, uveitis, glaucoma, diabetic macular edema or retinopathy, macular degeneration, retinoblastoma, and genetic diseases, and are particularly suited to drug delivery, such as drugs to localized regions at the posterior part of the eye, e.g., the retina-choroidal tissue, the macula, and the optic nerve at the posterior stage of the eye. The ocular injection device and method of use provided by the present invention can also be used in gene-based therapeutic applications to deliver a pharmaceutical solution containing a therapeutic gene fragment to the suprachoroidal space and any one or more carriers selected from DNA, RNA or oligonucleotides to a target ocular tissue.

[0139] The drug container 11 of the present invention contains a drug solution of one or more drug active agents, which may be selected from antibodies, antiviral agents, chemotherapy agents, analgesics, anesthetics, aptamers, antihistamines, anti-inflammatory agents, and antitumor agents.

[0140] Each embodiment of the present invention is described in a progressive manner, and each embodiment is described by focusing on the differences from other embodiments, and the same or similar parts between the embodiments can be referenced to each other. The apparatuses disclosed in the embodiments correspond to the methods disclosed in the embodiments, so they will only be briefly described, and reference may be made to the description of the method section for relevant content.

[0141] <<Example 10>> The ophthalmic injection assembly includes a sleeve 3 and a needle 2, as shown in Figures 19, 20 and 21. The needle 2 is fittable within the sleeve 3. As shown in FIGS. 22 and 23, a clamping opening 31 is provided at the end of the sleeve 3. When in use, the tip of the needle 2 can pass through the clamping opening 31 .

[0142] 23, the clamping mouth 31 has an annular end surface 33, that is, the end surface of the sleeve 3 is annular, including an inner curved line and an outer curved line. There is a certain distance between the inner curved line and the outer curved line. Both the inner and outer curves are smooth curves. The space surrounded by the inner curve is the clamping opening. The area between the inner and outer curves is the sleeve wall. In this embodiment, the clamping opening 31 is circular. The annular end surface 33 is an annular end surface as shown in FIG. In other embodiments, an elliptical annular end face as shown in FIG. 25 or a polygonal annular end face as shown in FIG. 26 can be used. Different jaw shapes, such as circular, elliptical, hexagonal, octagonal, rectangular or irregular, can all be used to achieve pressure of the jaw against the eye tissue. The annular end surface 33 being a circular end surface is not only more advantageous in avoiding damage to the eye conjunctiva, but also more advantageous for the healing of eye tissue during injection.

[0143] The minimum inner diameter of the clamping opening 31 is 0.5 mm to 10 mm, preferably 1 mm to 6 mm, and more preferably 1 mm to 3 mm.

[0144] 23, the end of the sleeve 3 is a contracted portion 32. The clamping opening 31 is located at the end of the contracted portion 32. The cross section of the contracted portion 33 gradually becomes larger in the direction away from the clamping opening 31 .

[0145] The length of the blade surface at the tip of needle 2 is less than 1100 μm, preferably less than 900 μm, further preferably less than 700 μm, even more preferably 550 μm or less, and most preferably 250 to 550 μm. The needle structure can be seen in Figures 7A and 7B.

[0146] When the needle 2 is engaged with the sleeve 3, the distance d shown in FIG. 23 is the length of the part where the tip of the needle 2 exceeds the clamping opening 21, which is 500 to 2000 μm. The distance from the tip of needle 2 to annular end surface 33 is the length of the part where the tip of needle 2 extends beyond clamping opening 31 . In this embodiment, the annular end surface 33 is a plane and the needle 2 is perpendicular to the annular end surface 33. That is, the axial direction of the needle 2 is perpendicular to the plane in which the annular end surface 33 lies.

[0147] When the clamping opening 31 of the sleeve 3 comes into contact with and is pressed against eye tissue, the clamping opening 31 is closed. As shown in FIG. 27, the eye tissue is formed with protrusions 200 that face inwardly into the sleeve. As shown in FIG. 28, when the clamping opening 31 is closed, the chamber 34 within the sleeve 3 forms a sealed chamber 34. If backflow occurs, the backflowing medicinal solution is contained in the sealed chamber 34, and when the clamping opening 31 is separated from the ocular tissue, the medicinal solution is less likely to leak from the sealed chamber 34, and dripping of the medicinal solution onto the ocular tissue can be prevented.

[0148] The sleeve 3 is provided with a flow passage, and the needle 2 is movably connected within the flow passage. The needle 2 is connected to the sleeve 3 through a channel, which is advantageous for the needle to maintain a relative position with the clamping opening of the sleeve when puncturing and reaching the injection point.

[0149] Once the needle 2 is connected to the sleeve 3, returning to Fig. 22, a needle hub 21 is connected to one end opposite the tip of the needle 2. The needle hub 21 includes a guide tube 211 at the front end. The needle 2 is fixed in a guide tube 211 and extends into a needle hub 21 . The sleeve 3 is attached to the guide tube 211, and the relative positions of the sleeve 3 and the needle 2 are fixed.

[0150] <<Example 11>> In this embodiment, in addition to the tenth embodiment, an adjustment assembly is provided between the sleeve 3 and the needle 2 for adjusting the length of the tip portion of the needle 2 beyond the clamping opening 31. A needle base 21 is connected to the needle 2 at one end opposite the tip, and is connected to the sleeve 3 by an adjustment assembly. The adjustment assembly includes a male threaded portion on the needle hub 21 and a corresponding female threaded portion 101 on the sleeve 3 . The male thread portion 102 and the female thread portion 101 can be engaged with each other to be connected. The engagement of the male screw portion 102 and the female screw portion 101 allows the needle hub 21 and the sleeve 3 to rotate relative to each other, thereby enabling adjustment of the needle length. Specifically, as shown in FIG. 29, the needle hub 21 includes a guide tube 211 on which a male thread portion 102 is provided. The guide tube 211 is connected to the front end of the needle base 21 and is fitted and connected to the needle, and is used to strengthen the strength of the needle and prevent the needle from bending or shaking during puncturing. As shown in FIG. 30, a female screw portion 101 is provided inside the sleeve 3 . An adjustment assembly is provided between the needle hub 21 and the sleeve 3 . When adjusting the length of the needle 2, it is hardly affected by other parts such as a syringe. The screw pitch is 50 to 200 μm, and more preferably 50 to 150 μm.

[0151] Another embodiment is shown in FIG. The side wall of the sleeve 3 is provided with a viewing window 35 made of a transparent material, or the sleeve is a member of a transparent material. Providing a viewing window 35 or using a sleeve made of a transparent material makes it easier to observe the backflow of the drug solution, allowing a quick determination of whether the injection was successful. The visible window 35 or the transparent sleeve 3 is provided with volume graduations 351 along the axial direction of the sleeve 3, which allows the backflow amount of the medicinal liquid to be observed in real time. If a warning limit is exceeded, it is useful to indicate to the operator that an injection has failed and to stop the injection.

[0152] An adjustment assembly is provided to facilitate adjustment of the length of the tip of needle 2 beyond jaw 31 to control the depth of penetration. It can be applied to different patients and can be punctured at different locations on the eye. For example, it can be applied to eye wall tissue for patients with abnormal scleral thickness.

[0153] <<Example 12>> In this embodiment, an adjustment assembly is added to the structure of Example 10. As shown in FIG. 32, a needle base 21 is connected to the rear end of the sleeve 3, and an adjustment assembly is provided therein. The adjustment assembly includes a telescopic rod assembly 42 and a drive mechanism 41. The telescopic rod assembly 42 includes an outer tube 421 and an inner tube 422. One end of the outer tube 421 is connected to the rear end of the needle hub 21 via a connection block 423, and the other end is fitted into the inner tube 422. The other end of the inner tube 422 is connected to the rear end of the needle 2. The outer tube 421, the inner tube 422, and the needle 2 are sequentially connected to each other. The driving mechanism 41 is connected to the inner tube 422 and can drive the inner tube 422 to move along the axial direction relative to the outer tube 421, thereby moving the needle 2 in conjunction with the inner tube 422. A guide tube 211 is fitted around the outside of the needle 2 , and both ends of the needle 2 are exposed from the guide tube 211 . The front end of the hub 21 is fitted outside the guide tube 211. The guide tube 211 and the hub 21 are capable of sliding relative to each other. FIG. 33 shows the reception of the front end of the needle 2 within the sleeve 3 via the adjustment assembly.

[0154] As shown in FIG. 34, the drive mechanism 41 includes a drive housing 411, a rack guide 413, a drive gear 412, and an operating rod 414. The drive housing 411 has one end connected to the outer tube 422 and the other end slidably connected to the inner tube 422 . The rack guide 413 is connected to the inner tube 422 and is disposed in the axial direction. In this embodiment, the inner tube 422 has a recessed portion at its center, and the rack guide 413 is provided directly in the recessed portion of the inner tube 422 . The drive gear 412 is hinged within the drive housing 411 and is meshingly connected to a rack guide 413 . One end of the operating rod 414 is connected to the drive gear 412, and the other end passes through a through hole in the drive housing 21 and a through hole in the hub to reach the outside of the hub 21. By rotating the operating rod 412, the drive gear 414 can be rotated in conjunction with the operating rod 412. By rotating the operating rod 414 in the drive mechanism, the drive gear 412 is rotated, and the drive gear 412 moves the rack guide 413 in conjunction with the drive gear 412 . The inner tube 422 moves together with the rack guide 413, and moves the needle 2 in the axial direction in conjunction with the inner tube 422, thereby adjusting the position of the needle 2.

[0155] Another embodiment is shown in FIGS. The inner pipe 422 is divided into upper and lower two sections, the upper inner pipe being fitted into the outer pipe 421 and the lower inner pipe being connected to the guide pipe 211 . The upper and lower inner tubes are connected by a rack guide 413 , which makes it easy to install the drive gear 412 in the center of the drive housing 411 .

[0156] Yet another embodiment is shown in FIG. The rear end of the needle 2 passes through the inner tube 422 and the outer tube 421 in sequence, and then passes beyond the outer tube 421 . The needle 2 is fixedly connected to the inner tube 422 via the guide tube 211 , and the rear end of the needle 2 extends beyond the inner tube 422 toward the outer tube 421 to the other end of the outer tube 421 . In use, it engages with a syringe and the rear end of the needle 2 enters into the syringe.

[0157] <<Example 13>> In this embodiment, a release assembly is added to the structure of Example 10.

[0158] As shown in Fig. 38, a hub 21 is connected to the rear end of the sleeve 3. A release assembly 5 including an elastic member 51 and a first stopper 52 is provided between the sleeve 3 and the hub 21. The sleeve 3 is connected to the needle hub 21 via an elastic member 51 . The first stopper 52 has one end detachably connected to the sleeve 3 and / or the other end detachably connected to the needle hub 21 . When the first stopper 32 is connected to the sleeve 3 and the hub 21, the elastic member 51 is in tension and provides an axial tensile force. The elastic member 51 may be a return spring, a compressed gas container, or a container containing a propellant. The first stopper 52 is a locking piece, a locking groove, a locking ring, or a pawl. In this embodiment, as shown in FIG. 40, the elastic member 51 is a return spring, and the first stopper 52 is a locking ring.

[0159] As shown in FIG. 38, the elastic member 51 is stretched to increase the distance between the needle hub 21 and the sleeve 3 . In order to maintain the distance between the hub 21 and the sleeve 3 , a first stopper 52 is inserted between the hub 21 and the sleeve 3 . At this time, the elastic member is in an extended state, and the front end of the needle 2 is withdrawn into the sleeve 3. During use, the clamping opening 31 is maintained in contact with the eye tissue. After the first stopper 52 is removed, the needle base 21 moves forward, causing the front end of the needle 2 to protrude from the clamping opening 31 and puncture the eye tissue as shown in FIG.

[0160] Similarly, an adjustment assembly is provided between the sleeve 3 and the hub 21 and includes a telescopic rod assembly 42 and a drive mechanism 41 . The telescopic rod assembly 42 includes an outer tube 421 and an inner tube 422 . One end of the outer tube 421 is connected to the front end of the needle hub 21, and the other end is fitted into the inner tube 422. The other end of the inner tube 422 is connected to the rear end of the needle 21. The outer tube 421 , the inner tube 422 and the needle 21 communicate with each other in sequence, or the rear end of the needle 2 passes through the inner tube 422 and the outer tube 421 in sequence and then passes beyond the outer tube 421 . The driving mechanism 41 is connected to the inner tube 421 and drives the inner tube 422 to move it in the axial direction relative to the outer tube 421, thereby moving the needle 21 in conjunction with it.

[0161] As shown in FIG. 34, the drive mechanism 41 includes a drive housing 411, a rack guide 413, a drive gear 412, and an operating rod 414. The drive housing 411 has one end connected to an outer tube 421 and the other end slidably connected to an inner tube 422 . The rack guide 413 is connected to the inner tube 421 and is disposed in the axial direction. The drive gear 412 is hinged within the drive housing 411 and is meshingly connected to a rack guide 413 . One end of the operating rod 414 is connected to the drive gear 412, and the other end passes through a through hole of the drive housing 411 and a through hole of the hub to reach the outside of the hub 21. The rotary operating rod 414 can rotate in conjunction with the drive gear 412 .

[0162] In yet another embodiment, the operating rod 414 is removably connected to the drive gear 412 . When the operating rod 414 is separated from the hub 21, the first stopper 52 can be interlocked to separate the first stopper from the sleeve 3 and / or the hub 21. By providing the operating rod 414 outside the needle base 21, after adjustment of the length of the needle 2 using the operating rod 414 is completed, the operating rod 414 can be removed by pulling out the operating rod 414, making observation easier. The operating rod 414 then cooperates with the first stopper 52 to separate it from the sleeve 3 and the needle hub 21, facilitating one-handed operation by the operator. In this embodiment, the structure of the adjustment assembly 4 may be the same as that of the previous embodiment, and the adjustment assembly may be located outside the needle hub, in the center of the elastic member 5 .

[0163] <<Example 14>> As shown in FIG. 41, the ophthalmic injection device includes a syringe 1 and an ophthalmic injection assembly according to any one of Examples 10 to 13 attached to the syringe.

[0164] 42, the syringe 1 includes a drug container 11 and a push rod 12. The push rod 12 is slidable within the drug container 11. The drug container 11 is used for storing a drug solution and is matingly connected to the injection assembly 2 . The injection device further includes a needle protection cap 8 which engages the needle 2 .

[0165] <<Example 15>> In this embodiment, in addition to the embodiment 14, a thrust assembly 6 is provided between the end of the push rod 12 and the drug container 11 for generating a constant thrust on the push rod.

[0166] The thrust assembly 6 may be a spring ball mechanism, spring pin, cylinder or container containing propellant, generating a constant thrust threshold of 6N or less. The thrust assembly 6 generating a constant thrust means that if the thrust received by the thrust assembly is less than a threshold, the thrust assembly cannot propel the thrust assembly, and if the thrust is greater than the threshold, the thrust assembly can offset the thrust to maintain the thrust at the threshold. For example, if the threshold is 5N, a force of 4N will not be able to propel the thrust assembly, and if the thrust is 7N, the thrust assembly will be able to hold the thrust at 6N.

[0167] The injection device further includes a second stopper 7 disposed between the push rod 12 and the drug container 11, which is used to limit the magnitude of the push stroke of the push rod. The second stopper 7 is a locking piece, a locking groove, a locking ring, or a pawl.

[0168] <<Example 16>> A method of using an ophthalmic injection device, comprising using the ophthalmic injection device of Example 14 or 15 to bring the clamping mouth 31 of the sleeve 3 into contact with and press against the ocular tissue at the injection site, so that the ocular tissue at the injection site forms a protrusion 200 within the sleeve 3.

[0169] The sleeve clamping opening 31 is brought into contact with and pressed against the ocular tissue at the injection site, and after the ocular tissue at the injection site forms a protrusion 200 within the sleeve, the tip of the needle 2 is caused to puncture the conjunctival tissue and scleral tissue at the injection site so that the distal end of the needle reaches the ocular target tissue at the injection site.

[0170] Before the sleeve clamping opening 31 comes into contact with and presses against the ocular tissue at the injection site, the length of the needle tip exposed from the clamping opening is adjusted according to the thickness of the ocular tissue at the injection site. The adjustment method is carried out using the adjustment assembly in the injection assembly described above.

[0171] Alternatively, one side of the sleeve clamping opening 31 is first brought into contact with the ocular surface, and then the needle is turned over using this contact point as a fulcrum to insert the needle into the ocular tissue at the injection site. Evertion continues until the other side of the clamping opening 31 contacts the ocular surface, causing the ocular tissue to form a protrusion within the sleeve 3. The ocular surface may be the conjunctival surface or other ocular tissue.

[0172] The thickness of the ocular tissue at the injection site is detected by one or more detection methods including optical coherence tomography (OCT), enhanced optical coherence tomography (EDI-OCT), sweeping optical coherence tomography (SS-OCT) or ultrasound biomicroscopy (UBM).

[0173] After the distal end of the needle 2 reaches the ocular target tissue at the injection site, the push rod 12 is pushed to inject at least a portion of the substance in the drug container 11 through the injection needle 2 into the ocular target tissue.

[0174] When the push rod 12 is pushed to deliver at least a portion of the substance in the drug container 11 through the distal end of the needle 2 to the target ocular tissue, the amount of reflux drug solution in the sleeve 3 is observed. A viewing window or transparent sleeve of the syringe device can be used to observe and record the volume of refluxed medication fluid by referencing the volume graduation lines.

[0175] <Test Example 1> Experiment No. 1-1. The ophthalmic injection assembly and syringe of Example 10 are used to form an injection device, and based on the normal thickness of the sclera tissue and choroid of New Zealand rabbits, a sleeve needle with an effective length of 700 μm and a blade length of 500±50 μm is set, and the clamping opening 31 of the sleeve is circular and has an inner diameter of 1.5 mm.

[0176] The effective length, ie the length of the tip of needle 2 beyond clamping opening 31, is 700 μm, ie the distance from the tip of needle 2 to the annular end face is 700 μm. Needle 2 is approximately perpendicular to the annular end face.

[0177] Test method: After anesthetizing with pentobarbital, propantheline hydrochloride eye drops were used to anesthetize the ocular surface, and 1 to 2 minutes after administration, a suprachoroidal injection was performed using a homemade sleeve needle. Test animals: healthy New Zealand rabbits, 1.8-2.2 kg Injection frequency: One injection in the right eye Injection reagent: 0.2% ICG, 100 μL

[0178] The method for injection into the suprachoroidal space is as follows. Step 1: Measure the distance with an ophthalmic caliper and identify the injection site. Step 2: The injection reagent is aspirated, and force is applied to the clamping opening 31 side of the sleeve via the syringe, so that the clamping opening 31 side of the sleeve is brought into close contact with the ocular tissue at the injection site, forming a fulcrum on the ocular surface at the injection site. Step 3: The injection device is inverted around the fulcrum as an axis to the other side of the sleeve clamping port 31, and the distal end of the needle 2 is inserted into the conjunctival tissue at the injection site. Step 4: Continue inversion via the fulcrum, and clamp the other side of the sleeve clamping mouth 31 against the ocular surface at the injection site, and clamp the ocular tissue with the sleeve clamping mouth 31 to form a protrusion 200 in the sleeve 3. Press the distal end of the needle 2 perpendicularly into the sclera to reach the ocular target tissue at the injection site. Step 5: Administer the injection so that it reaches the administration site.

[0179] During the injection process, any signs of reflux, ocular surface diffusion, and subconjunctival retention, diffusion, bleeding, or hyperemia are recorded. The rabbits are sacrificed, the eyes enucleated, and flat samples of fundus tissue are prepared. Photographs were taken to record the distribution of the ICG solution in the suprachoroidal space.

[0180] Test results: Observation revealed no reflux or subconjunctival residue due to ICG injection, and fundus tissue sections showed that ICG was transfected into all fundus tissues, and stained fundus tissues were light green. The fundus tissue sections are shown in Figure 44.

[0181] <Test Example 2> In addition to Test Example 1, the other conditions were not changed, but the inner diameter of the sleeve clamping opening was adjusted to consider the effect of the inner diameter of the sleeve 3 on the backflow of the drug solution. The inner diameters of the sleeve 3 were 0.25 mm (experiment number 1-2), 0.5 mm (experiment number 1-3), 1.0 mm (experiment number 1-4), 2.0 mm (experiment number 1-5), 2.5 mm (experiment number 1-6), 3.0 mm (experiment number 1-7), 5.0 mm (experiment number 1-8), and 10.0 mm (experiment number 1-9), respectively.

[0182] Test Examples 1 and 2 are summarized as follows.

[0183] [Table 1]

[0184] The test results showed that when the inner diameter was 1 to 3 mm, there was no obvious reflux or diffusion onto the ocular surface or subconjunctivally. Tissue section status showed that the stained area was 3 / 5 to 3 / 4, indicating the injection was successful.

[0185] <Test Example 3> The difference from Test Example 1 is that the injection reagent is an AAV8-EGFP recombinant adeno-associated virus, and the target gene is EGFP. Dose: 1.02E+11vg / eye, single injection in the left eye.

[0186] During the injection process, any signs of reflux, ocular surface diffusion, and subconjunctival retention, diffusion, hemorrhage, or hyperemia are recorded. Immediately after injection, an OCT examination is performed on the injected eye to observe whether the injection site is in the suprachoroidal space, whether there is any damage to the surrounding tissue, and to evaluate the degree of diffusion of the drug in the suprachoroidal space. After the injection, the animals will be kept under observation and an autofluorescence test will be performed on the 28th day. After euthanasia of the animals, the eyes will be isolated, cryosectioned, and stained to assess the transduction status of AAV-EGFP.

[0187] Test results: Observation showed that the drug injection had no reflux, no diffusion onto the ocular surface, and no conjunctival residue, bleeding or congestion was observed. The OCT scan results, as shown in Figure 45, showed that no scleral puncture hole was found, and obvious choroidal detachment was found in the OCT, and no retinal detachment, bulge, or tear was found, indicating that the injection depth was appropriate and did not penetrate the choroid or retina. As shown in Figure 46, autofluorescence was detected with fluorescent spots distributed all over the fundus, both above and below, and to the left and right, and was clearly detected above and below the optic disc. As shown in Figure 47, frozen retinal tissue sections clearly showed that the injected reagent was expressed in both retinal epithelial cells and photoreceptor cells. The above test results indicated the success of the injection.

[0188] Explanation: RGCs are ganglion cells, INL is the inner retinal nuclear layer, ONL is the outer retinal nuclear layer, and RPE are retinal pigment epithelial cells.

[0189] <Test Example 4> The ophthalmic injection assembly and syringe of Example 1 are used to form an injection device, and based on the normal thickness of the scleral tissue and choroid of rhesus monkeys, a sleeve needle is customized with an effective length of 700 μm and a blade length of 500±50 μm, and the inner diameter of the sleeve 3 is 1.5 mm.

[0190] The effective length, that is, the length of the tip of needle 2 beyond the clamping opening, is 700 μm. That is, the distance from the tip of needle 2 to the annular end face is 700 μm. Needle 2 is approximately perpendicular to the annular end face.

[0191] Test method: After anesthetizing with pentobarbital, propantheline hydrochloride eye drops were used to anesthetize the ocular surface, and 1 to 2 minutes after administration, a suprachoroidal injection was performed using a homemade sleeve needle. Experimental animals: Rhesus monkeys Injection frequency: One injection in each eye Injection reagent: 0.2% ICG, 100 μL Injection method: same as Test Example 1

[0192] During the injection process, any signs of reflux, ocular surface diffusion, and subconjunctival retention, diffusion, bleeding, or hyperemia are recorded. Immediately after injection, ICGA angiography and OCT examinations are performed on the injected eye to observe whether the injection site is in the suprachoroidal space and whether there is any damage to the surrounding tissue, and to evaluate the degree of diffusion of the drug in the suprachoroidal space.

[0193] Test results: When observing the results of the injection, there was a small amount of reflux in both eyes, the reflux liquid was absorbed by the sleeve, no ocular surface diffusion was observed, and no subconjunctival residue, diffusion, bleeding or congestion was observed. The results of ICGA imaging, as shown in Figure 48, showed stripe-shaped hyperfluorescence in both the left and right eyes, obvious localized fluorescence at the injection point, no intravascular hyperfluorescence, no dispersed sheet-like fluorescence, and the fluorescence diffused up to the superior temporal region. The results of the OCT scan, as shown in Figure 48, showed extrachoroidal dark areas in both the left and right eyes, shallow choroidal detachment, and no retinal detachment, elevation, or tear. The above test results indicated the success of the injection.

[0194] <Test Example 5> The difference between this test example and test example 4 is that based on the normal thickness of the scleral tissue and choroid of rhesus monkeys, a sleeve needle with an effective length of 800 μm and a blade length of 500±50 μm is customized, and the inner diameter of sleeve 3 is 1.5 mm.

[0195] Test results: Observation of the injection results showed that there was a small amount of reflux in the left eye and a very small amount in the right eye, but the refluxed fluid in both eyes was absorbed by the sleeve, and no ocular surface diffusion, subconjunctival retention, diffusion, bleeding, or congestion was observed in either eye. The results of ICGA angiography, as shown in Figure 49, showed stripe-shaped hyperfluorescence in both the left and right eyes, obvious localized fluorescence at the injection point, no intravascular hyperfluorescence, no dispersed sheet-shaped fluorescence, and fluorescence extending to the macular region and superior temporal region. The results of the OCT scan, as shown in Figure 49, showed extrachoroidal dark areas in both the left and right eyes, and the choroid had shallow detachment. The left eye had a slight retinal bulge, and the right eye had no retinal dropout, bulges, or breaks. The results of the test showed that the injection was successful.

[0196] <Test Example 6> The difference between this test example and test example 4 is that the thickness of the sclera was measured, the injection device used was a sleeve needle with a needle blade length of 500±50 μm and a screw adjustment member for adjusting the effective length, the adjustable effective length was 2000 μm, and a single injection was performed on the right eye.

[0197] The specific injection method is as follows. Step 1: The operator detects the thickness of the retina, choroid and sclera in the injection area of ​​the right eye of the rhesus monkey by any of the detection technologies such as optical coherence tomography, OCT-weighted deep imaging technology, sweeping OCT, or ultrasound biomicroscopy, and adjusts the length of the needle 2 exposed from the distal end clamping port 31 of the sleeve 3 based on the detected thickness through the adjustment assembly 4 of the ophthalmic injection device, and the adjusted length of the right eye is 650 μm. Step 2: Measure the distance with an ophthalmic caliper and confirm the injection site. Step 3: The clamping opening 31 of the sleeve 3 of the ophthalmic injection device is aligned perpendicular to the conjunctiva of the eye at the injection site. Step 4: Force is applied to the conjunctival tissue at the injection site by cooperation between the syringe 1 and sleeve 3 of the ophthalmic injection device, the clamping opening 31 of the sleeve 3 is brought into close contact with the conjunctival tissue to clamp it, and the clamped conjunctival tissue is protruded toward the sleeve 3. The distal end of the injection needle 2 is inserted perpendicularly into the scleral tissue to reach the ocular target tissue at the injection site. Step 5: Administer the injection so that the drug reaches the administration site.

[0198] During the injection process, any signs of reflux, ocular surface diffusion, and subconjunctival retention, diffusion, bleeding, or hyperemia are recorded. Immediately after injection, ICGA angiography and OCT examinations are performed on the injected eye to observe whether the injection site is in the suprachoroidal space and whether there is any damage to the surrounding tissue, and to evaluate the degree of diffusion of the drug in the suprachoroidal space.

[0199] Test results: When observing the results of the injection, no reflux, ocular surface diffusion or subconjunctival retention, diffusion, bleeding or congestion was observed. The results of ICGA angiography, as shown in Figure 50, showed stripe-shaped hyperfluorescence, obvious localized fluorescence at the injection point, no intravascular hyperfluorescence, no dispersed sheet-shaped fluorescence, and fluorescence extending to the macular region and superior temporal region. The results of the OCT scan, as shown in Figure 50, showed no scleral puncture hole, and the OCT revealed choroidal detachment, with no retinal detachment, protrusion, or tear. Test results showed the injection was successful.

[0200] <Test Example 7> The difference between this test example and test example 4 is that the thickness of the sclera was measured, the injection device used was a sleeve needle with a blade length of 400±50 μm of needle 2 and a screw adjustment member for adjusting the effective length, the adjustable effective length was 2000 μm, and a single injection was performed on the left eye.

[0201] The specific injection method was the same as in Test Example 6, and the adjustment length of the left eye was 750 μm.

[0202] During the injection process, any signs of reflux, ocular surface diffusion, and subconjunctival retention, diffusion, bleeding, or hyperemia are recorded. Immediately after injection, the injected eyeball was examined by OCT to see whether the injection site was in the suprachoroidal space and whether it caused damage to the surrounding tissue, and to evaluate the degree of drug diffusion in the suprachoroidal space. After injection, the mice were kept and observed for 28 days. After euthanasia of the animals, the eyes will be isolated, cryosectioned, and stained to assess the transduction status of AAV-EGFP.

[0203] Test results: Observation of the injection results showed no reflux, ocular surface diffusion, subconjunctival retention, diffusion, bleeding or congestion. The OCT scan results, as shown in Figure 51, showed that no scleral puncture hole was found, and the OCT showed obvious choroidal detachment. No retinal detachment, protrusion, or tear was found, indicating that the injection depth was appropriate and did not penetrate the choroid or retina. Frozen retinal tissue sections showed that after injection into the suprachoroidal space, AAV-EGFP primarily transduced RPE cells and photoreceptor cells, as shown in FIG. Test results showed the injection was successful.

[0204] In the diagram, RPE is the retinal pigment epithelium, IS / OS is the retinal photoreceptor inner / outer segment connection, INL is the inner retinal nuclear layer, ONL is the outer retinal nuclear layer, and RGC are ganglion cells.

[0205] <Test Example 8> The difference between this test example and test example 4 is that the thickness of the sclera was measured, the injection device used was a sleeve needle with a needle blade length of 300±50 μm and a screw adjustment member for adjusting the effective length, the adjustable effective length was 2000 μm, the injection device was provided with a thrust assembly, and a single injection was performed into the right eye.

[0206] The specific injection method is as follows. Step 1: The operator detects the thickness from the conjunctiva to the choroid in the injection area of ​​the rhesus monkey by either optical coherence tomography, OCT-weighted deep imaging technology, sweeping OCT, or ultrasound biomicroscopy, and adjusts the length of the needle exposed from the distal end clamping port of the sleeve based on the detected thickness from the conjunctiva to the choroid through the adjustment assembly of the ophthalmic injection device, the adjustment length for the right eye is 850 µm. Step 2: Measure the distance with an ophthalmic caliper and confirm the injection site. Step 3: The sleeve clamping opening 31 of the ocular injection device is aligned perpendicular to the ocular surface at the injection site. Step 4: The operator applies force to the ocular tissue at the injection site through the cooperation of the syringe and sleeve 3 of the ocular injection device via thrust assembly 6, clamping the sleeve clamping port 31 against the ocular tissue, protruding the clamped ocular tissue into sleeve 3, and pressing the distal end of needle 2 vertically through the distal end clamping port of sleeve 3 from the protruding ocular surface tissue into the sclera to reach the ocular target tissue at the injection site. Step 5: The operator opens the second stopper 7 and presses the distal end of the push rod 12, and the drug is injected by a constant thrust generated by the thrust assembly at the proximal end portion of the push rod 12, so that the drug reaches the administration site.

[0207] During the injection process, any signs of reflux, ocular surface diffusion, and subconjunctival retention, diffusion, bleeding, or hyperemia are recorded. Immediately after injection, an OCT examination is performed on the injected eye to observe whether the injection site is in the suprachoroidal space and whether it has caused damage to the surrounding tissues, and to evaluate the degree of diffusion of the drug in the suprachoroidal space. After the injection, the animals will be kept under observation and an autofluorescence test will be performed on the 28th day. After euthanasia of the animals, the eyes will be isolated, cryosectioned, and stained to assess the transduction status of AAV-EGFP.

[0208] Test results: Observation of the injection results showed no reflux, ocular surface diffusion, subconjunctival retention, diffusion, bleeding or congestion. The OCT scan results, as shown in Figure 53, showed no choroidal or retinal detachment, elevation, or break, indicating that the injection depth was appropriate and the choroid or retina was not penetrated. Frozen retinal tissue sections showed that after injection into the suprachoroidal space, AAV-EGFP primarily transduced RPE cells and photoreceptor cells, as shown in FIG. Test results showed the injection was successful.

[0209] <Test Example 9> The difference between this test example and test example 4 is the injection amount: 100 μL / injection.

[0210] Monocular injections were performed according to the injection method of Test Example 4, among which 3 monkeys were injected with ICG, 3 monkeys were injected with buffer solution, and the remaining 9 monkeys were injected with the drug containing AAV8.

[0211] During the injection process, any signs of reflux, ocular surface diffusion, and subconjunctival retention, diffusion, bleeding, or hyperemia are recorded.

[0212] Results: None of the 36 eyes showed reflux, ocular surface diffusion, subconjunctival retention, diffusion, hemorrhage, or hyperemia during injection. Test results showed the injection was successful.

[0213] <Comparative Example 1> Suprachoroidal injection using the open conjunctival injection method

[0214] The difference between this comparative example and Test Example 1 is that a general syringe was used for the injection. Syringe: BD syringe, 34G needle; WPI34G blunt needle Test method: After anesthetizing with pentobarbital, propantheline hydrochloride eye drops were used to anesthetize the ocular surface, and 1 to 2 minutes after administration, a suprachoroidal injection was performed using the open conjunctival injection method. The specific procedure is as follows: first, the conjunctiva at the injection site is incised using conjunctival scissors to completely expose the sclera, and then the sclera is punctured with a BD syringe needle of 34G. Finally, the suprachoroidal space is injected using a WPI 34G blunt needle.

[0215] During the injection process, any signs of reflux, ocular surface diffusion, and subconjunctival retention, diffusion, bleeding, or hyperemia are recorded. After the rabbits were sacrificed, the eyeballs were enucleated, and flat samples of the fundus tissue were prepared and photographed to record the distribution of the ICG solution in the suprachoroidal space.

[0216] Test results: Observation showed that the injected ICG had serious reflux and subconjunctival residue, serious diffusion on the ocular surface and subconjunctival, and conjunctival hemorrhage. As a result of the fundus tissue section, no staining of the fundus tissue was observed. Test results showed the injection was unsuccessful.

[0217] <Comparative Example 2> Suprachoroidal injection with hub microneedle (without sleeve)

[0218] Hub microneedle: Based on the normal thickness of scleral tissue and choroid in New Zealand rabbits, a hub microneedle with an effective length of 700 μm and a blade length of 450 μm is set.

[0219] Test method: After anesthetizing with pentobarbital, anesthetize the ocular surface with propantheline hydrochloride eye drops. 1-2 minutes after administration, a homemade hub microneedle is used to vertically puncture the sclera and perform a suprachoroidal injection. Test animals: healthy New Zealand rabbits, 1.8-2.2 kg Injection frequency: One injection in the right eye Injection reagent: 0.2% ICG, 100 μL

[0220] During the injection process, any signs of reflux, ocular surface diffusion, and subconjunctival retention, diffusion, hemorrhage, or hyperemia are recorded. After the rabbits are sacrificed, the eyes are enucleated and flat samples of fundus tissue are prepared. Photographs were taken to record the distribution of the ICG solution in the suprachoroidal space.

[0221] Test results: Observation revealed obvious reflux of ICG injection and subconjunctival residue, obvious diffusion on the ocular surface and subconjunctival, and slight hyperemia under the conjunctiva. As shown in Figure 55, the results of the fundus tissue section showed that the ICG stained area of ​​the fundus tissue was less than 2 / 3, and the stained fundus tissue was light green. The test results showed that the injection was unsuccessful.

[0222] Although the devices and methods of the present invention are described as providing for the delivery of drugs to the suprachoroidal space, in other embodiments, the disclosed devices and methods may be applied to deliver any suitable therapeutic substance to any portion of the eye, such as the cornea, conjunctiva, retinal region, or vitreous body. In other embodiments, any of the disclosed devices and methods may be used to deliver any suitable therapeutic substance to any desired ocular target tissue.

[0223] Certain components disposed in particular orientations or positions shown above in connection with the schematic diagrams and / or examples may be adaptively adjusted. Similarly, the particular methods and / or order of steps disclosed may be adjusted. Although embodiments have been specifically illustrated and described, it should be understood that various changes in form and detail may be made.

[0224] The foregoing provides a detailed description of the ophthalmic injection assembly, injection device and method of use provided by the present invention. In the present specification, the principles and embodiments of the present invention have been described using specific examples. The above description of the embodiments is only helpful for understanding the method of the present invention and its core idea. It should be noted that those skilled in the art may make some improvements and modifications to the present invention without departing from the principles of the present invention, and these improvements and modifications will also fall within the scope of protection of the claims of the present invention.

Claims

1. comprising a sleeve and a needle that can be fitted into the sleeve, a clamping opening is provided at an end of the sleeve, and a tip of the needle can penetrate through the clamping opening, When using the ophthalmic injection assembly, the clamping opening of the sleeve is brought into contact with and pressed against the eye tissue at the injection site to protrude the eye tissue at the injection site into the sleeve, characterized in that an ophthalmic injection assembly.

2. The clamping opening is characterized by having an annular end face, The ophthalmic injection assembly according to claim 1.

3. The minimum inner diameter of the clamping opening is 1 mm to 3 mm, characterized in that The ophthalmic injection assembly according to claim 1.

4. The end of the sleeve is a contraction part, the clamping opening is located at the end of the contraction part, The cross-sectional size of the contraction part gradually increases along the direction away from the clamping opening, characterized in that The ophthalmic injection assembly according to claim 1.

5. A visible window made of a transparent material is provided on the side wall of the sleeve, or the sleeve is a member made of a transparent material, characterized in that The ophthalmic injection assembly according to claim 1.

6. The length of the cutting edge surface at the tip of the needle is 550 μm or less, characterized in that The ophthalmic injection assembly according to claim 1.

7. When engaging the needle with the sleeve, the length of the tip of the needle exceeding the clamping opening is 500 to 2000 μm, characterized in that The ophthalmic injection assembly according to claim 1.

8. A flow path is provided in the sleeve, and the needle is movably connected in the flow path, characterized in that The ophthalmic injection assembly according to claim 1.

9. One end of the needle opposite to the tip is connected to a needle base, An adjustment assembly for adjusting the length of the tip of the needle beyond the clamping portion is provided between the sleeve and the needle base, characterized in that The ophthalmic injection assembly according to any one of claims 1 to 8.

10. A needle base is connected to the rear end of the sleeve, and an adjustment assembly including a telescopic rod assembly and a driving mechanism is provided in the needle base. The telescopic rod assembly includes an outer tube and an inner tube. One end of the outer tube is connected to the rear end of the needle base, the other end is fitted into the inner tube, the other end of the inner tube is connected to the rear end of the needle, and the outer tube, the inner tube, and the needle communicate with each other in sequence, or the rear end of the needle sequentially penetrates the inner tube and the outer tube and extends beyond the outer tube. The driving mechanism is connected to the inner tube, drives the inner tube to move relative to the outer tube along the axial direction, and the inner tube can move the needle in conjunction, characterized in that The ophthalmic injection assembly according to any one of claims 1 to 8.

11. A needle base is connected to the rear end of the sleeve, and a release assembly including an elastic member and a first stopper is provided between the sleeve and the needle base. The sleeve is connected to the needle base via the elastic member. One end of the first stopper is detachably connected to the sleeve, and / or the other end of the first stopper is detachably connected to the needle base. When the first stopper is connected to the sleeve and the needle base, the elastic member is in an extended state and can provide an axial tensile force, characterized in that The ophthalmic injection assembly according to any one of claims 1 to 8.

12. When the clamping opening is closed, the chamber in the sleeve forms a sealed chamber, characterized in that The ophthalmic injection assembly according to any one of claims 1 to 8.

13. An ophthalmic injection device, characterized by comprising a syringe and the ophthalmic injection assembly according to any one of claims 1 to 8 attachable to the syringe. Ophthalmic injection device.

14. The syringe includes a drug container and a push rod slidable within the drug container. The drug container is used for storing a drug solution, and the drug container is fitted and connected to the needle, characterized in that The ophthalmic injection device according to claim 13.

15. A thrust assembly for generating a certain thrust on the push rod is provided between the end of the push rod and the drug container, characterized in that The ophthalmic injection device according to claim 14.

16. The threshold value of the certain thrust generated by the thrust assembly is 6 N or less, characterized in that The ophthalmic injection device according to claim 15.

17. A second stopper is further provided between the push rod and the drug container to limit the push stroke of the push rod, characterized in that The ophthalmic injection device according to claim 15.

18. An ophthalmic injection device for ophthalmic treatment, the method of use thereof comprising the step of bringing the clamping opening of the sleeve into contact with and pressing the eye tissue at the injection site using the ophthalmic injection device, so that the eye tissue at the injection site forms a protrusion within the sleeve, characterized in that The ophthalmic injection device according to claim 13.

19. By bringing the clamping opening of the sleeve into contact with and pressing the eye tissue at the injection site, after or simultaneously with the formation of a protrusion of the eye tissue at the injection site within the sleeve, the distal end of the needle is caused to reach the eye target tissue at the injection site, and the tip of the needle is inserted into the eye tissue at the injection site. The ophthalmic injection device according to claim 18.

20. First, one side of the sleeve clamping opening is brought into contact with the eye surface, inverted with this contact point as a fulcrum, the needle is inserted into the eye tissue at the injection site, the inversion is continued, the other side of the clamping opening is brought into contact with the eye surface, and a protrusion is formed in the eye tissue within the sleeve. The ophthalmic injection device according to claim 19.

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